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Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.


10th European Congress on Epileptology London, UK, 30 September4 October 2012

Genetics 1 Monday, 01 October 2012

001 IDENTIFICATION OF NOVEL SYNTAXIN BINDING PROTEIN 1 (STXBP1) MUTATIONS IN PATIENTS WITH SEVERE EARLY ONSET EPILEPTIC ENCEPHALOPATHIES (EOEE) T. Djmi*, P. Holmgren, S. Weckhuysen, A. Suls, A. Jansen, D. Hasaerts, C. Dielman, L. L. Klitten, S. Von Spiczak**, I. Helbig**, R. S. Mller, I. E. Scheffer, H. Hjalgrim, and P. De Jonghe *University of Antwerp, Antwerp, Belgium; VIB, Antwerp, Belgium; Epilepsy Centre Kempenhaeghe, Oosterhout, The Netherlands; UZ Brussel, Brussel, Belgium; University of Copenhagen, Copenhagen, Denmark; **University Medical Center Schleswig-Holstein, Kiel, Germany; Danish Epilepsy Centre, Dianalund, Denmark; University of Melbourne, Melbourne, Australia; and Institute of Regional Health Services Research, University of Southern Denmark, Odense, Denmark
Purpose: Identification of additional STXBP1 mutations in a large cohort of patients with EOEE and further delineating the phenotype of STXBP1 encephalopathy. Method: We collected a cohort of 171 isolated patients with Ohtahara syndrome, West syndrome and a wide range of unclassified EOEE. Point mutations and deletions in STXBP1 have been described so we used two complementary strategies to detect both classes of variation. First, identification of point mutations was done using Sangersequencing. Subsequently we performed multiplex amplicon quantification (MAQ) analysis for detection of deletions. Result: Four novel STXBP1 point mutations were identified in four patients. Three are missense mutations: p.G544V, p.I77N and p.R551C. The fourth, p.Q203X, is a nonsense mutation. DNA of parents of three patients was available and these mutations were proven to occur de novo. p.G544V was found in a patient with a neonatal epileptic encephalopathy that evolved to West syndrome; p.I77N and Q203X in patients with neonatal epileptic encephalopathy. The patient with the p.I77N mutation later developed epileptic spasms without hypsarrythmia while the patient with the p.R551C mutation had West syndrome from onset. Although one patient became seizure free after 2.5 months, all patients had severe intellectual disability. The MAQ analysis did not reveal any deletions in STXBP1. Conclusion: Our results confirm that patients with an STXBP1 encephalopathy present with severe epilepsy of very early onset and frequently develop spasms early in disease course. Although mutation yield in this study was lower than initially reported, STXBP1 screening should be considered in patients with severe EOEE of unknown etiology.

002 SCREENING FOR SYNGAP1 MUTATIONS IN PATIENTS WITH NON-SYNDROMIC ID AND EPILEPSY WITH MYOCLONIC ABSENCES OR MYOCLONIC ASTATIC EPILEPSY R. S. Mller*, F. F. Hamdan, L. L. Klitten, S. Dobrzeniecka, D. Rochefort, H. Hjalgrim, G. A. Rouleau**, J. L. Michaud, and N. Tommerup *Danish Epilepsy Centre, Dianalund, Denmark; Center of Excellence in Neuroscience of Universit de Montral, Centre de Recherche du CHU Sainte-Justine, Montral, QC, Canada; Wilhelm Johannsen Centre for Functional genome Research, University of Copenhagen, Copenhagen, Denmark; Center of Excellence in Neuroscience of Universit de Montral, Centre de Recherche du Centre Hospitalier de lUniversit de Montral, Department of Medicine, Universit de Montral, Montral, QC, Canada; Institute of Regional Health Services Research, University of Southern Denmark, Odense, Denmark; and **Center of Excellence in Neuroscience of Universit de Montral, Centre de Recherche du Centre Hospitalier de lUniversit de Montral, Universit de Montral, Montral, QC, Canada
Purpose: Epilepsy with Myoclonic Absences (EMA) and Myoclonic Astatic Epilepsy (MAE) are rare and severe childhood-onset epilepsies. The underlying etiologies of these syndromes are largely unsolved, but increasing scientific evidence points to genetic factors for these severe epilepsies. Recently, it was shown that de novo mutations in the brainexpressed synapse gene SYNGAP1 cause Non-Syndromic Intellectual Disability (NSID). Worldwide, a total of 10 patients with mutations in this gene have been described. Surprisingly, 7/10 published patients have early-onset of epilepsy with generalized seizures, mainly manifesting as absence-, myoclonic- and/or atonic seizures. Method: In search for an underlying cause of EMA and MAE, we sequenced the SYNGAP1 gene in a cohort of 25 patients with a combination of NSID and early-onset of generalized seizures. Patients had EMA, MAE or unclassified epilepsy. DNA was extracted from blood and saliva specimens according to standard protocols. Result: In a single female patient we detected a mutation in the SYNGAP1 gene (c.283dupC) which was absent in 669 healthy controls. This mutation was predicted to cause a shift in reading frame and thereby create a truncated protein (p.His95ProX5). Surprisingly, this mutation was inherited from a mildly affected father without epilepsy. A mosaic state of the mutation in the father was detected via cloning and subsequent sequencing of blood- and saliva DNA. Conclusion: We report the second patient with EMA and SYNGAP1 mutation adding more evidence to SYNGAP1-dysfunction as cause of EMA. In this study, we detected the first patient with an inherited SYNGAP1 mutation and mosaicism in a mildly affected parent.

2 Abstracts
003 MUTATIONS IN CDKL5 AS A CAUSE OF EARLY ONSET EPILEPSY ska, M. Gos, D. Hoffman-Zacharska, M. Bartnik, K. Derwin I. Terczynska, H. Mazurkiewicz, T. Mazurczak, P. Stankiewicz, E. Szczepanik, E. Bocian, and J. Bal Institute of Mother and Child, Warsaw, Poland
Purpose: The cyclin-dependent kinase like 5 (CDKL5) gene, encodes serine-threonine kinase involved in the regulation MECP2 and DNA methyltransferase I activities. The aim of the study was the molecular analysis of CDKL5 gene, in which mutations are responsible for severe early onset epileptic encephalopathy with infantile spasms, intellectual impairment and Rett-like phenotype. Method: Together, 29 patients with clinical symptoms suggesting CDKL5 mutation were referred to our laboratory for molecular testing. The multiplex ligation dependent probe amplification (MLPA) method and SALSA MLPA P189 CDKL5 Kit containing probes specific for all CDKL5 exons were applied for the detection of gene deletions. In case of deletion presence, the results were validated with microarray-CGH, quantitative Real-Time PCR, long-range PCR or direct sequencing method. Result: The MLPA analysis revealed the presence of deletions in three children with early onset epilepsy. In two, the deletion encompassed one exon with flanking intron sequences (g.18542246_18553009del10764 deletion of exon 18 and g.18492177-?_18492235+?del deletion of exon 4), in the second case the deletion was present in mosaic state. In the third case, the sequencing analysis revealed the presence of small deletion in exon 6 - c.301_317del17bp (g.18507907_18507923del17) that partially overlapped with the MLPA probe binding site leading to the decrease in MLPA signal. The mutation causes a frame shift starting at codon 101 and creation of premature STOP codon three positions downstream. Further analysis of CDKL5 coding sequence in patients without deletion is in progress. Conclusion: The MLPA analysis allowed to identify molecular cause of early onset epilepsy in 3/29 (10.3%) patients. Purpose: The PRRT2 gene, located on chromosome 16p11.2, is coding for a presynaptic protein interacting with SNAP-25, which is important for the synaptic vesicle forming and transport in the brain. Mutations in PRRT2 have been described in paroxysmal kinesigenic dyskinesia (PKD) and ICCA (PKD with infantile seizures), and recently also in some families with the syndrome of benign familial infantile seizures (BFIS) alone. All syndromes are linked to chromosome 16p12-q12. BFIS is characterized by (complex-)partial and generalized tonic-clonic seizures occurring often in clusters between 3 and 12 months of age typically resolving after weeks to months and normal psychomotor development in the patients. Method: PRRT2 was sequenced in 49 BFIS families and three sporadic cases of Italian, German, Turkish and Japanese origin. Result: We identified the previously described mutation c.649-650insC in an instable series of nine cytosines to occur in 77% of index cases. Furthermore, three novel mutations were found in three other families. Conclusion: Our study reveals PRRT2 as the major gene for BFIS alone. In the presentation, we will describe our cohort and an overview of the mutations found in the different disease entities.

Basic Science 1 Monday, 01 October 2012

005 SEIZURE-INDUCED BRAIN-BORN INFLAMMATION AND BLOOD-BRAIN BARRIER DAMAGE ARE COUNTERACTED BY ANAKINRA IN THE ISOLATED GUINEA PIG BRAIN PREPARATION L. Librizzi*, T. Ravizza, F. No, A. Vezzani, and M. De Curtis* *Neurological Institute C Besta Foundation, Milano, Italy; and Mario Negri Institute for Pharmacological Research, Milano, Italy
Purpose: Recent findings support the concept that brain inflammation is an etiopathogenetic mechanism of epilepsy, promoting seizure precipitation and recurrence. In this study we investigated if seizures induce brain inflammation independently on extracerebral factors and if brain-born inflammation is required and sufficient to maintain seizure activity and support blood-brain barrier (BBB) impairment. For this purpose, we studied the relationship between seizures, inflammation and BBB permeability in a brain preparation isolated from extracerebral compartments. Method: Epileptiform activity was induced by arterial perfusion of bicuculline (50lM), a GABAa receptor antagonist. Seizure-induced brain inflammation was evaluated by quantitative immunohistochemical analysis of IL-1b in parenchymal cells. BBB damage was assessed by extravasation of intravascular FITC-albumin. The effects of arterially-perfused anakinra, a human recombinant IL-1b receptor antagonist, were investigated on epileptiform discharges, brain inflammation and BBB damage. Result: Seizures induction in the absence of extra-cerebral factors promoted the release of IL-1b from brain resident cells and enhanced its biosynthesis in astrocytes. Anakinra rapidly terminated seizures, prevented their recurrence and resolved seizure-associated BBB breackdown. Conclusion: We demonstrated that (i) seizure activity determines a rapid release of IL-1b from intrinsic brain cells, (ii) persistent brain inflammation originates in glia, independently on peripheral factors, (iii)

004 PRRT2 MUTATIONS ARE THE MAJOR CAUSE OF BENIGN FAMILIAL INFANTILE SEIZURES (BFIS) Y. Weber*, J. Schubert*, R. Paravidino, F. Becker*, A. Berger, N. Bebek, A. Bianchi, K. Brockmann**, G. Capovilla, B. Dalla Bernardina, Y. Fukuyama, G. Hoffmann, K. Jurkat-Rott***, A. Antonnen, G. Kurlemann, A. E. Lehesjoki, F. Lehmann-Horn***, M. Mastrangelo, U. Mause****, S. Mller*, B. Neubauer, B. Pst, D. Rating, A. Robbiano, S. Ruf, C. Schroeder, A. Seidel, N. Specchio*****, U. Stephani, P. Striano, J. Teichler, D. Turkdogan, F. Vigevano, M. Viri, P. Bauer, F. Zara, and H. Lerche* *University of Tbingen, Tbingen, Germany; Department of Neuroscience, Genova, Italy; Children's Hospital Harlaching, Munich, Germany; Istanbul, Turkey; Verona, Italy; **Gttingen, Germany; Mantova, Italy; Arezzo, Italy; Tokyo, Japan; Heidelberg, Germany; ***Ulm, Germany; Helsinki, Finland; Mnster, Germany; Finland; Milano, Italy; ****Frankfurt, Germany; Giessen, Germany; Hamburg, Germany; Tbingen, Germany; Celle, Germany; *****Rome, Italy; Kiel, Germany; Gaslini Institute, University of Genova, Genova, Italy; Zrich, Switzerland; and Institute Giannina Gaslini - Lab. Neurogenetics, Genova, Italy
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

3 Abstracts
the clinically used the immunomodulator anakinra, abates both seizure duration and their recurrence, and the associated BBB breakdown, supporting the conclusion that brain-borne inflammation, independent on systemic influences, initiates and sustains ictogenesis. This study supports the use of specific anti-inflammatory drugs in clinical conditions that present with recurrent seizures, such as status epilepticus or drugresistant chronic epilepsies. Purpose: Inflammation plays a prominent role in the affected brain tissue in temporal lobe epilepsy, and activation of the complement system is an important component of this response. Better understanding of inflammatory changes and correlation with electrophysiological and imaging characteristics may yield insights into the mechanisms underlying the development of epilepsy. Method: Epilepsy was induced by systemic injection of pilocarpine in Swiss mice. Animals were allocated to 3 groups comprising controls (CON, n=6), those with status epilepticus (SE, n=12) following injection of pilocarpine, and those that did not develop status epilepticus after injection (NoSE, n=6). MR images were acquired at 7 and 35 days after injection. The MR T2 relaxation times and apparent diffusion coefficient (ADC) maps were compared between the groups using voxel-based statistical parametric mapping. Spontaneous recurrent seizures were quantified with 3 week-long continuous video-EEG monitoring. Complement expression and glia activation were studied by immunocytochemistry at 7 days and 4 months post-SE. Result: SE group developed chronic recurrent seizures with a frequency of 0.5 sz/day. No EEG changes were observed in CON or NoSE group. Marked upregulation of complement C3 expression was found in reactive astrocytes in the hippocampus of SE group, but not in NoSE animals. Compared to NoSE group, SE mice had increased ADC and T2 values in the hippocampus corresponding to the areas of astrocyte activation and C3 upregulation. Conclusion: Persistent C3 upregulation following an epileptogenic insult is associated with destabilization of neuronal networks involved in seizure generation and progression of tissue damage.

006 SEVERE FUNCTIONAL DEFECTS OF THE KV7.2 CHANNEL CAUSED BY MUTATIONS ASSOCIATED WITH EPILEPTIC ENCEPHALOPATHIES S. Maljevic*, M. Bock*, G. Orhan*, D. Shepers*, S. Weckhuysen, S. Mandelstam, A. Suls, I. E. Scheffer, P. De Jonghe**, and H. Lerche* *Hertie Institute for Clinical Brain Research, Tuebingen, Germany; University of Antwerp, Antwerp, Belgium; 7Florey Neurosciences Institutes, Austin Health, Melbourne, Australia; University of Antwerp, Wilrijk, Belgium; Royal Children's Hospital, Parkville, VIC, Australia; and **Neurogenetics Group, Antwerp, Belgium
Purpose: Mutations in KCNQ2 and KCNQ3, encoding the voltagegated potassium channels Kv7.2 and Kv7.3, cause Benign Familial Neonatal Seizures (BFNS), an autosomal- dominant epilepsy syndrome with favorable prognosis. However, some KCNQ2 mutations lead to more severe clinical phenotypes, as reported for seven novel KCNQ2 mutations associated with an epileptic encephalopathy (Weckhuysen et al., 2012). In these patients, seizures were extremely refractory, profound intellectual disability was present and the MRI revealed transient T1 and T2 hyperintensities of the basal ganglia and thalamus. To elucidate the mechanisms behind the observed epileptic phenotypes we set out to functionally investigate these mutations. Method: Using site-directed mutagenesis the mutations were inserted into the KCNQ2 cDNA and potassium currents recorded in cRNAinjected Xenopus laevis oocytes, using a fully-automated injection and a two-voltage clamp system. Result: Mutations affecting the pore loop (p.A265P, p.T274M) and S6 segment (p.G290D) yielded barely measurable potassium currents and exhibited a prominent dominant-negative effect on the WT currents of Kv7.2, Kv7.3 or Kv7.2/Kv7.3 channels. A depolarizing shift by about 10 mV (p.I205V) or 60 mV (p.R213Q) was observed for the S4 segment mutants, as well as for the C-terminal mutation p.R532W (~20 mV). The second C-terminal mutation (p.M518V) reduced the maximal current amplitude to one third of the WT. Conclusion: Whereas haploinsufficiency of Kv7.2 presents the major pathomechanism of BFNS with only a few mutations exhibiting a dominant-negative effect, our electrophysiological findings indicate dramatic functional deficits for the majority of the epileptic encephalopathy mutations, which could present a plausible explanation for the more serious clinical phenotype.

008 GABAERGIC INTERNEURONS LEAD TO THE EPILEPTOGENESIS: INTERNEURON PATHOLOGY ASSOCIATED WITH ARX MUTATION M. Itoh*, S. Okazaki, H. Kawawaki, T. Inoue, and Y. Goto* *National Center of Neurology and Psychiatry, Kodaira, Japan; and Osaka City General Hospital, Osaka, Japan
Purpose: X-linked lissencephaly with abnormal genitalia (XLAG), showing severe neonatal seizure and developmental delay, is a rare disorder caused by mutations in the aristaless-related homeobox (ARX) gene, located in Xp22.13. Arx-null mice for human XLAG model showed loss of tangential migration of GABAergic interneurons. However, GABAergic interneuron distribution of XLAG brain has never been reported. In the present study, we investigated subpopulation of GABAergic interneurons in the brain of an infant with XLAG, who had a nonsense mutation of the ARX gene, compared with those of age-matched normal control and Miller-Dieker syndrome. Method: We performed immunocytochemistry for interneuron and migration markers. Result: Glutamic acid decarboxylase (GAD)- and calretinin (CR)-containing cells were significantly very few in the neocortex and, interestingly, located in the white matter and neocortical subventricular zone, while neuropeptide tyrosine and cholecystokinin positive cells were normal. From previous rodent studies, the imbalance of GABAergic interneurons may be derived from the caudal ganglionic eminence tangential migration. Also, in the neocortical subventricular region, the GAD- and CR-containing cells had Mash-1 protein, like a radial migration marker, and nestin protein. Conclusion: ARX protein controls not only tangential migration of GABAergic interneurons from the ganglionic eminence, but also may serve to induce radial migration from the neocortical subventricular zone.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x


4 Abstracts

Clinical Epileptology Monday, 01 October 2012

009 NEUROLOGICAL AND NEUROIMAGING OUTCOMES OF CHILDHOOD STATUS EPILEPTICUS: A 10-YEAR COHORT STUDY S. Pujar*, M. Martinos*, K. Chong, B. Neville*, R. Scott*, and R. Chin* *UCL Institute of Child Health, London, UK; and Great Ormond Street Hospital for Children NHS Trust, London, UK
Purpose: The long-term outcome following childhood convulsive status epilepticus (CSE) is uncertain. We report preliminary data on neurological and neuroimaging outcomes within 10 years of CSE from a prospective paediatric population-based study. Method: Enrolled children were invited to have clinical neurological evaluation and brain MR Imaging (MRI) on a 1.5T scanner. An experienced paediatric neuroradiologist qualitatively assessed all MRIs. Result: 72 children (33 male) have been investigated. Median follow-up 7.9 years. 49 had both clinical assessment and MRI. 20 had prolonged febrile seizures (PFS), 8 acute symptomatic (AS), 11 remote symptomatic (RS), 6 idiopathic, and 4 unclassified CSE. At follow-up, all children with PFS were neurologically normal and none had epilepsy. One with AS CSE (12%) developed epilepsy that remitted after 2 years. All with RS CSE, except two, had active epilepsy, and significant neurological impairments. None with idiopathic and unclassified CSE had epilepsy or neurological impairments except two (33%). Only one child (5%) in PFS group had abnormal MRI: unilateral reduction in hippocampal volume. Amongst AS CSE, 4 (50%) had normal MRI, 3 (37%) abnormalities unlikely to be clinically significant, and 1 (12%) had left mesial temporal sclerosis (MTS). The child with MTS had only one episode of CSE with meningitis and no further seizures. 8 children (73%) with RS CSE had abnormal MRIs. All children with idiopathic and unclassified CSE had normal MRI. Conclusion: Children without prior neurological insult and/or epilepsy have good neurological outcome within 10 years of CSE. Significance of the hippocampal abnormalities in three children without a clinical correlate is uncertain.

in 43/119 (36.1%), remote symptomatic in 49/119 (41.2%) and progressive symptomatic in 24/119 (20.2%) patients. In acute and remote symptomatic aetiology, the most common reasons were cerebrovascular diseases (14/119; 11.8% vs. 27/119; 22.7%), while in progressive symptomatic aetiology brain tumors (8/119; 6.7%) were the most frequent cause. 70/119 (58.5%) patients suffered from epilepsies before admission to the NICU. Conclusion: About a sixth of patients admitted to the NICU had SE or SZs. Aetiology was symptomatic in most of the cases. The main reasons for acute and remote symptomatic SE or SZs were cerebrovascular diseases. Approximately two fifth of the patients had new-onset SZs or SE.

Purpose: The data of this study suggests the involvement of the upper middle short gyrus in speech production. Method: 25 patients suffering from severe drug refractory partial epilepsy were investigated by stereo-electroencephalography (SEEG). At least one electrode explore the insula using an oblique approach (transfrontal or trans-parietal). 313 stimulations were performed in 27 insula. 83 responses induced by insular electrical stimulation (ES), eight (9.6%) were reported by five patients as speech arrest (5 responses) and a lowering of voice intensity (3 responses). The stereotactic approach allows us to identify the stimulation sites within the insula in terms of its gyri. Also, the stimulation sites were anatomically localized via image fusion between pre-implantation 3D MRI and post-implantation 3D CT scans revealing the electrode contacts. Result: 8 responses were reported as speech disturbances. 7 among them were evoked by stimulation in the middle short gyrus (25.9% of responses evoked in the middle short gyrus). The site of the 8th response was in the post-central insular gyrus in the same insular region where the oropharyngeal responses induced by other ES (pharyngeal construction) in this study. The data suggest the involvement of the middle short gyrus of the insula in the procedures of language. Conclusion: This study provides evidence that the middle short gyrus of the insula responds to ES producing speech disturbances. These results are the first to report language disorders in humans evoked by electrical stimulation of the insular cortex during SEEG explorations in terms of gyral anatomy.

010 ASSESSMENT OF STATUS EPILEPTICUS AND SEIZURES IN NEUROLOGICAL INTENSIVE CARE UNIT IN SALZBURG, AUSTRIA J. Dobesberger, A. Arkhundova, H. Novak, A. Zerbs, T. Moroder, J. Hfler, M. Leitinger, C. A. Granbichler, and E. Trinka Paracelsus Medical University, Salzburg, Austria
Purpose: Status epilepticus (SE) as well as aggravation of epileptic seizures (SZs) are common reasons for admission to a neurological intensive care unit (NICU). They may also occur as complications during the stay in patients at the NICU. The aim of this study was to evaluate incidence and clinical data of SE and SZs at a NICU. Method: We retrospectively analysed all consecutive patients who were admitted to the NICU of the Department of Neurology, Paracelsus Medical University, in Salzburg, Austria, between from January 2010 to May 2011. Result: A total of 719 patients were admitted to the NICU, 121/719 (16.8%) patients (68 men; mean age 59.0 19.6 years; range 1491) had SE or SZs: 84/121 (69.4%) had the referral diagnosis SE, 32/121 (25.5%) SZs and 5/121 (4.1%) developed SE or SZs during the stay. 116/119 (97.5%) patients had symptomatic aetiology: acute symptomatic
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

Purpose: Self-report measures of ictal consciousness suggest greater levels of awareness and subjective experiences in patients with NEAD compared to epilepsy. This study further investigated which specific aspects of consciousness alterations show most variability across seizure types. Method: A total of 77 adult out-patients (n=21 with a diagnosis of epilepsy, n=38 with NEAD and n=17 with a dual diagnosis) were recruited

5 Abstracts
from the specialist Neuropsychiatry Clinic at BSMHFT/University of Birmingham. All participants completed a standardised battery of psychometric measures, including the 20-item Ictal Consciousness Inventory (ICI). This instrument allows investigation of the level of awareness (ICI-level: items 110) and subjective consciousness experiences (ICIcontent: items 1120) during recalled seizures and non-epileptic attacks. Result: Item-by-item comparison revealed a statistically significant difference in Item 20, which captures the presence and vividness of ictal emotions (Kruskall-Wallis test, p=0.05; epilepsy mean score=3.6; NEAD= 4.2; dual diagnosis=3.3). Trends towards statistical significance were also demonstrated for Item 17, which assesses metamorphopsia (p=0.08; dual diagnosis mean score=4.2; epilepsy=3.3; NEAD=4.0) and Item 18, which assesses mnestic dysperceptions (p=0.09; epilepsy mean score=3.2; NEAD=4.0; dual diagnosis=4.2). Conclusion: The results of the present study are in accordance with previous findings, emphasizing the more florid interpretation of ictal experiences in patients with NEAD. This is particularly evident in items assessing the presence of positive ictal emotions, metamorphopsia and memory flashbacks, suggesting a possible role for dysregulation in the emotional processing of perceptual experiences in the pathophysiology of NEAD.

014 PSYCHIATRIC COMORBIDITY IN CHILDREN BEFORE AND AFTER TEMPORAL LOBE EPILEPSY SURGERY A. Michoulas*, C. Waisburg, S. J. Akdag, A. Chapman, and M. B. Connolly* *University of British Columbia, BC Children's Hospital, Vancouver, Canada; Institue of Neurosciences, Favaloro University, Buenos Aires, Argentina; BC Children's Hospital, Vancouver, Canada; and University of British Columbia, BC Children's Hospital, Vancouver, Canada
Purpose: The primary objective of this study was to establish the rate and types of psychiatric comorbidities among children with temporal lobe epilepsy before and after epilepsy surgery. The secondary objective was to examine for predictors of psychiatric comorbidity. Method: All pediatric patients who underwent temporal lobe epilepsy surgery at British Columbia Children's Hospital between 1995 and 2010, with a minimum 12 month follow-up were included. Sixty-three charts were retrospectively reviewed. Patients undergo multidisciplinary evaluation including screening and referral for psychiatric symptoms. Psychiatric disorders included: attention-deficit/hyperactivity disorder (ADHD), emotional disorder (depression and/or anxiety), pervasive developmental disorder (PDD), obsessive-compulsive disorder and psychosis. Result: Psychopathology was diagnosed in 26 (44.4%) patients preoperatively and in 31 (49.2%) patients post-operatively. The most common were emotional disorder (27% pre-operative and 36% post-operative) and ADHD (26% pre-operative and 20% post-operative). Notably, 58% of patients with an emotional disorder received psychological and/ or medical therapy. Five of 17 (29.4%) patients with depression had suicidal ideation. Pre-operative ADHD was significantly more common in patients with a family history of psychiatric illness (p=0.002). Pre-operative psychiatric comorbidity was a significant predictor of post-operative psychiatric comorbidity, p=0.006. No relationship was found between duration of epilepsy, pathology, seizure outcome and psychiatric diagnosis. Conclusion: Psychiatric comorbidity is common in pediatric temporal lobe epilepsy. Temporal lobe surgery did not influence the occurrence of post-operative psychopathology. Children with a pre-operative psychiatric comorbidity were significantly more likely to have a post-operative psychiatric comorbidity. Psychiatric assessment and treatment are important components of epilepsy surgery care.

Neuropsychiatry Monday, 01 October 2012

013 POSTICTAL PSYCHOSIS IN TEMPORAL LOBE EPILEPSY RISK FACTORS AND POSTSURGICAL OUTCOME R. A. Cleary*, P. J. Thompson*, and J. Foong *The National Hospital for Neurology and Neurosurgery and Institute of Neurology, London, UK; and The National Hospital for Neurology and Neurosurgery, London, UK
Purpose: Postictal psychosis (PIP) reportedly occurs in 410% of patients with temporal lobe epilepsy (TLE). Whilst the clinical characteristics are well described, less is known about the pathophysiological mechanisms and predisposing factors. The aims of this study were to identify risk factors that may predispose patients to developing PIP and to determine whether a history of PIP predicts postsurgical outcome. Method: We identified 20 patients with a history of PIP-TLE from a total of 280 TLE patients on the epilepsy surgery database at the National Hospital for Neurology and Neurosurgery, London. They were compared to 60 age-matched TLE patients without any psychiatric history, with respect to presurgical clinical and neuropsychological variables. Group differences in postsurgical psychiatric, cognitive and seizure outcomes over 4 years were also examined. Result: Our current analysis indicated that PIP-TLE patients were less likely to have localised interictal and ictal EEG abnormalities than the TLE controls, particularly regarding ictal EEGs. Other presurgical clinical and neuropsychological variables did not distinguish between the groups. PIP-TLE patients were more likely to develop postsurgical psychiatric disorders (p=0.018) within 4 years of surgery but there were no differences in seizure or cognitive outcomes. Conclusion: Our results suggest that more widespread or diffuse brain abnormalities as reflected by EEG findings may contribute to the development of PIP. Furthermore, patients with a history of PIP who undergo epilepsy surgery have an increased risk of developing postsurgical psychiatric disorders. This has implications for presurgical counselling and also highlights a need for postsurgical psychiatric monitoring for these patients.

015 HOW SODIUM VALPROATE CAUSES LANGUAGE DELAY AND AUTISM - A MOLECULAR STUDY R. Moldrich, G. Leanage, and D. Reutens University of Queensland, Brisbane, Qld, Australia
Purpose: The widely used anti-epileptic drug sodium valproate (VPA) vastly increases the risk of autism spectrum disorders (ASD) upon prenatal exposure. Our aim was to test the hypothesis that VPA is causing ASD via inhibition of histone deacetylase (HDAC) using a mouse model of in utero VPA exposure. Method: We created an mouse model of autism prenatally exposed to VPA (600mg/kg) at embryonic day 12 and compared it to an animal prenatally exposed to a specific HDAC inhibitor, trichostatin A (TSA) (1mg/kg). We measured HDAC enzyme activity, histone acetylation status and behavioural features in juvenile mice. Result: Treatments with 600 mg/kg VPA and 1 mg/kg TSA reduced HDAC enzyme activity to activity to 60% and 63% of control, respectively. We also measured acetylated histone levels by SDS-PAGE and
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

6 Abstracts
Western blot. We found that 600 mg/kg VPA, 200 mg/kg VPA and 1 mg/ kg TSA similarly increased acetylated histone H4, but not H3 levels to approximately 200% of control. Postnatally, 600 mg/kg VPA and 1 mg/ kg TSA treated mice demonstrated a similar lack of olfactory motivation, delayed motor ability and sociability deficits, analogous to deficits seen in infants with autism. Conclusion: Pharmacological or environmental inhibition of HDAC can lead to subtle morphological changes in the developing embryo, leading to ASD-like behavioural manifestations. Further, HDAC inhibition in embryos is likely the cause of developmental delay following VPA administration during pregnancy. Purpose: The aim of the study was analysis of efficiency and safety of oxcarbazepine at children and adults depending on patient's age and forms of epilepsy. Method: 155 patients receiving oxcarbazepine (male = 78, female = 77) of the age from 5 month till 59 years are observed in dynamics with video-EEG control at the period 20062011. Were identified: IGE with isolated GTCS 5, focal frontal lobe epilepsy 40, temporal lobe 63, parietal lobe 6, occipital lobe 13, idiopathic focal 5, epileptic encephalopathies 23 patients. Result: Oxcarbazepine was effective at 59.3% of patients (n=92), and among the patient at monotherapy effectiveness (68.5%, at 37 from 54 patients) was higher than in combined therapy (54.4% at 55 of 101 patients). Low efficiency was seen at 29.1% (n=45) patients. The aggravation effect has been noted at 11.6% (n=18) of patients. Drug compliance (for >1 year) was 56.8% (n=88). High efficiency in group <1 year (n=14) was 35.7% (n=5), low 35.7% (n=5), aggravation 28.6% (n=4); in group 13 years (n=24) high efficiency 37.5% (n=9), low 37.5% (n=9), aggravation 25% (n=6); in pediatric population >3 years (n=78) high efficiency 62.8% (n=49), low effect in 29.5% (n=23), and 7.7% aggravation (n=6), in adult population >18 years (n=39) the efficiency was 74.4% (n=29), low effect 20.5% (n=8) and aggravation in 5.1% (n=2). Conclusion: Oxcarbazepine is highly effective drug in therapy of IGE with isolated GTCS, in symptomatic focal forms and Panayiotopoulos syndrome. With increasing of patients age the efficiency of oxcarbazepine raises, while aggravation risks decrease.

016 PREVALENCE AND ASSOCIATES OF SUICIDAL BEHAVIOR IN FREQUENT TREATMENT-RESISTANT FOCAL SEIZURES: THE ASERT STUDY J. French*, D. Hesdorffer, K. Posner, B. Diventura*, J. Pollard, M. Sperling, C. Harden, G. L. Krauss**, and A. M. Kanner *New York University Comprehensive Epilepsy Center, New York, NY, USA; Columbia University, New York, NY, USA; University of Pennysilvania, Philadelphia; Thomas Jefferson University, Philadelphia; Long Island Jewish Medical Center, North Shore; **Johns Hopkins University, 21287 USA; and Rush Medical College, Chicago, USA
Purpose: To assess lifetime suicidal ideation (SI) and behavior (SB), and their associates in treatment-resistant focal seizures. Method: A mulitcenter, cross-sectional study at 6 epilepsy centers. Inclusion criteria were: 1870 years; EEG-confirmed focal epilepsy for >2 years; >1 simple partial (with motor component), complex partial/secondarily generalized seizure per month for the past 6 months; currently taking 13 AEDs; and failed >2 AEDS, including current therapy. Columbia Suicide Severity Rating Scale assessed SI/SB. MINI assessed major depression (MD). High risk SI included intent/intent and plan. SB included suicide attempt (SA), interrupted or aborted attempt, preparatory acts/behavior, and non-suicidal self-injurious behavior. Calculated frequency of lifetime SI/SB. Logistic regression examined demographic, seizure-related and psychiatric correlates of suicidality. Result: 95 of 206 participants (46.1%) had lifetime SI, 29 (14.1%) had high risk SI, 21 (10.2%) had SA and 21 (10.2%) had SB without SA. No demographic or seizure-related factors were associated with SI or SB. Lifetime MD was significantly associated with lifetime SI (OR=10.8), high risk SI (OR=4.7), SA (OR=4.7) and SB without SA (OR=4.9). Conclusion: SB without SA is as common as SA alone in treatmentresistant focal seizures. Only lifetime MD is associated with SI/SB. Prevention of SB in epilepsy requires identification of lifetime MD in order to counsel and offer treatment.

Purpose: Antiepileptic drugs (AEDs) control seizures, which is a priority in pregnancy to prevent harm to the mother and fetus. However, AEDs are associated with increased risk of congenital malformations. We examined the discontinuation of AED prescribing in pregnant women using UK primary care data from The Health Improvement Network. Method: In total, 174,055 pregnant women were identified aged 13 55 years of which 745 were prescribed AEDs for epilepsy in the three months before pregnancy. Time to the last consecutive AED prescription before delivery was estimated and comparisons made to non-pregnant women with epilepsy, using Cox's regression. Factors predicting discontinuation of AEDs amongst pregnant women were investigated. Result: Pregnant women with epilepsy were twice as likely to cease AEDs compared to non-pregnant women (Hazard Ratio (HR):2.00, 95% confidence interval (CI):1.622.47). Of 745 women, 601 (80.7%) continued treatment into pregnancy and 465 (62.4%) to the end of the second trimester. Of 1490 non-pregnant women with epilepsy, 1242 (83.4%) and 1071 (71.9%) continued for comparable time periods. Compared to pregnant women with more than one AED prescribed in 36 months before pregnancy, women with one prescription were more likely to cease treatment (HR: 3.31, 95% CI: 2.574.23), whilst those with no prior prescriptions were at an even higher risk (HR: 6.32, 95% CI: 4.578.73). Conclusion: Pregnancy is a determinant for the discontinuation of AED prescribing amongst women with epilepsy, despite the possible grave consequences of uncontrolled seizures in pregnancy. Women with little exposure to AEDs prior to pregnancy should be monitored closely to ensure they do not abruptly cease medication.

Antiepileptic Drugs Monday, 01 October 2012

017 ANALYSIS OF EFFICIENCY AND SAFETY OF OXCARBAZEPINE DEPENDING ON PATIENT'S AGE AND FORMS OF EPILEPSY A. A. Kholin*, E. S. Il`Ina, and N. N. Zavadenko* *Russian State Medical University, Moscow, Russian Federation; and Russian Children Clinical Hospital, Moscow, Russian Federation
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

7 Abstracts
019 TOLERABILITY AND SAFETY OF ZONISAMIDE IN ELDERLY PATIENTS WITH PARTIAL EPILEPSY: RESULTS OF A POOLED ANALYSIS E. Trinka*, J. Segieth, and L. Giorgi *Paracelsus Medical University, Salzburg, Austria; and Eisai Limited, Hatfield, UK
Purpose: To assess the tolerability/safety of zonisamide in elderly patients with partial epilepsy. Method: A pooled analysis of data from elderly (65 years) patients receiving zonisamide for partial seizures in clinical studies was conducted (N=95) and compared to pooled adult (1865 years) patient data (N=1389). Assessments included treatment-emergent adverse events (TEAEs), clinical laboratory parameters and weight. Result: Overall incidence of TEAEs was similar in elderly versus adult patients (82.1% vs. 83.9%). Incidence was lower in elderly versus adult patients for treatment-related TEAEs (55.8% vs. 72.7%), severe TEAEs (11.6% vs. 20.4%), serious TEAEs (12.6% vs. 16.6%), and TEAEs leading to withdrawal (17.9% vs. 22.1%). TEAEs reported by 5% of patients in either cohort and more frequently by elderly versus adult patients were fatigue (11.6% vs. 9.7%), nasopharyngitis (8.4% vs. 7.2%), constipation (7.4% vs. 4.8%) and pruritus (6.3% vs. 2.1%). Serious TEAEs reported by >2% elderly patients were convulsion (2.1%) and grand mal convulsion (2.1%). Three elderly patients died but only one death was considered treatment-related (circulatory collapse following pancreatitis). No severe TEAEs were reported by >2% elderly patients. For elderly patients, there were few clinically significant changes in clinical laboratory parameters, no reports of respiratory alkalosis or metabolic acidosis, and no significant weight changes. Conclusion: Zonisamide was well tolerated by elderly patients with partial epilepsy when compared to adult patients. Most TEAEs were of mild-to-moderate intensity and the overall incidence was similar to adult patients. No new or unexpected safety findings were identified. Supported by Eisai 3 years exposure was due to premature discontinuations and study completion because of the commercial availability of lacosamide. For 1-year, 2-year, 3-year, 4-year and 5-year completers, the median percent seizure frequency reduction from Baseline was 59.4%, 64.1%, 67.9%, 69.3% and 71.0%; the 50% responder rate was 60.2%, 65.9%, 68.0%, 72.6% and 70.2%. A total of 81.3% of patients reported 1 treatment-emergent adverse event, most commonly (10%) dizziness (21.5%), headache (14.0%), and nasopharyngitis (10.7%). Conclusion: Used in the approved dose range (up to 400mg/day), longterm adjunctive lacosamide provided sustained efficacy and was well tolerated in adults with POS. These subanalysis results are consistent with those for the entire OLE population. UCB-sponsored.

Clinical Pharmacology and Therapeutics Tuesday, 02 October 2012

021 ANTIEPILEPTIC DRUGS AND LIPID METABOLISM: VALPROATE NOT SO INNOCENT? I. Y. Tan, H. Hegge, M. Majoie, P. Verschuure, C. Vader, and M. Veendrick Kempenhaeghe, Heeze, The Netherlands
Purpose: Following the hypothesis that Antiepileptic Drugs (AED) influence lipid metabolism via the cytochrome P450 system, we studied the relation between drugload of enzyme-inducers (IND_AED) and enzyme-inhibitors (INH_AED) on the one hand and lipid fractions on the other hand in adult patients with polytherapy. Method: Blood samples were collected from 261 resident patients of an epilepsy center, who all had epilepsy and (intellectual) disability. Patients with interfering medication were excluded. Patients were grouped according to use of IND_AED (87 patients with carbamazepine, phenytoin and/or phenobarbital) or INH_AED (20 patients using valproate). Enzyme-neutral comedication was allowed. Assessment was done for lipid metabolism, including Cholesterol, High-density lipoproteins (HDL), Low-density lipoproteins (LDL), triglycerides (TG) and Total Cholesterol (TC). Drug load was computed by summing PDD/DDDs (Prescribed daily dose/defined daily dose) for AED in the same enzyme-group. Result: Not surprisingly, IND_AED correlated with higher levels of serum lipids LDL, HDL, TG and TC. This is consistent with evidence from literature. Higher drugload of IND_AED correlated with higher lipid fractions, but this effect just failed to reach statistic significance. Remarkably, INH_AED correlated with elevated levels of TG, which to our knowledge is a novel finding. Moreover, there was a statistic significant relation between drugload of INH_AED and TG and TC/HDL ratio. A possible explanation for this phenomenon is that the elevated TG levels are an expression of a metabolic syndrome, related to VPA. A remarkable anecdotic finding was that in one of the patients on valproate the TG level decreased considerably after discontinuing valproate.

Purpose: To evaluate long-term efficacy and tolerability of adjunctive lacosamide in adults with partial-onset seizures (POS) who received lacosamide doses within the approved dose range (400mg/day). Method: Data were pooled from three long-term, open-label extension trials (OLE; NCT00552305; NCT00522275; NCT00515619) in adults with POS who had completed one of three double-blind, placebo-controlled Phase II/III trials of adjunctive lacosamide. During OLE treatment, dosage adjustments of lacosamide (100800mg/day) and/or concomitant AEDs were allowed to optimize tolerability and seizure control. This subanalysis evaluates trial outcomes during the extension study for patients exposed to 400mg/day lacosamide during both double-blind and open-label treatment. Result: Of 1,054 patients who initiated open-label lacosamide treatment, 363 (34.4%) had been exposed only to lacosamide doses 400mg/ day. Patients exposed to 400mg/day lacosamide for >1, >2, >3, >4 and >5 years was 64.2%, 50.1%, 41.0%, 34.2%, and 15.7%; the decrease after

022 DOES CARBAMAZEPINE AFFECT THE QT INTERVAL? T. Yadee, and K. Unnwongse Prasat Neurological Institute, Bangkok, Thailand
Purpose: Pathologic cardiac repolarization may occur during seizures and has been linked to SUDEP. In this retrospective case control study, we investigated if Carbamazepine affects the QTc interval.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

8 Abstracts
Method: Nineteen patients with epilepsy on Carbamazepine were matched for age and sex to 19 patients on Carbamazepine for neuralgia or mood disorders and 19 patients admitted for elective surgeries who were not taking Carbamazepine. None of the patients had concomitant cardiovascular disease or were taking medications known to affect the QTc interval. QTc intervals and Carbamazepine doses and blood levels, were analyzed using one-way ANOVA. Result: Two out of 19 patients (11%) in the epilepsy group but none in other groups had QTc prolongation (>450 milliseconds). The mean QTc interval was longer in patients taking Carbamazepine for epilepsy, compared to both patients taking Carbamazepine for other reasons and patients without epilepsy not taking Carbamazepine (41726 vs 40017 vs 40316 milliseconds) (p=0.029). Mean dose and blood level of Carbamazepine in epilepsy and non-epilepsy groups did not differ (737389vs 716407 mg/d and 7.272.46vs 7.362.65 mg/dl) (p=0.87 and p=0.92). Conclusion: Carbamazepine may lead to QTc prolongation in patients with epilepsy but not in other neurologic disorders. A longitudinal study comparing QTc intervals before and after treatment with Carbamazepine is required to confirm this finding. Method: All outpatients who initiated treatment with ESL between 01/ 04/2010 and 31/03/2011 were included. We retrospectively collected data on demographics, clinical features, treatment response, compliance and side effects. Only patients with at least one follow-up (FU) visit were included in the safety analysis, and only those with 1 year follow-up were included in the effectiveness analysis. Result: We included 113 patients (58$), mean age 39yo (776), mean epilepsy duration 27.2 years (250) and mean seizure frequency 27/ month (0600); 57.5% were taking 2 AED and the remaining 3 AEDs. At the last FU visit (n=110), 71.8% were still on treatment [median dosage 1200mg (4001600)]. Therapy discontinuation was mainly due to side effects (17.7%) or lack of efficacy (7.1%). About 49% of patients (n=56) had 1 year follow-up. From these, 38.2% were responders (50% reduction in seizure frequency); 39.3% were greatly improved or seizure free (clinician global impression-CGI). Effectiveness was higher in patients treated with 2 AEDs vs 3 AEDs (Responder rate - 46.7% vs 28.0%, p=0.254; CGI - 51.6% vs 24.0%, p=0.068). Conclusion: In a one year FU, ESL was effective in a significant proportion of patients particularly in those with less refractory epilepsy. ESL was well tolerated, with few patients discontinuing drug due to side effects, none of which severe.

023 CHANGED CONSTITUTION WITHOUT CHANGE IN BRAND NAME - THE RISK OF GENERICS IN EPILEPSY V. I. Patel, D. J. Cordato, M. Dias, and R. G. Beran Liverpool Hospital, Liverpool, NSW, Australia
Purpose: Lamotrigine (LTG) is an Anti Epileptic Medication (AEM) for which blood levels are helpful for optimal dosing. In late 2010, patients attending an epilepsy clinic were becoming toxic without obvious cause. This paper reports altered levels without change in regimen and provides unexpected findings. Method: Patients with elevated LTG blood levels were assessed to determine change in AEM regimen or generic substitution. Method of blood level determination was reviewed and the company (GlaxoSmithKline) contacted regarding change in source of medication. Result: The sample comprised 18 patients; mean age 40 16 years, mean daily LTG dose 493 218 mg. Mean serum LTG concentrations from August 2010 to February 2011 [91.817.7 lmol L-1, range 69.9 133.7 lmol L-1] were significantly higher than those from January 2010 to July 2010 [50.39.1lmol L-1, range 3260.1 lmol L-1), p < 0.0001]. All patients received parent product (Lamictal) and the method of LTG blood level determination was unchanged. GlaxoSmithKline confirmed that Lamictal was sourced from a different site. Conclusion: These results indicate that, even using a parent compound, AEM levels can fluctuate if the product source has changed, resulting in toxicity. It also highlights the value of determining AEM levels and the risks attached to generic substitution.

Genetics 2 Tuesday, 02 October 2012

025 PRRT2 LINKS INFANTILE CONVULSIONS AND PAROXYSMAL DYSKINESIA WITH MIGRAINE R. Cloarec*, N. Bruneau*, G. Rudolf, A. Massacrier*, M. Salmi*, M. Bataillard, C. Boulay, R. Caraballo, N. Fejerman, P. Genton*, E. Hirsch, A. Hunter, G. Lesca, J. Motte**, A. Roubertie, D. Sanlaville, S. W. Wong, Y. Fu, J. Rochette, L. Ptacek, and P. Szepetowski* *INSERM U901 - INMED, Marseille, France; Strasbourg University Hospital, Strasbourg, France; Juan P. Garrahan Pediatric Hospital, Buenos Aires, Argentina; Children's Hospital of Eastern Ontario, Ottawa, Canada; University Hospital of Lyon, Bron, France; **American Memorial Hospital, Reims University Hospital, Reims, France; Montpellier, France; Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia; University of California San Francisco, San Francisco, USA; and Universit de Picardie Jules Verne, Amiens, France
Purpose: Whole genome sequencing and the screening of 103 families recently led us to identify PRRT2 (proline-rich transmembrane protein) as the gene causing autosomal dominant infantile convulsions (IC) with paroxysmal kinesigenic dyskinesia (PKD) (PKD/IC syndrome, formerly ICCA). There is inter- and intra-familial variability and the patients may present with IC and/or PKD. In order to explore the mutational and clinical spectra, additional cases and families with either typical PKD/IC or PKD/IC with migraine were analyzed. Method: Sanger sequencing of all PRRT2 coding exons and of exonintron boundaries was performed in the probands and in their relatives whenever appropriate. Result: PRRT2 mutations were detected in 18 of 34 families. The p.R217Pfs*8 recurrent mutation and a novel frameshift mutation (p.R145Gfs*31), were found in 50% of typical PKD/IC. In another family, p.R217Pfs*8 cosegregated with PKD associated with hemiplegic migraine (HM). p.R217Pfs*8 was also detected in one IC patient having migraine with visual aura and speech difficulties, and in related PKD/IC familial cases having migraine without aura. p.R217Pfs*8 was also detected in one sporadic case with complex migrainous disorder. The pre-

024 ONE YEAR FOLLOW-UP EXPERIENCE WITH ESLICARBAZEPINE ACETATE (ZEBINIX) IN A TERTIARY HOSPITAL IN OPORTO, PORTUGAL F. D. Correia, J. P. Domingos, J. G. Freitas, R. Loureiro, J. Lopes, J. Ramalheira, J. Chaves, and J. Lopes-Lima Hospital de Santo Antnio, Centro Hospitalar do Porto, Porto, Portugal
Purpose: Introduction: Eslicarbazepine acetate (ESL) is a new antiepileptic drug available in Portugal since April 1st 2010. Despite good safety and efficacy shown in clinical trials, little is known about its effectiveness in clinical practice. Objective: Assess one year follow-up post-commercialization experience
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

9 Abstracts
viously reported p.R240X mutation was found in one PKD patient with migraine without aura. A novel frameshift mutation (p.S248Afs*65) was identified in a PKD/IC family member with IC and migraine with visual and aphasic aura. Conclusion: Taken together, our data extend the spectrum of PRRT2 mutations and phenotypes to HM and to other types of migraine in the context of PKD/IC, and emphasize the phenotypic pleiotropy seen with PRRT2 mutations.

*University of Oxford, Oxford, UK; Oxford University NHS Trust, Oxford, UK; Leicester Royal Infirmary, Leicester, UK; and Imperial College, London, UK
Purpose: To assess the frequency and clinical features of childhood onset intractable epilepsy caused by the most common mutations in the POLG1 gene which encodes coding for the catalytic subunit of mitochondrial DNA polymerase gamma. Method: Children presenting with non-syndromic intractable epilepsy of unknown aetiology, but without documented liver dysfunction at presentation were eligible for the prospective, population-based study. The blood samples were analysed for the three common POLG1 mutations. If some of the three tested mutations were found, all the exons and the exon-intron boundaries of the POLG1 gene were sequenced. In addition we retrospectively reviewed the notes of patients presenting with intractable epilepsy in whom we had found POLG1 mutations. All available clinical data was collected by questionnaire and by reviewing the medical records. Result: We analysed 213 blood DNA samples from patients fulfilling the inclusion criteria of the prospective study. Among these, four patients (1.9%) were found with one of the three common POLG1 mutations as homozygous or compound heterozygous states. In addition, three patients were retrospectively identified. Six out of seven patients had either raised CSF lactate or brain MRI changes at the presentation of intractable epilepsy. Two of the three patients who later developed liver dysfunction died. Conclusion: We recommend POLG1 gene testing for patients with intractable seizures and 1 raised CSF lactate or suggestive brain MRI changes (with thalamic predominance) with or without status epilepticus, epilepsia partialis continua or liver manifestations typical for Alpers disease, especially when the disease course is progressive.

026 THE FAMILIAL EPILEPSY SYNDROME OF GENETIC EPILEPSY WITH FEBRILE SEIZURES PLUS: SYNDROME EVOLUTION OVER SEVENTEEN YEARS I. E. Scheffer*, J. P. Malone, G. C. Glubb, K. Helbig, L. Dibbens, L. Vadlamudi, A. Bleasel, R. Burgess, B. Grinton, D. Vears, Z. Afawi, H. Goldberg-Stern**, S. Kivity**, A. D. Korczyn, J. Mulley, S. Berkovic, and Y. H. Zhang *Royal Children's Hospital, Parkville, Vic., Australia; University of Melbourne, Melbourne, Vic., Australia; Women's and Children's Hospital, North Adelaide, SA, Australia; Westmead Hospital, Westmead, NSW, Australia; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; **Schneider Children's Medical Center of Israel, Petach Tikva, Israel; and University of Adelaide, Thebarton, SA, Australia
Purpose: GEFS+ (generalised epilepsy with febrile seizures plus) is a familial epilepsy syndrome characterized by phenotypic heterogeneity that we described in 1997. The GEFS+ spectrum includes Febrile Seizures (FS), Febrile Seizures Plus (FS+), FS/FS+ with generalised and focal seizures, and a range of epileptic encephalopathies including Dravet syndrome and epilepsy with myoclonic-atonic seizures. GEFS+ is associated with mutations of sodium channel and GABA receptor subunit genes; in addition, susceptibility genes have been identified in smaller families. We studied 31 new families and analysed the phenotypic spectrum in these families and our previously published families. Method: We performed detailed electro-clinical phenotyping on all available affected family members and reviewed EEG and neuroimaging studies. We reported the phenotypic findings on 408 affected individuals in a total of 60 families. Result: New phenotypes in GEFS+ families included focal seizures without preceding FS, classical genetic generalised epilepsies and afebrile generalised tonic-clonic seizures. FS remains the most frequent phenotype in GEFS+ followed by FS+. Large GEFS+ families are suggestive of autosomal dominant inheritance. Many smaller families exist where the inheritance pattern is more suggestive of complex inheritance. Conclusion: We suggest that GEFS+ should be renamed genetic epilepsy with febrile seizures plus in view of the significant number of individuals with focal epilepsies. The overlap between GEFS+ and the classical genetic generalised epilepsies is considerably greater than first thought and suggests that the two major groups of generalised epilepsies have shared genetic determinants.

028 INFLAMMATORY PROCESS AND MESIAL TEMPORAL LOBE EPILEPSY WITH EPILEPSY: THE ROLE OF IL-1b J. Chaves*, C. Brito, B. Leal, C. Carvalho, A. Bettencourt, R. Branco, A. Martins Da Silva, P. P. Costa, and B. Martins Da Silva *Hospital de Santo Antnio, Centro Hospitalar do Porto, Porto, Portugal; and Instituto Cincias Biomdicas Abel Salazar, Porto, Portugal
Purpose: Neuroinflammation appears as an important epileptogenic mechanism. Evidence from animal models demonstrated a rapid-onset inflammatory response to acute seizures involving interleukin-1b (IL1b). It was reported that a polymorphism (-511 T>C) in the promoter region of IL-1b gene leads to a higher protein production. The -511T allele has been well accepted as associated with Febrile Seizures (FS) nevertheless the association with Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (MTLE-HS) development is still controversial. In this study we proposed to analyse the association between -511T>C polymorphism and the development and clinical features of MTLE-HS in a cohort of Portuguese population. Method: Ninety-four MTLE-HS patients (49F, 45M, mean age=39.1610.21 years, 49 with FS antecedents), 95 patients with other focal epilepsies (OEF) and 217 healthy controls were studied. Genotyping was performed using Taqman Real Time PCR methodology. Result: The -511T allele frequency was higher in MTLE-HS when compared to controls (39% vs. 32%, p=0.06 OR=1.40 [0.992.00]). Considering the antecedents of FS we constitute 2 MTLE-HS sub-groups and no differences in -511T>C allelic or genotypic frequencies were found. There were no differences between the OEF group and controls or MTLE-HS patients.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

027 PROSPECTIVE STUDY OF POLG1 MUTATIONS PRESENTING IN CHILDREN WITH INTRACTABLE EPILEPSY-PREVALENCE AND CLINICAL FEATURES J. Uusimaa*, J. Poulton*, V. Gowda, T. Mcshane, C. Smith, J. Evans, A. Shrier*, Y. Rajabally, M. Narasimhan, A. ORourke, F. Cowan, and C. Fratter

10 Abstracts
Conclusion: Our data suggests that -511T allele may be a susceptibility factor to MTLE-HS, independently of FS antecedents. The exacerbated inflammatory reaction associated with this allele could lead to cell loss and progression of seizures. These observations must be confirmed in a higher cohort. Supported by a BICE Tecnifar Grant 2009 visuomotor and executive functions. Patients were examined clinically and myoclonus severity was evaluated with myoclonus with action -part from the Unified Myoclonus Rating Scale. On the basis of myoclonus with action score the patients were classified into three disability groups: mild, moderate and severe. 46 healthy volunteers (19 M, 27 F), mean age 32 years, were the controls for the neuropsychological evaluation. Result: The patients with ULD had lower Verbal and Performance IQs than the controls (p<0.001) and impaired performance in flexible visuomotor task (p<0.001). The patients had poorer immediate verbal memory (p<0.01) but delayed memory (percentage of retained material) did not differ between the groups. Patients with mild and moderate disability had impaired executive functions (p<0.01). Most patients with severe disability could not accomplish executive function tests and this group was excluded from this analysis. Conclusion: The ULD patients are impaired in several cognitive domains, in visuomotor, executive and intellectual functions. Delayed memory is normal and memory disorder is not characteristic to ULD. The study has been funded by the Academy of Finland, the NEURO Research Programme and UCB Pharma.

Neuropsychology Tuesday, 02 October 2012

029 NEUROPSYCHOLOGICAL FUNCTIONING IN PAEDIATRIC EPILEPSY SYNDROMES A. F. Lopes*, M. R. Simes*, M. J. Fonseca, J. P. Monteiro, and C. Robalo *University of Coimbra, Coimbra, Portugal; Hospital Garcia de Orta, Almada, Portugal; and Hospital Peditrico de Coimbra, Coimbra, Portugal
Purpose: The aim of the current investigation is to examine neuropsychological functioning in common childhood epilepsy syndromes [Frontal Lobe Epilepsy (FLE), Absence Epilepsy (AE), Benign Epilepsy with Centro-Temporal Spikes (BECTS)], compare them with matched controls and study the influence of epilepsy-related variables. Method: Neuropsychological status was examined in 90 children with epilepsy (30 FLE, 30 AE, 30 BECTS), aged 615 years and compared with a control group. Children with epilepsy were selected based on the following inclusionary criteria: (1) FSIQ 70 (WISC-III), (2) EEG that confirmed the diagnosis of epilepsy and (3) were receiving no more than two antiepileptic medications. Participants completed the following tasks: Memory (List Learning, Rey Complex Figure, Corsi), Language (Rapid Naming, Phonological Awareness, Comprehension, Verbal Fluency), Attention and Executive Functions (Cancellation Task, Trail Making Test (Parts A and B), Tower of London). Result: All epilepsy syndromes showed deficits in language, attention and executive functions. Children with FLE also scored lower in verbal and visual memory. Earlier age at onset was associated with problems in long-term visual memory, sustained attention and executive functions. Children with a longer duration of epilepsy were more likely to present deficits in sustained attention. Seizure frequency and side of focus did not influence results. Conclusion: This study demonstrates cognitive dysfunction in three common childhood epilepsy syndromes, especially in FLE. Also, our results suggest that age at onset and duration of epilepsy are associated with neuropsychological functions outcome. The neurocognitive screening will be an effective tool in assessing those children in risk of school difficulties.

Purpose: The objective of our study was to assess cognition in newly diagnosed and untreated patients with epilepsy in order to determine the prevalence and the determinants of cognitive deficits at this early stage of the disease. Method: A total of 247 untreated patients with newly diagnosed epilepsy underwent a brief test battery focusing on attention and executive functions (EpiTrack) and memory (short form of the VLMT). In addition, the assessment included ratings of self-perceived deficits in attention and memory. Result: Impairments in attention and executive functions were seen in 49.4% of the patients, memory deficits in 47.8%. Unimpaired performance in both domains was observed in 27.9% of the cases. Self-perceived deficits in attention were only reported by 28.7% of the patients and memory impairments were complained by 25.1% of the patients. A lower education and a symptomatic, i.e. lesional cause of epilepsy were associated with worse performance in attention and executive functions, whereas worse memory performance was related to generalized tonicclonic seizures. Conclusion: Results indicate a high prevalence of cognitive deficits at an early stage of epilepsy which calls for consideration in the daily clinical care. Patients appear to underreport cognitive deficits. Thus, a routine application of a brief standardized neuropsychological screening before the initiation of a pharmacological treatment would be appreciated to provide a baseline to evaluate subsequent treatment success, to eventually initiate countermeasures, and to monitor the course of the disease.

030 NEUROPSYCHOLOGICAL FUNCTION OF PATIENTS WITH UNVERRICHT-LUNDBORG DISEASE J. Hyppnen*, M. iki*, A. E. Lehesjoki, and R. Klviinen* *Kuopio University Hospital, Kuopio, Finland; and University of Helsinki, Helsinki, Finland
Purpose: Unverricht-Lundborg disease (ULD), an autosomal recessively inherited neurodegenerative disorder characterized by action-activated and stimulus-sensitive myoclonus and epileptic seizures. During years some of the patients become severely incapacitated. The aim of this study was to evaluate cognitive function of patients with ULD. Method: We evaluated cognitive performance of 68 genetically verified ULD patients (37 M, 31 F), mean age 35 years, with a neuropsychological test battery assessing intellectual ability (WAIS-R), verbal memory,
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

032 COGNITIVE FUNCTION IS IMPAIRED IN PATIENTS WITH IDIOPATHIC GENERALISED EPILEPSY AND THEIR UNAFFECTED FAMILY MEMBERS F. A. Chowdhury*, L. Nashef*, R. D. Elwes*, and M. P. Richardson *King's College Hospital, London, UK; and King's College London, London, UK
Purpose: The profile of neuropsychological impairments in patients with idiopathic generalised epilepsy (IGE) includes a wide range of fron-

11 Abstracts
tal lobe functions. Assessment of neuropsychological function is complex because of the interaction of the underlying aetiological process, consequences of seizures and anti-epileptic medications. Method: Forty age-matched normal control subjects, 36 patients with IGE, and 38 unaffected first-degree relatives of patients were studied using a range of neuropsychological tests; trail-making test, matrix reasoning, verbal fluency (letter and category), N-back working memory task, Stroop response inhibition and Connors Continuous Performance Task (CPT). Verbal IQ was measured using National Adult Reading Test (NART). Statistical testing used Bonferroni correction of 8 for each neuropsychological test administered. Result: Patients performed significantly worse than controls on NART (p=0.006), matrix reasoning (p<0.001), letter and category fluency (p<0.001) and CPT omissions (p<0.001). Relatives also performed significantly worse than controls on matrix reasoning (p=0.002) and CPT omissions (p=0.001), despite having no significant difference in verbal IQ (p=0.711) using NART. There were significant linear trends between the three groups in matrix reasoning (p<0.001), letter and category fluency (p<0.001) and CPT omissions (p<0.001), with relatives falling partway between controls and patients. Conclusion: Reduced cognitive performance is found in unaffected relatives of patients with IGE as well as the patients themselves, suggesting this is related to a familial risk of epilepsy rather than a consequence of seizures or anti-epileptic treatment.

034 RESECTIVE EPILEPSY SURGERY FOR MALFORMATIONS OF CORTICAL DEVELOPMENT IN INFANCY AND EARLY CHILDHOOD T. Otsuki, A. Takahashi, T. Kaido, Y. Kaneko, R. Honda, K. Sugai, E. Nakagawa, and M. Sasaki National Center of Neurology and Psychiatry, Tokyo, Japan
Purpose: Frequent epileptic seizures in infants cause sever epileptic encephalopathy with a catastrophic nature associated with progressive developmental delay. When epileptogenic pathology such as cortical dysplasia is identified, early surgical intervention is considered although risk and prognosis of surgical intervention in infancy and early childhood is not well known. Method: We have operated 56 children with cortical dysplasias less than 6 years old at surgery in our institute during 2000 to Aug 2011. The age at surgery was from 2 to 71 months old (mean 1y11m) and the follow-up period was from 6 months to 10 years (mean 3y10m). All the patients demonstrated disabling daily seizures such as frequent spasms and tonic seizures. Comprehensive presurgical evaluation including EEG, MRI, video-EEG monitoring, PET, MEG and developmental evaluation was indicated to all the children and ictal SPECT with SISCOM analysis was indicated in 27 selected cases. Intracranial EEG monitoring was performed in 7 cases elder than 3 years old under sedation and intensive care. The location of the MRI lesion was frontal in 20, temporal in 5, parietal in 5, occipital in 2, multilobar in 6 and hemispheric in 18 cases (16 hemimegalencephaly). Result: Surgical procedure was 18 hemispherotomy (17 vertical, 1 horizontal), 7 multilobar, 15 lober and 16 focal resection. Seizure outcome was Engel's class I in 39 cases (70%), class II in 2 (3%), class III in 6 (11%) and class IV in 9 (16%). There was no statistical difference in seizure outcome between surgical procedures. Surgical complications were 1 post-operative hydrocephalus, 1 chronic subdural hematoma and 1 transient meningitis. No motality nor sever morbidity was experienced in our series. Conclusion: Favorable surgical prognosis can be obtained by resective epilepsy surgery for children in infancy and early childhood when epileptogenic pathology is demonstrated by MRI and/or functional brain imaging.

Surgical Treatment Tuesday, 02 October 2012

033 SEIZURE OUTCOME TEN YEARS AFTER RESECTIVE EPILEPSY SURGERY - A POPULATION-BASED, PROSPECTIVE, LONGITUDINAL STUDY A. Edelvik*, B. Rydenhag*, R. Flink, and K. Malmgren* *Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; and Uppsala Akademiska Hospital, Uppsala, Sweden
Purpose: The aim of this study was to investigate seizure outcome 10 years after resective epilepsy surgery in a national population-based cohort of adults and children. Method: The Swedish National Epilepsy Surgery Register encompasses data on all epilepsy surgery procedures in Sweden since 1990 and is completely prospective since 1995. Data is collected before and at surgery, and after two, five, 10 and 15 years. In this study, we analysed seizure outcome for all patients who had resective epilepsy surgery in Sweden 19952000 and had undergone 10-year follow-up (N=287). Freedom from seizures with impairment of consciousness (ILAE class 1 and 2) is reported for the year before follow-up. The percentages/numbers of patients with sustained seizure freedom (ILAE class 1 and 2) are also reported. Result: Of the 287 patients, 211 had undergone temporal lobe resections (TLR) and 76 extratemporal resections (XTLR). 10 years after TLR 62% (131/211) were seizure free compared to 59% after two years. 36% (77/ 211) had sustained seizure freedom at 10 years compared to 51% (107/ 211) after two years. 43% (33/76) were seizure free 10 years after XTLR compared to 39% after two years. 26% (20/76) had sustained seizure freedom at 10 years, compared to 37% at two-year follow-up. Conclusion: In this prospective population-based study, the percentage of patients who were seizure free the year before follow-up was stable 10 years after epilepsy surgery, compared to the two years follow-up. However, the percentage of patients with sustained seizure freedom after surgery declined over time.

035 EXTRATEMPORAL EPILEPSY SURGERY IN ELOQUENT BRAIN REGIONS USING FUNCTIONAL NEURONAVIGATION AND INTRAOPERATIVE MRI (IOPMRI) K. Roessler, B. Sommer, P. Grummich, B. Kasper, I. Blmcke, H. M. Hamer, and M. Buchfelder University Hospital Erlangen, Erlangen, Germany
Purpose: A retrospective study was performed to analyze the impact of functional neuronavigation and intraoperative magnetic resonance imaging (iopMRI) during extratemporal epilepsy surgery on neurological and epilepsy outcome. Method: From 20032011 twenty-five patients with a mean age of 36 years (range: 1267; 14 female, 11 male) were resected on focal epileptogenic lesions close to speech/motor areas or adjacent to eloquent fibre tracts. Preoperatively, motor-sensory and speech areas and fibre tracts were mapped using functional MRI and DTI imaging, respectively. Functional data were integrated into intraoperative neuronavigation and displayed through the microscope during surgery. Histopathology was FCD in 5, gliosis in 6, dysembryoblastic neuroepithelial tumor in 2, cavernous hemangioma in 5, ganglioglioma WHOI in 4 and glioma WHOIIII in 3 patients. The postoperative follow-up period was 37.2 (489) months mean.

Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

12 Abstracts
Result: According to iopMRI scans, 100% resection of epileptogenic lesions was achieved in all patients. In 4 of them, an intraoperative second look procedure according to iopMRI was necessary to complete resection. Transient dysphasia was seen in 2/14 patients, permanent dysphasia found in 2/14 patients. Permanent quadrantanopia was observed in 2/8 patients. Of patients with functional mapping of the motor cortex and pyramidal tract, 1/19 experienced a temporary monoparesis. Favourable seizure control (Engel classification I and II) was achieved in 80% of the patients. Conclusion: In our retrospective analysis, we demonstrated that resection of epiletogenic lesions close to eloquent cortex and fibre tracts can be performed safely and efficiently by integration of multimodal neuronavigation and functional imaging during surgery.

A. Reznikov*, H. Valsamis, R. Cracco*, S. Malhotra*, A. Omurtag, A. Fenton*, and S. Zehtabchi *SUNY Downstate Medical Center, Brooklyn, NY, USA; Kings County Hospital Center, Brooklyn, NY, USA; and Bio-Signal Group, Brooklyn, NY, USA
Purpose: To identify the prevalence of EEG abnormalities in patients with altered mental status (AMS) presenting to the emergency department (ED). Up to 10% of patients evaluated in the ED present with AMS. The prevalence of EEG abnormalities in this population is not known. Method: Prospective study at two urban EDs in Brooklyn, NY. Inclusion: patients over 13 years old with AMS. Exclusion: an easily correctable cause of AMS (e.g. hypoglycemia, opioid overdose). A 30-minute EEG was performed on each subject as soon as possible after presentation, usually within 1 hour. Result: 301 patients were screened and 261 enrolled over 10 months. Mean age was 58.9y (SD 19.9). 78% of EEGs were abnormal. EEG findings: slowing only - 142 (54.4%), normal - 51 (19.5%), interictal epileptiform discharges + slowing - 32 (12.3%), triphasic waves - 9 (3.4%), burst-suppression - 8 (3.1%, iatrogenic in 7), status epilepticus (SE) - 7 (2.7%), seizure - 4 (1.5%), epileptiform only - 3 (1.1%), uninterpretable 5 (1.9%). 41 (15.7%) studies were partially obscured but contained sufficient interpretable data for clinical categorization. Conclusion: ED patients with AMS have a very high prevalence of EEG abnormalities, most often diffuse slowing. 4.2% revealed SE or isolated seizure(s), but another 2.7% demonstrated burst-suppression due to acute treatment of SE. Nearly 20% of EEGs were normal, which rules out SE, seizure and encephalopathy as causes of AMS. Fewer than 2% were completely obscured by artifact. EEG in the ED can provide useful information to narrow the differential diagnosis of AMS patients. Supported by 1RC3NS070658

036 USEFULNESS OF POSITRON EMISSION TOMOGRAPHY IN DECISION MAKING FOR EPILEPSY SURGERY C. Rathore*, J. Dickson, P. Ell, and J. Duncan *Sree Chitra Institute of Medical Sciences and Technology, Trivandrum, India; University College London Hospitals, London, UK; and National Hospital for Neurology and Neurosurgery, London, UK
Purpose: To investigate the utility of Flurodeoxy-glucose Positron Emission Tomography (FDG-PET) in decision making for epilepsy surgery Method: All patients with nonlocalizing or discordant information on non-invasive evaluation (clinical, electrophysiological and 3T-MRI) underwent FDG-PET at our centre. PET scans were reviewed by two investigators blinded to clinical data. PET was considered useful if it led to surgery directly, helped in planning intracranial EEG (icEEG) or made surgery improbable. Final localization was based upon the discussion in multidisciplinary meetings supported by icEEG and/or postoperative seizure freedom, when available. Result: Ninety adult patients (median age, 34years) underwent FDGPET; 76 had normal MRI and 14 had electrophysiological and MRI discordance. Final localization was mesial temporal lobe epilepsy (MTLE, n=6), lateral TLE (n=22), frontal lobe epilepsy (n=32), and temporal-plus epilepsy or other extratemporal lobe epilepsies (15 each). FDG-PET scan was normal in 46 patients. It led to surgery without intracranial EEG in four patients (right MTLE) and helped in planning icEEG in 31 patients. Seven patients had bilateral/diffuse hypometabolism making surgery improbable and FDG-PET gave false localizing information in two patients. Nine Of 14 patients who underwent surgery to date became seizure free and three patients could not proceed to surgery after icEEG. Others are awaiting icEEG (16) or declined surgery. Only three patients with normal PET scan proceeded to icEEG or surgery (p=0.001). FDG PET provided equivalent information in all epilepsy localizations. Conclusion: In ~45% of presurgical patients with normal or discordant MRI, PET scan provided information that helped decision making.

038 IS ECOG DURING EPILEPSY SURGERY FOR MESIAL TEMPORAL SCLEROSIS OF ANY USE? J. Chan, N. Lawn, and J. Dunne Royal Perth Hospital, Perth, WA, Australia
Purpose: The use of electrocorticography (ECoG) in epilepsy surgery varies widely as do methods of anaesthesia, recording and interpretation. Its role in guiding epilepsy surgery is debated particularly in patients with mesial temporal sclerosis (MTS). Significant inter-centre disparities in outcome are seen following MTS surgery, with some centres using ECoG reporting better outcomes. We sought to study the ECoG findings and seizure outcomes in patients undergoing epilepsy surgery for MTS. Method: We studied 73 consecutive patients with refractory epilepsy who had surgery for MTS with a minimum of 1-year follow up (median 8.9 years, range 118.8 years). All surgeries were performed under general anaesthetic, usually sevoflurane. Pre-resection ECoG was recorded with two 4-contact subdural strips (inferior temporal and lateral temporal). Antero-mesial temporal resection was performed and tailored based on the initial and postresection ECoG. ECoG was analysed blinded to patient details and outcomes. Result: Overall, 58 patients (79%) had an Engel class I outcome. Of 61 patients (84%) with pre-resection spikes, those with an inferomesial rather than lateral maximal field had a better outcome (88% mesial vs. 64% lateral Engel class I; p=0.04). Engel class I outcomes occurred in 75% of 12 patients with no pre-resection spikes, 94% of 34 patients with pre-resection spikes and none after initial/additional resection, and 63% of 27 patients with residual spikes after initial/additional resection (p=0.01). Conclusion: ECoG during surgery for MTS at our centre provides useful information for guiding surgery and predicting prognosis.

Clinical Neurophysiology Tuesday, 02 October 2012

037 EEG FINDINGS IN 261 SEQUENTIAL PATIENTS WITH ALTERED MENTAL STATUS PRESENTING TO THE EMERGENCY DEPARTMENT A. C. Grant*, S. Abdul-Baki*, V. Arnedo*, G. Chari*, E. Koziorynska*, D. Maus*, T. Mcsween*, K. A. Mortati*,

Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

13 Abstracts
039 IMPLEMENTATION OF HOME VIDEO-EEG-TELEMETRY AT KING'S COLLEGE HOSPITAL (KCH), LONDON F. Brunnhuber*, S. Goyal, D. Amin, Y. Nguyen, and M. P. Richardson *King's College Hospital, London, UK; London; and King's College London, London, UK
Purpose: Aim: We present KCH's experience of the first 50 home videotelemetry (HVT) patients. Method: HVT met the MRC definition of a complex intervention, and we used its guidance to evaluate the process of piloting, evaluating, developing and implementing this new clinical service. Result: Our feasibility study (n=5) with a test re-test design found no difference in the quality of recording or clinical yield between inpatient video-telemetry (IVT) and HVT. The pre-implementation study (n=8) showed an excellent patient satisfaction. We also discuss the findings of the main stakeholder survey (consultants and technicians). Our economic modelling demonstrates a clear financial superiority of HVT over IVT. Conclusion: Our findings show that diagnostic video-telemetry for seizure classification and poly-somnographies can be carried out safely at the patients home and poses no security risks for staff and can be effectively integrated into the service offering of a tertiary care centre as a routine home or community-based procedure. Community or home-based MDTs (multidisciplinary team meetings) is an unexpected advantage of HVT and has the potential for future development for patients with complex conditions. HVT was preferred by our patients over IVT and provides a means of reaching out to some of the most vulnerable patient groups (children, patients with learning difficulties or other mental health problems), who would not otherwise benefit from this investigation or only under great difficulties. We hope to encourage other clinical neurophysiology departments and epilepsy centres to take advantage of our experience and consider adopting and implementing HVT, with the aim of a nationwide coverage. depth recordings with up to 122 channels. The datasets provide EEG data for an average recording time of 150 hours at sampling rates of 2502500 Hz. EEG recordings have undergone standardized annotation with details on the timing, patterns and evolution of seizures. Data files are supplemented by comprehensive clinical patient information, MR imaging data and antiepileptic medication. Conclusion: The EU project has resulted in the by far largest and most comprehensive database for human surface and intracranial EEG recordings. Information on access to data from this database for research groups can be obtained at

Functional MRI Wednesday, 03 October 2012

041 IMAGING MEMORY IN TEMPORAL LOBE EPILEPSY: REORGANISATION OF MEMORY FUNCTION FOLLOWING ANTERIOR TEMPORAL LOBE RESECTION RESULTS OF A LONGITUDINAL FMRI STUDY S. Bonelli*, P. J. Thompson, M. Yogarajah, R. Powell, R. Samson, A. W. Mcevoy, M. Symms, M. Koepp, and J. Duncan *Medical University of Vienna, Vienna, Austria; Institute of Neurology, London, UK; and National Hospital for Neurology & Neurosurgery, London, UK
Purpose: Anterior temporal lobe resection (ATLR) may impair memory function, typically verbal memory following left and visual memory following right ATLR. We investigated reorganisation of memory function in patients with temporal lobe epilepsy (TLE) before and after left or right ATLR and the efficiency of postoperative memory networks. Method: We studied 46 patients with unilateral medial TLE (26 left) on a 3T GE-MRI scanner. All subjects had neuropsychological testing and performed an fMRI memory encoding paradigm for words, pictures and faces preoperatively and again four months after ATLR. Result: Event-related analysis revealed that left TLE patients had greater left activation in the posterior medial temporal lobe (MTL) for encoding words postoperatively than preoperatively. Relatively greater pre- than postoperative activation for encoding words in the ipsilateral posterior MTL correlated with better verbal memory outcome after left ATLR. Four months after left ATLR greater postoperative than preoperative activation in the ipsilateral posterior MTL correlated with less good postoperative verbal memory performance. These postoperative effects were not observed for visual memory after right ATLR. Conclusion: We found effective preoperative reorganisation of verbal memory function to the ipsilateral posterior MTL, suggesting that it is the capacity of the posterior remnant of the ipsilateral hippocampus rather than the functional reserve of the contralateral hippocampus that is important for maintaining verbal memory function after ATLR; early postoperative reorganisation to ipsilateral posterior or contralateral MTL structures is inefficient. We also conclude that visual memory function in right TLE is affected differently by right ATLR than verbal memory in left TLE.

040 THE EUROPEAN EEG DATABASE AS A NEW STANDARD FOR LONG-TERM EEG RECORDINGS IN EPILEPSY PATIENTS A. Schulze-Bonhage*, M. Levanquyen, F. Sales, M. Neufang*, A. Dourado, and M. Ihle* *University Hospital Freiburg, Freiburg, Germany; Hpital de la Piti-Salptrire, Paris, France; Hospitais de Universidade de Coimbra, Coimbra, Portugal; and Universidade de Coimbra, Coimbra, Portugal
Purpose: Access to high quality long-term EEG recordings of epilepsy patients has so far been limited for many research groups active in the field of clinical neurophysiology and epileptology. We here report on a newly established European Database offering high-quality surface and intracranial EEG data for EEG and epilepsy research. Method: Supported by the EU-project EPILEPSIAE (Evolving Platform for Improving Living Expectation of Patients Suffering from IctAl Events, Grant 211713), the epilepsy centers at the University Hospitals Freiburg, Germany, Hopital Piti-Salptrire in Paris, France, and the University Hospital Coimbra, Portugal have designed a database containing long-term intracranial and surface EEG recordings. Inclusion criterie were long-term recordings with a minimum of 4 days duration containing 5 clinically manifest seizures. Result: The complete European EEG database comprises 275 long-term recordings from epilepsy patients, 223 obtained by surface-EEG using the 1020 recording system and 52 based on intracranial subdural or

Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

14 Abstracts
Purpose: The aim of this study was to explore how Blood Oxygen Level Dependent (BOLD) responses to interictal epileptic spikes during EEGcorrelated functional MRI (EEG-fMRI) relate to the ictal onset zone (IOZ). Method: Twenty-one consecutive adults with refractory focal epilepsy and a well delineated IOZ after a full presurgical evaluation including subtraction ictal SPECT co-registered to MRI (SISCOM) were studied. We delineated the IOZ as the region of SISCOM hyperperfusion (Z>1.5) within the planned or effective resection zone. Positive and negative fMRI responses (p<0.001) to clinically concordant and visually marked spikes (after standard EEG artifact removal) were used for qualitative assessment of overlap with the IOZ. Result: We observed clinically concordant interictal spikes in 10 of 21 patients during fMRI, which resulted in both activations and deactivations in all 10 patients. The maximal activation was statistically more significant than the maximal deactivation in 8/10. The maximal significant activation cluster overlapped the IOZ in 9/10, although the voxel of maximal activation was found within the IOZ in only 3/9. The cluster of maximal deactivation was concordant with the IOZ in 2/10, with the voxel of maximal deactivation inside the IOZ in 1/2. Conclusion: EEG-fMRI in consecutive patients with refractory focal epilepsy undergoing presurgical evaluation recorded epileptic spikes in only 48%. The maximal significant fMRI activation cluster overlapped the ictal onset zone in 90% of patients with spikes during fMRI. However, the voxel of maximal activation was localized inside the IOZ in only one third. This study is funded by a grant for Applied Biomedical Research (TBM) of the Institute of Innovation by Science and Technology Flanders (IWT) (080658). ILAE-class-IV post-surgical outcome. One patient did not proceed to surgery. Conclusion: Simultaneous icEEG-fMRI reveals BOLD changes in distributed networks across the whole brain for very focal epileptic discharges. These data suggest that the test may have clinical utility for predicting surgical outcome.

044 PREOPERATIVE FMRI IN TEMPORAL LOBE EPILEPSY: ASSESSMENT OF LANGUAGE-RELATED AREAS F. Villani*, C. Rosazza*, F. Ghielmetti*, L. Minati*, F. Deleo*, A. R. Giovagnoli, G. Didato*, P. Vitali, A. Parente, L. DIncerti*, R. Spreafico, and M. Bruzzone* *IRCCS Foundation Besta Neurological Institute, Milan, Italy; Fondazione IRCCS Istituto Neurologico C. Besta, Milano, Italy; Istituto Neurologico Mondino, Pavia, Italy; and I.R.C.C.S. Foundation Neurological Institute, Milano, Italy
Purpose: Surgical removal of part of the temporal lobe (TL) for temporal lobe epilepsy (TLE) may be complicated by language impairments. Functional MRI (fMRI) may predict postsurgical language outcome. In our study we assessed the impact of TLE on the language network. Method: Data collected from 67 TLE patients (40 LTLE, 27 RTLE) were retrospectively analyzed with 15 controls. The fMRI assessment included response naming (RN), verb generation (VGEN) and fluency (FT) tasks. A whole-brain and a ROI-based analysis with lateralization indices were performed. Language tests were administered. Result: The overall activation was left-lateralized in patients and controls. The FT elicited weaker activation of the TL compared to the other tasks. TL was activated anteriorly by the RN task, posteriorly by the VGEN task. LTLE patients showed a decreased left-lateralization compared to controls. In RTLE patients the RN and FT revealed a left-lateralization similar to controls, but VGEN produced posterior temporal activations also on the right side with a less lateralized language activation pattern. The language assessment showed that left and right TLE patients had significantly lower scores than controls on the Boston naming test. Conclusion: RN and VGEN were the most useful tasks to lateralize and localize language areas in the TL. LTLE patients showed reorganization of language in the right TL, suggesting an adaptive recruitment of contralateral regions. The paradoxical recruitment of right posterior temporal areas in RTLE patients may be related to language processing, as also right temporal regions are involved in accessing lexical and semantic information.

043 MAPPING THE IRRITATIVE ZONE USING SIMULTANEOUS INTRACRANIAL EEG-FMRI AND COMPARISON WITH POSTSURGICAL OUTCOME U. J. Chaudhary*, D. W. Carmichael, R. Rodionov*, S. Vulliemoz, C. Scott, A. W. Mcevoy, C. Micallef, B. Diehl, M. C. Walker*, J. Duncan*, and L. Lemieux* *UCL Institute of Neurology, London, UK; UCL Institute of Child Health, London, UK; University Hospital of Geneva, Geneva, Switzerland; and National Hospital for Neurology and Neurosurgery, London, UK
Purpose: To determine the clinical significance and distribution of spike-related haemodynamic changes across the whole brain using simultaneous intracranial electroencephalography and functional magnetic resonance imaging (icEEG-fMRI), particularly as icEEG has limited spatial coverage. Method: Five patients with frontal lobe epilepsy undergoing invasive presurgical evaluation were scanned. One to two 10-minutes EPI-sessions (TE/TR 40/3000ms; slices/gap: 38x2.5mm/0.5mm) and T1 volume were acquired on 1.5T scanner using head RF-coil with patient at rest. 64 channels of icEEG were recorded during EPI and reviewed after removing scanner-related-artefacts. Pre-processed images were analysed using SPM8. Spikes were classified according to their morphology and spatiotemporal distribution on icEEG and represented as zero-duration events (different types were modelled in separate regressors) and convolved with the canonical HRF and derivatives. SPM[F] maps obtained for each spike type and for all types combined were overlaid on co-registered T1volume and compared with the irritative zone defined on icEEG. Result: All patients had statistically significant spike-related hemodynamic changes. BOLD changes were seen within the irritative zone in three patients; remote clusters were seen in all patients. BOLD clusters were predominantly in the hemisphere containing the irritative zone in three patients with ILAE class-I outcome post-surgically, and were distributed bilaterally remote from the irritative zone in one patient with
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

Structural and Functional Imaging Wednesday, 03 October 2012

045 DECREASED FUNCTIONAL FRONTAL LOBE CONNECTIVITY IS ASSOCIATED WITH COGNITIVE IMPAIRMENT IN PEDIATRIC FRONTAL LOBE EPILEPSY H. Braakman*, M. Vaessen*, J. Jansen*, M. Debeij-Van Hall, P. Hofman*, J. Vles*, A. ldenkamp*, and W. Backes* *Maastricht University Medical Center, Maastricht, The Netherlands; and Epilepsy Center Kempenhaeghe, Heeze, The Netherlands

15 Abstracts
Purpose: Cognitive impairment is frequent in frontal lobe epilepsy (FLE), but its etiology is unknown. With functional MRI, we explore the relationship between brain activation, functional connectivity and cognitive functioning in a cohort of pediatric FLE patients and healthy controls. Method: Thirty-four children aged 8 to 13 years with FLE of unknown cause and 41 healthy age-matched controls underwent neuropsychological assessment and structural and functional brain MRI. We investigated to which extent brain regions activated in response to a working memory task and assessed functional connectivity between distant brain regions. Data of patients were compared to controls and patients were grouped as cognitively impaired or unimpaired. Result: Children with FLE showed a global decrease in functional brain connectivity compared to healthy controls, while brain activation patterns remained relatively intact. Children with FLE complicated by cognitive impairment typically showed a decrease in frontal lobe connectivity. This decreased frontal lobe connectivity comprised both connections within the frontal lobe, as well as connections from the frontal lobe to the parietal lobe, temporal lobe, cerebellum, and basal ganglia. Conclusion: Decreased functional frontal lobe connectivity is associated with cognitive impairment in pediatric FLE. The importance of functional integrity within the frontal lobe network, as well as its connections to distant areas provides new insights in the etiology of the broadrange cognitive impairments in children with FLE. Purpose: To map hippocampal subfield degeneration in patients with mesial temporal lobe epilepsy (mTLE) and hippocampal sclerosis (HS) using conventional MRI. Method: We studied 82 patients with unilateral mTLE and HS (51 left, 31 right) in context of pre-surgical evaluation and 81 healthy controls. MRIs were acquired using standard MPRAGE sequences at 3 Tesla. Volumes of hippocampal regions CA1, CA2-3, CA4 and dentate gyrus, subiculum, presubiculum, fimbria, and hippocampal fissure were estimated using a recently developed method designed for automated analysis on conventional MRI (Van Leemput et al., 2009, Hippocampus 19:549). Result: Atrophy of all hippocampal subregions ipsilateral to HS other than the hippocampal fissure was observed (p=0.001). Global hippocampal volume was asymmetrically bilaterally atrophic in patients, as was fimbria volume in patients with left mTLE (p=0.01). The only clinicalanatomical correlation that existed was between duration of mTLE and volume of the ipsilateral fimbria (p=0.02). However, this effect did not survive the necessary correction for age, given that age and ipsilateral fimbria were also significantly related (p=0.03). Conclusion: These results are consistent with histological work indicating that diffuse/total HS is common in patients with mTLE, and that preservation of CA2 is seen in only a relatively small proportion of patients (Blumcke et al., 2007, Acta Neuropathol 113:235). The automated method of hippocampal subfield quantification used here is adaptable to pathological hippocampal structure, as illustrated in our patients with unilateral HS, and is therefore recommended for large-scale studies in neurological contexts.

046 STRUCTURAL CHANGES OF THE WHITE MATTER IN PATIENTS WITH JUVENILE MYOCLONIC EPILEPSY C. Roth, M. Belke, K. Menzler, S. Krach, F. Paulus, A. Jansen, M. Blanke, W. Einhuser-Treyer, F. Bremmer, F. Rosenow, and S. Knake Philipps University Marburg, Marburg, Germany
Purpose: Juvenile myoclonic epilepsy (JME) is a common type of generalized epilepsy. Amongst others it is characterized by the absence of structural brain abnormalities using magnetic resonance imaging (MRI) in the clinical routine. Recent findings in MRI studies however suggest regional changes of the brain in patients with JME, albeit those findings are partly inconsistent. There has been a spatial variability in the pathological findings even though a tendency towards changes in the frontal cortex can be remarked. Method: 19 patients with JME and 19 healthy controls, matched by sex, age and education were had a 3 Tesla MRI scan including a diffusion MRI scan (DTI). Those DTI images were analysed using Tract-Based Spatial Statistics (TBSS) and the fractional anisotropy (FA) as a measure of the integrity of the white matter was computed. Result: We found a significant reduction in the FA within the corpus callosum (CC) in patients with JME compared to healthy controls. The changes were mainly in the anterior region of the corpus callosum. Conclusion: The recuced FA within the corpus callosum suggests an impaired structural connectivity concerning the frontal lobe. Similar findings have been published by a british group last year, so this may be considered as a robust result. Our findings are further evidence that regional changes of the brain might exist in generalized epilepsy as well and support the hypothesis of impaired frontal network in patients with JME.

048 ALTERED INTERACTIONS WITHIN NEURAL NETWORK SUPPORTING VERBAL WORKING MEMORY DUE TO HIPPOCAMPAL SCLEROSIS P. Campo*, M. I. Garrido, R. J. Moran, I. Garca-Morales, A. Gil-Nagel, R. J. Dolan, and K. J. Friston *Universidad Autonoma de Madrid, Madrid, Spain; Wellcome Trust Centre for Neuroimaging, London, UK; University Hospital of San Carlos, Madrid, Spain; and Hospital Ruber International, Madrid, Spain
Purpose: To evaluate local and remote changes in effective connectivity among the regions of the neural network underlying encoding processes in patients with mesial temporal lobe epilepsy (mTLE) associated with unilateral hippocampal sclerosis (HS). Method: We compared dynamic causal models, extracted from magnetoencephalographic recordings during verbal WM encoding, in mTLE patients (n = 20) and controls (n = 12). Result: Bayesian model comparison indicated that the best model included bilateral, forward and backward connections, linking inferior temporal cortex (ITC), inferior frontal regions (IFC) and medial temporal lobe (MTL). Differences in model coefficients revealed that patients were characterized by a decreased ipsilesional MTL-ITC connectivity, and an increased bidirectional IFG-MTL connectivity in the contralesional hemisphere (all p < 0.05). The influence from right IFC to right MTL was inversely related to task performance (R2 = -.62, p < 0.05). A negative correlation was also found between the connectivity strength of ipsilesional MTL-ITC and that of the contralesional MTL-IFG interaction (R2 = -.44, p = 0.05). Conclusion: Left HS led to a dynamic adjustment/reorganization of the remaining network supporting verbal WM, affecting connections considered to be of great functional relevance for WM performance. This altered connectivity pattern may reflect compensatory, with varying degrees of efficacy, and pathophysiological mechanisms underlying verbal encoding deficits in left mTLE patients. Current results confirm those of a previous study and reinforce the hypothesis that a distributed neural network is affected as a result of localized brain damage.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

047 HIPPOCAMPAL SUBFIELD ANALYSIS IN MESIAL TEMPORAL LOBE EPILEPSY M. Deppe*, B. Weber, J. Schoene-Bake, and S. S. Keller *University of Muenster, Muenster, Germany; University of Bonn, Bonn, Germany; and King's College London, London, UK

16 Abstracts
Acknowledgments: PC was supported by Spanish Ministry of Science and Innovation (Grant # RYC-2010-05748).

Paediatric Epilepsy Wednesday, 03 October 2012

049 PAROXYSMAL NON-EPILEPTIC EVENTS IN INFANTS AND TODDLERS: A SEMIOLOGY STUDY L. Chen*, E. P. Knight, A. Shahid, and I. Tuxhorn *1st Affiliated Hospital of Guangzhou Medical College, Guangzhou, China; and Rainbow Babies and Childrens Hospital, Ohio, USA
Purpose: Paroxysmal non-epileptic events are frequently encountered in pediatric population. We report our experience with PNEEs in a group of infants and toddlers and analysis the clinical characteristic of the events. Method: Retrospectively reviewed all video EEG (VEEG) studies performed from January 2010 to April 2011. We included in the study consecutive patients 2 years old or younger who had PNEEs recorded. Semiological analysis included: type of event, time of occurrence, clear onset and end, etc. Result: Out of 81 patients 31 (38.3%) had non-epileptic events, 12 girls and 19 boys (P>0.05). Three had both epileptic and non-epileptic seizures and 28 had only non-epileptic events. Six had abnormal interictal EEG. Eight had family history of epilepsy (25.8%). Ten were developmental delay, and eleven had neurological abnormalities. Events occurred during wakefulness in 16 (51.6%, P<0.05); during sleep in 7 (22.6%); in both awake and sleep in 7 (22.6%). On semiology, 20 had behavioral features (64.5%), 10 with arrest of activity, 8 with staring, 6 with crying and 5 with vocalization. 23 had motor features (74.2%) and 9 had autonomic features (29.0%). Events classification: 8 staring spell (25.8%), 7 normal infantile behavior (22.6%), 7 sleep myoclonus (22.6%), 4 shuddering attacks (12.9%), 4 infantile masturbation (12.9%), one tic, onechoreoathetosis, one hyperekplexia, one gastro-esophageal reflux and one episode of discomfort. Conclusion: Paroxysmal non-epileptic events are very common in infants and toddlers. Males were more than female in the study group. Non-epileptic staring spell is the most common PNEEs seen in this age group.

Foundation Trust, Preston, UK; ***University of Glasgow and Royal Hospital for Sick Children, Glasgow, Glasgow, UK; Tayside Children's Hospital, Dundee, UK; Leeds General Infirmary, Leeds, UK; and University of Nottingham, Nottingham, UK
Purpose: To assess the quality of paediatric care for UK children, young people and families affected by epilepsies and seizures. Method: In 2009, the Royal College of Paediatrics and Child Health (RCPCH) Epilepsy 12 Audit began a pragmatic audit of UK paediatric epilepsy care against national guidelines. A project board representing UK stakeholders invited participation from all relevant local hospital and community paediatric services. Audit domains were: 1. clinical service description; 2. 12 clinical performance indicators and 3. a specially developed patient-related experience measure (PREM). The service description was completed at the onset. Lists of children referred for electro-encephalography helped identify eligible children aged 1 month to 16 years who had received a first paediatric assessment for afebrile paroxysmal episode(s) within a 6 month period from 2009. Retrospective data from case-notes review of the subsequent 12 months were entered onto a web-based database. Children commenced on anti-epileptic medication were invited by letter to complete an anonymised PREM questionnaire. Result: Data collection was completed in November 2011 and is currently undergoing further analysis. All 197 audit units and 21 regions enrolled. Participation rates were 98% (193/197) for clinical service description, 94% (186/197) for clinical audit and 87% (172/197) for PREM domains. The clinical cohort consisted of 4991 patients, median age 6.3 years, M:F 54:46%. 44% (2175/4991) of first paediatric assessments occurred within an acute presentation. 19% (974/4991) of children had a documented neurodisability. Diagnosis of paroxysmal episode(s) at first assessment was recorded as: 46% (2298/4991) epileptic; 18% (897/ 4991) non-epileptic and 36% (1796/4991) uncertain. Diagnosis after 12 months of care was recorded as: 6% (312/4991) single or single cluster epileptic seizure(s); 36% (1774/4991) 2 or more epileptic seizures; 44% (2198/4991) non-epileptic and 14% (707/4991) uncertain. Conclusion: The paediatric epilepsy community, including acute and community services and patient organisations, has contributed to the largest description of the performance of paediatric epilepsy care in the UK to date. From the preliminary analysis, just over half the children with paroxysmal episode(s) presented non-acutely with one third eventually diagnosed as having recurrent epileptic seizures. Over the 12 months of follow-up, diagnosis varied and diagnostic uncertainty decreased. Final results will be placed in the public domain in September 2012.

050 EPILEPSY12 - UNITED KINGDOM COLLABORATIVE CLINICAL AUDIT OF HEALTH CARE FOR CHILDREN AND YOUNG PEOPLE WITH SUSPECTED EPILEPTIC SEIZURES C. Dunkley*, B. Waldron, R. Maini, F. Williams, A. Brown, R. Ranmal, D. Flower**, F. Colaco, K. Bowyer, L. Notghi, K. Martin, R. Chin, H. Basu, J. Paton***, M. Kirkpatrick, C. Ferrie, and W. P. Whitehouse *Sherwood Forest Hospitals, Sutton in Ashfield, UK; Leicester Children's Hospital, Leicester, UK; University of Dundee, Dundee, UK; Nottingham University Hospitals NHS Trust, Nottingham, UK; Royal College of Paediatrics and Child Health, London, UK; **Bristol Royal Hospital for Children, Bristol, UK; Scottish Children's Research Network, Dundee, UK; Birmingham Children's Hospital, Birmingham, UK; University of Edinburgh and Royal Hospital for Sick Children, Edinburgh, UK; Lancashire Teaching Hospitals NHS
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

051 YOUNG ADULT ISCHEMIC STROKE-RELATED ACUTE SYMPTOMATIC AND LATE SEIZURES: RISK FACTORS R. Roivainen, E. Haapaniemi, J. Putaala, M. Kaste, and T. Tatlisumak Helsinki University Central Hospital, Helsinki, Finland
Purpose: We assessed risk and baseline factors associated with acute symptomatic seizure (ASS, occurring < 7 days), and late poststroke seizure (LPS, > 7 days) after ischemic stroke in young adults. Method: We included all consecutive patients aged 15 to 49 with firstever ischemic stroke (n=1008) between 1994 and 2007 treated at the Helsinki University Central Hospital, using Cox proportional hazard models to identify factors associated with seizures. Adjustment was for age, gender, vascular risk factors, admission hyperglycemia (> 6.1 mmol/L) and hyponatremia (< 137 mmol/L), use of psychiatric medication, stroke severity (NIH Stroke Scale), and anatomic (Bamford criteria) and etiologic (Trial of Org in Acute Stroke Treatment) stroke subtype. Result: ASSs emerged in 35 (3.5%) patients. LPSs (n=102) occurred at a cumulative rate of 6.1% at 1 year to 11.5% at 10 years. In multivariate

17 Abstracts
analysis, anxiolytic use at time of index stroke (hazard ratio 13.43, 95% confidence interval 3.9146.14), moderate stroke severity (3.95, 1.86 8.41), cortical involvement (3.69, 1.668.18), and hyponatremia (3.26, 1.417.57) were independently associated with ASSs. Risk factors for LPSs were total anterior circulation infarct (15.94 7.6233.33), partial anterior circulation infarct (3.48, 1.527.93), history of ASS (3.94, 2.07 7.48), antidepressant use at the time of LPS (3.88, 2.466.11), hemorrhagic infarct (1.94, 1.193.15), male gender (1.79, 1.102.92), and hyperglycemia (1.62, 1.052.51). Conclusion: Despite the more heterogeneous etiologic background of ischemic stroke in young adults, major risk factors are similar to older patients. Risk factors for ASS and LPS differ and include factors that are not directly related to stroke characteristics. regional neurosciences centre. Patients in whom VGKC antibodies were identified were given immunotherapy in addition to their antiepileptic drug (AED) therapy. Clinical characteristics and response to immunotherapy were analysed. Result: Out of 128 patients tested, 4 had high titres of VGKC antibodies (>400 pM). Three are male, age range was 36 to 77 years. Seizure semiology was suggestive of temporal lobe onset in all patients. All patients had on going seizures in spite of treatment with AED. One patient had CASPR2 antibodies, the other 3 were negative for both LGI1 and CASP2 antibodies. One patient had thymic enlargement. All patients were given immunotherapy with steroids and azathioprine, resulting in fall in VGKC titres. In the patient with thymic enlargement VGKC titres fell following thymectomy. All patients experienced improvement in seizure control with immunotherapy, and 3 have remained seizure free. Conclusion: Identifying patients with VGKC antibodies associated with epilepsy has significant therapeutic implications, as immunotherapy appears to result in complete control of previously AED resistant seizures. The pathogenic antibody in patients presenting with epilepsy maybe directed towards an as yet unidentified component of the VGKC receptor complex.

Purpose: To systematically review recent studies on efficacy and safety of ketogenic diet in pediatric refractory epilepsy. Method: Literature reviewed using Medline searches and Cochrane Library with the keywords epilepsy/therapy, refractory epilepsy, and the text word ketogenic diet. Bibliographies of papers located by searches and review articles were compiled. Papers published after year 2000, from various subcontinents worldwide, reporting use of ketogenic diet in children <18 years of age with medically refractory epilepsy of varied etiology like mitochondrial disorders, cortical dysplasia and symptomatic epilepsy were selected. The outcome measures used were the percentage of patients with complete elimination of seizures and >50% reduction in seizures, deaths and diet related adverse events. Result: Nineteen studies met all criteria for inclusion. It included 6 retrospective, 6 prospective, 2 multicentric trials, 3 systematic reviews and 2 randomized controlled trials. The estimated proportion for obtaining complete seizure control by combined analysis (confidence profile method) was 29.31% (95% confidence interval [CI]: 0.26310.3250) and was 41.81% (95% CI: 0.3838 0.4531) for greater than 50% reduction in seizures. Common adverse events observed were gastrointestinal disturbances, infrequent lipid abnormalities and renal stones, however few deaths 1.29%(CI: 0.66 2.21) were reported while on the diet. Conclusion: There is strong upcoming evidence in last decade to support the safe and effective use of ketogenic diet in children with refractory epilepsy.

054 EPILEPSY AND OTHER NEUROLOGICAL MANIFESTATIONS ASSOCIATED WITH TUBEROUS SCLEROSIS COMPLEX P. Major*, F. Mathieu, L. Ct*, L. Crevier*, A. S. Kristof, and J. Landry *CHU Sainte-Justine - Universit de Montral, Montral, Canada; University of Toronto, Toronto, Canada; and McGill University, Montral, Canada
Purpose: Tuberous sclerosis complex (TSC) is a frequent cause of structural focal epilepsy. This study aims to describe the characteristics of epilepsy and associated neurological manifestations in a large population of patients with TSC. Method: Retrospective analysis of all patients who were admitted to the hospital or evaluated in the emergency room at the CHU Sainte-Justine (Montral) with a diagnosis of definite TSC from January 1987 to July 2011. Result: In 98 patients with a definite diagnosis of TSC, 79 (80%) had epilepsy. The average age at seizure onset was 0.8 years (range = 0 to 8 y; SD = 1.6 y). Intractable epilepsy was found in 28/79 (35%), including 2 patients who became seizure free after surgery. Average age at last follow-up visit was 18 years (range = 0 to 43 y; SD 10). Developmental delay was diagnosed in 56 (57%) patients, including 47 (83%) with epilepsy and 22/56 (40%) with intractable epilepsy. Of 12 (12%) patients with autistic spectrum disorder (ASD), 11 (92%), and 5/12 (42%) had intractable epilepsy. By mutational analysis (25/98 patients), epilepsy was reported in 16/18 (89%) patients with mutations in TSC2, and in 2/4 (50%) patients with mutations in TSC1. Of the patients with subependymal giant cell astrocytoma (SEGA) (10/98), 5 underwent surgery, and 3 were treated with mTOR inhibitors. Conclusion: In patients with TSC attending a tertiary center, epilepsy, developmental delay, and ASD were common. Epilepsy was usually first observed in the first year of life, and was intractable in one third of patients.

Symptomatic Epilepsy Wednesday, 03 October 2012

Purpose: Voltage gated potassium channel (VGKC) antibodies are directed against trans-synaptic and neuronal cell adhesion molecules. Recent studies have identified the presence of these antibodies in various cohorts of patients with epilepsy, and have suggested a potential aetiological role for VGKC antibodies in epilepsy. Method: We have undertaken systematic testing for VGKC antibodies in patients with otherwise unexplained adult onset epilepsy, seen at a

055 TRAUMATIC BRAIN INJURY AND SUBSEQUENT RISK OF UNPROVOKED SEIZURES: A POPULATION-BASED CASE-CONTROL STUDY B. Mahler, C. Adelw, T. Andersson, A. Ahlbom, and T. Tomson Karolinska Institutet, Stockholm, Sweden
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

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Purpose: To study traumatic brain injury as risk factor for unprovoked epileptic seizures in a population based cohort with incident seizure cases. Method: In this population based case-control study, cases were 1885 patients with new onset unprovoked seizures included in the Stockholm Incidence Registry of Epilepsy. Controls, in total 15080-matched for gender, year of diagnosis, and catchment area- were randomly selected from the register of the Stockholm County population. Exposure was defined as a hospital discharge diagnosis of a traumatic head injury preceding the date of seizure onset. Odds ratios (ORs) were calculated to assess the risk of developing unprovoked seizures after hospital admission for various categories of head trauma defined by ICD codes from the Swedish Hospital Discharge Registry. Result: Odds ratio (OR) with 95% confidence interval (95%CI) for unprovoked epileptic seizures was 2.75 (2.193.45) after a discharge diagnosis of head trauma, 1.93 (1.462.55) after cerebral concussion and 8.86 (5.5514.15) after a more severe brain injury (contusion or traumatic intracranial hemorrhage). The risk of developing unprovoked seizures was highest during the first year, OR 5.42 (2.6111.27) after cerebral concussion and 30.53 (10.1292.09) after severe head injury. The risk declined gradually with time but still ten years after the trauma OR was 1.88 (1.272.79) for concussion and 2.44 (0.678.88) for severe head injury. Conclusion: We provide quantitative data on the risk of developing unprovoked seizures over time after brain trauma of different severity. Although highest the first year, the risk remains increased ten years after the trauma.

Basic Science 2 Wednesday, 03 October 2012

Purpose: The mammalian target of rapamycin (mTOR), a kinase regulating in the brain several physiological functions, seems to be involved in many CNS pathologies.1 Previous work in animal models of convulsive epilepsies, have suggested that mTOR modulators have beneficial antiepileptogenic effects. Method: We investigated the effect of some treatment schedules (earlychronic; sub-chronic; acute) with the mTOR inhibitor rapamycin, on the development of absence-seizures, seizure parameters and depressive-like behavior in WAG/Rij rats, a genetic model of absence epilepsy, epileptogenesis and mild-depression comorbidity. Furthermore, we studied the interaction between rapamycin and lypopholysaccharide (LPS) administration, which is known to aggravate absence seizures through increased inflammatory responses.3 Result: Rapamycin (early-chronic) exhibited antiepileptogenic properties also in this animal model; this effect was accompanied by pro-depressant effects. Both acute and sub-chronic (7day) treatments also had antiabsence properties, but the sub-chronic treatment produced contrasting anti-depressant properties in WAG/Rij rats not seen in Wistar rats. The rapamycin/LPS co-administration studies showed that rapamycin blocked/prevented LPS-dependent increase in absence-seizures, suggesting an anti-inflammatory-like protective action. Conclusion: Concluding, we demonstrated a novel rapamycin antiepileptogenic effect in a well-established absence epilepsy animal model; we suggest that this effect may be mediated by inhibition of inflammatory processes during epileptogenesis. The action of rapamycin and the role of mTOR on glial cell-mediated inflammation have never been studied before in epilepsy models; our experiments suggest new insights into this intriguing field which deserves to be further explored. References: 1 Garelick, Kennedy. Exp Gerontol. 2011 46:155. 2 Russo et al. Molecular Neurobiology. 2012. 3 Kovcs et al. Brain Res Bull. 2011 85:410.

Purpose: The present study is aimed to define the clinical characteristics and outcome of tumoral epilepsy. Method: This study is a section of the PERNO project - a prospective registry of Primary Brain Tumours (PBT) in Emilia-Romagna Region spanning a three year period (20092011). All patients with epileptic seizures were included in the study and followed up on a regular basis. Seizure semiology, tumour location and histology, and response to treatments were analyzed. A consent form was obtained by each patient or responsible guardian. Result: Out of 610 PBT cases collected over the first two years, 114 (19%) had epileptic seizures. Sufficient data for analysis are available for 107 (67 male and 40 female) patients. Seventy one patients (66%) had malignant PBT, mainly involving the frontal (61%) or temporal (36%) lobes. Seizures were the first symptom in 80 cases (75%) and led to the diagnosis on PBT in most cases. Seizure types were focal motor (27%), somato-sensitive (11%) or tonic-clonic (26%). High seizure frequency at the onset was observed in 21% of cases and status epilepticus in 10%. Preliminary follow up data are available in 59 cases with malignant gliomas and show an initial drug-resistance of the seizures, which are usually halted only by surgical treatment. Conclusion: In this group of mainly malignant PBT the seizures appear lesion-dependant: they are the initial symptom of the tumour, herald its relapse and may be controlled only by surgery. This project was funded by the Research Program Regione-Universit 20072009 Area 1a Innovative Research.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

058 DEVELOPMENTAL CHANGES IN THE NUMBER OF GABAERGIC NEURONS OF THE THALAMIC RETICULAR NUCLEUS IN ABSENSE EPILEPSY RATS ldy z*, and O. Kirazly * F. Onat*, S. Cavdar, H. Hacioglu*, S. Yy *Marmara University Medical School, Istambul, Turkey; and _ Koc University, Istanbul, Turkey
Purpose: Absence epilepsy models have shown that the production of seizures is related to an excess of GABAergic neurotransmission in the thalamus. The major source of GABAergic fibers to thalamic nuclei are from thalamic reticular nucleus (TRN). GABAergic neurotransmission in the thalamus and TRN plays a critical role in the generation and control of spike-and-wave discharge (SWDs) in absence epilepsy. This study aims to quantify the number of GABAergic neurons in the TRN developmentally (P10, P20, P30 and P60 days) of Wistar rat (n=5 for each developmental group) and compare the results with Genetic

19 Abstracts
Absence Epilepsy Rats from Strasbourg (GAERS; n=5 for each developmental group). Method: The intermediate TRN was removed from each animal and the GABAergic neurons were labelled using light-microscopy GABA immunohistochemistry. The disector method was used for the quantification and the data was statistically analysed. Result: The number of GABA labelled neurons in the TRN of Wistar animals showed reduction with increasing development (from P10 to P60), but was not statistically significant. However, the GAERS showed an increase in the number of GABA+iv neurons with increasing development between P10 and P60. The correlation of the number of GABA+iv neurons of each developmental group between Wistar and GAERS animals showed statistically significant difference in P30 (p=0.045) and P60 (p=0.011). Conclusion: The increase in the GABA+iv neurons, with development in GAERS, is likely to be related to the generation of SWDs or it may represent a compensatory response of the TRN to the thalamocortical circuitry in the absence seizures. Purpose: Temporal lobe epilepsy is characterized by a sclerosis of the hippocampus (Ammon's horn sclerosis) with a specific loss of pyramidal cells in CA1 and mossy cells in the hilus. Excitatory granule cells survive, but show a reorganization of their axonal connections. Their axons, the mossy fibres, loose their target cells due to mossy cell death and sprout backwards into the granule cell layer. It was suggested so far, that this leads to a recurrent, excitatory circuit. The aim of this study was to examine the target cells of mossy fibre sprouting, and determine whether mossy fibres impinge only on granule cells or also on other neurons, in particular inhibitory interneurons (basket cells). Method: Mossy fibres were traced with neurobiotin. In addition double immunohistochemistry against synaptoporin (mossy fibres) and parvalbumin (basket cells) was used. Synapses were examined with electron microscopy, labelled in addition with post-embedding gamma-aminobutyric-acid (GABA)-immunogold. Result: In human epileptic hippocampi sprouted mossy fibres innervated not only excitatory granule cells but also inhibitory interneurons. In addition, we show that the inhibitory axonal plexus around granule cells is preserved and that the number of inhibitory axon terminals exceeds the number of excitatory sprouted mossy fibre terminals on granule cells. Conclusion: Sprouting of mossy fibres does not simply results in an excitatory circuit of granule cells because recurrent mossy fibres also innervate inhibitory interneurons. This might lead to increased inhibition and synchronization of granule cells because the extensive inhibitory axonal plexus is preserved and shows an additional innervation through sprouted mossy fibres.

059 THE DISEASE-MODIFYING EFFECT OF CARISBAMATE IN THE LITHIUM-PILOCARPINE MODEL OF TEMPORAL LOBE EPILEPSY TRANSLATES INTO PRESERVED COGNITIVE FUNCTIONS J. Faure*, G. Akimana*, E. Marques*, J. Cassel*, and A. Nehlig *Universit de Strasbourg-CNRS, Strasbourg, France; and INSERM, Faculty of Medicine, Strasbourg Cdex, France
Purpose: Temporal lobe epilepsy (TLE) is one of the most frequent and disabling epilepsy forms. Since many patients are pharmacoresistant, new antiepileptic and antiepileptogenic drugs are needed. A recent study from our laboratory using a new drug, carisbamate (CRS), in the rat lithium-pilocarpine (li-pilo) model of TLE reported that CRS was neuroprotective and displayed disease-modifying effects in a subgroup of rats. These rats did not develop TLE but pharmacosensitive absence-like epilepsy (ALE). Here we studied the consequences of this neuroprotection on cognitive skills of ALE compared to TLE rats. Method: Lithium-pilocarpine or saline were administered to 55 adult rats. A 90 kg/mg dose of CRS or saline was given one hour after status epilepticus (SE) onset, repeated eight hours later and during six more days. The rats were video-monitored for two months and then their behavioral abilities were investigated. Tests including actography, plus-maze, beam-walking, Morris water maze, radial arm maze, double-H maze, and five-choice serial reaction time task were used. Result: The appearance of ALE occurred together with widespread neuroprotection in 8/25 CRS-treated rats. ALE rats that underwent li-pilo SE and CRS treatment did not present significant cognitive impairments compared to control rats. TLE rats, treated or not with CRS, performed significantly worse than control and ALE rats in all tests. Conclusion: The rats treated with CRS that developed ALE displayed nearly complete preservation of cognitive functions. Thus, treatment with this new drug has powerful disease-modifying effects that translate into both neuroprotection and impressive preservation of cognitive abilities.

Basic Science 1 Monday, 01 October 2012

p061 CHARACTERISING SEIZURE EVOLUTION IN PATIENTS WITH IDIOPATHIC GENERALIZED EPILEPSY USING A COMPUTATIONAL MODEL J. R. Terry*, A. Nevado-Holgado, F. Marten, and M. P. Richardson *University of Exeter, Exeter, UK; University of Oxford, Oxford, UK; University of Bristol, Bristol, UK; and King's College London, London, UK
Purpose: We propose that the dynamic evolution of EEG activity during epileptic seizures may be characterised as a path through parameter space of a computational model, reflecting gradual changes in underlying physiological mechanisms. Method: We use an evolutionary algorithm to estimate parameters of a computational model, according to the best fit obtained between the model output and specific features of the clinically recorded EEG waveform. We then evaluate the evolution of these parameters across the spike-wave discharge, by subdividing the discharge into individual spike-wave cycles and estimating parameters for each individual cycle. Result: We find that model parameters evolve consistently when different spike-wave discharges from an individual patient are considered. We further find that these evolutions vary between patients. Conclusion: Our study shows that variations in different underlying mechanisms can give rise to macroscopic dynamics (such as those recorded using EEG) that appear indistinguishable using standard clinical analysis tools. Our findings suggest that the evolution of model parameters is a useful tool for identifying subtle variations in EEG dynamics that may ultimately be useful for characterising epilepsy type and distinguishing between patients whom at present are given the same diagnosis.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x


20 Abstracts
p062 COMPUTER ASSISTED ANALYSIS OF ELECTRICAL STIMULATIONS DURING STEREO-EEG RECORDINGS OF PRE-SURGICAL EPILEPTIC PATIENTS D. F. Boido*, S. Francione, V. Gnatkovsky*, and M. De Curtis* *Istituto Neurologico C. Besta, Milan, Italy; and Ospedale Niguarda C Granda, Milan, Italy
Purpose: Surgical intervention is a preferred choice for the treatment of patients suffering from drug-resistant focal epilepsy. Invasive studies with intracerebral electrodes are routinely performed when the boundaries of the epileptogenic zone (EZ) are not well defined. During this procedure, low-frequency bipolar stimulation (3ms-3mA pulses at 1 Hz for 30s) at each recording site is systematically performed to identify EZ and to functionally map the explored region. Nowadays the analysis of the recorded electrical responses to these stimulations is performed by experienced physicians, prevalently by visual inspection with time-consuming protocols. Method: We developed an original computer assisted algorithm to analyze evoked responses based on Labview; mono or bipolar responses of each tested couple of contacts are averaged and reliability assessed. Averaged responses selected on the base of their amplitude/area and features (peak amplitude, delay and area) are computed and stored. 3D-plot of all the idealized responses are made available for interactive inspection and quantitative measures. Result: Evoked responses are divided into three reliable consecutive phases. By comparing these phases it is possible to appreciate physiological and pathological connectivity between EZ and surrounding tissue. Conclusion: Our analysis suite proved to be useful to assist the evaluations of physicians in order to establish both the epileptic zone borders and the functional connectivity of the explored region. Moreover it is a valuable instrument for testing basic research hypothesis. down this hierarchical tree the decision rules guide the path either to the left or right child node. The exact split values, and which network characteristics are assigned to which nodes, is found by fitting a decision tree to given training data with known outcome labels. Our model had the highest accuracy if trees were based on random selected subsets of 5 network characteristics (out of 18). Accuracy was defined as the proportion of both true positives and negatives. Eventually, the lowest tree nodes direct to the binary outcome labels: partial epilepsy or control. After building the random forest diagnostic prediction model, we assessed the ability to differentiate between children with and without partial epilepsy using the areas under the Receiver Operating Characteristic curve (AUC). Since the AUC is typically considered to be optimistic when testing the diagnostic model on the same data, we used internal validation methods to correct for this. Result: Based on epileptiform EEG activity only, the diagnosis of epilepsy was supported with a sensitivity and specificity of 0.77 and 0.91 respectively. Power spectral density of EEG measures revealed no differences between patients and the control group. Furthermore, none of the individual network characteristics used in our prediction model, was significantly different between groups. In contrast, the prediction model had a sensitivity of 0.96 [95% confidence interval (CI): 0.781.00] and specificity of 0.95 [95%CI: 0.761.00] in correctly differentiating patients from controls. Best model performance was found for the broadband frequency, with an AUC of 0.74. Conclusion: Diagnostic accuracy in children with partial epilepsy is highly improved with a diagnostic prediction model combining functional network characteristics derived from multi-channel EEG recordings. Early accurate diagnosis is particularly valuable in children to inform and guide parents, to prompt treatment decisions and to limit the period of uncertainty and unnecessary risks.

p063 PARTIAL EPILEPSY IN CHILDREN CAN BE PREDICTED WITH FUNCTIONAL NETWORK CHARACTERISTICS E. G. A. L. Van Diessen*, W. M. Otte*, K. P. J. Braun*, C. J. Stam, and F. E. Jansen* *UMCU, Utrecht, The Netherlands; and VUmc, Amsterdam, The Netherlands
Purpose: In children referred with a possible diagnosis of partial epilepsies interictal electroencephalogram (EEG) is routinely performed but appears to be normal in many cases. In addition, evaluation of EEG abnormalities may be subjective and not very sensitive. In this study, we aimed to develop a multivariable diagnostic prediction model based on EEG functional network characteristics. Method: Routinely performed interictal EEG recordings of 35 children diagnosed with partial epilepsies, and of 35 children in whom the diagnosis epilepsy was excluded (control group), were analyzed (11 girls and 24 boys, mean age 10 3 years). Children with partial epilepsy were individually matched on gender and age with children from the control group. Neither patients nor controls had a developmental delay, a history of febrile seizures, generalized epilepsy or were on chronic anticonvulsive medicine. Resting-state EEG epochs, free of abnormal slowing or epileptiform activity, were selected to construct functional networks of correlated activity. We calculated multiple network characteristics often used in functional network epilepsy studies and included them as predictors in a diagnostic prediction model. We used the random forest classifier, a robust ensemble algorithm, as a model. The core of the random forest classifier is the binary decision tree, a data type that stores elements hierarchically in nodes. One node represented a network characteristic and is followed by two children nodes. In the process of building a binary decision tree, decision rules are formed (split values). If we follow a path
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

p064 SPATIO-TEMPORAL MODELS TO PREDICT AND CONTROL EPILEPTIC SEIZURE DYNAMICS G. Baier, M. Goodfellow, P. N. Taylor, Y. Wang, and D. J. Garry Manchester Interdisciplinary Biocentre, Manchester, UK
Purpose: EEG/MEG and fMRI studies have revealed complex spatiotemporal patterns of brain activity during focal-onset and generalised epileptic seizures. The origins and mechanisms of these phenomena at the macroscopic scale are important for the elaboration of new ways of treatment in epilepsy. For example, predictions of the effect of stimulation of the epileptogenic network, (as in closed loop seizure termination devices), require knowledge about how neuroanatomical location correlates with widespread abnormal activity. Here we demonstrate the use of computational modelling of spatio-temporal epileptic patterns to interpret clinical recordings of epileptic seizures. Method: Mathematical multicompartment models of large regions of brain tissue on the macroscopic scale are introduced to explain spatiotemporal features of distinct seizure types in terms of interacting excitatory and inhibitory neural populations. The model connectivity is based on connectivity data from diffusion-tensor imaging in humans. Bifurcation studies from nonlinear dynamics, and quantitative interrelation measures from multivariate data analysis are applied for model validation and parameter estimation. Model output is compared quantitatively to clinical EEG recordings. Result: Large-scale multi-compartment models can recreate generic features of epileptic EEG in humans. Specifically, the distribution of spatial heterogeneities and heterogeneities in the connectivity lead to robust patient-specific epileptic patterns while allowing for large inter-patient variability. Knowledge of the distribution of heterogeneities (e.g. in the cortex) allows to optimise stimulation protocols to suppress seizure activity. Conclusion: Spatiotemporal computational models of the macroscopic neuropathophysiology in humans are a novel tool to describe epileptic seizure dynamics and provide a rationale to design patient-specific predictions protocols for stimulation therapy.

21 Abstracts
p065 GLUTATHIONE TRANSFERASE POLYMORPHISMS IN PATIENTS WITH PROGRESSIVE MYOCLONIC EPILEPSY M. Ercegovac*, V. Coric, T. Simic, N. J. Jovic, D. V. Sokic, J. Jakovljevic, M. Kecmanovic, D. M. Nikolic**, S. M. Jankovic*, A. Savic-Radojevic, and M. Pljesa-Ercegovac *Clinic of Neurology, Clinical Center of Serbia, Belgrade, Serbia; Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Serbia, Belgrade, Serbia; Clinic of Neurology and Psychiatry for Children and Youth, Belgrade, Serbia; Clinic of Neurology Clinical Center of Serbia, University of Belgrade, School of Medicine, Belgrade, Serbia; University of Biology, Belgrade, Serbia; and **Belgrade University Medical School, Belgrade, Serbia
Purpose: It has been reported that increased generation of free radicals or reduced activity of antioxidative defense mechanisms can cause some types of epilepsy and in addition, increases the risk of seizure recurrence. Glutathione transferases (GST) are superfamily of enzymes involved in detoxification and protection from oxidative damage. We hypothesized that genetic polymorphism of GSTM1, GSTT1, GSTA1, GSTO1and GSTP1may be associated with progressive myoclonus epilepsies (PME). Method: Genomic DNA was isolated from 26 patients with PME (Unverricht-Lundborg disease, Lafora body disease, Myoclonic Epilepsy with Ragged Red Fibers, ceroidlipofuscinosis) and 68 controls, matched for sex and age. The GSTA1, GSTO1 and GSTP1 genotypes were identified by PCR-restriction fragment length polymorphism method (RFLP). GSTM1 and GSTT1 genotypes were determined by multiplex PCR. Result: The frequency of GSTA1 low activity genotype TT was lower in patients with PME (3.8%) compared to controls (11.8%) (OR=0.27, p>0.05). Distribution of GSTM1 genotype did not significantly differ between cases and controls. Namely, GSTM1-null genotype was found in 51.5% controls and 53.8% cases (OR=1.10, p>0.05). Regarding GSTO1, low activity genotype AA was lower in patients with PME (3.8%) compared to controls (8.8%) (OR=0.5, p>0.05). The frequency of GSTP1 low activity genotype AG was lower in patients with PME (34.6%) compared to controls (44.1%) (OR=0.69, p>0.05). GSTT1-null genotype was found in 61.5% of patients with PME, which significantly differed from controls in which it was present in 25% (OR=4.80, p=0.001). Conclusion: It can be concluded that presence of GSTT1-null genotype increases the risk for progressive myoclonic epilepsy. psychological evaluation (Rey Auditory Verbal Learning Test, The ReyOsterrieth Complex Figure Test and Wechsler Memory Scale) focused to determine memory affection. We divided them into two groups: epilepsy with memory affection and epilepsy without memory affection and results were compared with those found in experiments using autopsy material. Result: Memory affection was found in 10 patients with MTLE (83%) and in 2 patients with TLE secondary to vascular lesion or tumor (18%). These patients demonstrated disturbances in short and/or longterm memory, including visual and/or verbal memory. Patients with memory disturbances demonstrated higher D1 receptors binding values (38%, p>0.05) in all cortical layers, when compared with patients without memory affection. No further comparisons were significantly different. Conclusion: Previous studies show that too much or too little stimulation of D1 receptors leads to working memory deficits. The present study indicates that patients with TLE showing high D1 receptor present a deleterious effect on memory. This effect may be associated with excessive D1 receptor stimulation. Study supported by CONACyT (project 98386).

p067 RARE CLINICAL FEATURE OF EPILEPSY, REPORT OF TWO CASES M. Nadeem Nishtar Medical College, Multan, Pakistan
Purpose: How Epilepsy causes abnormal behaviours that is false agressive. Method: Two patients 23 year and 27 year old with epilepsy were observed for three years, presented with false (pretended) agressive behaviour. When ever they want to flippant with other people, they fight and beat them. The intensity of fighting is low than original intensity. so in daily life activities, epilepsy patient present with false agressive behaviour. It is their way to flippant with others. The patients suffering from epilepsy have manifested a false aggressive behavior. This has been observed that such patients during showing aggressive behavior, do not want to give physical damage. Result: Although epilepsy causes abnormal behaviours, but abnormal false agressive behaviour is also caused by epilepsy. Conclusion: Abnormal false agressive behaviour is also caused by epilepsy.

p066 DOPAMINE RECEPTORS IN NEOCORTEX OF PATIENTS WITH TEMPORAL LOBE EPILEPSY: CORRELATIONS WITH MEMORY DISTURBANCES M. P. Mata Mendoza*, J. M. Cisneros-Franco, A. R. Martnez, M. A. Alonso Vanegas, and L. L. Rocha* *Center for Research and Advanced Studies, Distrito Federal, Mexico; and Instituto Nacional de Neurologa y Neurociruga, Distrito Federal, Mexico
Purpose: To correlate abnormalities in binding to D1 and D2 receptors as well as dopamine transporter in temporal cortex with memory disturbances of surgically treated patients with pharmacoresistant temporal lobe epilepsy (TLE). Method: By autoradiography experiments, D1 and D2 receptors and dopamine transporter binding was evaluated in temporal neocortex obtained from autopsies (n=8) and patients with TLE associated with mesial sclerosis (MTLE, n=12) and with TLE secondary to tumor or vascular lesion (n=11). The values obtained were correlated with neuro-

Purpose: Methyl CpG binding protein-2 (MeCP2) is a multifunctional nuclear protein. MeCP2 plays an important role in regulating dendritic morphology, mediating synaptic transmission, spontaneous neurotransmission and short-term synaptic plasticity in the central nervous system (CNS). Our aim was investigate the expression of MeCP2 mRNA and protein in intractable temporal lobe epilepsy patients and experiment animals. Method: Using reverse transcription polymerase chain reaction (RTPCR), immunohistochemistry and double label immunofluorescence, we detected MeCP2 expression in 35 temporal neocortex tissue samples from patients with intractable temporal lobe epilepsy (TLE) and 14 histological normal temporal lobe tissue samples from the control group. We also examined the timing of MeCP2 expression in the hippocampus and
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

22 Abstracts
adjacent cortex of rats with temporal lobe epilepsy (lithium chloride-pilocarpine model) at 1, 2, 7, 14, 30, and 60 days after kindling and the control group. Result: MeCP2 is expressed mainly in the nucleus of neurons, not expressed in astrocyte. MeCP2 expression was significantly higher in the TLE group and experiment animals group as compared with the control group. The expression of MeCP2 in the rat hippocampus and adjacent cortex after seizures gradually increased during the acute period (1, 2 days) and the latent period (7.14 days) but decreased during the chronic period (30.60 days). Conclusion: The up-regulation of MeCP2 in intractable TLE patients and experiment animals suggest that MeCP2 may involved in the pathogenesis of TLE.

Mario Negri Institute for Pharmacological Research, Milano, Italy

Purpose: We studied the role of TLR4 and RAGE in epileptogenesis using a mouse model of mTLE. These receptors are activated by endogenous proinflammatory danger signals, such as High Mobility Group Box 1 released in injured brain and previously shown to play a pivotal role in ictogenesis (Maroso et al, Nature Med, 2010). Method: C57BL/6 adult male wild-type mice (WT) were intrahippocampally injected with kainate to induce status epilepticus (SE) and spontaneous recurrent (drug-resistant) epileptic activity. Age and gendermatched C57BL/6 TLR4 and RAGE knock-out (KO) mice were similarly treated. We compared mice for epilepsy development, cognitive performance, neuropathology and neurogenesis (doublecortin, DCX staining) Result: SE duration and severity and the onset time to spontaneous epileptic activity were similar in all groups. However, the frequency of epileptic events was significantly reduced by 60% and 30% in TLR4 and RAGE KO, respectively, vs WT mice. Epileptic mice of either genotype and WT epileptic mice had similar memory impairment, comparable cell loss (except in CA1 where RAGE KO showed increased neurodegeneration) and granule cell dispersion. DCX staining was absent in epileptic WT and RAGE KO mice; notably, DCX positive cells were present in epileptic TLR4 KO mice similarly to non epileptic control mice. Conclusion: Activation of RAGE and TLR4 signaling by endogenous danger signals significantly contributes to the severity of epilepsy developing after SE. These receptors differentially affect the fate of newly generated neurons and CA1 cell survival in epileptic tissue. Our findings highlight new molecular mechanisms involved in epileptogenesis.

p069 NETWORK TOPOLOGY AND SEIZURE INITIATION IN IDIOPATHIC GENERALISED EPILEPSY M. P. Richardson*, F. A. Chowdhury*, T. Fitzgerald, O. Benjamin, R. D. Elwes, L. Nashef, and J. R. Terry *King's College London, London, UK; University College London, London, UK; Bristol University, Bristol, UK; King's College Hospital, London, UK; and University of Exeter, Exeter, UK
Purpose: We examined whether brain network topology in normal interictal EEG differed between patients with IGE and normal controls. We then examined a dynamic model of seizure initiation based on these networks, attempting to relate altered network structure in IGE with a greater liability to generate seizures. Method: We studied 35 patients and 40 normal controls, using EEG (21 scalp electrodes, sampling 256Hz, filtered 0.370Hz). Phase synchrony between EEG electrodes was assessed in 5 frequency bands using EEGlab. Unweighted undirected graphs were constructed for each subject and band; nodal degree variance (D) and small world index (SWI) were calculated for each network and compared between groups. Using a phenomenological model of seizure initiation, we examined the exit time in the presence of noise, which we equate with seizure frequency. Result: Using nonparametric statistical tests and Bonferroni correction for multiple comparisons, we found that D was lower in controls than in patients in the beta and gamma bands (beta: p=0.040; gamma: p=0.032). SWI was greater in controls than patients in the beta band (p=0.031). We found that network structure in patients correlates with shorter escape times relative to network structures from controls, especially in beta and gamma bands. Conclusion: EEG networks of functional connectivity in beta and gamma bands differ significantly between IGE and normals. Networks based on patient data generate seizures more readily than normal networks in a dynamic model.

Purpose: Literature suggests that heart rate changes may precede or occur concurrently with some seizure types. Monitoring heart rate, therefore, may be a useful diagnostic in seizure prediction or detection in some patients with epilepsy. Method: We analyzed simultaneously recorded EEG and ECG data from a large patient population during an epilepsy monitoring unit stay to assess the prevalence and frequency of ictal tachycardia. A seizure was classified as exhibiting ictal tachycardia if the heart rate reached at least 100 bpm during the ictal period, and in comparison to the pre-ictal period, the heart rate increased by either 35 bpm or 55%. Additionally, we compared heart rate changes associated with seizures to those measured during moderate exercise. Result: Annotated seizures with complete clinical diagnoses from sixtyfour patients were analyzed. Thirty-four of these patients (53%) had at least one seizure that met the definition of ictal tachycardia. Further, 50% of all seizures (84 of 167) within this subset of patients (n=34) exhibited ictal tachycardia. Compared with moderate exercise, seizures defined as ictal tachycardia exhibited higher magnitude and more rapid changes in cardiac rate. Conclusion: The data indicate that ictal tachycardia is prevalent in patients that primarily exhibit complex partial seizures originating in the temporal lobe. The results suggest that heart rate changes associated with seizures may be distinguishable from other factors which affect cardiac rate such as exercise. Therefore, monitoring heart rate may serve as a viable diagnostic for indicating seizure onset or logging seizure occurrence.

Basic Science 2 Monday, 01 October 2012

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23 Abstracts
Purpose: In this work we addressed the molecular cause for the mitochondrial dysfunction in hippocampal subfields of patients with hippocampal sclerosis, one of the most common forms of therapy-resistant temporal lobe epilepsy. Method: Applying long-range PCR, single molecule PCR and a next generation sequencing approach we identified, quantified and mapped mitochondrial DNA deletions in hippocampal subfields of patients with temporal lobe epilepsy, who underwent epilepsy surgery. These mitochondrial DNA rearrangements are an accepted cause for mitochondrial dysfunction in various neuromuscular disorders and aging. Result: The deletion loads approached in the CA3 subfield and the dentate gyrus of patients with hippocampal sclerosis 28% of total mitochondrial DNA content. A major fraction of the detected deletions had the 3 breakpoint at a hot spot around np 16070 implying ROS-caused mitochondrial DNA double strand breaks as potential mechanism of deletion formation. High levels of deleted mitochondrial DNA appear to correlate with the presence of cytochrome c oxidase-negative and succinate dehydrogenate-positive neurons in the CA3 and CA4 hippocampal subfields. Hippocampal samples from age-matched patients with epilepsy due to lesions in the temporal lobe did not contain elevated levels of deleted mitochondrial DNA. Conclusion: Dysfunction of mitochondrial oxidative phosphorylation in the epileptic focus of patients with Ammon's horn sclerosis appears to be related to clonal expansion of specific types of deletions of mitochondrial DNA generated very likely by increased oxidative stress. This mechanism is proposed to be relevant for seizure generation in the sclerotic hippocampus of patients with temporal lobe epilepsy and Ammon's horn sclerosis. Result: Our results showed that TNF and NFKB1 were significantly upregulated in TLE+HS patients (p=0.0035 and p<0.02, respectively) while KL expression was significantly downregulated (p<0.02). Conclusion: This is the first study relating KL with HS and epilepsy. Our data suggest that TNFa might affect KL expression in hippocampus. As a multifunctional protein, our finding on KL downregulation in TLE+HS patients opens several possible avenues of research that will help us to understand the complex pathophysiology in HS.

p074 EPILEPSY AND SLEEP; A PERFECT MARRIAGE!!! I. J. Poddar, and K. M. Haridas KMC, Kolkata, India
Purpose: Older studies of patient-reported seizure precipitants have not evaluated whether different epilepsy syndromes are differentially affected with pricipitating factors mainly sleep. Method: Patients of a tertiary-care epilepsy center were consecutively surveyed with the use of a standardized questionnaire that lists precipitants that might trigger or exacerbate seizures . Patients were classified into epilepsy syndromes according to International League Against Epilepsy criteria. Age and gender within groups defined by major precipitants were compared. Pearson's correlation was performed to evaluate common patterns of precipitants Result: Of 500 patients, 58% cited at least one precipitant. In order of frequency, stress (22%), sleep deprivation (28%), sound and light flashes (26%), fever (08%), fatigue (03%) and others (13%). Stress, light and sound flashes, and sleep deprivation positively correlated. Rankings of precipitants varied within epilepsy syndromes, with patients with temporal lobe epilepsy citing sleep infrequently compared with patients with other epilepsy syndromes. Menstrual effects were ranked highly within major precipitants among women over age 14 and were especially noted by women with temporal lobe epilepsy (34%). Conclusion: Many patients with epilepsy identify a precipitant that triggers or exacerbates seizures. The high correlation of stress, sleep deprivation, and fatigue suggests that they act through common mechanisms to worsen seizure control. Through identification of the effect of both endogenous and exogenous precipitants among syndromes, more research and counseling can be directed to specific precipitants.

Purpose: Previous research in animal seizure models point to the pleiotropic cytokine TNFa as an important effector/mediator of neuroinflammation and cell death. One of the primary events in seizure induced cell death is the excessive release of glutamate with a consequent increase in intracellular calcium influx. Klotho (KL), originally identified as an antiaging protein, is emerging as an important calciophosphoregulatory hormone. Its cerebral function is unclear; however, the klotho knockout mouse exhibits a phenotype resembling human aging presenting neural degeneration and a reduction of synapses in the hippocampus. Moreover, it was demonstrated that TNFa down-regulates KL through NF-jB in animal models of chronic kidney disease and colitis. Our objective is to prove that a similar downregulation occurs in temporal lobe epilepsy patients with hippocampal sclerosis (TLE+HS). Method: We evaluated TNF, KL and NFKB1 relative mRNA expression levels by Reverse Transcription quantitative PCR in resected hippocampal tissue samples from 14 TLE+HS patients and compared them to four post mortem controls. Two pairs of reference genes were used: GAPDH and HPRT1 (classical) and ENO2 and TBP (alternative).

p075 NMDAR1 EXPRESSION IN THE TEMPORAL LOBE FROM INTRACTABLE EPILEPSY PATIENTS Z. Wang, W. Lin, and L. Lu The First Hospital of Jilin University, China
Purpose: In order to study NMDAR1 in the temporal lobe from intractable epilepsy patients. Method: Cortical temporal lobe brain were collected from 20 patient with intractable epilepsy and 10 patients with traumatic brain injury . the NMDAR1 expression were detected by immunohistochemistry and western blot in both group. Result: The results showed that expression of NMDAR1 in the experimental group was higher than the control group (p<0.001), the absorbance value of NMDAR1 protein strip observed from intractable epilepsy patients was 0.41750.2321 compared to 0.24120.1458 in the control group (p<0.005). Conclusion: Expression of NMDAR1 in the temporal lobe from intractable epilepsy patients was higher than the control group

Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

24 Abstracts
p076 ARE GLUTAMINE SINTHETASE EXPRESSION LEVELS ASSOCIATED WITH MESIAL TEMPORAL LOBE EPILEPSY WITH HIPPOCAMPAL SCLEROSIS? A. Martins Da Silva*, R. Branco, B. Leal, R. Rangel*, C. Carvalho, A. Bettencourt, J. Chaves*, A. Santos, T. Magalhes, M. Honavar, M. Melo Pires*, B. Martins Da Silva, and P. P. Costa *Hospital de Santo Antnio - Centro Hospitalar do Porto, Porto, Portugal; Instituto Cincias Biomdicas Abel Salazar, Porto, Portugal; Instituto Medicina Legal - Delegao Porto, Porto, Portugal; and Unidade Local de Sude Matosinhos - Pedro Hispano, Matosinhos, Portugal
Purpose: Glutamate is an essential excitatory neurotransmitter involved in diverse brain functions. Excess of extracellular glutamate can lead to excitotoxicity and subsequent cell death. The glutamatergic system is regulated by glutamine synthetase (GS), an enzyme responsible for glutamate metabolism in astrocytes. Abnormalities in this pathway have been implicated in the onset and progression of several neurological diseases including mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). In this study, we evaluated the expression levels of GS in the surgical removed lesions from hippocampal tissue and in the adjoining temporal cortex of MTLE-HS patients. Method: Twenty two patients with refractory MTLE-HS submitted to surgery were studied. Surgical specimens of hippocampus (lesional and peri-lesional cortical area) were collected. These samples were compared with nine autopsy controls without Known neurological disorder. GS expression levels were quantified by Real-Time PCR. Result: The expression levels of GS were similar in the hippocampus and temporal cortex of MTLE-HS patients when compared to similar data from matched healthy controls. Conclusion: Our results demonstrate that GS expression levels are not altered in MTLE-HS. This absence of differences does not exclude the hypothesis of abnormalities in GS at protein and functional level. For this reason, complementary studies are being performed to evaluate the protein/activity of GS and to elucidate the role of glutamatergic system in the aetiology of MTLE-HS. Supported by a FCT grant PIC/IC/83297/2007 levels of EAAT1 in the surgically removed lesions (hippocampus and the adjoining temporal cortex) of MTLE-HS patients. Method: EAAT1 expression levels in the hippocampus (lesional and peri-lesional cortical area) were quantified by Real-Time PCR in 22 MTLE-HS patients submitted to surgery and compared with 9 autopsy controls with no history of neurological disorders. Result: EAAT1 was overexpressed in both the hippocampus (p=0.008) and in the temporal cortex (p=0.018) of MTLE-HS patients when compared to autopsy controls. Conclusion: Our results demonstrate that the glutamatergic pathway is altered in the hippocampus of MTLE-HS patients. Additionally, EAAT1 overexpression in adjoining cortex suggests that this area could be involved in disease progression. EAAT1 overexpression could be explained by a compensatory mechanism to overcome the accumulation of glutamate in epileptic focus. Supported by a FCT grant PIC/IC/83297/2007.

p078 DEVELOPING A MULTI-MODAL DEVICE FOR NONEEG, EXTRAMURAL NOCTURNAL SEIZURE MONITORING J. Van Andel TeleEpilepsy Research Consortium; UMCU, Kempenhaeghe, SEIN, Utrecht, The Netherlands
Purpose: In epilepsy, 25% of patients have regular, intractable seizures, especially children with epilepsy syndromes and patients with gross brain abnormality and cognitive impairments. About half of seizures are at night, posing problems in these vulnerable patient groups depending on caregivers not sleeping in the same bed. A reliable seizure detection and alert system will provide a major step in patient safety, quality of life and disease management, however presently this is lacking. A new multimodal device using an optimized combination of nonEEG sensors is developed. Based on preliminary studies 4 modalities were selected: audio, automated video frame analysis, ECG and 3D-accelerometry. Method: A diagnostic study design is used to define optimal combinations of algorithms analyzing the 4 modalities in the target population: children <18, and mentally impaired adolescents and adults with major nocturnal seizures. The multimodal device is tested in an in-hospital setting in 100 patients, simultaneously with the gold standard of clinical video-EEG. Modern methods of classification and regression analysis are applied to define optimal sets of joint thresholds for the modalities. The aim is to achieve a high detection rate for seizures, with a minimum of false alarms in seizure free periods. Patient factors are taken into account, potentially allowing for tuning thresholds to individual patients. Result: To demonstrate our method, an interim-analysis of results will be presented in September 2012. Conclusion: In this study, the validity of a newly developed device for home detection of epileptic seizures during sleep in patients with major nocturnal seizures is tested.

p077 EXCITATORY AMINO ACID TRANSPORTER 1 EXPRESSION IN HUMAN MESIAL TEMPORAL LOBE EPILEPSY WITH HIPPOCAMPAL SCLEROSIS B. Leal*, R. Branco*, R. Rangel, A. Bettencourt*, C. Carvalho*, J. Chaves, A. Santos, T. Magalhes, M. Honavar, M. Melo Pires, A. Martins Da Silva, P. P. Costa*, and B. Martins Da Silva* *Instituto Cincias Biomdicas Abel Salazar, Porto, Portugal; Hospital de Santo Antnio - Centro Hospitalar do Porto, Porto, Portugal; Instituto Medicina Legal - Delegao Porto, Porto, Portugal; and Unidade Local de Sude Matosinhos - Pedro Hispano, Matosinhos, Portugal
Purpose: Glutamate is the predominant excitatory neurotransmitter in the Central Nervous System. Its excessive accumulation causes an excitotoxic process that can result in cell death. Glutamate transporters play an important role in regulating glutamate extracellular concentrations. EAAT1 (Excitatory Amino Acid Transporter 1) is a glutamate transporter highly expressed in astrocytes. Dysfunction in EAAT1 has been implicated in the onset of several neurological disorders including epilepsy. However, controversy exists on whether EAATs expression is altered in patients with Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (MTLE-HS). To clarify this controversy we evaluated the expression
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

Basic Science 3 Monday, 01 October 2012

p079 THE RISK OF SEIZURES IN PROGRESSIVE MULTIPLE SCLEROSIS O. W. Howell*, R. Nicholas, D. Gveric, M. I. Rees*, F. Roncaroli, and R. Reynolds *Swansea University, Swansea, UK; and Imperial College London, London, UK

25 Abstracts
Purpose: Cortical pathology is thought to contribute to motor, sensory and cognitive difficulties experienced by people with multiple sclerosis (MS). The extent of cortical and deep grey demyelination is often greater than that of the white matter, and it has been shown that inflammation of the grey matter and subcortical areas is associated with an increased risk of epilepsy. We hypothesise that inflammation, demyelination and neuroaxonal damage, cardinal features of long-standing progressive MS, will likely contribute to an increased risk of seizures. Method: We compared clinical disease milestones and pathology with seizure status from a cohort of 115 cases of secondary progressive MS (73 female, disease duration: 26.510.8yrs; age died: 57.413.1yrs). Result: Twenty two (19%) cases had at least a single seizure event, and these cases differed to the MS group without seizures with respect to: a younger age at progression (37.89.1 vs 42.610.2yrs, p=0.045), younger age at wheelchair (41.410.3 vs 46.512.6yrs, p=0.035), younger age at death (51.511.6 vs 58.813.2yrs, p=0.018) and shorter duration of the progressive phase (12.76.3 vs 16.16.8yrs, p=0.05), but not total disease duration (p=0.127). Seizures risk was independent of gender or overlying meningeal inflammation (p>0.3). A more severe clinical disease reflected the increased severity of global neuropathology (mean rating 6.81 vs 5.62.3, p=0.005) and reduced brain weight (1082135g vs 1173134g, p=0.01) for the MS plus seizure cohort at post-mortem. Conclusion: Our analysis suggests that seizure occurrence in MS is influenced by disease course and likely reflects the accumulation of myelin and neuroaxonal damage in the cortex. les electronic health record innovative (it is designed to be compatible to the widely recognized HL7 Reference Information Model architecture), the ongoing work and results from the area of computer-based video analysis for detecting and quantifying epileptic seizures, will be presented.

Purpose: Few studies have addressed whether abnormal DNA methylation contributes to differential gene expression in epilepsy. This study aimed to define differential DNA methylation patterns in drug-refractory epilepsy patients and to investigate the role of DNA methylation in epileptogenesis. Method: We evaluated DNA methyltransferase 1 (Dnmt1) and Dnmt3a expression in brain tissues of epileptic patients and then performed DNA methylation profiling in brain tissues from epileptic and control patients (n = 3 of each) via methylated-cytosine DNA immunoprecipitation microarray chip. Differentially methylated loci were validated by bisulfite sequencing-PCR, and the mRNA levels of candidate genes were evaluated by reverse transcriptase PCR. Result: We found that Dnmt1 and Dnmt3a was up-regulated in the brain tissues of epileptic patients. We also found 224 genes that showed differential DNA methylation between epileptic patients and controls. These genes included those involved in the regulation of Rho, microtubulebased processes and mitogen-activated protein kinase scaffold activity. Among the seven candidate genes, three showed clear transcriptional regulation by DNA methylation. TUBB2B and ATPGD1 exhibited relatively hypermethylated promoters and decreased mRNA levels, whereas HTR6 displayed a relatively hypomethylated promoter and higher mRNA levels in the epileptic samples. Conclusion: Our findings suggest that certain genes become differentially regulated by DNA methylation in epilepsy.

p080 HERCULES: DEVELOPING AN INTEGRATED HEALTH CARE SCHEME, BASED ON BIOMEDICAL GENETICS, ADVANCED BIOMEDICAL INFORMATICS AND COMPUTER VISION FOR EARLY DIAGNOSIS, MONITORING AND TREATMENT OF CHILDREN WITH NEUROLOGICAL DISORDERS IN GREECE. PILOT APPLICATION IN ABSENCE LIKE SEIZURES P. Vorgia*, M. Pediaditis, V. Kritsotakis, H. Dimitriou*, M. Tsiknakis, S. Voutoufianakis, V. Danilatou, D. Kafetzopoulos, and D. Fotiadis *Medical School, University of Crete, Heraklion Crete, Greece; FORTH, Heraklion Crete, Greece; FORTH, Heraklion, Greece; Venizelion General Hospital, Heraklion Crete, Greece; and University of Ioannina, Ioannina, Greece
Purpose: Epilepsy is one of the most common chronic neurological disorders. Children and adolescents with active epilepsy in Europe are estimated at 0.9 million, meaning that 1% of the population of children is affected. A significant proportion of them, reaching 30%, are pharmacoresistant. Resistance to treatment has a heavy burden on children's quality of life. The Hercules project aims to the development of an integrated healthcare and research scheme specified for Childhood Neurological Disorders, and mainly for epilepsy. Method: The main idea is to integrate medical, behavioral (motionrelated) and genetic information in order to build innovative tools and networks for providing state-of-the-art quality of care. This health care improvement will be achieved through better disease classification, knowledge discovery and invention of decision support systems. The overall architecture of the Hercules project includes: (a) the development of a biobank, (b) the development of an electronic health record, (c) the acquisition and installation of a state-of-the art video- electroencephalogram monitoring system for the detection and quantification of epileptic seizures. Result: Absence like seizures are the first ones to be studied. Conclusion: The information related to the technological requirements, the architectural design, the functional specifications that render Hercu-

p082 EVOKED HIGH FREQUENCY OSCILLATIONS IN THE HUMAN HIPPOCAMPAL FORMATION D. Fabo*, E. Toth, A. Sakovics*, L. Er} oss, and I. Ulbert *Natl. Institute for Neuroscience, Budapest, Hungary; Peter Pazmany Catholic University, Budapest, Hungary; National Institute of Neuroscience, Budapest, Hungary; and Institute for Psychology, Hungarian Academy of Sciences, Budapest, Hungary
Purpose: Cortical electrical stimulation (CES) is an approved therapy for drug resistant focal epilepsies. Despite the advanced usage of intracortical evoked potentials (iEP) the neuronal circuit mechanisms of CES are poorly understood. We examined the effect of CES under general anesthesia in the hippocampal formation (HF) of five temporal lobe epilepsy (TLE) patients. Method: We used laminar multielectrodes to record local field potential (LFP), multiple unit activity (MUA), current source density (CSD) and spectral activation of iEPs elicited by singe pulse (SPS) and train (TrS), subdural cortical electrical stimuli (0.1ms; 515mA; 0.5Hz and 50Hz). High frequency oscillation packages, ripples, were detected by semi automatic methods. Result: High frequency oscillations (ripple and fast ripple) was associated to bi- or tri-phasic iEPs were elicited by SPS in the HF stimulating the temporo-basal areas. The central frequencies of different ripples were
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26 Abstracts
100, 150 and 250Hz. Ripple activity was elicited with high probability (6098%). Similar but higher power ripples and fast ripples associated to after discharges after TrS. Conclusion: We conclude that CES iEPs contain abundant amount of ripples and fast ripples. The evoked ripple activity raises questions about the long-term effects of CES in the temporal lobe. TLE the down-regulated limk1 did not correspond with up-regulated plimk1. Conclusion: These results may reflect limk1 expression as substance basis is not a leading reason for affecting p-limk1 expression in human TLE, probably impressed by some activators of limk1, such as P21-activated kinase (PAK) and Rho-associated coiled-coil domain kinase (ROCK). These indicated limk1 and p-limk1 are likely to involve in pathogenesis of epilepsy by affecting cytoskeletal reorganization, and different predominant reasons may affect cytoskeletal reorganization and synaptic plasticity by affecting at different stage and severity of TLE.

p083 THE EXPRESSION OF MIR-132 ASSOCIATED WITH CREB IN EPILEPSY H. Wang The Second Affiliated Hospital Chongqing Medical University, Chongqing, China
Purpose: Temporal lobe epilepsy (TLE) is a common and often neurological disorder. TLE is often associated with the formation of excitability of abnormal circuit. MicroRNAs (miRNAs) are small non-coding RNAs that play essential roles in synaptic development, synaptic plasticity and cytoskeletal reorganization. Mir-132 that is a CREB-adjusting protein can increase density and length of dendritic spines, and increase frequency of miniature excitatory post-synaptic currents (mEPSCs) and decrease synaptic depression through inhibiting P250GAP that is a family number of Rho GTPase. Method: We in a rat model of epilepsy and in the human TLE separately measured mir-132 expression with real-time PCR and P-CREB that is an active form of CREB with western blot and immunohistochemistry technology. Result: Were that mir-132 is up-regulated at 24 h after initiation of the seizure in the rat model of TLE, and this coincided with up regulation of P-CREB expression. But at the rest of time points in the rat model of epilepsy and in the human TLE mir-132 is down-regulated, and this does not coincide with up regulation of P-CREB expression. Conclusion: These results show that P-CREB is likely to partly adjust mir-132 expression especially at the acute stage of epilepsy, but at chronic stage and in the human TLE mir-132 is likely to be affected by other factors. The change of up regulation and down regulation of mir132 is likely to be easier to form the excitability of abnormal circuit. Similar to the alternate use of latrunculin A and jasplakinolide induce epileptic seizures and a long-term increase in neuronal excitability.

p085 A MATHEMATICAL MODEL OF EPILEPSY: SYNAPTIC REGULATION ACTS AS AN ANTI-EPILEPTIC REGULATORY MECHANISM A. Peterson*, I. Mareels*, and M. Cook *University of Melbourne, Parkville, Vic., Australia; and The University of Melbourne, Melbourne, Australia
Purpose: The spread of seizure-like behaviour through the cortex is facilitated not only by hyper-excitable, hyper-synchronous neuronal population firing, but by overcoming the regulatory mechanisms of the brain, such as feedback, feed-forward and surround inhibition. These control mechanisms attempt to stabilise such pathological behaviour. We suggest an additional network regulatory mechanism in the form of a shunting effect based on endogenous synaptic regulation of input currents, an important neurophysiological function whose mechanism is difficult to incorporate in macroscopic models of brain dynamics. Method: A mathematical neural model is modified to include more realistic synaptic dynamics as opposed to previous models which use simplified synapses. This is a more realistic description of synaptic behaviour that has a significant effect on the overall network dynamics. A nonlinear summation (as opposed to a linear one) of the synaptic currents is introduced that incorporates local feedback from the membrane potential and an active time constant that varies inversely with the amount of input or drive to the network. The result is a more physiologically detailed description of the synaptic current produced by post-synaptic potentials. The states of the new system are found and an analysis is performed. The stability of the system is determined and an exploration of pertinent parameters, namely the network input and network balance (inhibitory/ excitatory), highly relevant to epileptogenesis is produced. These results are then compared to that of the original model with simplified synapses and the differences interpreted physiologically. Result: The dynamics and oscillatory properties of the more detailed model differ significantly from the previous model. This is largely due to the shunting effect of synaptic regulation, which acts as a network control mechanism. In particular, within the same parameter ranges for the network input and balance, oscillatory behaviour is suppressed. Conclusion: Synaptic regulation of network behaviour is an important neuro-physiological function whose mechanisms of synaptic current transmission and homeostatic tendencies should not be neglected in neural models of epilepsy, particularly when examining seizure localisation, spread and termination.

p084 THE EXPRESSION OF LIM KINASE1 AND ASSOCIATED ACTIVE FORM IN HUMAN AND RAT TEMPORAL LOBE EPILEPSY X. Yang, and X. Wang The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
Purpose: Epilepsy is a common and often neurological disorder. Epilepsy is often associated with formation of excitatory circuit, including abnormal form of dendrites and axons, but the exact mechanism remains unknown. Lim kinase1 (limk1) is an associated cytoskeletal protein, phosphorylated at the site of threonine 508, and then by phosphorylating cofilin affects dynamics of cytoskeleton and synaptic plasticity. So we infer that limk1 and its active form phospho-limk1 (p-limk1) may involve in the pathogenesis of epilepsy by affecting cytoskeletal reorganization and synaptic plasticity. Method: Here, we investigated expression of limk1 and p-limk1 by immunohistochemistry and western blot analysis in a rat model of temporal lobe epilepsy (TLE) as well as in human TLE. Result: In the rat model of TLE, p-limk1 expression was up-regulated at 6h, 72h, 30d and 60d after initiation of the seizure, corresponding with up-regulated limk1 at 6h, 72h, 7d, 14d, 30d and 60d. Moreover, in human
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

p086 DEEP BRAIN STIMULATION EARLY DURING EPILEPTOGENESIS MODIFIES DISEASE PROGRESSION IN THE HIPPOCAMPUS B. Van Nieuwenhuyse*, K. Vonck*, R. Raedt*, A. Meurs*, W. Wytse, and P. A. J. M. Boon* *Ghent University, Ghent, Belgium; and Swammerdam Institute of Life Sciences, Amsterdam, The Netherlands

27 Abstracts
Purpose: Despite promising DBS results, the mechanism of action, the long-term effects and the possible anti-epileptogenic properties of DBS remain undetermined. In this animal experimental study, we evaluated the effect of DBS on the development of spontaneous seizures in the kainic acid rat model. Method: Rats were implanted with a bipolar DBS electrode in the right hippocampus and a bipolar EEG recording electrode in both hippocampi. 24 hours after kainic acid (KA) induced status epilepticus (SE), one group (n=6) was subjected to short term DBS (ST-DBS) (poisson distributed stimulation (PDS), 130 PPS, 100ls PW, 100lA) of 1 week, a second group (n=7) was subjected to long term DBS (LTDBS) (PDS, 130 PPS, 100ls PW, 100400lA) of 10 weeks. A control group (n=9) received sham stimulation (SHAM). EEG was recorded continuously during 14 weeks in the LT-DBS and SHAM group. In the ST-DBS group, EEG was recorded continuously during the first 8 weeks of the experiment. Result: Development in daily seizure frequency is significantly different between LT-DBS and SHAM. Seizure frequency in the SHAM group rose from 0.1 0.1 seizures/day in week 1 to 26.6 3.1 seizures/day in week 14. This rise in seizure frequency was significantly reduced in the LT-DBS group (0.5 0.1 seizures/day in week 1 to 1.2 4.14 1 seizures/day in week 14). No differences between SHAM and ST-DBS rats were observed. Conclusion: LT-DBS initiated shortly after SE reduces the development of spontaneous seizures. These results show that temporary treatment with hippocampal DBS can affect disease progression.

p088 LENTIVIRAL VECTOR-DELIVERED SMALL INTERFERING RNA TARGETING TO HIF-1A GENE EFFECT ON MDR1B GENE EXPRESSION IN RAT ASTROCYTES MODEL INDUCED BY CORIARIA LACTONE L. Chen*, T. Zeng*, Y. Li, and D. Zhou *West China Hospital of Sichuan University, Chengdu, China; Chengdu, China; and West China Hospital, Chengdu, China
Purpose: Over-expression of multidrug resistance gene (MDR1) is an important mechanism of refractory epilepsy. Epileptic seizure may lead to accumulation of hypoxia-inducible factor-1a (HIF-1a) in hippocampus and temporal lobe. MDR1 gene-promoter contains a functional HIF-1a binding site, which is known as the classical hypoxia response element (HRE). Thus, we have the hypothesis that expression of Pgp is up regulated by HIF-1a in refractory epilepsy, which has been observed in cancer pharmacoresistance research. So the objective of this study is to explore the correlation of Pgp expression with HIF-1a in refractory epilepsy rat model. Method: We established a kindling model of MDR temporal lobe epilepsy (TLE) by intramuscular injection Sprague-Dawley rat with coriaria lactone (CL), and served normal SD rats with normal sodium (NS) injection as control group. The fragment gene carrying rat HIF-1a siRNA was cloned into lentiviral vector, identified with PCR and sequencing analysis. The correct reconstructed lentiviral vector was packaged into HEK 293 cells, then amplified and purified and injected into rat lateral cerebral ventricle. The expression level of MDR1b and its translational product P-glycoprotein (Pgp) were monitored with Real-time PCR and Western-blot analysis before lentiviral vector transfection and after (at different times). Result: The recombinanted lentiviral vectors target to rat HIF-1a were successfully constructed and packaged. It can infected the rat astrocytes with higher efficiency. For the rat model, the mRNA and protein levels of HIF-1a increased significantly (P<0.05) in hippocampus and temporal lobe, compared with control group. An accordant result was obtained in the expression of Pgp. After reconstructed lentiviral transfection, the levels of HIF-1a and Pgp decreased at the same time in the same brain region. Conclusion: Our study demonstrates that HIF-1a expression increased in accordance with Pgp in hippocampus and temporal lobe of refractory epilepsy rat model induced by CL. And the recombinant lentivirus delivered Small Interfering RNA targeting to HIF-1a gene can suppressed not only the overexpression of HIF-1a, but also the expression of MDR1b in model brain without obvious cell toxicity. So that HIF-1a may take an more important role in the mechanism of refractory epilepsy. further more, this study may provide a promising technique for refractory epilepsy remedy.

p087 SUDEP FOLLOWING STATUS EPILEPTICUS A. Lacey*, M. I. Rees, P. Smith, and R. H. Thomas* *Swansea University, Swansea, UK; Institute of Life Science, Swansea, UK; and Wales Epilepsy Research Network, Swansea, UK
Purpose: Status epilepticus (SE) is a life-threatening complication of epilepsy and a medical emergency. However, for some, an episode of SE is their first presentation of epilepsy. Method: Using the Secure Anonymised Information Linkage (SAIL) databank at we scrutinised primary care records in Wales for patients who have had an episode of SE. In order to better understand the prognosis of epilepsy following SE we looked at contemporaneous comorbidities and mortality records. Result: Since 1991 there have been 2.9/100,000 episodes of SE recorded in Wales. 732 people were identified as having SE and there were 174 deaths recorded; 15.5% were within six months of SE. In total there were 13 potential cases of SUDEP. 12.8% of people who first presented in SE (and later died) had epilepsy as a cause of death compared to 3.1% of those who had pre-existing epilepsy prior to SE (p>0.02). 2.5 times more people presenting with SE without known epilepsy were known to have a brain tumour (n=10, 3.6%). On Seven occasions more people with epilepsy had a change of medication within a month of SE (32%) than people who had SE without a prior diagnosis of epilepsy (4%; p>0.0001). Conclusion: This nationwide study identifies that SE as a first presentation of epilepsy is associated with an increased risk of SUDEP although not all cause mortality. We believe that SE occurring from pre-existing epilepsy may be triggered by poor medication concordance or change in drug regime, rather than a new symptomatic cause such as tumour or stroke.

Basic Science 4 Monday, 01 October 2012

p089 ELECTROGRAFIC SEIZURES AND PERIODIC EPILEPTIFORM DISCHARGES IN PATIENTS WITH POSTANOXIC COMA E. Altindag*, Z. V. Okudan, B. Baykan, O. Gungor Tuncer *, B. Aksay Koyuncu*, S. Tavukcu Ozkan *, and Y. Krespi* _ *Istanbul Florence Nightingale Hospital, Istanbul, Turkey; Istanbul Bilim University, Istanbul, Turkey; and Istanbul University Istanbul Medical Fakulty, Istanbul, Turkey
Purpose: We aimed to examine the predictors and prognostic value of electrographic seizures (ESZs) and periodic epileptiform discharges (PED) of post-anoxic coma patients in intensive care unit (ICU).
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

28 Abstracts
Method: The clinical, EEG and neuroimaging findings of consecutive anoxic comatose patients due to cardiac arrest were studied between 2009 and 2011. EEG data was reviewed by 2 investigators independently. Result: Seventeen patients (7 F; mean age: 59.816.9) were admitted to our study. The mean duration of hospitalization was 54.6 days. The outcome included death in 7 patients, severe neurological deficits in 6 patients. Thirteen patients had Glasgow Coma Score. Conclusion: MSE and various electrographic patterns detected in patients with post-anoxic coma could not predict the mortality. Larger prospective studies are warranted to determine the impact of these patterns more precisely. Method: We reviewed the data concerning the efficacy and safety of IV Lacosamide for RSE in 21 consecutive patients. Result: Patients average age was 60 [1485] years-old. Eleven patients had preexisting epilepsy. The most frequent RSE was convulsive in 70%. Seizure semiology was most likely complex partial (11) or generalized tonic-clonic (6). The RSE was classified as remote symptomatic (9), acute symptomatic (8) and cryptogenic (3). The most frequent etiology was the vascular lesion (50%). The IV Lacosamide was started with an initial bolus of 200 mg, and then followed by maintenance or individualized daily dose increases, depending on the electroclinical response. Lacosamide was used as a second drug (1), third drug (7) or fourth drug (12). Overall, RSE cessation was achieved in 55% of patients, of whom 40% within 72 hours. The highest rates of success were obtained by combining benzodiacepines, levetiracetam and Lacosamide. Four patients died during the RSE and six required further sedation. Somnolence and gastrointestinal symptoms were all the adverse events attributable to lacosamide in two patients. IV LCM was switched to equal doses per oral at hospital discharged. Five patients died remotely and 10 have remained seizure-free during the follow-up (5 months [120]). IV LCM can be an option for RSE as a previous step to sedation in the protocol of treatment of the RSE.

Purpose: Little are studied the systemic clinical features of status epilepticus (SE) in Southern Taiwan. To have a basic understanding of these features, including age and sex distributions, SE types, aetiologies, prognosis, anatomic correlations, validities of the investigation tools, etc; and to promote further clinical researches in SE, a systemic cases review was carried out. Method: Epilepsy cases admitted to the Chiayi Christian Hospital or the National Cheng Kung University, Douliou branch, during 20012011, were reviewed. Inclusion criteria were those who fit current SE definition suggested by the ILAE, ie continuous seizures up to 5 minutes without stopping, or no return of consciousness to the baseline between 2 or more consecutive seizures. Exclusion criteria were those with incomplete medical records or poor evidence in suggesting SE. Result: Altogether 173 patients entered the systemic cases review. Male to female ratio was 103:73 (59.5% vs 40.5%). Most patients were in their seventies [40/173 (23.1%)] and sixties [37/173 (21.4%)]. 145 patients had convulsive SE, and 28 had non-convulsive SE. The leading causes in SE were cerebral vascular disease [59/173 (34.10%)], metabolic disorders [48/173 (27.7%)], and poor seizures control [43/173 (24.8%)]. Frontal and temporal lobe lesions were the leading damages seen in images. Epileptiform discharges did not always correlate the lesions found in images. Conclusion: Several issues raised that need further study, including the discrepancy in sex distribution; the correlation between EEG and images findings, the mechanism causing higher risks in having SE with frontaltemporal lesions, and the impact of co-morbidities in causing SE in the elderly.

p092 SELECTIVE LENTIVIRAL MEDIATED TARGETING OF GLIA CELLS IN THE CENTRAL NERVOUS SYSTEM M. Fassler, I. Weissberg, N. Levi, A. Monsonego, R. Taube, and A. Friedman Ben-Gurion University of the Negev, Beer Sheva, Israel
Purpose: In a complex tissue of the central nervous system (CNS), cell cross-talk is essential to preserve normal functions. Current tools for dissecting the molecular mechanisms that mediate cell-cell interactions within the brain are technically challenging, time consuming and difficult to control. In this study we report the establishment and validation of a lentiviral-mediated gene-targeting platform to specific cells in the CNS. Method: Using lentiviral-mediated gene-targeting platform that combines unique features of self-inactivated lentiviruses that promote stable gene delivery into non-dividing cells and efficient display of single-chain variable region human fragments (scFv) or soluble IgG on the surface of viral particles. Result: In vitro, cells that express the receptor-binding domain of the SARS-CoV spike glycoprotein were targeted by engineered sindbis pseudotyped lentiviruses that incorporate specific scFvFc attachment moieties. Additionally, in vitro targeted gene expression to primary astrocytes was also demonstrated, using engineered lentiviruses that incorporate Aquaporin 4 and GLAST IgG. In vivo, lentiviral targeting of astrocytes and oligodentrocytes progenitor cells that express the chondroitin sulfate proteoglycan, NG2 was obtained using viral particles that display an anti-GLAST and anti-NG2 IgG antibodies, repectively. Conclusion: We conclude, that this novel approach will be implemented in the model of epilepsy to study the role of astrocytes in the pathogenesis of the disease and challenge its use as a therapeutic tool.

p091 IV LACOSAMIDE AS THERAPEUTIC OPTION FOR REFRACTORY STATUS EPILEPTICUS BEFORE COMA INDUCTION E. Santamarina, M. Toledo, M. Sueiras, M. Raspall, N. Allouti, E. Lainez, M. Vicente, J. Conill, M. Roig, and X. Salas-Puig Vall dHebron University Hospital, Barcelona, Spain
Purpose: Refractory status epilepticus (RSE) is a neurological condition that often requires sedation to be controlled. IV Lacosamide is a novel antiepileptic drug that may provide some benefits in RSE before inducing coma.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

p093 ASYMMETRIES OF SLEEP SPINDLES IN HUMAN EPILEPSY WITH TEMPORAL OR FRONTOTEMPORAL FOCUS A. Kyrozis, C. Moschovos, E. Tsoukas, A. Bonakis, D. Pandis, A. Ghika, I. Evdokimidis, and N. Kalfakis Univ. Athens, Athens, Greece

29 Abstracts
Purpose: It is unclear whether temporal lobe epileptic foci can affect sleep spindles, which are generated in extratemporal thalamo-cortical circuits. We tested for such effects, the detection of which may have pathophysiologic and clinical diagnostic implications. Method: Sleep EEG recordings of 6 cryptogenic epilepsy patients with right temporal or frontotemporal focus (TR), 6 with left temporal or frontotemporal focus (TL) and 12 controls with non-epileptic paroxysmal events and normal MRIs were used. Central sleep spindles were detected by a custom-made computer algorithm (MATLAB software). Spectral power, peak frequency, inter-channel transfer function estimate (TFE) angle (reflecting phase difference) and inter-channel coherence were assessed. Result: No significant inter-hemispheric differences were found for peak frequency and spectral power. Spindles recorded at frontal electrodes appeared a few milliseconds earlier on the side of the focus in 11 of 12 epilepsy cases. The lateralization was highly significant (meanSEM TFE angles from F3 to F4: TR: + 0.2120.055; TL: - 0.2040.077, Tukey test p=0.0057). Coherence was also higher on the side of the epileptic focus [Coh (F3Fz)Coh (F4Fz): TR: -0.0550.06; TL: +0.090.025, Tukey test p=0.028], implying greater synchronization on the side of the focus. Conclusion: Temporal lobe epilepsy promotes initiation and synchronization of sleep spindles on the side of the focus. The observed changes may be the result of network modifications on the side of the focus and/or altered hippocampal-frontal networks that modulate sleep oscillations. The results suggest the possibility of using sleep spindles for the detection of the presence and side of an occult epileptic focus. adenosine into the ictal focus is likely to be effective in the control of intractable seizures.

p095 ALPHA-LACTOALBUMIN, A WHEY PROTEIN RICH IN TRYPTOPHAN, IS EFFECTIVE IN RODENT MODELS OF SEIZURES AND EPILEPTOGENESIS G. De Sarro*, F. Scicchitano*, R. Citraro*, S. Chimirri*, P. Mainardi, E. Perucca, and E. Russo* *University of Catanzaro, Catanzaro, Italy; University of Genova, Genova, Italy; and Pavia, Italy
Purpose: ALAC (alpha-lactoalbumin), a whey protein rich in tryptophan, shows protective activity in preclinical models of seizures and epilepsy and was recently associated with improved seizure control in patients with drug-refractory epilepsy.1,2 We evaluated the potential activity of ALAC in some other rodent models of seizures and epileptogenesis and we explored a possible mechanism of action. Method: The effects of ALAC (oral administration) were tested in two standard epileptogenesis protocols, namely the pilocarpine post-status epilepticus model in mice and the WAG/Rij rat model of absence epileptogenesis.2,3 The mechanism of action was investigated by assessing the effects of ALAC in two seizure models (NMDA and PTZ-induced seizures) including D-serine co-administration4. Result: ALAC showed protecting properties in both models of epileptogenesis, reducing spontaneous seizures development. In acute seizure models, ALAC possessed antiseizure properties at some of the doses tested (PTZ-seizures: 50% seizure-reduction at 250mg/kg; NMDA-seizures: 90% reduction at 250 and 500mg/kg). When a dose of D-Serine ineffective per se was co-administered with ALAC, ALAC effects were significantly reversed in both models. Conclusion: ALAC is active in experimental models of seizures and epileptogenesis. Its effects are likely mediated by the inhibition of NMDA receptors at the glycine binding site, possibly secondarily to the in-vivo enzymatic conversion of ALAC-generated tryptophan to kynurenic acid. However, other mechanisms of action contributing to ALAC effects cannot be excluded. References: 1 Mainardi, et al., 2008. Med Hypotheses 70, 8769. 2 Citraro et al., 2011 Epilepsy Res 95, 609. 3 Russo et al., 2011 Epilepsia 52, 134150. 4 Russo et al., 2004 Neuropharmacology 46:86578.

p094 WIRELESS INSTANTANEOUS ADENOSINE RECORDING DURING KAINIC ACID-INDUCED SEIZURE IN RAT: WINCS APPLICATION Y. Shon*, and S. Lim *Yeouido St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea; and St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea
Purpose: Adenosine, as the brain's endogenous anticonvulsant, is considered to be responsible for seizure arrest and postictal refractoriness. We performed ictal EEG & co-monitoring of neurotransmitter recording by WINICS (wireless instantaneous neurotransmitter concentration system, fast-scan cyclic voltammetry based) in the acute hippocampal seizure model of rat. Method: Rats (n=18) were implanted with bipolar hippocampal depth electrodes and a cannula for the injection of KA (1 mcg/4min) in the right hippocampus (CA3) under urethane anesthesia. WINCS recording electrode was inserted in left hippocampus (mirror site of R HC). Simultaneous recordings of EEG (8 channels) and WINCS were performed continuously after KA induced limbic status epilepticus (usually 10 15min after injection). Result: There were two patterns of adenosine release during the KA induced limbic status epilepticus. First, intermittent and phasic release of adenosine (n=2) was clearly observed only during the early period of slow, large-amplitude spike and wave, but not at the low-amplitude fast or repetitive spikes among the recurrent ictal EEG pattern. Second, there were a rapid adenosine and dopamine release immediately at the time point of sudden, transient disappearance of polyspike or spike-wave discharges in the EEG (n=7). Conclusion: Our study shows that the slow phase of spike-wave complex or its transient disappearance after prolonged status epilepticus may be linked to a suppression of neuronal hyperexcitability via adenosine release. We may suppose that the local delivery of

p096 THECX32 GENE EXPRESSION IN BRAIN FOCI OF PATIENTS WITH REFRACTORY EPILEPSY W. Lin, and L. Zhang the first hospital of Jilin University, 130021, China
Purpose: In order to study CX32 gap junction gene expression in the brain epileptic foci of patients with refractory epilepsy, and lay the foundation for clinical research and treatment of refractory epilepsy. Method: 24 patients with refractory epilepsy that have undergone surgery in the experimental group, 10 patients with traumatic brain injury that have undergone emergency surgery in control group. epileptic brain foci tissue were removed from surgery, immunohistochemistry and immune electron microscopy methods were used to observe CX32 expression in both group. Result: Immunohistochemistry results showed that CX32 expression in the experimental group was higher than the control group (p<0.001), There are more colloidal gold particles labelling CX32 on the membranes
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

30 Abstracts
of nerve cells in the brain tissue of the experimental group than the control group under electron microscopy (p<0.001). Conclusion: The expression of CX32 in the epileptic brain foci was increased, which may play an important role in the happen and development of epilepsy.

Epilepsy Surgery 1 Monday, 01 October 2012

p099 LATERALIZATION AND LOCALIZATION OF POSTTRAUMATIC EPILEPSY WITH DUAL PATHOLOGY USING FORAMEN OVALE ELECTRODES: A CASE REPORT H. Henninger*, D. T. Hsieh, E. N. Eskandar, and A. J. Cole *Maine Medical Partners Neurology, Scarborough, USA; Massachusetts General Hospital, Boston, USA; and MGH Epilepsy Service, Massachusetts General Hospital, Boston, USA
Purpose: Traumatic brain injury is typically multifocal and may consist of bleeding, gliosis, axonal injury, and hippocampal sclerosis. Each of these mechanisms may lead to post-traumatic epilepsy. When more than one possible seizure onset zone is present concomitantly, this is often referred to as dual or multifocal pathology. Foramen ovale electrodes can lateralize and localize mesial temporal lobe epilepsy in cases where clinical uncertainty exists. Method: A 57-year-old left handed man was evaluated for medically refractory epilepsy. Epilepsy began at age 19 following a motorcycle accident resulting in a left temporal intraparenchymal hemorrhage. MRI demonstrated marked left temporoparietal encephalomalacia as well as right hippocampal atrophy with increased T2 signal intensity. Surface EEG captured several right temporal lobe seizures, however concern about the role of the left hemisphere lesion led to prior rejection of resective epilepsy surgery. Results: Bilateral foramen ovale (FO) electrodes were surgically placed for continuous EEG recording. Six electro-clinical seizures were recorded with clear onset in the right FO electrodes. Right anterior temporal lobectomy was performed resulting in seizure freedom with minimal effect on memory. Conclusion: Post-traumatic epilepsy with dual or multifocal pathology can present a clinical dilemma, especially if the site of apparent seizure onset is contralateral to the most extensive post-traumatic injury. When mesial temporal seizure onset is suspected, foramen ovale electrode EEG monitoring can provide confirmation of lateralization and localization of the seizure onset zone without further invasive monitoring.

p097 GABAERGIC EXCITATORY MECHANISMS ARE INVOLVED IN THE GENESIS OF EPILEPTIC ACTIVITIES IN THE CORTEX SURROUNDING GLIOMA IN HUMANS G. Huberfeld*, J. Pallud*, M. Levanquyen, M. Baulac, F. Bielle, C. Duyckaerts, F. Roux, R. Miles*, and L. Capelle *CRICM - UPMC - INSERM - CNRS, Paris, France; Hpital de la Piti-Salptrire, Paris, France; CHU Pitie-Salpetriere, Paris, France; and CH Ste Anne, Paris, France; and
Purpose: Brain gliomas are associated with seizures in a majority of patients, but their pathophysiology and link with the tumor is still unclear. Method: The physiology of the resected tumor and surrounding security margin can be explored in neocortical slices providing a novel opportunity to explore epileptogenic mechanisms in human tissue. Result: We found that postoperative glioma tissues of 69% patients spontaneously generated interictal-like discharges. These events were synchronized in superficial layers of cortical columns in the neocortex surrounding glioma areas that presented a tumor infiltration. They were never recorded in the tumor core or in control tissues. Interictal-like events depended on both depolarizing GABAergic and glutamatergic transmission. Interneuron firing preceded them, and Chloride homeostasis was perturbed in 65% of pyramidal cells resulting in a depolarization induced by GABA. Ictal-like activities could be exclusively generated in these areas. They were preceded by a long range period characterized by the progressive emergence of glutamatergic preictal discharges. Conclusion: These epileptic activities sustained by excitatory effects of GABA, as those reported in human temporal lobe epilepsies, suggest that cellular Chloride regulation processes affecting oncogenesis are involved in the excitatory/inhibitory imbalance causing epileptic activity in peritumoral tissue.

Purpose: This work addresses the question of what drug(s) is(are) the next most effective when benzodiazepines fail to control convulsive status epilepticus. Method: A systematic search of literature for the outcome of the use of phenobarbital, phenytoin, valproate, levetiracetam and lacosamide has been carried out. Result: Ninety eight papers have been included in the review. The evidence base is categorized as level 111, and the use of each drug has advantages and disadvantages. Conclusion: The paper presents a detailed analysis of the published papers and a comparison of these widely-used drug therapies.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

p100 A PROSPECTIVE LONG-TERM STUDY ON THE OUTCOME AFTER VAGUS NERVE STIMULATION AT MAXIMALLY TOLERATED CURRENT INTENSITY IN A COHORT OF CHILDREN WITH REFRACTORY SECONDARY GENERALIZED EPILEPSY A. Cukiert*, C. Cukiert*, A. Lima*, J. Burattini*, C. Forster*, C. Baise, and M. Argentoni-Baldochi *Clinica De Epilepsia De Sao Paulo, Sao Paulo, Brazil; and Hospital Brigadeiro, So Paulo, Brazil
Purpose: We report the outcome after VNS in kids with secondary generalized epilepsy, and advance in the discussion of issues rarely addressed such as maximal stimuli intensity, seizure worsening, honeymoon effect, and specific seizure type control rates. Method: Twenty-four consecutive children with Lennox-Gastaut or Lennox-like syndrome under the age of 12 years by the time of surgery, were prospectively included in the study. The generator was turned on using 0.25mA, 30Hz, 500lsec, 30sec on, 5 minutes off stimuli parameters; current was then increased by 0.25mA every 2 weeks, until 3.5mA was reached or adverse effects were noted.

31 Abstracts
Result: Six kids got an end-of-study (24 months) post-implantation video-EEG and their findings were similar to those before vagus nerve stimulation. Quality of life and health measures improved in up to 50% (mean=25%) in 20 kids. Attention was noted to improve in 21 out of the 24 kids. Final intensity parameters ranged from 2 to 3.5mA (mean=3.1mA). An at least 50% seizure frequency reduction immediately after implantation and with the generator off was noted in 14 out of the 24 kids. There were 47 seizures types among the 24 children. An at least 50% seizure frequency reduction was noted in 35 seizure types and 17 seizures types disappeared after VNS. Atypical absence, myoclonic and generalized tonic-clonic seizures were significantly reduced by VNS; tonic and atonic seizures did not improve. Transient seizure frequency worsening was noted in 10 of the 24 kids, at a mean of 3.1mA. Conclusion: Our study showed that VNS was effective in reducing atypical absence, generalized tonic-clonic and myoclonic seizures (but not atonic or tonic seizures) in kids with Lennox-Gastaut or Lennox-like syndrome. A concomitant improvement in attention level and quality of life and health was also noted. Secondary generalized epilepsy might represent a subset of good candidates for VNS. it is still an unresolved question at which age surgery should best be performed. In light of decreasing plasticity and the cumulative impact of seizures and anticonvulsants on neurodevelopment, early surgery appears preferable. This study aimed to determine whether early hemispherectomy leads to better long-term outcome than surgery at an older age. Method: We retrospectively investigated the medical, cognitive-behavioral and psychosocial long-term outcome (follow-up: 9.4yrs [1.119.4]) of hemispherectomy as a function of age at surgery (early: <7yrs/intermediate: 716yrs/late: >16yrs) based on a structured postal questionnaire in a large patient sample (N=61/81, return rate: 75%). Result: Best seizure outcome was obtained for early surgery patients (90% seizure free). Patients with late surgery, however, had higher pre- and postsurgical intelligence and achieved better psychosocial outcome. Surgery at an intermediate age yielded cognitive-behavioral improvements most often. Binary logistic regression confirmed higher age at surgery and higher presurgical intelligence as positive predictors of postsurgical intelligence; lower presurgical intelligence and postsurgical seizure freedom predicted intellectual pre-post improvements. Conclusion: Contrary to expectations, we found no evidence for advantages of early surgeries regarding postsurgical cognition and achievement. These data do not suggest to postpone surgery but higher age should not exclude patients from hemispherectomy. Presurgical intelligence serves as indicator of the severity of the disease and the functional integrity of the contralateral hemisphere, which determine cognition and eventually psychosocial outcome. Postsurgical improvements are possible, particularly in case of seizure freedom.

p101 THE EFFICACY OF VNS IN PHARMACORESISTANT EPILEPSY OF TEMPORAL VERSUS EXTRA-TEMPORAL LOBE LOCATIONS A. Abubakr*, and I. Wambacq *University of Mississippi Medical Center, Jackson, USA; and Montclair State University, Bloomfield, NJ, USA
Purpose: This is a retrospective study evaluating the effectiveness of VNS therapy in patients with refractory epilepsy of temporal versus extra-temporal lobe locations. Method: The medical records of 31 patients implanted with VNS between1998 and 2001 were reviewed. Patients were divided into TLE group and extra TLE group based on the epileptogenic foci. Changes in seizures frequency was assessed at one year following VNS implant. Patients with >50% reduction in seizures frequency were considered responders to VNS therapy. Result: Out of 31 patients one died of unrelated cause, and another asked their device to be removed due adverse effects. There were 9 patients with TLE (5 males and 4 females), age range 2761 yrs, with epilepsy duration of 440 yrs, and seizures frequency of 1450/month and taking an average 25 AEDs a day. There were twenty patients with extra TLE (9 males and 11 females), age range 1462 yrs, epilepsy duration of 854 yrs, and seizures frequency of 3900/month and taking 24 AEDs a day. Six out of 9 with TLE (66%) and 11 out of 20 with extra TLE (55%) were considered responders to VNS therapy (>50% reductions in seizure frequency) at one year following the implant. There was no significant difference between the two groups (P = 0.88). Conclusion: This observation demonstrates that VNS is an effective therapy in patients with either TLE or extra TLE focus and there is no difference in the responder rate between various epileptogenic foci.

p103 CHILDHOOD TEMPORAL LOBE EPILEPSY: BEYOND HIPPOCAMPAL SCLEROSIS A. Mhlebner-Fahrngruber, M. Schmook, D. Prayer, A. Dressler, G. Kasprian, G. Grppel, G. Pahs, T. Czech, and M. Feucht Medical University Vienna, Vienna, Austria
Purpose: Herein, we focused on clinico-pathological variants of childhood drug-resistant temporal lobe epilepsy (TLE): pre- and postsurgical data of 17 patients (14 female; 9 left TLE), who underwent epilepsy surgery, were reviewed. Method: Video-EEG monitoring including sphenoidal electrodes was analyzed with regard to clinical lateralizing signs defining the clinical symptomatogenic, the seizure onset and the irritative zon. MRI was reviewed with respect to presence of hippocampalsclerosis, small temporal lobe, blurring of the grey-white matter junction, signal changes of the subcortical white matter, and thickening of the adjacent cortex. Histopathology was routinely processed for histopathology. Result: Six children had anterior temporo-polar resection. All six children displayed additional FCD IIIa. All six patients had a history of febrile seizures. In 5/6 the typical MRI changes in temporal lobe were found. All six of them were seizure free after surgery. Five children who underwent anterior temporo-polar resection showed HS without FCD IIIa. 2/5 had febrile seizures. Only 1/5 displayed the typical MRI changes. Outcome was Wieser 1a in 2 children, Wieser 2 was found in 1 and Wieser 3 in 2 patients. Six patients underwent selective amygdalohippocampectomy and therefore temporal cortex was not available. 4/6 had febrile seizures. None of them had changes in the temporal lobe on MRI scan. 5 were seizure free after surgery, 1 had outcome Wieser 3. Conclusion: In summary, the combination of certain clinical characteristics, clear-cut signal alterations on MRI scan, sufficient surgical resection as well as certain histopathological diagnosis is associated with a favourable outcome in childhood temporal lobe epilepsy.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

p102 HEMISPHERECTOMY AN OPTION ALSO FOR ADOLESCENT AND ADULT PATIENTS A. Althausen*, U. Gleissner, C. Hoppe*, R. Sassen*, S. Buddewig*, M. Von Lehe*, J. Schramm*, C. Elger*, and C. Helmstaedter* *University of Bonn, Bonn, Germany; and LVR-Klinik Bonn, Bonn, Germany
Purpose: Hemispheric neurosurgery is an established treatment for severe epilepsy caused by extended unilateral brain pathology. However,

32 Abstracts
p104 CENTROMEDIAN THALAMIC DEEP BRAIN STIMULATION FOR THE TREATMENT OF REFRACTORY GENERALISED AND FRONTAL EPILEPSY: A BLINDED CONTROLLED STUDY A. Valentin*, R. Chelvarajah, R. Selway, L. Vico*, R. Garca De Sola, E. Garcia Navarrete, and G. Alarcon* *King's College London - Institute of Psychiatry, London, UK; King's College Hospital, London, UK; and Hospital Universitario de la Princesa, Madrid, Spain
Purpose: Deep Brain Stimulation (DBS) of the thalamus is an emerging surgical option for medically refractory epilepsy sufferers who are not suitable for resective surgery, or where surgery has failed. In a singleblind within-subject control study, we evaluate the efficacy of DBS of centromedian nucleus (CMN) for seizure control as well as quality-of-life outcome in symptomatic generalised epilepsy (SGE), and frontal lobe epilepsy (FLE). Method: Eleven patients were recruited (8 males, 3 females) at King's College Hospital (London, UK) and Hospital de la Princesa (Madrid, Spain). Six patients had removal of the VNS device before DBS implantation. Ages at surgery range from 18 to 51 years (mean 37). Average follow-up period is 2 years. Six patients had SGE and five FLE. Seizure diaries were kept by patients/parents prospectively. Patient reported outcome measures (PROMs) were completed at regular time-points. Result: Among the 6 patients with SGE, 2 patients became seizure free for more than 4 years, 3 had seizure frequency reduction greater than 50% and one had seizure reduction of 37.5%. None of the patients with FLE became seizure free, 2 had a reduction greater than 50% and 2 showed no change. PRO questionnaires showed improvement in approximately 50% of patients. Conclusion: DBS of CMN appears to be effective in improving seizure control and patient related outcomes in patients with generalised epilepsy and possibly in frontal lobe epilepsy. two. Seizures originated from the temporal lobe in ten patients, from the temporo-parieto-occipital region in one, and were bitemporal in one. At 1 year follow-up eight patients were seizure free, one had worthwhile improvement and the remaining three had experienced no benefit. Postoperative outcome was available in ten patients at 2 years and in three at 5 years, and remained stable in all but one. The most frequent underlying pathology was dysembryoplastic neuroepithelial tumor (DNET). Conclusion: Epilepsy surgery can be performed effectively in patients with NF1 and drug-resistant seizures. In spite of the frequently multifocal nature of the disorder, a single and well-delimited epileptogenic zone can be recognized. The high prevalence of DNETs in this series might suggest that association of this developmental tumor with NF1 is not fortuitous.

Purpose: Palliative procedures such as callosotomy or VNS have been used for treatment of refractory secondary generalized epilepsy. We compared the outcome from these palliative procedures in two consecutive prospective cohorts of patients with secondary generalized epilepsy. Method: Twenty consecutive patients with refractory secondary generalized epilepsy submitted to callosotomy (Group 1) and additional 20 patients submitted to VNS were studied (Group 2). Patients with specific etiology (cortical dysplasia, tuberous sclerosis etc) were excluded from the study. Result: MRI showed atrophy in 70% of Group 1 and in 65% of Group 2 patients; non-specific gliosis was present in the remaining patients. All patients had multiple seizure types. Both procedures were similarly effective regarding the control of atypical absences and generalized tonic-clonic seizures, and both were not effective in controlling tonic seizures. Callosotomy was very effective in reducing atonic seizure's frequency, while VNS was ineffective. On the other hand, callosotomy was not effective in reducing myoclonic seizures, while VNS did so. Rupture of secondary bilateral synchrony was noted in 85% of Group 1 patients; there was no EEG modification after VNS in group 2. Attention improvement was equally noticed in both Groups. All but one Group 1 patients disclosed an acute callosal disconnection syndrome immediately postoperatively, lasting for up to 3 weeks. Longer hospital stays (including ICU) and blood transfusion were characteristics of Group 1 patients only. Conclusion: Both procedures were effective in treating patients with refractory secondary generalized epilepsy. Specific seizure types responded differently to each treatment.

p105 EPILEPSY SURGERY IN NEUROFIBROMATOSIS TYPE 1 C. Barba*, T. Jacques, P. Kahane, T. Polster, J. Isnard, F. S. S. Leijten**, C. zkara, L. Tassi, F. Giordano*, M. Castagna, A. John, B. Oz, N. Streichenberger, C. Salon, R. Guerrini*, and H. Cross*** *Children's Hospital Meyer, Florence, Italy; Great Ormond Street Hospital NHS Trust, London, UK; Grenoble University Hospital, Grenoble, France; Bethel Epilepsy Centre, Bielefeld, Germany; Hpital Neurologique, Lyon, France; **Rudolf Magnus Institute of Neuroscience, UMC Utrecht, Utrecht, The Netherlands; Istanbul University School of Medicine, Istanbul, Turkey; Niguarda General Hospital, Milan, Italy; University of Pisa, Pisa, Italy; Cerrahpasa Medical School, Istanbul, Turkey; and ***ILAE Commission Of Paediatrics, London, UK
Purpose: To report on 12 patients with Neurofibromatosis type 1 (NF1) and drug-resistant seizures, who underwent epilepsy surgery and describe their clinical presentation, outcome and histopathology. Method: We included in the study patients with NF1 who had undergone surgery for drug-resistant epilepsy and had at least one year postoperative follow-up. Result: We collected 12 patients from eight European epilepsy centers. MRI abnormalities were detected in all patients but one and were unilateral temporal in eight, bilateral in one and multilobar or hemispheric in
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

p107 BELGRADE EPILEPSY SURGERY PROGRAM: EARLY OUTCOME OF THE FIRST 35 OPERATED PATIENTS D. V. Sokic*, V. L. Bascarevic, A. J. Ristic*, N. M. Vojvodic*, A. Parojcic, S. Lavrnic, L. Brajkovic, M. M. Kovacevic, S. M. Jankovic, and B. Djurovic *Clinic of Neurology Clinical Center of Serbia, University of Belgrade School of Medicine, Belgrade, Serbia; Clinic of Neurosurgery, Clinical Center of Serbia, University of Belgrade, School of Medicine, Belgrade, Serbia; Clinic of Neurology, Clinical Center of Serbia, Belgrade, Serbia; Center for Magnetic Resonance, Clinical Center of Serbia, Belgrade, Serbia; and Institute of Nuclear Medicine, Belgrade, Serbia

33 Abstracts
Purpose: Although approximately 200 patients underwent surgery for medically intractable epilepsy between 1975 and 1995 in Belgrade, epilepsy surgery program was temporarily interrupted for almost 15 years. Contemporary Belgrade Epilepsy Surgical Program was restarted in 2006. Method: Noninvasive presurgical evaluation was performed in 281 pharmacoresistant epilepsy patients and included 510 days video-EEG telemetry, 1.5 T MRI with appropriate angulation, and neuropsychological testing in all, and interictal PET and/or interictal/ictal SPECT in 19% of patients. Indication for operation was established if the acquired data showed high concordance. Result: Surgery was performed in 35 (12%) patients: left side anterior temporal lobectomy with amigdalo-hippocampectomy in 21 (60%), and right side in 13 (37%) patients. Lesionectomy in right frontal lobe was performed in 1 patient. Histology showed hippocampal sclerosis in 22, dual pathology in 5, focal cortical dysplasia in 4, glioma in 2, DNET in 1 and cavernoma in 1 patient. Perioperative complications occurred in 10 (28%) patients and included dysphasia and dyslexia without permanent radiological infarction (4), hemiparesis (2), infection (3), and amnesia (1). All complications (except hemiparesis due to brain infarction in 2 patients) were transitory. Four patients had GTC seizures after surgery and in 2 of them seizures continued to occur. Seizure remission was obtained in 33 (94%) patients during 3 to 65 (median: 11) months of follow-up. New onset psychosis (3), depression (1) and anxiety (1) occurred after surgery but responded to appropriate therapy. Conclusion: Early surgical outcome in patients with pharmacoresistant, predominantly temporal lobe epilepsy is favorable. Complications are reasonably rare. resective surgery or failures of the same. There seems to be a tendency of an increased infection rate with the number of stimulator replacements. This would stress the importance of longer battery life times or the need for rechargeable devices.

p109 LENNOX-GASTAUT SYNDROME AND CALLOSOTOMYA IN ADULTHOOD M. Herbas Rocha*, J. D. D. Del Castillo Calcneo, M. AlonsoVanegas*, D. San Juan Orta, and B. A. Sandoval Bonilla *Instituto Nacional de Neurologa y Neurociruga Manuel Velasco Suarez, Mexico city, Mexico; Angeles Pedregal Hospital, Mexico City, Mexico; National Institute of Neurology and Neurosurgery, Mexico City, Mexico; and Instituto Mexicano de Seguro Social, Mexico City, Mexico
Purpose: The Lennox-Gastaut syndrome (LGS) is one of the most severe epileptic encephalopathies of childhood that extends into adulthood. We show the sociodemographic characteristics and surgical outcome of callosotomy in adults with SLG. Method: Adults with epilepsy were identified SLG of either sex undergoing open callosotomy through the Priority Program Epilepsy and the Neurosurgery Department at National Institute of Neurology and Neurosurgery from January 2003 to October 2011. Result: A total of 21 adult patients with LGS submitted to callosotomy, 7 women (33%) and 14 males (67%), mean age 25 7 years (range 14 to 39 years), with a mean age at the time of onset of their illness than 4 years (range 3 months to 11 years) and mean duration of epilepsy of 23 years (range 11 to 38 years). The seizures most frequently found in patients were: 66.6% atypical absence (14), tonic 57.7% (12), atonic 52.3% (11), complex partial seizures 42.8% (9). All patients underwent 2/3 anterior callosotomy. The prognosis at 12 months was; 3 patients were in class A (14.2%), 12 patients in class B (57.14%), 4 class C patients (19%) and 2 in Class D (9.5%). Conclusion: Surgical callosotomy of the anterior 2/3 in adults with LGS is a safe and effective procedure for control of seizures, especially drop attacks and generalized tonic-clinic seizures. Severe mental retardation does not affect the clinical outcome and should not be considered a contraindication. Structural brain abnormalities didnt show any effect on the outcome.

Epilepsy Surgery 2 Monday, 01 October 2012

Purpose: To longitudinally study surgical and hardware complications to vagal nerve stimulation (VNS) treatment in patients with drug resistant epilepsy. Method: In a longitudinally retrospective study we analyzed medical records of 143 patients (81 men and 62 women) whom between 1994 and 2010 underwent implantation of VNS-device for drug-resistant epilepsy. The mean follow up time was 62 46 months, the total number of patient years was 738. Result: 251 procedures were performed in 143 patients (76 stimulator replacements). 24 patients (16.8%) were afflicted by complications related to surgery and 24 patients (16.8%) suffered from technical malfunctions. Surgical complications were: superficial infection in 5 patients, deep infection needing explantation in 5, vocal cord palsy in 8, which persisted in at least 1 patient over one year and other complications in 8. Hardware related complications were: lead wire fracture in 17, disconnection in 4, spontaneous turn-off in 2 and stimulator malfunction in 2. A tendency though, not statistically significant, was that the frequency of infections around the stimulator seemed to increase with the number of stimulator replacements. Conclusion: The complication rate and the severity of the complications to VNS surgery are in an acceptable range. VNS can safely be used as an ad on therapy in patients with drug resistant epilepsy not suitable for

Purpose: A 23-year-old rihgt handed man with typical features of LennoxGastaut syndrome and epilepsy due to hypothalamic hamartoma underwent successful endoscopic resection with seizure freedom. Ha had history of epileptic seizures since 6 years of age. Method: The diagnosis of a hypothalamic hamartoma had been made by magnetic resonance imaging (MRI) of brain . He had received previous gamma knife therapy of the hypothalamic hamartoma at 22 years of age, which did not help his seizures. At the time of presentation for surgery, he was having multiple daily seizures, including gelastic seizures, atonic seizures and generalized tonic-clonic seizures. He had failed 4 antiepileptic drugs previously. Result: His electroencephalogram showed slow generalized spike-andwave discharges at 12- hertz as well as multifocal epileptiform discharges and abnormal slow background, consistent with and typical for LennoxGastaut syndrome . Ictal - photon emission computed tomogEpilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

34 Abstracts
raphy performed during typical gelastic seizures demonstrated hypermetabolism in the hamartomas, hypothalamic region without cortical or cerebellar hypermetabolism . Conclusion: The patient underwent resective surgery and has been free of seizures. (8 months follow-up). After operation his EEG was normal. lobe), located 34.9% right and 65.1% left hemisphere; and 7.4% with multiple cavernous malformations (3% only extratemporal and 4.4% temporal and extratemporal), 20% located on the right, 20% left and 60% both hemispheres. Surgical outcome: Engel I 88.2%, Engel II 7.3%. Engel III 4.4%. Seizure frequency pre and post OP showed a statistical significance (p < 0.05). Mean follow up was 40.3 months. Morbilities: 4.4% quadrantanopsia, infection 1.5% and 0% mortality. Conclusion: Complete surgical resection, included lesionectomy plus corticectomy guided by electrocorticography demonstrates significant beneficial results with total seizure control in the majority of cases. Electrical activity could be associated with dual pathology (cavernous malformation plus cortical dysplasia).

p111 VAGUS NERVE STIMULATION FOR MEDICALLY REFRACTORY EPILEPSY: OUR EXPERIENCE IN A TERTIARY EPILEPSY CENTER AT THE UNIVERSITY OF SEVILLE P. M. Martinez*, M. Caballero*, C. M. Quesada*, R. Vazquez*, M. Oliver, Y. Chocron, and M. D. Jimenez* *University Hospital Virgen del Rocio, Sevilla, Spain; and Hospital Virgen del Rocio, Seville, Spain
Purpose: To evaluate long term outcomes in patients treated with vagus nerve stimulation (VNS). Method: Our experience with VNS at the University Hospital Virgen del Rocio is comprised of 6 patients with a mean age of 23.8 years and a mean duration of epilepsy of 10 years. These patients have been diagnosed with cryptogenic epilepsy (2 patients), epileptic encephalopathy secondary to perinatal anoxia (3 patients) and hemiconvulsion-hemiplegia-epilepsy syndrome (1 patient). All patients underwent a comprehensive presurgical evaluation and were found to be unsuitable candidates for resective epilepsy surgery. Mean post-implantation follow-up is 31 months. Efficacy of treatment in terms of reduction in number of seizures and referred side effects was assessed after the implantation of a VNS. Result: A greater than 50% reduction in seizure frequency (66%) was achieved. Two of the patients (34%) did not experience any improvement after VNS implantation. One patient (17%) had the device removed after experiencing hoarseness of voice. After implantation, the average number of hospital admission/ER visits days was significantly decreased. Conclusion: VNS is an effective and relatively safe adjunctive therapy for patients with medically refractory epilepsy not amenable to resection.

p113 PRE- AND POST-OP ACTIVATION OF THE MOTOR CORTEX IN EPILEPSY WITH HEMIPARESIS AND ROLANDIC ISCHEMIA R. F. Severino, D. Crestani, A. Palmini, J. Rubio Hoefel, E. Paglioli, R. Nunes, and J. Costa Da Costa So Lucas Hospital, Porto Alegre, Brazil
Purpose: We want to study the role of the primary motor cortex (PMC) in patients with vascular destructive lesions in perirolandic regions. Neuroplastic mechanisms operate and these patients have some motor functionality. This picture is more complex when occur seizures arousing from the scar and these area is resected. We report pre-and post-operative motor functional magnetic resonance (fMRI) findings in 12 patients with refractory epilepsy. Method: Twelve patients with congenital hemiparesis underwent presurgical fMRI. All had cortical resections and were re-scanned 12 to 36 months after surgery. Activation maps were superimposed over anatomical images; analysis using Student t test with a P<0.0001. Limbs were evaluated with neurological exam in 12 to 36 months. Result: Pre-operatively, fMRI showed 3 main patterns. The first showed activation of PMC adjacent to the destructive lesion. The second was characterized by absence of activation of the PMC ipsilateral to the lesion; and activation in the normal hemisphere. A third displayed bilateral activation of PMC. Postoperatively, patients who did not have activation of the motor cortex adjacent to the lesion regained activation, and that was accompanied by improved motor function. Conclusion: These findings suggest that the PMC in the lesioned hemisphere may play a role in the motor function of the paretic limbs. Furthermore, the post-operative activation of previously silent PMC in some patients suggests that recurrent seizures and epileptogenic discharges may inhibit potentially preserved function. The improved motor function accompanied these positive fMRI changes adds credibility and raises the issue of new therapeutic.

p112 CAVERNOUS MALFORMATIONS SURGICAL EPILEPSY SERIES R. M. Buentello Garca*, C. Domnguez Rico*, D. San Juan Orta*, H. Sentes Madrid, E. Brust Mascher*, and M. A. Alonso Vanegas* *Instituto Nacional de Neurologa y Neurociruga, Distrito Federal, Mexico; and Instituto Nacional de Nutricin y Ciencias Mdicas Salvador Zubirn, Distrito Federal, Mexico
Purpose: To describe our surgical serie of patients presenting cavernous malformations and intractable epilepsy. Method: We retrospectively reviewed our series of 68 patients who underwent complete lesion/epileptogenic zone resection, operated at the National Institute of Neurology and Neurosurgery and the ABC Medical Center in Mexico City, from January 2005 to December 2011. Inclusion criteria were: patients presenting with diagnosis of cavernous malformation and intractable epilepsy. Presurgical evaluation was carried out utilizing a modified international protocol that included among others: complete medical history, MRI, surface EEG, Video-EEG, neuropsychological testing and psychiatric evaluation, and in some selected cases fMRI. Result: Mean age of seizure onset was 26.2 (SD 12.3) years, 53.1% were men and 56.9% women, mean seizure frequency per month before surgery was 15.2 (SD 29.6). Etiology: 92.6% of patients with single cavernous malformation (29.4% extratemporal and 63.2% temporal
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

p114 ROLE OF NEURONAVIGATION DURING INVASIVE MONITORING FOR EPILEPSY SURGERY R. Vazquez, M. Caballero, P. M. Martinez, M. Rivero, J. Marquez, and M. D. Jimenez University Hospital Virgen del Rocio, Sevilla, Spain
Purpose: Invasive electrodes are used to localize the epileptogenic area in patients where structural lesions cannot be seen in imaging techniques or the epileptogenic focus is not in the cerebral cortex and they are used to map precisely the area where seizures arise. Method: We present a case of a 13 years-old patient with daily complex-partial seizures refractory to medical treatment. Video-EEG showed left temporal interictal epileptiform discharges and left theta temporal rhythm during ictal recording. Neuropsychological studies were normal. SPECT showed an area of hipoperfusion in mesial and anterior region of

35 Abstracts
the left temporal lobe. MRI showed a 1-cm left temporal subarachnoid cyst. Result: Electrocorticography with subdural electrodes covering left basal frontal, left mesial temporal and left lateral temporal areas where held during four days. The accuracy of electrodes location was assured by neuronavigation. Four seizures starting in left temporal mesial area where registered. A resection of the anterior left temporal pole was done with very successful outcomes. Conclusion: Neuronavigation with MRI allows us to plan before the craniotomy the desirable location of the invasive electrodes. Invasive electrodes need to be placed exactly on the epileptic focus to avoid recording spreading cortical discharges. In addition, neuronavigation allows us to double check the location of the invasive electrodes and quantify slight displacement before the surgical resection takes place. report results of VNS in our institute for its significance based on super selection of patient's types of seizures and responsiveness. Method: We selected a cohort of 9 patients who underwent VNS implantation (Cyberonics, Model 102 and 103) for intractable seizures who had comprehensive epilepsy evaluation using; long term EEG monitoring, dedicated structural and functional neuroimaging and neuropsychological evaluation. We studied their demographics, types of seizures, duration of epilepsy, seizure frequency pre and post VNS insertion. Result: We had 9 patients (5-males, 4-females) who underwent VNS surgery over a period of 4 years with average (+SD) age 20.6 (6.4) years. Duration of seizures before they underwent operation was 15.7 (6) years. Six patients had multi-focal epilepsy with secondary generalization and three had primary generalized epilepsy. Average duration of follow up post VNS insertion was 18.4 (+11.3) months. Mean seizure frequency was 32.4 (range: 3180) per month. Seizure frequency post surgery was 5.4 (range: 3630) per month. All but 1 had >50% improvement in seizure frequency. 7 patients improved by >70% with 1 patient being seizure free. There was no statistically significant correlation to the type of seizure and response. Conclusion: About >70% responder rates were seen in our cohort which is higher probably because of super-selection of patients after comprehensive epilepsy evaluation. VNS should be considered for patients with intractable epilepsy who are not good candidates for epilepsy surgery.

p115 TEMPORAL LOBE EPILEPSY SURGERY RESULTS OF AN EPILEPSY SURGERY UNIT WITH UP TO TEN YEARS FOLLOW UP S. Gatzonis*, N. Georgakoulias, A. Siatouni*, C. Tsekou*, T. Bouras*, E. Aggelopoulos*, M. Papathanassiou*, E. Aggelakis*, P. Patrikelis*, I. Kaskarellis*, E. Patsouris*, and D. Sakas* *Athens Medical School, Athens, Greece; and Athens General Hospital G. Genimatas, Athens, Greece
Purpose: The surgical therapy of epilepsy is nowadays an established therapy of drug resisting (dr) partial epilepsy especially for temporal lobe epilepsy (TLE). Surgical procedures for drTLE result in a curative effect with no mortality and minimal serious side effects. We present the protocol of the presurgical evaluation of patients with drTLE, the surgical procedures and the results from a single center. Method: 47 patients aged 15- 63 ys, 22 men and 25 women who were proposed for surgical therapy for drTLE. 37 patients suffered from welldefined medial temporal lobe (MTLE) syndrome. Based on patients history, interictal EEGs, long term video-EEG, Wada test and neuropsychological evaluation they underwent surgery such as antero-medial temporal lobectomy modified by Spencer or selective amygdalohippocampal excision. Individualized procedures were performed in some of the other patients based on long term electrocorticography or/and intraoperative recordings. Result: 64, 9% (24/37) of the patients with drug-resisting epilepsy of the mesial temporal lobe are classified as Engel I after the surgical procedure. Nine patients show worthwhile seizures reduction (Engel II, III) and 2 patients do not show any appreciable improvement (Engel IV). Two patients did not present at the follow-up. The percentage of patients suffered from drTLE due to structural lesions who were proposed for surgical therapy and remains seizure free is 60% (6/10). Serious permanent side effects: one patient remains with left hemiparesis. Conclusion: Drug-resistant temporal lobe epilepsy is a syndrome with a very good response to surgical treatment. Our results are in concordance with the literature.

p117 SEIZURE REDUCTION AFTER DEEP BRAIN STIMULATION IN A PATIENT WITH PARKINSON DISEASE ASSOCIATED WITH IDIOPATHIC GENERALIZED EPILEPSY T. Hoshida*, N. Maruyama*, Y. Sawai*, K. Kawata*, H. Hirabayashi*, K. Tamura, and H. Nakase *National Hospital Organization, Nara Medical Center, Nara, Japan; and Nara Medical University, Kashihara, Japan
Purpose: We report a case of seizure reduction after deep brain stimulation (DBS) of the subthalamic nuclei (STN) in a patient with idiopathic generalized epilepsy and Parkinson disease. Method: A 61-year-old woman had experienced her first seizure at 10 years of age. Generalized tonic-clonic seizures occurred during sleep. Her seizures occurred several times per year while she was taking 800 mg valproate. She also started experiencing bradykinesia and limb tremor at 51 years of age. She was diagnosed with Parkinson disease and received medical treatment. She was finding it difficult to walk; as a result, she was referred to the neurosurgery department for DBS surgery at 54 years of age. Result: Presurgical evaluation revealed no epileptic discharges during long-term electroencephalography monitoring. Valproate was discontinued and STN-DBS was performed uneventfully. Bradykinesia and bilateral tremor improved markedly after DBS. When the estimated electrical current was changed from 31.9 to 12.2 microampere at 5 months after DBS, the first postoperative seizure occurred, and administration of 400 mg valproate was restarted. One year later, when the estimated electrical current was changed from 29.3 to 15.6 microampere, the second and third postoperative seizures occurred. The estimated current was changed from 15.6 to 20.5 microampere and the patient was administered 400 mg of valproate, after which she has remained seizure free for 5.5 years. Conclusion: Stimulation current conditions may be responsible for generalized seizure. The comorbidities of idiopathic generalized epilepsy and Parkinson disease showed improvement after STN-DBS. However appropriate stimulation conditions are required for seizure reduction.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

p116 HIGHER RESPONDER RATES TO VAGAL NERVE STIMULATION: IN SUPER-SELECTIVE PATIENTS S. Sinha, E. Khalid, F. Bamogaddam, M. Flatah, A. J. Sabbagh, and K. A. Siddiqui National Neurosciences Institute, King Fahad Medical City, Riyadh, Saudi Arabia
Purpose: Vagal nerve stimulator (VNS) is a well recognized treatment for intractable epilepsy patients with upto 50% reduction in seizures. We

36 Abstracts

Genetics 1 Monday, 01 October 2012

p118 WHOLE EXOME SEQUENCING WITHIN AN IRISH PEDIGREE OF IDIOPATHIC GENERALISED EPILEPSY M. Mccormack*, G. D. OConnor, E. Heinzen, K. V. Shianna, J. Conroy, S. Ennis, D. Goldstein, N. Delanty, and G. L. Cavalleri* *Royal College of Surgeons in Ireland, Dublin, Ireland; Beaumont Hospital, Dublin 9, Ireland; Duke University, Durham, USA; and University College Dublin, Dublin, Ireland
Purpose: Approximately 40,000 people in Ireland are diagnosed with epilepsy. Beaumont Hospital is the major tertiary referral centre for epilepsy in Ireland and through clinics we have recruited pedigrees with strong familial patterns of seizures, providing a resource for identifying causal mutations in the Irish population. Method: We present a large Irish pedigree containing 21 family members across three generations of which 8 individuals have a diagnosis or suspected history of epilepsy, including absence seizures. We performed whole exome sequencing on two siblings with idiopathic generalised epilepsy (IGE) and a third sibling with localisation-related epilepsy (LRE). Result: From our analysis we limited candidate variants to those that are shared between affected individuals, functional and rare (<3% minor allele frequency in general population). Resulting candidate causal variants included two novel non-synonymous SNPs in SLC2A1, a gene that encodes the glucose transporter type 1 (GLUT1). Follow-up sequencing among the extended pedigree showed near complete segregation with a seizure phenotype. Genotyping in a large combined cohort of sporadic epilepsy cases and population controls is currently ongoing to establish the background frequency of these variants in the Irish population. Conclusion: Through whole exome sequencing in just three individuals we have identified mutations in SLC2A1 as credible causal variants for IGE and/or LRE in an Irish pedigree. It remains to be seen if these specific risk variants contribute to more sporadic forms of epilepsy. These findings mirror recent discoveries which identified a defect in GLUT1 as a rare cause of IGE in patients with absence seizures.

both patients seizures started in infancy and occurred in clusters, mainly provoked by fever, but in the first one their frequency decreased with age, while in the second one a tendency to epileptic status was present. Conclusion: Both cases confirm that seizures in clusters, initially provoked by fever, are the most common epilepsy phenotype within EFMR. Our first case is among the very few reported, where a heterozygous female PCDH19 mutation carrier did not manifest any clinical features. In our case totally skewed X-inactivation is a possibility that might explain the lack of clinical history in patient's mother, although it is not in correlation with previous study. Acknowledgments: The study was supported by Grant #49/2011, Medical University - Sofia, Bulgaria.

p120 BORDERLINE DRAVET SYNDROME - BROADENING THE PHENOTYPIC SPECTRUM OF PYRIDOXINEDEPENDENT EPILEPSY A. Baumgart*, M. Van Kempen, N. Verhoeven, R. Stensbjerre Mller, R. Boor, H. Muhle*, J. Albers*, L. L. Klitten, H. Hjalgrim, D. Lindhout, U. Stephani*, I. Helbig*, and S. Von Spiczak* *University Medical Center Schleswig-Holstein, Kiel, Germany; University Medical Centre Utrecht, Utrecht, The Netherlands; Danish Epilepsy Centre, Dianalund, Denmark; and Northern German Epilepsy Centre, Schwentinental/Raisdorf, Germany
Purpose: Pyridoxine dependent epilepsy (PDE) and pyridoxal-5-phosphate deficiency are rare autosomal recessive enzyme defects in vitamin B6 metabolism due to mutations in the ALDH7A1 and PNPO gene. The phenotypic variability, however, is broad. The aim of this study was to asses the frequency of vitamin B6 deficiencies in unexplained infantile epilepsy. Method: We screened 113 patients with unclear epilepsy syndromes starting in the first year of life for mutations in ALDH7A1 and PNPO. Mutation analysis of the entire coding region of both genes including adjacent splice sites was performed. Result: No pathogenic mutations in PNPO were found. Sequence analysis of ALDH7A1 identified one patient as compound heterozygous for both a novel, likely pathogenic c.1468A>G; p.Arg490Gly variant and a known mutation c.1195G>C; p.Glu399Gln. The patient had a single neonatal seizure on postnatal day 5. In the course of the disease, he presented with a Dravet-like phenotype including alternating hemiclonic seizures, prolonged seizures with febrile infections, theta rhythms and generalized discharges on the EEG and developmental delay plateauing from the age of 2 years onwards. Partial response to antiepileptic drugs was observed as well as long seizure-free periods in adolescence. The patient never received pyridoxine treatment and died at age 31 from epileptic status prior to genetic diagnosis. Conclusion: PDE should be considered in infants with severe epilepsies including Dravet-like phenotypes. PDE may result in atypical phenotypes mimicking well-defined epilepsy syndromes with partial response to anticonvulsive drugs and seizure-free periods without pyridoxine treatment.

p119 PILOT STUDY FOR PCDH19 GENE TESTING IN BULGARIA P. Dimova*, A. Kirov, A. Todorova, T. Todorov, B. Sukhudyan, V. Bojinova*, and V. Mitev *St. Naum University Hospital of Neurology and Psychiatry, Sofia, Bulgaria; Medical University, Sofia, Bulgaria; and Arabkir Joint Medical Center and Institute of Child and Adolescent Health, Yerevan, Armenia
Purpose: To report the results of the first genetic study for detection of PCDH19 mutations in Bulgaria. Mutations in this gene cause the Xlinked Epilepsy and Mental Retardation Limited to Females (EFMR), which is characterized by seizure onset in infancy or early childhood, cognitive impairment, and large phenotypic, including intrafamilial variability. Usually, the PCDH19 mutations arise de novo, or are inherited by the unaffected carrier fathers or by affected mothers. Method: Whole PCDH19 gene sequencing was performed in 10 female patients with early onset epileptic encephalopathy. Result: The molecular genetic study showed two novel PCDH19 mutations - c.2705dupA; p.Asp902Lysfs*6, and c.1091delC; p.Pro364Argfs*4. In the first case, the healthy mother was a heterozygous asymptomatic carrier. The second mutation c.1091delC was de novo. In
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

p121 PAEDIATRIC DIAGNOSIS NOT MADE UNTIL ADILTHOOD: A CASE OF WOLF-HIRSCHHORN SYNDROME A. Coppola*, V. K. Chintaphalli*, P. Hammond, J. W. Sander, and S. M. Sisodiya *Institute of Neurology, University College London, London, UK; UCL Institute of Child Health, London, UK; Heemstede, The Netherlands; and UCL Institute of Neurology, London, UK

37 Abstracts
Purpose: Wolf-Hirschhorn Syndrome (WHS) is a well-known syndrome caused by 4p terminal deletion. The distinctive clinical features (facial dysmorphism, somatic defects, neurological impairment and seizures) typically lead to a genetic diagnosis early in life. Seizure onset is typically within the first year of life with febrile seizures, sometimes leading to status epilepticus. Seizures tend to improve/cease with age. We report on a person in whom the diagnosis was only made in adulthood through array-CGH. Method: The patient is aged 34 years. At 7 months she experienced a tonic-clonic convulsion, at 10 months spasms, at 3 years convulsive status epilepticus and at 13 atonic seizures. At 23, she came under our care. Examination showed moderate learning disability and minor dysmorphisms, but no syndromic diagnosis was made despite three clinical genetics reviews. Her epilepsy has always been drug-resistant. Currently, she continues to experience 13 seizures/month, exacerbated by high temperature. Genome-wide comparative genomic hybridization and three-dimensional quantitative facial analysis have been performed. Result: Array-CGH showed a 1.8 Mb 4p16.3 deletion. 3D quantitative facial analysis classified her subtle facial dysmorphism as WHS-like. Conclusion: This case highlights several issues: milder dysmorphic features can be missed by clinical examination; quantitative facial analysis can suggest diagnosis; array-CGH is an important diagnostic tool in adults with drug-resistant epilepsy and additional features, even when clinical diagnoses have not been made; the phenotypic spectrum of even well-known syndromes may be broader than typically appreciated.

p123 HIPPOCAMPAL SCLEROSIS WORSENS ADNFLE PHENOTYPE RELATED TO CHRNB2 MUTATION A. Labate*, L. Mumoli*, A. Fratto*, A. Quattrone*, and A. Gambardella *University Magna Graecia Catanzaro, Catanzaro, Italy; and Institute of Neurological Sciences, Mangone (CS), Italy
Purpose: Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a distinct epileptic syndrome with a broad range of severity even among affected members of the same pedigree, and the level of pharmacoresistance may reach 30%, close to that seen in sporadic focal epilepsies. Method: To investigate this issue of phenotypic heterogeneity, we carried out a high-resolution MRI study in the ADNFLE family carrying the V287L mutation of the CHRN beta2 subunit (CHRNB2), which includes one pharmacoresistant patient. All 10 affected members were prospectively examined using a 3 Tesla MR750 GE MRI scanner with a 8-channel head coil, based on a protocol routinely used at our clinic for patients with epilepsy. MRI studies were evaluated in a manner blinded to the electro-clinical data. Result: The brain MRI was normal in all affected individuals except the right-handed 22 year-old girl (member III-7) with normal intellect, who had refractory seizures and typical radiological signs of left hippocampal sclerosis (Hs). She had also had febrile seizures at age of 10 months. Conclusion: The results of this study illustrate that Hs has offered a fertile substrate to develop intractable ADNFLE.

p122 DISTRIBUTION OF ELP4 POLYMORPHISMS IN ROLANDIC EPILEPSY PATIENTS IN RELATION TO CLINICAL PARAMETERS A. Gkampeta, L. Fidani, E. Pavlou, T. Katopodi, and F. Athanasiadou-Piperopoulou Aristotle University of Thessaloniki, Thessaloniki, Greece
Purpose: Rolandic epilepsy (RE) is one of the most frequent epileptic syndromes in children. ELP4 is a component of the elongator complex, involved in transcription and tRNA modification. The aim of this study was to investigate the possible effect of ELP4-Ear1 and ELP4-BsrGI genotypes to specific clinical characteristics of children with RE. Method: 31 children from northern Greece diagnosed with RE (age range: 416 years) were genotyped for the ELP4-Ear1 and ELP4-BsrGI polymorphisms. The polymorphisms were detected with a PCR-RFLP method, after designation of specific primers, PCR amplification and enzyme digest of the relevant fragment. The relationship of ELP4 polymorphisms to clinical characteristics such as electroencephalographic (EEG) features, type of seizures and response to medication were rated with the Chi-square test of independence. Result: ELP4-Ear1 polymorphisms (A/A, G/G, A/G) when compared with EEG features, type of seizures and response to medication did not show any significant difference (P=0.681, P=0.359 and P=0.454 respectively). Similarly, neither ELP4-BsrGI polymorphisms (G/T, G/G, T/T) showed any significant difference (P=0.599, P=0.704 and P=0.787 respectively). Conclusion: The presence of ELP4-Ear1 G allele was associated with bilateral EEG features, while the ELP4-BsrGI G allele associated with lateral EEG features and a better outcome with complete control of seizures for more than two years after seizure onset. Further studies in larger cohort of patients are needed in order to clarify the effect of ELP4 genetic variations on clinical parameters in children with RE.

p124 EUROEPINOMICS RES AR WORKING GROUP - A SHARED RESOURCE FOR THE IDENTIFICATION OF RISK FACTORS IN AUTOSOMAL RECESSIVE EPILEPSIES A. Suls*, S. Weckhuysen*, P. De Jonghe*, and A. W. G. Euroepinomics Res Crp *VIB, Wilrijk, Belgium; and euroepinomics/index.php/projects-crps/res-main, Europe
Purpose: The aim of the autosomal recessive (AR) working group of the EuroEPINOMICS consortium on rare epilepsy syndromes (RES) is to elucidate the role of AR variants in epilepsies, as this is for the moment not well documented. Method: Within the consortium we collect all families that are or can be compatible with an AR mode of inheritance. We apply homozygosity mapping in a subtype of families followed by whole exome sequencing (WES) and copy number variation analysis to identify causal variants. Result: We ascertained within our consortium 23 consanguineous epilepsy families and 32 sibs with different types of epileptic encephalopathies (EE). Collection of additional families is an ongoing effort. In consanguineous families homozygous variants are most likely causing the disease. By performing homozygosity mapping on one consanguineous epilepsy family we could identify a disease locus on chromosome 21 (~9Mb). The analysis of the sequencing data of this locus is ongoing. If no homozygous variants/locus is identified in these families, other genetic hypotheses will also be tested on the generated data. In sibs with EE several genetic hypotheses are tested: homozygous model, compound heterozygous model and de novo mosaic autosomal dominant model. Analysis of WES data on the sib pairs is ongoing. Conclusion: The large amount of families with different ethnical backgrounds compatible with an AR mode of inheritance we collected and the preliminary genetic data we generated shows furthermore that recessive variants are likely to cause some genetic epilepsies. Further genetic analyses will elucidate the proportion of AR inheritance in epilepsies.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

38 Abstracts
p125 IDENTIFICATION OF A NOVEL GENE IN A FAMILY WITH SEVERE INFANTILE-ONSET EPILEPSY C. Depondt*, Y. Hitomi, E. Heinzen, S. Donatello*, H. Dahl, S. Berkovic, I. E. Scheffer, B. Legros*, M. Pandolfo*, D. Goldstein, and P. Van Bogaert* *Universit Libre de Bruxelles, Brussels, Belgium; Duke University, Durham, USA; and University of Melbourne, Melbourne, Australia
Purpose: To describe the clinical characteristics, genetic analysis and functional studies in a family with autosomal recessive, infantile-onset epilepsy and psychomotor retardation. Method: We identified a family with 3/3 siblings with infantile-onset epilepsy and psychomotor regression. Two siblings were exome sequenced. Shared homozygous, novel variants were sequenced in all 3 siblings and their parents. Result: Onset of focal seizures was between 19 and 35 months and psychomotor regression occurred soon after. Seizures were refractory to medical treatment. Exome sequencing identified a homozygous missense variant in the gene TNK2, encoding a brain-expressed tyrosine kinase. All 3 siblings were homozygous for the variant and both parents were heterozygous. Genotyping of the variant in 3034 patients with epilepsy and 1663 controls revealed no further homozygotes and very low frequencies of heterozygotes (0.002). Sequencing of all 15 exons and splice sites of the TNK2 gene in 110 patients with infantile-onset epilepsies, as well as analysis of next-generation sequencing data in 131 cases with genetic generalized epilepsies and 297 controls showed no enrichment of putative functional variants in cases compared to controls, although heterozygous truncating variants were overrepresented in patients with severe infantile epilepsy. Functional studies demonstrated that the identified variant abolishes NEDD4 binding to TNK2, preventing its degradation after epidermal growth factor stimulation. Conclusion: The combined results of our genetic and functional studies suggest TNK2 as a novel gene for severe infantile-onset epilepsy. Definitive confirmation of pathogenicity will require identification in unrelated patients. Result: The epilepsy phenotypes due to p.Arg1596 substitutions in all three families fit to the spectrum of GEFS+. The epilepsy phenotypes differ between probands and in mutation carriers range from asymptomatic, through FS, GEFS+ to borderline DS and focal seizures. In all families, we were able to analyse three generations and we observed the worsening of the symptoms in following generations. Conclusion: The differences in clinical DS/GEFS+ picture resulting from the mutations of the same residue in the SCN1A gene may suggest involvement of genetic modifiers in final phenotype development.

p127 PHENOTYPING DRUG RESPONSE IN EPILEPSY E. Caruana Galizia, K. Chinthapalli, J. Novy, J. W. Sander, and S. M. Sisodiya Institute of Neurology, London, UK
Purpose: Little attention has been given to the spectrum of drug response in epilepsy. With a much recognized need for multicentre collaborations, case definition will be key for appropriate case ascertainment. We propose definitions for different response groups in patients exposed to levetiracetam and demonstrate the emergence of six different response patterns. Method: All data were collected retrospectively by accessing patient medical. The following definitions were applied in order to classify the response pattern: the seizure-free group was defined as those cases that achieved seizure freedom for a minimum of 12 months; partial responders were defined as any case in which the number of seizures improved by >25% from baseline; non-responders were defined as those cases with no more than a 25% fluctuation above or below baseline; seizure-worsening was defined as >25% worsening of seizure frequency from baseline. Result: Data were collected on 859 individuals and were distributed within the different response groups as follows: Seizure free group, 105 cases; Partial responders, 147 cases; Non-responders, 92 cases; Seizure worsening, 82 cases. Response could not be classified in 242 cases. Two other response patterns emerged: response before return to baseline (48 cases) and response before worsening (45 cases). Conclusion: We demonstrate that for the majority of cases the pattern of drug response can be classified into one of six different response-phenotypes. This work lays down the foundations for phenotyping of drug response in much needed multi-centre studies in epilepsy pharmacogenetics.

p126 CLINICAL VARIABILITY RESULTING FROM THE MUTATIONS AT THE P.ARG1596 RESIDUE IN THE SCN1A GENE D. Hoffman-Zacharska, E. Szczepanik, R. Tataj, I. Terczynska, ska-Ciuchta, Z. Zalewska-Miszkura, D. AntczakA. Goszczan Marach, and J. Bal Institute of Mother and Child, Warsaw, Poland
Purpose: SCN1A, the gene encoding the sodium channel alpha 1 subunit, is one of the most important epilepsy genes. Mutation in SCN1A are associated with various types of epilepsy. The clinical spectrum of SCN1A mutations ranges from benign FS through spectrum of GEFS+ to severe epilepsy syndromes such as Dravet Syndrome (DS) and intractable childhood epilepsy with generalized tonic-clonic seizures (ICEGTC). All identified SCN1A mutations are dominant and usually occur de novo, however familial cases also are described (510%). In the most families proband, shows the severe form of disease, while the remaining family members milder GEFS+ spectrum. We present unrelated DS/ GEFS+ families, where disease is caused by missense mutations at residue p.Arg1596 of the Nav1.1 protein. Method: Three unrelated multi-generations families with p.Arg1596 missense mutations p.Arg1596His (2 families) and p.Arg1506Cys in the SCN1A gene were enrolled into the study. Mutations were identified by direct sequencing of the SCN1A gene. Phenotypes of epilepsies were classified according to ILAE classification.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

p128 GLRB IS THE 3RD MAJOR GENE-OF-EFFECT IN HYPEREKPLEXIA S. K. Chung*, C. A. Hunt*, A. V. Derrick*, T. D. Cushion, S. E. Wood*, C. Drew*, O. W. Howells*, R. H. Thomas*, and M. I. Rees* *Institute of Life Science, Swansea, UK; and Swansea University, Swansea, UK
Purpose: Glycinergic neurotransmission is a major inhibitory influence in the central nervous system (CNS) and defects are primarily associated with paroxysmal neuromotor disorder, hyperekplexia or startle disease. The alpha1 subunit of the glycine receptor (GlyR) gene (GLRA1) and its cognate postsynaptic transporter (SLC6A5) are well-established genesof-effect in hyperekplexia, nevertheless, up to 60% of hyperekplexia cases remain gene-negative. The beta subunit of the glycine receptor (GLRB), the heteropentameric partner subunit to GlyRa1, was selected for further analysis in gene-negative cases. Method: 92 gene-negative hyperekplexia patients were selected for variation screening of the GLRB using multiplex PCR and direct Sanger sequencing approach. All variants were excluded from normal controls and mutation constructs were prepared for functional characterisation.

39 Abstracts
Molecular modelling was also used to predict protein-damaging outcomes. Result: This study identified 9 novel GLRB mutations within 8 independent hyperekplexia index-cases accounting for approximately 9% of the gene-negative cohort. This included 5 recessive, 2 dominant and 1 compound heterozygote inheritance scenarios, and were classified as 2 nonsense, 5 indels and 2 missense variants. The biological consequence of the nonsense and indel mutations was unambiguous and the 2 missense mutations were further investigated for electrophysiological analysis. Conclusion: This study describes the largest genetic screening of GLRB in hyperekplexia and represents a 3rd major gene for hyperekplexia. It further implicates the glycinergic proteome as the basis for further analysis. Purpose: The Val66Met (rs6265) polymorphism in the brain-derived neurotrophic factor gene (BDNF) has been associated with cognitive performance as well as structural and functional hippocampal differences, in healthy controls and some clinical populations. Deregulation of BDNF expression has also been implicated in the mechanisms underlying epileptogenesis. Mesial temporal lobe epilepsy (mTLE) is the most common partial epilepsy in adults who medically refractory. Patients with mTLE usually present cognitive dysfunction with memory impairment as a prominent cognitive deficit. Approximately one third of patients also experience significant post-operative memory decline and transient language dysfunction following epilepsy surgery. Method: We investigated the association of Val66Met polymorphism with the results of cognitive tests (n=282), hippocampus volume (n=108) and fMRI data (n=47) during memory-encoding and language paradigms in a group of patients with mTLE. Result: Independently of the age, gender and seizure laterality (right or left) the patients with mTLE and carriers of met allele (n=83) had significantly lower scores in delayed memory tasks and were significantly more likely to display post-operative decline in measures of both verbal and visual memory than Val homozygotes patients (n=199). There was no significant effect of the genotype on immediate memory, fluency or hippocampus volume. fMRI activation during memory encoding and verbal fluency revealed the Met allele carriers had significantly reduced default mode network activation compared to Val/Val carriers. Conclusion: These results suggest the BDNF Val66Met polymorphism may contribute to memory function in patients with mTLE and may influence the responsiveness of the default mode network.

p129 PHARMACOGENOMICS OF VALPORATE INDUCED WEIGHT GAIN J. Chukwu*, S. Tirupathi, M. King, B. Lynch, B. Mccoy, D. Goldstein, N. Delanty**, G. L. Cavalleri*, and D. Webb *Royal College of Surgeons in Ireland, Dublin, Ireland; Royal Hospital Belfast, Belfast, UK; Children's University Hospital, Dublin, Ireland; Our Lady's children's Hospital Crumlin, Dublin, Ireland; Duke University Institute for Genome Sciences and Policy, Durham, NC, USA; **Beaumont Hospital, Dublin, Ireland; and Adelaide & Meath Hospital Incorporating National Children's Hospital Dublin, Dublin, Ireland
Purpose: Sodium valproate (VPA) is one of the most commonly used AEDs in the treatment of partial and generalised seizure disorders. Weight gain is one of the known side effects of VPA. It has been estimated that between 10 and 70% of people exposed to VPA experience some weight gain. About 10% of these patients have significant weight gain (> 10% of pre-VPA initiation weight) necessitating discontinuation of therapy. The exact mechanism of weight gain in VPA is not fully understood. This study seeks to test the hypothesis that individuals with common genetic variants associated with obesity are more prone to developing VPA-induced weight gain than those who do not. This will be explored in a paediatric cohort diagnosed with epilepsy and take VPA as antiepileptic drug. Method: Retrospective study looking at clinical phenotype of paediatric epilepsy patients in Dublin. Phenotypic data will be utilised in correlating the results with genome wide association analysis on patient DNA samples. Result: 152 patients have been recruited to the study to date. It is hoped that by December 2012, 250 individuals would have been recruited. Conclusion: Using the latest technology in the study of human genome it is hoped that the genomic factors responsible for the weight change in children with epilepsy taking valproic acid will be determined.

p131 A COMPOUND HETEROZYGOUS MISSENSE MUTATION AND A LARGE DELETION IN THE KCTD7 GENE PRESENTING AS AN OPSOCLONUS-MYOCLONUS ATAXIALIKE SYNDROME L. Blumkin*, S. Kivity, D. Lev, E. Leshinsky-Silver, and T. Lerman-Sagie *Holon, Israel; and Wolfson Medical Center, Holon, Israel
Purpose: To describe a new presentation of KCTD7 mutation: an opsoclonus-myoclonus ataxia like syndrome with subsequent development of generalized continuous epileptic activity without clinical correlation, and partial clinical response to steroid therapy. Method: We recorded the clinical course of the disease, the evaluation and the response to steroid therapy. The patient is a five-year-old boy who was diagnosed as having opsoclonus-myoclonus ataxia syndrome at the age of 16 months and was therefore treated by an OMS protocol including high dose ACTH, and later dexamethasone. After the appearance of continuous epileptic activity on recurrent video -electroencephalographic studies at the age of 3 and a half year a neurodegenerative disorder was suspected. After excluding possible genetic causes, whole genome exome sequencing was performed in order to identify the causative gene. Sequence variants were filtered according to the phenotype. Sanger sequencing was performed to confirm the point mutation and MLPA was used for screening for a possible deletion in the second allele. Result: Two pathological variants were found in the KCTD7 gene: R84W and a large deletion of exons 3 and 4. The father is heterozygous for the R84W mutation and the mother is heterozygous for the exon 3+4 deletion. Conclusion: KCTD7 mutations were described in a single family with progressive myoclonus epilepsy. Our patient presented with non epileptic myoclonus, ataxia and opsoclonus responsive to corticosteroid treatment and only two years later developed an epileptic EEG witout overt seizures. The different phenotype broadens the spectrum of KCTD7 related diseases.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

Genetics 2 Monday, 01 October 2012

p130 DOES THE BDNF VAL66MET POLYMORPHISM INFLUENCE COGNITIVE FUNCTION IN PATIENTS WITH MTLE? J. Stretton, A. Foulkes, P. J. Thompson, S. Baxendale, M. K. Sidhu, E. Williams, J. Burdett, S. M. Sisodiya, J. Duncan, and M. Matarin UCL, London, UK

40 Abstracts
p132 SUDEP AND FAMILIAL EPILEPSY R. H. Thomas*, W. O. Pickrell*, A. J. Johnston*, C. Hammond, C. Drew*, P. Smith, and M. I. Rees *Wales Epilepsy Research Network, Swansea, UK; Guy's and St Thomas NHS Foundation Trust, London; University Hospital of Wales, Cardiff; and Swansea University, Swansea, UK
Purpose: The Wales Epilepsy Research Network has been continually recruiting epilepsy families since 2006 into genetic studies. The causes of sudden unexpected death in epilepsy (SUDEP) are yet to be fully determined but amongst competing theories are genetic causes of cardiac or respiratory failure. Method: The first eighty families recruited into our study were available for analysis. The consensus definition for SUDEP was used to identify cases (Nashef 2011) and project records and clinical notes were scrutinised for clinical characteristics. Result: Sixteen of the eighty families had a probable or definite SUDEP case; no family had two SUDEP deaths. Not one of these occurred following recruitment (and so we have no DNA for analysis) and there were no clear clinical patterns to be identified from the familial epilepsy diagnosis. It was common for the sibling of the person who had a SUDEP to be the affected index case. Conclusion: We are unable to conclude that familial epilepsy is a proven risk for SUDEP. Rather we propose that families with epilepsy that have had a SUDEP death are strongly motivated to participate in research and that investigators should not be deterred from involving them in genetic research. mutations were identified in the KIF17. 5. The mutation probably lies elsewhere in the identified homozygous region.

p134 STXBP1 MUTATIONS AS A CAUSE OF DRAVET SYNDROME S. Weckhuysen*, P. Holmgren*, A. Suls*, R. Hendrickx*, R. Steensjberre Mller, H. Hjalmgrim, G. Carvill, H. Mefford, I. E. Scheffer, and P. De Jonghe* *University of Antwerp, VIB Department of Molecular Genetics, Antwerp, Belgium; Danish Epilepsy Centre, Dianalund, Denmark; Instute for Regional Health Services, University of Southern Denmark, Odense, Denmark; University of Washington, Division of Genetic Medicine, Seattle, USA; and 7Florey Neurosciences Institutes, Austin Health, Melbourne, Australia
Purpose: STXBP1 mutations have been described in Ohtahara syndrome, West syndrome and in patients with an unclassified early onset epileptic encephalopathy. Although a phenotypic spectrum of STXBP1 encephalopathy is emerging, further delineation of the spectrum is still needed. Furthermore, the genetic cause for 20% of Dravet patients is still unknown. With this study we aimed to identify additional genes for Dravet syndrome, and to specify whether STXBP1 mutations are present in this severe epilepsy syndrome. Method: We combined two complementary strategies: STXBP1 screening was performed in a wide range of severe epilepsies including 22 patients with Dravet syndrome. Additionally whole exome sequencing (WES) was performed on a cohort of SCN1A negative Dravet patients and their parents. Findings were confirmed by classical Sanger sequencing. Result: We detected 2 de novo missense mutations in 2 patients with Dravet syndrome. c.1334A>C was detected by direct Sanger sequencing of STXBP1 and c.847G>A by WES. Seizure onset was at 6 and 11 months respectively. Both patients had febrile seizures and multiple afebrile seizure types. EEG showed multifocal epileptiform activity in both patients. Development slowed down after epilepsy onset in both patients, although in the first patient some delay was noticed already at the age of 3 months. At age 19 years he is severely mentally disabled and wheel chair bound. The second patient has a normal neurological exam. Conclusion: STXPB1 mutations are a rare cause of Dravet syndrome. Screening of STXBP1 in larger cohorts of SCN1A negative Dravet is currently ongoing.

p133 FAMILIAL MOVEMENT-INDUCED REFLEX EPILEPSY (FMIRE): A NOVEL GENETIC EPILEPSY SYNDROME WITH POSSIBLE MAPPING TO CHROMOSOME 1P S. Schirwani, and D. Crompton Institute of Genetic Medicine/Newcastle University, Newcastle upon Tyne, UK
Purpose: 1. To evaluate relative merits of various linkage and homozygosity mapping tools in a small UK family with a novel movementinduced reflex epilepsy in two siblings. Repetitive voluntary movement of any body part evokes voluntary clonus in that body part, clonus either subsided within seconds or culminates in generalized tonic-clonic seizures. 2. Attempt to identify the causative gene. Method: Various linkage analysis and homozygosity mapping methods were evaluated then applied to genome wide SNP data from the FMIRE family. Copy number variant (CNV) analysis was also performed. Candidate genes were selected from the homozygous region. The most likely candidate gene was sequenced. Result: A 2.0 Mb homozygous region was identified on chromosome 1. This region was homozygous in the affected sib-pair but not in the unaffected sibling or parents. KIF17, which is a brain specific motor protein involved in transporting ion channels, was identified as the most likely candidate gene. Sequencing KIF17 gene revealed many variants, though non of these were likely to be pathological. No pathological CNV was found, this result therefore did not contradict the homozygous model for FMIRE. Parametric linkage analysis using a recessive model did not show linkage signals. This result was expected due to small size of FMIRE family. Conclusion: 1. In Familial movement-induced reflex epilepsy voluntary movement induces focal clonus, then generalised tonic-clonic seizures. 2. Recessive inheritance is likely. 3. Homozygosity mapping identified a promising homozygous region on chromosome 1. 4. No pathogenic
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

p135 DENSE SURFACE MODELS OF FACE SHAPE ASSIST IN PREDICTING PATHOGENIC COPY NUMBER VARIANTS K. Chinthapalli*, E. Bartolini*, J. Novy*, M. Suttie, C. Marini, M. Falchi, Z. Fox, L. Clayton*, J. W. Sander*, R. Guerrini, C. Depondt, R. Hennekam**, P. Hammond, and S. M. Sisodiya* *UCL Institute of Neurology, London, UK; UCL Institute of Child Health, London, UK; Children's Hospital Meyer, Florence, Italy; UCL, London, UK; Universit Libre de Bruxelles, Brussels, Belgium; and **University of Amsterdam, Amsterdam, The Netherlands
Purpose: Copy number variants (CNVs) are increasingly recognised as genetic contributors to epilepsy. Pathogenic CNVs can manifest as a

41 Abstracts
range of phenotypes, such as intellectual disability, autism, partial or generalised epilepsy syndromes, and are important to detect. Facial dysmorphism also arises from CNVs and we show that people with epilepsy related to CNVs have a more atypical face shape. Furthermore, in people with epilepsy, face shape analysis is shown to successfully predict those carrying pathogenic CNVs. Method: Stereophotogrammetry was used to capture 3D face surface images of 181 patients with epilepsy and 336 control subjects. All patients underwent molecular analysis to determine the occurrence of CNVs. Images of 118 patients and all controls were used to build dense surface models for the face, periorbital region and perinasal region. We then quantified a measurement of face shape difference (FSD) for face regions and determined correlation of FSD with occurrence of CNVs. Predictive accuracy of the correlation was tested unseen on a second group of 63 patients. Result: FSD predicted presence of a pathogenic CNV in 63 new patients with high sensitivity (80%) and specificity (78%). Within all 181 patients, 43 had pathogenic CNVs and significantly more atypical periorbital (Mann-Whitney test; p<0.001), perinasal (p<0.001) and facial (p<0.001) shapes. These differences were not explained by age, ethnicity, anti-epileptic drug use or facial injury. Conclusion: In people with epilepsy, stereophotogrammetry and face shape analysis can successfully and objectively assist in identifying those with pathogenic CNVs. This can lead to earlier diagnosis and improved management of their epilepsy.

p137 EFFECT OF UGT1A6*2 GENETIC POLYMORPHISM ON THE DOSES, PLASMA CONCENTRATION AND METABOLISM OF VALPROIC ACID IN PATIENTS WITH EPILEPSY FROM R.MACEDONIA Z. Sterjev*, G. A. Kiteva-Trencevska, J. T. Ribarska*, E. Cvetkovska, I. Kuzmanovski, I. Petrov, A. K. Nestorovska*, N. Matevska*, Z. Naumoska*, A. Dimovski*, and L. Suturkova* *Faculty of Pharmacy, Skopje, Macedonia; and University Clinic of Neurology, Skopje, Macedonia
Purpose: The GG genotype of UGTIA6 A541G polymorphism has been associated with high enzyme activity compared to the wild type AA genotype. The aim of our study was to investigate the distribution and frequency of UGTIA6*2 genotype in epileptic patients (113 VPA responders/40 VPA resistant patients) and to evaluate the effects of this polymorphisms on maintenance doses, plasma concentrations and metabolism of VPA. Method: TaqMan assay-real time PCR, fluorescence polarization immunoassay and HPLC method. Result: No statistically significant difference in the allelic frequency and genotype distribution (0.49, 0.35, and 0.15, and 0.32, 0.52 and 0.15 for AA, AG and GG genotypes, p=0.46) was determined between VPA responders and VPA resistant patients, respectively. The mean values of daily maintenance doses of VPA in patients with AA, AG and GG were: 883mg+/)350.4, 977.5mg+/)359.1 and 961.7mg+/)346.6, respectively. The values of total plasma levels corresponding to the genotypes were 367.5 133.5 lmol/L for AA, 380.2+/)111.2 lmol/L for AG and 353.6+/)122.5 lmol/L for GG genotype. The differences in doses and plasma concentrations were not statistically significant (KW test H=2.45 p=0.29 and ANOVA F=0.28 p=0.76). Patients with GG genotype were associated with higher value for Ke compared to patients with AA genotype (0.04h-1 +/) 0.01 vs 0.03h-1 +/) 0.01, respectively). Patients with GG genotype had lower values for E1/2, AUC, Mean Residence Time MRT, Cmax and Tmax of VPA. Conclusion: Our data suggest that patients with GG genotype for UGTIA6 A541G polymorphisms are associated with higher maintenance daily doses of VPA, lower plasma concentrations and faster elimination of this antiepileptic drug.

p136 ALICE IN WONDERLAND SYNDROME: EPILEPSY, MIGRAINE OR BOTH? W. O. Pickrell*, R. H. Thomas, A. J. Johnston, C. White, and M. I. Rees *Institute of Life Sciences, Swansea, UK; Wales Epilepsy Research Network, Swansea, UK; and Morriston Hospital, Swansea, UK
Purpose: We present a family where 10 members of the pedigree suffer distinct, stereotyped episodes of hyper and hyposchematia, metamorphopsia including teleopsia and pelopsia and altered time awareness consistent with the Alice in Wonderland Syndrome (AIWS). Descriptions of the episodes include sensations of time slowing and speeding, sensations of hand and jaw enlargement and feelings of being detached from reality. Amongst the 10 affected family members, 4 also have epilepsy, 1 also has migraine and 3 people only have AIWS. Method: We conducted an study of AIWS incidences in epilepsy and migraine to assess its potential as a synergistic feature bridging both phenotypes (if not more). Result: Since the first published description of AIWS in 1955, there have been several reports describing associations with migraine, epilepsy, viral Illnesses (Epstein Barr Virus and H1N1) and also drugs including topiramate and dihydrocodeine. The fact that AIWS can occur with or without migraine or typical epileptic seizures raises the question as to its exact nature is it a form of migraine, epilepsy, both (migralepsy) or neither? Conclusion: There is phenotypic overlap between migraine and epilepsy and presentation of AIWS: Mutations in genes encoding ion channels have recently been associated with both migraine and epilepsy. The abnormally high incidence of AIWS, migraine and epilepsy in this family means there is a underlying genetic cause which we are currently investigating. A biological model for the pathogenesis of AIWS could help further our understanding of both migraine and epilepsy - the two most common paroxysmal brain disorders.

Purpose: Although 30% of all epileptic patients are resistant to antiepileptic drugs (AEDs), currently a trial-and-error approach is employed to determine the most effective AED and dosage for a patient. Pharmacogenetic testing for variations in the genes encoding drug-metabolizing enzymes and drug transporters has been proposed as a personalized medicine for these patients. The aim of this study is to describe our experience in 10 consecutive refractory epileptic patients. Method: Ten mentally retarded and refractory epileptic patients were enrolled in this study. A genetic test (Neurofarmagen epilepsy) for measurement of 11 genetic variations of single nucleotide polymorphisms was performed. Number of pharmacogenetic variations, AEDs affected for these pharmacogenetic variations, antiepileptic therapy modifications, clinical improvement of the patients and decrease of seizures were collected and analyzed. Result: All enrolled patients displayed pharmacogenetic variations (3.80.8) and all of them showed affected AEDs (7.84.2). Most
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

42 Abstracts
frequently involved genes were ACBC1, SCN1A and EPHX1. According to these results, antiepileptic therapy was modified in 7 patients (70%) including AEDs changes and their dosages. A clinical improvement was achieved in 5 patients (50%): 3 of them obtained a better control of their epilepsy while 2 of them achieved a better side effects profile. Conclusion: Personalized medicine for epilepsy based on pharmacogenomic testing is a new avenue for optimizing AED therapy. According to our results, some refractory epileptic patients may benefit from pharmacogenetic testing for variations in the genes encoding drug-metabolizing enzymes and drug transporters of AEDs. More studies are warranted to confirm these results. assumed a recessive model, either homozygous or compound heterozygous in the multiplex families, while in the sporadic cases a de novo mutation is an additional possibility. Whole exome sequencing was performed to identify candidate mutations. Result: So far, we have identified mutations in X-linked genes CDK16 and GABRE as possible candidates in male patients. Further analysis of the remaining families may identify more candidate mutations. To confirm their pathogenicity, we will combine our results with those of other research groups. Conclusion: Whole exome sequencing can be used to identify genetic causes for monogenic disease when performed in families.

p139 EXPANDING THE ROLE OF COPY NUMBER VARIATION IN EPILEPSY PATHOLOGY L. Addis, D. A. Collier, and D. K. Pal Institute of Psychiatry, King's College London, London, UK
Purpose: Copy Number Variation (CNV) has a well-documented association with epilepsy. We seek to expand the genotype-phenotype relationships between epilepsy and other neurodevelopmental disorders with CNV using the clinical genetics database, Brain and Body Genetic Resource Exchange (BB-GRE). Method: 10,397 individuals referred for cytogenetic investigation were analysed for CNV using a customized 44K Agilent comparative genomic hybridization (aCGH) array. aCGH results were entered into BB-GRE. We searched BB-GRE for the phenotype epilepsy or seizure. Cases were compared with controls in DECIPHER and DGV databases. Result: We identified 186 patients with epilepsy or seizures. 63% of these patients also had developmental delay or intellectual disability. 30% reported ADHD, speech/language problems or autism. We found 23 patients with large CNVs at known neurocognitive disorder hotspots; 16p11.2 (n=8), 15q13.3 (n=6), 22q11.21 (n=4), 16p13.11 (n=3), 1q21.1 (n=2). Another patient had a large novel deletion of 11.7Mb on 1p36. Several patients had disruptions of known epilepsy genes: a double deletion of only CNTNAP2 (n=1) a deletion of KCNQ2 and CHRNA4 (n=1), duplications of both CDKL5/STK9 and MECP2 on ChrX (2 male). Several patients harboured novel microdeletions or duplications. Conclusion: Our large clinical genetics database confirms and expands the role of CNV in the pathology of the epilepsies, especially the comorbidity with neurodevelopmental disorders. Identified CNVs frequently occurred in known hotspots or epilepsy genes. Rare or de-novo CNVs containing potentially pathogenic gene aberrations will be investigated further. The BB-GRE database and the clinical genetics service are important to drive genotype-based diagnoses and the delineation of genomic syndromes.

Purpose: Background: Tuberous sclerosis complex (TSC) is a genetic disorder involving the mammalian target of rapamycin (mTOR) second messenger pathway. This results in non-malignant tumours such as subependymal giant cell astrocytomas (SEGAs) and also complex pathways leading to intractable epilepsy. Aim: To evaluate the efficacy and side effects of mTOR inhibitors in patients with TSC and intractable epilepsy and or SEGA. Method: A retrospective single centre series of 5 patients with TSC and refractory seizures treated with Rapamycin. An additional 7 patients with TSC and SEGA who received Rapamycin (R) or Everolimus (E), both mTOR inhibitors for non-surgical management between 2010 and 2012. Medical records and MRI brain imaging were reviewed to assess seizure control, side effects, and surveillance performed. SEGA volumes were assessed longitudinally using 1.5T MRI and using the Analyze software. Result: Seizure efficacy: One participant experienced seizure freedom and another experienced >90% seizure reduction. Another experienced a >50% seizure reduction. Three patients reported subjective improved learning. SEGA reduction: By three months of treatment there is statistically significant reduction in the SEGA volumes in at least 2 patients who received mTOR inhibitors (p<0.006). All seven patients had reductions of SEGA at 6 months by 3765% Side effects: Aseptic meningitis requiring hospitalisation (1 patient), dyslipidaemia (3 patients), and anorexia (1 patient). Conclusion: Preliminary data suggests mTOR inhibitors may be useful for controlling seizures in patients with TSC who are refractory to anticonvulsants and for reducing the volume of SEGAs in patients with TSC. Only one patient had a significant adverse event (aseptic meningitis).

p140 IDENTIFYING GENES INVOLVED IN EPILEPTIC ENCEPHALOPATHY BY WHOLE EXOME SEQUENCING IN FAMILIES E. H. Brilstra, R. Van T Slot, S. Van Lieshout, B. Koeleman, and C. G. F. De Kovel UMC Utrecht, Utrecht, The Netherlands
Purpose: Epileptic encephalopathies are characterized by slowing or regression of development that is attributed to epileptiform activity. When no external cause is prevalent, the condition is assumed to be genetic. In some families, multiple sibs are affected. A few genetic causes for epileptic encephalopathy are known, but many cases cannot be explained. Probably, there is high genetic heterogeneity. We aim to identify new genes as causes for these encephalopathies. Method: We have collected patients with healthy parents. Five families had multiple affected sibs, ten patients had no affected relatives. We
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

Genetics 3 Monday, 01 October 2012

p142 IDENTIFICATION OF A NOVEL GENETIC LOCUS FOR FEBRILE SEIZURES IN A MALTESE FAMILY C. Farrugia*, M. Cassar, and J. Mifsud* *University of Malta, Msida, Malta; and MLSBioDNA, Paola, Malta
Purpose: The aim of this study was to narrow down a previously identified region of about 20cM on chromosome 20 linked to familial febrile

43 Abstracts
seizures (FEB) by performing another linkage study using short tandem repeat (STR) markers. Method: The study was carried out on a Maltese three generation family having seven members with a phenotype compatible with FEB. A total of seven STR markers, from D20S1085 until the end of the telomere, at an average spacing of 2cM were genotyped in the thirteen family members using fluorescent methods. Following genotyping, multipoint parametric and non-parametric linkage analysis were performed. Penetrance was given to be 0.9. Result: The previously identified linkage region was confirmed and reduced to approximately 5cM on cytogenic band 20q13.3. Assuming autosomal dominant inheritance with incomplete penetrance, the highest logarithm of the odds score was 2.67 (p Conclusion: This study has identified a novel locus of interest associated with the FEB phenotype in a Maltese family, thus contributing to a better understanding of the syndrome and adding to the growing knowledge of the genetics of such complex diseases. Purpose: The epilepsies are a very heterogeneous group of common neurological disorders comprising many individually rare diseases. Thus, genetic diagnosis oft remains difficult. With our approach we aim to reveal the genetic basis of epileptic disorders in so far unresolved cases. Method: We enriched a panel of 323 epilepsy-associated genes using a custom designed Agilent SureSelect in solution kit and sequenced on a SOLiD 4 platform. Result: We screened >50 unknown cases with a broad spectrum of epilepsy phenotypes. We detected causative aberrations in commonly mutated ion channel genes (e.g. SCN1A, SCN2A) as well as in rarely affected genes (e.g. STXBP1, MFSD8). Surprisingly, we detected many mutations in extremely uncommon genes (e.g. KCTD7, ARHGEF9, KCNJ10, SMS). We also revealed SCN1A mutations in three patients where conventional testing (Sanger sequencing/HRM) failed to detect the mutations. Conclusion: We have successfully established a fast and cost efficient genetic screening method for patients with seizure disorders. We were able to uncover the genetic basis of many so far unresolved cases with epilepsy. We detected mutations in patients with both clear and unspecific epilepsy phenotypes. We revealed false negatives in conventional genetic testing methods. Many mutations were detected in genes that only in very rare instances have been associated with epileptic disorders. Thus, many rare epilepsy disorders might perhaps be more common but simply underdiagnosed due to unspecific and diffuse phenotypes. Therefore, our approach may contribute in collecting information on both well-known and unacquainted epilepsy disorders and in revealing their true phenotypic spectrum.

p143 CHROMOSOMOPATHIES AND EPILEPSY J. P. Domingos, F. Correia, and J. Chaves Hospital de Santo Antnio, Centro Hospitalar do Porto, Porto, Portugal
Purpose: Chromosomopathies may originate CNS malformations, associated with cognitive impairment. Although being a rare cause, they constitute a risk factor for epilepsy. They are typically related to certain types of epilepsy. Method: We present 9 patients with chromosomopathy and epilepsy followed in our outpatient clinic. Result: 1 58 year-old woman, Trisomy 21, generalized epilepsy with generalized tonic-clonic seizures (GTCS) controlled with valproic acid (VPA) 500+500mg/day. 2 56 year-old woman, Trisomy 21, senile myoclonic epilepsy, not controlled with levetiracetam 1000+500mg/day. 3 9 year-old boy, free Trisomy 21, generalized epilepsy with GTCS, controlled with VPA 200+200mg/day. 4 45 year-old man, Klinefelter syndrome, generalized epilepsy with GTCS controlled with VPA 500+1000mg/day. 5 -20 years-old man, fragile X syndrome, generalized epilepsy with GTCS, controlled with VPA 200+200mg/day. 6 37 yearold woman, 3p25 Deletion, juvenile absence epilepsy controlled with VPA 500+500mg/day. 7 31 year-old woman, trisomy 15, probably symptomatic focal epilepsy with subependymal heterotopia controlled with topiramate 50mg/day. 8 22 year-old woman, ring chromosome 20 syndrome, severe symptomatic encephalopathy with febrile seizures and recently GTCS under VPA (2ml+2ml/day). 9 - 19 year-old man, fragile X syndrome, neonatal seizures, sensory seizures, controlled with oxcarbazepine 600+600 mg/day. Conclusion: Trisomy 21 was the most frequent cromosomopathy found. These patients have a bimodal distribution: in those starting after 50 yearold an association with GTCS and senile myoclonic epilepsy is described. Deletion 3p25 is usually associated with febrile seizures and developmental delay, unlike our patient. The association between chromosome 15 and subependymal heterotopia is not described.

p145 EARLY EPILEPTIC ENCEPHALOPATY: A PECULIAR GENETIC CASE P. Guimares*, M. Santos*, R. Choro*, J. S, and I. Carrilho* *Centro Hospitalar do Porto - Hospital Maria Pia, Oporto, Portugal; and Hospital Peditrico do Centro Hospitalar de Coimbra, Coimbra, Portugal
Purpose: To present the case of a child with a deletion in the STXBP1 gene with a peculiar electroclinical presentation and good outcome. Method: Case Report. Result: We describe a five years-old girl, with development marked by cognitive delay and early-onset epilepsy. Seizures started in the neonatal period predominantly with sleep related episodes that occurred in clusters, and with pleomorphic phenomenology evolution until the present: first focal seizures with automatisms and right hemiconvulsions, later epileptic spasms and finally seizures with right eyes deviation and fencer's posture. The general examination was normal, with no dysmorphic features, and neurological evaluation only detected cognitive handicap. The sequential electroencephalografic analysis showed distinct ictal and interictal patterns: initially localized to the anterocentral bilateral regions with burst-suppression pattern, later on both anterolateral regions with subsequent progression to a predominantly bilateral posterior epileptiforme activity, and finally lateralized to the anterior left region. Investigation excluded metabolic and exclusively structural brain diseases, but functional imaging with PET revealed parietal hypometabolism, more pronounced on the right. The extensive genetic analysis revealed presence of deletions in the genes STXBP1 (9q34.11) and MACROD2 (20p12.2). Despite initial refractory, she is now seizure free on carbamazepine and vigabatrin. Conclusion: The case described above is a particular example of presentation of an early epileptic encephalopathy that is believed to be primarily associated with STXBP1 disruption. We discuss the contribution of additional gene MACROD2 deletion to the epileptic phenotype.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

p144 TARGETED NEXT GENERATION SEQUENCING AS DIAGNOSTIC TOOL IN EPILEPTIC DISORDERS J. Lemke*, E. Riesch, T. Dorn, Y. Weber, H. Lerche, D. Bhm, and S. Biskup *University Children's Hospital, Bern, Switzerland; CeGaT GmbH, Tbingen, Germany; Swiss Epilepsy Center, Zrich, Switzerland; and University of Tbingen, Tbingen, Germany

44 Abstracts
p146 ANALYSIS OF COPY NUMBER VARIATIONS AFFECTION ION CHANNEL GENES IN IDIOPATHIC GENERALIZED EPILEPSY -A CASE-CONTROL SURVEY USING A CUSTOMIZED MICROARRAY-BASED COMPARATIVE GENOMIC HYBRIDIZATION (IONCHANNEL ARRAY) P. Striano*, R. Paravidino*, M. Pezzella*, G. Giudizioso*, M. Montera*, A. Bianchi, A. Coppola, F. Dagna Bricarelli, D. A. Coviello, C. Minetti*, and F. Zara* *Gaslini Institute, University of Genova, Genova, Italy; Arezzo, Italy; Institute of Neurology, University College London, London, UK; and Galliera, Genova, Italy
Purpose: To perform an extensive search for genomic rearrangements (CNVs) involving ion channel genes in patients with idiopathic generalized epilepsy (IGE) by custom microarray-based comparative genomic hybridization (custom array-CGH). Method: Probands with familial (i.e., at least two first-degree or three affected relatives) IGE (classified according to the ILAE classification, 1989) and 110 healthy controls were screened by custom CGH-array designed to identify small CNVs affecting 429 candidate epileptogenic genes. This IonChannel array Agilent platform has 60.000 probes at the minimum resolution of 100 bp in exons and of 1000 bp in introns. Segregation analysis will be also performed. Result: One-hundred twenty probands from familial IGE and 110 healthy controls have been. CNVs involving ion channel genes were identified in both patients (mean size 412 Kb) and controls (mean size 354 Kb). In patients, we identified chromosomal microrearrangements involving different epilepsy candidate genes, including GABRG2, GABRAA1/A4, SCN1B, KCNE1/2, KCND2, TRPV2. Segregation analysis is ongoing for many cases but intragenic CNVs affecting GABRG2 and KCND2 were found in affected parents. Conclusion: IGE patients show a significantly increased burden of ion channel genes-rich CNVs. The identification of rearrangements affecting strong candidate epilepsy genes (e.g., GABRG2, KCND2) provides a compelling evidence that this method is a promising, powerful approach to improve dissection of complex pathogenesis of IGE. Result: Three polymorphisms in SCN1A, three in CACNA1A, and four in CACNA1B were identified in eight Japanese AHC patients. Of these polymorphisms, one in SCN1A, three in CACNA1A, and two in CACNA1B showed amino acid substitutions. Statistical examination showed no significant differences between healthy subjects and those with polymorphisms. Conclusion: Since AHC onset in our patients was within seven days after birth, we believe that AHC is caused by genetic abnormalities.

p148 GENETICS OF EPILEPSY, A DUTCH COHORT STUDY B. Berghuis*, G. De Haan, B. Koeleman, J. W. Sander, and D. Lindhout *SEIN, Zwolle, The Netherlands; Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede, The Netherlands; University Medical Center Utrecht, Utrecht, The Netherlands; UCL Institute of Neurology, London, UK; and University Medical Centre Utrecht, Utrecht, The Netherlands
Purpose: To identify genetic variants for disease susceptibility in epilepsy, genetic variants that contribute to refractoriness to antiepileptic medication and genetic variants involved in common side effects of antiepileptic medication. We hypothesize that carriers of genetic mutations that cause epilepsy present a distinct and recognizable clinical phenotype. Method: The studypopulation exist of patients attending our outpatient epilepsy clinics, with a firm diagnosis of epilepsy, regardless of type. Characteristics of the epilepsy, including types and frequency of seizures, neurophysiology, imaging and response to medication are documented for each patient. We plan to perform Next Generation Sequencing, Genome Wide Association Studies and Copy Number Variation analysis in search for genetic variants in genes already known to cause epilepsy in families, associated with hyponatriema caused by carbamazepine, associated with obestiy and valproate use and with influence on anti-epileptic drug metabolism and transport. Result: Inclusion of patients started September 2010. At the start of 2012 over 700 patients provided informed consent and their DNA was sampled. Clinical phenotype was described of 453 patients. 83%(n=375) of patients had a focal epilepsy, 12%(n=56) a generalized epilepsy, 5%(n=22) was not well defined. 34%(n=155) of the epilepsies were symptomatic. 82% of patients had ever used carbamazepine, oxcarbazine or both. We plan to test for genetic variation in vassopressin pathway genes that may contribute to hyponatriema induced by these drugs. Conclusion: The main outcome of this project will be a description of clinical factors correlated to specific genetic risk variation, to enable clinical guidelines for early diagnosis and personalized treatment.

p147 GENETIC ANALYSIS OF SPORADIC ALTERNATING HEMIPLEGIA OF CHILDHOOD A. Ishii*, Y. Saito, M. Sasaki, and S. Hirose* *Fukuoka University, Fukuoka, Japan; and National Center of Neurology and Psychiatry, Tokyo, Japan
Purpose: To find candidate genes for Alternating Hemiplegia of Childhood (AHC). AHC begins with abnormal eye movement at around 23 months of age; hemiplegia follows at about 67 months; and later, quadriplegia (Alternating distonia in children) appears. Convulsions begin around the age of six, often causing tonic-clonic seizures and tonic seizures. Ultimately, paralysis and the patient's resultant bed-ridden condition lead to severe intellectual disabilities. Blood and spinal fluid tests, MRI images, and EEGs give no indication of the disease. The genes responsible for AHC are unidentified and its molecular genesis remains unclear. Method: In eight Japanese AHC patients, we investigated the genetic abnormalities of four genes encording a1 subunit of voltage-gated sodium channel, a2 subunit of ATP-dependent Na/K pump, a1 subunit of P/Q-type voltage-dependent calcium channel and a1B subunit of P/Qtype voltage-dependent calcium channel respectively, SCN1A, ATP1A2, CACNA1A and CACNA1B genes.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

p149 CLINICAL FEATURES OF EPILEPSY IN DENTATORUBRAL-PALLIDOLUYSIAN ATROPHY PATIENTS H. Nakano, M. Kinoshita, and H. Sawada National hospital of Utano, Kyoto-shi, Japan
Purpose: We assessed the clinical features in dentatorubral-pallidoluysian atrophy patients who had epileptic seizures. Method: We included 5 DRPLA patients from different families (5 men; mean age, 31.2 years) who had expanded CAG repeat in DRPLA gene and epileptic seizures. And analyzed their clinical features based on medical recording. Result: All patients had marked dementia and cerebellar ataxia. A patient could perform simple verbal communication but other 4 patients

45 Abstracts
could utter only fragmented words or couldn't speak. The mean disease duration was 17.6 years. Three patients had positive family history. The mean onset age of epileptic seizure was 13.6 years. All patients had generalized tonic clonic seizures and 2 also had partial seizures. The frequency of generalized seizures was monthly in 2 patients and yearly in 1. Two patients had no seizure over 1 year. The frequency of myoclonus was daily in 3, and monthly in 1. One patient had no myoclonus. Electroencephalography showed generalized epileptiform discharges in 4 patients and both generalized and focal epileptiform discharges in 3. In 2 patients, localization of focal epileptiform discharges corresponded to seizure semiology. Number of antiepileptic drugs co-administered was 5 in 1 patient and 4 in 4. Conclusion: DRPLA is one of the primary disease which induces progressive myoclonus epilepsy whose seizures in young onset patients are intractable. Our data suggest that in some patients critical seizures may be controlled with co-administration of multiple drugs.

*University of Antwerp, Antwerp, Belgium; and University Hospital Gasthuisberg, Leuven, Belgium
Purpose: Determine frequency of recurrent reciprocal genomic rearrangements of 17q12 in generalized epilepsy with febrile seizures plus (GEFS+). Method: De novo copy number variations (CNV) and inherited genomic rearrangements have been recognized as causal variants and risk factors for a variety of diseases. So on, CNV analysis has become an established tool in clinical diagnostics. Molecular karyotyping was performed with the 180k Cytosure ISCA v2 array (OTG) in a proband of a four generation GEFS+ family with eight affected members. Multiplex Amplicon Quantification was used for segregation analysis of the findings and screening of a follow up cohort. Result: Initially a 2.12Mb microduplication of 17q12 was identified in a proband whom has febrile, myoclonic, tonic-clonic seizures, absences and intellectual disability (ID). Subsequent analysis showed clear co-segregation of the variant with the phenotype in four additional family members. The follow up screening of other families, patients and controls is on going. Conclusion: Recent findings revealed that recurrent reciprocal genomic rearrangements of 17q12 (both deletions and duplications) can be associated with a combination of all previously described symptoms. Our results confirm, however, that microduplications of 17q12 can be associated with a restricted phenotype consisting of ID and seizures but without renal disease or diabetes. Epileptic phenotypes are often poorly described but our family falls within the GEFS+ spectrum. The presence of ID could be a clue for CNV screening but is not a requirement as most affected family members had a normal intellect. It remains an intriguing question how these rearrangements can lead to specifically epilepsy.

Purpose: The present study aimed to assess the distribution of the CYP3A4*18/*19/*1G and CYP3A5*3 genotype in Han Chinese epileptic patients with carbamazepine (CBZ)-therapy and their effect on serum CBZ concentrations at steady-state. Method: The serum concentrations of CBZ and the CYP3A4*18/*19/ *1G and CYP3A5*3 genotype was determined in 247 Han Chinese including 177 monotherapy patients and 70 valproate-add-on patients. Result: In total group, the mutations of CYP3A4*18/*19 were not found. And the normalized concentrations of CBZ (concentration/ (weightdose)) were 0.250.067lgkgd (mlg)-1 for CYP3A4*1G non-expressors (AA and AG allele) and 0.280.080lgkgd (mlg)-1 for CYP3A4*1G expressor (GG allele)(P=0.003). It was 0.230.060lgkgd (mlg)-1 for CYP3A5*3 expressors (AA and AG -1 allele) and 0.300.076lgkgd (mlg) for CYP3A5*3 non-expressors (GG allele)(P<0.0001). The similar result was found in monotherapy and add-on group with CYP3A5*3 genotype, but not in add-on group with CYP3A4*1G. In monotherapy group, the normalized concentrations of CBZ were 0.250.065 lgkgd (mlg)-1 for CYP3A4*1G non-expressors and 0.280.074 lgkgd (mlg)-1 for CYP3A4*1G expressor (P=0.001). It was 0.240.054lgkgd (mlg)-1 for CYP3A5*3 expressors (AA and AG allele) and 0.310.072lgkgd (mlg)-1 for CYP3A5*3 non-expressors (GG allele) (P<0.0001). In add-on group, the normalized concentrations of CBZ were 0.240.070 lgkgd (mlg)-1 for CYP3A4*1G non-expressors and 0.260.087 lgkgd (mlg)-1 for CYP3A4*1G expressor (P=0.257). It was 0.210.068lgkgd (mlg)-1 for CYP3A5*3 expressors (AA and AG allele) and 0.290.078lgkgd (mlg)-1 for CYP3A5*3 non-expressors (GG allele) (P<0.0001). Conclusion: In generally, the CYP3A4*1G, CYP3A5*3 genotype affected the CBZ concentrations in Han Chinese patients that the normalized concentrations of CBZ in patients with CYP3A4*1G expressor (GG allele) and CYP3A5*3 non-expressors (GG allele) was higher than AG and AA allele. And it is a factor that may contribute to inter-individual variability in CBZ disposition in Han Chinese epileptic patients.

p152 A RAT MODEL FOR LGI1-RELATED EPILEPSY S. Baulac*, S. Ishida, T. Mashimo, M. Boillot*, N. Fumoto, M. Kuwamura, Y. Ohno, A. Takizawa, T. Aoto, M. Ueda, A. Ikeda**, R. Takahashi, E. Leguern*, and T. Serikawa *ICM, Paris, France; Institute of Laboratory Animals, Kyoto, Japan; Veterinary Pathology, Saka, Japan; Laboratory of Pharmacology, Osaka, Japan; PhoenixBio Co. Ltd, Utsunomiya, Japan; and **Graduate School of Medicine, Kyoto University, Kyoto, Japan
Purpose: Mutations of the leucine-rich glioma-inactivated 1 (LGI1) gene cause autosomal-dominant partial epilepsy with auditory features also known as autosomal-dominant lateral temporal lobe epilepsy (ADLTE). Besides, immune-mediated disruption of LGI1 results in seizures and limbic encephalitis. We aimed to generate an animal model for Lgi1related epilepsies. Method: The ENU (N-ethyl-N-nitrosourea)-mutagenized F344/NSlc rat archive (KURMA: Kyoto University Rat Mutant Archive) of the NBRPRat project was screened for mutations in the Lgi1 gene. We recovered an Lgi1-targeted rat carrying a missense mutation (L385R). Result: We provided evidence that L385R mutation prevented secretion of Lgi1 protein in COS7 transfected cells. However, low abundance of L385R-Lgi1 protein was found in the brains and primary cultured neurons of Lgi1-mutant rats, suggesting that mutant protein is destabilized in vivo. Phenotype of homozygous and heterozygous L385R-Lgi1 mutant rats was investigated. Behavioral observations and intracranial electroencephalographic monitoring recapitulated several features of the human disease: homozygous L385R-Lgi1 mutant rats by P10 experienced early-onset spontaneous epileptic seizures, and died prematurely. Moreover, adult heterozygous L385R-Lgi1 rats exhibited markedly higher susceptibility to sound-induced seizures (generalized tonic-clonic seizures) compared
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

p151 RECURRENT RECIPROCAL GENOMIC REARRANGEMENT OF 17Q12 AS A CAUSE OF GEFS+ K. Hardies*, E. Peeters, A. Suls*, S. Weckhuysen*, P. Holmgren*, W. Van Paesschen, and P. De Jonghe*

46 Abstracts
to control animals. Audiogenic seizures were suppressed by the administration of several antiepileptic drugs (carbamazepine, phenytoin and levetiracetam) commonly used to treat partial seizures, but not by ethosuximide, a drug of choice for absence seizures. Conclusion: Our findings provide the first rat model harboring a missense mutation in the Lgi1 gene, yielding a complementary model to classical knockout mice to study Lgi1-related epilepsies. tion, EEG, ECG, and plasmatic levels of AED were performed before and after LCM treatment. The efficacy was calculated in relation to seizure frequency reduction using parents diaries. LCM dose ranged between 200 and 400 mg/die in young adult and 6 mg/kg/die in children. Result: The follow-up ranged from 4 to 18 months. At the end of the follow-up, seizure frequency reduction was of 75% in 9 patients (45%) of the group A and in 2 patients (28.5%) of the group B. In only 1 patient LCM was discontinued because of inefficacy. Diplopia, nausea and dizziness reported during the titration period in 11 patients of the group A disappeared reducing the associated sodium channel - blocking AED. Conclusion: LCM showed good tolerability in add on in pediatric population. Despite the small sample of the group B, our preliminary data suggested that LCM seems more efficacy in reducing seizure frequency in patients with refractory focal epilepsy treated with concomitant traditional sodium channel- blocking AED.

p153 EPILEPSY ASSOCIATED WITH 22Q11.21 MICRODUPLICATION S. Tang*, E. Hughes, and D. K. Pal* *King's College London, London, UK; and King's Health Partners, London, UK
Purpose: Epilepsy is a little known association in 22q11.21 duplication. Here we describe the phenotype of affected children from two large databases of genomic variation. Method: After finding an index affected child, we searched the clinical genetics database [] of 10,397 individuals, as well as DECIPHER database. Result: The index child carried a de novo 2.49MB duplication of 22q11.21 (between LCR22B and LCR22E) as well as a maternally inherited 15kB microdeletion of chromosome 2p16.3 in an intronic region of neurexin-1. He presented age five with atypical benign partial epilepsy with left centro-temporo-parietal discharges, focal atonic seizures progressing to ESES. He also had some autistic spectrum, attentional and memory difficulties but no MRI evidence of malformation. Both parents were asymptomatic. In BBGRE we found 30 other individuals with 22q11.21 duplications: 19 had developmental delay; 8 had autism spectrum disorders; 17 had dysmorphism or congenital malformations; and only one other individual had epilepsy (infantile spasms). In DECIPHER, we identified 73 individuals with 22q11 duplication and variable phenotypes of whom only two were reported to have epilepsy with no further details. In the literature, five children with 22q11.21 dup have been reported with epilepsy or abnormal EEG and a variety of other features: one with nocturnal focal seizures and waking state epileptic spasms (Shimojima, 2010); another with occipital epilepsy and polymicrogyria in a child with co-existing inverted 9p dup/del (Mosca, 2009). Conclusion: The 22q11.21 duplication is associated with a variable phenotype; epilepsy is an uncommon association and both focal nocturnal seizures and epileptic spasms are specific findings.

Purpose: To evaluate the cost-utility profile of Phenobarbital as monotherapy among adult epilepsy patients in a tertiary hospital. Method: Adult epilepsy patients receiving Phenobarbital for at least a year, consenting and capable of answering the questionnaire were included in the study. The overall costs of treating epilepsy in this population in terms of the direct costs (visits, hospitalizations, diagnostics, treatment, transportation, nursing care) and indirect costs (employmentrelated losses) were determined. Outcome measures were described in this study as seizure frequency, patient satisfaction, adverse symptoms, and quality-of-life measurement using a multiattribute utility scale to derive QALYs (quality adjusted life years). Result: Monotherapy with Phenobarbital has shown high efficacy with 77% of patients experiencing a seizure attack of only once every 2 months or less. Tolerability is also good as 84% of the population expressed satisfaction with the drug despite 41% experiencing side effects of drowsiness and forgetfulness. Overall health state preference of 0.78 using the HUI-III among these patients on Phenobarbital is comparable to those with self-reported epilepsy from other studies. The overall cost of treating epilepsy with Phenobarbital per patient per year was Php 5, 255.62. The overall gain in health as expressed in QALYs per patient was 41.80, and the cost per QALY gained was Php 124.33. Conclusion: Phenobarbital monotherapy among adult epilepsy patients has shown overall favorable results, particularly in terms of cost per quality adjusted life years gained, with reference to current pharmacoeconomic standards.

Medical Therapy and Pharmacology 1 Monday, 01 October 2012

p154 LACOSAMIDE IN ADD-ON IN CHILDREN AND YOUNG ADULTS AFFECTED BY DRUG-RESISTANT EPILEPSY D. Battaglia, C. Brogna, I. Contaldo, F. Perrino, E. Albamonte, E. Losito, S. Veltri, G. Leo, D. Ranalli, and D. Lettori Catholic University, Rome, Italy
Purpose: To evaluate efficacy and tolerability of LCM in add-on with traditional sodium channel - blocking AED [SCB (+)] and other AED [SCB (-)] in children and young adults with drug-resistant epilepsy Method: 27 patients, aged between 3 and 31 years, affected by refractory epilepsy, were enrolled and divided in 2 groups: 20 patients treated by LCM in add on with SCB (+) (group A), and 7 patients treated by LCM in add on with SCB (-) (group B). Epilepsy type consisting of symptomatic (23) and presumed symptomatic (3) focal epilepsy. Neurological examinaEpilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

p156 EFFECTS OF VALPROIC ACID TREATMENT IN LIPID PROFILE AND HS-CRP IN EPILEPTIC PATIENTS S. Markoula*, D. Chatzistefanidis*, C. Tzallas, G. Lagos*, E. Bairaktari, and A. P. Kyritsis* *University of Ioannina, Ioannina, Greece; and University Hospital of Ioannina, Ioannina, Greece
Purpose: To investigate the role of daily dose, valproate's blood level and treatment duration in lipid profile alterations and HS-CRP blood level of epileptic patients receiving valproic acid. Method: Epileptic patients receiving valproic acid were consecutively recruited. Sex, age, daily dose and duration of treatment were recorded.

47 Abstracts
Waist perimeter, weight and height were measured. Fasting blood samples were collected to measure triglycerides, LDL, HDL, total cholesterol and valproic acid along with HS-CRP blood level. Result: Forty-six patients (29 males and 17 females) were included. Mean age was 39.5 years (males 41.2 years, females 36.6 years). Daily dose level was not related to BMI, waist perimeter, total cholesterol, triglyceride, LDL or HDL level. Treatment duration over 24 months was related to a significant increase in BMI and total cholesterol level (p < 0.05), as well as LDL level (p=0.057). This effect was statistically significant only in men, although women showed a similar trend. HS-CRP blood level was positively related to drug's daily dose and blood level. Conclusion: Alterations in lipid profile and body weight are mainly a result of treatment duration. On the other hand, HS-CRP blood level was positively influenced by daily dose and drug blood level. This knowledge is important when deciding the daily dose and treatment duration in patients with metabolic syndrome and/or evidence of cardiovascular disease. seizure type and number of concomitant antiepileptic drugs (AEDs) were summarized for the three studies. Result: 388, 386 and 706 patients were included in the safety population in studies 304, 305 and 306, respectively. Mean age was similar in each study (36.0, 35.5 and 33.8 years for 304, 305, 306, respectively); 8.5 11.4% of patients were aged <18 years. Approximately half of patients were female: 51.5%, 51.8% and 51.1%. The majority of patients were white (>65.0%); however, study 306 had a higher proportion of Asian/ Chinese patients (34.6%) compared with 304 or 305 (1% and 10.9%, respectively). Mean time since diagnosis was 23.7, 22.0 and 19.1 years. At Baseline, simple partial seizures (without motor signs) occurred in 36.9%, 34.5%, 29.7% of patients in 304, 305 and 306, respectively; simple partial seizures (with motor signs) occurred in 33.0%, 27.7%, 30.2%; complex partial seizures occurred in 88.9%, 85.0%, 84.0%; and complex partial plus secondary generalization occurred in 71.9%, 67.9%, 69.0%. The mean number of AEDs received in the past 5 years was 2.8, 3.2 and 3.4 for patients entering 304, 305 and 306, respectively. Conclusion: Patient populations in the three phase III trials of adjunctive perampanel for treatment of refractory partial-onset seizures were similar. Support: Eisai Inc.

p157 RECTAL CARBAMAZEPINE AS EFFECTIVE TREATMENT FOR ESCALATING SEIZURES AND STATUS EPILEPTICUS D. J. Cordato*, V. I. Patel*, and R. G. Beran *Liverpool Hospital, Liverpool, NSW, Australia; and Griffith University, South Port, Qld, Australia
Purpose: Carbamazepine (CBZ) is the gold standard anti-epileptic drug (AED) for focal onset seizures. The aim of this study is to examine the potential use of rectal (PR) CBZ as an alternative to parenteral AEDs in status epilepticus (SE) or cluster seizures. Method: Oral CBZ syrup was given PR using 400mg equivalent aliquots. Serum CBZ levels were requested 30 to 60 minutes after administration to confirm absorption and achievement of minimum therapeutic levels (total CBZ > 20 lmol L-1). Where levels were sub-therapeutic, the procedure was repeated using 400mg CBZ bolus aliquots until therapeutic levels were achieved. Result: 6 patients received PR CBZ, to manage cluster seizures following initial treatment with IV benzodiazepines. All patients seizures ceased and therapeutic CBZ levels were achieved in 5 of 6 subjects with 510 hours of initial CBZ dosing. Conclusion: PR CBZ is a viable alternative to parenteral AEDs in patients presenting with SE or cluster seizures.

p159 EFFICACY AND SAFETY OF LACOSAMIDE AS ADJUNCTIVE THERAPY IN A COHORT OF CHILDREN WITH REFRACTORY PARTIAL-ONSET EPILEPSY J. Kaleyias, A. Koukouletsos, A. Frimas, E. Tsekoura, A. Anagnostopoulou, A. Varvarigou, and S. Mantagos University Hospital of Patras, Patra, Greece
Purpose: To evaluate the efficacy and safety of lacosamide (LCM) as adjunctive treatment in a cohort of children with uncontrolled partialonset seizures taking one to three concomitant AEDs (Guilhoto LM et al. Pediatr Neurol 2011; 44: 414419). Method: Retrospective review of charts identified 14 children (11 males, mean age 10.7 years, range 4.517) with refractory partial-onset seizures on LCM. Seizure count and side effect (SE) profile were maintained during therapy. Good responders were defined those with 50% seizure frequency reduction. Statistical analysis was performed with SPSS. Result: Causes of epilepsy included tuberous sclerosis complex (n=3), Rett (n=1), Aicardi (n=1), Sotos syndrome (n=1) and CP (n=2). The median age of seizures onset was 2 years (Intraquartile range: IQR 15), median length of follow-up 7 years (IQR 210) and the median duration on LCM was 23 months (range 348). The median number of AEDs before LCM was 7 (range 210). LCM dosage was 5 mg/k/d (range 310). Good responders were 50% (7/14) [(2/14 (14%)] became seizure-free and currently in LCM monotherapy). In 7 children (50%) LCM had to be discontinued: 4 (28%) due to poor seizure control and 3 (21%) due to SEs and marginal benefit. The mean number of previous AEDs in responders was 4.4 while in non-responders was 8 (p <0.008). SEs were reported in 57% (8/14) (nausea, dizziness, somnolence, irritability, agitation); 3/14 side effects prompted LCM discontinuation [persistent somnolence (n=2), agitation (n=1)]. Conclusion: Lacosamide was demonstrated to be effective and safe in this cohort of children with refractory partial-onset seizures.

p158 PHASE III TRIALS OF ADJUNCTIVE PERAMPANEL, A SELECTIVE AMPA RECEPTOR ANTAGONIST, IN PATIENTS WITH TREATMENT-RESISTANT PARTIALONSET SEIZURES: ANALYSIS OF PATIENT DEMOGRAPHICS AND BASELINE CLINICAL CHARACTERISTICS V. Villanueva*, G. L. Krauss, C. Brandt, D. Squillacote, H. Yang, D. Kumar, and A. Laurenza *Hospital Universitario y Politcnico La Fe, Valencia, Spain; Johns Hopkins University, Baltimore, MD, USA; Bethel Epilepsy Centre, Mara Hospital, Bielefeld, Germany; and Eisai Neuroscience Product Creation Unit, Woodcliff Lake, NJ, USA
Purpose: To describe demographics and baseline characteristics of patients in three phase III trials of adjunctive perampanel for treatmentresistant partial-onset seizures (studies 304, 305, 306). Method: Patients were randomized to once-daily placebo, perampanel 2 mg, 4 mg, 8 mg or 12 mg. Patient demographics, time since diagnosis,

Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

48 Abstracts
*BSYS GmbH, Witterswil, Switzerland; and University of Porto, Porto, Portugal
Purpose: Eslicarbazepine is the major active metabolite of eslicarbazepine acetate, a once-daily antiepileptic drug approved in Europe as adjunctive therapy for refractory partial-onset seizures in adults. This study was aimed to determine the effects of eslicarbazepine and R-licarbazepine on the human NaV1.7 and NaV1.8 sodium channels expressed in CHO cells. Method: About 2448 hours following transfection with human NaV1.7 cDNA or NaV1.8 cDNA, cells were ready for electrophysiological experiments. The whole-cell patch-clamp technique was used to investigate the effects of eslicarbazepine and R-licarbazepine on NaV1.7 and NaV1.8 inward peak currents. Compounds were tested at -80 mV holding potential. The affinity for the resting (KR) and inactivated (KI) states was examined after 15 s conditioning pre-pulses ranging from -120 mV to -40 mV. Result: At -80 mV holding potential, eslicarbazepine and R-licarbazepine were equipotent in inhibiting inward sodium currents through NaV1.7 and NaV1.8 channels. However, the affinity of eslicarbazepine for the inactivated (KI) state of Nav1.7 and Nav1.8 channels was 10 to 2 times higher than that for R-licarbazepine. On the other hand, both compounds demonstrated a 10- to 5-times higher affinity for the inactivated (KI) state versus the resting (KR) state of the NaV1.7 channels, when compared to NaV1.8 channels. Conclusion: Eslicarbazepine is endowed with a greater selectivity for the inactive state of NaV1.7 and NaV1.8 sodium channels, when compared with R-licarbazepine.

p162 EFFICACY OF INTRAVENOUS LACOSAMIDE IN PATIENTS WITH CONVULSIVE VERSUS NON-CONVULSIVE STATUS EPILEPTICUS E. Y. Moreno, M. Peleterio, E. Bondy, J. Domnguez, E. Pardellas, and A. Fernandez University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
Purpose: To compare the efficacy of intravenous lacosamide in patients with convulsive versus non-convulsive status epilepticus. Method: In this prospective, observational study, patients with convulsive or non-convulsive SE that received iv lacosamide 200400 mg iv for 8 days were compared for electroencephalographic response and seizure termination. Result: Among 53 patients treated with iv lacosamide (mean dose 390.6 mg for 8 days) as first- (34%) or second-line (66%) treatment for convulsive (43.4%) or non-convulsive (56.6%) SE, the mean age was 55.2 years and 13.2% had prior epilepsy. The majority (73.6%) of patients had a comorbid condition, predominantly hypertension (35.8%) and head injury (11.3%). The majority (79.2%) of patients received concomitant antiepileptic drugs, either 1 (34%), 2 (22.6%) or 3 (22.6%) agents, including midazolam (54.7%), valproic acid (52.8%), and levetiracetam (30.2%) The other AEDs were used in principle to stop the SE but the patients did not respond and so we used lacosamide, however there are some exceptions in whichinput was used. EEG confirmation of improvement following lacosamide treatment was very positive in 56.6% of patients; 69.6% of the convulsive and 46.7% of the non-convulsive SE groups. Among all patients, 90.6% showed clinical improvement and there was no significant between-group difference for achievement of seizure termination, 90% and 91.3% of the non-convulsive and convulsive SE groups, respectively. There were no reports of adverse events Conclusion: Intravenous lacosamide was safe and similarly effective in patients with convulsive or non-convulsive SE . Further investigation into the use of lacosamide in the treatment of SE is warranted.

p161 SYMPTOMS AND COURSE OF INTOXICATION WITH MESUXIMIDE C. Brandt*, R. Hoepner, B. Rambeck, H. Ottenottebrock*, and T. W. May *Bethel Epilepsy Centre, Bielefeld, Germany; St. Josef Hospital, Bochum, Germany; and Society for Epilepsy research, Bielefeld, Germany
Purpose: We report on a patient who presented with somnolence due to intoxication by the antiepileptic drug (AED) mesuximide (MSM). The purpose is to highlight the symptoms and treatment of MSM intoxication and thus to raise awareness for a severe, but treatable condition in association with an AED that is used quite rarely nowadays. Method: Case report. Result: This 31-year-old, mentally impaired female patient suffered from cryptogenic focal epilepsy with complex-partial and secondarily generalized tonic-clonic seizures since the age of twelve. She was admitted to a local hospital because of frequent falls supposed to be of epileptic origin. Primidone 62.5 mg was added. When she was transferred to our hospital, she was somnolent, vomited and responded undirectedly to painful stimuli. AED serum concentrations were as follows: Valproic acid 70.9 mg/L (reference range 40100 mg/L), lamotrigine 8.1 mg/L (2 10 mg/L), n-desmethyl-mesuximide (NDM) 85.7 mg/L (1040 mg/L). MSM was withdrawn, and she was treated by hemodialysis. After the first course of hemodialysis NDM serum concentration had decreased, and the patient was awake and responsive. Conclusion: In somnolent patients treated with MSM and NDM levels above the therapeutic range (1030 mg/L), drug intoxication here probably chronic with a vicious circle of loss of appetite, add-on of primidone and subsequent further increase of serum concentrations should be considered, adequate treatment initiated. Due to the rare use of MSM it is even more important to know the symptoms of intoxication in order not to miss a potentially life-threatening, treatable condition.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

p163 RESPONSE TO ADD-ON LACOSAMIDE IN PATIENTS WITH REFRACTORY EPILEPSY J. Rodrguez Uranga Instituto de Especialidades Neurolgicas (IENSA), Sevilla, Spain
Purpose: Evaluate the efficacy and safety of adjunctive lacosamide in patients with refractory epilepsy receiving up to 3 other antiepileptic drugs. Method: In this retrospective, observational, non-interventional, postauthorization study, patients with partial-onset seizures receiving 13 AEDs received adjunctive lacosamide with doses from 100 to 400 mg (with a mean of 249.2 mg) for up to 5 months. Change in seizure frequency from pre- to post-treatment was assessed using the McNemar's test of change. Result: Sixty four patients of mean age 38.4 years with a median history of epilepsy of 2 (15) months received add-on oral lacosamide (mean dose 249.2 [100400] mg/day) for a mean of 2.6 months. Most patients had complex partial (34.4%), or complex (15.6%) or simple (9.4%) partial with secondary generalization subtype of epilepsy. For patients receiving 1, 2 or 3 AEDs, lacosamide was add-on treatment in 15 (23.4%), 36 (56.3%) and 13 (20.3%), respectively. AEDs most commonly used included levetiracetam (39.1%), carbamazepine (35.9), valproic acid (32.8%), lamotrigine (25%), and oxcarbazepine (20.3%). Initially, 63 patients (98.4%) had a seizure; by study end, this was reduced to 47 (73.4%). Among the patients with baseline seizures, 25%

49 Abstracts
had no seizures at end of treatment, a statistically significant reduction (p < 0.001). Median percentage reduction in seizure frequency was 56.7%. The response rate was 66.7% (seizure free [27%], reduction in seizure frequency 50% [39.7%]), 15.9% had a reduction <50%, 17.5% had no change in seizure frequency. Conclusion: Add-on lacosamide was safe and effective in a broad range of patients with refractory epilepsy receiving 13 AEDs.

Medical Therapy and Pharmacology 2 Monday, 01 October 2012

p165 ZONISAMIDE MONOTHERAPY IN ADULT PATIENTS WITH PARTIAL, GENERALIZED & COMBINED SEIZURES: FINDINGS OF A OPEN-LABEL, NON-COMPARATIVE, OBSERVATIONAL STUDY A. Dash*, S. C. Mehta*, N. C. Manjunath, A. Kiran, B. Jyothi, V. Bajpai, V. N. Mathur**, S. Shah, and D. Langade *Eisai Pharmaceuticals India Private Limited, Mumbai, India; Brain & Nerve Care Centre, Bangalore, India; Ayush Neuro Care, Secunderabad, India; Mediplus Clinic, Hyderabad, India; Sai Neurology Clinic, Lucknow, India; **Vivekananda Hospital, Hyderabad, India; Advanced Neurology & Superspecilaity hospital, Jaipur, India; and Institute of Medical Science & Research, Faridabad, India
Purpose: To evaluate efficacy and safety of Zonisamide monotherapy in adult patients with partial, generalized & combined seizures. Method: In this open, non-comparative, multi-center, observational study, 59 patients (36 males, 23 females) having partial, generalized and combined seizures were treated with Zonisamide monotherapy (100 500mg/day) for 24 weeks. Seizure frequency, clinician's global assessment of response to therapy (CGART) and patient's global assessment of tolerability to therapy (PGATT) were assessed every 4 weeks. Primary outcome was reduction in seizure frequency and secondary outcomes were responder rate (50% reduction in seizure frequency) and seizure freedom over 24 weeks. Adverse events were recorded during the study period. Change in seizure frequency from baseline was analyzed by Friedman test (non-parametric repeat measures ANOVA). Result: Fifty one patients completed 24 weeks study period, and 8 did not complete the study (4 lost to follow up, 3 due to medication error, and 1 withdrew due to adverse event). Mean percent reduction in seizure frequency at 24 weeks was 78.02% (95% CI 61.75131.02). After 24 weeks, the responder rate was 74.29% (26/35), whereas 24 weeks seizure freedom was 22.86% (8/35). Adverse events were reported in 3 (5.08%) patients, of which 1 (1.69%) patient each reported loss of appetite, dizziness, and aggressive behavior with sleep disturbance. Patient reporting aggressive behavior with sleep disturbance withdrew from the study. Conclusion: Zonisamide monotherapy demonstrates favorable efficacy and tolerability in adult patients with partial, generalized & combined seizures, however small sample limits the generalization of the findings.

p164 LEVETIRACETAM IS SUPERIOR TO CARBAMAZEPINE-SR IN NEWLY DIAGNOSED EPILEPSY IN THE ELDERLY: RESULTS OF THE STEP-ONE TRIAL K. J. Werhahn*, E. Trinka, J. Dobesberger, C. Ruckes, and G. Krmer *University Medical Center of the Johannes Gutenberg University, Mainz, Germany; Paracelsus Medical University, Salzburg, Austria; University Medical Center Mainz, Mainz, Germany; and Swiss Epilepsy Centre, Zurich, Switzerland
Purpose: Rationale: A multicentre, double-blind, randomized, head-tohead comparison of levetiracetam (LEV), slow-release carbamazepine (CBZ-SR), and lamotrigine (LTG) in newly diagnosed elderly patients with focal epilepsy (Study on the Treatment of Elderly Patients with Older and Newer antiepileptic drugs; NCT00438451; EudraCT Number: 2005-003324-19). Method: Patients aged 60 years or above with new onset focal epilepsy (either at least one seizure and spike discharges on EEG or a relevant lesion on CT/MRI or a total of 2 spontaneous seizures) were eligible; those with symptomatic epileptic seizures due to acute (< 2 weeks) cerebral lesions were excluded. Patients received LEV, CBZ-SR, or LTG (initial target dose of 1000mg LEV, 400mg CBZ-SR, or 100mg LTG) in a parallel group design over 58 weeks (6 weeks titration and 52 weeks maintenance). Following titration patients were treated individually in a double-blind manner depending on efficacy and tolerability on doses between 500 3000mg for LEV, 200 1200mg for CBZ-SR, or 50 300mg for LTG. Result: A total of n=361 patients were randomized and n=359 included in the intention-to-treat (ITT) population. Mean (SD) age was 71.8 7.5 for LEV (n=122, 34% female), 71.7 6.7 for CBZ-SR (n=120, 46%), and 70.7 7.4 for LTG (n=117, 41%). The mean number of seizures prior randomization were 3.8 9.9, 4.8 10.8, and 2.7 3.1 for LEV, CBZ-SR, and LTG respectively (p < 0.05 for CBZ-SR vs. LTG, t-test). Based on the ITT population retention rates at 58 weeks (primary endpoint) were 61% (95%CI: 5370) for LEV, 46% (95%CI: 3755) for CBZ-SR, and 56% for LTG (95%CI: 4765) [pvalues: overall 0.048; LEV vs. CBZ-SR 0.02, LEV vs. LTG 0.36, LTG vs. CBZ-SR 0.15, Fisher exact test]. Logistic regression revealed an odds ratio (OR) for a retention to treatment at 58 weeks of 1.838 (95%CI: 1.0923.093) for LEV vs. CBZ-SR, of 1.169 (95%CI: 0.689 1.984) for LEV vs. LTG, and of 0.636 (95%CI: 0.3771.073) for CBZ-SR vs. LTG. The number of concomitant diseases significantly influenced 58-week retention (OR 0.921; 95%CI 0.8590.987), i.e. chances to remain on therapy were reduced by 7.9% with each additional concurrent disease. There were no significant differences in seizure-freedom rates at week 30 (LEV 48%, CBZ-SR 39%, LTG 49%) and 58 (LEV: 43%, CBZ-SR 33%, LTG 38%) and in time-to-first seizure from randomization or after titration (after week 6). Conclusion: Results demonstrate evidence of superiority of LEV in monotherapy to CBZ-SR in new-onset focal epilepsy in the elderly. As the trial was not powered for the comparison of LEV and LTG there was no significant difference between these treatment arms. However, results do suggest that LEV should be among the first-line treatments in newonset epilepsy of the elderly population. Future head-to-head trials with novel or other antiepileptic drugs in the elderly population need to consider LEV as comparator.

Purpose: Zonisamide is currently licensed for adjunctive treatment of adults with partial seizures (with or without secondary generalisation). A Phase III trial recently assessed the efficacy/safety of adjunctive zonisamide in paediatric patients with partial epilepsy. Presented here are preliminary results of assessments of cognition that were included in the trial.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

50 Abstracts
Method: Paediatric patients (617 years) with partial epilepsy received adjunctive zonisamide 8 mg/kg/day (N=107) or placebo (N=100) for 20 weeks (8 weeks titration, 12 weeks maintenance) in a Phase III trial. Effects on cognition (including power of attention, continuity of attention, quality of working memory, speed of memory, and picture recognition sensitivity index) were assessed in around 80 patients with intelligence quotient 75. Last observation carried forward (LOCF) and observed case data were analysed using analysis of covariance. Result: No treatment effect was observed on power of attention (primary variable), continuity of attention, quality of working memory, and picture recognition sensitivity index (p>0.05 for all). Some evidence of impairment with zonisamide was observed on speed of memory at final visit, but only for the LOCF analysis using reciprocal transformed raw data (p=0.0275). Conclusion: No significant effects on psychomotor/information processing speed, attention (focussed and sustained), working memory (verbal and visuo-spatial), or episodic memory (visual recognition) were observed following 20 weeks treatment with adjunctive zonisamide in paediatric patients with partial epilepsy. Supported by Eisai

*Eisai Pharmaceuticals India Private Limited, Mumbai, India; Advanced Neurology & Superspecilaity hospital, Jaipur, India; Vivekananda Hospital, Hyderabad, India; Brain & Nerve Care Centre, Bangalore, India; Mediplus Clinic, Hyderabad; **Caring Hands Neuro Centre, Vishakhapatnam, India; Metro Hospital & Heart Institure, Noida; Sai Neurology Clinic, Lucknow, Indonesia; Institute of Medical Science & Research, Faridabad, India; and 1. Eisai Pharmaceuticals India Private Limited, Mumbai, Mumbai, India
Purpose: To evaluate efficacy and safety of Zonisamide in adult patients with partial, generalized & combined seizures. Method: In this open, non-comparative, multi-center, observational study, 113 patients (65 males, 48 females) having partial, generalized and combined seizures were treated with Zonisamide (100500mg/day) for 24 weeks as first add-on to the primary antiepileptic drug of clinician's choice. Seizure frequency, clinician's global assessment of response to therapy (CGART) and patient's global assessment of tolerability to therapy (PGATT) were assessed every 4 weeks. Primary outcome was reduction in seizure frequency and secondary outcomes were responder rate (50% reduction in seizure frequency) and seizure freedom over 24 weeks. Adverse events were recorded during the study period. Change in seizure frequency from baseline was analyzed by Friedman test (nonparametric repeat measures ANOVA). Result: Eighty five patients completed 24 weeks study period, and 28 did not complete the study (20 lost to follow up, 7 due to medication error, and 1 withdrew due to adverse event). Mean percent reduction in seizure frequency at 24 weeks was 71.21% (95% CI 57.94103.88). After 24 weeks, the responder rate was 76.81% (53/69), whereas 24 weeks seizure freedom was 30.88% (21/68). Adverse events were reported in 4 (3.54%) patients, of which 2 (1.77%) patients reported loss of appetite and one had weight loss (0.88%) during study. One (0.88%) patient was withdrawn from the study due toincrease in seizure frequency. Conclusion: Zonisamide demonstrates favorable efficacy and tolerability as first add-on in adult patients with partial, generalized & combined seizures.

p167 SEXUAL HORMONAL PROFILE OF EPILEPTIC MALE PATIENTS RECEIVING VALPROIC ACID D. Chatzistefanidis*, S. Markoula*, A. Giaka*, C. Tzallas, E. Bairaktari, and A. P. Kyritsis* *University of Ioannina, Ioannina, Greece; and University Hospital of Ioannina, Ioannina, Greece
Purpose: To study the impact of daily dose level and duration of treatment on hormonal profile of male epileptic patients receiving valproic acid. Method: Male patients receiving valproic acid and hospitalized in the Department of Neurology were consecutively recruited. Age, daily dose and duration of treatment were recorded. Blood samples were collected to measure testosterone, sex hormone-binding globulin (SHBG), FSH and LH blood levels. Result: Twenty six patients (mean age 37.9 years) were enrolled in our study. Testosterone level was significantly higher in patients receiving valproic acid doses of more than 2000 mg (mean testosterone value of 7.2 ng/ml versus 4.1 ng/ml, p < 0.05). Additionally, FSH (2.8 IU/l vs 4.1 IU/ l) and LH (2.8 IU/l vs 3.8 IU/l) blood levels were lower, while SHBG blood level was higher (62.3nmol/l vs 38.5 nmol/l) in patients receiving doses higher than 2000 mg, although these differences didn't reach statistical significance. Regarding treatment duration, none of the differences reached statistical significance, although there was a trend of increased mean testosterone (5.3 ng/ml vs 4.1 mg/ml) and decreased LH blood levels (2.7 IU/l vs 4.5IU/l) when treatment duration was longer than 24 months. Conclusion: Testosterone blood level is significantly affected by a daily dose exceeding 2000 mg. There is a trend for higher SHBG and lower FSH and LH blood levels, which may result from negative feedback of testosterone, in patients receiving daily doses higher than 2000 mg. Treatment duration longer than 24 months caused a non-significant increase in patients mean testosterone and decrease in LH blood level.

p169 RETIGABINE - A CHALLENGE FOR THERAPEUTIC DRUG MONITORING U. Juerges, and B. J. Steinhoff Epilepsy Centre Kork, Kehl-Kork, Germany
Purpose: Retigabine (RTG) is a new antiepileptic drug that was approved and introduced in Germany in 2011. For most antiepilectic drug therapies drug monitoring has proved a useful and valuable tool. The special feature of retigabine is its excessive metabolization. The major metabolites are RTG-N-glucuronide and N-acetyl-RTG, where the Nglucuronide and RTG have a constant ratio of 25:1. Although we do not know what kind of anticonvulsive properties the metabolites have, it is helpful to quantify not only the active agent RTG, but the metabolites also. What method is suitable for analyzing retigabine and its metabolites in serum or plasma? Method: RTG is quantified with a mass spectrometric method. The sodium adducts are analyzed as target ions: RTG-Na ion=326; acetylRTG-Na ion=296. Chromatographic settings include: column: 150x4PerfectSil5lm, mobile phase: 1mM sodium acetate/methanol isocratic. Sample preparation via methanol precipitation and dilution of extract with sodium acetate solution (0.2%). Internal standard. Result: The quantification of RTG as sodium adduct allows a selective and sensitive analysis of RTG and the metabolite N-acetyl-RTG. Using a pH neutral mobile phase and excluding all acidic additives allows to represent the in vivo metabolite distribution. Solutions of pH < 6 lead to the decomposition of N-glucuronide and so to falsely increased retigabine

p168 EFFICACY AND SAFETY OF ZONISAMIDE AS FIRST ADD-ON THERAPY IN ADULT PATIENTS WITH PARTIAL, GENERALIZED & COMBINED SEIZURES S. C. Mehta*, S. Shah, V. N. Mathur, N. C. Manjunath, B. Jyothi, B. Demudubabu**, V. Kumar, V. Bajpai, D. Langade, and A. Dash
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values. To obtain stable sodium adducts for RTG and N-acetyl-RTG an excess of sodium ions is needed. Conclusion: RTG drug monitoring via a selective and sensitive analysis method is possible using mass spectrometry. The analysis as sodium adduct in a pH neutral solution with sodium ion excess is recommended. reduction in countable seizures and 6 had a 2550% seizure reduction, while seizure frequency remained unchanged in 6. 9/14 responders had a reduction in drop attack and 6/14 patients had 50% decrease in seizures. 11/24 patients reported mild adverse effects. 5 of 24 patients discontinued the treatment after 35 months because of serious adverse events. 19 remaining patients were observed for mean period of 44.5 weeks. Efficacy on seizure frequency remained steady until the end of the study. Cognitive and adaptive assessments reperformed after 12 months of rufinamide treatment showed that 19/24 patients didn't have a change in IQ and adaptive behaviour score. Conclusion: Our data suggest that rufinamide may be effective and well tolerated in the treatment of young patients with LGS. Moreover rufinamide treatment was associated with low incidence of cognitive and psychiatric adverse events.

p170 EFFECTS OF ESLICARBAZEPINE, R-LICARBAZEPINE AND OXCARBAZEPINE ON FAST AND SLOW INACTIVATION OF VOLTAGE-GATED SODIUM CHANNELS C. Aires*, S. Hebeisen, and P. Soares-Da-Silva *BIAL - Portela & Ca. SA, So Mamede do Coronado, Portugal; BSYS GmbH, Witterswil, Switzerland; and University of Porto, Porto, Portugal
Purpose: Eslicarbazepine, the major (94.5%) active metabolite of eslicarbazepine acetate (ESL), preferentially enhances the slow inactivation of voltage-gated sodium channels (VGSC). This study was aimed to compare the effects of eslicarbazepine with the effects of R-licarbazepine and oxcarbazepine (OXC), two minor metabolites (5.0% and 0.5%, respectively) of ESL, on the fast and slow inactivated states of VGSCs. Method: The whole-cell patch-clamp technique was used to investigate the effects of eslicarbazepine, R-licarbazepine and OXC (all at 250 lM) on sodium channels endogenously expressed in N1E-115 cells, in conditions of fast and slow inactivation of sodium currents. Result: Steady state fast inactivation curves were shifted in the hyperpolarizing direction by OXC (-17 mV), but not by eslicarbazepine (-2.4 mV) or R-licarbazepine (-3.2 mV). OXC-treated fast inactivated channels required long pulses to recover (Dt = 391 ms), whereas eslicarbazepine- and R-licarbazepine-treated fast inactivated channels recovered similar to control conditions (Dt = 11 ms). The voltage dependence of the slow inactivation (shift V0.5) for OXC, R-licarbazepine, and eslicarbazepine was -28.1, )31.9, and )31.2mV, respectively. For eslicarbazepine, R-licarbazepine and OXC the affinity to the slow inactivated state was 5.9, 5.8, and 1.8 times higher than to the channels in the resting state, respectively. For eslicarbazepine, R-licarbazepine, and OXC, the time constants for entering the slow inactivated sate were 7.00, 7.03, and 12.36 s, respectively. Conclusion: Both eslicarbazepine and R-licarbazepine preferentially enhance the slow inactivation of VGSC, whereas OXC appears to modify kinetics and voltage-dependence of fast inactivation states.

p172 EXPOSURE-RESPONSE MODELING OF LACOSAMIDE IN ADJUNCTIVE TREATMENT OF PATIENTS WITH PARTIAL-ONSET SEIZURES C. Laveille*, R. Schoemaker*, and A. Stockis *Exprimo, Mechelen, Belgium; and UCB, Braine LAlleud, Belgium
Purpose: To develop a retrospective exposure-response model for lacosamide based on daily seizure counts of individual patients with focal epilepsy and to identify potential prognostic factors in reducing seizure frequency (SF) by performing a covariate analysis. Method: Individual daily seizure records (N=210,234) were obtained from 1308 patients who participated in three double-blind, placebo-controlled clinical trials (SP667, SP754, SP755). Probability of daily seizures was estimated by nonlinear mixed effects modeling using statistical distributions appropriate for count data. Plasma concentrations were estimated using a population pharmacokinetic model. Drug effect on seizure frequency reduction was modeled using a Hill function. Result: A negative binomial distribution with zero-inflation and Markovian element provided the best fit for all phases (baseline, titration, maintenance). Patients who were not taking concomitant sodium channel blocking (SCB) anti-epileptic drugs (AEDs; 18% of population) underwent a greater SF reduction from baseline compared with patients taking concomitant SCB AEDs (82%). The EC50 (trough concentration producing half the maximum SF reduction) was 4.6lg/mL (90%CI 3.55.7lg/ mL). Median SF reduction in improving patients was 23% (placebo), 48% (lacosamide with SCB) and 70% (lacosamide with non-SCB) at lacosamide 400mg/day. Conclusion: An exposure-response relationship was demonstrated between lacosamide plasma trough concentration and SF reduction from baseline in patients with uncontrolled focal seizures. The combination of lacosamide with non-SCB AED(s) resulted in greater reductions in SF compared with the combination of lacosamide with SCB AED(s), as identified previously (Sak et al, CNS Drugs 2010; 24:105568). UCB-sponsored.

p171 RUFINAMIDE AND LENNOX-GASTAUT SYNDROME: EFFICACY, TOLERABILITY AND NEUROPSYCOLOGICAL OUTCOME IN YOUNG PATIENTS C. Cerminara*, M. Pinci*, A. Luchetti, D. Battaglia, P. Curatolo*, M. G. Marciani, and A. Romigi *Tor Vergata University, Rome, Italy; Catholic University, Rome, Italy; and University of Rome Tor Vergata, Rome, Italy
Purpose: The aim of our study was to explore the effectiveness, safety and tolerability of rufinamide in young patients with LGS. Neuropsycological outcome has been valuated. Method: 24 patients of 631 years with LGS. These were treated with rufinamide added to the baseline therapy at the mean dose of 38.7 mg/kg/ die for a mean period of 44.5 weeks. Effectiveness was evaluated comparing the frequency of seizure between baseline period and. 3 months and 12 months after treatment beginning. Neuropsycological assessments were performed at baseline and at end point. Result: Rufinamide was effective on seizure in 58.3% of patients already after 3 months: 1 patient seizure free, 7 had 50% seizure

Purpose: To evaluate efficacy and tolerability of levetiracetam as a monotherapy in patients with medicaly refractory epilepsy Method: The study was randomized, prospective of 12-month duration and included 16 patients with newly diagnosed epilepsy. We evaluated
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efficacy primary by evaluating reduction of seizure frequency and secondary by improvement of quality of life using QOLIE 89 questionnaire. We also registered development of adverse effects. Result: The patients were on age from 1465 years. From seizures types most representing was patients with SGS 46.5% and from etiological factors (by CT and MRI) most of the patients was with hyppocampal sclerosis, tumors and trauma. Analysis of reduction of seizures frequency show significant reduction >50% in 56.25% of patients, <50% in 18.75% of patients and without effects in 18.75% patients, without significant differences by seizures types (p<0.05). The improvement of QOLIE 89 score in levetiracetam treated patients was 72.5% also without significant differences by seizures types (p<0.05). Fatigue, somnolence, headache, and irritability were adverse effects considered drug-related and reported in 6% of patients. Conclusion: Our results suggest that levetiracetam is highly effective in treatment of patients with refractory epilepsy, probably due to reduction of seizure frequency, but also because of improvement of social, mood and cognitive function. Purpose: Eslicarbazepine acetate (ESL) is a novel once-daily voltagegated sodium-channel blocker approved in Europe for use in adults as adjunctive therapy for refractory partial-onset seizures (POS) with or without secondary generalisation. This phase III study aims to assess the efficacy and safety of ESL as adjunctive therapy in 252 children and adolescents (2 to 16-years old) with refractory POS, treated with 1 or 2 AEDs. Method: After an 8-week baseline-period, patients with >4 seizures/4weeks will be randomised (stratified by age: 26; 712 and 1316 years) in 1:1 ratio to ESL or placebo once-daily. Following titration to target dose of 20 mg/kg/day over a 6-week period, they will enter a 12-week maintenance-period. The primary endpoint is the responder rate (at least a 50% decrease in seizure frequency), based on patients seizure diaries. Secondary endpoints include changes in seizure frequency, the proportion of seizure-free patients and seizure duration and severity (Hague seizure severity scale). Safety will be assessed by adverse events, clinical laboratory tests, physical and neurological examinations, and measurement of growth and development. An open-label extension with the possibility of conversion to monotherapy in cases such as seizure freedom will follow the double-blind phase. Result: The study is expected to be completed by the end of 2012, and the results will be reported thereafter. Conclusion: ESL efficacy data in adults with POS cannot be extrapolated in this population. This study is designed to evaluate the risk/benefit ratio as part of the clinical development plan of ESL in children.

Purpose: Lacosamide (LCM) and carbamazepine (CBZ) are antiepileptic drugs both acting on neuronal voltage-gated sodium channels. Patchclamp studies have demonstrated that LCM enhances slow inactivation of voltage-gated sodium channels, and, in contrast to CBZ, does not affect steady-state fast inactivation. The enhancement of slow inactivation of sodium channels by LCM is a novel manner to modulate sodium channels and leads to normalization of activation thresholds and a reduced pathophysiological hyper-responsiveness, thereby effectively controlling neuronal hyperexcitability without affecting physiological activity. Method: The present study was designed to explore dose-depended effects of LCM on motor cortex excitability with transcranial magnetic stimulation (TMS) in a randomized, double-blind, placebo-controlled crossover trial in young healthy human subjects, and to compare the pattern of excitability changes induced by LCM with those of CBZ. Result: The two antiepileptic agents show distinct patterns, with differential neuronal inhibitory and excitatory subsystems involved. Conclusion: TMS can be used for testing acute drug effects at the systems level of the cerebral cortex in awake humans and offers a broad array of measures of motor cortical excitability, which cover different aspects of excitability, such as axon excitability, and distinct forms of inhibitory and excitatory synaptic excitability.

p176 DRUG RESISTANCE AND SEIZURE SEVERITY OF PATIENTS IN PARTIAL-ONSET SEIZURE REGISTRATION TRIALS OF PERAMPANEL COMPARED WITH RECENTLY APPROVED ANTIEPILEPTIC DRUGS G. L. Krauss*, F. Kerling, V. Villanueva, D. Squillacote, H. Yang, J. Zhu, L. Verdian, and A. Laurenza *Johns Hopkins University, Baltimore, MD, USA; Ulm University, Ulm, Germany; Hospital Universitario y Politcnico La Fe, Valencia, Spain; Eisai Neuroscience Product Creation Unit, Woodcliff Lake, NJ, USA; and Eisai Ltd, Hatfield, UK
Purpose: Successive registration studies of new adjunctive antiepileptic drug (AED) therapies recruit many patients resistant to newer AEDs. We describe baseline seizure frequency and demographic factors in perampanel registration trials in the context of 5 previously approved newergeneration AEDs. Method: We evaluated baseline seizure severity and baseline AED use in registration trials for perampanel, levetiracetam, zonisamide, lacosamide, eslicarbazepine and retigabine. Result: Mean patient ages (32.941.3 years) were similar across all 6 AED registration trials; mean duration of epilepsy was similar for perampanel (19.123.7 years) and the 5 other AEDs (15.725.4 years). Median number of seizures/28 days at baseline was generally higher for perampanel (9.314.3) versus other AEDs: levetiracetam (6.710.5); lacosamide (5.515.0); eslicarbazepine (6.79.0); and retigabine (7.912.1) (zonisamide data not available). More patients had a history of secondary generalized seizures in perampanel studies (67.971.9%) versus levetiracetam (26.027.0%); zonisamide (21.024.0%); lacosamide (43.8 78.8%); eslicarbazepine (28.247.1%); and retigabine (23.233.7%). A high proportion of these refractory patients required 3 concomitant AEDs at baseline in perampanel trials (28.938.6%) compared with most other AEDs: levetiracetam 5.05.1%; zonisamide 21.728.8%; lacosamide 0.036.9%; eslicarbazepine 0.09.9%; retigabine 0.033.8%. As the last of these registration studies, concomitant AEDs in perampanel studies

Medical Therapy and Pharmacology 3 Monday, 01 October 2012

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included all 2nd- and 3rd-generation AEDs available in 20082009; 71.5% of patients received at least one newer AED. Conclusion: Compared with registration trials for previous 2nd- and 3rd-generation AEDs, patients entering the perampanel trials generally had higher seizure frequencies, more often had histories of secondarily generalized seizures, and were receiving 3 concomitant AEDs. Support: Eisai Inc. Method: This was a Phase II, open-label extension of a pharmacokinetic and tolerability study, in which paediatric patients with uncontrolled seizures received adjunctive zonisamide (112 mg/kg/day; administered twice-daily). Patients were grouped by age at entry: 511 (n=20) and 12 18 (n=9) years. Safety assessments included adverse events (AEs), vital signs, physical examination and clinical laboratory tests, conducted monthly for the first 3 months, and then at 6 months. Some data were collected beyond 6 months since the original protocol specified treatment up to 12 months. Result: Overall, 24/29 (82.8%) patients completed the study. Mean exposure to zonisamide was 259 days. In total, 24/29 (82.8%) patients reported treatment-related AEs; most commonly, anorexia (37.9%), somnolence (34.5%) and asthenia (24.1%). Most AEs were mild/moderate in intensity. Ten new serious AEs were reported in five patients, only two of which were considered zonisamide-related. Few patients experienced clinically relevant laboratory abnormalities. Overall, 75.0% patients had bicarbonate levels below the normal range, and 28.6% had chloride levels above the normal range, at any time during the study. There were no reports of oligohydrosis, severe rash or renal calculi and no notable changes in body weight. Conclusion: Long-term zonisamide therapy was generally well tolerated in these paediatric epilepsy patients. Given the small sample size, further studies are needed to confirm these findings. Supported by Eisai.

Purpose: Zonisamide is currently licensed for adjunctive treatment of adults with partial seizures (with or without secondary generalisation). This study aimed to characterise the pharmacokinetics and tolerability of zonisamide in paediatric epilepsy patients. Method: In this Phase II, open-label study, 33 paediatric patients (aged 515 years) with uncontrolled seizures received adjunctive zonisamide (112 mg/kg/day; administered twice-daily) for approximately 60 days. Steady-state pharmacokinetics, including observed maximum concentration (Cmax), area under curve to 12 h (AUC012h), apparent oral clearance (CL/F) and total body weight-normalised CL/F (CL/F/TBW), were assessed at zonisamide doses of 1, 7 and 12 mg/kg/day. Analysis was performed by age (511 and 1215 years) and concomitant use of CYP3A4inducing or non-inducing antiepileptic drugs (induced and noninduced patients). Tolerability was assessed by evaluating adverse events (AEs). Result: Overall, 21/33 (63.6%) patients completed the study. Zonisamide pharmacokinetics were dose-dependent and peaktrough fluctuations were relatively small over each 12-h evaluation period. Although patient numbers were too low for statistical comparison, the following observations were of note: for non-induced patients, Cmax, AUC012h and CL/F were numerically lower, and CL/F/TBW was numerically higher, in patients aged 511 versus 1215 years; in both age groups, Cmax and AUC012h were numerically lower, and CL/F and CL/F/TBW were numerically higher, in induced versus non-induced patients. Overall, 81.8% patients reported treatment-related AEs; most commonly, somnolence (30.3%), anorexia (27.3%), asthenia (21.2%), dizziness (15.2%) and nervousness (15.2%). Most AEs were mild/ moderate in intensity. Conclusion: Zonisamide displayed dose-dependent pharmacokinetics and was generally well tolerated in this paediatric epilepsy population. Supported by Eisai.

p179 EFFICACY AND TOLERABILITY OF LAMOTRIGIN MONOTHERAPY IN NEWLY DIAGNOSED EPILEPSY I. Marinkovic*, S. T. Ristic, H. Kocic, J. Cukuranovic*, and D. T. Ristic *Medical Faculty of Nis, Nis, Serbia; Clinical Centre of Nis, Nis, Serbia; Medical faculty University of Maribor, Maribor, Slovenia; and Institutae of Pulmonary Disaeses, Nis, Serbia
Purpose: Evaluation of Lamotrigine monotherapy outcome in epilepsy outpatients and comparison of adverse effects, in patients with newlydiagnosed epilepsy. Method: In open- label, non randomized, add-on trial over a period of 2 years, from January 2010. until January 2012. we analysed efficacy and tolerability of lamotrigin monotherapy in total of 147 untreated patients (84 male) with a recent diagnosis of epilepsy (41 idiopathic generalized epilepsy, 96 localisation- related epilepsy, 10 unclassified epilepsy). The follow-up period was minimum six months. Efficacy was classified as:1. remission without adverse effects; 2. remission with adverse effects; 3. >50% seizure reduction; 4. <50% seizure reduction; 5. seizure worsening. We analysed age at onset, manifestations and frequency of seizures, before and after treatment, tolerability and advese effects. Seizure frequency was compared before and after treatment. Result: A total of 147 patients (median age 48.15 years, range 1884) evaluable at this analysis. The median doses of lamotrigine was 250 mg./ daily. Remission without adverse effects was obtained in 62 patients (42.17%); remission with adverse effects in 29 patients (19.72%); seizure reduction of >50% in 39 patients (26.53%); seizure reduction of <50% in 14 patients (9.52%) and seizure worsening in 3 patients (2.04%). The tolerability of lamotrigine was generally good. The most frequent adverse effects were imbalance/dizziness (10.88%), headaches (6.80%), trembling (5.44%), epigastric discomfort (4.76 %), rash (2.72%). Therapy was withdrawn in 2 (1.36%) patients. Conclusion: Our study suggests high efficacy and good tolerability of lamotrigin in patients with newly- diagnosed epilepsy.
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Purpose: Zonisamide is currently licensed for adjunctive treatment of adults with partial seizures (with or without secondary generalisation). This study aimed to characterise the long-term tolerability of zonisamide in paediatric epilepsy patients.

54 Abstracts
p180 ANTIEPILEPTIC DRUG USE AND SEIZURE REFERRAL PATTERNS BY NON-EPILEPSY SPECIALISTS AT A LONDON REGIONAL NEUROSCIENCE CENTRE: A CLINICAL AUDIT D. P. Holland*, W. Hall, A. Blochberger, and H. Cock* *St. George's, University of London, London, UK; and St. George's Healthcare NHS Trust, London, UK
Purpose: Evidence based guidelines support the use of short term (714 days), prophylactic antiepileptic drugs (AEDs) for acute provoked seizures and/or patients at very high risk, but with no evidence of longer term benefit. Guidelines also recommend that all patients with suspected seizures or epilepsy have minimum safety information provided, and are promptly referred to an epilepsy specialist. We set out to audit clinical practice around stroke and neurosurgery patients with respect to AED initiation and seizures against published guidelines. Method: All in-patients initiated on AEDs under neurosurgery or stroke teams over a 4 month period were prospectively identified. Patients with a prior epilepsy diagnosis were excluded. Medical records were then retrospectively reviewed using a pre-designed audit proforma, including diagnoses, demographics, AED details (including duration), documented indication, follow up and referral. Result: 43 patients were identified of whom 1 died, and 2 were lost to follow up. Of the 40 patients included in the study, 30 AED initiations were undertaken by neurosurgery, meeting 59% of AED audit criteria. Stroke clinicians initiated AEDs in 10 patients, meeting 71% of AED audit criteria. Of the 20 who had seizures, 25% had documented counselling, and 25% were referred to epilepsy services. At least one audit criteria was not met in 73% of patients. Conclusion: Shortfalls exist in AED and seizure management in neurosurgical and stroke patients, with clinical governance and financial implications. Measures to promote the use of existing pathways and available expertise are now being implemented, and a re-audit planned. to the channels in the resting state, respectively. For eslicarbazepine and CBZ, the time constants for entering the slow inactivated state were 7.00 and 14.49 s, respectively. Conclusion: Eslicarbazepine does not share with CBZ the ability to alter fast inactivation of VGSC, but rather appears to modify the kinetics and voltage-dependence of slow inactivation states.

p182 CLINICAL EXPERIENCE WITH ORAL LACOSAMIDE AS ADJUNCTIVE THERAPY IN ADULT PATIENTS WITH UNCONTROLLED EPILEPSY: A MULTICENTRE STUDY IN EPILEPSY CLINICS IN THE UNITED KINGDOM R. D. Cary Elwes*, S. Kemp, L. Flores*, K. Colbeck, L. Nashef*, P. Goulding, and M. P. Richardson *King's College Hospital, London, UK; St Jame's Hospital, Leeds, UK; and King's College London, London, UK
Purpose: To evaluate the efficacy and tolerability of add-on Lacosamide in an out-patient epilepsy clinic setting to obtain useful information for everyday practice. Method: A retrospectively case note study of patients with refractory epilepsy was carried out in whom lacosamide had been prescribed in 19 hospitals across the United Kingdom. Result: Four hundred and three patients were included (mean age 41.9 years, 50.6% women, 18.1% with learning disabilities). Mean follow-up was 11.6 months (range one day to 42 months). Most (86.9%) had symptomatic partial epilepsy and were taking a mean of two other antiepileptic drugs. Retention rates were 80% at six months, 68% at one year and 45%t at two years. The efficacy of lacosamide was evaluated at three months and at the final FU. At three months one hundred and eight patients (31.1%) reported 50% seizure reduction and 32 (9.2%) were seizures free. At final FU 102 (37.5%) reported 50% seizure reduction and 28 (9.8%) were seizures free. One hundred and ninety three patients (48.7%) reported adverse effects (AEs). The most frequent were sedation and dizziness, followed by nausea. Lacosamide was discontinued in 150 patients (38%), mostly due to AEs and lack of efficacy. No major neuropsychiatric complications were identified and outcomes in cases with learning difficulties were similar to those without. Conclusion: Lacosamide appears to be an effective and safe AED when used as adjunctive therapy in patients with refractory partial epilepsy.

p181 SLOW AND FAST INACTIVATION OF VOLTAGEGATED SODIUM CHANNELS BY ESLICARBAZEPINE AND CARBAMAZEPINE P. Soares-Da-Silva*, and S. Hebeisen *BIAL - Portela & Ca. SA, So Mamede do Coronado, Portugal; and BSYS GmbH, Witterswil, Switzerland
Purpose: The efficacy of adjunctive eslicarbazepine acetate (ESL) in reducing the frequency of partial-onset seizures in adults receiving carbamazepine (CBZ) or another antiepileptic drug was similar (Epilepsia, 50, 454463, 2009; Epilepsy Res., 89, 278285, 2010). This study was aimed to determine the effects of eslicarbazepine, the major active metabolite of ESL, and CBZ on the fast and slow inactivated sates of voltage-gated sodium channels (VGSC). Method: The whole-cell patch-clamp technique was used to investigate the effects of eslicarbazepine and CBZ (both at 250 lM) on sodium channels endogenously expressed in N1E-115 cells, in conditions of fast and slow inactivation of sodium currents. Result: Steady state fast inactivation curves were shifted in the hyperpolarizing direction by CBZ ()12.0 mV), but not by eslicarbazepine ()2.4 mV). Eslicarbazepine-treated fast-inactivated channels recovered similarly to control conditions (Dt = 11 ms), whereas CBZ-treated channels required longer pulses to recover (Dt = 391 ms). CBZ shifted by )4.6 mV, the voltage dependence of the slow inactivation, whereas for eslicarbazepine the shift V0.5 was )31.2 mV. For eslicarbazepine and CBZ, the affinity to the slow inactivated state was 5.9 and 1.7 times higher than
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p183 THE LONG-TERM EXPERIENCE OF MONOTHERAPY WITH OXCARBAZEPINE AND LEVETIRACETAM IN THE TERTIARY EPILEPSY CENTER J. Lim, B. S. Kang, J. Byun, B. S. Park, J. W. Shin, Y. S. Kim, K. Chu, and S. K. Lee Seoul National University Hospital, Seoul, Korea
Purpose: We tried to evaluate the long-term efficacy and safety of Oxcarbazepine (OCB) and Levetiracetam (LEV) treatment as monotherapy in the tertiary epilepsy center on broad population. Method: All patients who had been treated with LEV or OCB as monotherapy at Seoul National University Hospital from 2007 to March 2009 were recruited. The patients who had brain surgery for seizure control or who associated dynamic disease were excluded. Electronic medical records were retrospectively reviewed. Efficacy was measured using a five point scale. Adverse events were also recorded. Retention rates were calculated using life-table method.

55 Abstracts
Result: Total 184 patients with OCB were recruited, including 137 (89.1%) localization related epilepsy patients. Of total 188 patients with LEV, 127 (62.8%) patients were localization related epilepsy. Mean duration of follow up in group of OCB (67.4 month) was longer than in group of LEV (22.3 month). The seizure free rate in OCB and LEV was 53.3% and 61.7%. Tolerance in OCB was significantly higher than with LEV (21.7% versus 8.5%, P<0.001). Dose of LEV was inversely correlated with seizure free outcome and tolerance. The retention rates at 3-year were 78% in group of OCB and 75% in LEV. The incidence of adverse events of OCB was significantly higher than LEV (41.3% versus 24.5%, p<0.001). However, the incidence of irritability was higher in the patients with LEV (13.8%) than in OCB (3.8%). Conclusion: Oxcarbazepine and levetiracetam was effective and safe on monotherapy and the retention rates were well maintained up to three years. types of glutamate receptors. Recently, besides acting as an antiepileptic drug, it is also being investigated as a candidate in treating periodic limb movement disorder (PLMD). Here we report a case that has excellent response to topiramate in controlling PLMD, but later developed tardive dyskinesia involving jaw and tongue. Method: The detail medical history, clinical presentation, and responses to medications (including madopar, rivotirl, topiramate) of this patient were reviewed and summarized. The pathogenesis of PLMD, the mechanism of topiramate in controlling PLMD, a comparison with other medications, and a hypothesis in how topiramate might induce tardive dyskinesia are discussed. Result: Madopar and rivotril did not show any effect in controlling PLMD and later on the dyskinesia. Topiramate stopped the PLMD completely, however is suspected to have caused dyskinesia. Conclusion: While the mechanism of topiramate in controlling epilepsy, and the underlying pathogenesis of PLMD are not entirely understood, our case report might help in understanding both by providing evidence that ion channels and receptors may play a role.

p184 GENERIC SUBSTITUTION OF ANTIEPILEPTIC DRUGS A SURVEY OF THE PATIENT'S PERSPECTIVE K. Hensler*, C. Uhlmann, T. Porschen, R. Benecke*, and J. Rsche* *Universittsmedizin Rostock, Rostock, Germany; Sdwrttembergisches Zentrum fr Psychiatrie, Weissenau, Germany; and Landesverband fr Epilepsie Selbsthilfe Nordrhein-Westfalen e.V., Kln, Germany
Purpose: In this study we tried to determine the patient's attitudes to generic substitution of antiepileptic drugs (AEDs) and their experiences with the usage of generic antiepileptic drugs in Germany and other German speaking countries. Method: In April 2011 2000 copies of a 25-item questionnaire were delivered with a magazine edited by a patient's organisation. Each item consisted of a 5-point Likert scale. Additionally the questionnaire was placed on the internet platform of another patient's organisation from May to September 2011. We calculated Spearman correlation coefficients between the answers in different items. Result: When responses of relatives and of patients, who could not determine whether they had experiences with generic AEDs or not, were excluded, 99 paper questionnaires and 128 internet questionnaires could be analysed. 95% of the patients (128 female, 99 male) were from Germany. 112 (= 49%) patients reported experiences with generic substitution of AEDs. 34% of them complained about difficulties with the generic substitution (Likert scale 4 or 5) and 25.5% had a breakthrough seizure (Likert scale 4 or 5). 9.6% of the patients admitted compliance problems after generic substitution (Likert scale 4 or 5). Compliance problems were correlated with breakthrough seizures (r = 0.48, p < 0.001). Conclusion: A considerable amount of patients experiences breakthrough seizures after generic substitution of AEDs. The percentage of breakthrough seizures in our study is in line with results from earlier surveys in English speaking countries. Compliance problems may be the result or in some cases the cause of breakthrough seizures.

Neuroimaging and Neurophysiology 1 Monday, 01 October 2012

p186 ICTAL [99MTC] HMPAO SPECT IN NONLESIONAL EXTRATEMPORAL EPILEPSY E. Pataraia, S. Aull-Watschinger, R. Jung, T. Traub-Weidinger, and S. Asenbaum-Nan Medical University Vienna, Vienna, Austria
Purpose: Ictal SPECT has been applied successfully in temporal lobe epilepsy (TLE) to localize the seizure onset zone with high sensitivity, especially in mesial TLE. The sensitivity of ictal SPECT is significantly lower in extratemporal lobe epilepsies (ETLE). The delineation of the epileptogenic zone in patients with non-lesional ETLE is the major challenge in epileptology. The aim of the present study was to evaluate the clinical benefit of ictal SPECT in non-lesional extratemporal epilepsy (ETLE). Method: The patients with suspected non-lesional ETLE (non-localizing or discordant non-invasive data during the prolonged Video-EEGMonitoring and negative MRI) were subjected to ictal SPECT studies for planning invasive monitoring or surgery strategy. Ictal SPECT was considered to be useful for decision-making if it obviated the need for invasive monitoring or influenced its planning. Result: Ictal [99mTc] SPECT results of 25 patients (14 men, 11 women) with suspected non-lesional ETLE (mean age 32.689.6 years) were included in final analysis. The time from clinical onset of seizure and injection was from 6 to 38 sec (mean 13.289.07 sec). The patients were divided into two groups: those where the non-invasive evaluation presumed a seizure onset zone in one region (localizable), and those where the seizure onset zone was not lateralizable or localizable (non-localizable). Ictal SPECT was decided to be successful if it provided any additional information in regard to localization of epileptogenic zone. In 6 of 14 patients (43%) of localizable group ictal SPECT provided additional information, whereas only in 1 of 11 patients (9%) of non-localizable group ictal SPECT was helpful in decision-making and planning the invasive recordings (p=0.07). Additionally in 17 patients [18F] FDG and/ or [11C] FMZ PET were available. FDG and FMZ did not demonstrate any abnormalities except in one patient. Conclusion: Ictal SPECT provided more localizing information and influenced the final decision-making only in patients were based on the
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p185 TOPIRAMTE AND DYSKINESIA Y. Liang*, H. Tsai, and C. Lo* *National Chen Kung University Hospital, Douliou branch, Yulin, Taiwan; and Chiayi Christian Hospital, Chiayi, Taiwan
Purpose: Topiramate is a sulfamate substituted monosaccharide. It acts to reduce voltage gated sodium channels and also enhances postsynaptic GABA-receptor currents and limits activation of the AMPA-kainate

56 Abstracts
non-invasive monitoring results the seizure onset zone could be localized to one region of the brain. In opposite to TLE clinical benefit of ictal SPECT preoperatively in non-lesional ETLE seems to be limited. Due to rapid changes of perfusion state peri-ictally (for example due to rapid seizure spread especially in frontal lobe epilepsy) successful ictal SPECT investigations might lack clinical benefit with respect to possible surgical interventions. These findings need to be validated in a larger group of patients. The subtraction with interictal SPECT would also improve these results. Method: A 15 year old boy with drug-resistant cryptogenic epilepsy underwent continuous EEG- fMRI acquisition using a 3T MR scanner. During the examination 26 interictal electric abnormalities were registered. The fMRI data analysis was performed by different event-related (ER) design adopting respectively canonical hemodynamic response function (HRF), Fourier and Finite Impulse Response (FIR) basis functions. The localization of activation/deactivation clusters obtained by each statistical approach was compared with the localization of the seizure onset zone obtained by invasive stereo-EEG. Result: Similar activation maps were obtained by ER design using FIR basis functions and Fourier basis functions as HRF. Both approaches provided clusters of activation concordant with the seizure-onset zone identified by depth electrodes. On the other hand, ER design combined with standard HRF was not able to identify clusters within the seizureonset zone. Conclusion: The ER approach using Fourier and FIR basis functions might provide adjunctive information with respect to standard HRF. The role of non-canonical approaches in identifying the epileptogenic zone needs to be evaluated on large series of patients.

p187 MAGNETOENCEPHALOGRAPHIC MEASURES OF ABNORMAL SENSORY OSCILLATIONS: A WINDOW ON PHOTOSENSITIVE EPILEPSY G. Perry*, L. M. Brindley*, S. M. Muthukumaraswamy*, K. Hamandi, and K. D. Singh* *Cardiff University, Cardiff, UK; and University Hospital of Wales, Cardiff, UK
Purpose: Photosensitivity is a common trait in a number of epilepsy syndromes. Measuring visual responses with magnetoencephalography (MEG) provides a unique opportunity for the non-invasive study of abnormal cortical oscillations in these patients. Evidence points to photosensitivity being due to abnormalities in cortical inhibition, and this may be reflected in oscillations in the gamma frequency range (30100Hz), which are believed to reflect GABAergic inhibitory processes. The purpose of the present study was to use MEG to identify differences in these oscillations between photosensitive patients and non-photosensitive controls. Method: Data were collected from ten patients with photosensitive epilepsy and two age-matched control groups. Participants underwent MEG recording while viewing static visual gratings. Responses were localised to the visual cortex and the relationship between visually-induced oscillations and stimulus parameters (contrast and size) were compared between the different participant groups. Result: Contrary to our expectations, we did not find clear evidence for a difference between groups in the main gamma-band response (40 70Hz). Instead our results suggest differences at a lower frequency around 28Hz, and in the alpha frequency (812Hz) range. Conclusion: Our evidence suggests that there may indeed be characteristic differences in visually-induced oscillations between individuals with photosensitive epilepsy and controls, which may have potential use as diagnostic markers. The finding of differences in the high beta/low gamma and alpha frequency ranges suggests that pathophysiological disturbances may be localised to thalamo-cortical processes, and thus our data could guide future research into the mechanisms of seizure generation in photosensitive epilepsy.

p189 STRESS AFFECTS EMOTIONAL PROCESSING IN LEFT TEMPORAL LOBE EPILEPSY J. Szaflarski, J. Allendorfer, H. Heyse, and L. Mendoza University of Cincinnati Academic Health Center, Cincinnati, OH, USA
Purpose: To assess how stress (S) affects emotion processing in patients with left temporal lobe epilepsy (LTLE). Method: Included were 22 LTLE patients who believed (+S; n=15) and did not believe (-S; n=7) that stress played a role in their seizure control. Subjects were presented a pseudo-randomized series of faces with different expressions (happy/fearful/sad/neutral) during fMRI and instructed to press 1 for male and 2 for female face. After scanning, subjects were asked to indicate the expression on each of the previously presented faces; fMRI analysis only included correctly rated faces. FMRI image coregistration, spatial normalization, single-subject and group statistical modeling, and visualization were performed using AFNI. Single-subject fMRI response to emotion was determined using general linear modeling (happy, fearful, or sad faces contrasted with neutral faces). Group differences in neural processing of each emotion were performed using 2-sample t-tests (p<0.05, cluster threshold of 20 voxels). Result: Overall accuracy on post-scan rating of faces was better for -S than +S (p=0.012); the +S showed overall greater involvement of the prefrontal and medial temporal/amygdala regions. The groups also showed differential patterns of activation for each emotion (fear/sadness/happiness). Compared with -S, +S exhibited diminished response particularly in superior frontal regions when processing fear and sadness, but increased response in left temporal regions when processing happiness. Conclusion: Patients who do and do not believe that stress affects their seizure control recruit different brain regions during emotional processing; this difference may underlie the decreased accuracy of +S patients in rating emotional faces. (Support: Shor Foundation for Epilepsy Research).

p188 COMPARISON OF EEG-FMRI DATA TO INVASIVE ELECTROPHYSIOLOGICAL REGISTRATION IN CRYPTOGENIC FOCAL EPILEPSY I. Pesaresi*, S. Fabbri, C. Barba, E. Bartolini, P. Cecchi, F. Giordano, F. M. Quaglia, D. Pruna, M. Cosottini, and R. Guerrini *AOUP, Pisa, Italy; Pisa University, Pisa, Italy; Children's Hospital Meyer, Florence, Italy; Pisa University, Pisa, Italy; and Azienda Ospedaliero Universitaria of Cagliari, Cagliari, Italy
Purpose: To compare different methodological approaches in a patient with cryptogenic epilepsy who underwent invasive neurophysiologic investigation.
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*University of Modena and Reggio Emilia, Modena, Italy; University of Parma, Parma, Italy; and Ospedale NiguardaCa Grande, Milano, Italy
Purpose: To illustrate a paradigmatic case of concordance between presurgical EEG-fMRI and subsequent Stereo-EEG data. Method: We report the case of a 27 year-old left-handed man, who underwent epilepsy surgery after an extensive pre-operatory investigation. Epilepsy started at age of 5 months. Staring, flushing, and bimanual automatisms characterized his drug-resistant partial seizures. The patient underwent prolonged Video-EEG recordings and two EEGfMRI studies, both performed with subsequent Independent Component Analysis (ICA) on EEG data. He also performed an intracranial monitoring. Result: Scalp EEG revealed bilateral frontal interictal paroxysmal abnormalities, while prolonged video-EEG recordings showed a left fronto-temporal localization of ictal events. Different interictal spikes dataset (ISD) were recorded during the first EEG-fMRI study and two distinct cluster of BOLD signal increase were identified: one located in the left frontal pole and the other in the ipsilateral dorso-lateral frontal cortex. Structural brain MRI revealed thickening and blurring of the fronto-polar cortex suggesting the presence of a focal cortical dysplasia and a tailored cortectomy involving the fronto-polar region was then performed. After three-months seizure-free period the patient experienced seizures recurrence. Post-operative EEG-fMRI, with the recording of ISD and one ictal event, and intracranial EEG results with the recording of several seizures, confirmed the involvement of the dorso-lateral frontal cortex, spared by the first cortectomy. In conclusion this data show how EEG-fMRI could identify the epileptogenic zone as demonstrated by concordance with Stereo-EEG results and clinical outcome. It represents a promising tool that should be implemented in the diagnostic work-up of patients with surgically-remediable epilepsies.

p192 HOW TO IMPROVE THE YIELD OF FDG-PET IN THE PREOPERATIVE WORK-UP FOR EPILEPSY SURGERY M. A. Van T Klooster*, F. S. S. Leijten*, G. J. M. Huiskamp*, R. M. C. Debets, E. F. I. Comans, S. Bouvard, and P. Ryvlin *UMC Utrecht, Utrecht, The Netherlands; 2 Epilepsy Institute of The Netherlands Foundation (SEIN), Heemstede, The Netherlands; VU University Medical Center, Amsterdam, The Netherlands; CERMEPImagerie du Vivant, Lyon, France; and Institute for Child and Adolescent with Epilepsy (IDEE), Hospices Civils de Lyon, Lyon, France
Purpose: Fluorodeoxyglucose PET (FDG-PET) is a costly, semi-invasive, interictal method to localize epileptogenic foci, marked by decreased FDG uptake. Since PET facilities and experienced reviewers are scarce we investigated how to improve the yield of the preoperative FDG-PET scan. We, retrospectively, compared three FDG-PET assessments to ictal electrocorticography (ECoG): initial clinical visual assessment (PETclin), blinded visual re-assessment (PETre) and Statistical Parametric Mapping (SPM) analysis (PETspm). Method: 44 Refractory focal epilepsy patients (mean age 25y, 19 female, 75% extra-TLE) who underwent chronic ECoG monitoring were included. All patients and 38 healthy controls underwent a static FDGPET scan (ECAT EXACT HR+). PETclin reports were collected. PETre was executed by the same two experts as for PETclin. Thirdly, PETspm was performed; each patient scan was compared, at cluster level (puncorr<0.001), to the healthy controls. The ictal ECoG electrodes were co-localized. Results were classified into ten predefined brain anatomical regions, and analysed on group (kappa, sensitivity, specificity) and patient level. Result: The number of scans without abnormalities for PETclin, PETre and PETspm were 5, 1 and 0, respectively, without overlap. Preliminary results indicate that PETre increases the overall sensitivity compared to PETclin, maintaining equal specificity. On patient level PETspm reveals new results in case of normal PETclin, or additional information regarding the focus. Conclusion: Visual re-assessment should be considered when initial assessment is negative. We advise to use more than one method when judging a FDG-PET scan in these types of difficult patients since re-evaluation has the potential to increase epilepsy surgery eligibility.

p191 UNVEILING THE MYSTERY OF DJ VU M. Brazdil*, R. Marecek, T. Urbanek, T. Kasparek, M. Mikl, I. Rektor*, and A. Zeman *Brno Epilepsy Center, Brno, Czech Republic; CEITEC MU, Brno, Czech Republic; Academy of Sciences of the Czech Republic, Brno, Czech Republic; Masaryk University, Brno, Czech Republic; and University of Exeter, Exeter, UK
Purpose: Dj vu is an eerie experience that is characterized by the recognition of a situation concurrent with the awareness that this recognition is inappropriate. This feeling of irrelevant familiarity is a common phenomenon occurring both in clinical (mainly epileptic) and nonclinical population. Despite numerous theories have been suggested as to what nonpathological dj vu is and what causes it, until now no ultimate explanation has been generally accepted. Method: We investigated differences in brain morphology between healthy subjects with and without dj vu using a novel multivariate neuroimaging technique, Source-Based Morphometry. Result: The analysis revealed a set of cortical (predominantly mesiotemporal) and subcortical regions in which there was significantly less gray matter in subjects reporting dj vu. In these regions gray matter volume was inversely correlated with the frequency of dj vu. Conclusion: Our results demonstrate for the first time a structural correlate of dj vu in healthy individuals and implicate a direct pathogenetic link between nonpathological and epileptic dj vu. We hypothesize our findings reflect an alteration of hippocampal function and postnatal neurogenesis in subjects with dj vu.

p193 MULTIMODAL EVOKED POTENTIALS BE USEFUL TOOL IN THE STUDY OF ENCHEPHALOPATY WITH STATUS EPILEPTICUS DURING SLOW SLEEP REPORT 5 CASES P. A. Ruiz, J. J. Ortega, J. R. Diaz, A. D. Ghinea, E. Canovas, and J. M. Pinzon Hospital General De Castellon, Castellon De La Plana, Spain
Purpose: Encephalopathy with status epilepticus during sleep is characterized by severe impairment of neuropsychological development, characteristic EEG pattern of continuous spike-wave during slow sleep and seizures in children. We appreciate the usefulness of Multimodal Evoked Potentials in the diagnosis and evolution of this disorder. Method: We studied 5 children (mean 7 years old) with ESES with severe developmental deficit and few seizures; we performed a Polysomnogram, Neuropsychological Development Test and Visual-Evoked Potentials, Somatosensory-Evoked Potential and Cortical and Brainstem Auditory-Evoked Potential. Only in cases found altered evoked potentials, we make annual checks, followed until the continuous spike-wave
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58 Abstracts
pattern during sleep was resolved. Normal values were taken from a group of healthy children (313 years). Result: Four cases showed a rate spike-wave in slow sleep > 85% and seizures. Three cases, showed behavior disorders and severe deterioration in the language area. Find a delay P100 wave in VEP of two cases with significant visual deficit. PEAC was altered in a case with Auditory Verbal Agnosia, showing normal BAEP; and SSEP was normal in all cases. These alterations disappear at the same time it solves the continuous spike-wave pattern of sleep EEG. Conclusion: EPs have been studied as diagnostic evidence for epilepsy, but there are few data on the usefulness of Multimodal Evoked Potentials in children with ESES. The close relation between changes in EP and the EEG is very important redefine which neuro-behavioral areas would be involved in patients with this encephalopathy, being useful in the diagnosis and evolution. correlates with underlying pathological changes of tubers, as well as their epileptic potential. Method: In this study we plan to analyze the perfusion patterns both within tubers and in the surrounding perilesional regions in two populations of TSC patients, those with epilepsy (6 patients), and those with no history of seizures (6 patients). Epileptic tubers will be cross-identified with scalp EEG, and this data will be correlated with ASL perfusion maps. Result: We have obtained and analyzed ASL and MRI data on 4 TSC patients with epilepsy. Thus far, it appears that epileptic tubers and surrounding perilesional areas show hyperperfusion in comparison with average cerebral blood flow. Analysis of the nonepileptic tubers reveals no significant differences in perfusion compared to average cerebral blood flow. Conclusion: Our preliminary data shows that ASL can accurately identify epileptic networks in TSC. Using ASL to identify epileptic networks can be potentially applied to all patients with neocortical epilepsy, with the ultimate goal of improving seizure freedom rates from resective surgery.

p194 MESIAL TEMPORAL SCLEROSIS WITH MRI SIGNALS EXTENDING TO THE FORNIX S. Baz*, A. Alsemari, and F. Almuhailib *KFSHRC, Riyadh PO Box 3354, Saudi Arabia; and King Faisal Specialist Hospital & Research Centr, PO Box 3354, Saudi Arabia
Purpose: Mesial temporal sclerosis had been reported with ipsilateral fornix atrophy, however the extension of the MRI signals to the fornix is seldom reported. Method: To demonstrate the clinical, electrophyological and the imaging data of the findings. Result: 39 years old lady with refractory left temporal lobe epilepsy since adolescent on multiple anti-epileptics admitted to epilepsy monitoring unit for surgical evaluation. 5 seizures were captured at different interval then MRI was arranged several days after the last seizures. It showed mesial temporal sclerosis but with minor swelling of mesial temporal structures and a significant signal intensity and swelling of the fornix. The patients had slightly bigger sized fornix and mesial temporal structures several days after repeated seizures. However the previous MRI brain few years earlier demonstrated thin asymmetric left fornix. Conclusion: Recurrent seizures may influence the apparent thickness of the fornix however other possibilities may be entertained as neoplastic infiltration or inflammatory process.

Neuroimaging and Neurophysiology 2 Monday, 01 October 2012

p196 THE EFFECT OF GENERALIZED SPIKE AND WAVES DISCHARGE DURATION AND IGE SUB-SYNDROME ON BRAIN NETWORKS AS REVEALED BY EEG-FMRI M. Pugnaghi*, D. W. Carmichael, A. Vaudano, U. J. Chaudhary, F. Benuzzi*, C. Di Bonaventura, A. T. Giallonardo, R. Rodionov, M. C. Walker, J. Duncan, S. Meletti*, and L. Lemieux *University of Modena and Reggio Emilia, Modena, Italy; UCL Institute of Child Health, London, UK; University of Rome La Sapienza, Rome, Italy; UCL Institute of Neurology, London, UK; and Department of Clinical and Experimental Epilepsy, London, UK
Purpose: To investigate the hemodynamic correlate of generalized spike wave discharges (GSWD) duration and in particular the relationship between discharge duration and the magnitude and extent of the BOLD changes. Method: We studied 42 adult patients with Idiopathic Generalized Epilepsies (IGE) who underwent simultaneous recordings of EEG and functional MRI (EEG-fMRI) in three centres (London, UK; Modena and Rome, Italy). We applied a parametric analysis at the single subject level in order to explore the presence of non-linear effects of duration of GSWD on the BOLD changes. A full-factorial ANOVA design was performed as a random effect group analysis to model possible effects of IGE sub-syndrome and different MRI scanners. Result: The group analysis of the GSWD linear effect revealed BOLD signal changes in a network of brain regions: mainly transient BOLD increases in the thalami and bilateral insulae, and transient BOLD decreases in the posterior cingulate, precuneus and bilateral parietal regions. No significant non-linear effect of GSWD duration on BOLD was found. The full-factorial ANOVA analysis disclosed no main effect of the MRI scanner across the three centres, and no main effect of the sub-syndrome. Conclusion: Our findings support the idea that the amplitude of the BOLD response is linearly related to the GSWD duration with no

p195 LOCALIZING EPILEPTIC NETWORKS IN TUBEROUS SCLEROSIS USING ARTERIAL SPIN LABELING MRI PERFUSION A. Azarion, and K. A. Davis Hospital of the Univeristy of Pennsylvania/University of Pennsylvania School of Medicine, 4127829, USA
Purpose: The goal of this study is to utilize the noninvasive technique of arterial spin labeling (ASL) magnetic resonance imaging (MRI) to identify epileptic networks in patients with tuberous sclerosis complex (TSC), a subtype of neocortical epilepsy. Given that patients with TSC often have better seizure control after surgical resection of epileptic lesions as well as the neighboring perilesional tissue, this cohort is ideal for testing the hypothesis that ASL can accurately identify epileptic networks. Recent studies have shown that the quantitative ASL signal
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59 Abstracts
non-linear (or threshold) effect of duration. These results do not support the existence of a critical GSWD duration underlying consciousness impairment.

p197 SPECT PERFUSION PATTERNS IN PAEDIATRIC EPILEPSY OF TEMPORAL LOBE ORIGIN CORRELATION WITH SURGICAL OUTCOME P. S. Lakkunta*, S. J. Sattaluri, and M. Panigrahi *Krishna Institute Of Medical Sciences, Secunderabad, India; and Cecunderabad, India
Purpose: To assess the role of ictal SPECT in paediatric Temporal lobe epilepsy (TLE) and to correlate Ictal perfusion patterns with Surgical outcome. Method: A retrospective analysis of Ictal & Interictal SPECT, Ictal Video EEG, MRI and surgical outcome was performed in 27children of TLE. SPECT Perfusion patterns were classified as Typical (anteromedial, anterolateral, inferior) and Atypical (extra temporal). Surgical outcome was assessed according to Engel's classification. Result: Ictal and Interictal SPECT were done in 21, Interictal alone in 6. Sixteen had Hippocampal sclerosis (HS), while nonHS group had neuronal loss in four, Dual pathology in two, FCD in 2, ganglioglioma in 1, gliosis in one and normal in one . Sensitivity of ictal SPECT is 95%, interictal is 78%. SPECT was diagnostic in 85.7% of normal MRI patients. Typical pattern with anteromedial and lateral hyperperfusion is commonest in HS (75%). Atypical pattern is more commonly seen in nonHS group than with HS (45.4% vs 25%). 91.6% of HS group with typical pattern are in Engel's class 1 outcome. Whereas 80% of nonHS group with atypical pattern are in poor surgical outcome (p < 0.05). Conclusion: Ictal SPECT is highly sensitive (95%) in pre surgical evaluation of paediatric TLE. Typical pattern is commonest in HS (75%) and shows good surgical outcome. Significant association of atypical pattern with poor surgical outcome is noted in nonHS group (p value<0.05).

p199 CONVERGENT EVIDENCE OF REGIONAL THALAMIC ABNORMALITIES IN MESIAL TEMPORAL LOBE EPILEPSY S. S. Keller, C. Traynor, J. OMuircheartaigh, G. J. Barker, W. Crum, and M. P. Richardson King's College London, London, UK
Purpose: Multiple MRI studies have revealed global thalamic atrophy in human mesial temporal lobe epilepsy (mTLE). In animal limbic epilepsy, the medial nuclei of the thalami have been described as the consistent neuroanatomical alteration (Bertram et al., 2001, Epilepsia; 42:967). Using MRI and DTI, we sought to investigate the topology of intra-thalamic alterations in mTLE. Method: For 12 patients with mTLE and 18 healthy controls, we acquired DESPOT structural sequences for T1 and T2 mapping of six thalamic sub-regions per hemisphere based on a previously described protocol (Traynor et al., 2011, Neuroimage; 56:939) and DTI sequences for connectivity-based segmentation of the thalamus (Behrens et al., 2003, Nat Neurosci; 6:750) using a 3 T GE system. T1/T2 thalamic maps used the work of Morel et al. (1997, J Comp Neurol; 387:588) for anatomical reference. Result: Left (p=0.03) and right (p=0.02) Region 5 (including anteroventral, anteromedial, and ventral lateral posterior nuclei), and right (p=0.01) Region 3 (including medial pulvinar, mediodorsal and central lateral nuclei) were significantly reduced in volume in patients relative to controls. Furthermore, right Region 3 had significantly greater T2 values in patients (p=0.01). From connectivity-based segmentation, the thalamic sub-region classified as connecting to the right temporal target region was significantly smaller in patients (p=0.05). Conclusion: Thalamic sub-regions known to connect with the hippocampus are architecturally altered in mTLE. These thalamic regions may represent a central hub for the propagation and synchronisation of temporal lobe seizures, mediating the spread of hippocampal epileptiform activity to neocortex.

p198 FUNCTIONAL CONNECTIVITY STUDY IN PATIENTS WITH TEMPORAL LOBE EPILEPSY AND DEPRESSIVE SYMPTOMS R. Rocamora*, N. Roe-Vellve, R. M. Vivanco-Hidalgo*, M. Picado, B. Villoria*, A. Merino*, C. Garcia-Ribera*, A. Bulbena*, and O. Vilarroya *Parc de Salut Mar-Hospital de Mar, Barcelona, Spain; and Fundacio IMIM, Barcelona, Spain
Purpose: Our objective is the evaluation and characterization of neurofunctional, psychopathologic and neuropsychologic abnormalities present in a group of 15 TLE patients and 15 healthy controls. Method: We obtained fMRI scans from all participants and performed resting state analyses based on ROIs in order to study markers associated with abnormalities in functional connectivity relate to mood alterations. Result: Our preliminary results indicate hyperactivation in right anterior cingulate cortex (ACC), bilateral thalamus and insula; and hypoactivation in the left amygdala in the TLE patients as compared with the control group. We also performed a-priori ROIs of thalamic and ACC regions, which previous studies relate with depression. We found increased activation in such areas correlated with depression symptoms severity. Conclusion: Our results indicate the presence of neurofunctional differences in TLE patients that might be due to shared neural pathophysiological abnormalities underlying both epilepsy and depression, and might explain the presence of mood alterations in epilepsy.

p200 MR IMAGING IN STATUS EPILEPTICUS SECONDARY TO PARANEOPLASTIC ENCEPHALITIS S. Sarria, M. Toledo, C. Lorenzo I Bosquet, E. Lainez, S. Siurana, C. Auger, E. Santamarina, X. Salas-Puig, R. Mitjana, C. Vert, L. Fraschieri, and A. Rovira Vall dHebron University Hospital, Barcelona, Spain
Purpose: Patients with systemic cancer may have new-onset status epilepticus (SE) as the main clinical feature of paraneoplastic encephalitis. Five such patients who underwent MRI during SE or immediately after recovery are described. Method: We retrospectively reviewed the MR scans of five consecutive patients who experienced SE as the onset of paraneoplastic encephalitis between January)2005 and July-2011. All patients met the criteria for paraneoplastic syndrome. Three patients had small-cell lung carcinoma, two of them with anti-Hu antibodies. The two remaining patients had intestinal and lung adenocarcinoma. The SE episode was convulsive in two patients and none-convulsive in three patients. Result: All patients showed hyperintense lesions on T2-weighted images involving the limbic structures, specifically the hippocampus. Three patients additionally had scattered extralimbic areas of high-signal intensity. The T2 hyperintensities were related to the electroclinical onset of the seizures. Perfusion MRI obtained with arterial spin labeling (ASL) in one patient showed hyperperfusion overlapping the inflammatory lesions. SPECT and PET performed in 4 patients demonstrated increased metabolism limited to the areas of encephalitis. Mild to moderate contrast
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

60 Abstracts
enhancement was seen in only one patient. In images performed following recovery, atrophy of the affected hippocampus was observed. In two patients who had recurrent paraneoplastic encephalitis manifesting as SE, new T2 lesions with a different topography were detected. Conclusion: Limbic and extralimbic encephalitis can be secondary to paraneoplastic syndrome in new-onset SE. MR study shows consistently hyperintense lesions on T2-weighted imaging, sometimes with mild contrast enhancement, and increased perfusion or metabolism as demonstrated by ASL or PET/SPECT. Method: The EEG-functional MRI (fMRI) was used to measure the resting state functional connectivity during interictal GSWDs in drugnave CAE, and three different brain networksthe default mode network (DMN), cognitive control network (CCN), and affective network (AN)were investigated. Result: Cross-correlation functional connectivity analysis with priori seed revealed decreased functional connectivity within each of these three networks in the CAE patients during interictal GSWDS. It included precuneus-dorsolateral prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC), and inferior parietal lobule in the DMN; DLPFC-inferior frontal junction (IFJ), and pre-supplementary motor area (pre-SMA) subregions connectivity disruption in CCN; ACC-ventrolateral prefrontal cortex (VLPFC) and DMPFC in AN; There were also some regions, primarily the parahippcampus, paracentral in AN, and the left frontal mid orb in the CCN, which showed increased connectivity. Conclusion: The current findings demonstrate significant alterations of resting-state networks in drug nave CAE subjects during interictal GSWDs and interictal GSWDs can cause dysfunction in specific networks important for psychosocial function. Impairment of these networks may cause deficits both during and between seizures. Our study may contribute to the understanding of neuro-pathophysiological mechanism of psychosocial function impairments in patients with CAE.

p201 DYNAMIC EFFECTIVE CONNECTIVITY OF EPILEPTIC NETWORKS DETERMINED WITH HIGH DENSITY EEG SOURCE ANALYSIS S. Vulliemoz*, R. Tyrand, L. Astolfi, B. He, M. Seeck*, C. Michel*, and G. Plomp *University Hospital of Geneva, Geneva, Switzerland; University of Geneva, Geneva, Switzerland; La Sapienza University, Roma, Italy; and University of Minnesota, Minneapolis, USA
Purpose: Analyzing the dynamic behaviour of epileptic networks could help to better understand the way pathologic neural activity propagates, and leads to spikes, seizures, and their electro-clinical and cognitive manifestations, with implications for epilepsy surgery candidates. Method: In 6 patients with temporal lobe epilepsy we studied effective connectivity of large-scale cortical networks at high temporal resolution around interictal spikes, recorded with high density (256 channels) EEG. The cortical electric source activity was obtained for 90 cortical regions of interest (ROI) using a distributed inverse solution. Multivariate, timevarying (millisecond resolution), and frequency-resolved (150Hz) Granger causality analysis (Partial Directed Coherence) was applied to the source signal for all ROIs. In all patients subsequent intracranial recording or surgical resection was used for validation. Result: Information flow occurred predominantly in the theta and beta bands. The key driving structures where located in the anterior and medial temporal regions, with peak information transfer before the spike maximum. We found fast-varying connectivity patterns between the antero-medial and lateral temporal lobe and basal frontal lobe, but also transient transfer towards the contralateral temporal lobe. In two patients with a multifocal irritative zone, we found evidence of connectivity from the main anterior temporal driver towards the secondary spike focus remote from the epileptogenic zone. Conclusion: EEG-based time-varying effective connectivity of epileptic spikes provides a clear characterization of the epileptic networks that is concordant with invasive electro-clinical findings. This could have major clinical implications for tailoring resective, disconnective, and functional surgery.

p203 COMPARISON OF FDG-PET AND ICTAL SPECT IN CHILDREN WITH FOCAL EPILEPSY UNDERGOING PRE-SURGICAL EVALUATION N. Vora*, V. I. Venegas, L. Biassoni, H. Cross, and C. M. Eltze *Lilavati Child Neuro Care, Ahmedabad, India; Clinica Alemana Santiago, Las Condes Santiago de Chile, Chile; Great Ormond Street Hospital for Children, London, UK; UCLInstitute of Child Health, London, UK; and University College London, Institute of Child Health, London, UK
Purpose: Ictal SPECT and fluorodeoxyglucose (FDG) - PET provide additional information to localise the epileptogenic zone especially when magnetic resonance imaging (MRI) is negative. Requirements for videoEEG and tracer injection close to seizure-onset pose logistic difficulties that may limit usefulness of ictal SPECT in pre-surgical evaluation. Here we compare the yield of ictal SPECT and FDG-PET in children with focal epilepsy undergoing pre-surgical evaluation. Method: Children evaluated in the supra-regional epilepsy surgery program who underwent both ictal SPECT and FDG-PET were identified. Reports issued by the program radiologist were analyzed. Additional clinical information was obtained from patient's records. Result: 24 children (14 males, mean age of seizure onset 3.5 years, sd +/)3.4) were identified, of which MRI was negative in 18 (75%). Ictal EEG was focal in 13 (54%) cases, concordant with FDG-PET in 5 and SPECT in 6. FDG-PET provided localising information in 17 (71%) and SPECT in 14 (58%) cases with concordance of both in 10 (42%). In 7 children with focal FDG-PET changes, ictal SPECT was not localising (5 multifocal/bilateral, 2 negative), whilst SPECT indicated a focal lesion in 4 with non-localising FDG-PET (2 multifocal/bilateral, 2 negative). Surgery was offered to 11 children (45%). Conclusion: FDG-PET provided additional localising information in a large proportion of mostly MRI negative patients justifying selective utilisation of Ictal SPECT. The high proportion of discordance of both imaging modalities emphasises the importance of a multidisciplinary approach considering multiple data sources i.e. neurophysiology, neuropsychology and other structural/functional imaging modalities.

Purpose: To investigate the intrinsic brain connections at the time of interictal generalized spike-wave discharges (GSWDs) to understand their mechanism of effect on brain function in untreated childhood absence epilepsy (CAE).
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

61 Abstracts
p204 EX VIVO HIGH-RESOLUTION MR (7T) MICROSCOPY OF THE HUMAN HIPPOCAMPUS R. Coras*, R. Garbelli, G. Milesi, C. Frassoni, I. Zucca, A. Mastropietro, A. Mhlebner*, A. Hess, E. Aronica, I. Blmcke*, and R. Spreafico *University Hospital Erlangen, Erlangen, Germany; I.R.C.C.S. Foundation Neurological Institute, Milan, Italy; University of Erlangen-Nuremberg, Erlangen, Germany; and Academic Medical Centre, Amsterdam, The Netherlands
Purpose: The human hippocampus is morphologically affected in many neurological disorders such as Alzheimer's disease or mesial temporal lobe epilepsy (MTLE). Its internal structure remains, however, difficult to recognize at 1.5T- or 3T-MR imaging. Herein, we aimed to anatomically delineate all subregions and layers of the human hippocampus combining high-field 7T-MRI and microscopy from same tissues specimens. Method: Different imaging protocols were applied on a 7T experimental scanner to examine eight post-mortem human hippocampus specimens. Anatomical layers along the anterior-posterior axis of the hippocampus were characterized on T2-weighted coronal sections. Histological analysis of same specimens was performed to co-register and validate 7T-MRI. Three-dimensional T2-weighted imaging and coronal planes with different angulations were acquired to anticipate the arched shape of the hippocampal head. Fractional anisotropy and color fiber orientation maps were used to visualize intrahippocampal projections and fiber tracts. Result: MR-Intensity differences between anatomical boundaries were confirmed by exact confrontation with histology and could be assigned to ten clearly recognizable layers. These findings were best visible at the hippocampal mid-body-level. We were able to distinguish all these hippocampal subregions also in the hippocampal head with three-dimensional T2-weighted imaging and angulated coronal planes. Fractional anisotropy and color fiber orientation maps visualized intrahippocampal projections and fiber tracts connecting the hippocampus with the mesial temporal lobe. Conclusion: High resolution MR-microscopy identified anatomical subcompartments and sublayers as well as distinct fiber tracts along the entire anterior-posterior hippocampal axis, and will be a promising tool for the investigation of subtle pathology in neurological or neurodegenerative disorders. using F-contrasts across the alpha and beta band effects (taken separately and together). Result: a bands were from sensory cortex, b bands were predominantly recorded from primary motor cortex. During finger tapping a and b activity correlated significantly respectively with BOLD changes in the right motor cortex and bilateral sensory cortices. During rest, activity correlated with BOLD changes in the precuneus (a, b), cingulate (a), middle and superior-frontal gyri (a, b), angular (a, b), supramarginal (a, b), lingual (b) and inferior-temporal gyri (a) and lateral-occipital (a) cortex. Conclusion: Intracranial-EEG-fMRI allowed the investigation of a and b generators and the role played in marking brain networks. Indeed, a and b correlated with BOLD changes which mapped the default mode, fronto-parietal, occipital-visual and occipital-parietal networks and the visual system.

Neuroimaging and Neurophysiology 3 Monday, 01 October 2012

p206 DEFINITION OF A STEREOTACTIC 3D MODEL OF THE HUMAN INSULA FOR NEUROSURGICAL APPROACH (EPILEPSY AND STEREOTAXIC SURGERY) A. Afif*, G. Becq, and P. Mertens* *Neurological Hospital, Hospices Civils de Lyon, Lyon, France; and Grenoble, France
Purpose: Design a method for 3D reconstruction of the insula, including its gyri and sulci, in AC-PC reference usable individually for imaging or for epilepsy and stereotactic surgery. Method: Morphometric study using 100 MRI of normal insular region. 56 male/44 female, 50 left/50 right hemispheres. Stage 1: Reconstruction in AC-PC reference of the insula from 3D-T1-MRI slices 1 mm thick. Stage 2: Digitalization and superposition of data in 3D using PhotoStudio software (Photo Editing Software) system with PC as the center of coordinates. Stage 3 : MATLAB software (Mathworks Inc.) was used to transform in color values each pixel to obtain a color scale corresponding to the probability of insula sulci localization between 0% and 100%. Result: Demonstration of very significant correlations between the coordinates of the main insular structures (angles, sulci ..) and the length of AC-PC. This close correlation allows to describe a method for 3D reconstruction of the insula on MRI slices that requires only the positions of Ac and PC and then the inter-commissural (AC-PC) length. This procedure defines an area containing insula with 100% probability. Conclusion: 3D reconstruction of insula will be potentially useful for: 1 To improve localization of cortical areas, allowing to differentiate insular cortex from opercular cortex during stereoelectroencephalographic exploration of patients with epilepsy (SEEG) or in morphological and functional imaging. 2 For microsurgical approach of Insula using Neuronavigation techniques. 3 Identification of Insula during stereotactic surgery (SEEG, biopsy).

p205 INTRACRANIAL EEG-FMRI: MAPPING BRAIN NETWORKS RELATED WITH ALPHA AND BETA IN SENSORIMOTOR CORTEX S. Perani, S. Vulliemoz, R. Rodionov, L. Lemieux, and D. W. Carmichael UCL Institute Of Neurology, London, UK
Purpose: Alpha (a) and beta (b) are EEG features in the frontal cortex. However, whether alpha and beta originate in spatially independent regions across the sensorimotor cortex and their relationship to different brain networks remain unclear. In this study we used simultaneous intracranial-EEG-fMRI to study local a and b oscillations and map their haemodynamic correlates. Method: One patient with intracranial-EEG (1x57 grid) over the left sensorimotor cortex underwent T1, two sessions of resting-state and one finger-tapping fMRI during simultaneous acquisition of intracranialEEG data. After artifact corrections, electrophysiological signal was time-frequency transformed and averaged into frequency bands. For each frequency band, the power was spatially averaged by taking the first principal component and convolving with a canonical haemodynamic response. Statistical parametric maps of the fMRI changes were obtained

p207 MYOCLONUS CORTICAL GENERATORS IN UNVERRICHT-LUNDBORG DISEASE: AN ELECTRIC SOURCE IMAGING STUDY A. Del Felice*, C. Arcaro*, L. Canafoglia, S. Franceschetti, A. Fiaschi*, and P. Manganotti*
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

62 Abstracts
*Universit degli Studi di Verona, Verona, Italy; and IRCCS Foundation Besta Neurological Institute, Milan, Italy
Purpose: To localize the cortical generator of myoclonic jerks in progressive myoclonic epilepsy (Unverricht-Lundborg disease) applying the Electrical Source Immaging method (ESI). Method: 3 patients (2 female, 1 male, age: 1748 yrs) affected by Unverricht-Lundborg disease underwent a 256channels EEG with concomitant polygraphic recording. Provocative manouvres were conducted during the exam to elicit myoclonic jerks. EEG (electroencephalographic) and EMG (electromyographic) traces were analyzed off line. For the other 2 patients, a back-averaging of the myoclonic EMG activity and corresponding EEG abnormalities was performed. Analysis was conducted off line. A mean of 15 jerk-locked EEG potentials for each patients were averaged, and projected through a LORETA algorithm on an MNI (Montreal Neurological Institute) brain template in order to identify the cortical generator. Result: Jerk-locked EEG potentials were recognizable over the centrofrontal derivations, with a slight lateralization in each single case. ESI elaboration localizes the cortical generator over the anterior premotor frontal cortex (pt 1: Brodman area 6, pt 2: Brodman area 10; pt 3: Brodman area 11), with a lateralization concordant with the EEG potentials (2 right hemisphere, 1 left). Conclusion: ESI is a technique that permits cortical source localization of EEG potentials. Its application to this rare form of epilepsy depicts the important role of the pre-motor and frontal cortex in the myoclonic jerk's generation. To our knowledge, this is the first report describing the cortical source generation from the anterior/premotor cortex. Since only the jerk-locked potential was examined, we can not infer on the involved networks. The level of concordance between fMRI maps derived from the Wave_clus classification and the electro-clinical data was higher for 5 patients compared to the manual classification, and unchanged in the remaining 3. Conclusion: We propose that the use of spike sorting algorithms to classify IED is an efficient tool for mapping the fMRI changes linked to IED, potentially saving time and effort, and increasing the technique's clinical value.

p209 FLUMAZENIL IS A WEAK SUBSTRATE FOR P-GLYCOPROTEIN IN HUMANS. A PET STUDY IN PHARMACORESISTANT PATIENTS WITH UNILATERAL MTS F. E. Froklage*, A. Postnov*, N. H. Hendrikse*, J. C. Reijneveld*, J. J. Heimans*, R. Boellaard*, A. A. Lammertsma*, and R. A. Voskuyl *VU Medical Center, Amsterdam, The Netherlands; and Leiden/Amsterdam Center for Drug Research, Leiden, The Netherlands
Purpose: Pharmacoresistance in epilepsy may be caused by limited drug transport across the blood-brain barrier (BBB) due to increased activity of efflux transporters, such as P-glycoprotein (P-gp). Recent data suggest that flumazenil might be a P-gp substrate. If this is correct, increase in Pgp function in epilepsy could confound the interpretation of results obtained in PET studies with [11C]flumazenil. Method: For this study 10 pharmacoresistant patients with unilateral mesial temporal sclerosis were selected. They were studied twice with [11C]flumazenil, i.e. in the morning and in the afternoon. Before the afternoon scan 2 mg/kg tariquidar (a P-gp blocker) was administered i.v. In 5 patients both [11C]flumazenil scans were preceded by [15O] water scans to measure possible changes in blood flow. Result: Blood flow was not affected. Analysing the [11C]flumazenil data with the one-tissue plasma input model demonstrated a slight increase in distribution volume (VT) from 5.3 0.8 to 5.7 0.3 (p = 0.1, paired t-test). The simplified reference tissue model with the Pons as reference was used to determine BPND. The morning scans demonstrated a BPND of 4.7 1.0 which slightly decreased to 4.2 0.5 in the afternoon scan (p = 0.2). Transfer of the tracer across the BBB was estimated by taking the ratio of VT and 1 + BPND which equals to K1/k2. The K1/ k2 value of 0.92 0.14 increased significantly to 1.1 0.1 (p = 0.003, paired t-test) after the second scan. Conclusion: The significant increase in K1/k2 suggests that flumazenil may be a P-gp substrate. Whether the small decrease in uptake in pharmacoresistant patients is clinically relevant remains to be determined.

p208 A NOVEL METHOD FOR THE CLASSIFICATION OF INTERICTAL EEG ABNORMALITIES IN PARTIAL EPILEPSY: AN EEG-FMRI VALIDATION STUDY A. E. Vaudano*, C. Pedreira, R. Thornton, U. Chaudhary, S. Vulliemoz, H. Laufs, R. Rodionov, R. Quian Quiroga, and L. Lemieux *University of Modena e Reggio Emilia, Modena, Italy; The University of Leicester, Leicester, UK; University College of London Institute of Neurology, London, UK; University Hospital of Geneva, Geneva, Switzerland; and Johann Wolfgang Goethe University, Frankfurt, Germany
Purpose: Scalp recordings and classification of interictal EEG discharges (IED) in patients with epilepsy potentially provide valuable information about the epileptogenic network, particularly by defining the boundaries of the irritative zone, and hence being helpful during presurgical evaluation. Detection and classification of the signals rely in expert observers which can be a time-consuming procedure and presents inter-observer variability. Here, we propose a novel approach: the automatic classification of events using the spike sorting algorithm Wave_clus. This method aims to reduce processing time and provide more objective classification of events. Method: We applied the automatic sorting to the signals collected from EEG/fMRI presurgical evaluation recordings in 8 patients (6 males, mean age: 27) affected by refractory partial epilepsy. For each patient, two fMRI analyses were performed: one based on the visual classification and the automatic IED sorting. All fMRI data were pre-processed and analysed using SPM8. Result: In all cases, BOLD mapping of IED classified with wave_clus reproduced the hemodynamic maps related to the visually labeling. In 7 cases, Wave_clus classification also provided additional fMRI clusters.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

p210 ICTAL PET FINDINGS IN PATIENTS WITH REFRACTORY FOCAL EPILEPSY G. Kuester*, S. Marca*, D. Ladron De Guevara*, L. Rios*, F. Solari*, R. Gejman, M. Galvez*, and M. Campos* *Clinica Las Condes, Santiago, Chile; and P.U. Catolica De Chile, Santiago, Chile
Purpose: To present four patients whose PET showed well-localized hypermetabolic foci corresponding to the seizure onset area. Method: Four patients with refractory focal epilepsy studied with Video-EEG monitoring, brain MRI, PET, intraoperative EcoG. Result: Case-1: R. frontal FCD, R. frontal seizures. PET: R. anterior frontal hypermetabolism. Surgery: frontal topectomy. Histopathology:

63 Abstracts
type II-B FCD. Seizure free, 24 mo. follow-up. Case-2: R. hippocampal sclerosis, R. mesial temporal seizures. PET: R. hippocampal hypermetabolism, mild/diffuse R. temporal hypometabolism. Surgery: R. anteriormesial temporal resection. Histopathology: type II-B FCD of the end folium of the hippocampus, WM gliosis. Seizure free, 21 mo. follow-up. Case-3: MRI-1: R. occipital FCD, MRI-2: R. anterior temporal FCD. Video-EEG-1: R. temporo-occipital seizures, Video-EEG-2: R. temporal seizures. PET-1: R. occipital hypermetabolism, PET-2: R. anterior temporal hypermetabolism. Surgery 1: R. occipital lobectomy, Surgery 2: R. temporal lobectomy-frontal topectomy. Histopathology: II-A FCD/polymicrogyria. Seizure free, 18 mo. follow-up. Case-4: R. posterior-mesial temporal cavernoma, R. hippocampal sclerosis. EEG: intermittent R. frontotemporal slowing without ictal findings. PET: R. amigdala hypermetabolism. ECoG: continuous ictal/interictal discharges over R. hippocampus/amigdala. Surgery: cavernoma/anterior hippocampus/amigdala resection. Seizure free, 3 mo. follow-up. Conclusion: Interictal PET showing hypometabolic foci is a valuable tool in presurgical evaluation of focal epilepsy. However, correlations of well-localized hypermetabolic abnormalities/histopathology/postsurgical outcomes has not been delineated. In our patients hypermetabolic foci had excellent correlation with seizure onset/histopathology. Hypermetabolic changes could be a signal of very frequent electrographic/subclinical seizures. Although this is a small series and follow up is not long enough, we suggest that ictal PET can provide good information about seizure onset area. Differences in FA of thalamo-cortical and cortico-striatal motor tracts may reflect differences in excitatory and/or modulatory connections, with impacts upon control of voluntary movements and motor learning. Acknowledgement: This research was funded by the Waterloo Foundation.

p212 TEMPORAL POLE ASYMMETRY IN TEMPORAL LOBE EPILEPSY PATIENTS L. Martinkovic*, D. Horinek, O. Bradac, T. Belsan, and P. Marusic *Charles University in Prague, Prague 5, Czech Republic; Marburg, Germany; and Prague 6, Czech Republic
Purpose: The aim was to assess temporal pole volume (TPV) in a group of patients with mesial temporal lobe epilepsy (MTLE) and in healthy controls. Our hypothesis was that TPV asymmetry can distinguish MTLE patients from controls. Method: Fifteen patients diagnosed with refractory unilateral MTLE associated with hippocampal sclerosis (6 right-sided, 9 left-sided) and 30 healthy controls were included. Based on high-resolution MRI left (L) and right (R) temporal pole volumetry was manually performed. The first slice where temporal stem was clearly identified was considered as posterior border. TPV asymmetry was defined by asymmetry index (AI) calculated as 2*(L-R)*100/(L+R). TPVs (ipsilateral vs. contralateral side to the epileptogenic zone) were also compared in MTLE patients. Result: There was high variability in TPV asymmetry in control group (AI 2.4; SD 10.0) and in patients (AI 2.2; SD 17.1). In four MTLE patients only AI was significantly (>2 SD) higher than values observed in controls. In patients TPV ipsilateral to the epileptogenic zone was smaller (17.4 3.7 cm3) than contralateral volume (19.2 3.4 cm3; p < 0.005). Conclusion: There is a high variability in TPV asymmetry both in MTLE patients and in healthy controls. Asymmetry index itself does not allow to differentiate most of MTLE patients from controls. Temporal pole ipsilateral to the side of epilepsy is likely to be smaller in refractory unilateral MTLE patients.

p211 MOTOR CIRCUIT TRACTOGRAPHY PREDICTS MOTOR PERFORMANCE IN CHILDREN WITH ROLANDIC EPILEPSY L. M. Brindley*, F. M. Gibbon, A. Kirby, L. Peters, J. Te Water Naude, M. Thomas, N. Williams, K. D. Singh*, D. K. Jones*, and K. Hamandi *Cardiff University, Cardiff, UK; Cardiff and Vale University Health Board, Cardiff, UK; University of Wales, Newport, Newport, UK; and University Hospital of Wales, Cardiff, UK
Purpose: Rolandic epilepsy, characterised by focal motor seizures, has been associated with motor coordination disorders. This was investigated using the Movement Assessment Battery for Children (MABC-2) and constrained spherical harmonic deconvolution (CSD) tractography in children with rolandic epilepsy. Method: Eight right-handed children with rolandic epilepsy (3 females) aged 912 years completed the MABC-2 and underwent diffusionweighted magnetic resonance MR imaging. Whole-brain CSD tractography was computed and the AAL-labelling atlas warped back into native DWI space for each individual. Partial volume correction for CSF contamination was applied. Mean fractional anisotropy (FA) was assessed for left hemispheric tracts between the following ROIs: SMA; M1; thalamus; cerebellum; basal ganglia. These data were entered as predictor variables in separate stepwise linear regression procedures for each of the age-normalised MABC-2 sub-component and overall percentile scores. Result: MABC-2 scores (mean:18.1, SD:16.9) were variable but significantly below the population mean (t (7)=-5.322, p=.001). Three children scored below the 5th percentile. Higher mean FA of tracts connecting SMA and thalamus predicted better scores upon overall MABC-2 (r=.892, p=.003), manual dexterity (r=.917, p=.001) and balance (r=.968, p<.001). Lower mean FA of tracts connecting basal ganglia with SMA predicted better ball skills (r=-.758, p=.029). Conclusion: Mean FA within specific motor tracts is predictive of motor abilities in a population of children with rolandic epilepsy and variable motor function.

p213 COMPARATIVE VALUE OF SISCOM, FDG-PET AND INTRACRANIAL EEG IN PATIENTS WITH NON-LESIONAL EXTRATEMPORAL EPILEPSY M. Kudr*, P. Krsek*, A. Jahodova*, J. Rybar*, J. Trnka, M. Jaruskova, K. Michalova*, J. Sanda*, M. Kyncl*, J. Zamecnik*, M. Tichy, and V. Komarek* *University Hospital Motol, Charles University, 2nd Medical School, Prague, Czech Republic; Charles University, 1st Medical School, Prague, Czech Republic; Na Homolce Hospital, Prague, Czech Republic; and University Hospital Motol, Prague, Czech Republic
Purpose: To assess a practical value of SISCOM, FDG-PET and intracranial EEG in the localization of the epileptogenic zone in patients with intractable focal epilepsy and normal MRI finding. Method: A group of 14 patients operated on because of intractable epilepsy due to MRI-negative focal cortical dysplasia (FCD) was retrospectively studied. We coregistrated preoperative SISCOM and PET images with postoperative MRI and visually determined whether cerebral cortex underlying the SISCOM focus, PET hypometabolism area and cerebral cortex exhibiting prominent abnormalities on EEG was completely resected, incompletely resected or non-resected. These results and histopathological findings were compared with postoperative seizure outcomes.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

64 Abstracts
Result: 13 from 14 patients had a localizing SISCOM. PET findings were normal in three subjects; two of them had favorable postsurgical outcomes. All patients with completely resected SISCOM focus (n = 2), PET hypometabolic area (n = 2) or cortical region exhibiting significant intracranial EEG abnormality (n = 7) had favorable outcomes. By contrast favorable outcome was achieved only in some patients with incompletely (five of nine) or non-resected SISCOM focus (one of two), incompletely (four of seven) or non-resected PET hypometabolism area (one of two) and incompletely resected intracranial EEG abnormality (two of seven). No correlation between histopathological types of FCD and seizure outcome was found. Conclusion: Complete resection of the dysplastic cortex localized by a combination of SISCOM, FDG-PET and intracranial EEG is a reliable predictor of favorable postoperative seizure outcome in patients with intractable non-lesional extratemporal epilepsy. Supported by IGA NT/114435, Kontakt Program ME09042, CZ.2.16/3.1.00/24022 and GAUK 17010. Purpose: Granger causality analysis(GCA) was used to investigate how the temporal epileptic network(TEN) relates causally with other restingstate networks(RSN) and what changes are observed in post-traumatic epilepsy(PTE) patients. Method: This study encompassed 24 healthy subjects and 3 PTE patients. Resting-state fMRI data was acquired in a 1.5T scanner using a BOLD sequence with TR=2 s. Data was pre-processed in DPARSF1.0 software, using a 0.010.073 Hz filter. REST1.6 software was used for GCA based on signed path coefficients(SPC) and order 1. RSN were used as ROI seeds: TEN, comprised of the amygdala, hippocampus and parahipocampus; default-mode network(DMN); sensorimotor network(SMN); visual network(VN); attention network(AN); anterior cingulate(AC), and insula. ROI-wise analysis was done between pairs of networks and voxel-wise analysis was done using TEN as seed. Causal influences between networks were studied in healthy subjects and changes in patients were evaluated using two-sample t-test(p < 0.05). Result: TEN was shown to influence all RSN (positive SPC), with the exception of the VN(probably because a visual stimulus is first processed at the VN before being made available to other networks). The positive causal effect is stronger with the AC, AN and insula, which could translate a stronger influence on cognitive and emotional processes. All patients showed causal changes involving TEN, DMN and SMN, in agreement with known memory and motor impairments. Additional changes were observed in the AN and insula for individual patients. Conclusion: Although preliminary, this study shows GCA as a potential tool to evaluate causal functioning of RSN in PTE patients. In particular, changes were consistently observed in TEN, DMN and SMN.

p214 RELIABILITY OF MEMORY FMRI IN TEMPORAL LOBE EPILEPSY PATIENTS K. Towgood*, A. Caceres*, S. Costafreda*, G. J. Barker*, W. Crum*, R. D. Elwes, M. Mehta*, and M. P. Richardson* *King's College London, London, UK; and King's College Hospital, London, UK
Purpose: Functional MRI (fMRI) of memory functions is emerging as a modality of investigation in presurgical evaluation of mesial temporal lobe epilepsy (mTLE). The reliability and reproducibility of the method is not known. Method: Eighteen subjects with mTLE were scanned over three sessions at intervals of 2 weeks. Each session comprised; (1) Hometown Walk, blocked design; (2) Scenes protocol, block design (Scene Viewing) and event-related design (Scene Encoding); (3) Words and pictures protocol, material-specific blocked designs (Picture Viewing, Word Viewing) and event-related designs (Picture Encoding, Word Encoding). Therefore 7 activation maps were produced per subject per session, 378 datasets in total. We examined between-sessions reliability of activation using intraclass correlation coefficients; the spatial overlap of the anatomical location of activation peaks between sessions; and the ability of each activation map to predict the side of seizure onset. Result: Reliability between sessions 1 and 2 was similar to reliability between sessions 2 and 3. Hometown Walk and Scene Viewing were most reliable (ICCs 70.73 and 64.88 respectively), and Word Encoding least (ICC 30.79). The spatial overlap of the anatomical location of activation peaks between sessions showed similar differences between protocols. Conclusion: We recommend that future evaluations of memory fMRI in mTLE should use two fMRI tasks: Word Encoding, and either Hometown Walk or Scene Viewing.

Paediatric Epileptology 1 Monday, 01 October 2012

p216 SEIZURE BURDEN IN NEONATAL HYPOXIC ISCHEMIC ENCEPHALOPATHY: THE MODIFYING ROLE OF PHENOBARBITONE DURING THERAPEUTIC HYPOTHERMIA N. E. Lynch*, N. J. Stevenson*, B. P. Murphy*, J. M. Rennie, and G. Boylan* *University College Cork, Cork, Ireland; and University College Hospital, London, UK
Purpose: Our aims were to investigate the distribution of seizure burden over time in infants with Hypoxic Ischemic Encephalopathy (HIE) receiving whole-body hypothermia (TH) and to investigate the effect of phenobarbitone (PB). Method: Full- term newborns with moderate and severe HIE, seizures, and continuous video EEG monitoring who received TH were included in this study. All EEG seizures were annotated and the seizure period, defined as the period between the first and last recorded electrographic seizure, the seizure burden per hour and the time-point of maximum seizure burden was identified. Subgroup analysis of seizure burden distribution in moderate and severe HIE was performed. Pearson's correlation coefficient was used to investigate correlation between maximum seizure burden and time of PB administration. A significant correlation between maximum seizure burden and PB administration indicates a reduction of seizure burden after PB. Result: 24 infants were included, 13 with moderate HIE, 11 with severe HIE. Infants with severe HIE had a short period of high seizure burden followed by a long period of low seizure burden (median total period 47.9 hrs). There was no correlation between maximum seizure burden and PB administration. In moderate HIE, there was a shorter total seizure

p215 GRANGER CAUSALITY ANALYSIS OF RESTINGSTATE NETWORKS IN POST-TRAUMATIC EPILEPSY PATIENTS H. A. Ferreira*, A. C. Borralho, P. M. Gonalves-Pereira, R. Manaas, and A. Andrade* *Faculdade de Cincias da Universidade de Lisboa, Lisboa, Portugal; Instituto Politcnico de Lisboa, Lisboa, Portugal; Hospital dos Lusadas, Lisboa, Portugal; and Hospital dos Capuchos, Lisboa, Portugal
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

65 Abstracts
period (median 11. 3 hrs) and strong correlation between PB administration and maximum seizure period (correlation coefficient= 0.9919; pvalue<0.001). Conclusion: In this study we demonstrate a significant correlation between maximum seizure burden and PB administration in moderate HIE indicating a reduction of seizure burden following PB. This is not seen in severe HIE. Method: All neurologically sick term newborn aEEG records stored since 2004 where no seizures had been seen using standard methods were reviewed using a 60 second view which allowed slow seizures (<4 Hz) to be easily recognized. The final discharge diagnosis in those with and without such seizures were examined. Result: delta frequency seizures were common in neurologically sick infants without higher frequency seizure activity. They were often of relatively low voltage (<25 mcV) but commonly prolonged for over 10 minutes. Conclusion: seizures in the delta frequency are common in sick term neonates although not much described in the EEg literature and not reported in the aEEG literature. At present their prognostic implications are unknown.

p217 IN DEPTH PERFORMANCE ANALYSIS OF A NOVEL AUTOMATED SEIZURE DETECTION ALGORITHM FOR NEONATAL EEG S. Mathieson*, R. M. Pressler, J. M. Rennie*, N. J. Stevenson, L. Marnane, and G. Boylan *University College Hospital, London, UK; Great Ormond Street Hospital for Children, London, UK; and University College Cork, Cork, Ireland
Purpose: Neonatal seizures can be reliably detected with EEG but availability of trained neurophysiologists out of hours is often limited. To facilitate seizure detection for clinical purpose, a novel seizure detection algorithm (SDA) has been developed (Neonatal Research Group, UCC, Ireland). The aim of this study was to introduce a novel neurophysiologybased performance analysis of the SDA in which multiple features of seizures were quantified so as to determine the differences between detected and non-detected groups (by the SDA) and sources of artifact causing false detections. Method: Seizures from 20 neonates were visually annotated and characterised using 10 criteria, including length, frequency change, rhythmicity, peak amplitude, waveform morphology, number of EEG channels involved and background pattern. Seizure annotations from the SDA were compared to those from visual analysis to derive detected and non-detected groups and seizure characteristics were statistically compared. Causes of false detections were determined. Statistical tests included the Mann Whitney U test, Chi Squared and Fisher's Exact Test. Result: There were significant differences between the groups in 9/10 criteria. Detected seizures were longer, more rhythmic, had higher peak amplitude, involved more EEG channels, and had greater frequency and morphology change over the seizure. Certain seizure morphologies were better detected than others. Background EEG had no influence on detection. Primary causes of false detections included respiration, sweat or pulse artefact or a highly rhythmic background. Conclusion: This analysis has identified key areas for SDA modification, which should lead to improved performance.

p219 AMPLITUDE-INTEGRATED ELECTROENCEPHALOGRAPHY AND ELECTROENCEPHALOGRAPHY IN NEONATES W. Kim*, and G. Sim *Chungbuk National University Hospital, Cheongju, Korea; and Cheongju Saint Mary Hospital, Cheongju, Korea
Purpose: Amplitude-integrated electroencephalography (aEEG) allows simplified monitoring of cerebral function and its use for bedside decision-making is increasing. We studied aEEG in a cohort of neonates. Method: We studied 32 neonates who were admitted to our hospital from January 2009 to February 2010. We retrospectively studied EEG, aEEG and brain sonography of neonates who had clinical seizures, apnoea or desaturations. Result: Twenty-two (71.9%) of 32 neonates who had clinical seizures, apnoea or desaturations in the neonatal intensive care unit (NICU) had an aEEG. In the aEEG, 15 (62%) showed seizures, 4 (16%) showed suppression, 5 (20%) showed an abnormality. The correlation between EEG and aEEG was significant (p < 0.005). Of the neonates who had aEEG, 11 (34.3%) had clinical seizures, 22 (68.7%) had apnoea and 21 (65.6%) had desaturations. In patients with abnormal aEEG, the following brain sonography abnormalities were demonstrated: increased periventricular echodensities (41%), germinal matrix hemorrhage (41.1%) and brain swelling (8%). Abnormal aEEG was significantly associated with abnormal sonography (p < 0.05). Conclusion: The correlation of EEG and aEEG in NICU has been demonstrated in this study. Therefore, aEEG monitoring can help with the detection of seizures in neonates.

Purpose: Delta frequency seizures were accidentally noted in an infant undergoing routine amplitude integrated EEGs (aEEG) whilst being treated for gram negative meningitis. We elected to discover how commonly electrical seizures in the delta range were recognizable in aEEGs performed in sick newborns where seizure activity had not previously been reported to be present, and to delineate in which newborn conditions they were most commonly seen.

Purpose: To assess the accuracy of amplititude-integrated EEG (aEEG) used to diagnose neonatal seizure, using video EEG (VEEG) as a gold standard, with regard to both the background pattern and the recognition of epileptiform discharges in neonates who have suspected clinical seizures. Method: 66 neonates with suspected clinical seizure were investigated and bedside VEEG was recorded for 3 hours. VEEG signals were transformed into aEEG signals. Background pattern of aEEG and VEEG were
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analyzed independently and classified. 39 infants with VEEG epileptiform activities (10 s) were investigated, and calculated for single- and multichannel aEEG identified with 1 epileptiform activity. Result: 62 traces were suitable for analysis. A normal background aEEG corresponded with a normal or mild abnormal EEG in 100% of the cases. The PPV for a severely abnormal aEEG (BS, CLV, FT) to correspond with a severely abnormal EEG was 83% (NPV, 96%; sensitivity, 83%; specificity, 96%). On VEEG, 326 epileptiform activities with a mean duration of 78 s were identified. The sensitivity of aEEG for the detection of epileptiform activities was 40% for single-channel aEEG and 51% for multichannel aEEG. Multichannel aEEG identified 95% patients with 1 epileptiform activities, whereas single-channel aEEG (C4C3) identified 82%. Conclusion: CFM is a reliable tool for monitoring both background patterns (especially normal and severely abnormal) and epileptiform activities. Epileptiform detection rate is slightly better with multichannel aEEG compared with single-channel aEEG. We recommend using multichannel aEEG as a monitoring device and performing intermittent standard VEEG whenever there is any doubt about the classification of the aEEG. Purpose: Clinical recognition of neonatal seizures is challenging. Electrographical (EEG) ictal activity have various clinical presentations and electro-clinical Decoupling (ECD) is common after AED. Method: Analysis of video EEGs (30 minutes) recorded before 44 weeks corrected age neonates at risk of or already with suspect seizure disorders. Result: Of 164 consecutive recordings (20072010), 37 neonates (22.5%) had either EEG or clinical events; 7 preterm and 20 (54%) preloaded with AED, 31 had manifest suspect seizures before recording & 6 encephalopathic. 165 EEG seizures were captured in 23 infants, 50 (30.3%) had clinical correlates; 170 suspect clinical events were captured, 120 (70.5%) lacked EEG ictal discharge; 14 (37.8%) babies had only non-ictal events. No relation was relevant between EEG seizure frequency, onset zone, regional or contralateral propagation and the manifest clinical phenomena. 3 EEG seizures less than 10 seconds were associated with subtle events. Mouth twitching was apparent in two cases with ipsilateral Rolandic ictal discharges. EEG seizures were adversely correlated to clinical development (p = 0.045), not the mortality (p = 0.07). Their number was highly predictable of postneonatal seizures (p = 0.003). This was true for number of electro-clinical decoupling (p = 0.025), and captured clinical events (p = 0.001). Conclusion: Most of recognizable suspect clinical phenomena are not genuine seizures. Avoidance of prompt treatment with non-indicated AED on clinical suspicion might prevent unnecessary deleterious developmental iatrogenic effects on growing brain. Despite the poor prognostic implications, probably denoting underlying pathology rather than direct seizure effect, lack of clinical consistency of neonatal seizures might be explained by the immature cortical topographic functional differentiation.

p221 DIAGNOSIS OF NEONATAL SEIZURES: EFFECTIVENESS OF CURRENT CLASSIFICATION SYSTEMS L. Menzies*, H. Cross, and R. M. Pressler* *UCL-Institute of Child Health, London, UK; and University College London, London, UK
Purpose: It is agreed that classification of seizures is important to organizing information for purposes of drug development, clinical and basic research, and of course, clinical practice. In contrast to an agreed and repeatedly updated system for older children and adults (ILAE), at least 3 systems are in use for neonatal seizures with little agreement of their value and practicability. We aimed to assess how well these systems identify and classify neonatal seizures in clinical practice. Method: We identified neonates with seizures form the EEG database at tertiary referral centre (GOSH, UK). Electroclinical, clinical only (no EEG correlate) and electrographic (subclinical) events were classified according to semiology in three classification systems used in clinical practice: Volpe, Mizrahi and ILAE 2010 proposed system. Result: We identified 47 infants (85% term babies) with a total of 285 events (38% electroclinical, 26% clinical, 36% electrographic) and a duration of 857 sec/hour (26% electroclinical, 6% clinical, 68% electrographic). In the Volpe classification 45% of events were classifiable, 18% partially classifiable and 36% unclassifiable, in the Mizrahi classification 77% of events were classifiable, 22% partially classifiable and 1% unclassifiable and in the ILAE classification 41% of events were classifiable, 19% partially classifiable and 40% unclassifiable. Unclassifiable events were mostly electrographic events. Conclusion: Overall the value of classifications was poor: 2 of the 3 classification systems could classify less than half of seizures. This is thought to be due to the high proportion of electrographic seizures and due to the differing seizure semiology in new-born babies.

Semiology, Aetiology and Classification 1 Monday, 01 October 2012

p223 SCREENING FOR SYMPTOMS OF ANXIETY AND DEPRESSION IN PATIENTS WITH PSYCHOGENIC NONEPILEPTIC SEIZURES A. Z. Ilic*, and D. J. Milivojevic *Health Center Studenica, Kraljevo, Serbia; and Medical Centre Petrovac, Petrovac, Serbia
Purpose: Psychogenic nonepileptic seizures (PNES) are somatic manifestations of psychologic distress. This study compared anxiety and depression in patients presenting with psychogenic non-epileptic seizures (PNES) with those suffering from epilepsy. Method: This clinically descriptive, prospective study involved consecutive patients who fulfilled the clinical and video-EEG criteria for PNES and epilepsy, and who were recruited over an 18month period. All subjects were assessed for symptoms of anxiety and depression with Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale. Quality of life was assessed with Sickness Impact Profil. Clinical follow-up was conducted 812 months after the first evaluation. Result: A total of 22 patients were recruited: 11 presented with PNES without epilepsy; and 11 had epilepsy. Both patient groups had similar age, sex and education level. Anixiety and depression values were in 91% and in 54,5% of the ptients with PNES; and in 45,4% and in 18,8% in epilepsy group. Depression and anxiety were increased in PNES group compared to the group with epilepsy and correlated significantly with perceived restrictions due to disease, tolerability and efficacy of drug therapy, financical situation and education, self-efficacy, social support and with the global quality of life. Although seizure control is important

p222 CLINICAL AND ELECTROGRAPHIC PATTERN CORRELATES IN NEONATAL SEIZURES M. M. Awadh*, V. Jain, and M. E. ORegan *Ain Shams University Hospitals, Cairo, Egypt; and Royal Hospital for Sick Children, Glasgow, UK
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in both disorders, seizure remission is not a comprehensive measure of good outcome in PNESs. Conclusion: The prevalence of anxiety and depression in PNES group is considerably higher than in the epilepsy group. Seizure control should not be the only focus of treatment in PNES patients and should be complemented by appropriate psychiatric and psychological care. ences in the numbers of somatic symptoms of arousal between the two groups, particularly occurring during the recent seizure, which otherwise tended to be higher in the DS group. Of particular interest, the DS patients reported higher levels of cognitive symptoms of panic after, rather than during, either their most recent or ever experienced seizures than did the ES group; for both time periods anxiety was a significant predictor of symptom number. Conclusion: Anxiety level was a significant predictor of seizure-related autonomic and somatic symptoms that appear to differentiate between DS and ES patients. Evidence of more extensive negative cognitive interpretations following DS seizures, even after adjusting for anxiety levels, suggests that negative seizure-related cognitions are particularly characteristic of DS patients, may serve to maintain the disorder and should be addressed in cognitive behavioural therapy.

Purpose: To evaluate the effectiveness of provocative technique in patiens with psychogenic nonepileptic seizures (PNES). Method: We reviewed medical records of 1378 patients with pharmacoresistant seizures who underwent long term (57 days) video-EEG monitoring at tertiary care epilepsy center from January 2000 to December 2011. All patiens underwent routine evaluation (video-EEG, brain MRI and complete neuropsychological examination). In patiens who had not had spontaneous seizures we used suggestion and intravenous saline injection. Result: We identified 231(17%) patients with various types of PNES without background of epilepsy. There were 154 (67%) women and 77 (33%) men. 81(36%) patients had their habitual seizure spontaneously, 64 (42%) of women compared to 20 (26%) of men. 110 (49%) patients were induced. In 98 (89%) of them the procedure was diagnostic, 67 (44%) women and 31 (40%) men. In 12 (11%) the procedure was negative. In 23 (10%) patients the diagnosis of PNES was based on a clinical history. 12 (5%) of patients signed negative revers. Conclusion: Our results proved a high effectiveness of suggestive seizure provocation. Considering controversies of this technique we are convinced about its usefulness as only a minority of patiens had their spontaneous seizures during video-EEG monitoring. Delayed diagnosis could lead to iatrogenic complications, is costly to patients, the health care system and society. It is obvious that correct diagnosis is neccessary to prevent these consequenses.

p226 THE ROLE OF ELECTROENCEPHALOGRAPHY IN DIAGNOSTICS OF CENTRAL NERVOUS SYSTEM (CNS) STRUCTURAL LESIONS IN CHILDREN WITH MINOR NEUROLOGICAL SYMPTOMS O. Kozhevnikova, O. Klochkova, O. Logacheva, L. NamazovaBaranova, and A. Anikin Scientific Centre of Children Health, Moscow, Russian Federation
Purpose: to assess the possibilities of electroencephalography (EEG) in detecting the structural lesions of CNS, to evaluate its correlation with magnetic-resonance imaging (MRI) findings in children with minor neurological symptoms. Method: 182 children (7 months 18 years old) with minor neurological symptoms underwent video-EEG on digital electroencephalography machines Bravo NicOne (Nicolet, USA). All children under 3 years and some after 3 years underwent EEG during the day sleep. Patients main complaints included headaches (27%), single or first episode of seizures (25%), hyperexcitement (14%), fatigability (13%), syncopes (10%). All children had pathology according to perinatal anamnesis. Brain MRI's were done on Signa Twin speed Excite 1,5 T1 Tomography Machine (GE, USA). Result: 163 (89,6%) children with minor neurological symptoms and minimal changes on EEG had alterations of structure or/and brain vessels according to MRI. 140 patients (76,9%) had pathological changes on EEG accompanied by structural changes on MRI, herewith 36 children (26%) had angiopathy. Among structural disorders dominated local subatrophy and ventriculomegaly 23 (12,6%) patients with EEG disorders had only vessels deviations (S-shape deformation of internal carotid artery (ICA), flexura of ICA or vertebral artery (VA), hypoplasia of VA and combination of hypoplasia and deformation of ICA and VA, narrow ICA). Conclusion: We recommend to analyse the EEG in children under 3 years only during the sleep and send children with EEG changes to MRI investigation in the following cases: 1) minor local disorder or resistant lateralization of changes in routine EEG; 2) pathological EEG with hypersynchronization of b or h rhythms, disorganized EEG with absent or decreased a-rhythm;3) paroxysmal types of EEG in children of any age, even with no pathology in wakeful state.

p225 COGNITIVE AND SOMATIC SYMPTOMS OF ANXIETY DURING DISSOCIATIVE AND EPILEPTIC SEIZURES L. H. Goldstein*, R. S. Delamont, and J. D. C. Mellers *Institute of Psychiatry, King's College London, London, UK; King's College Hospital NHS Foundation Trust, London; and South London & Maudsley NHS Foundation Trust, London, UK
Purpose: To extend our previous investigations of the presence of anxiety-related seizure symptoms in adults with dissociative (psychogenic nonepileptic) seizures (DS) compared to partial epilepsy patients (ES). Method: 28 DS and 35 ES patients, without comorbid panic disorder, were recruited from an inpatient videoEEG telemetry unit. Within 36 hours of a seizure, patients completed questionnaires indicating the presence or absence (before/during/after that seizure or ever related to a seizure) of epilepsy-related symptoms and somatic or cognitive symptoms of anxiety, particularly panic. Measures of anxiety and depression were also completed. Result: Unlike our previous study, DS patients had significantly higher anxiety and depression scores than the ES group. Adjusting for anxiety (as well as duration of seizure disorder) reduced between-group differ-

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*Yerevan State Medical University, Yerevan, Armenia; Somnus Sleep Disorders Clinic, Yerevan, Armenia; and Erebouni Medical Center, Yerevan, Armenia
Purpose: To perform a preliminary screening of restless legs syndrome (RLS) among adult patients with epilepsy in Armenia. Method: The screening has been performed among consecutive patients attending Armenian Republic Epilepsy Center Erebouni. Only adult patients aged 18 and above with definite epilepsy diagnoses (both de novo and chronic) were included. The four essential criteria to diagnose RLS proposed by International RLS Study Group (IRLSSG 2003) have been used by a trained clinician-researcher team. Only patients positive for all four criteria have been considered to have a clinically significant RLS. Additional brief interview has been conducted to exclude other possible mimics of RLS. Assessment of RLS severity and form (idiopathic or symptomatic) was not a purpose of this screening. Descriptive statistics was used for evaluation. Result: Eighty one out of the 93 patients screened had confirmed allcause epilepsy diagnoses (n = 81). They had 1864 age interval (mean age 32.1, 37 females 45.7%). We found 10 patients fulfilling all 4 criteria for RLS (12.3%), and among them 6 males and 4 females (accordingly m:f = 60%:40%). RLS in females was 10.8%, and in males 13.6%. Our previous telephone survey (Khachatryan et al. Sleep Medicine 2007) showed 7,9% prevalence of RLS in general adult Armenian population and higher prevalence in males. Conclusion: We found high prevalence of RLS in Armenian epilepsy patients. It was found higher among males. As a sleep restricting and disrupting factor, RLS could contribute to difficulties in the management of epilepsy patients and thus should be screened for carefully.

p229 HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH EPILEPSY, NON-EPILEPTIC ATTACK DISORDER AND DUAL DIAGNOSIS F. Ali*, and A. E. Cavanna *Birmingham and Solihull Mental Health NHS Foundation Trust, Birmingham, UK; and Institute of Neurology, London, UK
Purpose: Little is known about the differential impact of epilepsy and non-epileptic attack disorder to patients health-related quality of life (HR-QOL). In this study, we sought to compare self-reported HR-QOL in patients with epilepsy, NEAD and dual diagnosis. Method: We recruited a total of 66 adult out-patients (n = 17 with a diagnosis of epilepsy, n = 34 with NEAD and n = 15 with a dual diagnosis) from the specialist Neuropsychiatry Clinic at BSMHFT/University of Birmingham. Each participant completed a standardised psychometric battery which included the Quality of Life in Epilepsy-31 (QOLIE-31). Result: We found significant differences in cumulative HR-QOL scores (Kruskall-Wallis test, p = 0.041) across the three groups. Patients with dual diagnosis demonstrated poorest HR-QOL ratings (mean=28.4), followed by NEAD (mean=30.7) and epilepsy (mean=43.5). The most significant differences were in the Emotional Well-Being domain (p = 0.008), where patients with dual diagnosis reported the lowest scores (mean=28.9), followed by NEAD (mean=29.3). Patients with epilepsy reported considerably higher HR-QOL in this domain (mean=45.9). Conclusion: Patients with a dual diagnosis of epilepsy and NEAD report poorest cumulative HR-QOL, with significantly lower scores on Emotional Well-Being. Future investigation should be targeted to elucidate causal links between specific ictal and inter-ictal variables and HR-QOL subdomains.

Purpose: It is well described that psychogenic non-epileptic seizures (PNES) and epileptic seizures (ES) may co-exist in the same patient, but how to best define this co-existence and its incidence are debated. Method: We reviewed all epilepsy monitoring patients at the University of Maryland Medical Center and Veterans Administration Medical Center Baltimore over an 18 month period to assess the incidence of both PNES and ES co-existing in the same patient as documented by capturing both PNES and ES during the same admission. Patients who had more than one admission were counted only once. Result: Of our 272 total epilepsy monitoring patients, 172 (63%) were female, and the mean age was 41 years (range 1688, standard deviation 14.6). Of the total patients, 74 (27%) had documented PNES during their admission, and 11 (14.9%) of these PNES patients had co-existing epileptic seizures determined by video EEG during that same admission. Conclusion: The percentage of co-existing PNES and ES captured on video EEG monitoring in our patients (14.6% of all PNES patients) was higher than expected, and may relate in part to more aggressive seizure medication tapers to provoke events, thereby unmasking more epileptic seizures in our patients. In addition, embellished auras mimicking PNES cannot absolutely be ruled out in a small number of cases. Still, the incidence of co-existing PNES and ES in such a high percentage of patients is notable and suggests that caution is warranted when tapering medication in some patients with PNES.
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p230 DISSOCIATIVE EXPERIENCES AND QUALITY OF LIFE IN PATIENTS WITH NON-EPILEPTIC ATTACK DISORDER J. W. Mitchell, F. Ali, and A. E. Cavanna Birmingham and Solihull Mental Health NHS Foundation Trust, Birmingham, UK
Purpose: A wide range of dissociative experiences have been reported in clinical samples of patients diagnosed with non-epileptic attack disorder (NEAD). This study investigated the possible impact of dissociative experiences on health-related quality of life (QOL) in this patient population. Method: In this cross-sectional study we consecutively recruited 37 patients (67% female; mean age=44, sd=13.7) with a diagnosis of NEAD from a specialist neuropsychiatry clinic. Nine patients (24.3%) had concomitant epilepsy (dual diagnosis). Clinical diagnoses were validated by neuroimaging and neurophysiology findings. Result: Our sample reported a high level of dissociative experiences, with a mean score of 24.9 (sd=18.2) on the Dissociative Experiences Scale (DES). We found no significant differences in DES scores between patients with NEAD and patients with a dual diagnosis (Mann-Whitney U = 117.5, p = 0.884). There was significant negative correlation between DES scores and QOL, as measured by the QOLIE-31 inventory (n = 35: Pearson's r=-0.664, p < 0.01). This association remained significant when accounting for measures of depression (Beck Depression Inventory, BDI) and anxiety (Spielberger State-Trait Anxiety Inventory, STAI). A multiple regression analysis model accounted for 73.6% of the variation in total QOLIE-31 scores (n = 33: adjusted R square=0.736). Total DES scores accounted for 52.5% of the variance, whilst the BDI and STAItrait scores accounted for 16.6% and 4.5%, respectively.

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Conclusion: These findings confirm previous reports of high prevalence of dissociative experiences in clinical populations with NEAD and highlight the importance of routinely screening patients for these symptoms. The strong association with QOL suggests that patients with NEAD would benefit from treatment interventions targeting dissociation. be placed on the new waiting list. 10 patients passively declined to be placed on the waiting list due to non-responding. A total of 19 patients requested a triage appointment. Of these, patients, 7 were assessed and discharged, 6 were assessed and a treatment plan was formulated and 6 were reviewed and referred to local mental health services with a review planned. Conclusion: The development of this waiting list initiative and triage clinic has resulted in a reduction in waiting list size. Furthermore, patients who are referred to this clinic now receive an initial appointment within three months following inpatient review. Results will be discussed with respect to the pro's and con's of approaches to waiting list management.

p231 MUTATIONS WITHIN THE GLRA1 GENE ASSOCIATED WITH HYPEREKPLEXIA S. E. Wood*, S. Ali*, C. Drew*, O. W. Howell*, R. H. Thomas, M. I. Rees*, and S. Chung* *Swansea University, Swansea, UK; and Wales Epilepsy Research Network, Swansea, UK
Purpose: Hyperekplexia is a paroxysmal neurological disorder caused by defects in glycinergic neurotransmission and is characterized be exaggerated startle reflexes and hypertonia in response to sudden, unexpected auditory or tactile stimuli and in some instances, can result in life-threatening infantile apnoea episodes. This rare, but potentially fatal, neurological disorder is associated with mutations in genes encoding the a1 (GLRA1) and b (GLRB) subunit of the glycine receptor and the presynaptic glycine transporter GlyT2 (SLC6A5). Method: As part of an ongoing screening program, we have analysed the entire coding regions of GLRA1 in 66 patients referred to our screening project. All sequence variants identified were regarded as mutations after exclusion from a panel of human controls and assessed for protein damaging outcomes with molecular modelling. Result: Direct sequencing analysis revealed 15 GLRA1 variants including 11 non-synonymous changes, 3 nonsense and a recurrent large deletion of exon 1 to 6; eight variants identified were novel and not in the public domain. Recessive inheritance was revealed in 13 cases, including 2 cases of compound heterozygote inheritance, and a dominant inheritance in 3 cases. Consistent with previous studies, all deletion and nonsense mutations were associated with recessive onset of phenotype, whereas missense mutations could exert dominant or recessive influences depending on the position of the mutation in the polypeptide. Conclusion: Identification of novel mutations in this study increases the compendium of GLRA1 mutations in the diagnostic domain for hyperekplexia and promote further work into the pathophysiological mechanisms underlying the ancient startle response.

Semiology, Aetiology and Classification 2 Monday, 01 October 2012

Purpose: This retrospective study analyses the comorbid diagnoses of patients with psychogenic non-epileptic seizures (PNES) and the outcome after in-patient treatment including cognitive behavioural therapy, family therapy and non-verbal therapies. Method: Within 7 years 377 in-patients were treated in the department for epileptology and psychotherapy of the Epilepsiezentrum Berlin-Brandenburg. 131 patients were diagnosed with PNES. All diagnoses reported at the time of discharge were reviewed. Follow-up interviews of 111 patients were made within 6 months after discharge. Result: Comorbid somatic diagnoses were found in 42 patients. 64% were related to the brain. Concomitant epilepsy was confirmed in 31 patients. Comorbid psychiatric diagnoses were anxiety disorders (47), personality disorders (41), posttraumatic stress disorder (39), substance abuse(14), depressive disorders (11), somatoform disorders (6), bipolar disorder (5), factitious disorder (4), Asperger syndrome (3) . Psychic traumas were found in the history of nearly all patients. Sexual assault was reported by 28 patients and strongly suspected for another 21 patients. 89 patients complained about massive and long running conflicts within their families. After in-patient treatment 57 patients remained free of seizures. 36 patients had less frequent seizures, 17 were unchanged, 1 had committed suicide. Conclusion: In-patient treatment including intensive psychotherapy and additional non-verbal therapies in a clinic with an expertise in epileptology, psychiatry and psychotherapy is successful for nearly 3/4 of patients with PNES. Beside sexual assault 68% of the patients with PNES reported severe and longlasting conflicts in the family causing psychological distress. This confirms the importance of family therapy besides cognitive behavioural therapy.

Purpose: To develop a waiting list initiative and early intervention outpatient clinic for patients with non-epileptic attack disorder to reduce waiting list times and improve access to psychological treatment. Method: A waiting list analysis was conducted (n-64). An opt-in system was then introduced. Patients who opted-in received a 30minute triage appointment to review their case and plan towards further intervention where necessary. Standardised intake measures and patient satisfaction data were obtained. Result: Following waiting list analysis, 47 patients were entered into the opt-in system. Those patients who opted in, all received a triage appointment resulting in a treatment contract or a discharge to local services. Following an invitation to opt-in, 18 patients actively declined to

Purpose: To evaluate the significance of activation of habitual auras in the activation clinic in patients with suspected PNES.
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Method: We studied consecutive 105 patients, confirmed to have PNES in our activation clinic over the last five years. The diagnosis of PNES was made based on electro-clinical features of the recorded event(s). They were confirmed to be habitual by patients and/or their eyewitnesses. Result: The mean duration of PNES before the activation clinic was 9.7 years (range: 156 years). Suggestions alone brought out habitual PNES in five patients, photic stimulation alone was used as an induction procedure in 49 and combination of photic stimulation and hyperventilation was used in another 20 patients. No active activation procedure was performed in 15 patients and various combinations of the above procedures were used in the remaining. 41 patients reported their habitual aura in the activation clinic. They were epigastric aura (n = 6), olfactory aura (n = 2), gustatory aura (n = 4), visual aura (n = 1), auditory (n = 2), sensory (n = 5) and nonspecific auras (n = 23). No statistically significant correlation was noted between the presence of aura and duration of PNES. Conclusion: Auras that are commonly regarded as epileptic auras do occur as dissociative auras in PNES during activation and thus do not imply the coexistence of epilepsy. Activation of epileptic auras in the activation clinic appears to be a strong point in favour of the diagnosis of PNES. Purpose: Both epileptic seizures (ES) and psychogenic non epileptic seizures (PNES) can coexist in the same patient. According to published data, between 8 and 60% of patients with PNES also can have ES. Longterm videoEEG (LTVE) is the diagnostic tool used to differentiate them. But it is not well established how long LTVE should be to make a proper diagnosis in these cases. Objetive: To describe clinical and LTVE features in patients with both ES and PNES admitted in Epilepsy Unit (EU) and estimate LTVE duration to make diagnosis. Method: We reviewed LTVE, medical history and complementary tests in 94 adult patients admitted in our EU between 2010 and 2011. We divided them into 3 groups: patients with only ES, only PNES and both ES+PNES. We compared them. All the episodes were checked with the family. Result: 84 patients had seizures. 62 had only ES, 16 PNES and 6 both ES+PNES. Non statistically significant differences were found between time of appearance (TOA) (days) of PNES and ES groups, median 2 (1 3) vs 3 (14), p 0.63. In ES+PNES group, ES TOA was 3.5 (2,54,25) vs PNES 2 (1,753,25). All patients in ES+PNES group had PNES first. 83.3% of them had the first ES after the second day. In our study, 27% with PNES had also ES. Patients with both ES+PNES had first PNES during monitoring. An early monitoring disruption could lead to a misdiagnosis in this group. A prolonged LTVE (>72 hours) to record both episodes is justified and necessary to make a correct diagnosis.

p235 USE OF ANTI-EPILEPTIC DRUGS IN THE SETTING OF NON-EPILEPTIC SEIZURES M. Stefanidou, S. Nadkarni, and C. Carlson New York University, New York, USA
Purpose: Non-epileptic seizures (NES) without concurrent epilepsy account for about 10% of patients evaluated in epilepsy monitoring units. Many of these patients are on anti-epileptic drugs (AEDs) upon admission for their events and/or co-morbid psychiatric and pain disorders. We evaluated if presence of AEDs at the time of diagnosis of NES affects their long term exposure to these agents, given concerns of unnecessary use of AEDs in this patient population. Method: A retrospective review of all admissions to the epilepsy monitoring unit at NYU for 2010 was conducted. Inclusion criteria required capturing the targeted event and a normal video-EEG. AEDs and other psychotropic agents were recorded upon initial admission, discharge, and at follow up. Result: Of 900 patients, 75 (8%) patients were diagnosed with NES with 44 (60%) on AEDs upon admission. The most prevalent co-morbid psychiatric conditions were anxiety, mood and panic disorders without significant difference between patients on or off AEDs at admission (p = 0.73). AED use at admission correlated with higher use of AEDs at discharge (p = 0.0001). 70% of patients had outpatient follow-up. Patients on AEDs at admission were more likely to be on AEDs at follow-up (p = 0.0001) and use these agents for treatment of concurrent psychiatric and/ or pain conditions (p = 0.02). Conclusion: Presence of AEDs upon admission for evaluation of NES increases probability of long term exposure to AEDs. Although this study does not compare clinical outcomes, it suggests a possible benefit from early evaluation of events prior to the initiation of AEDs in patients with high suspicion for NES.

p237 RINCH MOTIONS (RHYTHMIC ICTAL NONCLONIC HAND MOTIONS) ANALYSIS: INCIDENCE AND LATERALIZING VALUE K. Musilov*, R. Kuba*, N. M. Vojvodic, M. Brzdil, I. Tyrlikova, and I. Rektor *Brno Epilepsy Centre St. Anne's University Hospital and Faculty of Medicine, Brno, Czech Republic; Clinic of Neurology Clinical Center of Serbia, University of Belgrade School of Medicine, Belgrade, Serbia; Epilepsy Center Brno, St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic, Brno; and St. Anne's University Hospital and Faculty of Medicine, Masaryk Univerzity, Brno, Czech Republic
Purpose: The principal aim of this retrospective study was to analyse occurrence and lateralizing value of Rhythmic Ictal Nonclonic Hand (RINCH) motions symptom in temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) or with other lesion of temporal lobe (TLE-oth) in our group of patients. Method: Retrospectively, we analysed 120 patients with temporal lobe epilepsy (TLE). All patients were classified as Engel I at the 2year follow-up visit. Histopathological examination revealed hippocampal sclerosis (TLE-HS) in 70 patients and other lesions in 45 patients (TLE-oth); 5 patients had no lesions. We reviewed 491 seizures. RINCH motions were defined as unilateral, rhythmic, nonclonic motions occurring during the seizure, sometimes in the relation to the dystonic posturing of the hand on the same side. Result: RINCH motions were observed in 24 of 120 patients (20%), and in 48 of 491 seizures (9.8%). There was no significant difference between occurrence of RINCH motions in patients with TLE-HS and in patients with TLE-oth (21.4% vs. 18%). RINCH motions were contralateral to the seizure onset in 83.3% of patients, and in 91.7% of seizures. RINCH motions were more frequent in patients with left- than right-sided TLE (68.63% vs. 31.37%) and they were associated with dystonic posturing on the affected side in 33.33%. There were no differences in lateralizing value of RINCH motions between patients with TLE-HS and TLE-oth.

p236 CLINICAL AND LONG-TERM VIDEOEEG FEATURES OF PATIENTS WITH BOTH PSYCHOGENIC NON EPILEPTIC AND EPILEPTIC SEIZURES: A PROSPECTIVE STUDY IN A SPANISH EPILEPSY UNIT R. M. Vivanco-Hidalgo, J. Jimenez-Conde, A. Massot, J. Herraiz, C. Garcia-Ribera, J. Roquer, and R. Rocamora Parc de Salut Mar-Hospital de Mar, Barcelona, Spain
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71 Abstracts
Conclusion: RINCH motions symptom is a relatively frequent ictal sign in patients with TLE. The side of RINCH motions in patients with TLE lateralizes the seizure onset to the contralateral temporal lobe. Aknowledgements: This work was supported by MSMT CR research project MSM0021622404. coinciding with reduced epilepsy admissions. Outpatient interventions have increased. The number of telephone contacts have more than doubled in the second year, appearing static in years three and four. Educational and supportive visits to the child's home and school have also increased. Activities of an ESN changes over time towards non-admission and community-based activity.

p238 WHAT ABOUT A TRANSITION PROGRAM ON EPILEPSY? J. Carrizosa, and T. Rodriguez University of Antioquia, Medelln, Colombia
Purpose: Transition from a family to an individual centered service, could carry troubles for persons with chronic diseases. General guidelines from IBE and ILAE are lacking. The purpose is to built up a transition reference guideline for persons with epilepsy. Method: Literature review; questionnaires on transition during the VI Latin American Congress in Cartagena. Framework on goals and key topics. Result: Goals: 1. Preparing adolescents and young adults for transfer of care 2. To provide uninterrupted health care 3. Education on specific and individual issues 4. To promote self advocacy skills and independence 5. To optimize quality of life, life expectancy and future productivity. Key points: 1. Timing of transition and transfer 2. Family Dynamics 3. Health Supervision Issues 4. Anticipatory Guidance 5. Sexuality, Reproductive Issues and Pregnancy 6. Genetic Counseling 7. Education and Degree Choices 8. Physical Activity Sports 9. Drivers Licence 10. Mortality 11. Psychiatric Aspects 12. Medical Social Insurances. Conclusion: A transition program, with prepared communication between pediatric -adolescent and adult health services, could foster a better quality of life in persons with epilepsy.

Purpose: The American Academy of Neurology (AAN) quality indicators for epilepsy care describe the tasks that should be performed during a patient encounter and specify details to be documented in the medical record. With these, quality of epilepsy care can be monitored, gaps identified and ultimately improvements made. Aim: An epilepsy electronic patient record (EPR) was used to implement AAN quality indicators to assess performance of an out-patient service. Method: A sample of out-patient clinics at Beaumont Hospital, Dublin was assessed. The epilepsy EPR was examined to determine if it supported the capture of data relevant to four AAN indicators of interest. Using a specialised database query language, structured and unstructured data fields were interrogated to generate the numerator and denominator for the indicators. Result: Over a sample of 5 weekly out-patient clinics there were 161 individual patient encounters. Of these 87% (142/161) conformed with the requirement to document seizure type and seizure frequency at each visit (indicator 1); etiology or epilepsy syndrome was documented/ updated for 57% (93/161) (indicator 2); evidence of querying and counselling about anit-epileptic drug side-effects for that encounter was present in 30% (49/161) of records. Over a 1 year period, counselling for women of childbearing potential (indicator 8) was present in 30% (102/ 346) records. Conclusion: Feasibility of the epilepsy EPR for efficient performance monitoring was demonstrated. Results indicate either failure to carryout recommended clinical tasks or poor documentation. Whichever is the case, a baseline is provided against which improvement goals can be set.

p239 A REVIEW OF AN EPILEPSY NURSE SPECIALIST'S CLINICAL ACTIVITY & ASSOCIATION WITH PAEDIATRIC EPILEPSY ADMISSIONS K. Johnson*, and C. Dunkley *Kings Mill Hospital, Nottinghamshire, UK; and Sherwood Forest Hospitals, Sutton in Ashfield, UK
Purpose: To quantify and characterise clinical activity for the ENS over time and to assess whether the introduction of an ENS is associated with a change in paediatric epilepsy admission rates. Method: A prospective review of the ENS diary was undertaken documenting all client contact. Activity was collated comparing the types of client contact over a 4 year period 20072011. Local admission rates of children with epilepsy were also obtained using the Child and Maternal Health Observatory (CHIMAT) Data Atlas which maps Hospital Episode Statistics (HES) data to geographical areas. Result: The prospective diary review showed a yearly median of 29 ward visits; 2 Emergency Department visits, 35 home visits; 560 telephone contacts; 15 Buccal Midazolam training sessions and 32 ad-hoc paediatric outpatient reviews, Each year there was a median of 22 multidisciplinary epilepsy clinics; 19 nurse led clinics; 4 paediatric neurology clinics and 71 school visits. Mean admission rates over 3 years before the ESN commenced were 67/100,000 children/year (range 6272.1). Mean rates over 3 years after ESN commencement were 35.2/100,000 children/ year (range 32.337.5). Conclusion: The diary review clearly shows the diversity of the ENS activity and how this has changed over time. Ward visits have reduced

p241 TRANSITION'S GAP FROM PAEDIATRIC TO ADULT SYSTEM CARE OF PATIENTS WITH EPILEPTIC ENCEPHALOPATHY: A MYTH OR A REALITY? M. Kuchenbuch*, N. Chemaly*, C. Chiron, O. Dulac*, and R. Nabbout *Necker, Paris Cedex 15, France; and Inserm, Paris, France
Purpose: In order to understand the reality of a transition gap between pediatric and adult care system in patients with epileptic encephalopathy, we compared medical care between childhood and adulthood with a detailed description of factors that impacted the transition in a cohort of patients with Dravet syndrome. Method: 52 surveys realized by a group of experts with help of IPSOS institute and Wyeth foundation were filled by patients and families with Dravet syndrome, aged over 18 years. Student t-tests and fisher exact tests were used. After validity conditions verification, we compared the experience of patients and their family in paediatric versus adult care system and then we studied the factors that impacted the quality of transition.
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72 Abstracts
Result: Sixty one percent had a transition and 92% of them noted that there wasn't any gap during their transition to adult care. Factors that positively impacted their transition were the transition preparation quality (p<.000001), longer duration of follow-up in the same pediatric structure (p<.001), good availability of the pediatric staff (p<.01), age over 18 years at transition (p<.01) and good health's condition before transition (p<.05). All families had a positive experience in paediatric health system. Paediatricians were considered as welcoming, taking time to explain and helping. Contrarily to the impression of child neurologist, the adult care system experience was identical and showed no statistical difference. Conclusion: Transition in Dravet's syndrome showed a lack of gap between pediatric and adult care health system. the hospitalization. For over 10 years, there has been a patient education program primarily for parents at the department. The teaching has been organized from a commonsense approach without any genuine formalized educational goals, and without any proven pedagogical approach to learning. In order prospectively to reinforce patient education in the department, this project started August 2011 and will be concluded in August 2014. Method: The study is a combination of observation and interview studies where interviews are conducted with teachers, parents, children in a pediatric ward in Denmark and Norway. The purpose of the study is to compare the learning environment in Denmark and Norway. Result: Aim: To explore how children learn mastering the everyday life with epilepsy during hospitalization. The project deals with children with epilepsy and there learning processes during hospitalization. The project takes a broad life history as well as cultural and social view on the learning processes. Parents have a central role in patient education at the ward, and the purpose of the study is to bring an analytical look at the learning environment, understood as the interaction between the department, teacher and patient. Conclusion: Research questions: How do children learn to live with epilepsy with all its consequences for the individual's everyday life? Which learning processes imply the everyday life with epilepsy and in which way does it appear in the learning environments at the paediatric department?

p242 AUDIT OF PATIENT SATISFACTION AT THE TRANSITION ADOLESCENT EPILEPSY CLINIC IN THE WALTON CENTRE NHS FOUNDATION TRUST, LIVERPOOL M. Rodriguez*, T. Marson*, and R. E. Appleton *Walton Centre for Neurology and Neurosurgery NHS Foundation Trust, Liverpool, UK; and Alder Hey Children's Hospital, Liverpool, UK
Purpose: We assess the satisfaction of patients attending the Transition Adolescent Epilepsy Clinic at the Walton Centre, a monthly clinic run jointly by an adult and a paediatric neurologist. Method: A Patient Satisfaction Questionnaire was sent to 108 patients (new or follow up) who attended the clinic between March 2009 and September 2010. Result: Questionnaires were returned by 30 patients (response rate 27%), 16 were female, age range 1822. 11 had focal, 4 generalized and 4 unclassified epilepsy. 21 had experienced seizures within the preceding 12 months. 29 patients were receiving an antiepileptic drug, of whom 15 were on monotherapy. Regarding the handover, 53% stated that they were told what to expect when they attended the clinic. Regarding clinic appointment, 87% found the waiting area pleasant, 87% felt the clinic appointment met their expectations, 80% had an opportunity to voice their own opinion, 50% felt all their questions were answered with 33% stating most questions were answered. 50% were provided with written information and found it useful. 17% would like to have been seen without their parents. 27% had phoned the epilepsy nurse. Regarding appointment number, 70% feel they have the right number, 20% too few, 7% too many. Regarding time spent in clinic, 83% think it was enough, 10% too little. Conclusion: The response rate was low highlighting the difficulty engaging with teenagers. Respondents indicate a high level of satisfaction with the service, but there is room for improvement including provision of better information about the service and improving the environment.

p244 CAN A NURSE INTERVENTION PROMOTE THE SELFMANAGEMENT OF PATIENTS WHO ATTEND EMERGENCY DEPARTMENTS WITH ESTABLISHED EPILEPSY? A NESTED QUALITATIVE STUDY A. J. Noble*, C. Virdi, M. Morgan, and L. Ridsdale *Institute of Psychiatry, King's College London, 8AF, UK; Department of Clinical Neuroscience, London, UK; and King's College London, London, UK
Purpose: People with epilepsy (PWE) frequently attend emergency departments (EDs). Attendance is associated with AED non-adherence, low knowledge of epilepsy and stigma. Reducing unnecessary emergency hospitalisations could help patients and reduce costs. We are conducting a trial aimed to reduce epilepsy ED visits, by a self-management intervention with an epilepsy nurse-specialist (ENS). We here describe patients perceptions of acceptability and benefits. Method: N = 85 adults with epilepsy were prospectively recruited from 3 London EDs. The first 20 (age=41, SD=17; 10 males; median years since diagnosis=12) receiving the intervention were invited for semistructured interview. Transcripts were analysed thematically. Result: Participants reported not having been previously confident in managing their epilepsy, but that the intervention improved this. It did this by meeting a need for information on epilepsy, with the ENS being available in a way GPs and consultants are not: Responses included: It was the first time someone had sat down and really told me a huge amount; she took the time to go through my needs, you felt you could ask questions, not that wasting her time. Patients felt not so frightened of seizures. One said I don't feel as if I now need to go to hospital every time. Learning about epilepsy prevalence helped patients not feel so alone and less ashamed. They also felt AED adherence improved. Conclusion: This short intervention was acceptable to PWE who attended ED. It satisfied a perceived need for information and in turn increased confidence. We will report whether the intervention leads to reduced ED use subsequently.

Semiology, Aetiology and Classification 3 Monday, 01 October 2012

p243 LEARNING ENVIRONMENT AT A PAEDIATRIC WARD A QUALITATIVE STUDY T. Lvenskjold Danish Epilepsy Center, Dianalund, Denmark
Purpose: At the paediatric department at Danish Epilepsy Center patient education given to children and parents is an important part of
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

73 Abstracts
p245 FACILITY OF EPILEPSY SERVICE IN THAILAND S. Towanabut*, S. Tiamkao, and S. Pranboon *Prasat Neurological Institute, Bangkok, Thailand; and Integrated Epilepsy Research Group, Khon Kaen University, Khon Kaen, Thailand
Purpose: This study was aimed at investigating the readiness of epilepsy services in Thailand. Method: The data was collected through questionnaires sent out to 1,033 public hospitals all over the country on their readiness in providing services to epileptic patients. 559 hospitals returned the questionnaires (54.11%). The data was then analyzed in percentages. Result: The results show that most epileptic doctors are general practitioners (30.4%). Epileptic specialists and neurologists account only for 11.1 and 14.4%, respectively. There are altogether 52 EEGs, 54 CT Scanners, and 6 MRIs. Four main types of antiepileptic drugs are prescribed to patients, namely, Phenobarbital, Phenytoin, Carbamazepine, and Valproic acid, at 99.9, 96.0, 97.9, and 89%, respectively. New antiepileptic drugs include Gabapentin, Topiramate, Levetiracetam, Lamotrigine, and Pregabalin (77.6, 63.9, 46.0, 45.3, and 33.6%, respectively). Vigabatin and Oxcarbazepine accounted for only 14.5 and 14.3%. Intravenous anticonvulsants used for status epilepticus patients include Phenytoin (54.2%), Gardinal sodium (33.9%), and Sodium valproate (12.1%). Only 45.7% of therapeutic drug monitoring can be done. Conclusion: There is still a limitation in the readiness of services in public hospitals. This is primarily due to a lack of doctors who specialize in treating epilepsy. Hospitals also lack diagnostic tools for antiepileptics and therapeutic drug monitoring. Therefore, a study needs to be conducted to develop a prototype model for epileptic treatment that is appropriate to the constraints and conditions of our country. Conclusion: The introduction of a strict protocol for pre-surgical patients leaving their room, usage of cot sides and a higher staff to patient ratio with increased training has made this Epilepsy Monitoring Unit more productive with a safer environment for those undergoing pre-surgical assessment. This study emphasises the benefit of staff training and telemetry protocols.

p247 NATIONAL AUDIT OF SEIZURE MANAGEMENT IN HOSPITALS: INITIAL FINDINGS A. G. Marson*, P. Dixon*, M. Pearson, J. Kirkham*, and K. Billington* *University of Liverpool, Liverpool, UK; and University Hospital Aintree, Liverpool
Purpose: Little is known about the organisation and delivery of epilepsy care in the UK. The National Audit of Seizure management in Hospitals (NASH) is the first comprehensive UK-wide epilepsy audit. Method: NASH assessed the immediate care, onward care pathways and prior care of patients attending Emergency Departments with seizures. Sites provided anonymous data on 30 consecutive cases via a bespoke web-based database. Result: Data were collected from over 3750 patients across 127 sites in the UK (mean age = 45.8 (SD 19.9), 57% male). 67% of the patients had established epilepsy whilst 18% presented as a result of their first seizure. Results show considerable variability, with a few sites performing well demonstrating that good care is possible. But overall, assessment on arrival was inadequate, routine measurements were not done (temperature in only 83% of patients), a proper neurological examination with plantar responses recorded in 37% (IQR 20.0 49.1), an attempt to gain an eyewitness description in 58% (IQR 43.3 73.3), and an ECG performed in 59% (IQR 43.3 75.8). It was not routine in most hospitals to ask patients who have had a seizure about driving despite the obvious road safety implications for themselves and others. Only 51% of first seizure patients were referred for any form of neurology specialist assessment. Conclusion: Basic care currently provided shows wide variability and in many centres is inadequate to achieve good patient outcomes. Neurologists and epileptologists have to engage with acute services to improve this. I can confirm that none of the authors for the abstract I submitted have conflicts of interest.

p246 IMPACT OF STAFFING LEVELS AND TRAINING ON PATIENT SAFETY & MANAGEMENT ON THE EPILEPSY MONITORING UNIT C. A. Mclaughlin*, M. C. Walker, B. Diehl, C. Scott*, T. Wehner*, and C. Milabo* *The National Hospital for Neurology and Neurosurgery, London, UK; Department of Clinical and Experimental Epilepsy, London, UK; and UCL Institute of Neurology, London, UK
Purpose: This audit aimed to assess the impact of changes to staffing levels, protocols and training on ictal and postictal management and interview in the Epilepsy monitoring Unit. Method: We carried out a retrospective analysis reviewing Video-EEG data and reports from Jan-Feb 2011 and compared findings to an earlier study. Since 2002 core nursing staff had been increased by 50%, a ward sister added and bed capacity increased. Speed of seizure attendance, care given, proportion of unrecognised seizures and seizure type were considered. Up to 5 seizures per extracranial pre-surgical patient were included. Seizures with subjective symptoms & no clear clinical change were excluded, giving a total of 90 seizures in 30 patients. Result: Significantly more seizures were attended in 2011 than 2002 (77% versus 59%, P < 0.05 Chi Square). There was also a non-significant tendency for a faster response time: median 28 s (range 0240s) in 2011 c/w 41s (range 0600s) in 2002 (P = 0.2 for difference, MannWhitney U test). Cot sides were more likely to be up during all seizures (81% in 2011 c/w 35% in 2002, P < 0.001) and this was particularly evident in tonic-clonic seizures (15/16 in 2011 versus 0/4 2002, P = 0.001 Fisher's Exact).

p248 AMBUFLEX/EPILEPSY IMPLEMENTATION OF PATIENT-REPORTED OUTCOMES IN EPILEPSY CLINICS L. M. V. Schougaard*, P. Sidenius, J. Christensen, L. Overbeck, B. J. Hanner, and N. H. Hjollund *Regional Hospital West Jutland, Herning, Denmark; and Aarhus University Hospital, Aarhus C, Denmark
Purpose: Patient-reported outcomes (PRO) are commonly used in clinical trials and observational studies. However, use of PRO in clinical practice is rare but may have several advantages. AmbuFlex is a web-based questionnaire system that implements PRO in the clinical decision making. Implementation of AmbuFlex for epilepsy involves several issues including disease related questions, setting and frequency of assessment, presentation of results and evaluation of the effect on the organization of patient care. Purpose: To implement AmbuFlex in 3 epilepsy outpatient clinics in Jutland, Denmark and thereby provide the patients with a more flexible care, improve; quality of treatment, patient self-management and utilization of resources in the health care system.
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74 Abstracts
Method: The target group was all patients with epilepsy (n G 6500) associated with the 3 outpatient clinics. Three clinical expert groups were involved in the development of the epilepsy-questionnaire, which was tested on 20 epilepsy outpatients. Patients could choose to respond in either web or paper form. The results of the questionnaire were presented graphically for the clinicians within the individual, electronic medical records. Result: The pilot study provided useful information and apart from some problems due to recall bias and linguistic skills, most outpatients found the questionnaire easy to use. Patient referral to AmbuFlex is ongoing and the aim is to include the majority of patients associated with the 3 outpatient clinics. Conclusion: The results suggest that AmbuFlex is a flexible assessment program that may improve care for persons with epilepsy and optimize the use of resources in the health care system.

*HSE Dr Steevens Hospital, 8, Ireland; Change Management Training, 8, Ireland; HSE, 8, Ireland; and RCPI, 2, Ireland
Purpose: There is considerable variation in the provision and delivery of epilepsy care worldwide. Variation is at the root of disparities in quality, safety, access and value. In aviation, standard operating procedures (SOPs) are the distilled wisdom of professionals plus scientific evidence and have been developed over the last 3 decades, resulting in unparalleled quality and safety achievements. Healthcare is more complex than other industries but the use of SOPs, particularly by medical staff is rare. Method: In July 2011 the NECP in Ireland began a process of SOP development. Key clinical staff, patients and carers were invited to a professionally mediated workshop to determine key elements of excellence in epilepsy care covering ambulatory and acute care, diagnostics, therapeutics and prolonged Video-EEG monitoring units. Over the next 6 months, smaller groups met for 45 sessions to develop the SOPs. Result: 45 SOPs were developed which were put in a standardized Health Services Executive format. Twelve priority SOPs covering the three most important initial processes under each heading were endorsed by the clinical advisory group in Dec 2011 . All draft SOPs were posted in draft form on line in the spring on 2012 ready for small Plan, Do, Study, Act trials. Conclusion: The increasing complexity of modern healthcare demands that standardized procedures to reduce variation are required which will lead to improvements in quality, safety and cost. The NECP has developed 45 draft SOPs for improving epilepsy care that can act as templates for other national services.

p249 EPILEPSY CARE BY RAIL IN RURAL INDIA THINKING OUT OF THE BOX! M. B. Singh, R. Bhatia, M. Padma, M. Tripathi, and K. Prasad All India Institute of Medical Sciences, New Delhi, India
Purpose: To explore the possibility of a mobile clinic on the Lifeline Express using India's vast railroad network for spreading epilepsy awareness and conducting epilepsy screening clinics in remote, underserved parts of rural India. Method: The Lifeline Express arrives and stays at a new destination every month. We have organized a 23 day epilepsy clinic at each of its stops over the last 2.5 years. The epilepsy clinic screens patients who come in response to an extensive door-to-door campaign urging them to avail free services. Patients are interviewed, examined clinically, given a prescription and advised to follow-up and continue regular treatment. Epilepsy awareness activities amongst school children and teachers, and villagers are also carried out at each stop. Result: At Morena in the Central Indian state of Bihar, 144 patients (96 male) were examined on the LLE. The mean age was 24.7 years. A family history of epilepsy was present in 22.9% of the patients and a neurological deficit in 11.8%. A seizure frequency of at least 1/day, 1/week, 1/ month, 1/year or rarer was present in 15.7, 10.4, 58.3, 10.4 and 5.2 percent of patients respectively. Only 20.8% of the patients had ever been investigated with CT/MRI and 17.4% with an EEG. Patients who had never been treated with any AED were 37.5% Conclusion: Epilepsy treatment gap of >90% is reported from many parts of rural India. Innovative means of delivering epilepsy services combined with an emphasis on increasing epilepsy awareness are needed urgently. The Indian railways with its wide rural reach holds promise.

p251 LATE-LIFE REMISSION IN INTRACTABLE EPILEPSY: BURNT OUT EPILEPSY OR NATURAL HISTORY? M. Belluzzo*, J. Novy, G. Bell, M. Koepp, S. M. Sisodiya, and J. W. Sander *University of Trieste, Cattinara Hospital, Trieste, Italy; and UCL Institute of Neurology, London, UK
Purpose: Terminal seizure freedom in people with epilepsy is commonly considered an unlikely event if this is not reached in the early stages of the condition. In a subset of elderly people with long-standing refractory epilepsy, we aimed to see whether spontaneous remission can occur despite a life-long history of continuous seizures. Method: We carried out a retrospective evaluation of seizures patterns amongst people with longstanding pharmacoresistant epilepsy, institutionalized at the Epilepsy Society Chalfont Centre and who died between 1988 and 2009. Result: Among 122 people who had epilepsy for longer than 10 years, 26 (21%) reached a late, sustained remission (more than two years of seizure freedom). Seizure remission occurred at median age of 71 years and the median duration of seizure freedom was 6 years. Onset of remission was unrelated to medication changes in the vast majority of cases (92%). People who had experienced a previous interval of remission were more likely to be in remission at the time of death (p = 0.004, chi2). The length of the terminal remission was similar to that of previous remissions (p = 0.128, t test), but end of life remissions were more frequently spontaneous (p = 0.0016, Fisher exact test). Multivariate analysis suggests that older age at death was the only variable directly linked to the likelihood of late remission. Conclusion: Our study provides some preliminary evidence that for some people with epilepsy there is a natural tendency for seizures to stop with advancing age.

Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

75 Abstracts
Purpose: Epileptic seizure is very often present as a first manifestation of stroke. The aim of our study was to compare the prognosis between patients with and without epileptic seizures as a first manifestation of stroke. Method: We studied patients with acute stroke admitted to our hospital during the same period, using a standard protocol including at least one MR/CT scan, electroencephalography (EEG) and neurological examinations. The patients were divided into the two groups:1. study group with epileptic seizures as a first manifestation of acute stroke 2. control group with acute stroke and without epileptic seizures. All of those patients were analyzed within 3,6,9 and 12 months of stroke. Result: 104 patients with acute stroke were attended,46 female and 58 male, age range 39 to 83.48 were observed in the study group and 56 in the control group. After 3 months 5/48 patients from the study group and 3/56 from the control group had died. After 6 and 9 months 40 patients(15 from the study and 25 from the control group) were not available, but 12 from the study group and 5 from the control group had died. After 12 months of follow-up 15 patients were hospitalized again.10 of those have had a repetitive or the first epileptic seizures but without acute stroke. Conclusion: We did not find significant differences in prognosis between all patients after 3 and 6 months, but increased mortality after 9 and 12 months of follow-up. The frequncies of repetitive seizures and mortality were higher between patients with previous seizures, but also depend of type of stroke. Result: At two years, in the surgical group there was 19/26 patients seizure free (73%), 4 patients (15%) had a seizure frequency lower than a seizure per month, and only a patient (4%) had more than one seizure per month. At five years 15 patients remained for analysis: 11 were seizure free (73,3%), and 4 (26,7%) had less than a monthly seizure. 7 patients had postoperative neurological sequelae. In the medical treatment group, 12/17 patients were seizure free (70.6%), without significant differences (p = 0.2 and 0.3 respectively). Conclusion: In patients with non-refractory epilepsy surgical approach of cavernomas did not raised a significative better control of seizures than medical treatment, and surgery has potential serious risks. As these results are not definitive, it is still necessary a prospective and randomized study to resolve this uncertainty.

p254 ANTIEPILEPTIC DRUG SUSPENSION IN ADULT PATIENTS-ASSESSMENT OF RISK FACTORS S. M. Vujisic, D. B. Milikic, L. B. Radulovic, and S. Vodopic Clinical Centre of Montenegro, Podgorica, Montenegro
Purpose: To deremine risk factors for the appearence of relapse attacks after antiepileptic drugs suspension. Method: A group of patients who had the AE treatment stopped, by advise and agreement with the doctor, or on the basis of self-initiative were examined. The study only included patients who had repeated epileptic attacks. All the patients had detailed questionnaire filled up, and all of them had neurological examination, EEG and MRI done. Etiology was classified into simptomatic, idiopatic and kriptogenic. Result: A group of 43 patients (aged from 16 to 75 years) were examined due to epileptic attacks after exlusion of the AE therapy. There were 20 male and 23 female patients. Most of the patients were 16 to 35 years old, i.e 34 (79%). Eighteen patients had idiopatic (42%), thirteen patients had kriptogenic (30%), and twelve had symptomatic epilepsy (28%). Our study has shown that significantly large number of patients (p Conclusion: The most relapses of epileptic attacks occur in the first two years after discontinuation of AE therapy. Risk factor for recurrence is patological EEG. Our study has shown that there was no significant diferences in the occurance of relapse regarding etiology.

Semiology, Aetiology and Classification 4 Monday, 01 October 2012

p253 SURGICAL VERSUS CONSERVATIVE TREATMENT IN PATIENTS WITH CEREBRAL CAVERNOMAS AND NON REFRACTORY EPILEPSY S. Fernndez*, J. Mir, M. Falip, G. Plans, S. Castanyer, A. Fernndez-Coello, and J. J. Acebes *Hospital Plat, Barcelona, Spain; and Hospital Universitari de Bellvitge, LHospitalet de Llobregat, Spain
Purpose: Patients with cerebral cavernomas often presents with seizures. It is still unclear if surgery is the optimal approximation in patients with cavernomas and new onset epilepsy, sporadic seizures or non well established refractory epilepsy. The aim of this study was to compare the seizure frequency of patients with cerebral cavernomas operated and non operated, in order to obtain more information to the correct management of these patients. Method: We studied retrospectively 43 patients with non refractory epilepsy secondary to cerebral cavernoma. 26 patients (60.5%) underwent surgery and made up the surgical group, and 17 patients were treated medically and constituted the medical group. Seizure frequency, need of antiepileptic drugs post-treatment and other clinical variables were compared between both groups.

p255 PROVOKED SEIZURES AND FUNCTIONAL OUTCOME ONE YEAR AFTER ACUTE ISCHAEMIC STROKE H. Sentes-Madrid*, E. Chiquete*, C. Cant-Brito*, J. L. RuizSandoval, M. Alonso-Vanegas, and G. Garca-Ramos* *Instituto Nacional de Ciencias Mdicas y Nutricin Salvador Zubirn, Mexico City, Mexico; Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Mexico; and Instituto Nacional de Neurologa y Neurociruga MVS, Mexico City, Mexico
Purpose: To describe the factors associated with provoked seizures after acute ischaemic stroke and the impact on functional outcome at one year of follow up. Method: This is a descriptive cohort study on 1246 non-epileptic patients with acute ischaemic stroke included in a multicentre Mexican registry, who received long-term follow up after a first-ever or recurrent brain infarction. Multivariate analyses were performed to evaluate factors associated with provoked seizures and the functional outcome at 12 months of follow up.
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76 Abstracts
Result: The frequency of provoked seizures after acute ischaemic stroke was 8.1% [95% confidence interval (CI): 6.7% to 9.8%]. In a binary logistic regression model, risk factors significantly associated with provoked seizures were a scoring of the National Institutes of Health Stroke Scale (NIHSSS, US) >10 [odds ratio (OR): 2.21, 95% CI: 1.403.47], recurrent ischaemic stroke (OR: 2.17, 95% CI: 1.34 3.53) and age 3) at 12 months of follow up [hazard ratio (HR): 1.37, 95% CI: 1.041.83], as well as NIHSS >10 (HR: 4.47, 95% CI: 3.53 5.65), age 65 years (HR: 1.74, 95% CI: 1.382.20), heart failure (HR: 1.61, 95% CI: 1.222.13) and atrial fibrillation (HR: 1.35, 95% CI: 1.051.74). Conclusion: The frequency of provoked seizures after acute ischaemic stroke in this cohort was 8%. Age. of epilepsy in patients suffering CVT. Our objective was to analyse the risk factors for epilepsy after CVT, in a long-term follow-up. Method: This is a cohort study on consecutive non-selected patients with acute cerebrovascular disease, systematically registered from 1986 to 2010 in two referral centres of Mexico City. Here we analysed 340 patients who survived the first 6 months after CVT, who were not epileptic at baseline and for whom complete long-term information on neurological outcome was available. Result: Seizures occurred in 183 (54%) patients, in 26% of them as a clinical presentation and 74% at some point during the follow-up. Focal motor seizures occurred in 6.5%, secondary generalised focal seizures in 13.8%, and generalised tonic-clonic seizures in 22.4%. Status epilepticus occurred in 13 (7%) cases. In all, during a median follow-up of 28 months (range 2 to 288 months), epilepsy was present in 14.7% (27.3% of those who presented seizures). In a multivariate analysis adjusted for multiple confounders, risk factors associated with an increased risk of epilepsy during follow-up were having seizures as the clinical presentation of CVT [odds ratio (OR): 4.32, 95% confidence interval (CI): 2.208.48], pregnancy and puerperium (OR: 2.03, 95% CI: 1.113.71) and thrombosis of the longitudinal sinus (OR: 1.86, 95% CI: 1.013.41). Conclusion: Seizures are common at CVT presentation, but the risk increases during the following days after the thrombotic event. Most seizures resolve during the first month, but epilepsy occurred in 15% of patients with CVT in the long run.

p256 EPILEPSY REMISSION STAGE STATEMENT BY NONLINEAR METHODS FOR EEG RESULTS PROCESSING S. Artsiomenka*, V. Kistsen*, V. Golovko, and V. Evstigneev* *Belarussian Medical Academy of Postgraduate Education, Minsk, Belarus; and Brest State Technical University, Brest, Belarus
Purpose: Epilepsy remission stage statement and well-founded AEP dose lowering decision are the key points in epilepsy patients treatment. We created and used the automatic diagnostic system (ADS) for EEG paroxysmal activity detection to estimate epilepsy remission stage and to early exacerbation prognosis. Method: We applied the Neural-Net Method to make the assistant diagnostic system and examined this system on real EEG data. The largest Lyapunov's exponent is used as a criterion for the paroxysmal activity detection. Therefore a value of the largest Lyapunov's exponent was positive for chaotic behavior of a system and decrease when the epilepsy activities occur. There were observed 36 patients in epilepsy clinical remission stage by EEG every 3 month during 13 years and then estimated results by our ADS. ADS detect parts of EEG which are not chaotic unlike normal electrical brain activity and gives 2dimension map with colored abnormal parts red. Result: ADS display paroxysmal activity when usual analysis EEG not detects anomalies. ADS showed periodically anomaly activity various duration in background and particularly photostimulation EEG of all patients with tendency to disappearance of it during correct therapy (p < 0.05). ADS revealed a growth presence of hidden paroxysmal activity near 612 months before exacerbation of disease. Conclusion: Automatic diagnostic system for EEG paroxysmal activity detection can use to estimate epilepsy remission or exacerbation stage with prognosis of pre-seizure changes in the EEG signal dynamic to predict a seizure occurrence and to correct the AEP doses.

p258 LONG-TERM OUTCOME AFTER COGNITIVE AND BEHAVIORAL REGRESSION IN NON-LESIONAL EPILEPSY WITH CSWS E. Roulet Perez*, T. Deonna*, C. Mayor-Dubois*, M. P. ValentiHirsch, E. Hirsch, M. Metz-Lutz, A. De Saint-Martin, and C. Seegmller *Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; and University regional hospital centre of Strasbourg, Strasbourg, France
Purpose: To present the long-term outcome (LTO) of 10 adolescents and young adults with documented cognitive and behavioral regression as children due to non-lesional focal, mainly frontal epilepsy with continuous spike-waves during slow wave sleep (CSWS). Method: Past medical and EEG data of all patients were reviewed and neuropsychological tests exploring main cognitive functions were administered. Result: After a mean duration of follow-up of 15.6 years (range 823 years), none of the 10 patients had recovered fully, but four regained borderline to normal intelligence and were almost independent. Patients with prolonged global intellectual regression had the worst outcome, whereas those with more specific and short-lived deficits recovered best. The marked behavioral disorders that were so disturbing during the active period (AP) resolved in all but one patient. Executive functions were neither severely nor homogenously affected. Three patients with a frontal syndrome during the AP disclosed only mild residual executive and social cognition deficits. The main cognitive gains occurred shortly after the AP, but qualitative improvements continued to occur. LTO correlated best with duration of CSWS. Conclusion: Our findings emphasize that cognitive recovery after cessation of CSWS depends on the severity and duration of the initial regression. None of our patients had major executive and social cognition deficits with preserved intelligence as reported in adults with destructive lesions of the frontal lobes during childhood. Early recognition of epilepsy with CSWS and rapid introduction of effective therapy are crucial for a best possible outcome.

p257 EPILEPSY AS A CHRONIC COMPLICATION IN CEREBRAL VENOUS THROMBOSIS: A 20YEAR FOLLOWUP E. Chiquete*, C. Cant-Brito*, M. Merloz-Benitez, A. Arauz, H. Sentes-Madrid*, and M. Alonso-Vanegas *Instituto Nacional de Ciencias Mdicas y Nutricin Salvador Zubirn, Mexico City, Mexico; and Instituto Nacional de Neurologa y Neurociruga MVS, Mexico City, Mexico
Purpose: Seizures represent a common clinical presentation of cerebral venous thrombosis (CVT); however, little is known about the future risk

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77 Abstracts
p259 TEN-YEAR MORTALITY AMONG PEOPLE WITH EPILEPSY (PWE) AT A PRIMARY HEALTH CARE LEVEL: THE CASE OF THE MBAM AREA OF CAMEROON J. Y. Fonsah*, R. Nchufor, R. Nditanchou*, Y. F. Fogang*, A. Acho*, R. F. Doh*, F. Dema*, E. N. Tabah, V. Sini*, A. C. Z. Bissek*, W. F. Muna, and A. K. Njamnshi *Central Hospital Yaounde, Yaounde, Cameroon; Sub Divisional Hospital Ndu, Yaounde, Cameroon; and Neurology Department, Central Hospital Yaounde, Cameroon; FMBS UYI Cameroon, Yaounde, Cameroon
Purpose: We aimed at contributing to the improvement of epilepsy care in PWE, understand the natural history of epilepsy, determine the mortality and its principal causes in a group of PWE in the Mbam area of Cameroon. Method: A retrospective analysis of all case files diagnosed with epilepsy from 1999 to 2000 in the Mbam area was done. A total of 820 files of patients followed up in an existing, community-dependent, nurse-controlled and neurologist-supervised missionary epilepsy programme were studied amongst which 192 were analysed. Result: A mortality rate of 15.1% was obtained with a SMR of 8.9. More deaths were recorded amongst females (65.5%) and people of the age group 1625 years (73.2%). Most people lived with the epileptic condition for 1115 years (42%) before dying with a mean duration of illness of 11.65 years. Bilomo and Badissa alone recorded more than 50% of all deaths. The main causes of death were status epilepticus (42.3%), drowning (23.1%) and sudden unexplained death (7.7%). Conclusion: The mortality amongst PWE is high in the Mbam area and involves more females and youths. Status epilepticus and drowning are common causes of death.

p261 PROGNOSTIC FACTORS FOR TIME TO TREATMENT FAILURE AND TIME TO 12 MONTH REMISSION FOR PATIENTS WITH GENERALISED EPILEPSY: POST HOC AND SUBGROUP ANALYSES OF SANAD L. J. Bonnett*, C. Tudur Smith*, D. Smith, P. Williamson*, D. Chadwick, and A. Marson *University of Liverpool, Liverpool, UK; and Walton Centre for Neurology and Neurosurgery NHS Foundation Trust, Liverpool, UK
Purpose: Epilepsy is a heterogeneous condition with outcomes ranging from immediate remission on a first antiepileptic drug through to frequent unremitting seizures with multiple treatment failures. There are currently few published prognostic models for epilepsy that allow informed decision making based on predicting outcomes overall and on specific treatments. Method: A list of potential prognostic factors was established and univariate and multivariable analyses using Cox regression models were undertaken. Variables were centred to diminish multicollinearity and continuous variables were investigated by log or fractional polynomial transformations. Parsimonious multivariable models were produced with variable reduction by Akaike's Information Criterion. Result: Multivariable models identified a number of significant factors. For time to treatment failure, treatment history (recent seizures following previous remission vs treatment naive: HR 2.01 95% CI (1.18 to 3.41)), EEG results (no results vs normal results: HR 2.45 95% CI (1.46 to 4.09)), total number of seizures before randomisation (e.g. 48 vs 2: HR 1.49 95% CI (1.19 to 1.85)) and treatment (topiramate vs valproate: HR 1.62 95% CI (1.22 to 2.16)) were significant factors. For time to 12 month remission significant factors were relatives with epilepsy (present vs absent: HR 0.75 95% CI (0.59 to 0.95)), neurological insult (present vs absent: HR 0.70 95% CI (0.52 to 0.93)) and total number of seizures before randomisation (e.g. 48 vs 2: HR 0.41 95% CI (0.33 to 0.51)). Conclusion: Subject to external validation, this prognostic model should aid individual patient risk stratification and the design and analysis of future epilepsy trials.

p260 LONG-TERM OUTCOME IN ABSENCE EPILEPSIES M. Holtkamp, D. Janz, and A. Kirschbaum Epilepsie-Zentrum Berlin-Brandenburg, Berlin, Germany
Purpose: Absence epilepsies are classified regarding age at onset into childhood (10th year of life) and juvenile (>10th year) and regarding clinical course with high- and low-frequency seizures into pyknoleptic and non-pyknoleptic forms. Prognostic data may help to clarify if these represent different entities or constitute parts of a clinical continuum that is based on the same neurobiological syndrome. Method: 147 patients with absence epilepsies and a follow-up of 20 a were included. Diagnostic allocations were made on the basis of clinical and EEG data derived from patient charts. Terminal remission was defined as seizure freedom in the last 5 years. Result: After a mean follow-up of 45 15 years, 75 patients (51%) were seizure free, 22 of those were tapered off antiepileptic drugs (AED). Following multivariate analysis, history of generalised tonic-clonic seizures (GTCS) (OR 7,680; CI95% 1.54638.159; p = 0.013) and age at investigation (OR 0.958; CI95% 0.9350.982; p = 0.001) were independent predictors for lacking remission. Conclusion: More than half of the patients with absence epilepsies were seizure free for the last 5 years, one third of those did not take AEDs. Thus, nearly one in six patients was cured from absence epilepsy almost half a century after onset. Lack of remission was a function of patients age and occurrence of GTCS. Neither age at epilepsy onset nor the clinical course with pyknoleptic vs. non-pyknoleptic absences was associated with long-term outcome. This important clinical feature biologically rather argues for a continuum than for a dichotomisation of absence epilepsies into a childhood and juvenile form.

p262 MORTALITY AND SUDEP IN EPILEPSY PATIENTS TREATED WITH VAGUS NERVE STIMULATION C. A. Granbichler*, L. Nashef, C. E. Polkey, and R. Selway *Christian Doppler Klinik, Salzburg, AustriaKing's College Hospital, London, UK; and Kings College London, London, UK
Purpose: Data on mortality with Vagus Nerve Stimulation (VNS) for epilepsy are limited. In one study, standardized mortality ratio (SMR) was 5.3 [95% confidence interval (CI) 3.08.7] with a rate of definite/ probable SUDEP of 4.5/1,000 person-years (py) (Epilepsia 1998 Feb;39(2):20612). Mortality rates were lower (SMR = 3.6) with extended follow-up. Stratified by duration of use, SUDEP rate was 5.5/ 1,000 over the first 2 years, and 1.7 per 1,000 thereafter (Epilepsia 2000 May;41(5):54953). To establish mortality rates, identify epilepsyrelated deaths and calculate SUDEP rates in patients treated with VNS for epilepsy. Method: All UK-based patients undergoing VNS at King's College Hospital, London, between 1st January, 1995 and 31st December, 2010 were included. Deaths were ascertained from the national death register. Information on cause and circumstances of death were obtained as appropriate. Deaths were designated as epilepsy or not epilepsy related and SUDEP cases classified using the unified definition (Epilepsia, 53(2):227233, 2012). SMRs were calculated on an intention to treat basis.
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78 Abstracts
Result: There were 445 patients (2734 person-years [py], median follow-up 6.1 years) and 29 deaths (SMR 7.6 [95% Confidence Intervals (CI), 5.310.9]. On preliminary classification, 13 deaths were epilepsyrelated, including 7 SUDEP (5 definite, 2 probable), and 3 are unclassified (further information awaited). Overall SUDEP rate/1000 py was 2.6, 2.4 during the first two years, and 2.7 thereafter. Conclusion: SMR in our cohort is higher but not significantly so. Preliminary results do not confirm a decrease in SUDEP rate beyond the first two years in this cohort. DEP). The exact mechanisms of SUDEP are not known and several hypotheses (such as cardiac, respiratory, autonomic causes) have been advanced. People with epilepsy also seem to have more concomitant medical conditions than the general population; some cardiac co-morbidities (such as Brugada syndrome) may play a role. We aim to explore the prevalence of significant cardiac arrhythmias in these people. Method: To date, we have collected consecutive standard (12 leads) ECGs of 100 people assessed for chronic epilepsy in 2010 in a tertiary referral centre. ECGs were reviewed by an experienced cardiologist (HLT), looking for subtle abnormalities. All concomitant medications as well as cardiovascular risk factors and history were taken into account. Result: In those 100 people, amongst other abnormalities detected, the ECGs of two were highly suggestive of Brugada syndrome. Neither was previously known to have this condition and this had not been detected by automated analysis of the ECGs or by previous review. Conclusion: The prevalence of Brugada syndrome may be higher in people with chronic epilepsy than in the general population where it was found in several studies to be less than 0.1%. This condition is known to be lethal and could be responsible for some cases of SUDEP. Channelopathies affecting both heart and brain could explain its increased occurrence in epilepsy. We aim to increase the size of our sample to confirm these findings.

Semiology, Aetiology and Classification 5 Monday, 01 October 2012

p263 IS TERMINAL REMISSION WITHOUT THERAPY POSSIBLE IN PATIENTS WITH JUVENILE MYOCLONIC EPILEPSY? N. J. Jovic, and A. Kosac Clinic of Neurology and Psychiatry for Children and Youth, Belgrade, Serbia
Purpose: It has been generally accepted that juvenile myoclonic epilepsy (JME) is lifelong and that it is unwise to discontinue treatment once seizure control has been established. The evolution of JME in patients with long-term seizure freedom and antiepileptic drugs (AEDs) discontinuation was assessed. Method: We retrospectively analyzed clinical course of 87 JME patients (38 male, 49 female) aged from 17.5 to 43.5 years (mean 27.6), with mean seizure onset of 14.6 years (range 8.320.8). Result: Complete seizure control was achieved in 67 (77.0%) patients mainly with valproate (55 patients). Pseudo-resistant seizures occurred in 9.2%, while JME was refractory in 13.8% patients. Therapy was discontinued in 34 (39.1%) patients (in 13 by their own choice after 5.3 + 2.4 and in 21 following advice of a physician after 8.5 + 5.2 years of seizure freedom). In 18 subjects seizures relapsed after mean 1.1 year (range 7 days to 4 years) and AED was restarted. In two patients the AED was reintroduced because of EEG aggravation. Seizure and drug freedom of mean 5.1 years (range 3.512 years) was noted in 11.5% patients. Nonintrusive myoclonic seizures recurred for 2.44 years as their only seizure type in 4 subjects, but without restarted medication. Conclusion: Terminal remission without AEDs is possible in JME patients. Non-compliant individuals have lower chance to achieve it. All seizure types in JME resolved in 11.5% and for 4.6%, only myoclonus persisted. Therefore, 16.1% of adolescents and young adults with JME have troublesome seizures vanished and AED treatment was no needed for years.

p265 HAS TREATMENT OF EPILEPSY IMPROVED IN THE PAST 10 YEARS? THE IMPACT OF EPILEPSY TREATMENT IN THE PAST 10 YEARS; A COMMUNITYBASED COMPARISON STUDY M. Wassenaar*, F. S. S. Leijten, P. Van Der Linden, S. G. Uijl, A. C. G. Egberts, and J. A. Carpay *UMC Utrecht, Utrecht, The Netherlands; Rudolf Magnus Institute of Neuroscience, UMC Utrecht, Utrecht, The Netherlands; Tergooi ziekenhuizen Blaricum, Blaricum, The Netherlands; Julius Center for Health Sciences and Primary Care, UMC Utrecht, Utrecht, The Netherlands; and Utrecht Institute for Pharmaceutical Sciences, University Utrecht, Utrecht, The Netherlands
Purpose: New-generation AEDs have increased the number of treatment options for epilepsy and are promoted because of better safety profiles. It is unknown if this has resulted in better patient outcomes in daily practice. We describe 10year changes in quality of life (QoL), seizure control and drug-related adverse effects (DRAEs) in a community-based sample of epilepsy patients and assesses potential predictors of QoL. Method: From two cross-sectional community-based studies performed in 2000 and 2010 in a Dutch suburban region, responses to standardized questionnaires on treatment outcomes were compared. Epilepsy patients were identified using pharmacy records, 344 and 247 patients were included respectively. Additionally, factors, among which seizure control and DRAEs, predicting QoL were assessed by multivariate linear regression. Result: New-generation AEDs prescription in 2010 increased to 44.5% from only 10.5% in 2000. Treatment outcomes did not differ between new and old-generation AEDs. In 2010 compared to 2000, QOLIE-31 scores did not differ (72.48 vs 72.54), neither did the proportion of patients reporting well-controlled seizures (55.1% vs 50,5%). However, seizure acceptability increased (54.3% vs 40.3%) and AEs were significantly more reported (82.0% vs 58.9%). Seizure control, DRAEs and seizure acceptability jointly predicted QoL score (R2 = 51%). Conclusion: The introduction of new AEDs has not improved QoL in the past decade. Whereas seizure acceptability increased, seizure control

p264 CARDIAC ARRHYTHMIAS MAY BE UNDERESTIMATED IN PEOPLE WITH CHRONIC EPILEPSY R. J. Lamberts*, J. Novy, H. L. Tan, R. D. Thijs*, and J. W. Sander *SEIN-Epilepsy Institute in the Netherlands Foundation, Heemstede, The Netherlands; UCL Institute of Neurology, London, UK; and University of Amsterdam, Amsterdam, The Netherlands
Purpose: People with chronic epilepsy are known to be at risk of premature mortality mainly due to sudden unexpected death in epilepsy (SUEpilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

79 Abstracts
remained similar and DRAEs were reported more frequently. Since all these factors contributed to QoL, reduction of DRAEs should be prioritized to improve QoL in epilepsy patients. Conclusion: Neurological status and EEG are crucial parameters which could identify infants at risk of CP and epilepsy.

p266 CARBAMAZEPINE AND OXCARBAZEPINE TRIGGERED EPILEPTIC NEGATIVE MYOCLONUS AGGRAVATION IN CHILDHOOD K. Y. Mukhin, and M. B. Mironov St. Luka's Institute of Child Neurology and Epilepsy, Moscow, Russia, Moscow, Russian Federation
Purpose: Investigation of patients with ENM induced by Carbamazepine (CBZ) and Oxcarbazepine(OXC). Method: The 12 patients with ENM who have been taking CBZ or OXC in the course of treatment. In 10 of 12 cases, ENM was induced by these drugs. Result: In 10 cases (83,3%) ENM aggravation was noted. As our results show, there are several CBZ/OXC triggered ENM aggravation risk factors: males prevail over females at a ratio of 4 to 1; age of onset of epilepsy: from 1 year to 13 years of age with a peak between the ages of 3 and 8 years; forms of epilepsy: FEBL-BEDC 5 cases, epileptic encephalopathies associated with BEDC 3 cases, symptomatic focal epilepsy with SBS on EEG 1 case, progressive myoclonus epilepsy (PME) 1 case. Types of seizures preceding the ENM events: hemiconvulsive 7 patients; SGTCS 5 cases; tonic seizures 2; occipital focal seizures 2; GTCS 1; myoclonic seizures 1 case.

p268 RELIABILITY AND VALIDITY OF A SPANISH VERSION OF THE IMPACT OF PEDIATRIC EPILEPSY SCALE IN A CUBAN POPULATION N. Garfalo Gmez, O. Fernndez Concepcin, and A. M. Gmez Garca Cuban Institute of Neurology and Neurosurgery, Havana, Cuba
Purpose: The Impact of Pediatric Epilepsy Scale (IPES) is a brief, accurate, and acceptable measurement scale of the impact of pediatric epilepsy on the Health Related Quality of Life (HRQOL) of both the child and family as perceived by the child's parent(s) and has been previously validated in Canadian and Chinese children with epilepsy. The aim of this study was to validate a Spanish language version the IPES in Cuban children with epilepsy. Method: The IPES was translated and adapted to Cuban culture and administered to 76 parents of children with epilepsy. Result: The principal component analysis indicated that two factors accounted for 72% of the variance of IPES scale (family relationships and health and social well-being). The IPES also was able to detect differences in health-related quality of life (HRQOL) between subjects according to epilepsy severity. Internal consistency coefficients were 0.962 and the test-retest reliability was 0.979. Conclusion: The Cuban Spanish version of IPES has good validity and reliability, and can be used to measure a child's epilepsy specific HRQOL in Cuba and probably in other Spanish speaking communities.

p267 NEONATAL PARAMETERS AS PROGNOSTIC FACTORS FOR EPILEPSY OR CEREBRAL PALSY IN INFANTS WITH HYPOXIC-ISCHEMIC ENCEPHALOPATHY N. M. Cerovac, and N. J. Jovic Department for Neurology and Psychiatry for Children and Youth, Medical School, Belgrade, Belgrade, Serbia
Purpose: The survivours with hypoxic-ischemic encephalopathy (HIE) were studied to evaluate the prognostic value of neonatal parameters as risk factors for cerebral palsy (CP) and epilepsy. Method: A group of 45 infants with HIE were retrospectively assesed at birth and at seven year of age. Perinatal conditions, neonatal parameters, neurological status, 5-minute Apgar score and early electroencephalogram (EEG) were analysed. Result: The neurological outcome at the age of seven years was normal in 9 infants (20%) and abnormal in 36 (80%). Both epilepsy and CP developed in 9 infants (20%), only motor delay in 30%, only epilepsy in 4% or only CP in 26%. Seizures were classified as infantile spasms (4 infants), complex focal (3) and generalized tonicclonic (2). Obstretic complications were:pre-eclampsia (13%), abruptio placentae (11,1%), chorioamnionitis (20%), breech delivery (11%), cord prolapse (11%), meconium (20%) and caesarean section (33%). The mean gestational age of the group was 36 weeks, mean birth weight 2,4 kg and the mean Apgar score 6,9. The neonatal neurological status was normal in 31% of infants and abnormal in 69%. Early EEG was normal in 22% of infants and abnormal in 78% (abnormalities in EEG background rhythm and/or pathologic patterns). The results of our study confirm that neonatal neurological status (v2 = 11,431; p = 0,0007) and early EEG (v2 = 8,481; p = 0,0036) were a good predictive factors in terms of neurological sequelae, while other neonatal parameters did not show such a good correlation.

Purpose: Acute symptomatic seizures (ASS) are seizures occurring at the time or in close temporal association with a documented systemic or brain insult. The major issues involved in their management are the diagnosis and treatment of the underlying cause, whether seizures should be treated or not, and the choice and duration of anti-epileptic drug (AED) treatment. These decisions are not straightforward and currently no clear guidelines exist to guide management in this area. Method: We reviewed the literature on risks of ASS and epilepsy following a number of common conditions. Result: We outline our current practice in this area which is based on the evidence available on risks of seizure recurrence, and on our own experience. Conclusion: Most ASS only need short term therapy (up to 3 months) if there is complete recovery from the acute insult. Patients with residual structural brain abnormalities with focal neurological deficit and/or MRI changes need long term prophylactic treatment. We make some suggestions for duration of treatment for ASS associated with a number of common conditions, including; subarachnoid and intracerebral haemorrhage 1 year ischaemic stroke and venous sinus thrombosis 1 year mild to moderate head injury acute seizure control only severe head injury 2 years -metabolic and toxic disorders (including alcohol withdrawal) correction of underlying cause only meningoencephalitis with complete recovery, normal MRI 3 months, residual focal deficit and/or MRI changes 2 years - cerebral abscess, tuberculoma and parasitic granuloma 2 years
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p270 REFRACTORY SEIZURES AND QOL: CAN A PATIENT BE WORSE OFF ON AEDS? 3 CASE STUDIES S. White, and L. D. Mewasingh Imperial College Healthcare NHS Trust, London, UK
Purpose: 3 clinical cases are discussed whereby the common theme is that of refractory seizures, of different aetiologies, but nontheless raising the question of whether polypharmacy is justified when clinically there do not seem to be any significant clinical response to various AEDS in different combinations over time. In each case the seizures have been proven to be concordant with numerous electrographic recordings over a period of time. Method: Aetiologies: Case 1: a 2 year old with severe neonatal herpes encephalitis with significant sequelae (4limb cerebral palsy, cortical blindness, numerous seizure types as well as non-epileptic movement disorder) and feeding problems Case 2: a young boy with Wolf Hirshorn and refractory epilepsy disorder including episodes of nonconvulsive status epilepticus, resistant to various AEDs as well as no clincal response to ketogenic diet Case 3: a teenager with herpes simplex encephalitis acquired in her primary school years with frontal disinhibition, moderate learning difficulties and refractory seizure disorder. Result: In the first two cases parents were clear that they did not wish for further medications, perceived as of minimal benefit and resulting in decreased alertness. In the third case, parents and professionals differed in what was perceived as optimal QOL for the young person, with the former keen to pursue various therapeutic avenues with little clinical tangible improvement. Conclusion: The issues of QOL, polypharmacy, perceived side effects of treatment versus benefits are raised and discussed. This can at times lead to the dilemma of whether to treat and how aggressively to treat seizures in this context. Conclusion: Clinical record keeping was generally poor particularly regarding the circumstances surrounding deaths and raising awareness of SUDEP among patients/carers. There was also an absence of post-mortem reports and no record of support provision for families to cope with their bereavement in the majority of cases.

p272 EPILEPSY AND PSYCHIATRIC DISORDERS IN A LEARNING DISABILITY PATIENT'S SERIES V. C. Monetti, E. Fallica, V. Govoni, and E. Cesnik Azienda Ospedaliero Universitaria di Ferrara, Ferrara, Italy
Purpose: Epilepsy is most frequent in Learning Disability (LD) patients. The frequency ranges from 6% (moderate LD) to 50% (severe/profound LD). The object of our study is to analyse a LD outpatients series followed up in the Adult Epilepsy Center of Ferrara Hospital to evaluate their long-term prognosi and eventual conditioning clinic and psycosocial factors involved. Method: In the Ferrara Hospital Adult Epilepsy Center database LD patients, in follow-up from more than 10 years with the last examination in the years 20102011, were identified. Their data were crossed with the data of the same patients who were previously followed-up in the Paediatric Epilepsy Center to obtain a long-term observation. Result: 86 patients were identified (35 F, 51 M, mean age 41 years). 76% of them had a symptomatic Epilepsy (mainly pre- post-natal injury anda cerebral malformations) whereas 9% had a chromosomal-genetic disorder. In the 43% of the cases the seizures frequency was high (>2/ month) from the onset with no significant improvement over time. 48% of patients had a drug-resistant epilepsy. Psychiatric disorders were present in 48% of patients and almost all of them were institutionalised. Conclusion: Our findings support limited evidence from the literature that the LD severity does not affect the prognosis of epilepsy as the high frequency of seizures at onset. Psychiatric comorbidity is prognostically unfavourable factor for an institutionalization.

Purpose: To calculate the mortality rate of Sudden Unexpected Death due to Epilepsy in people with intellectual disability and evaluate the quality of epilepsy management they received from an adult intellectual disability service. Method: All adults, with an intellectual disability, who had died because of epilepsy between 1993 and 2010 were identified using the Leicestershire Intellectual Disability Register database. Death certificates and post-mortem reports were used to ascertain the cause of death. Case notes review was then carried out to collect further information. Result: A total of 898 patients with intellectual disability had died over the 18 year study period. The all cause specific Standardised Mortality Ratios were 2.4 (95% CI=2.12.6) and 3.0 (95% CI=2.63.3) for males and females respectively. 244 of deaths occurred in people with a diagnosis of epilepsy rendering a Standardised Mortality Ratio of 3.2 (95% CI=2.63.8) for men and 5.6 (95% CI=4.66.7) for women. SUDEP Standardised Mortality Ratio was 39.6 for men (95% CI=23.163.4) and 52.0 for women (95% CI=23.7 98.8). The majority of these service users were male, of Caucasian ethnicity, and with a significant degree of intellectual disability (IQ<50). A significant number of patients had comorbid autism, physical and mental health problems, poorly controlled epilepsy and took more than one antiepileptic agent.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

Semiology, Aetiology and Classification 6 Monday, 01 October 2012

Purpose: Mixed connective tissue disease (MCTD) diagnosis is based on specific clinico-laboratory criteria with rare onset in childhood. We present a 16year-old adolescent with complex partial status epilepticus as the initial manifestation of pediatric-onset MCTD. Method: The patient was admitted following a prolonged (>12 hours) state of altered consciousness and disorientation, which ended up with two secondary generalized tonic-clonic seizures. Family/personal history for epilepsy was negative. No perinatal problems, febrile seizures or head trauma were reported. Result: Interictal EEG showed spikes/sharp waves over the left anteriortemporal regions and a 4sec duration paroxysmal generalized 3 Hz

81 Abstracts
spike-wake discharge. MRI-brain was compatible with left-sided hippocampal sclerosis (HS) (ipsilateral hippocampal and fornix atrophy, lateral ventricle dilatation and high T2/FLAIR signal of the hippocampus). On interviewing he reported muscle weakness and joint aches on the lower extremities. Physical examination revealed swollen fingers. Laboratory tests showed elevated CPK, positive anti-snRNP70 and ANA. Based on the Kasukawa criteria a definite MCTD diagnosis was made. Conclusion: Genetic or environmental factors may lead to hippocampal tissue injury and HS, evolving to mesial temporal lobe epilepsy (MTLE). Although MCTD-associated HS has not been reported, Central Nervous System (CNS) may be affected via vascular or inflammatory mechanisms, leading to early neurological manifestations. Correlation of MCTD with anti-SSA/ro seropositivity with neurological manifestations is already established. We hypothesize on probable similarities with Systemic Lupus Erythematosus regarding vasculitis-induced CNS involvement and HS development. Our case indicates that MTLE may be a consequence of MCTD. Should HS is revealed an underlying vasculitic mechanism could be hypothesized. Results: Patients were investigated by clinical examination, neuropsychological test, brain computed tomography, vascular related blood tests, EEG studies, angio MRI in selected cases. We find 72% generalized seizures and 28% focal seizures. Among generalized seizures 74% had only seizures and headache with no neurological objective signs. Regarding the etiology of these cases we find: tumors 6.3%, silent cortical ischemic lesions 6%, unexplained sequel lesion (porencefalia) 3.6%, no imagistic lesion 71% and focal vascular lesion in 13% (dural sinus thrombosis 49%, cerebral cavernous malformation 30%, cerebral vascular aneurysm 21%). We describe the 2 cases of female patients with generalized seizure as first neurological manifestation due to a frontal cavernoma and to a longitudinal sinus thrombosis with no objectives neurological signs. EEG revealed synchronous paroxysm of generalized polyspikes and the MRI angiogram detected 2 type of focal vascular impairment. Conclusion: Despite the focal vascular lesions, the existence of clinical first manifestation as primary generalized seizures must underlie a complementary, still unknown, pathological mechanism.

p274 STATUS EPILEPTICUS AND MULTIPLE SCLEROSIS CASE OVERVIEW D. Sahovic, and Z. Savic Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina
Purpose: To present the case of a patient with a several years history of multiple slerosis with sudden status epilepticus. Method: The patient is 41 years old, with a 12-years clinical history of multiple sclerosis. The patient was treated and monitored well, and did not show any symptoms of any form of epileptic seizure. She suddenly presented a partial motor seizure with secondary generalization which evolved to the epileptic status of tonic and clonic spasms. Upon admission to the Intensive Care Unit, electroencephalographic investigations revealed EEG changes with specific epileptiform discharges (3.5 Hz S-W complexes) over the frontal lobe. EEG control showed normalization following medical therapy. Result: Since the previous treatment of the patient for the basis disease never revealed a possibility of developing of any form of epileptic seizure, a sudden and serious nature of her current status indicates the need for continuous caution and regular EEG monitoring of such patients. Conclusion: Multiple sclerosis patients may at any stage of the disease be at risk of a symptomatic form of epilepsy as an isolated seizure or a permanent form of epilepsy.

Purpose: To examine the role of initial precipitating events (IPE) in patients with drug resistant temporal lobe epilepsy (TLE) with and without hippocampal sclerosis. Method: Retrospective chart review of 171 patients diagnosed to have temporal lobe epilepsy based on clinical history, ictal video-EEG and MRI. Patients were categorized into two groups; [Group 1] with history of drug resistant TLE and MRI evidence of HS and Group 2 without HS, with or without other structural abnormality. Both groups were compared for age, gender, age at onset and duration of epilepsy, time to intractability, age at first febrile seizure (FS), frequency of FS, history of IPEs [including history of perinatal asphyxia, meningitis, encephalitis, head trauma], age at spontaneous remission. Statistical analysis was carried out using Mann Whitney test for continuous variables and Fisher's exact test for discrete variables (p Result: Seventy-two patients [24 female] with mean age of 26 + 11 years [range 8 to 55] fell in Group 1 with 99 patients [24 female] with mean age 21.6 + 10 years [range 3 to 60] in Group 2. Age at onset of epilepsy was significantly lower in Group 2 while a history of perinatal asphyxia and prolonged FS were more frequent in Group 2 (p Conclusion: A younger of age of presentation, (IPE) history of prolonged FS and a history of perinatal asphyxia were significant in patients with drug resistant TLE without hippocampal sclerosis. These findings raise the possibility of a distinct subgroup of patients with TLE who are treatment resistant with an early onset of epilepsy.

Purpose: Background: To characterize and discuss an unusual etiology for generalized seizures in a small series of cases. Methods: We reviewed the clinical features and laboratory data of 1120 patients hospitalized for epilepsy in our neurological service during past 5 years, and we emphasize 2 cases with generalized seizures as first clinical manifestation of different focal cerebrovascular impairment.

p277 TREATMENT EFFICACY OF SYMPTOMATIC EPILEPSY IN POST STROKE PATIENTS H. D. Hambardzumyan, and H. M. Manvelyan Yerevan State Medical University, Yerevan, Armenia
Purpose: Post stroke patients often develop not only physical or motor impairment, but also cognitive decline and in some cases, mainly associated with cystic transformation of the brain tissue, they develop epileptic seizures also.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

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The aim of this study is effective treatment of post stroke patients with symptomatic epileptic seizures. Method: 27 patients (12 women and 15 men) of the age of 62 6 years, who met selection criteria: arterial hypertension, ischemic stroke, intracerebral cyst verification by MRI or CT scans and symptomatic epilepsy, were selected for this study. All of them had at list one seizure and positive EEG. Result: Cognitive impairment was assessed by modified Wechsler scale (71 point maximum), was in range of 33 8. 13 out of 27 patients took Carbamazepin 600 mg daily, in two months of observation period they were free of seizures, but the Wechsler score decreased till 28 6. 14 patients took Gabapentine 900 mg daily, in two months period they were free of seizures also, and Wechsler score was 32 6. Conclusion: Both medications in mean therapeutic doses are effective in prophylaxis of seizures in post stroke patients, but Carbamazepin causes decline in cognitive function in two months, whether patients on Gabapentine kept cognition level constant. The choice of medication in treatment of post stroke epilepsy must be done in accordance of their influence on cognitive functions also. Method: Observational case-control study (1:3) of patients with a nonlacunar acute cerebral infarct, seen in a Stroke Unit (20082009). Cases: patients treated with IV rt-PA. Controls: patients not treated with IV rtPA, paired with cases according to severity (NIHSS), and cerebral artery involved. Patients with previous epilepsy, brainstem infarct, or neurointerventionist treatment, were excluded. Variables: basal data, stroke severity (NIHSS), etiology, involvement of cerebral cortex and appearance of early (<7 days) or late (>7 days) symptomatic seizures. Result: 147 patients, 49 cases. Mean age was less in cases than in controls (66.51 Vs 72.78; p = 0.007). Proportion of males was similar (57.1% Vs 44.9%; p = 0.162). Cases had more frequently uncommon etiology infarcts (14.3% Vs 4.1%; p = 0.042). There were no differences in vascular risk factors, previous treatment, nor cerebral cortex involvement. Early and late seizures were similar between cases and controls (6.1% Vs 7.1%, and 10.2% Vs 7.1%, respectively; p=NS). Hemorrhagic transformation was the only independient predictor factor in early (OR 5.69; CI 90% 1.4422.45) and late (OR 3.71; CI 95% 113.76) seizures, adjusted by age, sex, NIHSS, cerebral cortex involvement and IV rt-PA. Conclusion: Treatment with IV rt-PA doesn't influence in the development of symptomatic seizures after an acute cerebral infarct. Hemorrhagic transformation is a predictor factor of such seizures.

Purpose: To compare the frequency and variety of somatic comorbidity in young adult patients with idiopathic (IE) and symptomatic epilepsy (SE) and duration of the disease more than 5 years. Method: We followed up (in the course of 510 years) two groups of patients aged 1840 years: 38 persons with IE (12 males, 26 females) with persistence of seizures from childhood or adolescence and mean duration of the disease 13.7 years and 94 persons (47 males, 47 females) with SE and mean duration of the disease 9.7 years. Complete clinical neurological and somatic examination with adequate para-clinical investigations were used to confirm the presence of somatic pathology. Result: In patients with IE somatic diseases were found in 50.0% of males and 42.3% of females, in SE patients in 53.2% and 72.3% accordingly. The most common somatic comorbidities in SE group were chronic ENT diseases (20.2%), GIT pathology (20.2%), ANS disorders (7.4%), urological (6.4%) and skin and joints diseases (3.2%). In patients with IE the most frequent pathology was endocrine one (especially menstrual disorders in females) 15.8%, ENT (13.2%) and GIT diseases (7.9%) as well as migraine (7.9%). Females with IE have higher frequencies of menstrual disturbances and polycystic ovaries than women with SE (t= )1.99, p 0.05), which may be explained by usage of valproates. Women with SE have higher incidence of other somatic comorbidities (t=)2.61, p 005). Conclusion: A high percentage of patients with epilepsy have somatic comorbidity, which should be taken into account while selecting an appropriate AED treatment.

p280 EPILEPSY ASSOCIATED WITH CEREBROTENDINOUS XANTHOMATOSIS SUCCESFULLY TREATED BY CHENODEOXYCHOLIC ACID P. Vrielynck*, A. Marchese, D. Roland, F. Linard, S. Andries, S. Ghariani, and K. Van Rijckevorsel *Centre Neurologique William Lennox, Ottignies, Belgium; Centre Neurologique William Lennox, Reference Center for Refractory Epilepsy, Universit Catholique de Louvain, Ottignies, Belgium; and Institut de Pathologie et de Gntique, Gosselies, Belgium
Purpose: Cerebrotendinous xanthomatosis (CTX) is a rare autosomic recessive metabolic disease causing cholesterol and cholestanol accumulation in multiple tissues. Clinical phenotype is variable, includes progressive neuropsychiatric deterioration. Epilepsy could occur in up to 50% of patients. Chenodeoxycholic acid (CDCA) may lead to clinical improvement. Here we describe electro-clinical evolution of epilepsy associated with CTX in a young male patient . Method: The patient was seen for the first time at our clinic at 16 yearold. He presented with mental retardation, behavioral disturbance, ataxia, peripheral neuropathy, bilateral cataract and epilepsy. MRI showed multifocal lesions of white matter. Cholestanol elevation in blood and CYP27A2 homozygous mutation (c. 1263 + 1 G>A) were found, establishing diagnosis of CTX. 24 hour EEG was performed before and after CDCA introduction. Result: Between 6 and 14 months, the patient had frequent bilateral myoclonia leading initially to diagnosis of benign myoclonic epilepsy, with good response to valproate. At 12 years, different seizures types occurred: myoclonia, generalized tonic-clonic and drop attacks. EEG showed diffuse slowing of background activity and diffuse polyspikes during wake and sleep, sometimes associated with myoclonia. Seizures became resistant to lamotrigine, levetiracetam and topiramate. CDCA was introduced at 17 years. A few months later, neuropsychiatric status improved, myoclonia and tonic-clonic seizures disappeared and frequency of drop attacks decreased to less than one episode per month. Three years later, improvement persists. Epileptiform discharges have disappeared on wake and sleep EEG . Conclusion: CTX is a rare cause of generalized symptomatic epilepsy. Early diagnosis and treatment may improve neurological status and epilepsy.

Purpose: Evaluating if intravenous (IV) treatment with rt-PA influences in appearance of symptomatic epileptic seizures after acute cerebral infarct.
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83 Abstracts
p281 EPILEPSY IN PATIENTS WITH TUBEROUS SCLEROSIS COMPLEX S. T. Ristic*, D. T. Ristic, I. Marinkovic, and G. Djordjevic* *Clinical Centre of Nis, Nis, Serbia; Institutae of Pulmonary Disaeses, Nis, Serbia; and Medical Faculty of Nis, Nis, Serbia
Purpose: Tuberous sclerosis complex (TSC) is frequently associated with refractory seizures and development delay in children. Our purpose is to analyse epilepsy, AEDs (antiepileptic drags) therapy and cognitive development in adult patinets with TSC. Method: We revised data of 3 patients with TSC (diagnostic criteria revised by Gomez, 1999), with respect to the onset, type of epilepsy, neuroimaging, cognitive and mental alteration (using the Griffiths Mental Development Scales, 1996. god. Revison), response to antiepileptic therapy. Result: First patient is a 47 year old women, with typical skin abnormalities: hypomelanotics macules (more than three), shagreen patch, nontraumatic peringual fibromas and typical three types of brain tumors: cortical tubers, subependymal nodules and subependymal giant- cell astrocitomas. She has low cognitive potentials and refractori partial epilepsy with secondary generalisation. Second patient is 25 year old man, with litle skin abnormalitis (hypomelanotics macules and periungual fibromas), typical brain tumors (cortical tubers, subependymal giant-cell astrocitomas), low cognitive potencials end refractori partial epilepsy without secondary generalisation. Third patient is 51 year old women with facial angiofibromas and typical three types of brain tumors (cortical tubers, subependymal nodules and subependymal giant- cell astrocitomas), low cognitive potentials and refractori partial epilepsy with secondary generalisation. Conclusion: We discussed clinical caracteristic, diagnostic and therapeutic diferences. All patients have multiple lesions. Epilepsy began as partial seizures with secondary generalisation in 2 patients and one patient had complex partial seizures. All patients have global intelectual impairmant. One patient with monotherapy is seizure free while 2 patients with polytherapy have a reduction of seizure frequenty and intensity. Conclusion: MTLE may be a characteristic manifestation of NPSLE. Most previous reports indicate that generalized seizures occurs often epilepsy in SLE, and a few reports indicate that partial or focal seizures are frequent. However it is possible that most of generalized seizures in SLE reported before could in fact be focal epilepsy with secondarily generalized seizures. MTLE is therefore an important differential diagnosis in NPSLE patients with seizures.

Semiology, Aetiology and classification 7 Monday, 01 October 2012

Purpose: To evaluate the inter-observer reliability of the definition of drugresistant epilepsy provided by the International League Against Epilepsy (ILAE). Method: We randomly selected ninety-seven charts from 700 available from the epilepsy clinic of the Royal University Hospital in the province of Saskatchewan, Canada (1 million population). Two independent chart reviewers underwent training regarding the four definitions of intractable epilepsy used in this study. Both individuals performed a small pilot with 10 charts. None of the reviewers knew the patients and the evolution of the cases. We used the definition of drug-resistant epilepsy published by Kwan and Brodie, Berg, Camfield and the one provided by the ILAE. The reviewers abstracted demographic data, diagnostic of epilepsy, classification, evolution and medications. After the extraction of the necessary clinical information the four definitions were applied. Charts were reviewed with less than two months difference between reviewers to avoid misclassifications of patients over the time. Kappa was used to compare the agreement between observers. Results: The kappa for the Berg's definition was 0.56 (moderate), for the Kwan and Brodie's definition was 0.58 (moderate), for the Camfield's definition 0.69 (substantial) and for the definition of the ILAE was 0.77 (substantial). Other analysis will be shown in the meeting. Conclusion: The definition of drug-resistant epilepsy provided by the ILAE showed the best agreement between observers. Both observers considered that the definition of the ILAE was more complex to extract than the other three definitions due to the need of more information.

p282 MESIAL TEMPORAL LOBE EPILEPSY AS A NEUROPSYCHIATRIC SYNDROME OF SYSTEMIC LUPUS ERYTHEMATOSUS T. Toyota, N. Akamatsu, A. Tanaka, T. Shouzaki, and S. Tsuji University of Occupational and Environmental Health School of Medicine, Kitakyushu, Japan
Purpose: Different types of seizures are grouped together without distinction from epilepsy in the standard nomenclature and case definitions for neuropsychiatric syndromes of systemic lupus erythematosus (NPSLE) which has developed by the American College of Rheumatology. We aimed to investigate the types of seizures and epilepsy associated with systemic lupus erythematosus (SLE). Method: We searched the medical records at a tertiary referral center to identify a cohort of epilepsy patients with SLE who were treated between January 2000 and August 2011. We analyzed the clinical and immunological profile of these patients, their seizure and epilepsy classifications, electroencephalography and MRI assessments, and the treatment administered for epilepsy and SLE. Result: Seventeen patients with SLE and epilepsy were identified. Seven patients had mesial temporal lobe epilepsy (MTLE), 8 had epilepsy secondary to stroke, and 2 had generalized epilepsy. Of the 7 patients with MTLE, temporal spikes were noted in all patients on EEG and, MRI findings suggesting hippocampal sclerosis was noted in 4. Clobazam and levetiracetam were effective in treating 3 patients, and 1 underwent amygdalahippocampectomy.

p284 EPILEPSY AMONG THE STUDENTS OF ANAKKALE ONSEKIZ MART UNIVERSITY H. I. Ozisik Karaman, C. Bakar, and Y. Degirmenci Canakkale Onsekiz Mart Universitesi, Canakkale, Turkey
Purpose: Aim of this study was to investigate the frequency epilepsy among the students of Canakkale Onsekiz Mart University. Method: This sectional epidemiological study was performed on 4762 of the 19988 Canakkale Onsekz Mart University students in 20072008 education period. Participants who answered epilepsy to the question Do you have any disease disgnosed by a doctor? in a questionnaire including 4 subgroups were detected. Data were transferred to Epi-Info Version 6.0 statistics program and controlled data were analyzed in SPSS 15.0 statistics program.
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84 Abstracts
Result: Fifty three point one percent of the students were female, 46.9% were male. Mean age was 20.4 2.1 years. Twelve (0.3%) students had epilepsy diagnosis. Among these, 66.7% were female (n = 8), 33.3% (n = 4) were male and the mean age was 20.8 1.8 years. Conclusion: In our study, epilepsy was detected in 0.3% of the students (n = 12). Conclusion: We didn t encountered any data for this age group in our literature review for epilepsy which has a variable frequency for age and counttries. Thus, we considered that it would be epidemiologically significant to share the results of our cross sectional study. deities such as Apollo the physician or the supreme Egyptian god Ammon (the occult). Greek and Roman deities and their artistic representation date indeed back to Ancient Egyptian times. Depicted with a rams horn, Ammon was adopted by the Greeks as Zeus and later by the Romans as Jupiter. A transition that can be found in Greek coinage devoted to Alexander the Great as well as in provincial Roman coins struck under Claudius. Result: Inspired by the Renaissance school of Padua French anatomists continued to recover gods and myths of Classical Antiquity during the Enlightenment, renaming brain structures like the curve shaped inner portion of the temporal lobe as Cornu Ammonis. Among the most remarkable contemporary neuroscientists who studied this hidden part of the brain outstands Cajal and his disciple Lorente de N, who described the tri-synaptic circuit and the different CA (Cornu Ammonis) fields within. CA1 is also known as Sommers sector to acknowledge the latter description of mesial temporal sclerosis in temporal lobe epilepsy. Conclusion: Ancient Greek and Roman coinage illustrate the role that myths and gods of Classical Antiquity keep playing in modern neurology.

Purpose: We conducted a survey in order to determine the level of knowledge that parents of children with epilepsy have about epilepsy: what the epilepsy is for parents, we wanted to assess if they know how epilepsy's diagnosis is made. This study aimed to know the endpoints of seizure's severity, the seizure's trigger, and the concerns during seizure for parents. This study also aimed to highlight the impact of epilepsy in lifestyle of children and their parents. Method: We conducted a qualitative survey, based on semi-structured interviews with parents of children with epilepsy between April and November 2010 in paediatric neurology department in 4 French university hospitals: Amiens, Marseilles, Nancy and Robert Debr Hospital (Paris). Physicians conducted all the interviews. Parents of children with epilepsy were interviewed: 34 relatives aged 0 to 6 years, 38 relatives aged 7 to 12 years and 34 relatives aged more than 12. In total 106 interviews were conducted. Result: This study allows assessing the knowledge and believes of parents of children and adolescents with epilepsy and showed that knowledge of epilepsy among parents was generally limited. On average 34% of parents were unaware of their children's cause of epilepsy. Regarding to the endpoints of seizure's severity, the main criteria for all parents is the duration of the seizure. The anti epileptic drugs have a positive image to parents; they are with psychological support and lifestyle the three main points of their child's treatment. Parents confirm that epilepsy has a strong impact on their child's lifestyle. Conclusion: So many patients, parents of children with epilepsy are not well informed about their disorder. There is slightly a need for educational intervention to optimize self-management strategies. An understanding of preseizure activity from the patients and carers perspective has great utility if the information can be combined with more objective data to identify gaps in patients and carers knowledge, which can then be used to develop education and intervention programs. Parents are reassured by a medical team that treats the whole child and not just epilepsy.

p287 AUDIT OF LOCAL NEUROPATHOLOGY PRACTICE IN SUDEP AUTOPSIES M. Thom*, J. Liu*, J. W. Sander, and S. M. Sisodiya *UCL, Institute of Neurology, London, UK; Heemstede, Netherlands; and UCL Institute of Neurology, London, UK
Purpose: There is an urgent need to understand the underlying mechanisms of sudden and unexpected death in epilepsy (SUDEP). Research based on post mortem (PM) brain collections may identify novel pathological and molecular mechanisms. This necessitates collection of a sufficient numbers of adequately sampled cases with complete clinical and post mortem reports. Method: We audited all epilepsy PMs at our centre for the completeness of data and regional brain sampling. We re-classified SUDEP cases according to revised definitions [Epilepsia 2011]. Questionnaires were also sent to local general histopathologists (HP) regarding current practice in epilepsy related deaths. Result: We identified 62 SUDEP PMs (from 1991 to 2011), the majority referred cases for neuropathology examination. The median age at death was 24 years (range 279 years); 38 in males. The few cases with inadequate regional brain sampling were those where the whole brain had not been fixed. Neuropathological changes were identified in the majority of cases, hippocampal sclerosis the commonest finding in 25. Cases were re-classified as possible SUDEP where full PM report was lacking or contributing cause of death identified. Reponses from HPs indicated that of those that conduct PMs, 70% virtually never retain the whole brain in epilepsy related deaths. Conclusion: Systematic sampling in SUDEP brain demonstrates frequent neuropathological abnormalities and provides a useful research resource. We highlight the importance of complete PM reports for correct classification SUDEP and the need to increase awareness among HPs of the value of a complete neuropathological examination.

p286 ON THE ORIGIN OF CORNU AMMONIS (AMMON'S HORN) I. Iniesta The Walton Centre NHS Foundation Trust, Liverpool, UK
Purpose: To investigate the origin of the term Cornu Ammonis (Ammons horn), introduction in medical literature and current meaning. Method: As primary historical sources, Greek and Roman coins are essential archaeological remains that inform about the myths and gods of Classical Antiquity, from the arrival at Rome of a snake shaped god Aesculapius to save the Italians from the plague to invocations of major
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85 Abstracts
Purpose: The aim was correlation of the brain lateralization and variables of cognitive P300 potentials during the usage of arms among righthanded girls. Method: 60 right-handed girls, age 2024, participated in investigation. First group: strong expressed right-hand girls; second group: moderately expressed right-hand girls; third group: right-hand learned girls. The research workers were using the "oddball paradigm with two tones:"standard and "expected-target. The subjects got instructions to press a button, as fast as they can, whenever they hear the expected tone. The response was measured with the use of the right hand (firstrecording) and left hand (second-recording). P300 evoked potentials were registered above Fz and Cz area. Result: It was shown that subjects with higher degree of dominance of the left brain hemisphere have significantly shorter latencies and higher amplitudes of P300 when the dominant hand was used, while the subjects with weak or average degree of dominance of the left brain hemisphere show no significant difference. Cognitive P300 amplitude waves are higher above central regions independently of the hand used. Also, subjects with higher degree of dominance of the left brain hemisphere had shorter RT but the difference was not statistically significant. The number of false response was higher in right-hand learned girls. Conclusion: The hemispheric dominance has influence on the eventrelated potential.

*I. Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia; and Institute of Neurology and Neuropsychology, Tbilisi, Georgia
Purpose: Epilepsy is found in 0.88% of Georgian population. Sleep disorders are common conditions that frequently coexist with epilepsy. The present study was aimed to identify insomnia and restless legs syndrome (RLS) in treated epilepsy patients (T) and newly diagnosed individuals having epilepsy (UT). Method: Among the 161 consecutive subjects admitted to the Institute of Neurology and Neuropsychology, 119 had epilepsy diagnosis treated with antiepileptic drugs (AEDs) and 42 were newly diagnosed epilepsy patients never taken AEDs before. Sleep impairment index was filled out by 84 subjects (60, T and 24, UT), group 1, and the questionnaire for the RLS was completed by 77 subjects (59, T and 18, UT), group 2. Data analysis was performed by SPSS statistical software, version 13.0. Result: Among the 161 consecutive subjects admitted to the Institute of Neurology and Neuropsychology, 119 had epilepsy diagnosis treated with antiepileptic drugs (AEDs) and 42 were newly diagnosed epilepsy patients never taken AEDs before. Sleep impairment index was filled out by 84 subjects (60, T and 24, UT), group 1, and the questionnaire for the RLS was completed by 77 subjects (59, T and 18, UT), group 2. Data analysis was performed by SPSS statistical software, version 13.0. Conclusion: These findings clearly indicated that the understanding the relationship between epilepsy and sleep disorders is important for the developing of appropriate treatment strategy for the epilepsy patient.

p289 PHARMACO-RESISTANT EPILEPSY-CASE PRESENTATION C. Panea, G. D. Vanghelie, N. Ploscutanu, and G. Cioara Emergency University Hospital Elias, Bucharest, Romania
Purpose: Drug-resistant epilepsy is defined as the persistence of seizures despite adequate antiepieleptic treatment with at least two first-line AEDs, monotheraphy or in combination, using different mechanisms of action and at maximum tolerated doses. Method: Pseudoresistance must be also taken into consideration, in which seizures persist because the underlying disorder has not been appropriately diagnosed and treated or misdiagnosis of epilepsy with other conditions that mimic epileptic seizures (vasovagal syncope, cardiac arrhythmias, metabolic disturbances, transient ischemic attacks, migraine, psychogenic seizures that are estimated to account for more than 25% of adult cases of apparently drug-resistant epilepsy). Result: We present the case of a 33 years old male, diagnosed with focal epilepsy with complex partial seizures and secondary generalization that was considered to be resistant to antiepileptic drugs, with positive family history (his brother has idiopathic primary epilepsy), cerebral imagery that revealed hippocampal asimmetry and right frontal angioma and an interictal EEG that did not allow a certain diagnosis as regarding the type of epilepsy. Ictal recordings showed an EEG ictal pattern with its onset on the left temporal and fast propagation to the right fronto-temporal with secondary generalisation. Conclusion: Possible clinical predictors of drug resistance have been identified including a high number or frequency of seizures in the early phase of the disorder and a presence of a structural cause of epilepsy, particularly hippocampal sclerosis. For this case, it is imposed to asses the benefit-risk of treatment alternatives that should also consider epilepsy surgery.

p291 NEUROAMINOACIDS STATE IN PATIENTS RECOVERING FROM TRAUMATIC BRAIN INJURY WITH CONVULSIVE SYNDROME I. I. Chernenko*, and N. Sych *Kharkiv Medical Academy of Postgraduate Education, Kharkiv, Ukraine; and Institution, City, Russian Federation
Purpose: The aim of work was to study the content neuroaminoacids (NAC) in whey of blood patients with traumatic brain injury (TBI) with a convulsive syndrome. Method: Material and methods. We examined 42 patients with TBI at the age of 23 to 65 years. The level of NAC was determined in the first days after TBI received. The first group consisted of 20 persons moderate TBI with convulsive syndrome, mean age 53,39 0,42 years, the second 22 people with mild TBI with a convulsive syndrome, mean age 52,71 0,49 years. The groups were comparable in age, sex. Result: The results. The study revealed that patients with mild TBI level of excitatory NAC (glutamic 1,145 0,24 mg, aspartic 0,228 0,05 mg) were significantly higher than in patients with moderate TBI with convulsive syndrome (0,805 0,07 mg and 0,164 0,02 mg, respectively), p < 0,05. At the same time, there was a trend to an increase in brake NAC in patients with mild TBI with a convulsive syndrome compared with patients with moderate TBI with a convulsive syndrome (glycine 1,427 0,13 mg and 1,345 0,19 mg respectively, proline 1,556 0,24 mg is the 1,211 0,17 mg, respectively), p > 0,05. Conclusions: Thus, patients with mild TBI with a convulsive syndrome marked by an imbalance of NAC: NAC increase in excitatory (glutamate, aspartate) and a tendency to increase the level of brake NAC (glycine, proline) compared with patients with mild TBI with convulsive syndrome.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x


86 Abstracts
p292 EPILEPSY AND NEUROCYSTICERCOSIS IN NORTH WEST CAMEROON: A SEROLOGICAL STUDY A. J. Akeneck, C. O. Snead, I. E. Elliott, N. K. Alfred, A. S. Angwafor, L. C. Cockburn, I. T. Takougang, and M. L. Lou Association of Orphans and the Disabled ASODI Cameroon, Mankon Bamenda, Cameroon
Purpose: The prevalence of epilepsy in Cameroon is higher than that of the industrialized?world. The prevalence of epilepsy appears to be especially high in the Momo Division of the Northwest Province of Cameroon. Because neurocysticercosis is a major cause of epilepsy in developing countries, we sought to test the hypothesis that those patients in Momo who have epilepsy have a higher percentage of seropositivity to Taenia solium than a matched control population. A case control study was conducted in the Momo sub-division of Ngie which has nineteen villages. Epilepsy patients were recruited from the epilepsy clinics in Ngie and control subjects were randomly selected from members of the Ngie villages. An adapted form of a previously validated screening questionnaire was applied by trained field workers to identify potential cases of epileptic seizures to be included in the study. Blood samples were taken from all consenting individuals by finger prick, stored in StabilZyme Select, and assayed for antibodies to Taenia soleum as described. Method: This study was carried out under the ethical precepts found in the World Medical Association Declaration of Helsinki (http:// Ethics approval was obtained from the Research Ethics Board (REB) of the Hospital for Sick Children, Toronto, Canada, the National Ethics Committee, Cameroon, and the local district ethics committee, Alpha Royal Clinic REB. Community consent was first obtained by having medical health volunteers explain the goal of the study to village traditional and administrative and health authorities. Community information sessions were then conducted, the purpose of which was to allow individuals to discuss their questions and concerns. Village coordinators, who helped study participants to complete the questionnaires, were trained on how to obtain informed consent. In addition, the coordinators determined who could read. Ngie language is not written. Therefore, to make things clear a translated version of the informed consent was made on an audiotape and played where necessary. Following these community meetings, potential subjects and controls were provided further information and if they agreed to participate, consent for the administration of the questionnaire and blood sampling was obtained. Result: We accrued 249 patients with epilepsy and 245 age-matched controls. The number of patients with epilepsy who participated in this study represent about 75% of the total number of seizure patients in Ngie where the population is around 40,000 inhabitants. The mean age of control subjects was 17.5 years and that of the seizure population 18.8 years (P > 0.1). There were 53% male and 47% female in the seizure group and 57% male and 43% female in the control group (P > 0.1). Seizure onset was at 11.64 yrs. Sixty-eight percent of patients had generalized convulsive seizures with 25% having localization-related epilepsy with secondary generalized seizures. There was no significant difference between the control and seizure populations in seropositivity to Taenia soleum which was 4.9% in the control group vs. 5% in the seizure group. These data demonstrate that those patients in the Ngie sub-division of Momo who have epilepsy do not have a higher percentage of seropositivity to Taenia solium than a matched control population and make it highly unlikely that neurocysticercosis plays a causative role in the increased prevalence of epilepsy in the Momo Division of the Northwest Province of Cameroon. Supported in part by The Bloorview Children's Hospital Foundation. Conclusion: This data does not support the hypothesis that those individuals in Ngie sub division of Momo Division who have epilepsy have a higher percentage of teania solium than a matched contro population. The data makes it highly unlikely that neurocysticercosis plays a causative role in the increased prevalence of epilepsy in the sub region. These results and preveiousely published results suggest that the high prevalence of epilepsy reported in some areas in Cameroon could be attributed to a complex yet to be elucidated, interplay of several factors.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

SEMIOLOGY, AETIOLOGY AND CLASSIFICATION 8 MONDAY, 01 OCTOBER 2012 p293 HEALTH-RELATED QUALITY OF LIFE OF PATIENTS IN THE PATIENTSLIKEME EPILEPSY COMMUNITY C. De La Loge*, S. Dimova, K. Mueller, T. Durgin, M. Massagli, and P. Wicks *UCB Pharma, Brussels, Belgium; UCB Pharma SA, Brussels, Belgium; UCB Pharma Monheim, Monheim, Germany; UCB Pharma SA, Smyrna, GA, USA; and PatientsLikeMe Inc, Cambridge, MA, USA
Purpose: To describe health-related quality of life (HRQoL) of members of the PatientsLikeMe Epilepsy Community and identify predictors of poor HRQoL. Method: Analyses were based on patient-completed information: sociodemographic and disease characteristics, treatments, symptoms, seizure occurrence, Quality of Life in Epilepsy (QOLIE-31/P) and Hospital Anxiety and Depression Scale (HADS). Result: By May 2011, 1025 patients had completed the QOLIE-31/P and HADS and were included in this analysis (mean age 37.5 years; 72.7% female; mean epilepsy duration from diagnosis 17.5 years). HRQoL was highly correlated to HADS Anxiety and Depression scores. Poor HRQoL was more likely in patients reporting (Odds Ratio [95% Confidence Interval]; multivariate logistic regression): i) moderate/ severe problems concentrating (3.19 [2.005.08]), depression (2.61 [1.773.85]), memory problems (2.04 [1.293.24]), fatigue (1.75 [1.12 2.71]), anxiety (1.49 [1.002.22]); ii) severe side effects (2.34 [1.39 3.92]); iii) at least one tonic-clonic seizure during the 4 weeks before QOLIE-31/P completion (2.72 [1.654.50]); iv) age 2550 years (1.77 [1.013.11] vs age 025 years) and v) shorter epilepsy duration (1 year 2.25 [1.234.13]; 110 years 1.70 [1.122.58]; both vs >10 years). Patients on polytherapy with newer antiepileptic drugs (AEDs) were less likely to report poor HRQoL than patients on polytherapy with older AEDs (0.29 [0.110.74]). Conclusion: These analyses indicate that moderate/severe problems concentrating, depression, and the occurrence of generalized tonic-clonic seizures and severe side effects were the most predictive factors of poor HRQoL in the PatientsLikeMe Epilepsy Community. These results suggest that a holistic approach beyond seizure control should be considered when treating people with epilepsy.

p294 EVALUATING EPILEPTIC POPULATION AND ITS COST IN THE SOUTH OF SPAIN G. Garcia Martin, M. I. Chamorro Muoz, M. Romero Acebal, and F. Perez Errazquin Virgen de la Victoria Hospital, Malaaga, Spain
Purpose: Epilepsy is a common disorder around the world and a big effort in order to know the features of the population with this illnesss is being done nowadays. Although there is quite information of some parts of Europe, information from the south west is not enough. Moreover knowing the cost of the illness is really interesting in the current economic situation. The purpose weas to evaluate the features of people with epilepsy in Malaga (Spain) and the cost of visiting this population in a General Hospital. Method: To describe the features of all the patients with active epilepsy or epilepsy on treatment visited in Virgen de la Victoria Hospital in Malaga, in one of the Epilepsy Offices. To calculate the cost of epilepsy taking into account number of visits, tests made and the consumption of drugs in one year but not emergency assistance.

87 Abstracts
Result: 515 patients were selected of a total of 2282 patients visited in all the Epilepsy Offices. Features of patients and the costs of illness are presented. We compare our results with those from other studies in Europe. Conclusion: The features of the epileptic population in Malaga are similar to those from other parts of Europe. The cost of epilepsy in our Hospital is quite similar to that of other studies in Europe. The main cost in Hospitla for this population depends on the nmumber of visits to the neurologist and on the chronic treatment. epilepsy; individual epilepsy management; and aspects of epilepsy that matter most to people with epilepsy. During July-October 2011, 513 people with epilepsy (63.8% female; ages ranging from <16 to >65 years) from 29 countries completed the survey. All survey responses were anonymised and collated in a central database for analysis. Result: Over 60% of respondents considered their seizures to be sufficiently controlled, but >40% still had seizures at least every month and >40% would have changed medication to improve seizure control. Approximately 70% of respondents suffered medication side effects and >30% would have changed medication to reduce side effects; however, almost 25% had never proactively discussed side effects with their doctor/nurse. Different side effects mattered more/less to different respondents (e.g. weight gain tended to matter more to females than males). Approximately 30% of respondents admitted missing medication at least once a month. Conclusion: The survey provides valuable insights into the real challenges and needs of people with epilepsy and may play a part in shaping future management strategies. Supported by Eisai.

p295 PSEUDO-REFRACTORY EPILEPSY: FOLLOW UP 105 PPATIENTS G. Kutlu, A. Erdal, Y. Bier Gmceli, and L. E. Inan Ministry of Health, Ankara Research and Training Hospital, Ankara, Turkey
Purpose: Pseudo-Refractory epilepsy is defined as seizures inadequately treated due to incorrect diagnosis, use of incorrect and/or low dose antiepileptic drug (AED) and poor compliance of patients. The aim of this was to investigate the patients with pseudo-refractory epilepsy. Method: The files of two thousand nine hundred twenty patients were reviewed by the same neurologist and the patients with pseudo-refractory epilepsy were eliminated. The patients who had not enough control of seizures despite the two different AED treatment before follow up in our department and had no seizure at least one year after the revision of the diagnosis and/or treatment of epilepsy, were accepted as pseudo-refractory. Demographic data, medical and epilepsy history, electroencephalography (routine and/or induction of seizure by using normal saline or self induction), home video and neuro-imaging findings were examined. Result: One hundred five patients were included in this study. The mean age was 29 11.53. Seventy-four patients (70.5%) was female, the remaining 31 patients were male. Incorrect diagnosis of epilepsy was observed in 57 patients (forty seven non-epileptic psychogenic seizure, seven syncope, two sleep disorder, one hypoglycemia). Epilepsy classification and treatment error was present in eighteen patients. Forty two patients had poor compliance of treatment and inappropriate life style. Twelve patients had more than one reason for pseudo-resistance (together with classification and/or treatment error, and poor compliance). Conclusion: Pseudo-refractory patients are still a big problem in our clinical practice. Differentiation of pseudo-refractory and true refractory epilepsy is so important for avoiding unnecessary treatment approach and future management of true refractory epilepsy.

p297 SOMATIC CO-MORBIDITIES ARE A MAJOR ISSUE IN PEOPLE WITH EPILEPSY J. Novy, G. Bell, S. M. Sisodiya, and J. W. Sander UCL Institute of Neurology, London, UK
Purpose: People with epilepsy seem to have more concomitant medical conditions than the general population. Co-morbid conditions may be a factor in the increased risk of premature death seen in people with epilepsy, including those in remission. While there are several studies exploring epidemiological patterns of psychiatric co-morbidities in epilepsy, less is known about somatic co-morbidities. We aimed to explore the epidemiology of somatic co-morbidities in people with epilepsy. Method: We collected clinical, demographic and somatic co-morbidity data in >2000 consecutive people with drug-resistant epilepsy assessed at a tertiary centre and in 1350 patients with epilepsy in the community. Underlying causes of epilepsy were not taken as co-morbidities, neither were symptoms of the cause. Result: Somatic co-morbidities were found in 48% of people with drugresistant epilepsy and in 35% in the community (p < 0.0001). People with drug-resistant epilepsy were younger (median age 35) than those in the community (median age 45). Somatic co-morbidities were more frequent than psychiatric ones (25% in people with drug-resistant epilepsy, 10% in the community). Preliminary analysis suggests that older age, older age at epilepsy onset and no identifiable cause may be independent predictors of a higher burden of co-morbidities. Conclusion: This seems to suggest that epilepsy itself influences the occurrence of somatic co-morbidities. Somatic co-morbidities should not be overlooked as they appear as frequent as psychiatric co-morbidities. The reasons for this are not entirely clear as this stage but common genetic predisposition cannot be discounted. Further studies are urgently warranted.

p296 WHAT REALLY MATTERS TO PEOPLE WITH EPILEPSY? RESULTS FROM AN INTERNATIONAL PATIENT SURVEY J. A. Cramer*, S. Dupont, M. Goodwin, and E. Trinka *Yale University School of Medicine, Houston, TX, USA; PitiSalptrire Hospital, Paris, France; Northampton General Hospital NHS Trust, Nothampton, UK; and Paracelsus Medical University, Salzburg, Austria
Purpose: To conduct an international survey amongst people with epilepsy, in order to define issues of importance in their daily lives, correlated with duration of epilepsy, age, as well as other characteristics. Method: A web-based survey, translated into 12 languages, was distributed through the International Bureau for Epilepsy member association websites and via email. The predominantly multiple-choice questionnaire focused primarily on personal experiences of the impact of

p298 DEVELOPMENT AND PILOT OF A QUESTIONNAIRE FOR REPORTING EPILEPSY-RELATED DEATHS L. Flores*, K. Osland, J. Hanna, and L. Nashef* *King's College Hospital, London, UK; and Epilepsy Bereaved, Oxfordshire, UK
Purpose: Aim: To assess the applicability of a detailed questionnaire administered by a lay person to bereaved relatives on sudden death in epilepsy.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

88 Abstracts
Method: After basic training, the questionnaire, based on a previously used tool, was administered through telephone interviews carried out by two workers from Epilepsy Bereaved with relatives of deceased patients. Result: The survey obtained complete and detailed data on most items included. SUDEP was stated as the cause of death in 17 of 31 transcribed interviews, three with reportedly mild epilepsy, four with relatively recent onset of seizures and three witnessed cases. Three relatives reported having received some information about SUDEP from the medical team. More than half the families were not contacted by the medical team after death and counselling was offered to 15 only. Conclusion: The applicability of administering this questionnaire by a lay person familiar with the field was demonstrated. Data obtained was assessed as high quality with limited modifications to the questionnaire needed. This tool may be useful for a SUDEP register. The increase in death certificates listing SUDEP in 54.8% of cases compared to 3.8% (1/ 26) in an older study of circumstances of death in SUDEP carried out 16 years ago suggests a greater awareness by pathologists and coroners. On the other hand, counselling and a meeting with the treating specialist were reportedly infrequently offered.

*SEIN-Epilepsy Institute in the Netherlands Foundation, Heemstede, The Netherlands; Institute of Neurology, London, UK; and UCL Institute of Neurology, London, UK
Purpose: Postictal generalized EEG suppression (PGES) seems to be a pathophysiological hallmark in the ictal recordings of sudden unexpected death in epilepsy (SUDEP). It has recently been suggested that the presence and duration of PGES might be predictors of SUDEP risk [1]. Little is still known about its aetiology. Method: A retrospective case-control study was conducted in 50 people with convulsive seizures (CS) registered on digital video-EEG. Per individual one CS was reviewed for the presence and duration of PGES by two independent assessors: 37 (74%) patients showed PGES and 13 (26%) did not. Pre- and postictal heart rate (HR) and frequency domain measures of heart rate variability (HRV) including the ratio of low versus high frequency power were analyzed . The relation between PGES and peri-ictal autonomic changes was evaluated, as well as its association with several clinical variables. Result: PGES was neither associated with peri-ictal HR (mean HR difference between PGES+ and PGES- seizures: -5 bpm, 95% CI -13 to +3 bpm) nor HRV change. There was no relation between duration of the tonic-clonic phase of the seizure and PGES. Patients with PGES were more likely to be asleep prior to seizure onset (OR 4.7, 95% CI 1.218.3) and had a higher age of onset (median age; 15 vs. 5 years). Conclusion: PGES was not associated with substantial changes in measures of cardiac autonomic instability but more prevalent in CS arising from sleep. PGES might be an expression of excessive neuronal inhibition acting as a seizure termination mechanism. Reference: 1.Lhatoo SD, Faulkner HJ, Dembny K, Trippick K, Johnson C, Bird JM. An electroclinical case-control study of sudden unexpected death in epilepsy. Ann Neurol 2010; 68(6): 787796.

p299 PLACE OF VIDEO-EEG MONITORING IN DIAGNOSIS AND MANAGEMENT OF IDIOPATHIC GENERALIZED EPILEPSY L. Iuhtimovschi*, S. Groppa*, and A. Bunduchi *State Medical and Pharmaceutical University Nicolae Testemitanu, Chisinau, Moldova; and Medical Center Excellence, Chisinau, Moldova
Purpose: To appreciate electro-clinical correlations in patients with active focal epilepsy treated unsuccessfully with Carbamazepine. Method: Our study included 32 patients (21 women and 11 men), age range 1854, diagnosed with epilepsy 1,5 to 30 years ago, previously examined only by routine EEG (1015 minutes). All patients were evaluated by video-EEG monitoring 3 to 6 hours. Result: 13 patients had EEG electro-clinical patterns petit mal typical for absence epilepsy. 5 patients revealed electro-clinical patterns of myoclonic seizures. 14 patients presented subclinical discharges of typical generalized spike-wave, poly-spike-wave, and sharp wave-slow wave activity. All changes appeared on preserved general cortical activity. Accordingly patients were divided in groups: I group Absence epilepsy, II group Juvenile Myoclonic Epilepsy, III group Idiopathic Generalized epilepsy. In all patients treatment was substituted with Valproate (I, II, and III group) or Ethosuximide (I group). Video-EEG monitoring was repeated 4 month later. In 100% cases EEG revealed substantially reduced epileptiform activity. Follow-up period of 1,5 to 3 years showed clinical remission in 3 patients (I group), 2 patients (II group), and 7 patients (III group); while electro-clinical remission in 8 patients (I group), 3 patients (II group) and 5 patients (III group). Conclusion: Routine EEG investigations are insufficient for a clear diagnosis of idiopathic generalized epilepsy, because myoclonic and absence seizures are often neglected by patients and observers. When addressed to specialist patients present generalized seizures incorrectly diagnosed as secondarily generalized and treated with Carbamazepine. Video-EEG monitoring helps to establish epileptic patterns, correct diagnosis and initiate adequate treatment.

Purpose: Wavelet transformation is applied to electroencephalogram records from epileptic patients. The temporal sharpness associated with interictal spikes at different resolutions is observed and two ways for representing the multiresolution sharpness of the spikes. Method: Patient consist of 349M, 234F, ages 368 years. Clinical status: epileptic (136M, 80F: EEG with spike;47M, 40F without); clinical status: nonepileptic: (98M, 65F EEG with spike; 68M, 49F without). Numerical data were acquired with EEG dump diagnostic Biologic system at Sarjito hospital Yogyakarta etc, 20022011. The wave components were sorted out according to their amplitudes, time span between zerocrossings, and different frequencies wavelet. Result: The experimental results the spikes show consistent large outputs throughout the wavelet set, they have sharpness at several different resolutions. Utilizing the hardware and software facilities at hand, marking the starts and ends of abnormal waves could be done with +100 lV threshold. The zerocrossings and crosscorelation detection could automatically distinguished according to the 2070 ms time period for the spikes (89M, 58F),70120 ms for sharps (160M, 101F), and the existence of multiple peaks for polyphase(100M,75F). Conclusion: The research carried out so far was to find the prospect of this digital signal processing on EEG waves to support the doctors work in this field.

p300 PGES IS MORE FREQUENT IN CONVULSIVE SEIZURES ARISING FROM SLEEP R. J. Lamberts*, S. Laranjo, S. Kalitzin*, D. Velis*, I. Rocha, J. W. Sander*, and R. D. Thijs
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

89 Abstracts
p302 REFLEX MYOCLONIC EPILEPSY IN INFANCY: A MULTICENTER CLINICAL STUDY S. Matricardi*, A. Verrotti*, G. Capovilla, C. DEgidio*, R. Cusmai, A. Romeo, D. Pruna, P. Pavone**, S. Cappanera, T. Granata, G. Gobbi, P. Striano, S. Grosso***, P. Parisi, E. Franzoni, S. Striano, A. Spalice, R. Marino*, F. Vigevano, and G. Coppola *University of Chieti, Chieti, Italy; C. Poma Hospital of Mantova, Mantova, Italy; Bambino Ges Children's Hospital of Rome, Rome, Italy; Fatebenefratelli e Oftalmico Hospital of Milan, Milan, Italy; Azienda Ospedaliero Universitaria of Cagliari, Cagliari, Italy; **University of Catania, Catania, Italy; Ospedali Riuniti of Ancona, Ancona, Italy; IRCCS Foundation Neurological Institute C. Besta of Milan, Milan, Italy; Maggiore Hospital of Bologna, Bologna, Italy; Gaslini Institute, University of Genova, Genova, Italy; ***University of Siena, Siena, Italy; La Sapienza University of Rome, Rome, Italy; University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy; Federico II University of Napoli, Napoli, Italy; and University of Salerno, Salerno, Italy
Purpose: Reflex myoclonic epilepsy in infancy (RMEI) is a rare clinical entity and most of the available evidence (Ricci S et al. Epilepsia 1995;36:342348; Giovanardi Rossi P et al. Brain Dev 1997;19:473 479; Caraballo R et al. Rev Neurol 2003;36:429432), based on anecdoctal cases, are inconclusive regarding its evolution and prognosis. We describe the clinical and electroencephalographic (EEG) features and long-term cognitive outcome. Method: We enrolled 31 children from 16 neuropediatric centers in Italy, who underwent periodical clinical and video-EEG evaluation. Cognitive assessment was performed in all patients using standardized psychometric tests according to their age. Result: The age at onset ranged from 3 to 24 months of age. Seizures were characterised in all patients by symmetric myoclonic seizures (MS), triggered by sudden unexpected acoustic (38.7%) or tactile stimuli (29%) or both (29%). Photosensitivity was absent in all patients. Spontaneous attacks were reported in 32.2% of the cases. Interictal EEG was normal in all cases. Ictal EEG showed generalized high-amplitude 3 Hz polyspike and wave discharges, synchronous with brief rhythmic bursts of electromyographic activity . Patients were re-evaluated after a period of 7.2 5.6 years. The prognosis for seizure control was excellent in all cases and reflex MS disappeared spontaneously or after valproate treatment. The cognitive outcome was excellent in 90.3% of children. Conclusion: RMEI appears to be a variety of idiopathic generalized epilepsy with specific features that occurs in developmentally normal children, which should be classified as a distinct nosographic syndrome. Purpose: The conventional research method to screen for epilepsy is with a written questionnaire administered door-to-door (WQ). Although this enables comprehensive capture of undiagnosed and untreated cases, it is resource intense, insensitive to non-convulsive seizures and inefficient for large-scale recruitment for aetiologic or prognostic studies. Our aim was to field test a novel digital animation seizure-screening questionnaire that may be more suitable for community-based recruitment. Method: We developed a series of high-resolution digital animations depicting visual sequences of young people with seizures (AQ) consisting of: tonic-clonic, simple partial motor, complex partial temporal lobe, absence and myoclonic. We administered AQ to parents of primary and secondary school students and secondary school students by a specially constructed website All students underwent epilepsy specialist assessment (ESA) including EEG when indicated, to confirm the diagnosis of epilepsy. AQ was repeated after first completion, to estimate repeatability. Result: 206 AQ internet surveys were conducted (157 parental, 38 students) with all undergoing ESA: 8 screened positive with 3 confirmed cases of epileptic seizures, 2 of which were new. Both parental and student's surveys combined: sensitivity 1.00 (1.001.00), specificity 0.95 (0.920.99), Youden's Index a summary measure of sensitivity and specificity 0.95 (0.930.99). Surveying only parents improved specificity slightly without affecting sensitivity. Repeat survey (n = 62) demonstrated 100% concordance. Conclusion: Although numbers are relatively small, early results suggest that AQ may be a more effective population-screening instrument than WQ. In addition, it should greatly improve efficiency as it can readily recruit individuals and households through devices that access the internet rather than door-to-door.

p304 AN COMPETENCY FRAMEWORK FOR ADULT EPILEPSY SPECIALIST NURSES Y. Leavy*, M. Goodwin, S. Higgins, and V. Myson *Western General Hospital, Edinburgh, UK; Northampton General Hospital, Nothampton, UK; Glocestershire Royal Hospital, Gloucester, UK; and Cardiff and Vale NHS trust, Cardiff, UK
Purpose: Epilepsy affects approximately 600,000 people in the UK (UK) (Joint Epilepsy Council 2011). For over twenty years adult Epilepsy Specialist Nurses (ESNs) have been managing epilepsy and supporting people with epilepsy (PWE). However, despite this long association there are currently no guidelines for employers or stakeholders regarding the entry experience or qualifications when recruiting an adult ESN. The adult ESN competency framework attempts to address this. It also defines core competencies thought to be central to effective performance and attempts to articulate progression from a novice specialist nurse through to competent and ultimately expert specialist nurse. In practice this framework should provide practical and aspirational guidance for ESN's and for those involved in assessing their competence to practice. Method: The Adult ESN Competency Framework has been developed by a UK-wide steering group of ESNs with a variety of experience, and reviewed by academics, and researchers. Literature reviews of relevant healthcare policy, nurse training and epilepsy guidelines were undertaken. This work has been led by the Epilepsy Nurses Association (ESNA) and accredited by the Royal College of Nursing (RCN), with the support of Epilepsy Action to provide a patient perspective. Result: The competency framework consists of nine dimensions: A Knowledge of Epilepsy B Clinical Management of Epilepsy C Independent Living D Joint Working/Professional Relationships E Personal Planning and Organisation F Teaching Patients G Audit H Research I Epilepsy Surgical Management/VNS.
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Semiology, Aetiology and Classification 9 Monday, 01 October 2012


90 Abstracts
Conclusion: The adult ESN competency framework provides practical and aspirational guidance for ESN's and employers regarding entry and ongoing qualifications, experience and clinical competence. word shorthand diary Gowers kept when apprenticed to a country doctor in Essex in 18623. These discoveries have enabled the authors to offer a fuller account of Gowers early professional development and later interests, the social context within which he functioned, and his contributions to the expanding neurological understanding of his day. Conclusion: This new biography brings to a wide readership the life and work of a great medical neurologist, offering additional insights on Victorian medicine more generally; and it makes available a rich store of archival material never previously published.

p305 TREATMENT GAP OF EPILEPSY IN PAKISTAN: A POPULATION-BASED STUDY Z. Mogal, S. W. Akhtar, R. Malik, and H. Aziz National Epilepsy Centre, Jinnah Postgraduate Medical Centre, Karachi, Pakistan
Purpose: To assess any change in treatment gap status of epilepsy in Pakistan following a countrywide intensive and sustained epilepsy awareness program. Background: According to the population-based epidemiologic and knowledge, attitude and practice study of 1987, prevalence of epilepsy in Pakistan was 0.98% with a treatment gap of 86%; lack of knowledge and wrong cultural beliefs about the condition being main reasons (Aziz H et al. Epilepsia 1994;35(5):950958). Intensive and sustained countrywide epilepsy awareness through Comprehensive Epilepsy Control Programme of Pakistan is ongoing since 2001. Five years after initiation of this public awareness campaign, another population-based study was performed and treatment gap status re-assessed. We are presenting part results of this study. Method: A door-to-door population-based epidemiologic study was conducted in urban and rural areas of Sialkot in northern Pakistan. Sample collection was done by random block selection method in proportion to the population structure of the area. Questionnaire based on ICBERG protocol (same as used in 198589 study) was applied. Result: Of the 3780 people screened from 762 households, 55 (1.46%) had epilepsy. Of the 53 people with epilepsy (data on 2 is unsubstantiated), 30 (56.6%) were taking atleast one antiepileptic drug whilst 23 (43.4%) were not taking any medications at the time of survey. Conclusion: Treatment gap of epilepsy in Pakistan has decreased from 86% to 43.4% after five years of intensive epilepsy awareness campaign, countrywide. With all other variables remaining constant, an intensive and sustained public awareness campaign has been instrumental in decreasing the treatment gap.

p307 TROPONIN LEVELS AFTER SEIZURES AND RELATIONSHIP TO CARDIOVASCULAR RISK FACTORS A. Fawaz*, W. Nasreddine, S. Atweh*, J. Wazneh*, A. Rabah*, M. Arabi*, and A. Beydoun* *American Unveristy of Beirut, 2020, Lebanon; and Rafic Hariri University Hospital, Beirut, Lebanon, Beirut, Lebanon
Purpose: Troponin is a very sensitive marker of cardiac injury. Conflicting data regarding elevation of troponin level following generalized tonic clonic seizures (GTCs) have been reported. In this study we hypothesized that troponin elevation after GTCs occurs more frequently in patients with cardiovascular risk factors. Method: Consecutive patients who presented to ER over a one year period with a GTC and whose work up included troponin T level were included. Patients with cardiac symptoms at the time of admission or renal insufficiency were excluded. The frequency and risk factors for elevated troponin levels in this cohort were analyzed. Result: Fourteen patients (mean age: 54 years; range: 1987) were included. Four patients (28.6%) had an elevated troponin level (Mean = 0.06, range: 0.0350.076). Those four patients were significantly older than those with normal levels (77.5 vs. 45.5 years, P = 0.035). EKGs in these patients were normal. Of the eight patients 60 years or older, four (50%) had an elevated troponin level. The coronary heart disease score (CHD) was significantly higher in patients with high troponin compared to those with normal troponin levels (13.5 vs. 9.75, P = 0.012). Conclusion: Elevated troponin levels can occur after a GTC. The significantly higher frequency in the elderly and in patients with high CHD scores strongly suggests that this increase is mostly due to cardiac injury.

p306 WILLIAM RICHARD GOWERS 18451915: EXPLORING THE VICTORIAN BRAIN A. Scott The University of Queensland, Brisbane, Australia
Purpose: The Victorian neurologist William Richard Gowers was a clinician, researcher, writer, and teacher, whose prolific output included the two-volume Manual of Diseases of the Nervous System (1886 and1888), and numerous publications on epilepsy, culminating in The Borderland of Epilepsy (1907) (which introduced this term into the medical literature). In 1949 Macdonald Critchley wrote a biographical appreciation of Gowers in which he referred to the peculiar dificulties in gathering objective material about a man admired but not understood. Method: This more comphrehensive biography, to be published in 2012 by Oxford University Press, is by Professor Ann Scott (Gowers greatgranddaughter), and neurologists Professors Mervyn Eadie and Andrew Lees. The aim of the authors has been to draw on newly-available resources to re-examine Gowers life and his contributions to neurological science. Result: The authors uncovered important new primary sources from the Gowers family papers and other archives, including significant finds at the National Hospital, Queen Square. Scott also transcribed the 83,000Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

p308 OCCURRENCE OF ICTAL ARRHYTHMIA IS ASSOCIATED WITH A FIRST-DEGREE FAMILY HISTORY OF EPILEPSY G. O Connor, A. O Donnell, G. Mullins, E. Chaila, and N. Delanty Beaumont Hospital, Dublin, Ireland
Purpose: Seizure-induced disturbances in cardiac rhythm (known as ictal arrhythmias) are well recognised phenomena, the causes of which are unclear. To explore a possible genetic basis for this phenomenon, we sought to quantify the strength of association of ictal arrhythmia with a first-degree family history of epilepsy. Method: We identified all patients admitted to the Epilepsy Monitoring Unit in our centre between January 2005 and August 2011. For inclusion, patients had to have had definite epileptic events during the period of monitoring, and to have their details recorded on our epilepsy-specific electronic patient record. For all patients included, we recorded demographic details, family history of epilepsy, imaging findings and EEG findings, and we recorded the occurrence or not of any ictal arrhythmia. For all the specified features, we calculated the significance of the association between them and the occurrence of ictal arrhythmia.

91 Abstracts
Result: A total of 224 patients met the criteria for inclusion. Of these, 13 patients (5.8%) had an ictal arrhythmia other than sinus tachycardia. A first-degree family history of epilepsy was found to be associated with the occurrence of ictal arrhythmia (p = 0.0067). There was no statistically significant association for any of the other features studied, including hemisphere of seizure onset, extratemporal seizure focus or imaging findings. Conclusion: The association of ictal arrhythmia with a first-degree family history of epilepsy has not been demonstrated previously, and suggests an underlying genetic basis for this phenomenon. Further research into the underlying genetic mechanism of ictal arrhythmia is warranted. radiation therapy and chemotherapy at age 1 year. Her complex partial seizure started at age 19 years. She was treated with various medications including valproate (VPA) (as monotherapy for 1 year) without effects nor relevant side effects. We gave her LTG up to 200 mg/day without seizure control. We added VPA 200 mg/day, then she became seizure free. Shortly after addition of VPA, normocytic normochromic anemia emerged and rapidly progressed to reticulocyte count 0&. Leukocytopenia and thrombocytopenia were not observed. Drug-induced acute PRCA was suspected and VPA was discontinued, but anemia still progressed to hemoglobin (Hb) 5.7 g/ml. Transfusion of two units of packed red cells was needed. As reticulocyte count still remained 1& on 20th day after cessation of VPA, LTG was discontinued. Soon after discontinuation of LTG, reticulocyte count increased dramatically up to 116&, and subsequently anemia improved. Two months after discontinuation of LTG, RBC and Hb were normalized. Conclusion: To our knowledge, this is the second case report of PRCA following LTG treatment in a patient without known hematological disorder. Monitoring blood count is highly recommended after initiation of LTG treatment.

p309 ASSOCIATION BETWEEN EPILEPSY AND CYSTICERCOSIS AND TOXOCARIASIS: A POPULATION-BASED CASECONTROL STUDY IN AN URBAN SLUM IN INDIA G. Singh, J. Bawa, D. Chinna, A. Chaudhary, K. Saggar, M. Modi, and J. W. Sander Dayanand Medical College and Hospital, Ludhiana, India
Purpose: To study the association between epilepsy and exposure to the parasites, Toxocara canis and Taenia solium. Method: A door-to-door community-based survey of epilepsy was carried out in an urban slum area with a population of 15,750. People with active epilepsy were subjected to detailed epileptological assessments, sleep and awake EEGs and high-strength (1.5 Tesla) epilepsy protocol magnetic resonance imaging. For every case, one age- and gendermatched control was selected from the same community. Serological evaluation was carried out for both cases and controls to detect antibodies against T. canis and T. solium. Result: The crude prevalence of active epilepsy was 7.2/1000. 114 people with confirmed active epilepsy (45 females; 69 males) and 114 controls were enrolled. The prevalence of antibodies to T. canis was similar in people with active epilepsy (4.4%, 5 of 114 people) and in controls (6.1%, 7 of 114 people). The prevalence of antibodies to T. solium was 23.7% (27 out of 114 cases) in people with active epilepsy, which was significantly higher than the prevalence in controls (13 out of 114 cases; 11.4%) (P = 0.02). After adjusting for potential confounding factors, conditional (fixed-effects) logistic regression provided an odds ratio of 2.55 (95% CI, 1.14 to 6.28). Nineteen people with active epilepsy demonstrated evidence of neurocysticercosis on MRI, (solitary cysticercus granuloma 7, solitary calcification 7 and multiple mixed stages 5). Conclusion: Although significant association between T. solium exposure and epilepsy was observed but no such association was seen between T. canis and epilepsy.

p311 THE ROLE OF MINOCYCLINE ON DEVELOPMENT OF AMYGDALA KINDLING IN WISTAR RATS S. M. Beheshti Nasr, and M. Mohammad-Zadeh Sabzevar University of Medical Sciences, Sabzevar, Iran
Purpose: Minocycline is a derivative of tetracycline that has antiinflammatory, antiappoptic and antioxidant properties. Minocycline readily crosses the blood brain barrier and attenuates inflammation, it also affect on neural cell activity. For example it has been shown minocycline inhibit microglia activation and reduce astrocytic reactivation addition it has neuroprotective effects. As far as there is interaction between cell death and seizure, the aim of this study is examination of the role of minocycline on amygdala kindled seizures in rat. Method: In this experimental study, three group animals (21 rats), after sterotaxic surgery and 1 week recovery period, rats received kindling stimulations (twice daily at 6 hour interval). Group 1(n = 7) animals received daily kindling stimulations. Group 2 (n = 7) and 3(n = 7) 60 min before kindling stimulation received saline (1 ml/kg) and minocycline (25 mg/kg) respectively. Cumulative Afterdischarge duration (ADD), Cumulative Seizure duration (SD) and Seizure Stage (SS) were recorded and compared relative to control group. Data analyzed with Statistica software (Ver 5.5). Repeated measure ANOVA and Post hoc tukey test for comparison within groups and student's t-test was used for comparing two groups of data. A P-value of less than 0.05 was considered to represent a significant difference. Result: In group 3 intraperitoneal administration of minocycline for 10 days reduced cumulative ADD [F(18, 216)=3.5, p < 0.001] and cumulative SD [F(19, 228)=3.8, p < 0.001] significantly relative to control group (group 2). It also significantly increased the mean number of stimulations to achieve to seizure stages of 3 (P < 0.05), and 5 (P < 0.001). Conclusion: According to obtained results it may be concluded that application of minocycline have anticonvulsant effect on kindling model of epilepsy.

p310 ACUTE PURE RED CELL APLASIA. RARE COMPLICATION OF LAMOTRIGINE TREATMENT H. Ikeda, H. Ikeda, and Y. Inoue National Epilepsy Centre, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan
Purpose: To report that pure red cell aplasia (PRCA) can occur as a rare side effect of lamotrigine (LTG). Method: We report a patient presenting with acute PRCA following LTG treatment. Result: Patient is a 25 year-old female with focal epilepsy and mental retardation. She has a history of surgery for cerebellar tumor, subsequent

p312 DIFFERENT TYPES OF HEADACHE IN PATIENTS WITH EPILEPSY CLINICAL INVESTIGATIONS C. Lorenzen, M. Prieschl, M. Bergmann, G. Walser, C. Gneis, I. Unterberger, and G. Luef Medical University Innsbruck, Innsbruck, Austria
Purpose: Epilepsy is known to be associated with different comorbidities in particular headache. The aim of our study was to examine the
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92 Abstracts
distribution of different headache types in patients with epilepsy. We tried to determine whether migraine is the most common headache type in epilepsy and if antiepileptic drugs are useful for headache prophylaxis. Method: In this single-centre study we consecutively investigated patients with epilepsy using a validated self-administered headache questionnaire for screening for migraine (MIG), tension-type headache (TTH), and trigeminal-autonomic cephalgias (TAC). Additionally we asked for onset and type of epilepsy, seizure associated headache, antiepileptic drug treatment and their influence on headache followed by a question regarding seizure frequency. Result: Five hundred epileptic patients with equivalent sex distribution and a mean age of 45.52 years (+-17,26) were enrolled. One hundred sixty three patients, 43.2% female and 22.0% male, reported to suffer from headache. Migraine was the most frequent type in general (41.7%), and in women (47,2%), TTH in male (41,8%). Antiepileptic drug treatment was used by 158 patients, sixty (38.0%) reported to have a reduction in frequency of headache. With regard to the different headache types, levetiracetam reduced frequency of headache best (50.0%), followed by valproic acid (41.2%) and lamotigine (26,3%). Conclusion: Three different headache types are present in epilepsy patients. A short questionnaire seems to be helpful in diagnosing headache. AED treatment improved headache and polypharmacy. Levetiracetam followed by Valproat was shown to have the best influence on headaches in general.

Purpose: This study was conducted to compare (QOL) in patients with epilepsy, patients with MS and healthy controls from Saudi population. Method: The QOL of (110) patients with epilepsy, (114) patients with MS, and (136) healthy controls all from Saudi Arabia was assessed using two scales (QOLIE-31 and the RAND SF-36). Translation and validation of the QOLI-31 from English to Arabic was done. Result: A comparison between the three groups QOL will be presented as preliminary results. Conclusion: Preliminary results show the QOL within the three groups.

Semiology, Aetiology and Classification 10 Monday, 01 October 2012

p313 PSYCHOSOCIAL OUTCOME AND PATIENT SATISFACTION 10 YEARS AFTER TEMPORAL LOBE RESECTION FOR EPILEPSY L. Andersson-Roswall, E. Engman, H. Samuelsson, and K. Malmgren Institute of Neuroscience and Physiology, Gothenburg, Sweden
Purpose: Knowledge about long-term psychosocial outcome of temporal lobe resection (TLR) for epilepsy is limited. The aim of this study was to explore long-term psychosocial outcomes and patient satisfaction with TLR and to investigate the relationship between long-term vocational and memory outcomes. Method: A cohort of 51 patients was prospectively followed 10 years after TLR. Psychosocial and neuropsychological data was prospectively ascertained at baseline and 10 years after surgery and at corresponding time-points for 23 controls. 40/51 patients (78%) also answered two surveys at long-term follow-up including the Hospital Anxiety and Depression Scale (HAD), a global quality of life (QOL) assessment and questions on patient satisfaction with surgery. Result: Fewer patients worked 10 years postoperatively (TLR: 61%; controls: 96%; p = 0.002) compared to baseline (TLR: 73%; controls: 83%; NS). The odds of working full time 10 years after surgery were 9.5 times higher with seizure freedom (p = 0.022). There were no associations between working at 10 years and side of resection and verbal memory outcome. Most patients scored low on HAD indicating few emotional problems. Seizure-free patients were more satisfied with surgery (p = 0.027), experienced less disadvantages of their TLR (p = 0.022), and had a better QOL (p = 0.014). Conclusions: In this study TLR did not lead to better vocational outcome. However, seizure-free patients were more likely to work full-time 10 years postoperatively and verbal memory impairment did not have an influence on vocational outcome. Patients were in general satisfied with epilepsy surgery, those seizure-free more than those with seizures.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

p315 EPILEPTIC ENCEPHALOPATHIES OF THE LANDAUKLEFFNER AND CONTINUOUS SPIKE AND WAVES DURING SLOW-WAVE SLEEP TYPES: GENOMIC DISSECTION MAKES THE LINK WITH AUTISM G. Lesca*, G. Rudolf, A. Labalme, E. Hirsch, A. Arzimanoglou*, P. Genton, J. Motte, A. De Saint Martin**, M. Valenti**, C. Boulay**, J. De Bellescize, P. Keo-Kosal, N. Boutry-Kryza, P. Edery*, D. Sanlaville*, and P. Szepetowski *CRNL, CNRS UMR 5292, INSERM U1028, Lyon, France; Strasbourg University Hospital, Strasbourg, France; University Hospital of Lyon, Bron, France; Henri Gastaut Hospital, Marseille; American Memorial Hospital, Reims University Hospital, Reims, France; **Strasbourg University Hospital, Strasbourg; Epilepsy, Sleep and Pediatric Neurophysiology Dpt, Lyon, France; Lyon University Hospital, Claude Bernar University Lyon 1, Lyon; and Mediterranean Institute of Neurobiology (INMED), Marseille,
Purpose: The continuous spike and waves during slow-wave sleep syndrome (CSWSS) and the Landau-Kleffner (LKS) syndrome are two rare epileptic encephalopathies sharing common clinical features including seizures and regression. Both CSWSS and LKS can be associated with the EEG pattern of electrical status epilepticus during slow-wave sleep and are part of a clinical continuum that at its benign end includes Rolandic epilepsy (RE) with centro-temporal spikes. Patients can also have behavioral manifestations that overlap the spectrum of autism disorders (ASD). An impairment of brain development with complex interplay between genetic and non-genetic factors has been suspected but the pathophysiology of CSWSS and of LKS remains unknown. In the recent years, the participation of rare copy number variations (CNVs) in the susceptibility to various brain diseases including epileptic and autistic disorders has been demonstrated. Method: The involvement of rare CNVs in 61 CSWSS and LKS patients was questioned using comparative genomic hybridization assays (4 180 Agilent microarrays). Result: Whereas the patients showed highly heterogeneous in genomic architecture, several potentially pathogenic alterations were detected. Many of these corresponded to genomic regions or genes that have been associated with either ASD, or speech or language impairment, or RE. Particularly, CNVs encoding cell adhesion proteins were detected with high frequency.

93 Abstracts
Conclusion: Overall our data bring the first insights into the possible molecular pathophysiology of CSWSS and LKS. The detection of cell adhesion genes and the strong overlap with the genetic and genomic ASD networks, provide an exciting and unifying view on the clinical links between CSWSS, LKS and ASD. characterized by desynchronization of basic EEG-rhythm. The most important diagnostic criteria for epileptic patients are dynamic characteristics of the DV: elongation, increased appearance of negative emotions. Conclusion: There was allocated of two types of deja-vu: pathological-epileptic, characteristic of patients with epilepsy and equivalent to an epileptic seizure, nonpathological-nonepileptic deja-vu, which is characterized for healthy people.

p316 SEIZURE SEMIOLOGY OF A HOT WATER SEIZURE CASE O. Karadas*, I. Ipekdal, and H. L. Gul *Erzincan Military Hospital, Erzincan, Turkey; Marasal Cakmak Hospital, Erzurum, Turkey; and Kartal Education and Research Hospital, Istanbul, Turkey
Purpose: Hot water epilepsy (HWE) or bathing epilepsy is the group of reflex epilepsies. It is induced by hot water pouring over the head, face, neck, or trunk during bathing. The aim of this study was to demonstrate the seizure semiology by following up the seizure with all the changes that occured before, during and after the seizure. Method: An informed consent form was signed by the patient and the needed precautions were taken. Under the supervision of a doctor and a nurse; the patient's seizure was induced by having a bath with 40C hot water. Each step of the semiology was recorded by a neurologist. Result: 1,5 minutes after starting to bath, the patient's breathing became deeper and a fearful facial expression had developed. This status had continued for 510 seconds, then a pause in the speech and pupillary dilatation was detected. 5 seconds after this status, the patient became unconscious with oral automatisms and the deviation of the head and eyes to the right. At this state, intervention was made and while taking the patient out of the bath, he had a 68 seconds of generalised tonic seizure followed by a 20 seconds of generalised clonic seizure. His postictal confusion continued for 10 minutes and after that period, his neurological examination had turned to normal. Conclusion: This case is important for; the determination of the seizure semiology of hot water epilepsy as a reflex epilepsy and the comparison of hot water epilepsy with the other epilepsies.

p318 TRANSIENT EPILEPTIC AMNESIA: DESCRIPTION OF TWO CASES S. Meregalli, and M. Brioschi A. O. Niguarda C Granda, Milano, Italy
Purpose: Case reports over the past 100 years have raised the possibility that epilepsy can manifest itself in episodes of amnesia. Transient Epileptic Amnesia (TEA) is a relatively recently characterized syndrome of temporal lobe epilepsy. Method: Transient Epileptic Amnesia (TEA) is a distinctive syndrome of temporal lobe epilepsy principally affecting middle-aged people, giving rise to recurrent, brief attacks of amnesia, often occurring on waking. It is associated with a form of persistent interictal memory impairment, i.e. accelerated long-term forgetting and remote memory impairment. The syndrome is of clinical importance, as the amnesic episodes are often misdiagnosed initially but respond promptly to antiepileptic drugs. The diagnostic criteria for TEA are as follows: 1) A history of recurrent witnessed episodes of transient amnesia. 2) Cognitive functions other than memory judged to be intact during typical episodes by reliable witness 3) Evidence for a diagnosis of epilepsy based on one or more of the following: (a) epileptiform abnormalities on electroencephalography (b) the concurrent onset of other clinical features of epilepsy (c) a clear-cut response to antiepileptc drugs. We describe two new cases of TEA, filling these diagnostic criteria. Result: WE describe two middle-aged womans, with episodes of TEA, promptly responding to antiepileptic drugs-therapy. Conclusion: Transient Epileptic Amnesia is an under-recognized but treatable cause of transient memory impairment. It is important to make a differential diagnosis with other forms of transient impairment of memory, like Transient Global Amnesia etc.

p317 DEREALIZATION DISORDERS IN EPILEPSY P. Vlasov*, and A. Chervyakov *Moscow State Medical and Stomatology University, Moscow, Russian Federation; and Research Center of Neurology RAMS, Moscow, Russian Federation
Purpose: To examine the clinical and diagnostic value of derealization disorders in epilepsy. Deja vu (DV) phenomenon is the most common and recognizable derealization disorder. Method: Study group of 166 persons (average age 25,2 9,2; 63,2% of women). Derealization was compared in two groups: I healthy people (n = 139), II patients with epilepsy (n = 27). Provided that healthy respondents have never had any of the paroxysmal manifestations. Longtime EEG monitoring was performed for all patients of the second group and for 5 healthy participants with frequent DV. We used our own unique questionnaire. Result: For patients with epilepsy DV phenomenon occurs in cryptogenic and symptomatic focal epilepsy, it can be combined with virtually all types of seizures, could be aura of a seizure, and self-attack. For the first time there was recorded EEG-pattern of DV phenomenon in epilepsy, that is characterized by the beginning of spike activity in the right temporal lobe and, in some cases (longer duration of phenomenon), ended in slow wave, theta-delta activity in the right hemisphere. In one healthy volunteer the EEG-pattern of DV-phenomenon was

p319 EPILEPTC APHASIA: A DESCRIPTION OF 10 NEW CASES A. Lpez-Ferreiro*, X. Rodrguez-Osorio*, J. C. FernndezFerro, T. Garca-Sobrino*, M. Rodrguez-Yaez*, M. Arias*, J. Pardo*, E. Corredera*, and F. J. Lpez-Gonzlez* *Complejo Hospital Clnico Universitario de Santiago de Compostela, Santiago de Compostela, Spain; and Hospital Infanta Elena, Madrid
Purpose: Recurrent or prolonged aphasia as sole clinical manifestation of epilepsy is a rarely described phenomenon. We aim to describe the epileptic aphasias diagnosed in our hospital. Method: We considered ictal aphasia as language production with aphasic features in conscious patients. Episodes were classified as status epilepticus or simple partial seizures according to ILAE guidelines, and may present as Broca, Wernicke or mixed aphasia. Diagnosis was based on clinical features plus EEG findings or clear response to antiepileptic drugs (AED), with exclusion of acute structural aetiologies on MRI. We

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94 Abstracts
analyzed demographic, clinical and EEG characteristics, response to treatment and follow-up. Result: Ten women (100%), with a mean age of 66.6 years old were included (4985) Two had previous history of epilepsy. Mixed aphasia occurred in 5 patients, Broca in four and Wernicke in one. In 9 cases an ictal EEG was obtained: 4 demonstrated left regional epileptiform activity and other 4, left hemisphere slowing. Six patients presented with status epilepticus and four with simple partial seizures. One patient showed transitory edema in the MRI. Benzodiazepines were used as first-line AED in 6 patients, with clinical response in 4, EEG response in 1 and both in 1. All patients clinically recovered with AEDs (LEV 70%). In the follow-up, 7 cases achieved an excellent control and three recurred. Conclusion: Diagnosis of epileptic aphasia is challenging. An epileptic aetiology should be considered in the differential diagnosis of episodic speech errors. Ictal EEG findings and response to AEDs are useful in the diagnosis and management of these patients. Purpose: To elucidate features of the seizure semiology in children with protocadherin 19-related epileptic encephalopathy (PCDH19EE), because of lack of detailed description regarding seizure manifestation based on video-EEG recordings in the literature. Method: We analyzed ictal video-EEG recordings of 26 seizures in three girls with PCDH19EE. Result: The sequence of seizure manifestation was very similar among all three patients, consisting of five common segments, which we named Jerk, Reactive, Mild tonic, Fluttering and Post-ictal/Oral automatism. Some segments are brief or lacking, while others are long or pronounced. Reactive, Mild tonic and Fluttering segments are more characteristic. In Reactive, the patients seemed so startled by sudden Jerk that they reactively turned over. Tonicity in Mild tonic was less intense than that of tonic-clonic seizures of other epilepsies. Fluttering was characterized initially by asymmetric, less rhythmic, less synchronous tremulous movement and later by subtle clonic movement. There was subtle oral automatism in the postictal phase. Seizure lasted from a few to sixty seconds. All seizures occurred in clusters associated with high fever. Ictal EEGs started initially bilateral in some, but asymmetric at the very onset in some others, and later showed apparent asymmetric rhythmic discharges. Conclusion: Seizures have more or less asymmetric focal features in the electro-clinical aspects. Characteristic seizure sequence in PCDH19EE was so unique that its occurrence in clusters associated with high fever in girls would readily suggest PCDH19EE.

p320 SEMIOLOGIC AND EEG FEATURES OF PATIENTS WITH TEMPORAL LOBE EPILEPSY AND HIPPOCAMPAL SCLEROSIS WHO WERE SEIZURE-FREE FOLLOWING SURGERY lu Toydemir*, C. zkara, and M. Uzan H. Ertas og *S is li Etfal Research and Education Hospital, Istanbul, Turkey; Istanbul University School of Medicine, Istanbul, Turkey; and _ Istanbul University Cerrahpas a Medical Faculty, Istanbul, Turkey
Purpose: Despite the high rate of favorable outcome after standardized surgery, 2030% of patients with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS) still continue to experience seizures. The aim of this study is to determine whether there is evident semiologic and EEG features which may predict the seizure freedom after surgery. Method: Semiologic and EEG findings of 126 ictal video-EEG recordings corresponding to 50 patients who stayed seizure free for at least 3 years (mean: 9.46 3.20; range: 314.5 years) after surgery were reviewed. About 94% of them have already discontinued drugs. Result: Aura was reported in 82% (n:41) of the patients. Epigastric sensation was the most common aura. Early symptoms (within the first 30 seconds) were contralateral arm dystonia (%60), ipsilateral hand automatisms (%54) and oro-alimentary automatisms (%48). Two or three of these symptoms were seen together in %56 of the patients without any unique sequence. Ictal EEG findings revealed localized and lateralized activity in 66% of them. Conclusion: The presence of three semiological features during the early ictal period and localized and lateralized ictal EEG activity seem to be common features in this highly selected patient population. Although, other types of semiologic and EEG findings detected besides them suggest a more extended epileptogenic zone, the fact that they benefit from the same surgical procedure may be associated with the critical role of resected area in both the generation and propagation of the seizure activity.

Semiology, Aetiology and Classification 10 Monday, 01 October 2012

p322 RELIABILITY OF POSTICTAL NOSE RUBBING FOR LOCALIZATION AND LATERALIZATION OF EPILEPTOGENIC ZONE IN FOCAL EPILEPSIES N. M. Vojvodic*, A. J. Ristic*, L. M. Popovic, V. L. Bascarevic, D. V. Sokic*, A. Parojcic*, S. M. Jankovic*, M. M. Kovacevic*, L. Brajkovic, and B. Djurovic *Neurology Clinic, Belgrade, Serbia; St Sava Hospital, Belgrade, Serbia; Clinic of Neurosurgery, Clinical Center of Serbia, University of Belgrade, School of Medicine, Belgrade, Serbia; and Institute of Nuclear Medicine, Belgrade, Serbia
Purpose: To evaluate the usefulness of postical nose rubbing (PNR) as the localization and lateralization sign in focal farmacoresistant epilepsies. Method: Retrospectively, we analyzed seizure semiology in 266 patients with focal farmacoresistant epilepsy. All patients were undergone five day noninvasive video-EEG monitoring in our telemetry unit and brain MRI according to the presurgical protocol. In 162 patients we were able to establish the lobar diagnosis. In all patients we analyzed clinical seizure semiology in order to determine the occurrence of PNR in temporal lobe epilepsies (TLE) vs. extratemporal lobe epilepsies (ETLE), and it's lateralizing value (ipislateral or contralateral to the epileptogenic zone) when perform exclusively with one hand. Result: We found PNR in 40 out of 106 patients with TLE and in 7 out of 56 patients with ETLE (37,7% vs. 12,5%, p = 0.001). In 27 (57,4%) patients, PNR was performed always with hand ipsilateral to the epileptogenic zone, in 11 (23,4%) patients with contralateral hand and in 9 (5,2%) patients with both hands (p = 0.008).

p321 CHARACTERISTIC SEIZURE SEMIOLOGY IN PCDH19-RELATED INFANTILE EPILEPTIC ENCEPHALOPATHY H. Ikeda, K. Imai, H. Ikeda, R. Takayama, H. Ohtani, H. Shigematsu, Y. Takahashi, and Y. Inoue National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan
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95 Abstracts
Conclusion: We found PNR was reliable localizing sign for TLE and when performed exclusively with one hand, it was significantly more common with ipsilateral hand to the epileptogenic zone. has been seizure-free for a long period since he developed Status Epilepticus followed by Refractory SE, than Super Refractory SE occurred. EEG and MRI changes occurred during his follow-up: serial MRI examinations showed progressive cortical laminar necrosis while EEG recordings showed paroxysmal epileptiform discharges. Suppression burst never appeared after anesthetic therapy. These findings suggest an ongoing neuronal injury that currently persists after 5 months of SE despite all treatments. Result: These findings suggest an ongoing neuronal injury that currently persists after 5 months of SE despite all treatments. Conclusion: Morbidity and mortality in Super Refractory SE is very high. The outcome depends on the underlying etiology but, in our patient, no cause was found until now.

Basic Science 5 Tuesday, 02 October 2012

Purpose: The purpose of this report is to provide a comprehensive analysis and synthesis, from the published literature from 1981, of the outcome of therapies used in refractory or super-refractory status epilepticus, and to provide recommendations about a treatment protocol. Method: We analysed all 141 papers reporting outcome of 1168 patients with refractory and super-refractory status epilepticus, treated with various therapies. Result: Control of refractory and super-refractory status epilepticus was reported in 74% of the cases treated with anaesthetics 64% for barbiturate, 78% for midazolam and 68% for propofol. Variable rates of control were achieved for other therapies including other anaesthetics, antiepileptics, the use of hypothermia, immunotherapy, the ketogenic diet, magnesium, pyridoxine, immunotherapy, electroconvulsive therapy (ECT), cerebrospinal fluid (CFS) drainage, VNS and emergency resective surgery. The reported mortality rate of this stage of status epilepticus was 35% and a further 13% of patients were left with severe neurological deficit. Conclusion: There is a remarkable dearth of information about the outcome of the various therapies used, often widely so, to control refractory or super-refractory status epilepticus despite its high mortality and morbidity. There are no controlled studies, and information is based almost entirely on open, often small and retrospective, case series or case reports. Based on our findings, we make recommendations about first and second line therapy, and suggest a protocol of therapy. We also emphasis the need for an international case registry to provide better quality outcome information.

p325 EPILEPTIC STATUS IN ADULTS D. Ndoja, N. Bendo, A. Seferi, A. Kuqo, and Z. Ndroqi UHC, Tirana, Albania
Purpose: Electro-clinical-etiological finding of SE. Method: We studied 28 patients hospitalized in ICU (17 F, 11 M with median of 46 years old), from 2008 to 2010, with mean SE duration of 2 hours. Result: SE prevalence had 2 picques; in adolescentes-younger adults (10), and in older(10). All displayed generalized GSE: 11 primary PGSE, 17 secondary SGSE (Shorvon 1983). Among PGSE : 9 had convulsive, myoclonic, atonic SE in 2. In SGSE; 14 had PMS onset: hemy without, with Jaksonian march (4,2) superior 5; whereas versive and CPS onset (3,3). Etiology of PGSE; IgE in 7, metabolic in 3, eclampsy in one. Triggeref factors were AEDs changes, fever and alcol. In SGSE: vascular origin in 7, trauma 3, Tu 4, non-lesional 2, hygroma, FCD dementia in 1 respectilvely. EEG post-SE: diffuse/ bilateral in 8, lateralized 7; ictal with partial onset in 2; not available 7; normal in 3 patients. Two pt died, while BZD and PHT in refractory cases provided the good outcome, in others. Conclusion: SGSE prevailed more than PGSE. In PGSE, IGE were more frequent than metabolic SE. in SGSE the vascular etiology was more frequent than trauma and Tu, then than DA, MCD, and non-lesional. EEG : diffuse/ bilateral more than lateralized, normal finding.

Basic Science 5 Tuesday, 02 October 2012

p324 EEG AND MRI FINDINGS IN SUPER REFRACTORY STATUS EPILEPTICUS DUE TO UNKNOWN UNDERLYING ETIOLOGY A. Ferrari, P. Renzetti, M. Ferretti, F. Piccardo, N. Mavilio, and G. A. Ottonello IRCSS A.O.U San Martino, Genova, Italy
Purpose: Super Refractory Status Epilepticus is a stage of Refractory Status Epilpticus and it is characterized by unresponsiveness to initial anesthetic therapy. It is defined as a condition that continues or recurs 24 hours or more after the onset of anesthesia. Method: We report the case of 40-years-old man affected by cerebellar atrophy who suffered myoclonic seizures with onset at 3 years old. He

p326 A CASE OF SEVERE FORM OF PANDAS-LIKE COURSE L. C. Heberle*, D. Neubauer, A. Altawari*, and N. Alothman* *Al Sabah Hospital, Kuwait, Kuwait; and University Children's Hospital Ljubljana, Ljubljana, Slovenia
Purpose: Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infections (PANDAS) presents as a spectrum of postinfectious neurological disease that extends well beyond Syndenham chorea and includes different neuropsychiatric conditions including complex tic disorders and obsessive-compulsive behavior. Method: We describe a boy with an extremely severe and life-threatening course who responded well to immunotherapy but is left with residual epilepsy and depression. Result: K. was 11-year old boy who had had tics one year before admission due to low grade fever, throat infection and progressive lethargy with absence like attacks followed by epileptic status and apneas. After
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

96 Abstracts
institution of anticonvulsive treatment and antibiotics seizures subsided and a full-blown clinical picture emerged with very frequent complex tics, fidgety and psychiatric behavior to be soon followed by another period of status epilepticus and apneas necessitating intubation and intensive care. Results showed very high titers of ASOT (3200 IU/ml), MRI brain faint thalamic changes, CSF study was normal. EEG showed progressive slowing of background activity which later normalized. Despite no epileptiform discharges he had occasional focal seizures. With penicillin prophylaxis, combined treatment with immunoglobulins and methylprednisolone the child gradually improved, however he still has occasional epileptic seizures, tics and depressive behavior. His recent minimental test proved normal result. Conclusion: We believe that this boy had s severe form of PANDASlike condition, presenting also as epileptic statuses, finaly leading to residual epilepsy and depressive behaviour. Purpose: Convulsive Status Epilepticus (CSE) is one of the most common neurological emergencies in children with high mortality and morbidity. Prognostic value of risk factors as age, etiology, duration, quality of pre hospital treatment is not well studied. Purpose- to study correlation of duration, etiology and type of status on outcome. Also Effect of quality of pre hospital treatment on short term outcome. Method: Hospital based study. Children admitted to Central Children Hospital with CSE from 01.01.09 till 31.12.10 were evaluated and monitored for at least 12 months. Result: Among 870 hospital admissions, were 46 cases of CSE (5.3%). Average age was 4.9 years. In 5 cases status was first manifestation of epilepsy. 20 patients had previous history of epilepsy, 9 were on AED. 5 had drug resistant epilepsies. 12 patients had developmental delay. Status was focal in 24 and generalized in 22 cases. In 8 cases CSE was febrile, infections of CNS in 7 cases. Stroke was manifested with CSE in 3 cases (2 ischemic, one hemorrhagic) . Duration of CSE varied from 30180 min. mean 50.5. Mortality rate was 4.3% (2 patients). Data revealed poor pre hospital care over treatment with BZD. All patients received 12 doses of BZD, 14 patients 3 or 4 doses. Conclusion: Analysis of data showed no correlation of outcome with age, type of epilepsy, duration of status. There was negative correlation between prehospital care and outcome. Patients receiving 34 doses of BZD at prehospital level had longer stay on ventilation and worst short term outcome (p < 0.001).

p327 EFFICACY OF INTRAVENOUS LACOSAMIDE IN SYMPTOMATIC FOCAL MOTOR STATUS EPILEPTICUS: A CLINICAL AND VIDEO-POLYGRAPHIC STUDY M. Trivisano, G. DOrsi, M. G. Pascarella, F. Pacillo, M. Ferrara, E. Carapelle, C. Luisi, M. T. Di Claudio, and L. M. Specchio Epilepsy Center Clinic of Nervous System Diseases, University of Foggia, Riuniti Hospital, Foggia, Italy
Purpose: To evaluate efficacy and tolerability of intravenous lacosamide (LCM) in the treatment of Non-Convulsive Status Epilepticus (NCSE) after failure of conventional therapy. Method: Patients presented with refractory NCSE underwent LCM i.v. therapy and a long-term video-EEG/polygraphic monitoring before and after LCM treatment. Result: Three patients (2 female, 1 male), aged between 60 and 70, with symptomatic (gliomatosis cerebri, brain metastasis of lung adenocarcinoma, ischemic stroke) focal motor status epilepticus were investigated. The first patient showed left fronto-central polyspike-and-wave activities associated with tonic contraction of right orbicularis oris followed by tonic-clonic activity in the right masseter and orbicularis oris, hypersalivation and aphasia. The second one presented with aphasia and tonic-clonic activity of right extensor hand muscles associated with left fronto-temporal epileptic discharge. The third one had repetitive left leg tonic-clonic activity with epileptic discharge over the vertex and right anterior region. All patients achieved a clinical and polygraphic disappearance of the focal motor status within 24 hours since the first administration of 400 mg of LCM i.v. after an ineffective treatment with DZP (10 mg i.v.) and LEV (3000 mg i.v.). In all patients the treatment with PHT was not possible because of hypotension in two and sinus bradycardia in one. All patients did not have any seizures with a maintaining dose of 400 mg/day. Conclusion: Our clinical and polygraphic study suggest that LCM i.v. may be effective in the treatment of refractory focal motor NCSE, but larger studies are needed to confirm the efficacy of LCM in the treatment of this type of NCSE.

Purpose: To identify the prevalence of non-convulsive status epilepticus [NCSE] in patients with altered sensorium in a rural based medical intensive care unit [ICU] using one hour portable Electroencephalography [EEG] record and to assess its utility/ impact by assessing the number of patients in whom treatment decisions changed after the portable EEG record. Method: 70 adult patients admitted in medical ICU with altered sensorium underwent one hour EEG for assessing presence of NCSE using preset defined clinical and EEG criteria. We assessed the relationship between demographic characteristics, clinical features and the presence of NCSE. We also assessed the number of patients in whom EEG recording lead to change in treatment by addition/ change/modification/stopping of anti-epileptic drug [AED] therapy and assessed its relationship to overall patient outcome. Result: NCSE was present in 13(18.57%) of our cohort of 70 patients. The common aetiologies for altered sensorium were metabolic encephalopathy (52.94%), intracranial infections (17.64%) and stroke(5.84%). Treatment was changed in 16 patients (22.85%) after EEG recording, of whom 11(68.75%) had NCSE and required addition of AED. After changing treatment clinical improvement occurred in 7 patients (43.75%). Conclusion: Our pilot study shows that one hour portable EEG in resource limited settings can identify NCSE in significant number of patients with altered sensorium in medical ICU and lead to treatment change and better outcome.

p328 CONVULSIVE STATUS EPILEPTICUS IN CHILDRENPREDICTORS OF OUTCOME N. Tatishvili, and T. Shatirishvili Central Children Hospital, Tbilisi, Georgia
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

97 Abstracts
Purpose: We describe three cases of pediatric-aged patients diagnosed of medulloblastoma who presented atypical absence nonconvulsive status epilepticus probably related to radiotherapy. Method: Three children; 10 year-old-boy, 11 year-old-girl and 11 yearold-boy, previously diagnosed of medulloblastoma with complete response to treatment after chemotherapy and craniospinal irradiation who presented tonic or generalized tonic-clonic seizures in the course of the disease, were admitted in our institution with the clinical suspicion of tumor-recurrence after presenting acute impairment of mental status. Patients underwent various diagnostic techniques such as structural MRI, lumbar puncture, blood and cerebrospinal fluid (CSF) cultures and videoelectroencephalographic (EEG) recording. Result: In all three patients, diagnostic structural MRI did not show any significant change comparing with previous exams and other tests discarded tumor recurrence. Video-EEG showed continuous generalized slow spike-wave complexes in all children with no clinical changes of basal state during the recording. Three patients were diagnosed of atypical absence nonconvulsive status epilepticus and were treated with LEV in two cases and with VPA in the other one, with complete remission of symptoms and epileptiform activity. Conclusion: Despite medulloblastomas are tumors arising from cerebellum, epileptic seizures are common in the course of the disease, probably related with radiotherapy which is an essential component in postoperative management. Atypical absence nonconvulsive status epilepticus is an unexpected late sequel that must be suspected, probably also related with cerebrospinal radiation, classically also considered as one of the etiologies of Lennox-Gastaut syndrome. Early suspicion, diagnosis and treatment of this entity, could prevent secondary morbidity and mortality in these oncologic patients. and/or prolonged refractory status) had complications compared with 30% of those not admitted to ICU (p < 0.05). Of 17 previously treated patients, 10 were monotherapy, 7 polytherapy. 29.4% 1st generation drugs, 41.2% 2nd and 29.4% both. Prior untreated patients: 85.7% initiated monotherapy (100% 1st generation). Of those treated 33.3% increased number of drugs, decreased 6%. The most widely used drug was valproic acid monotherapy (on 50%, high 40%) and levetiracetam in combination (on 100% high 81%). Conclusion: Focal complexwas the most frequent NCSE. There were more complications in patients with altered level of consciousness and refractory status.

p332 EFFICACY OF DIFFERENT THERAPEUTIC AGENTS IN STATUS EPILEPTICUS J. Rsche, K. Rantsch, U. Walter, and R. Benecke Universittsmedizin Rostock, Rostock, Germany
Purpose: We evaluated the efficacy of different antiepileptic drugs and narcosis in different forms of status epilepticus in a retrospective study. Method: We reviewed the medical charts of all patients, who were treated for status epilepticus in our department from January 2000 to December 2009. The last drug given before termination of status epilepticus was considered as termination drug. The quotient of status epilepticus episodes in which an antiepileptic drug or narcosis was the termination drug and all status epilepticus episodes in which the therapeutic agent had been used was considered as efficacy rate. Differences in efficacy were tested for significance by chi-square-tests. Result: 167 episodes of status epilepticus in 118 patients (58 female, 60 male) could be evaluated. 9 patients died without termination of status epilepticus. Efficacy rates ranged from 20% (Lacosamid) to 51% (Clonazepam) and 68% (narcosis). Efficacy of Phenytoin (44 episodes), Valproate (53 episodes), Levetiracetam (41 episodes) and Lacosamid (10 episodes) did not differ significantly. Clonazepam (121 episodes) was more efficient than other benzodiazepines (p < 0.000008) and i.v. antiepileptic drugs (p < 0.04). Narcosis was more efficient than i.v. antiepileptic drugs (p < 0.005). But its efficiency was lower in nonconvulsive status epilepticus than in status of generalized tonic-clonic seizures (p < 0.02). Conclusion: The results of this retrospective study are confounded by many factors. Nevertheless Clonazepam was more effective in the termination of status epilepticus than other antiepileptic drugs und narcosis worked better in generalized tonic-clonic status epilepticus than in nonconvulsive status epilepticus.

Purpose: Description of patients with non-convulsive status epilepticus (NCSE). To assess factors associated with mortality, complications and treatment. Method: Retrospective observational study of patients admitted for NCSE between 20082010. We analyzed demographic data, history of epilepsy, treatment, type NCSE and variables associated with mortality and complications. Result: 30 patients (60% M). Mean age 62 years. Previous epilepsy : 85% and 15% generalized. 70% symptomatic. 17 patients had focal complex NCSE, 7 and 6 simple focal SENC status of absence. 15% caused by changes in medication. 46.7% had complications (64% respiratory) and 6 patients died. No significant differences in complications and mortality in age, sex, type, etiology and treatment of epilepsy, or type of NCSE. 70% of patients admitted to ICU (due to impairment on level of consciousness

Basic Science 6 Tuesday, 02 October 2012

p333 NON-CONVULSIVE STATUS EPILEPTICUS: PREVALENCE, PRECIPITATING FACTORS, CLINICAL MANIFESTATIONS, RADIOLOGICAL, ELECTROENCEPHALOGRAPHIC FINDINGS AND MORTALITY IN A TERTIARY CARE HOSPITAL IN MEXICO V. Gijn-Mitre*, M. Alonso-Vanegas, and H. Sentes Madrid *Instituto Nacional de Ciencias Mdicas y Nutricin Salvador Zubirn, Mxico D.F, Mexico; Instituto Nacional de Neurologa y Neurociruga Manuel Velasco Suarez, Mexico
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

98 Abstracts
City, Mexico; and Instituto Nacional de Nutricin y Ciencias Mdicas Salvador Zubirn, Distrito Federal, Mexico
Purpose: To determine the prevalence, causes, clinical features, radiological and EEG, treatment and mortality in patients with non-convulsive status epilepticus (NCSE) in the Instituto Nacional de Ciencias Mdicas y Nutricin Salvador Zubirn. Method: A retrospective, descriptive, observational study. Result: Seventy-nine cases of status epilepticus (SE) of which 8 were for NCSE (10.12%), 5 women, mean age 52 years, 3 had a family history of epilepsy, 2 history of neonatal hypoxia, 5 had reported seizures previously, 2 by migralepsia, 1 traumatic brain injury, 1 as a complication of chronic meningitis from tuberculosis and another one for cryptogenic epilepsy, 2 had previously presented convulsive SE. 6 had NCSE admission. The causes were diverse: meningoencephalitis (2), metabolic (2), suspension of drugs (1), migralepsia (2), 1 after cesticide treatment, 4 had initially behavior alterations, temporal disorientation and focal seizures, 2 tonic-clonic seizures. The average Glasgow was 9, all cases showed alteration of the alert and the duration was longer than 30 minutes (prolonged SE) in 5 patient. The neuroimaging was abnormal in 3 patients and the EEG showed unilateral epileptic activity in 6 and bilateral in 2. The treatment was based on BZD and PHT in all patients, 4 underwent barbiturate coma, 2 had refractory SE. Mortality was 12.5% (1) and 1 patient was left with serious neurological sequelae. Conclusion: A history of epilepsy was common in patients with NCSE, the alert and conduct disorders were the main clinical manifestations, mortality appeared similar to that reported in the literature.

p335 DELAY IN DIAGNOSIS: A NEW PREDICTOR OF REFRACTORINESS AND MORTALITY IN NONCONVULSIVE STATUS EPILEPTICUS? M. Sanchez, L. Romano, F. Latini, P. Alvarez, M. Ayala, A. Aleman, I. Etchepareborda, E. Sottano, P. Ioli, and S. Gonorazky Hospital Privado de Comunidad, Mar del Plata, Argentina
Purpose: The mortality of non-convulsive status epilepticus (NCSE) ranges from 18 to 52% depending on the presence of different prognostic factors. Recognizing these factors in NCSE helps to differentiate the group of patients requiring special care or benefit from specific therapeutic strategies. Objective: To evaluate the delay in the diagnosis of NCSE as a predictor in refractoriness and mortality at day 30 in patients with NCSE. Method: In this prospective study we recorded all cases of NCSE between April 2007 and March 2011, in patients 21 years. The baseline prognostic variables were analyzed using stepwise logistic regression analysis. Result: There were 125 patients with NCSE. The median age was 76 years and 65% were women. The etiology of NCSE was unknown in 9%, remote symptomatic in 10%, and in 81% acute symptomatic. The median diagnostic delay time was 48 hours. The mortality rate was 37%. After analysis of all the aforementioned variables using stepwise logistic regression analysis, only delayed diagnosis >56 hs was an independent predictor of refractoriness(OR:4.7, p = 0.0002). Acute symptomatic etiology (OR:7.2, p = 0.003), partial NCSE (OR:3.9, p = 0.008), delayed diagnosis >56 hs (OR:4.6, p = 0.001), and refractoriness (OR:5.3, p = 0.0008) were independent predictors of mortality at day 30 in patients with NCSE. Conclusion: Our data suggest that a delayed diagnosis is an independent variable of refractoriness and mortality in patients with NCSE. We propose that delayed diagnosis should be included as a prognostic variable when analyzing the efficiency of different treatments for this entity. Our findings should be confirmed in future prospective studies in different populations.

p334 SUCCESSFUL USE OF KETAMINE IN PEDIATRIC SUPER-REFRACTORY STATUS EPILEPTICUS CASE REPORT C. Andrade*, S. Frana*, M. Sampaio*, A. Ribeiro, J. M. Oliveira*, J. A. M. Ribeiro*, and R. Rego *Hospital de So Joo, Porto, Portugal; and Servico de Neurofisiologia, Porto, Portugal
Purpose: Treatment failure in refractory status epilepticus (SE) and progression to super-refractory SE may be related to a depletion of GABA receptors, decreasing the efficacy of most general anesthetic drugs. Ketamine, an antagonist of NMDA receptors, seems therefore a rational option in super-refractory SE. We report our experience using this drug on a pediatric case of super-refractory SE. Method: Clinical case report. Result: 5 year-old girl with DiGeorge syndrome, extensive bi-hemispheric polymicrogyria, severe psychomotor retardation and epilepsy. During the course of a respiratory infection the patient developed generalized myoclonic SE. She was admitted in the ICU, where baseline anti-epileptic drug treatment was optimized and burst-suppression was achieved with midazolam, propofol, thiopental or combinations of these drugs. However, tapering anesthetics repeatedly resulted in clinical and EEG evidence of recurrent SE. After 30 days of ICU stay, ketamine was tried, with rapid clinical and EEG response, allowing UCI discharge one week later. At the 2-month follow-up visit, the patient had complete clinical recovery, with a return to her baseline neurological status. Conclusion: In this case of pediatric super-refractory SE, the response to ketamine was prompt and sustained, despite being initiated one month after ICU admission. We speculate if an earlier use of this drug might have aborted the SE sooner. Further case reports and clinical trials of ketamine in super-refractory SE are needed.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

p336 IN HOSPITAL DEATHS ASSOCIATED WITH STATUS EPILEPTICUS: A DR FOSTER ALERT E. F. Cant*, G. Cook, C. Wasson, and P. Talbot *Manchester University, Manchester, UK; Stepping Hill Hospital, Manchester, UK; and Salford Royal Hospital, Manchester, UK
Purpose: Dr Foster highlighted Stepping Hill hospital as having an abnormally high number of deaths among patients with a primary discharge code of status epilepticus (SE) from 20002011. This audit focused on why this occurred and if improvements could be made to prevent this in the future. Method: The notes of 15 out of the 17 patients who died with a discharge diagnosis code of G41 (SE) from 20002011 were audited assessing the care given in hospital and to determine whether the death was avoidable. Result: All patients were admitted in SE and had a mean age of 76. They were found to have significant comorbidities such as dementia, cerebrovascular disease and excess alcohol consumption. All had appropriate immediate management against guidelines. 8 patients were given phenytoin during admission;4 did not have their serum levels monitored and 4

99 Abstracts
had sub-therapeutic serum levels. 1 patient's ITU admission was delayed, 1 other patient may have been appropriate for ITU but referral was not discussed. 1 died from a pulmonary embolism. Conclusion: These deaths were unavoidable due to severe underlying disease triggering the seizures. The alert was due to inaccurate discharge coding where the primary diagnosis was inappropriately given as SE. However the audit of the management of SE highlighted areas for improvement. These included a need for closer and more rigorous monitoring of therapeutic Phenytoin levels; greater patient review for ICU and quicker transfer; optimising DVT prophylaxis early in SE management and the consistent use of measures to prevent aspiration. Updated guidelines are being implemented. 15 cases became refractory despite aggressive treatment with IV Benzodiazepines, Phenytoin, Valproate and Levetiracetam. 1 g Methyprednisolone for 5 days was administered to all 15 cases. In the meantime, the aetiology of NCSE was verified. Frequent follow-up EEG recordings were performed. Result: 7 patients clinically deteriorated, their EEG patterns remained unchanged and died within weeks or months afterwards. The mean age was 68.5 and the underlying disease was brain tumor (4 cases), herpes simplex encephalitis (HSE) (1), acute disseminated encephalomyelitis (ADEM) (1) and Creutzfeldt Jacob disease (1). Clinical improvement and EEG normalization was evident in 8 cases. The mean age was 48 and the underlying disease was neurosarcoidosis (1 case), Systemic Lupus Erythematosus (1), ADEM (1), stroke (2), Alzheimer's Disease (1) and HSE (1). Conclusion: High-dosage corticosteroid treatment should always be considered in the treatment of refractory NCSE. Furthermore, the clinical outcome is strongly influenced by the underlying disease and the patient's age.

Purpose: Newer antiepileptic drugs (AED) are increasingly prescribed, and seem to have a comparable efficacy as the classical AED in patients living with epilepsy; however, their impact on status epilepticus (SE) prognosis has received little attention. Method: In our prospective SE registry (200610) we assessed the use of newer AED (for this purpose: levetiracetam, pregabalin, topiramate, lacosamide) over time, and its relationship to outcome (return to clinical baseline conditions, new handicap, or death). We adjusted for recognized SE outcome predictors (Status Epilepticus Severity Score, STESS; potentially fatal etiology), and the use of >2 AED for a given SE episode. Result: Newer AED were used more often towards the end of the study period (42% versus 30% episodes), and more frequently in severe and difficult to treat episodes. However, after adjustment for SE etiology, STESS, and medication number, newer AED resulted independently related to reduced likelihood of return to baseline (p < 0.01), but not to increased mortality. STESS and etiology were robustly related to both outcomes (p < 0.01 for each), while prescription of >2 AED was only related to lower chance of return to baseline (p = 0.03). Conclusion: Despite increase in the use of newer AED, our findings suggest that SE prognosis has not been improved. This appears similar to recent analyses on patients with refractory epilepsy, and corroborates the hypothesis that SE prognosis is mainly determined by its biological background. Since newer AED are more expensive, prospective trials showing their superiority (at least regarding side effects) appear mandatory to justify their use in this setting.

p339 NONCONVULSIVE STATUS EPILEPTICUS IN NORMOGLICEMIC DIABETIC PATIENTS J. Klem*, L. Stancetic Bacvanin, and A. Bacvanin *General Hospital, Sombor, Serbia; and General Hospital, Sremska Mitrovica, Serbia
Purpose: Nonconvulsive status epilepticus (NCSE) causes many different neurologic deficits, particularly in alertness and cognitive function, and may be one of the most frequently missed diagnoses in patients with altered neurologic function. NCSE may constitute one quarter up to 40% of all status epilepticus. Diabet type 1 can cause an acute confusional state due to NCSE. Method: In our two 48 and 65 years-old patients, the lack of a predominant motor component differentiates NCSE from convulsive status epilepticus. First they were seen with bizarre, and fluctuating behaviour from lack of responsiveness to confusion with oral or manual automatisms lasting 48 hours before hospital addmision. During hospitalization altered mental status, subtle twitching, blinking, nystagmus, stupor and confusion were seen. They were diabetic. They had normal blood sugar levels . Both patients have had history of often comatose hypoglicemic states with generalized convulsiones due to low blood sugar levels. Result: laboratory screening including normal blood sugar levels showed no abnormalities . EEG showed prolonged repetitive complex partial seizures and/or continuous seizure activity in both patients. Computed tomography showed reductive cortical changes . After phenobarbital administration in the next 34 days, they became more responsive, and oral or manual automatism slowly resolved . Up to next 10 days after NCSE they were amnestic, and their verbal function recovery delayed. Conclusion: NCSE may occur in patients with diverse clinical diagnoses. Preventing missed diagnosis, EEG should be perfomed in all patients with unexplained reccurent altered mental status, stupor and confusion.

p338 CORTICOSTEROIDS IN THE TREATMENT OF NONCONVULSIVE STATUS EPILEPTICUS (NCSE) D. Tsiptsios, D. Kiourtidis, T. Tsironis, P. Petrou, E. Ameridis, M. Krommida, A. Mastrokosta, E. Markousi, G. Deretzi, E. Koutlas, J. Rudolf, A. Tichalas, G. Xiromerisiou, X. Fitsioris, and I. Tsiptsios Papageorgiou General Hospital, Thessaloniki, Greece
Purpose: NCSE is a neurological condition that is often missed or misdiagnosed in emergency neurology when immediate EEG recording is not available. Due to this fact NCSE often becomes refractory, ie lasting >24 hours. The aim of this study is to investigate the efficacy of high-dosage corticosteroid treatment in refractory NCSE. Method: During a 19 month period, June 2010 February 2012, 27 patients were diagnosed with NCSE based on EEG patterns, such as PLEDs, GPEDs and BiPEDs.

p340 FOCAL MYOCLONUS STATUS IS NOT UNCOMMON MANIFESTATION IN THE PATIENTS WITH ANTIFOSFOLIPID SYNDROME L. M. Stancetic Bacvanin*, J. Klem, and A. G. Bacvanin* *Srem.Mitrovica, Serbia; and Sombor, Serbia
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

100 Abstracts
Purpose: We present patients with antifosfpolipid syndrome (APS) and focal myoclonic status. Method: A medical files of 25 patients with APS (16 femals and 9 males) that were hospitalized from April 1999 to August 2010 in our department were evaluated. Result: We found four patients (16%) that had prolonged myoclonic seizures in their medical history. Myoclonic status lasted from 12 hours to 10 days . Half of the patients had secondary APS. Reccurent palatal myoclonus had 46 years-old female with brainstem vasculitic changes, 52 years-old female had hemiclonic status and bilateral brachial spinal myoclonic yerks.. Two men (52 and 65 years-old) had prolonged hemifacial myoclonic yearks . All patients were MRA pozitive to focal cerebral ischemia and focal cortical atrophy changes and all had increased titers of anticardiolipin antibodies (IgG 24,352 GPLU/ml; IgM 1462,9 MPLU/ml). Patient with Epilepsia partialis continua Kozevnikow had excessive unilateral or bilateral frontocentral polyspikes and spike waves discharges . During spinal myoclonic yearks there was no EEG-epileptic activity. MRI showed left focal frontotemporal atrophy. Patient with palatal myoclonus had frontocentroparietal polyspikes, and frontal slow activity on its EEG. MRI showed lacunar vascular supratentorial and brainstem ischemic lesions. Two men with hemifacial myoclonia had no specific EEG changes after the attacks. One had luetic gummous formation, the other microlacunar and extended predominantely temporal cortical atrophy. Conclusion: In this group four patients (16%) had prolonged myoclonic seuzures . Seizures were partially ameliorated by a complex of medications: anticonvulsants and pulse corticosteroid therapy.

p342 USE OF INTRAVENOUS LACOSAMIDE IN STATUS EPILEPTICUS AND CLUSTER SEIZURES Y. Handouk, C. Bomprezzi, C. Minardi, S. Malag, S. Morresi, and A. Mauro U.O. Neurologia, Cesena, Italy
Purpose: To test the efficacy and safety of the intravenous drug formulation in SE and cluster seizures. Some antiepileptic drugs (AEDs) used in status epilepticus (SE) are associated with potential respiratory and cardiovascular complications. Lacosamide (LCM), a new AED, has an intravenous formulation with a potential role in the treatment of SE. Method: 11 patients with symptomatic epilepsy (6 female and 5 male; mean age 66 (2390); 8 with SE and 3 with cluster seizures), was treated, after failure of other AEDs, with simultaneous administration of intravenous and oral LCM for two days (200 mg intravenous + 50 mg oral LCM twice daily), then switched to oral LCM (400 mg daily). Result: EEG improvement occured in the first 24 hours after the beginning of LCM therapy. All patients were responsive with no serious adverse event, except two old patients who died for severe comorbidities. Conclusion: LCM could be efficacious and safe in the treatment of SE.

Basic Science 7 Tuesday, 02 October 2012

p341 SUPER-REFRACTORY STATUS-EPILEPTICUS: THERE IS ALWAYS HOPE Z. Agirre-Arrizubieta*, and N. Moran *King's College Hospital, London, UK; and East Kent Hospitals NHS University Foundation Trust, Canterbury, Kent, UK
Purpose: Two male patients, 20 and 28 years, presented with acute seizures and encephalopathy. Multiple brain MRI examinations were normal and extensive metabolic, haematological and serological tests were negative. Cerebrospinal fluid (protein, glucose, microbiology, oligoclonal bands) was normal except patient A had 7 white cells/ml. Both received broad spectrum antimicrobials. Method: In patient A generalized tonic-clonic seizures led to ventilation and ultimately treatment with six anti-epileptic drugs (AED). The EEG initially showed a suppression burst pattern; following reduction of sedation, status epilepticus (SE) with a right temporal focus, plus generalized periodic epileptiform discharges (GPEDs). It was some three months before control was achieved but recovery was good with mild amnesia only. Result: Patient B had focal seizures with secondary generalization and then SE. The EEG revealed a right anterior focus, generalized seizures and GPEDs. He was ventilated and subsequent treatment comprised seven AED, including thiopentone, plus human pooled immunoglobulin and plasmapheresis. Six months following presentation, deep brain stimulation as associated with substantial improvement in the EEG but the patient was left in a persistent vegetative state. Conclusion: Each patient displayed similar clinical pictures of obscure aetiology with super-refractory SE (SRSE) (Shorvon S. Epilepsia. 2011 Oct;52 Suppl 8:536). However, the outcomes were radically different. Even when prolonged and of unknown aetiology, SRSE should not be regarded as hopeless.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

p343 THE EFFECTS OF ANTIEPILEPTIC DRUGS ON THE VOLTAGE-GATED SODIUM CHANNELS OF THE PERIPHERAL MYELINATED NERVE FIBERS OF THE ADULT RAT G. Zafeiridou*, A. Kagiava, M. Spilioti, A. Karlovasitou, and G. Theophilidis *Aristotle University, Thessaloniki, Greece; School of Biology, Aristotle University, Thessaloniki, Greece; and Medical School, Aristotle University, Thessaloniki, Greece
Purpose: One of the major targets of many widely used antiepileptic drugs (AEDs) are voltage-gated sodium channels (VGSCs). Some of these drugs have been associated with effects on the peripheral nerve function. In this study we investigated in vitro the effects of three AEDs on the VGSCs of the peripheral myelinated nerve fibres, of the adult rat. Method: The effects of phenytoin (PHT), topiramate (TPM) and lacosamide (LCM) were tested on the electrophysiological properties of the Wistar rat isolated sciatic nerve. Result: Incubation of the sciatic nerve fibers in therapeutic doses (72.9, 36.46, 18.23 lM) of PHT, caused a gradual decreased in the amplitude of the CAP and increase in the latency (p < 0.05). TPM was applied at much higher concentrations than the therapeutic doses (178.5 Mm, 500 lM), yet it had no effect on the amplitude of the CAP and the latency (p > 0.05). LCS was also investigated at high concentrations (100, 250, 400, 500 lM) but in this case, an acute, dose-respondent, decrease in the amplitude of the CAP was caused (p < 0.001). This intense decrease in amplitude was followed by a similar increase in the latency (p < 0.001). Conclusion: These findings confirm the adverse effect of PHT, in the peripheral nerve function even in very low concentrations. In contrast, LCS had effects at concentrations much higher than the therapeutic doses. LCS also demonstrates a different mode of action that causes rapid

101 Abstracts
and acute alteration on the electrophysiological properties of the peripheral nerve. Finally, TPM had no effects on the peripheral nerve function, although high concentrations were used. where characteristic slow potential shifts, but no reduction of diffusion tensor magnetic resonance (MR) signal and MAP-2 immuno-staining (typical of ischemic core) was observed. Recording of responses evoked by low- and high-frequency stimulations of the lateral olfactory tract showed no excitability changes in the early hours that follow ischemia in the olfactory cortical areas supplied by ACAs. Conclusion: The absence of early hyperexcitability changes in an isolated whole brain model of ischemia, strongly suggests that brain anoxia per se does not contribute to the generation of early seizures. These findings support the view that blood-borne events (such as hemorrhage and inflammation) may play a major role in early postischemic seizures.

p344 A NEW IN VITRO MODEL OF HIGH FREQUENCY ELECTRICAL STIMULUS INDUCED SEIZURE AND EFFECTS OF STANDARD ANTIEPILEPTIC DRUGS A. Wahab*, K. Albus, and U. Heinemann *University of Karachi, Karachi, Pakistan; and Charit Universitatsmedizin Berlin, Berlin, Germany
Purpose: In the hippocampus intense high frequency electrical stimulation induces a long lasting rhythmic synchronization (primary afterdischarge). In order to examine the suitability of primary afterdischarges (PADs) in organotypic hippocampal slice cultures (OHSCs) as an in vitro model of evoked seizures we have investigated in detail the sensitivity of PADs to standard antiepileptic drugs (AEDs). Method: OHSCs were prepared using interface culture method from eight to 11 day old Wistar rats. A PAD in CA1 was elicited by stimulating the stratum radiatum with an intensity of two times that required to elicit a maximal population spike. The effects of AEDs on the duration and on frequency properties of PADs and the tonic-like and clonic-like subdivisions of PADs were determined and EC50 values were calculated from concentration response curves. Result: All the standard AEDs except ethosuximide reduced the durations of PADs and tonic-like and clonic-like subdivisions of PADs. The effects were concentration dependent and reversible. The effects on subdivisions of PADs differed between AEDs. Carbamazepine and phenytoin shortened the tonic-like and clonic like subdivisions at similar proportions whereas phenobarbital, diazepam and valproic acid preferentially shortened the clonic-like subdivision. Diazepam at low concentrations increased the duration of tonic- like subdivisions an effect not seen with the other AEDs. The suppressive effects of AEDs on frequency properties observed only at higher concentrations. Conclusion: We conclude that the PAD test in OHSCs is a suitable in vitro model of evoked seizures. The validity of this model could be further examined by studying the effects of newer AEDs.

p346 INVESTIGATION OF ANTIEPILEPTIC DRUG TRANSPORT BY SOLUTE CARRIERS OATP1A2 AND MCT1 H. L. Jones, D. Dickens, A. Owen, M. Pirmohamed, and G. J. Sills University of Liverpool, Liverpool, UK
Purpose: We have investigated the trans-membrane transport of antiepileptic drugs (AEDs) by organic anion transporting polypeptide 1A2 (OATP1A2) and monocarboxylic acid transporter 1 (MCT1), members of the solute carrier super-family. Method: Xenopus laevis oocytes were transfected with OATP1A2/ MCT1 cRNA and transport determined three days thereafter by comparison of the uptake of radiolabelled AEDs (25 mM phenytoin, 20 mM carbamazepine, 300 mM sodium valproate, 10 mM lamotrigine, 10 mM gabapentin, 10 mM topiramate and 6 mM levetiracetam) in transfected vs untransfected oocytes. Estrone-3-sulfate (1 lM) and lactic acid (5 lM) were employed as positive control compounds for OATP1A2 and MCT1, respectively. Results from at least three independent replicates, each employing eight oocytes per group, were expressed as mean (SEM) percentage of control transport in untransfected oocytes. Result: Transport of estrone-3-sulphate in OATP1A2-transfected oocytes was 1326 171% of that observed in untransfected controls (p < 0.01). Transport of lactic acid in MCT1-transfected oocytes was 2607 240% of that observed in untransfected controls (p < 0.001). There were only minor changes in the mean transport of AEDs in transfected vs untransfected oocytes for both OATP1A2 (98.1 8.2% phenytoin, 91.3 2.8% carbamazepine, 111 7.3% sodium valproate, 128 7.7% lamotrigine, 104 17% gabapentin, 111 6.5% topiramate, 94.5 7.0% levetiracetam) and MCT1 (108 2.6% phenytoin, 110 4.1% carbamazepine, 94.0 3.8% sodium valproate, 77.6 5.7% lamotrigine, 164 15% gabapentin, 110 3.0% topiramate, 115 5.9% levetiracetam), none of which reached statistical significance. Conclusion: None of the seven AEDs investigated in this study appeared to be a substrate for either OATP1A2- or MCT1-mediated transport in selectively transfected Xenopus laevis oocytes. These findings discount the involvement of OATP1A2 and MCT1 in the transmembrane transport of AEDs.

p345 PENUMBRA REGION EXCITABILITY IS NOT ENHANCED ACUTELY AFTER CEREBRAL ISCHEMIA IN THE IN VITRO ISOLATED GUINEA PIG BRAIN G. L. Breschi*, A. Mastropietro, I. Zucca, L. Librizzi*, and M. De Curtis *Neurological Inst. C. Besta, Milano, Italy; and I.R.C.C.S. Foundation Neurological Institute, Milan, Italy
Purpose: Early seizures are a frequent consequence of stroke. The main goal of the present study is to verify whether anoxic ischemia per se is able to induce early changes in excitability that may be a prelude to the generation of seizures and, ultimately, to epileptogenesis. Excitability changes in the very acute postischemic phase are here analyzed in a new model of ischemia developed in the isolated guinea pig brain preparation. Method: Permanent bilateral occlusion of the anterior cerebral arteries (ACAs) was performed in the isolated guinea pig brain maintained in vitro by arterial perfusion. Magnetic resonance imaging and immunohistochemistry were utilized to identify the penumbra and core regions induced by ACA occlusion (ACAo). Slow potentials and evoked responses recorded in olfactory cortices were utilized to evaluate excitability changes in the acute phase after ischemia. Result: ACAo induces a core area located in the shell of the nucleus accumbens and a region of penumbra in the underlying olfactory cortices,

p347 L-TYPE VOLTAGE GATED CALCIUM CHANNELS AFFECT SEIZURE-LIKE ACTIVITY IN AN AMBIVALENT MANNER, BUT PROMOTE THE INDUCTION OF PAROXYSMAL DEPOLARIZATION SHIFTS H. Kubista, L. Rubi, M. Lagler, P. Geier, K. Dasgupta, and S. Bhm Center of Physiology and Pharmacology Medical University of Vienna, Vienna, Austria
Purpose: The role of L-type voltage-gated calcium channels (LTCCs) as regulators of neuronal excitability relies on the coupling of
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

102 Abstracts
LTCC-mediated Ca2 + -influx to Ca2 + -dependent conductances. We have shown previously that in moderate (with respect to duration and amplitude) depolarisations excitatory Ca2 + -activated nonspecific cation channel-activation prevails, which diminishes and gives way to the activation of hyperpolarising Ca2 + -dependent potassium channels as the depolarization grows. These findings prompted us to test in a similar approach the effects of LTCC modulation on (long-lasting) seizure-like activity (SLA) and on (brief) paroxysmal depolarization shifts (PDS). Method: Current-clamp experiments were performed on primary hippocampal neurons. SLA was induced by pharmacological means (e.g. lowMg2 + buffer). Induction of PDS was facilitated by caffeine. LTCC activity was modulated by BayK 8644 (LTCC agonist) and isradipine (antagonist). Result: Potentiation of LTCCs affected SLA activity in opposing manners, leading to enhancement involving plateau potentials on the one hand and reduction involving more pronounced after-hyperpolarisations on the other hand. Caffeine alone was hardly sufficient to induce PDS, but PDS were readily induced when LTCC activity was augmented by co-application of BayK. Conclusion: The bimodal effects of LTCC activation on excitability can be extended to epileptiform discharges. Hence, therapeutic reduction of LTCC activity may have little beneficial or even adverse effects on epileptic seizures. However, our data identifies enhanced activity of LTCCs as one precipitating cause of PDS. Because evidence is continuously accumulating that PDS represent important elements in epileptogenesis, LTCC inhibitors may prove useful in anti-epileptogenic therapy (supported by the Austrian Science Fund, project P-19710). Conclusion: Our results suggest that neocortical slices derived from both epileptic and tumor patients can generate multiple types of SSPA. Supragranular layers might have a leading role in the generation of SSPA. Features of SSPA were similar in epileptic and tumor slices, indicating that the emergence of neocortical SSPAs may not be related to epileptic processes.

Purpose: Proper balance of neuronal activity is essential for normal brain function. When the balance is compromised, neurological disorders may result. Temporal lobe epilepsy (TLE), a neurological disorder, is the most common form of adult focal epilepsy. The purpose of this study was to characterize the cellular and population dynamics of subiculum under hyperexcitable conditions. Method: 4-Amino Pyridine with reduced magnesium model of epilepsy was used in this study. Cellular and population electrical activity was recorded through whole cell patch clamp and local field potential recording techniques. Result: We have observed a distinct phenomenon in subiculum wherein an early hyperexcitable phase was followed by a late silent phase (LP) upon application of 4-AP. Silent state in pyramidal neuron was characterized by periodic inhibitory post-synaptic potentials (pIPSPs) at a frequency of 0.21 Hz. GABAA receptor mediated inhibition coincided with excitatory inputs to countermand burst discharges. Gap junctions were found to be critical for these pIPSPs generation. Fast spiking interneurons showed bursting discharges during the silent phase which might be triggering pIPSPs. The pIPSPs in pyramidal neurons ceased if the CA1-alveus was fissured. A strong coupling between CA1 discharge and subicular pIPSPs indicates an important role of CA1 region. Conclusion: We conclude that the action of feed forward inhibition concerted by gap-junctions triggered homeostatic control leading to suppression of epileptiform activity in subiculum, during the late phase (LP). Our work suggests that gap junctions are important in suppression of epileptiform activity in subiculum and argues the general notion of gap junctions being pro-epileptic.

p348 PATTERNS OF SYNCHRONOUS POPULATION ACTIVITY IN THE NEOCORTICAL TISSUE OF EPILEPTIC AND NON-EPILEPTIC TUMOR PATIENTS, IN VITRO K. Tth*, . Kandrcs, C. Szab, A. Bag, L. Er} oss, L. Entz, P. Orbay , S. Czirjk , P. Vrady , L. Sipos , T. Freund, I. Ulbert, and L. Wittner *Institution of Experimental Medicine, HAS, Budapest, Hungary; Pzmny Pter Catholic University, Budapest, Hungary; National Institute of Neuroscience, Budapest, Hungary; Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary; and Institute for Psychology, Hungarian Academy of Sciences, Budapest, Hungary
Purpose: The subiculum and hippocampal CA2 region of patients with temporal lobe epilepsy generate spontaneous population bursts in vitro, which is thought to be in relation with the epileptic reorganization. We asked whether neocortical tissue of epileptic patients generates similar spontaneous synchronous population activity (SSPA). As control we used tissue of patients with brain tumor, without epilepsy. Method: Slices were prepared from the postoperative tissue and the local field potential gradient (LFPg) was recorded. Pyramidal cells were characterised in intracellular records. Result: 48% of epileptic and 42% of tumor slices displayed SSPA. SSPAs were characterized by LFPg transient superimposed with high frequency oscillations and increased multi unit activity. The pattern of SSPAs varied among the samples, but all types were present in both epileptic and tumor samples in a similar ratio. In 60% of the cases SSPAs were observed in the supragranular layers. Cell clustering analysis showed that ~67% and ~50% of the cells increased their firing rates in relation to SSPA, in epileptic and tumor slices, respectively. Generally, the discharge rate of supragranular cells was enhanced before the LFPg peak, whereas infragranular cells fired after it. 2/3 of the intracellular recorded cells showed depolarizing responses during SSPAs.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

p350 EPILEPTIFORM ACTIVITY IN THE PIRIFORM CORTEX AFTER 4AP ADMINISTRATION IN THE ISOLATED GUINEA PIG BRAIN L. M. Uva, F. Trombin, G. Carriero, and M. De Curtis Fondazione IRCCS Istituto nazionale Neurologico, Milano, Italy
Purpose: We recently showed that arterial application of the K+ channel blocker 4-aminopyridine (4AP) induces two different and independent seizure-like event (SLE) patterns in the olfactory and limbic regions (Carriero et al., 2010). We further characterize here the network and cellular features of SLEs in the olfactory cortices. Method: 4AP was arterially administered (50 lM; 5 min) or locally injected (2.5 mM) in the in vitro isolated guinea-pig brain. Field potentials (FPs) were simultaneously recorded from different limbic subregions. Simultaneous extracellular and intracellular recordings and [K+]o shifts were recorded to characterize the activity in PC. Result: We observed runs of fast activity (FRs) and SLEs featuring runs of high frequency activities superimposed to slow components followed

103 Abstracts
by a serie of spikes. Lesions and local 4AP applications demonstrated that SLEs initiate in PC. We found that layer II neurons discharged during FRs and that during SLE there was a progressive inactivation of firing that was blocked at the peak of the membrane depolarization and resumed during the spikes. The firing block was rescued injecting hyperpolarizing current, suggesting a depolarization block. We found the abolishment of the evoked response during SLEs after lateral olfactory tract stimulation and a partial recovery during the spikes. Simultaneous recordings of FPs and [K+]o shifts showed a gradual [K+]o increase during FRs and a secondary faster increase during SLEs. Synaptic activity recovers after synchronous spiking and levels of [K+]o recovered. Conclusion: The PC is the generator of the described activities. We observed a hypo-excitable status of PC networks that initiates a focal seizure-like discharge. intracerebroventricular des-acyl ghrelin administration affected food intake via the orexin pathway. Recently, des-acyl ghrelin has been proposed to have beneficial effects on limbic seizures. In this study, we further characterised the role of des-acyl ghrelin in seizures using the focal pilocarpine model for limbic seizures. Method: In this study we used the in vivo rat model for pilocarpineinduced limbic seizures. Intrahippocampal administration of des-acyl ghrelin, the dual orexin receptor antagonist almorexant, or co-administration of des-acyl ghrelin and almorexant was performed in rats for 2 h prior subsequent administration of pilocarpine directly in the hippocampus. Rats were monitored following pilocarpine perfusion, and seizure behavior grades were evaluated according to a modified Racine's scale. Result: We noted that while des-acyl ghrelin attenuated pilocarpineinduced limbic seizures at different concentrations, almorexant did not affect seizure severity. To determine whether des-acyl ghrelin utilizes the orexin pathway for its anticonvulsant effect, des-acyl ghrelin was coadministered with almorexant. Dual orexin receptor blockade did not prevent des-acyl ghrelin's anticonvulsant effect. Conclusion: We confirmed that des-acyl ghrelin attenuates limbic seizures and established that the orexin pathway is not involved. This is also first evidence that simultaneous antagonism of hippocampal orexin receptors does not affect seizure severity. This study highlights the need of identifying the mechanism of action of des-acyl ghrelin in epileptic seizures.

Purpose: GABA undergoes complex receptor modulations in epileptic tissue, forming inhibitory and excitatory networks. GABAB receptors (GABABRs) underlie various phenotypes of Idiopathic Generalized Epilepsy (IGE). Generally, GABAB agonists exacerbate absence seizures. GABAB antagonists reduce absences. Convulsive seizures may be induced by GABABR inhibition, and alleviated by GABAB agonists. GABABR isoforms B1a, B1b and B2 perform specific roles allowing normal GABABR functioning, hence directly impact IGE phenotypes. Controversially, atypical absence seizures have been observed in GABAB knockout models, implying a contradiction to prior research. Method: A metasearch was conducted to determine how altered GABABRs in rodent models produce different IGE phenotypes, producing 28 articles. Result: A minority of papers noted normal GABABR expression in typical absence seizures, contradicted by pharmacological studies where they were exacerbated by GABAB agonists. Other studies showed increased GABABR expression with age and seizure occurrence. This was attributed to increased neocortical GABAB autoreceptor expression and increased presynaptic GABAB thalamic expression. Transgenic upregulation of B1a and B1b induced atypical absence seizures in thalamocorticolimbic networks. Knockout studies in corticolimbic networks caused clonic seizures. Atypical absences were only observed in a minority of GABAB1-/- mice. Seizure severity is subtype specific; B1a rescued the clonic phenotype, and increased absence severity when upregulated. Conclusion: Absence seizures are predominantly caused by excess inhibition in thalamocortical networks, due to increased GABABRs expression; these seizures become atypical when GABABRs are upregulated in the limbic network. Clonic seizures are associated with reduced GABABR expression. Seizure severity is modulated by varying expression of GABAB subtypes.

Basic Science 8 Tuesday, 02 October 2012

p353 ANTI-SEIZURE ACTION OF THE ANTIDEPRESSANT, SERTRALINE M. Sitges, and B. I. Aldana Instituto de Investigaciones Biomdicas, Universidad Nacional Autnoma de Mxico, Mxico D.F., Mexico
Purpose: Investigate the potential anticonvulsive action of sertraline, as recently we found that sertraline inhibits cerebral presynaptic Na+ channels controlling release of the excitatory amino acid neurotransmitter glutamate (Aldana & Sitges J Neurochem 2012; in press); like several antiepileptic drugs do (Sitges M et al. Neuropharmacology 2007;52:598 605). Method: Pentilenetetrazole (PTZ, 50 mg/kg i.p.)-induced seizures and cortical excitability changes, as judged by the EEG highest peak amplitude value (HPAV), were respectively evaluated in non anesthetized and in anesthetized animals previously administered with: vehicle (control group), sertraline (range from 1.5 to 25 mg/kg) and carbamazepine (15 and 25 mg/kg), as positive control. Result: In all the non anesthetized animals injected with vehicle the first generalized tonic-clonic seizure was presented near the first minute following PTZ and 40% of the animals died. In animals administered with 2.5 mg/kg sertraline the latency of the first seizure to PTZ increased and its duration decreased but seizures were not prevented. At a high dose (25 mg/kg) sertraline completely prevented seizures to PTZ. None of the animals pre-administered with sertraline at any dose died. In the anesthetized animals injected with vehicle, the baseline EEG HPAV (42 1 lV) increased to 164 6 lV in the first 120 s interval following PTZ. This PTZ-induced increase in the HPAV was: insensitive to 15 mg/kg carbamazepine, lost in half of the animals injected with 2.5 mg/kg sertraline and absent in all the animals injected with sertraline above 5 mg/kg or with 25 mg/kg carbamazepine. None of the anesthetized animals died. Conclusion: Present findings demonstrate the anti-seizure effect of sertraline.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

p352 THE OREXIN PATHWAY IS NOT INVOLVED IN THE ATTENUATION OF LIMBIC SEIZURES BY DES-ACYL GHRELIN J. Coppens, J. Portelli, Y. Michotte, and I. Smolders Vrije Universiteit Brussel, Brussels, Belgium
Purpose: Once considered inactive, des-acyl ghrelin is now implicated in a number of biological functions. Unlike ghrelin, des-acyl ghrelin is unable to activate the ghrelin receptor and recently one study implied that

104 Abstracts
p354 PROTEOMIC PROFILING OF THE HIPPOCAMPUS OF EPILEPTIC MICE WITH AND WITHOUT SCLEROSIS A. Mago*, K. A. Kekesi, A. Simor, K. Tth, E. HunyadiGulyas, Z. Darula, K. Medzihradszky, T. Freund*, G. Juhasz, and Z. Magloczky* *Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary; Etvs Lornd University, Inst. Biology, Budapest, Hungary; Institution of Experimental Medicine, HAS, Budapest, Hungary; Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary; and Etvs Lornd University, Inst. Biology, Research Group of Proteomics, Budapest, Hungary
Purpose: Abnormal expression of certain proteins was found in neurodegenerative diseases. We analyzed proteomic networks in the pilocarpine-model of epilepsy in mice. Method: After one-month survival the animals were sacrificed and the brain was removed. The right hippocampus was processed for proteomic analyses, the left one for morphological characterization. Proteins were separated by 2-dimensional gel electrophoresis, and identified by Liquid chromatography-mass spectrometry. Animals were classified on the basis of the hippocampal cell loss as non-sclerotic or sclerotic. Result: We examined the proteomic alterations compared sclerotic to control and non-sclerotic to sclerotic animals. A network was built from these proteins using Ariadne Genomics Pathway studio software establishing direct interactions of proteins, and their relationships with schizophrenia, Alzheimer's disease (AD), Parkinson's disease, temporal lobe epilepsy and anxiety. In the networks there were 54 out of 93 (in case of control-sclerotic) and 44 out of 82 (in case of non-sclerotic-sclerotic) proteins with at least one interaction with protein or disease. These proteins were analyzed by establishing three functional groups: metabolisms, synaptic and receptor functions and cytosceleton. Their contributions in epileptic reorganization are analyzed. Overlap with other neurological disorders was found. The altered proteins showed the most connection with AD and the least connection with anxiety. Conclusion: On the basis of the data, some neurological diseases may have overlapping molecular mechanisms. Furthermore, no direct interactions with proteins/diseases were found in the networks in case of certain proteins. It might mean that available data about the functions and interactions of proteins are incomplete in the scientific literature. iod). At the end of training period, convulsive dose of homocysteine thiolactone (8.0 mmol/kg) was intraperitoneally injected to rats from both groups and convulsive behavior was assessed by seizure incidence, latency to first seizure, number of seizure episodes and its severity (04 grades scale). Result: There were no statistically significant differences in seizure incidence induced by homocysteine thiolactone between exercised and sedentary rats (p > 0.05). Latency to first seizure was increased in exercised comparing to sedentary group of rats. Exercised rats displayed lower number of seizure episodes per rat in comparison with sedentary rats (p < 0.05), but severity of these seizures did not differ significantly between groups. Conclusion: These results indicate beneficial effects of chronic aerobic exercise in model of homocysteine thiolactone-induced seizures in rats, supporting the promotion of sport and physical exercise among patients with epilepsy.

p356 EARLY AND LATE MRI CHANGES IN RAT BRAIN AFTER STATUS EPILEPTICUS AND BEHAVIORAL IMPAIRMENT E. Suleymanova*, M. Gulyaev, A. Barkova, and N. Chepurnova *Lomonosov Moscow State University, Faculty of Biology, Moscow, Russian Federation; Lomonosov Moscow State University, Moscow, Russian Federation; and Lomonosov Moscow State University, Biological faculty, Moscow, Russian Federation
Purpose: Status epilepticus is a dangerous condition which can lead to brain damage and impairment of memory and cognitive functions later in life. The purpose of our study was to investigate the relationship between acute damage caused by prolonged seizures and later consequences of status epilepticus. Method: The lithium-pilocarpine model of status epilepticus (SE) in rats was used. MRI study of rat brain was performed 2, 7 and 30 days after SE. High-resolution T2 images and T2-maps were obtained, and total damaged area, hippocampal volume, and T2 relaxation time in several brain structures were calculated. After the MRI study, animals were tested in an open field. The test was performed three times with 24-hour intervals. To study depression-like behavior in rats, forced swim test and taste preference test were performed to evaluate depression. Result: Two days after SE, an increase of T2 signal was found in hippocampus and associated structures. The patterns of brain damage in rats after SE varied considerably. All rats after SE demonstrated hyperactivity in an open field one month later and did not habituate. These rats also were more active in the forced swim test, however some animals demonstrated the lack of taste preference. Rats with considerable acute changes in brain, tended to demonstrate higher activity in an open field in comparison with rats with less pronounced early MRI changes and were more prone to anhedonia. Conclusion: Rats with severe MRI abnormalities in brain found two days after SE tend to develop more pronounced behavioral impairment 1 month later.

p355 BENEFITS OF AEROBIC EXERCISE FOR ADULT RATS WITH SEIZURES INDUCED BY HOMOCYSTEINE THIOLACTONE D. Hrncic*, A. Rasic-Markovic*, R. Sarhan, V. Susic, D. Macut*, D. Djuric*, and O. Stanojlovic* *Belgrade University School of Medicine, Belgrade, Serbia; Menoufia University Faculty of Medicine, Tanta, Egypt; and Serbian Academy of Sciences and Arts, Belgrade, Serbia
Purpose: Homocysteine, together with its reactive thioester homocysteine thiolactone is proven risk factor for numerous CNS disorders including epilepsy. The aim of this study was to determine the effects of chronic aerobic exercise on rat model of homocysteine thiolactone induced seizures. Method: Adult male Wistar rats were familiarized with the treadmill apparatus (NeuroSciLaBG-Treadmill, Elunit, Serbia) for 3 days in sessions of 10 min at ramp belt velocity of 510 m/min. Afterwards, rats were randomly divided into 2 groups: chronic aerobic exercise (30 min treadmill training at 20 m/min velocity for 30 days) and sedentary control (the same time spent in treadmill apparatus at 0 m/min for the same perEpilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

p357 BRIEF SEIZURES INDUCE A SEVERE ISCHEMIC/HYPOXIC EPISODE G. C. Teskey, and J. S. Farrell University of Calgary, Calgary, Canada
Purpose: Ischemic/hypoxic episodes and seizures both result in a number of deleterious effects to brain functioning including enhanced

105 Abstracts
inflammatory responses, blood brain barrier permeability, astrocyte activation and neuronal death. This suggested to us that seizures may result in an ischemic/hypoxic episode. We tested this hypothesis by measuring local brain oxygen levels, before during and after brief seizures in a number of forebrain structures. Method: Adults rats had both an electrode and an oxygen sensing optrode implanted in their motor neocortex, amygdala or hippocampus. One week after implantation surgery, oxygen levels were recorded in awake, freely moving rats during and following electrically elicited seizures or other types of patterned electrical stimulation that did not result in seizures. Result: Immediately following termination of the afterdischarges we observed a severe hypoxic episode (<10 mm pO2) that lasted on the order of tens of minutes in the neocortex and an hour in the hippocampus. Electrical stimulation that did not give rise to a seizure did not result in a hypoxic episode. Pharmacological agents that did not affect the seizure but enhanced vasodilation and blocked vasoconstriction prevented the seizure-induced severe ischemic/hypoxic episode (SISIHE). Conclusion: Seizures result in vasoconstriction that leads to reduced local blood flow and severely reduced oxygen levels. It is possible that it is not the seizures per se that directly cause the long-term disruption of brain function, but the resulting ischemic/hypoxic episode. This phenomenon has potentially important implications for the management of seizure disorders. Purpose: Oxidative stress is known to decrease convulsion threshold and depletion of endogenous antioxidants was suggested to provide a molecular mechanism that triggers ictogenesis in a genetic mouse model for secondary generalized seizures (Takaki et al. Brain Res 2008;1228:15). We therefore investigated total glutathione (GSH) content in somatosensory cortex (SSC) of pre- and symptomatic WAG/Rij rats, a well-validated model for absence seizures. Moreover, protein expression levels of xCT (specific subunit of the cystine/glutamate antiporter) as well as EAAC1 were measured in these rats. These transporters provide respectively glial cells and neurons with cyst(e)ine, the rate-limiting building block in the synthesis of GSH. Method: Semi-quantitative western blotting was performed on SSC tissue of respectively presymptomatic and symptomatic WAG/Rij animals and age-matched ACI control rats using rabbit EAAC1 antibody (1:4000; Alpha Diagnostic) and rabbit xCT antibody (1:10000; Massie et al. Neuroreport 2008;19:15891592.). Total GSH content was examined using a Quant-iT Protein Assay Kit (Invitrogen). Result: A significantly decreased expression of xCT (ACI 100,0 5,8%; WAG/Rij 73,5 5,8%; p = 0,03) and EAAC1 (ACI 100,0 15,1%; WAG/Rij 53,7 2,5%; p = 0,002) was observed in the young WAG/Rij rats. In the symptomatic WAG/Rij rats, protein levels of xCT (ACI 83,9 2,0%; WAG/Rij 161,4 28,9%; p = 0,002) were significantly increased compared to the age-matched ACI rats. Total GSH content was unaffected in presymptomatic WAG/Rij rats. Conclusion: Although expression levels of xCT and EAAC1 were altered in SSC samples of both presymptomatic and symptomatic WAG/Rij rats, total GSH content was unaffected compared to ACI control rats.

Purpose: Generalized absence seizures are generated within the corticothalamo-cortical system. We analysed thalamic and cortical-thalamic interactions via multisite local-field-potentials with the aid of non-linear association analyses. Method: WAG/Rij rats with multiple electrodes targeting subgranular layers of the somatosensory-cortex, rostral and caudal RTN, VPM, anterior-(ATN) and posterior (Po) thalamic nucleus were used. Dynamics of association strength, coupling-direction and time-delays between all channel pairs were analyzed pre-ictally, ictally and in control periods. Result: Earliest and strongest increases in coupling-strength were seen between cortical layer 5/6 and Po. Other thalamic nuclei became involved later in SWD activity. The cortex guided most thalamic nuclei while cortex and Po kept a bidirectional crosstalk during the first 500 ms of SWDs. Most thalamic nuclei guided the Po until the end of the SWD. While the rostral RTN showed increased coupling with Po, the caudal RTN decoupled. Instead, it directed its activity to the rostral RTN. Conclusion: Next to the focal cortical instignation zone of SWDs, the Po seems crucial for their occurrence. This nucleus shows early increases in coupling and is the only nucleus which responds to the cortex within the first 500 ms of SWDs. Other thalamic nuclei seem to have only a function in SWD maintenance. Rostral and caudal-RTN have opposite roles in the occurrence of SWD.

Purpose: Epileptic vulnerability in rodents is frequently evaluated by observing the effects of a seizure-inducing insult, such as pilocarpine injection. However, seizure scoring is difficult, user dependent, and requires an elaborate setup. Lately, several new simplified ways of grading seizure response have emerged in the litterature. The correlation between these behavioural observations and EEG-verified seizure activity has not been investigated. This pilot study aimed to use video-EEG to evaluate novel simplified behavioural seizure correlates such as latency to grade 56 seizure, number of grade 56 seizures, or seizure index (an arbitrary grouping of high-grade seizures), in the pilocarpine-induced status epilepticus model in mice. Method: Video-EEG was performed on mice from the 129-strain, which is commonly used for genetic modification. Pilocarpine was administered as a single peritoneal injection and the animals were observed for 90 minutes. EEG and video was then interpreted separately and statistical correlation sought between behavioural correlates and EEG seizure activity. Result: Similar number of grade 56 seizures were observed in mice with very different duration of electrographic seizure activity. Latency to the first grade 56 seizure correlated best with duration of EEG seizure activity, but did not reach statistical significance. Conclusion: Some of the novel behavioral correlates may not be optimal surrogate markers for electrographic seizure activity, indicating that EEG should ideally be performed when screening transgenic mice in this model. We plan a larger study to asess which behavioural correlate is best to use in the absence of EEG.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

p359 AGE-DEPENDENT CHANGES IN XCT AND EAAC1 EXPRESSION IN SOMATOSENSORY CORTEX OF WAG/RIJ RATS J. Van Liefferinge*, A. Schallier*, G. Van Luijtelaar, Y. Michotte*, A. Massie*, and I. Smolders* *Vrije Universiteit Brussel, Brussels, Belgium; and Radboud University Nijmegen, Nijmegen, Netherlands

106 Abstracts
Purpose: We have performed fast Fourier transformation (FFT) analysis on the afterdischarge (AD) induced by chronic hippocampal kindling of the rabbit and revealed that enhancement of the higher frequency band (HFB: 1230 Hz) component is associated with kindled stage. In the present study, we examined effect of low-frequency stimulation (LFS) on ADs induced by acute kindling of the rabbit hippocampus to reveal the underlying mechanism of anti-kindling effect of LFS. Method: Fourteen adult rabbits were used. Under deeply anesthesia, kindling stimulations (1 msec, biphasic 50 Hz, 1 sec train) with suprathreshold intensity for AD were delivered at 20-min intervals to the right hippocampus. The LFS was added at 1 Hz for 15 min immediately or 20 sec after the kindling stimulation to the ipsilateral or contralateral side when HFB in AD increased to the kindled level. FFT analysis on each AD was performed to reveal the LFS effect. Result: During the acute kindling, the power spectral density (PSD) ratio of HFB component against total PSD changed from 16.1 9.7% (meanSD) at the initial stage to 45.9 17.6% (p < 0.001) at the final stage. Both types of LFS application could not suppress the enhancement of HFB component, but suppress the appearance of kindling-induced spontaneous seizure activity. Conclusions: An enhancement of HFB component also occurred in the acute kindling. Anti-kindling effect of LFS may depend on stimulation site and timing. multilobar, 2(5%) hemispheric and 5(12%) bilateral. Favorable seizure outcomes were achieved in 6/6 (100%) patients with completely resected, 8/23(35%) with partially resected, 5/7(71.5%) with non-resected hyperperfusion zone and in 1/8(12.5%) subjects with no ictal SPECT activation. Conclusion: Complete resection of the ictal SPECT hyperperfusion zone is a strong predictor of surgical success in children with TSC. Epilepsy surgery planning in TSC is nevertheless highly complex; SPECT findings should be correlated with clinical, electrophysiological and other neuroimaging data. Supported by Kontakt Program ME09042, IGA NT/11443-5, CZ.2.16/3.1.00/24022 and GAUK 17010.

p363 EFFICACY OF VAGUS NERVE STIMULATION IN 28 CONSECUTIVE PATIENTS WITH TREATMENT RESISTANT EPILEPSY NOT ELIGIBLE FOR EPILEPSY SURGERY F. Dainese*, G. Randazzo, G. Pauletto, F. Paladin*, C. Lettieri, C. Conti, M. Skrap, L. Comelli, A. Volzone, and P. Bonanni *SS Giovanni e Paolo Hospital, Venice, Italy; IRCCS Eugenio Medea, Conegliano (TV), Italy; SM della Misericordia Hospital, Udine, Italy; and DellAngelo Hospital, Mestre (VE), Italy
Purpose: The aim of this study was to assess the efficacy and safety of vagus nerve stimulation (VNS) in a consecutive series of patients with refractory epilepsy (RE) not eligible for epilepsy surgery. Method: This is a retrospective study of 28 patients who underwent VNS implantation for RE between 1996 and 2011. Patients were recruited from 3 epilepsy units in the North-East of Italy. The age at time of implantation was from 8 to 59 years (mean age 32,34; SD 12,7 y). All patients were classified according to the epileptic phenotype and the etiology. Twenty-one patients had focal or multifocal epilepsy, of whom 7 with bitemporal epilepsy, 4 had Lennox-Gastaut syndrome, 2 had Dravet syndrome, 1 had Angelman syndrome. According to the last proposal of classification, the etiology was structural in 16 patients, genetic in 3 and unknown in 9. All patients had a long duration of epilepsy before implantation (mean age 24 y). Result: Duration of VNS treatment varied from 0 to 15 years (mean 3 y). Mean seizure frequency significantly improved following implantation in 64% of patients. Interestingly 56% of patients showed also improvement in quality of life. No important side effects were reported by patients. Conclusion: VNS is a safe and effective palliative treatment option for RE not eligible for epilepsy surgery. Interestingly our data show that VNS is an effective treatment not only in cases of epilepsy with structural or unknown etiology but also in case of epilepsy due to a specific genetic cause as Dravet Syndrome and Angelman Syndrome.

Epilepsy Surgery 3 Tuesday, 02 October 2012

p362 LOCALIZING VALUE OF ICTAL SPECT IN PATIENTS WITH TUBEROUS SCLEROSIS COMPLEX AND INTRACTABLE EPILEPSY A. Jahodova*, M. Kudr*, P. Krsek*, V. Komarek*, P. Jayakar, C. Dunoyer, T. Resnick, and M. Duchowny *University Hospital Motol, Prague, Czech Republic; and Brain Institute, Miami children hospital, Miami, FL, USA
Purpose: To assess a practical value of ictal SPECT in localizing the seizure onset zone in pediatric patients with tuberous sclerosis complex (TSC) and intractable epilepsy. Method: We visually evaluated 52 ictal SPECT studies in 26 children with TSC surgically treated in Miami Children's Hospital between 1994 and 2010. The extent and location of the ictal hyperperfusion was evaluated and completeness of its surgical removal was assessed. The extent of the hyperperfusion zone resection was classified as completely resected, partially resected and non-resected and correlated with postsurgical seizure outcomes. Outcomes were regarded as favourable in patients with 90% seizure reduction and unfavourable in subjects with <90% seizure reduction. Result: There were 35 studies in previously non-operated patients, nine postsurgical studies in patients who subsequently underwent a reoperation and eight postsurgical studies in patients who had no further surgery (excluded from outcome analyses). Cortical hyperperfusion was present in 41(79%) ictal studies and absent in 11(21%) studies. In 41 positive SPECT studies, 10(24%) were well-localized, 13(32%) lobar, 11(27%)
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

p364 RESECTIVE SURGERY FOR REFRACTORY STRUCTURAL EPILEPSY IN INFANTS AND YOUNG CHILDREN G. Ramantani*, N. E. Fritz, K. Strobl, G. Wiegand, S. Schubert-Bast, H. Mayer, R. Korinthenberg*, U. Stephani, J. Zentner*, A. Schulze-Bonhage*, and T. Bast *University Hospital Freiburg, Freiburg, Germany; University Childrens Hospital, Heidelberg, Germany; Epilepsy Center Kork, Kehl-Kork, Germany; and University Medical Centre Schleswig-Holstein, Kiel, Germany

107 Abstracts
Purpose: Resective surgery is becoming an important treatment option for refractory structural epilepsy in early childhood. We report on indications, complications and outcomes in very young children undergoing epilepsy surgery at the Epilepsy Centre Freiburg. Method: We retrospectively reviewed the electroclinical, neuroimaging and neurodevelopmental findings, surgical procedures and complications, histologically defined epilepsy substrates and outcomes of children under 3 years of age that underwent epilepsy surgery in the years 2001 2011. Result: 30 children were included in this study. Seizure onset was in the first year of life in 28 (93%) patients and mean age at first surgery was 20.6 months (533.6 months). 18 (60%) infants had a historyof infantile spasms. Epilepsy substrates consisted in malformations of cortical development in 24 (80%) cases, glioneural tumor alone or in combination with cortical dysplasia in 3 (10%), and infarct in 3 (10%). 34 surgical procedures were performed including 16 (47%) functional hemispherectomies, 7 (21%) multilobar resections and 11 (32%) intralobar resections. 3 children underwent repeat surgery in our institution, while a single child had three consecutive resections. No mortalities occurred. Surgical complications included hydrocephalus in 3 patients as well as meningitis and hemorrhage in single cases. In follow-up from 1 to 11 years, seizure freedom was achieved in 23 (77%) children (Engel I), while 5 (17%) demonstrated a worthwhile improvement (Engel II or III) and 2 (7%) children showed no remarkable improvement. Developmental outcomes were generally preserved. Conclusion: Benefit in terms of seizure control and developmental progress is achievable in the majority of very young children with structural epilepsy selected for resective surgery. While early complication rates are infrequent and manageable, late complications are limited to extensive, hemispheric procedures. Cognitive outcomes were not compromised in the majority of our cohort. Conclusion: Lesional TLE in young children may present as a catastrophic epilepsy. Although with generalized clinical and electrographic features, a resective epilepsy surgery should be considered as early as possible to achieve seizure control and improvement of mental development.

p366 LONG-TERM OUTCOME OF RESECTIVE SURGICAL PROCEDURES IN ADULT PATIENTS WITH REFRACTORY EPILEPSY-THE KORK SERIES A. M. Staack*, A. Wendling*, I. Wisniewski*, J. Scholly*, S. Bilic*, C. Kurth*, U. Kraus*, J. Saar*, B. Oehl, D. Altenmller, T. M. Freiman, A. Schulze-Bonhage, J. Zentner, G. Reinshagen*, and B. J. Steinhoff* *Kork Epilepsy Centre, Kork, Germany; and Epilepsy Centre, University of Freiburg, Freiburg, Germany
Purpose: Epilepsy surgery is an established treatment option for a well defined and pre-selected group of patients with drug-resistant epilepsy. The long-term follow-up is important to identify predictive factors for a favourable outcome. Method: We collected data for 340 adult patients from the Kork Epilepsy Centre who had undergone surgery for drug-resistant epilepsy. We used a standardized questionnaire to obtain updated information about postsurgical outcome and classified seizure outcome according to the ILAE surgery outcome scale (OC 1 OC 6). Result: In total 211 (62%) patients have been completely seizure free (OC1), 228 (67%) patients have remained seizure free, apart from simple partial seizures (OC2) at the time of the most recent evaluation. Mean post-operative follow-up time was 6.7 years (range 1.021.6 years). A running-down phenomenon (initially seizures and finally complete remission) has been seen in 38 (11.2%) patients. The majority of patients (266; 78.2%) underwent temporal lobe resections. 64% of the temporal resected patients and 52% of the patients with extra-temporal resections became seizure-free (OC1). Only 38% of the patients with negative MRI achieved complete seizure-freedom (OC1). Conclusion: With 62% (OC1) to 67% (OC2) seizure-free patients, our study shows satisfying long-term outcome results over more than six years. In our study, best results were seen in lesional temporal lobe epilepsy, whereas MRI-negative epilepsy was associated with a less favourable outcome in line with the literature.

Purpose: This study is to discuss the features of seizure semiolgy and electroencephalography(EEG) in young children with lesional temporal lobe epilepsy. Method: 11 children with temporal lobe lesions were received presurgical evaluation for intractable epilepsy. The age of seizure onset was under 3 years. All patients were seizure-free after temporal lobectomy with more than 1 year follow-up. We reviewed medical history and videoEEG monitoring to analyze semiology of seizures and EEG findings and compared to that of adult TLE. Result: All patients have daily seizures although with anti-epileptic drugs (AEDs). 84 seizures were recorded and analyzed in 11 children (aged from 23 months to 108 months; mean 50.5 months). The age of seizure onset was from 1 month to 26 months (mean; 17.6 months). All patients exhibited prominent motor manifestations, including epileptic spasm, tonic seizure(symmtric or asymmtric) and unilateral clonic seizure. seven children manifested behavioral arrest similar to automotor seizures in adult TLE, but with shorter duration and more frequency. Automatisms were mostly orofacial and mannual automatism is rarely observed. EEG recording revealed that generalized discharges patterns were more common in younger children while focal or unilateral patterns usually in older children. All children have mental development delay or regression but with significant improvement after surgery, especially with early operation.

p367 RISK FACTORS FOR EPILEPTIC SEIZURE OF CAVERNOUS MALFORMATIONS IN THE CENTRAL NERVOUS SYSTEM: 52 CASES C. Huang*, J. Li, and D. Zhou *Sichuan University, Chengdu, China; and West China Hospital, Chengdu, China
Purpose: To determine the risk factors for preoperative and postoperative epileptic seizure in patients with cavernous malformations (CMs). Method: We retrospective studied 52 consecutive patients diagnosed with CMs who were surgically treated and histopathologically confirmed in West China Hospital of Sichuan University from January 2009 to June 2001. Clinical data, treatment procedure and follow-up information were collected. Result: In the univariate analysis, factors associated with preoperative epileptic seizure were low birth weight (p = 0.017), temporal lobe involvement (p = 0.003) and cortical lesion (p = 0.025). In the multivariEpilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

108 Abstracts
ate analysis, the cortical lesion showed a high risk for preoperative epileptic seizure (OR=10.48; 95% CI 1.6168.23). In the univariate analysis, patients with temporal lobe CMs were found more likely to be seizure free after surgery (p = 0.016). The maximum diameter of CMs longer than 2.5 cm (p = 0.012) and disease course longer than 1 year (p = 0.050)predicates an unfavorable outcome. In the multivariate analysis, temporal lobe involvement still showed a favorable outcome (OR=0.038; 95% CI 0.0020.833). Application of ECoG did not make significant difference to seizure outcome (p = 0.430). Conclusion: Surgical treatment of patient with CMs is satisfactory in most cases and temporal lobe involvement usually predict favorable postoperative seizure outcome whether under the monitoring of ECoG or not. Thus, epileptic patients with CMs should be considered for surgical treatment especially when cortical brain layer or temporal lobe was involved. All clinical notes were reviewed in order to evaluate the age at onset, the seizure type at onset and during the follow-up, treatment and epilepsy outcome. HH were defined according to the classification proposed by Delalande et al (Delalande et al., 2003). In 4 out of 17 studied patients an intraoperative endoscopic intralesional recording was performed. In 3 cases intraoperative stereo-EEG was carried out using foramen ovale electrodes (Dixi Medical ACS798S, 5 contacts), and DBS leads in 1 case (Medtronic 3389, 4 contacts). Scalp-EEG was performed in all patients (referential montage, lacking frontal and central leads for surgical reasons). Result: In 10 out of 17 cases a surgical approach was performed: 4 of them underwent a one stage stereo-endoscopic disconnection, 3 cases a double stage stereo-endoscopic disconnection, and 1 case required a multistage stage stereo-endoscopic disconnection. One patient performed a bilateral deep brain stimulation (DBS) protocol, 1 a surgical resection, 1 radiotherapy, and 1 radiosurgery. Following Delalande classification HH were mostly of type 2 (8 out of 17), followed by type 3 (6 out of 17) and lastly type 4 (3 out of 17). No cases were classified as type 1. Data on intraoperative stereo-EEGAll patients (4 cases) presented gelastic seizures, associated to focal with secondarily generalization. Seizures frequency ranged from multiple per day to multiple per week. Seizure duration was between few seconds to 60 seconds. Following Delalande classification 2 patients had type 2 HH and other two had type 4 HH. Interictal scalp EEG showed epileptiform abnormalities in all patients, in 2 cases they were evident on temporal region, in one over bilateral parieto occipital, and in one over central and parietal regions. In all patients intraoperative scalp-EEG showed synchronous interictal epileptic discharges which were recorded from the same side of the lesion. From the depth electrode high amplitude fast activity in sequences of variable duration was recorded. In all cases the predominant side of the EEG abnormalities was ipsilateral to the activity recorded within the hamartoma. Conclusion: We detected the electrical activity of the lesion, and compared it with the scalp-EEG activity recorded in the same time. Our data confirm the epileptogenicity of HH. Clinical and neurophysiological findings in all described cases suggest that the cortical activation is secondary to the epileptogenic activity of HH. Intraoperative electrographic recording may be considered as part of a strategy of trans-endoscopic surgery for HHs.

p368 SHORT-TERM RESULTS OF STEREOTACTIC ANTERIOR CALLOSOTOMY IN THE TREATMENT DRUG RESISTANT EPILEPSY K. Kostiantyn, V. Tsymbaliuk, Y. Medvedev, Y. Zinkevich, A. Popov, S. Dichko, and O. Kanaykin Institute of Neurosurgery, Kyiv, Ukraine
Purpose: The purpose of study is to evaluate seizure outcome in patients with intractable primary and secondarily generalized epilepsy who underwent stereotactic anterior corpus callosotomy. Method: Eight patients aged 428 years with drug-resistant epilepsy underwent stereotactic anterior callosotomy, among them were 6 children. 5 pts had daily seizures and all 8 pts had episodes of status epilepticus in their history. 4 pts had partial seizures with secondarily generalization and one patient had primary generalized seizures. 7 pts had symptomatic epilepsy and 1 pt cryptogenic. Result: In postoperative follow up 4 22 months (mean 12 months) 1 pt became seizure free, in 4 cases achieved 90% and in other 3 cases 50% or greater seizures reduction respectively. In1 case seizure frequency did not change significantly. There were no postoperative complications in our series. Conclusion: Our short-term study confirms that stereotactic anterior callosotomy is a safe palliative surgical procedure that is suitable for some patients with drug-resistant epilepsy, suffering from primary or secondarily generalized seizures who are not candidates for focal resective surgery.

p369 ACUTE INTRALESIONAL RECORDING IN HYPOTHALAMIC HAMARTOMAS: DESCRIPTION OF 4 CASES N. Specchio*, M. Rizzi, L. Fusco*, A. Medda*, S. Cappelletti*, C. Marras*, F. Vigevano*, and O. Delalande* *Bambino Ges Children's Hospital, Rome, Italy; and Neurological Institute C. Besta, Milan, Italy
Purpose: To report the results of acute intralesional recording of the interictal activity arising inside the Hypothalamic hamartomas (HH) in 4 cases and to compare it with concurrent scalp EEG. Method: We have reviewed the medical records of 17 children affected by drug resistant focal epilepsy associated to HH, referred between January 1990 and December 2011 to the Neurology Division of the Bambino Ges Children's Hospital in Rome, and Carlo Besta Neurological Institute in Milan.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

p370 VAGUS NERVE STIMULATION DECREASE EMERGENCY ASSISTANCE AND HOSPITALIZATION IN DRUG-RESSISTANT EPILEPTIC PATIENS T. Garca-Sobrino, X. Rodrguez-Osorio, A. Lpez-Ferreiro, M. Santamara-Cadavid, E. Corredera, A. Prieto, M. Peleteiro, and F. J. Lpez-Gonzlez Complejo Hospital Clnico Universitario de Santiago de Compostela, Santiago de Compostela, Spain
Purpose: VNS is an effective method to reduce seizure frequency in refractory epilepsy when resective surgery is ruled out. We aim to study efficacy and need of medical resources after VNS implantation in relation with the preimplantation period. Method: Restrospective study of patients with VNS implantation (20022011) with 1 year of follow-up. Response to VNS was achieved after 50% of reduction of seizures. We analyzed demographic data, efficacy, emergency assistance, hospitalization days in relation with epilepsy and outpatient follow-up after one, two and three years postimplantation, compared with 1 previous year period. Result: Thirthy-nine patients (57.5% females) with a median age of 41 [31,52] years old were studied. Median frequency of seizures per month was 25 [6.25,144.5], with a time of evolution of epilepsy of 26 [18,37]

109 Abstracts
years. Response to VNS after 1, 2 and 3 years was achieved in 47.37% (n = 39), 51.6% (n = 38) and 54.84% (n = 32) of patients. After VNS, median emergency assistance due to epilepsy was 0[0,0], 0[0,1] and 0[0,0.5], reduced in comparison with the preimplantation period 1 [0,1] (p = 0.002; p = 0.027; p = 0.062), with a median of hospitalization days of 0[0,0] at 1, 2 and 3 years, compared to pre-VNS period 0 [0,2] (p = 0.025; p = 0.007; p = 0.05). However, attendance to the epilepsy clinic did not show significant reduction after VNS implantation with a median of 4[2,7], 5[3,7] and 4[3,5] annual visits compared to the year before VNS 5 [4,6] (p = 0.108; p = 0.462; p = 0.085). Conclusion: VNS is effective and reduces the need for emergency assistance and days of hospitalization in refractory epileptic patients.

*UK ILAE Chapter, London, UK; and Societyof British Neurological Surgeons, London, UK
Purpose: Epilepsy surgery is increasingly recognised as an important modality of treatment for people with epilepsy and particularly for people with medically refractory epilepsy. The last assessment of adult epilepsy surgery services was completed in 20001. We sought to provide an up to date picture of the state of adult and paediatric epilepsy surgical services in the UK. Method: We obtained a list of SBNS representatives in all UK Neurosurgical units. We wrote to the relevant consultants in the (17) identified epilepsy surgery centres across the country asking them to prospectively complete a questionnaire detailing all epilepsy surgery carried out at their centre between April 2010 and March 2011. The response rate was 100%. Result: In total there were 874 procedures (excluding invasive electrode recording) with the common resective procedure being temporal lobe surgery for hippocampal sclerosis (142 in adults, 13 in children). In contrast extra-temporal lesionectomies were far less common (78 adults, 18 adults) while non-lesional extra-temporal lobe procedures were rare (24 adults, 2 children). VNS implantation was carried in 401 people (276 adults). Conclusion: In comparison to the figures from ten years ago, there is no evidence that the number of adult temporal lobe resections carried out has significantly changed in the intervening years. VNS implantation is the most commonly performed procedure in both adults and children with the numbers carried out in adults increasing. These figures suggest that epilepsy surgery remains an under utilised service with a large number of people with refractory epilepsy not treated surgically.

p371 EVOLUTION UP TO 18 YEARS AFTER SURGERY FOR TEMPORAL EPILEPSY WITH HIPPOCAMPAL SCLEROSIS: IMPACT OF TECHNIQUE, MEDICATION MANAGEMENT AND PRESURGICAL VARIABLES D. Crestani*, M. Hemb*, R. F. Severino, A. Palmini*, E. Paglioli*, E. Paglioli*, J. Costa Da Costa*, M. Portuguez*, N. Azambuja*, and M. Nunes* *Hospital Sao Lucas, Porto Alegre, Brazil; and Sao Lucas Hospital, Porto Alegre, Brazil
Purpose: The chances of remaining seizure free for long periods are still unclear for patients undergoing surgery for mesial temporal lobe epilepsy and unilateral hippocampal sclerosis (MTLE/HS). Likewise, the impact of practical variables such as surgical technique and post-operative reduction of medication needs clarification. Method: We followed 108 patients with unilateral MTLE/HS for 8 to 18 years and generated Kaplan-Maier survival curves for the probability of remaining seizure free and for the modulating effect of medicaton and surgical technique. Univariate and multivariate regression analyses were perfomed to determine the impact of these and other variables. Result: A history of generalized tonic clonic seizures (GTCS) was present in 10% of the patients and only 16% needed intracranial EEG. The probability of remaining completely seizure-free at 12 and 18 years was 65% and 62%. 75% of patients have discontinued or significantly reduced antiepileptic drugs (AEDs). The type of surgical technique did not impact. Multivariate analysis showed that both a history of GTCS and remaining on full or almost full doses of AEDs significantly diminished the probability of remaining seizure free (Cox regression: p = 0.003 CI: 1.8422.41 for GTCS; p = 0.048, CI: 0.075.27 for AED management). Conclusion: Patient selection may be the most important determinant of remaining seizure free over the years. When the epileptologic profile indicates more restricted disease, removal of neocortical structures does not lead to better chances of seizure control and the reduction or discontinuation of AED does not prevent favorable results.

p373 LONG-TERM OUTCOME OF FUNCTIONAL TEMPORAL LOBE DISCONNECTION FOR NON-LESIONAL MESIOTEMPORAL EPILEPSY B. Legros, N. Massager, P. Tugendhaft, C. Depondt, T. Coppens, L. Drogba, N. Benmebarek, O. De Witte, and P. Van Bogaert ULB-Hpital Erasme, Brussels, Belgium
Purpose: In refractory mesial temporal lobe epilepsy (MTLE), surgical treatment is used to obtain seizure freedom, generally through the anatomical removal of the mesial structures. We developed a technique of functional disconnection of the temporal lobe (TLD). Here, we present long-term seizure outcome and complications of TLD in MTLE. Method: Data of 45 patients operated on for intractable MTLE using TLD were studied. Indication for TLD surgery was retained after a standard preoperative evaluation of refractory epilepsy and using the same criteria as for standard MTLE resection surgery. The epilepsy outcome of 41 patients with minimum 1-year follow-up was analyzed. Morbidity outcome was assessed on the whole population. Result: Mean follow-up duration was 3.48 y (range 19.5 y). At last follow-up 27 patients (66%) were completely seizure-free. Actuarial outcome display a probability of being seizure-free after 5 years of 67.3% and after 9.5 years, of 44.9%. No patient died after surgery and no subdural hematoma or hygroma occurred. Neurological impairment after surgery included speech fluency deficit, hemiparesis, hemianopsia and oculomotor nerve palsy. Permanent hemiparesis occurred in 3 patients, hemianopsia in 5 patients and oculomotor paresis in 1 patient. Conclusion: TLD is a valuable surgical technique for patients with intractable MTLE. The morbidity and long-term seizure outcome of TLD are similar to standard surgical removal techniques. This functional surgery could be an interesting alternative to resection that can reduce operating time and risks for subdural collections after surgery.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

Epilepsy Surgery 4 Tuesday, 02 October 2012

p372 EPILEPSY SURGERY IN THE UNITED KINGDOM IN 2011, AN UPDATE A. Neligan*, J. K. Solomon*, B. Pettorini, and W. F. Harkness

110 Abstracts
Purpose: Infantile spasms (IS) are specific of severe early epileptic encephalopathy. They can be the unique ictal manifestation in patients with early ischemic lesions. Method: We present 3 patients out of our series of 215 hemispherotomies performed between 1990 and 2009, who presented with IS without focal seizures related to perinatal stroke in the distribution of the middle cerebral artery. Interictal as well as ictal video-EEGs were retrospectively studied. We considered postoperative follow-up. Result: Seizure onset was between 5 and 7 months of age. Mean age at the time of EEG-video recording was 22 months, and 27 months at the time of surgery. All patients had hemiparesis; a psychomotor regression occurred after onset of the IS. Interictal EEG favoured unilateral epilepsy with lack of physiological activity over the damaged hemisphere and multifocal sharp waves, whereas physiological activity was recorded over the safe hemisphere. In two cases, sharp waves were also recorded synchronously over both hemispheres. During the spasms, asymmetry was clinically and/or electrically obvious. No other seizure type was disclosed. Follow-up ranged between 26 and 144 months; all three patients are seizure-free without medication. The two patients who underwent early hemispherotomy acquired normal verbal intelligence, whereas the third, operated on at 38 months of age, remained with severe mental retardation. Conclusion: Isolated IS can be a presentation of hemispheric epilepsy related to a post-ischemic lesion. Efficiency of hemispherotomy to control seizures is very high and can prevent mental retardation. Predictive factors for a favourable post-operative development remain to be studied. any relevant benefit with regard to seizure outcome. As expected, postoperative hemianopia was found in all patients. In single cases, an ischemia of the basal ganglia, an infarction of the lateral thalamus or a bleeding in the postcentral region with (transient) motor or sensory deficit was observed. According to MRI criteria, in 10 patients (55%) complete resection or disconnection of the presumed epileptogenic lesion was achieved by MLE. In 14 patients (78%), histopathology revealed focal cortical dysplasia. 3 patients subsequently underwent hemispherotomy, which led to seizure freedom. Conclusion: MLE based on a thorough presurgical epilepsy evaluation can be a successful treatment option with acceptable risks, particularly in children with widespread dysplastic lesions.

p376 OUTCOME OF EXTRA TEMPORAL EPILEPSY SURGERY AND HEMISPHERECTOMY D. D. Ruikar, S. Jayalakshmi, M. Surath, M. Panigrahi, and R. Varma Krishna Institute of Medical Sciences, Secunderabad, India
Purpose: To assess the outcome of surgery in patients with medically refractory extra-temporal epilepsy (ETLE) and hemisperectomy patients evaluated with a non invasive protocol and to determine the predictors of outcome following surgery. Method: Retrospective analysis of pre-surgical (ictal EEG, MRI, fMRI, SPECT, PET, neuro-psychology) surgical and post surgery data was performed in 48 patients who underwent surgery for ETLE and 14 patients following hemispherectomy and who had at least one year post surgery follow up. Outcome was assessed according to Engel's outcome classification. Stepwise multiple logistic regression analysis was employed in data analysis. Result: Mean follow up was 32 months; 36(60%) were males. Intraoperative electro-corticography was done in 42 and cortical stimulation in 23 and neuronavigation in 6. Frontal resections were the commonest (28), followed by parietal resections. The pathology showed cortical dysplasia in 21, gliosis in 8 and low grade tumoral lesions in 10. Transient post surgery complications occurred in 3. Functional hemispherotomy was performed in 6 and vertical parasagittal hemispherectomy in 8. Hemispherical atrophy due to childhhood insult was the etiology in 6, hemispherical dysplasia in 5 and Rassmussen's encephalitis in 3. At last follow up seizure free outcome was noted in 37(77%) with ETLE and 9(75%) after functional hemispherectomy. After stepwise multiple logistic regression analysis, the variables found to be significant (P=<05) and predicting favourable outcome were normal IQ and absence of acute post operative seizures. Conclusion: Favourable outcome after epilepsy surgery can be obtained in patients with ETLE and hemispherectomy after evaluation with noninvasive protocol if presurgical evaluation is carefully planned.

p375 LONG-TERM OUTCOME AFTER MULTILOBAR EPILEPSY SURGERY D. Altenmller*, T. Bast, S. Schubert-Bast, K. Strobl, G. Wiegand, T. M. Freiman**, and J. Zentner** *Epilepsy Center, University Hospital Freiburg, Freiburg, Germany; Kork Epilepsy Centre, Kork, Germany; University Children's Hospital, Heidelberg, Germany; Epilepsy Center Kork, Kork, Germany; University Medical Centre SchleswigHolstein, Kiel, Germany; and **University Hospital Freiburg, Freiburg, Germany
Purpose: In patients with pharmacoresistant (multi-)focal epilepsy, multilobar surgery might be required if the epileptogenic area cannot be localized within a single lobe. We analyzed the pre- and postoperative findings of patients in whom a multilobectomy (MLE) was performed. Method: The data of all patients who underwent MLE at the Epilepsy Center Freiburg between 2001 and 2010 were retrospectively reviewed. Result: 18 patients (median age at MLE 71 months; median follow-up 31 months) fulfilled inclusion criteria. 10 patients received resection of two lobes (1 temporo-parietal; 3 parieto-occipital; 6 temporo-occipital). In 8 patients, resection of 3 lobes (all temporo-parieto-occipital) was performed, often after failure of more circumscribed previous surgical procedures. 11 patients (61%) gained seizure freedom, which mostly was accompanied by developmental progress and EEG recordings without epileptiform potentials after surgery. 3 patients (17%) did not experience
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

p377 SEIZURE OUTCOME AFTER HEMISPHERECTOMY DATA FROM THE SWEDISH NATIONAL EPILEPSY SURGERY REGISTER I. Olsson*, A. Edelvik, R. Flink, B. Rydenhag, and K. Malmgren *Institute of Clinical Sciences, Gothenburg, Sweden; Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Uppsala Akademiska Hospital, Uppsala, Sweden; and Sahlgrenska Academy at Gothenburg University, Gteborg, Sweden
Purpose: To present data from a population-based series of hemispherectomies.

111 Abstracts
Method: The Swedish National Epilepsy Surgery Register, which includes data on all epilepsy surgery procedures in Sweden since 1990 (completely prospective since 1995), was analysed for hemispherectomies 1995-June 2010. The outcome two years after surgery is presented. Twenty-three patients were identified, 12 males and 11 females. The median age at epilepsy onset was four months (range zero to 11 years). Preoperatively 19/23 (83%) had more than 50 seizures per month, 52% more than 100/month. The mean number of antiepileptic drugs (AEDs) was 2.3 (range 15). The side of operation was right in ten cases and left in 13. The median age at hemispherectomy was five years and three months (range six months to 20 years seven months). Result: The aetiology was developmental in 16 cases (12 with malformations of cortical development, four with hemimegalencephaly), acquired in four and progressive in one (Rasmussen). There were no major complications. Thirteen were seizure-free at the two-year followup (57%), three had more than 75% reduction in seizure frequency. Ten out of sixteen (63%) with developmental aetiology became seizure-free. Six out of the 13 seizure-free patients were off medication, the mean number of AEDs was 1.1 (range 03). Conclusion: The seizure outcomes in this population-based series of hemispherectomies were well in accordance with results of larger series. However, we had more patients with developmental aetiology than is usually reported, with equally good results, and most of the patients could stop or reduce medication, within two years after surgery. and in 77% of pure lesionectomies (P = 1.0, CI=95%). Thus there was not a significant improvement in outcome when MEG was incorporated but we found MEG to impact surgical approach and decision making in 60% of tumor cases. Conclusion: MEG contributes to surgical decision making in lesional epilepsy. Extra-operative utilization includes conventional localization of diploles to localize ictal onset, localization of epileptogenesis beyond the lesion and by allowing study of tissue that is difficult to study with other functional imaging modalities. Intra-operative utilization includes fusion with frameless navigation systems allowing guidance of IC-EEG electrode placement with greater accuracy. Outcome is not directly impacted by MEG incorporation but surgical approach often is.

p378 THE CONTRIBUTIONS OF MEG IN SURGICAL DECISION MAKING OF LESIONAL EPILEPSY J. P. Blount*, C. B. Smith, R. C. Knowlton, H. Kim, M. Goyal , C. J. Rozzelle*, P. Kankirawatana, and K. O. Riley *Children's of Alabama/University of Alabama at Birmingham, Birmingham, USA; and University of Alabama at Birmingham, Birmingham, USA
Purpose: Lesional epilepsy has traditionally referred to cases of tumors or vascular cavernous malformation that are readily visualized on MRI scans. However as the quality of imaging has improved other substrates have become increasingly defined as MRI evident lesions that are epileptogenic. The approach to such lesions remains controversial and incompletely understood. Resection of the lesion is straightforward and efficient yet may fail to control seizures in up to 40% of cases. Whether the lesion or peri-lesional tissue is primarily epileptogenic remains uncertain. The necessary extent of pre-operative evaluation and operative resection of peri-lesional tissue varies between experienced centers and remains controversial. We reviewed a large contemporary surgical series of lesional epilepsy to address the contribution of magnetoencephalography (MEG/MSI) studies to localization of lesional epilepsy. Method: A 10 year (20012011) retrospective review of a 2 institution (University of Alabama at Birmingham/Childrens Hospital of Alabama) experience was undertaken after IRB approval. Among 320 patients operated for lesional epilepsy a seizure occurrence rate of greater than or equal to two seizures was confirmed in 122 (44 adults, 78 Pediatric) patients. These were identified who had epilepsy, an abnormal pre-operative vEEG and a pre-operative MRI that revealed a lesion in the region of EEG abnormality. Lesions were broadly interpreted and included tumors (n = 46), FCD (n = 38), encephalomalacia from infarcts (n = 13), cavernous malformations (n = 6) and lesions associated with the phakamotoses (n = 10). Histopathologic confirmation was attained in all cases. MEG was utilized in 50 cases (9 tumors, 19 FCD, 1 cavernoma, 22 other). Result: The seizure freedom rate for pure lesionectomy was 81% for tumors with complete resection and 61% if residual disease was observed. Lesionectomy in FCD resulted in 50% class I outcome. MEG contributed to surgical localization by demonstrating dipoles both within the lesion and extending beyond the lesion into the peri-lesional tissue. Engel class I outcomes were seen n 77% of MEG directed lesionectomies

p379 COMPARATIVE STUDY OF EFFICACY AND SAFETY BETWEEN RADIOSURGICAL CALLOSOTOMY AND OPEN CALLOSOTOMY FOR LENNOX-GASTAUT SYNDROME IN A THIRD-LEVEL NEUROLOGICAL CENTER J. D. D. Del Castillo Calcneo*, D. San Juan Orta*, M. A. Alonso Vanegas, S. Moreno Jimenez*, and M. Herbas Rocha *National Institute of Neurology and Neurosurgery, Mexico City, Mexico; and Instituto Nacional de Neurologa y Neurociruga Manuel Velasco Suarez, Mexico City, Mexico
Purpose: Determine & compare the effect of surgical corpus callosotomy (SC) and radiosurgical corpus callosotomy (RC) in seizure frequency reduction in Lennox-Gastaut Syndrome (LGS) and to stablish safety of SC and RC in LGS. Method: Retrospective analysis (20042012) of patients who underwent either RC or SC was performed. Clinical, neurophysiological, neuroimaging and follow up variants were obtained and analyzed using descriptive statistics (means and standard deviations) as well as Student's T test for independent samples. Result: 33 subjects were included 21 [14 males] in SC and 12 [5 males] in RC. The average age at time of surgery was 20.6 7.9 years in RC and 25 7.9 in SC. Average time to diagnosis was 2.4 2.5 y in RC and 2.1 2.9 y in SC. All subjects were diagnosed with cryptogenic Lennox-Gastaut Syndrome and multi-focal epileptic activity. To perform the surgery in the RC group a mean dose of 43.2Gy (4) were used. Follow-up was performed at 12 (4) months. There was a decline in monthly seizure frequency for RC (-60%) as well as for SC (-55%) with no significant difference between them (p = 0.64). Tonic and Atonic seizures were the most reduced in both groups. In RC 6 subjects presented with complications related with severe cerebral edema. There were no complications reported on SC. Conclusion: RC shows similar efficacy compared with surgical corpus callosotomy in reducing seizure frequency in subjects with LGS. Even though there is a major incidence of complications in the RC group.

p380 CORRELATION OF FDG-PET AND VOXEL-BASED MRI MORPHOMETRY WITH INVASIVE EEG FINDINGS AND SURGICAL RESULTS IN MRI-NEGATIVE EPILEPSY J. Scholly*, A. M. Staack*, I. J. Namer, U. Kraus*, S. Bilic*, K. Strobl*, T. Bast*, M. P. Valenti-Hirsch, P. Kehrli, E. Hirsch, A. Schulze-Bonhage, J. Zentner, and B. J. Steinhoff*
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

112 Abstracts
*Kork Epilepsy Centre, Kork, Germany; University Regional Hospital Centre of Strasbourg, Strasbourg, France; Strasbourg University Hospital, Strasbourg, France; and Epilepsy Centre, University of Freiburg, Freiburg, Germany
Purpose: Conventional MRI fails to identify the lesion in about a quarter of patients with surgically remediable epilepsy. In MRI negative surgical candidates we investigated the localizing value of FDG-PET, voxel-based morphometric MRI analysis (VBM) and scalp video-EEG and correlated the findings with the epileptogenic zone defined by invasive EEG and histological findings after surgery. Method: 20 MRI-negative patients were prospectively investigated. Scalp video-EEG recordings, the visual analysis of FDG-PET overlaid onto a 3D-set of the patient's anatomic MRI scans as well as VBM MRI analysis based on algorithms of the statistical parametric mapping software (SPM5) were performed. 14 patients underwent invasive EEG, 12 were operated. Result: The epileptogenic zone defined by invasive EEG was temporal in three, temporal plus in two and extratemporal in nine cases, confirming the electro-clinical hypothesis after scalp recording in all but one case. The outcome was favorable (Engel class I) in ten patients (83%). The histological examination revealed focal cortical dysplasia (FCD) in nine cases and other pathologies in the rest. A topographic concordance with the epileptogenic zone could be demonstrated by FDG-PET in eight of nine FCD cases (89%). The VBM MRI analysis detected abnormalities suggesting FCD in six cases. Only two of them corresponded to the electro-clinical epileptogenic focus and only one to a confirmed FCD. Conclusion: Our data suggest a good localizing value of FDG-PET especially in cases of MRI obscure FCD, whereas a VBM MRI analysis showed low diagnostic sensitivity and specifity (11% and 33% respectively) in our series. Conclusion: Previous studies of HFO from intracranial microelectrodes and/or single neuron recordings consistently showed the frequencies at ictal onset above 100 Hz. In our study, HFO were preceded by lower frequency activity, and the presence of the lower frequencies synchronization correlated with post-operative seizure freedom. HFO may not be the first ictal manifestation in some cases, and the lower range ictal frequencies should not be overlooked. Larger studies are underway.

Medical Therapy and Pharmacology 4 Tuesday, 02 October 2012

p382 STATUS DYSTONICUS IN A CASE OF WILSON'S DISEASE O. Cokar, A. Mutlu, F. F. Ozer, M. Gurbuz, H. Acar, and F. Genc Haseki Educational and Research Hospital, Istanbul, Turkey
Purpose: Dystonia is a movement disorder characterized by sustained muscle contractions producing torsional and repetitive movements or abnormal postures. Status dystonicus is a generalized, intense and potentially fatal exacerbation of muscle contractures which is necessitated urgent hospital admission. It mainly affects patients with primary or secondary dystonia and is often triggered by fever, infection, trauma, surgery, abrupt introduction, withdrawal or change in medical treatment. We report one case of Wilson's disease presented with dystonic status. Method: A 49 year-old male with a previous diagnosis of Wilson's Disease treated trientine and zinc sulfate presented with generalized tonic clonic seizure. At time of admission he had hyperthermia up to 39 ordm; C. After control of seizure with diazepam and levetiracetam infusions the patient presented severe episodes of dystonia involved face and left arm and leg. Elevated serum creatine phosphokinase level was documented. Symptoms were resistant to conventional medication. Result: Gabapentin 900 mg/day, brought significant improvement and the patient remained clinically stable. Conclusion: Although status dystonicus is a rare but serious condition, prompt diagnosis is needed and gabapentin can be used to control severe episodes of dystonia.

p381 INTRACRANIAL EEG ICTAL ONSET FREQUENCY: HIGH OR LOW? J. Chung*, U. Maoz, N. Tsuchiya, O. Tudusciuc, S. Ye, A. Mamelak*, and D. Eliashiv* *Cedars-Sinai Medical Center, Los Angeles, USA; California Institute of Technology, Pasadena, USA; and Riken Institute, Tokyo, Japan
Purpose: Identifying ictal onset frequencies with wide spectrum EEG frequency analysis. Method: Eight patients with medically refractory partial epilepsy undergoing intracranial macroelectrode monitoring (4 depth electrodes, 4 subdural grids) were analyzed. Digital EEG data was sampled at 2 kHz at various intervals. Multiband frequency and power analysis were performed to characterize the predominating frequency during the interictal, pre-ictal, ictal, and postictal periods. Result: Thirty-one seizures14 seizures collected from subdural grid and 17 from depth electrodeswere analyzed. In each of the 18 seizures from six patients, the ictal onset was localized to one contact and was characterized by a significant increase of 10 30 Hz frequencies preceding the increase of 30 100 Hz frequencies by 3 seconds before propagation. Focal surgical resections were performed in the areas correlated to the synchronization of these alpha-beta range frequencies and HFO prior to and during the patients clinical seizures. These six patients have seizure-free outcomes confirming the localization of seizure onset. On the contrary, 13 seizures from two patients did not demonstrate the synchronization of alpha-beta range frequencies, and the patients did not achieve seizure freedom post-operatively.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

p383 EARLY TREATMENT WITH LACOSAMIDE: RESULTS OF RELACOVA STUDY M. Garcs*, E. Lpez Gomariz, P. Giner, N. Torres, E. Noe, J. Lpez-Trigo**, C. Santafe, R. Muoz, M. Bonet, and V. Villanueva* *Hospital Universitario y Politcnico La Fe, Valencia, Spain; Hospital Luis Alcanyis, Xativa, Xtiva, Spain; Hospital Universsitario Dr. Peset, Valencia, Spain; Hospital Dr. Peset, Valencia, Spain; Hospital Valencia al MAr, Valencia, Spain; **Consorcio Hospital General Universitario Valencia, Valencia, Spain; Hospital Clinico Universitario Valencia, Valencia, Spain; Hospital de La Ribera, Alzira, Spain; and Hospital Arnau de Vilanova, Valencia, Spain
Purpose: To analyze early use of lacosamide (LCM) in RELACOVA study, a large multicenter prospective collection of patients on LCM in clinical practice. Method: Consecutive patients with partial epilepsy where LCM was used as 1st, 2nd or 3rd antiepileptic drug (AED) (monotherapy or

113 Abstracts
combination) and at least a follow-up of 3 months were studied. The information was obtained at baseline, 3, 6 and 12 months. Efficacy and adverse events (AE) were analysed. Concomitant AEDs and number of prior AEDs were also evaluated. Result: Fifty-six patients were included. Forty-nine patients were followed for 6 months and 40 patients for one year. Six patients had tried none AEDs, 20 patients one AED and 30 patients 2 AEDs. None patients withdrew before 3 months, retention rate at 6 months was 91.8% and at 12 months was 82.5%. Seizure free patients were 37.5%, 32.7% and 37.5% at 3, 6 and 12 months. Responders were 64.3%, 71.4% and 70% at 3, 6 and 12 months. No significant differences were observed according to the number of prior AEDs although a trend to a better response appeared when LCM was used as 1st or 2nd drug. Better response was observed when LCM was used with a non-sodium channel blocker (SCB (-)) (responder rate at 3 months showed p 0.033). AE were reported by 26.8%, 34.7% and 35% of patients at 3, 6 and 12 months. No differences were observed according to concomitant drugs. Conclusion: Efficacy of LCM in partial epilepsy is high when used early and seems to be better when used with SCB (-). Method: Children under 18 years of age, starting VPA or CBZ 01/11/ 0731/10/10 were ascertained using the hospital pharmacy database. Paper and electronic patient records were reviewed and data captured using a standard proforma. Simple descriptive statistics, Chi-squared, logistic regression and Kaplan-Meyer survival plots in SPSS (v19) were used. Result: 84 children (Males 45) aged 017 years (median 8.0) were identified, 44/84 had CBZ, 40/84 VPA, and 13/84 both. In 61/84 (73%) this was their 1st antiepileptic drug (AED). 30/44 (68%) on CBZ had focal epilepsies and 28/40 (70%) on VPA had generalized epilepsies. The audit comprised 29 person years of CBZ exposure, and 34 for VPA. 37/44 (84%) of patients on CBZ had >50% seizure reduction, including 13/44 (30%) seizure free. 36/40 (90%) on VPA had >50% seizure reduction, including 12/40 (30%) seizure free. 48/84 (57%) experienced adverse events, none serious, 7/44 (16%) on CBZ had increased seizures, 3/44 (7%) had rash; 6/40 (15%) on VPA complained of excessive weight gain. Conclusion: The audit of outcome showed CBZ and VPA to be effective first line AEDs, however we caution the use of CBZ as a first line AED because of the risk of seizure aggravation.

p384 ON THE USE OF INTRA RECTAL VALIUM IN PATIENTS WITH DRAVET SYNDROME: FAMILIES OPINION N. Coqu*, N. Chemaly, and R. Nabbout *Alliance Syndrome de Dravet, Brest Cedex 2, France; and Hpital Necker Enfants Malades, Paris, France
Purpose: Intra rectal Diazepam (DZ) remains the first rescue medication for acute prolonged convulsive seizures in children. In this study, we aimed at assessing the experience of the families of patients presenting Dravet syndrome (DS) concerning DZ use. Method: We invited 53 families of patients with DS to complete an auto-administered on-line questionnaire. Questions addressed the different aspects of intra rectal DZ use: usual administrators, and time, easiness, and risk of errors in the preparation and administration. Parents were questioned about their feeling concerning efficacy, usefulness in emergency setting, facility of its administration, and possible refuse of care givers to use it. Result: 52 families answered the questionnaire. DZ was usually administered by mothers and less frequently by other care givers. Almost all parents (92%) agreed on its efficacy. However, 50% found that preparation and administration are affected by errors especially when carried out of the parents presence. Many educational and non-medical institutions refused to use DZ. Conclusion: Parents confirm the efficacy of intra rectal DZ and emphasized the need for a medication that is easier to prepare and administer.

Purpose: Pyridoxine dependent epilepsy (PDE) is a rare autosomal recessive disorder, characterized by early-onset, drug-resistant seizures, responsive only to pharmacological doses of pyridoxine. Mutations in the ALDH7A1 gene, which encodes the protein antiquitin, have been described. Buccal midazolam is now the standard treatment for prolonged seizures in children with epilepsy, in the community setting. We report two siblings from a consanguineous family of Asian origin with PDE, responding only to buccal pyridoxine for prolonged seizures. Method: A 4-year-old boy, developed multifocal seizures in the neonatal age, not responsive to standard anticonvulsants but responding to pyridoxine. Serum Pipecholic acid was high. Homozygous mutation in ALDH7A1 gene confirmed the diagnosis of PDE. Currently seizures are relatively well controlled on oral Pyridoxine. He does get intermittent, prolonged, generalized tonic-clonic seizures with infectious illness. Repeated doses of buccal midazolam and rectal diazepam have failed to control seizures in the community setting. Buccal pyridoxine has been extremely effective in stopping these seizures and preventing admissions to hospital. His 12-year-old sister was diagnosed with PDE, after his diagnosis became apparent. She has spastic quadriplegia with drug resistant multifocal epilepsy, currently well controlled on oral pyridoxine and Oxcarbazepine. Breakthrough prolonged seizures have failed to respond to benzodiazepines and only respond to buccal pyridoxine. Result: Not applicable. Conclusion: Buccal pyridoxine may have a role as rescue medication in controlling breakthrough seizures in children with PDE and should be considered as a therapeutic option in the community setting.

Purpose: In 2006, ILAE criticised the lack of primary evidence for the use of Carbamazepine (CBZ) and Sodium Valproate (VPA) in the treatment of epilepsies in children and young people. This is a single centre, retrospective, registered clinical audit of process and outcome to assess the use, efficacy, tolerability, and retention of CBZ and VPA.

p387 COGNITIVE EFFECTS OF LACOSAMIDE D. Ijff, M. Majoie, and A. Aldenkamp Kempenhaeghe, Heeze, Netherlands
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

114 Abstracts
Purpose: Lacosamide is a novel antiepileptic drug (AED) with potential benefit as adjunctive treatment in patients with partial-onset seizures.13 The cognitive effects have, as yet, not been studied. In this open clinical prospective study the cognitive effects of Lacosamide (VIMPAT) when used as adjunctive antiepileptic therapy in adolescent and adult patients with epilepsy was evaluated. Method: We included 33 patients (24 females, 9 males) aged between 1674 years (mean 37 years sd:14.5). All patients suffered from focal epilepsy: 42% had cryptogenic and 58% had symptomatic epilepsy. Patients were using LCS treatment with a daily dose of between 100 to 600 mg (mean daily dose of 298.2 mg/day). Mean follow-up time was 7 months (range 124). Patients were treated with up to four concomitant AEDs (mean: 1.9). Subjective complaints were evaluated using the SIDAED; effects on cognition were evaluated using the CVST, a test measuring speed of central information processing. Result: On the CVST a significant faster reaction time was found at the second evaluation (p=.010). On the SIDAED (subjective list of 46-items with possible AED-related complaints), patient complained more about their cognitive function at the second evaluation (p=.002). Conclusion: Lacosamide has a positive effect on the information processing speed although patients complained more, especially about their cognitive function. Possible explanations for this discrepancy are the effect of reduction of co-medication and increased worries of patients during a trial, causing overestimation of cognitive effects.

p389 LONG-TERM EFFICACY AND TOLERABILITY OF ZONISAMIDE AS ADJUNCTIVE THERAPY IN PATIENTS WITH REFRACTORY PARTIAL EPILEPSY A. La Neve*, N. Pietrafusa*, G. Pontrelli*, T. Francavilla*, V. Durante*, M. Ladogana*, T. Lisi*, and G. Boero *Policlinico di Bari, Bari, Italy; and SS. Annunziata Hospital, Taranto, Italy
Purpose: To assess long-term efficacy and tolerability of zonisamide (ZNS) as add-on treatment in patients with refractory partial epilepsy. Method: prospective, open label study conducted in 69 patients with refractory partial epilepsy. The study included 3 periods: Baseline (3 months); drug titration (> 2 months) to ZNS 300 mg/day; Observation, during which the ZNS could be increased up to the maximum tolerated dose. Inclusion criteria were: age >16 years, diagnosis of focal epilepsy, pharmacoresistance to at least 2 adequate previous antiepileptic drugs, stable concomitant antiepileptic therapy for 3 months during baseline. Exclusion criteria were: systemic or progressive neurological diseases, poor compliance, history of pseudo-seizures, pregnancy. Efficacy was evaluated comparing mean monthly seizures frequency during last three months of observation to baseline seizures frequency; statistical analysis was made using Poisson models for count data. Result: mean number of antiepileptic drugs before ZNS was 5.5 2.5; mean duration of follow-up was 19.5 months. 59 patients were included in the efficacy analysis and statistically significant reduction of the mean monthly seizures frequency was found at 12 months (19.14 38.60 vs. 9.73 18.10, p = 0.004) and at 24 months (19.14 38.60 vs. 8.86 17.51, p = 0.008). 24 patients (34%) complained adverse events wich led to drug discontinuation. Conclusion: Our data suggest good efficacy and a good tolerability of ZNS in the long term, especially considering the severe pharmacoresistance of our patients and the drug administration in polytherapy regimen.

p388 STEADY-STATE PHARMACOKINETICS AND TOLERABILITY OF ESLICARBAZEPINE ACETATE AND OXCARBAZEPINE IN HEALTHY VOLUNTEERS A. Falco*, M. Vaz-Da-Silva, T. Nunes, L. Almeida, and P. Soares-Da-Silva *4Health Consulting, Cantanhede, Portugal; University of Porto, Porto, Portugal; BIAL Portela & Ca. SA, So Mamede do Coronado, Portugal; and University of Aveiro, Aveiro, Portugal
Purpose: To investigate the steady-state pharmacokinetics and assess the tolerability of once-daily (QD) regimen of eslicarbazepine acetate (ESL) and twice-daily (BID) regimen of oxcarbazepine (Trileptal; OXC) in healthy volunteers. Method: Single centre, open-label, randomised, three-way crossover study in 12 healthy volunteers. The study consisted of two 8-day treatment periods separated by a washout period of 1015 days. In each treatment period the volunteers received either a daily oral dose of ESL 900 mg QD or ESL 450 mg BID (data not shown) or OXC 450 mg BID. Result: Eslicarbazepine was the major drug entity in plasma, accounting for 93.0% and 82.2% of total exposure with ESL 900 mg QD and OXC 450 mg BID, respectively. Eslicarbazepine Cmax (lmol/L) was 82% higher following ESL QD (87.34) compared to OXC BID (47.96). The ratio eslicarbazepine exposure(mmol*h/L)/dose(mmol) was 0.3733 (1133.71/3037.25) and 0.2695 (961.35/3567.60) for ESL and OXC, respectively, which translates in a 39% increase in efficiency of ESL versus OXC to deliver eslicarbazepine. ESL was 19% more efficient than OXC to deliver all active moieties. The extent of exposure to drug entities R-licarbazepine and oxcarbazepine was approximately 4-fold higher with OXC as compared with ESL. 30 and 18 treatment-emergent adverse events were reported in the OXC 450 mg BID group and the ESL 900 mg QD group, respectively. Conclusion: In comparison to OXC, administration of ESL resulted in 39% more eslicarbazepine, less R-licarbazepine and less oxcarbazepine, which may correlate with the tolerability profile reported with ESL.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

p390 THE EFFECTS OF ESLICARBAZEPINE ON RECEPTORS, ION CHANNELS, ENZYMES AND TRANSPORTERS A. I. Loureiro*, M. J. Bonifcio*, L. Wright*, and P. Soares-DaSilva *BIAL Portela & Ca. SA, So Mamede do Coronado, Portugal; and University of Porto, Porto, Portugal
Purpose: This study was aimed to determine the interaction of eslicarbazepine, the main active metabolite of eslicarbazepine acetate, with potential biological targets. Method: Displacement of binding of specific ligands or substrates for 95 human G-protein coupled and ligand gated receptors, ion channels, enzymes and transporters was tested in the presence of 400 lM eslicarbazepine. Some eletrophysiological experiments were conducted with mouse N1E-115 cells and transfected cells expressing human Cav3.2 channels. Result: In the presence of 400 lM eslicarbazepine, no relevant interactions were observed with receptors (acetylcholine, adenosine, adrenergic, angiotensin II, cannabinoid, cholecystokinin, dopamine, GABA, glutamate, histamine, melatonin, neurokinin, neurpeptide Y, neurotensin, opioid, purine, serotonin, somatostatin and TRH), ion channels (type N calcium, GABA chloride, potassium ATP-sensitive and Ca2 + -activated), enzymes (acetylcholine esterase, acetylcholine transferase, carbonic

115 Abstracts
anhydrase I and II, glutamic acid decarboxylase, COX-2, MAO-A and MAO-B, caspases [110], kinases [CK1d, Fyn, GSK3b, MAPK1, MAPK3, PKA, PKCb2, PHCz, ROCK2, SGK1] and nitric oxide synthase) and transporters (dopamine, noradrenaline, serotonin and GABA). Eslicarbazepine does not alter fast inactivation of voltage-gated sodium channel (VGSC), but reduced VGSC availability through enhancement of slow inactivation with an affinity to the slow inactivated state 5.9 times higher than to the channels in the resting state. Eslicarbazepine inhibited high and low affinity CaV3.2 inward currents with IC50`s of 0.4 and 62.6 lM, respectively. Conclusion: Eslicarbazepine is a selective slow inactivator of VGSC and potent Cav3.2 blocker devoid of effects upon major G protein coupled and ligand gated receptors, ion channels, enzymes and transporters. epilepsy after failure of at least 3 lifetime antiepileptic drugs. This study is being conducted to document patient demographics, lacosamide dosing, evolution of seizure control, and tolerability during a 6-month period in a real-life setting. Method: Patients were either already being treated (Group 1) or initiated treatment with lacosamide at enrollment (Group 2). Seizure control was determined by investigators using a 4-category scale (much improved, improved, stable, worsened), and tolerability by spontaneous patientreported treatment-related adverse events (AEs). Result: At interim analysis, 51 patients (28 female, age 1777 years) of 150 had completed an observational period of at least 4.5 months or had dropped out. Patients were highly refractory; all had 3 lifetime AEDs and 35% had 7. Following a mean study duration of 162 days, the mean daily lacosamide dose in Groups 1 and 2 was 347 and 297 mg (range 150600 mg), respectively. On study completion, seizure control was improved or much improved in 53% of patients in Group 1 and in 56% of Group 2. AEs occurred in 29% of patients (most frequently fatigue, dizziness or vertigo). Thirteen patients discontinued (29% of completers, 10% of enrolled) due to AEs (n = 8) or lack of efficacy (n = 5); 2 were lost to follow-up. Conclusion: Conclusion Data from this study so far suggest that in routine clinical practice, lacosamide is well tolerated and improves seizure control in highly refractory patients. Sponsored by UCB Pharma.

Purpose: Levetiracetam is an anti-epileptic which is metabolised primarily in blood cells by enzymatic hydrolysis. The use of levetiracetam has not been reported in patients with sickle cell disease. Such patients with abnormal red blood cells may have difficulties metabolising levetiracetam. We report the use of levetiracetam in a patient with sickle cell disease. Method: A 22 year old Nigerian gentleman with sickle cell disease (homozygous SS) suffered from childhood bilateral strokes resulting in secondary generalised seizures that have been refractory to treatment. He has severe learning difficulties, spastic quadriplegia (uses a wheelchair), no speech and needs assistance with all activities of daily living. He has tried multiple anti-epileptic drugs and a ketogenic diet to no avail. He was started on levetiracetam during an episode of status epilepticus aged 20. He has now been on levetiracetam for just over 2 years and is currently on a dose of 1 g twice a day. Result: His seizures have remained refractory and he is on polytherapy. Although difficult to assess because of polytherapy, he has not suffered from any obvious side effects. Trough levetiracetam level was 19.1 (normal range (1037). In the 2 years prior to starting levetiracetam, he needed 21 units of blood to manage his anaemia. In the 2 years since starting levetiracetam, he has needed 7. Conclusion: This case illustrates that levetiracetam is not only safely tolerated in this patient with sickle cell anaemia but also that levetiracetam has not adversely affect his sickle cell disease.

Medical Therapy and Pharmacology 5 Tuesday, 02 October 2012

p393 A RETROSPECTIVE OBSERVATIONAL STUDY OF COMPARATIVE LACOSAMIDE COST IN A REAL WORLD SETTING IN THE USA (VOYCE) S. Janssens*, H. Benhaddi*, T. Durgin, and S. Borghs *UCB Pharma, Brussels, Belgium; and UCB Pharma SA, Smyrna, GA, USA
Purpose: To compare the changes in treatment cost after lacosamide is added to monotherapy, versus after another antiepileptic drug (AED) is added, in patients with epilepsy in clinical practice. Method: This was a retrospective, observational, 1-to-n matchedcohorts study on a US claims database (SDI). The observation period was 6 months, both pre- and post-index. Index was defined as the date when lacosamide or one of eight other AEDs (controls) was added to existing therapy, which in this report consisted of AED monotherapy. Costs of inand outpatient visits, and medication for epilepsy and non-epilepsy, were collected from the database. The percentage in average change from preto post-index was calculated. Result: From pre- to post-index, total treatment cost decreased by 23.2% when lacosamide (n = 410) was added to monotherapy and by 5.5% with controls (n = 1908). Cost of inpatient visits decreased in both groups (96.5% with lacosamide versus 78.7% with controls), as did cost of epilepsy-related outpatient visits (26.4% versus 26.7%). Non-epilepsy-related outpatient visit cost remained stable with lacosamide (0.9%), but increased with controls (22.8%). AED medication cost increased by 153.8% with lacosamide and 66.1% with controls. Cost for non-AED medication increased in both groups; by 23.2% with lacosamide compared with 37.5% with controls. Conclusion: In clinical practice, adding lacosamide to monotherapy resulted in a greater decrease in total treatment cost compared with other AEDs, despite the greater increase in AED medication cost. Further analyses, looking at adding to polytherapy, and in focal epilepsy patients only, are ongoing. Sponsored by UCB Pharma.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

p392 DRUG UTILIZATION STUDY WITH LACOSAMIDE IN DAILY CLINICAL PRACTICE IN BELGIUM: AN INTERIM ANALYSIS W. Van Paesschen*, H. Hauman, B. Legros, M. De Backer, E. Webster, and P. Dedeken *University Hospital Gasthuisberg, Lueven, Belgium; General Hospital St. Maarten, Duffel, Belgium; ULB Erasme Hospital, Brossels, Belgium; UCB Pharma, Brussels, Belgium; and UCB Pharma, Raleigh, USA
Purpose: Lacosamide was approved in 2010 for reimbursement in Belgium as add-on therapy for patients (16 years) with uncontrolled focal

116 Abstracts
p394 HEPATOTOXICITY AND ANTICONVULSANT THERAPY IN CHILDREN AND ADOLESCENTS S. Karkelis, O. Papadaki-Papandreou, M. Lykogeorgou, M. Nikita, and G. Chrousos University of Athens, Athens, Greece
Purpose: Epilepsy and sufficient epilepsy treatment is a challenging problem for all clinicians taking care of children and adolescents. The aim of the study was to investigate the impact of epilepsy treatment on liver function tests in children and adolescents. Method: 287 children and adolescents(165 males, 122 females) epilepsy diagnosed during the last 5 years and aged 2 months-16 years were enrolled. All patients medical files were reviewed in order to estimate: age of treatment initiation, type of treatment, number of seizures per month, presence of status epilepticus and liver function tests using blood samples(ALT, AST, gGT, ALP, total bilirubin, direct bilirubin, total protein, albumin) at baseline, 6 months and 12 months after treatment initiation. Abnormal baseline liver tests were found in 29 patients who were excluded. SPSS-19 statistical software and x2-test were used for data statistical analysis. Result: Abnormal liver function tests were found in 48 patients, autoimmune hepatitis in 2 patients and acute liver failure in 1 patient. Statistical significant correlation(p < 0,05) was found between the number of seizures, the duration of therapy and the number of anticonvulsant drugs used from the one hand, and the liver enzymes values from the other hand: the higher the number of seizures and/or drugs used, the higher the liver enzymes values. The most hepatotoxic drugs were sodium valproate, carbamazepine and phenobarbital. Conclusion: Study results show very clearly that antiepileptic medications can cause liver dysfunction in children and adolescents, but in most cases this is a tolerable side effect and also that significant hepatotoxicity is very rare. mechanisms than other combinations. However, age, duration of exposure to AEDs, or frequency of seizures between 2 AEPs were not related the the score of AEP. Conclusion: The AE are related with burden of AEDs and the number of AEDs.

p396 COMPARISON OF DRIED BLOOD SPOTS AND PLASMA VALPROIC ACID AND CARBAMAZEPINE LEVELS S. T. Kong*, W. H. Lim, H. Y. Wang, Y. L. Ng, P. C. Ho*, and S. Lim *National University of Singapore, Singapore, Singapore; Singapore General Hospital, Singapore, Singapore; and Duke-National University of Singapore-Graduate Medical School, Singapore, Singapore
Purpose: Gas chromatography mass spectrometry (GC-MS) has been utilized for quantitative analyses of individual antiepileptic drugs (AEDs), one AED at a time but not simultaneously. To facilitate faster therapeutic AED monitoring process by healthcare professionals for patients with epilepsy (PWE), we (1) develop a GC-MS assay to concurrently measure both Valproic Acid (VPA) and Carbamazepine (CBZ) levels using one dried blood spot (DBS), and (2) correlate DBS measured VPA and CBZ levels with their plasma levels. Method: 30 PWE taking VPA and CBZ concomitantly were recruited. One DBS, containing ~15 lL of blood, was acquired for the simultaneous measurement of both drug levels using GC-MS. Measured DBS levels were correlated to therapeutic drug monitoring of plasma levels done at the hospital laboratory. Analysis was done using Statistical Package for Social Sciences (SPSS) version 19. Result: DBS levels were well-correlated to plasma levels: r2 > 0.85 for VPA and r2 > 0.73 for CBZ. Percentage differences between plasma and DBS levels were found to be consistent, with the mean values of 58.2% (95%CI=55.3561.14) for VPA and 3.1% (95%CI=-1.177.46) for CBZ. To calculate VPA plasma level, the conversion formula is 1.775 x (DBS VPA level) + 13.525. To calculate CBZ plasma level, the formula is 0.692 x (DBS CBZ level) + 2.644. Conclusion: The consistent correlation of DBS to plasma measured drug levels could make DBS an alternative tool for monitoring clinical levels of VPA and CBZ. Further study incorporating more patients and validation of the DBS assay are currently undergoing.

Purpose: Epilepsy surgery is available in selected patients, still the mainstream of treatment of epilepsy is antiepileptics (AED). The adverse effects (AE) of AEDs are major obstacle preventing maintenance of compliance and control of AE is important issue in clinical practice. Method: We performed this study with a brief 19-item self-report instrument, the Adverse Events Profile (AEP). Two AEPs were screened separately with interval of at least 1 month. The inclusion criteria were 1) taking AEDs for at least 6 months, 2) no change of AED dosage between 2 AEPs, 3) no adding on other medications between 2 AEPs, 4) at least 80% of compliance between 2 AEPs. AED loads were calculated as the sum of prescribed daily dose (PDD)/defined daily dose (DDD) ratios for each co-prescribed AED. Result: 218 patients were eligible for this study. 121 patients were on monotherapy and 97 patients were on polytherapy. The correlation between scores of 1st AEP (baseline) and 2nd AEP was excellent (Spearman correlation coefficient= 0.82, p < 0.0001). AED loads was related with the score of AEP?the score of AEP with over dose (>1 PDD/DDD) Vs with target dose (1 PDD/DDD), p = 0.006 by Mann-Whitney test?. Also, AEP scores were significantly different between patients with monotherapy and patients with polytherapy ?the score of AEP with monotherapy Vs polytherapy, p = 0.0002 by Mann-Whitney test?. In the 2 AEDs combination, the score of AEP was marginally lower in the combination of 2 AEDs acting on sodium channel blocker with multiple
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

p397 SERUM CONCENTRATIONS OF LACOSAMIDE IN PATIENTS WITH EPILEPSY: INFLUENCES OF DOSE, AGE, GENDER AND COMEDICATION S. Markoula*, R. Teotonio, P. Patsalos, and J. Duncan* *Epilepsy Society, Chalfont St Peter, UK; Hospitais da Universidade de Coimbra, Coimbra, Portugal; and UCL Institute of Neurology, London, UK
Purpose: To investigate the influence of lacosamide doses, gender, age and comedication on lacosamide serum concentrations in epilepsy patients. Method: Lacosamide concentrations were measured in the Therapeutic Drug Monitoring Unit at The Chalfont Centre for Epilepsy. Daily dose, demographic data and comedication were recorded. Patients were further stratified in two groups according to the interval between last lacosamide administration and blood collection (collection 2 h and 8 h after lacosamide administration or in 28 hours).

117 Abstracts
Result: 299 patients (150 females) on lacosamide with a median age of 41 (1879) years and a median daily dose of 300 (50600) mg were retrospectively recruited. 123 patients took enzyme-inducing comedication. The mean lacosamide serum concentration was 28.5 16.4 lmol/l. 27,4% of the patients presented toxic symptoms at a mean lacosamide concentration of 29.6 15.4 lmol/L. This was independent of sodium channel acting comedication. Lacosamide concentrations were correlated with the dose and the intervals from dosing with no correlation with age. Women had higher concentrations (31.3 19.1 vs 25.6 12.6 lmol/L, p = 0.003) but not higher daily dose or percentage of toxic symptoms. Mean lacosamide concentrations were lower in patients taking enzyme-inducing comedication (21. 8 11.7 vs 33.8 18.6 lmol/L, p < 0,001). After multivariate regression analysis with respect to daily dose and intervals, enzyme-inducing medication and gender were statistically significantly related to serum concentrations. Conclusion: Lacosamide concentrations are decreased by enzymeinducing comedication. Higher concentrations in women could be explained by lower body mass and the absence of higher frequency of toxicity may imply a potentially higher female tolerance.

Brossels, Belgium; UCB Pharma, Brussels, Belgium; and UCB Pharma, Raleigh, USA
Purpose: Lacosamide was approved in 2010 for reimbursement in Belgium as add-on therapy for patients (16 years) with uncontrolled focal epilepsy after failure of at least 3 lifetime antiepileptic drugs. This study is being conducted to document patient demographics, lacosamide dosing, evolution of seizure control, and tolerability during a 6-month period in a real-life setting. Method: Patients were either already being treated (Group 1) or initiated treatment with lacosamide at enrollment (Group 2). Seizure control was determined by investigators using a 4-category scale (much improved, improved, stable, worsened), and tolerability by spontaneous patientreported treatment-related adverse events (AEs). Result: At interim analysis, 51 patients (28 female, age 1777 years) of 150 had completed an observational period of at least 4.5 months or had dropped out. Patients were highly refractory; all had 3 lifetime AEDs and 35% had 7. Following a mean study duration of 162 days, the mean daily lacosamide dose in Groups 1 and 2 was 347 and 297 mg (range 150600 mg), respectively. On study completion, seizure control was improved or much improved in 53% of patients in Group 1 and in 56% of Group 2. AEs occurred in 29% of patients (most frequently fatigue, dizziness or vertigo). Thirteen patients discontinued (29% of completers, 10% of enrolled) due to AEs (n = 8) or lack of efficacy (n = 5); 2 were lost to follow-up. Conclusion: Data from this study so far suggest that in routine clinical practice, lacosamide is well tolerated and improves seizure control in highly refractory patients. Sponsored by UCB Pharma.

p398 THE MTLE MOUSE AS A MODEL OF HUMAN TEMPORAL LOBE EPILEPSY: A COMPARATIVE STUDY OF THE MOST COMMONLY-USED ANTIEPILEPTIC DRUGS V. Duveau*, M. Langlois*, C. Bouyssieres*, T. Chabrol, C. Dumont*, A. Depaulis, and C. Roucard* *SynapCell, La Tronche, France; and Grenoble Institut des Neurosciences, Grenoble, France
Purpose: Mesiotemporal lobe epilepsy is one of the most prominent form of focal drug resistant epilepsy. A better understanding of mechanisms underlying this resistance would help to identify new active compounds. However, the need to have relevant models of MTLE has emerged. Recently, morphological and electroclinical features of MTLE has been observed in adult mice after unilateral injection of kainic acid in the dorsal hippocampus. In this work, we investigated the effect of the most commonly used antiepileptic drugs (AEDs) on the occurrence of focal and spontaneous hippocampal paroxysmal discharges (HPD). Method: Using the MTLE mouse model, we studied the dose response effect of commonly used AEDs, with acute or chronic administration protocols, on the occurrence and the duration of HPD by deep EEG recording. Result: Injection of classical AEDs (e.g. valproate and lamotrigine) failed to suppress HPD in a dose-dependent way. Indeed only high doses are effective (400 and 90 mg/kg, respectively) and are associated with modifications of the general behavior and/or EEG basal activity. A dosedependent suppression of HPD was observed with some other AEDs: carbamazepine, levetiracetam, vigabatrin, pregabalin, tiagabine and also with diazepam without noticeable behavioral or EEG side-effects. Conclusion: Our data show that our MTLE mouse model display a pharmacological profile similar to the one observed in patients suffering from refractory MTLE. The MTLE mouse model therefore provides a critical tool to find new treatments against epilepsy.

p400 EFFICACY OF PROGABIDE ADD-ON FOR REFRACTORY EPILEPSY X. Zou, T. Yuan, and B. Wu West China Hospital, Sichuan University, Chengdu, China
Purpose: Our objective is to evaluate the efficacy of progabide when used as an add-on treatment for people with refractory epilepsy. Method: We searched the Cochrane Epilepsy Group Specialized Register, the Cochrane Central Register of Controlled Trials, PubMed . We also contacted the manufacturers of progabide and researchers in this aspect. Result: A total of seven studies were included. For the whole studies, compared with placebo, progabide was more effective on refractory epilepsy (P < 0.01). The results of subgroup analysis showed that progabide was no effective on refractory partial epilepsy (P > 0.05), and more effective on refractory partial and generalized epilepsy (P < 0.01). Global clinical judgment OR, compared to placebo, was 14.42 (95% CI 3.6856.58). Conclusion: In people with refractory partial epilepsy, progabide when used as an add-on therapy may be not reduce seizure frequency. A large scale, randomized controlled trial with refractory partial epilepsy over a greater period of time is required in future clinical researches.

p399 DRUG UTILIZATION STUDY WITH LACOSAMIDE IN DAILY CLINICAL PRACTICE IN BELGIUM: AN INTERIM ANALYSIS W. Van Paesschen*, H. Hauman, B. Legros, M. De Backer, E. Webster, and P. Dedeken *University Hospital Gasthuisberg, Lueven, Belgium; General Hospital St. Maarten, Duffel, Belgium; ULB Erasme Hospital,

p401 LEVETIRACETAM IN ORAL SOLUTION SAFETY, TOLERABILITY AND EFFICACY IN PAEDIATRIC PATIENTS. SINGLE-CENTRE CLINICAL TRIAL O. Horak, and H. Oslejskova Epilepsy Center Brno, Brno University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

118 Abstracts
Purpose: To determine the occurrence, severity and impact of adverse reactions (ADRs) of levetiracetam in oral solution, and so assess the grade of tolerability for this drug-form in paediatric patients. In addition, to focus on the spectrum of efficacy. Method: A single-centre clinical trial of 19 paediatric patients (median of age 2,67 years) treated with levetiracetam in oral solution over a 6 months period was conducted (monotherapy in 68,4%). Adverse drug reactions (ADRs) have been judged in 3-degree scale in three visits since the initiation of the treatment. Descriptive statistics such as minimum, maximum, mean, median and percentiles were used to describe the dose profile. 100% stacked bar graphs were used to describe proportions of patients according to number of seizures as well as according to ADRs severity. The assessment of efficacy was proved by means of non-parametric McNemar's test for the each type of epileptic seizure and each period individually. Result: 68, 4% of patients had no ADRs. In 31, 6% of cases the therapy was associated with (mostly weak) negative effect on mood, less often the nausea, aggressiveness, fatique or agility occurred. Only one patient had to stop the therapy. The relation with dose-titration profile wasn't improved. Statistically significant efficacy in secondary generalised tonic-clonic seizures and partial complex seizures was proved. Conclusion: Levetiracetam in oral solution seems to be well tolerated and safe drug in paediatric patients. ADRs, mostly of weak severity, were observed in 31, 6%. Emotional lability was the most frequent ADRs.

p403 EVALUATION OF SUDDEN UNEXPECTED DEATH IN EPILEPSY (SUDEP) OCCURRING IN LAMOTRIGINE (LTG) CLINICAL TRIALS T. Tomson*, L. Hirsch, D. Friedman, N. Bester, A. Hammer, M. Irizarry, L. Ishihara, A. Krishen, T. Spaulding, A. Wamil, and R. Leadbetter *Karolinska Institute, Stockholm, Sweden; Yale University, New Haven, CT, USA; New York University Langone Medical Center, New York, NY, USA; GlaxoSmithKline, Uxbridge, UK; and GlaxoSmithKline, Research Triangle Park, NC, USA
Purpose: Previous non-randomized studies reported an increased risk of SUDEP with LTG, but the association may be confounded by tonic-clonic seizure frequency, polypharmacy, and other potential SUDEP risk factors. We evaluated the risk of SUDEP with LTG compared to other AEDs and placebo in randomized controlled clinical trials conducted by GlaxoSmithKline. Method: Among 7,774 subjects in 42 randomized clinical trials, there were 39 all-cause deaths. Ten deaths occurred >2 weeks after discontinuation of study medication and were excluded from on-treatment events. Narrative summaries of deaths were independently reviewed by three clinical experts (TT, LH, DF), blinded to randomization arm. The risk of definite or probable SUDEP (Annegers criteria,1997) was compared between treatment arms for each trial design (placebo-controlled, activecomparator, cross-over), using exact statistical methods. Result: Of 29 on-treatment deaths, there were 8 definite/probable SUDEPs, 4 possible SUDEPs and 17 non-SUDEPs. The overall rate of definite/probable SUDEP for LTG was 2.2 per 1000-patient-years (95% CI=0.715.4). The odds ratios (OR) for on-treatment, definite/probable SUDEP in LTG arms relative to comparator arms, adjusted for length of exposure and trial, wereplacebo-controlled: OR=0.22 (95%CI 0.00 3.14; p = 0.26); active-comparator: OR=2.18 (95%CI 0.17117; p = 0.89); placebo-controlled cross-over: OR=1.08 (95%CI 0.0042.2; p = 1.0). Conclusion: Although the rate of SUDEP was not statistically different between LTG and comparator groups, the confidence intervals were wide and a clinically important increased or decreased risk cannot be excluded. Funded by GlaxoSmithKline.

Purpose: Brivaracetam (BRV) is a novel high-affinity synaptic vesicle protein 2A (SV2A) ligand which also displays inhibitory activity at neuronal voltage-dependent sodium channels. Levetiracetam (LEV) has been reported to be associated with behavioral problems. The objective of this analysis was to compare the incidence of behavioral problems in LEV and BRV clinical trials. Method: All global phase II/III double-blind placebo-controlled trials of adjunctive LEV (n = 4) and BRV (n = 5) in adults with uncontrolled focal epilepsy were analyzed. The number of subjects with at least one nonpsychotic behavioral treatment emergent adverse event (TEAE) was calculated for LEV, BRV, and respective placebo groups. Preferred terms were selected a priori from the psychiatric System Organ Class of MedDRA 9.0. Placebo-adjusted incidence was compared using the MantelHaenszel odds ratio stratified by study and 95% confidence interval. Result: The incidence of nonpsychotic behavioral TEAEs was found to be a third lower in BRV (83/1214, 6.8%) compared with LEV (73/672, 10.9%), whereas the incidences in placebo arms were similar (18/425, 4.2% and 17/351, 4.8%, respectively). The placebo-adjusted incidences were 2.6% for BRV and 6.1% for LEV. The odds ratio (BRV/LEV) was 0.68 [95% CI 0.321.45]. Subjects without concomitant LEV treated with BRV experienced a similar rate of nonpsychotic behavioral TEAEs (67/983, 6.8%) compared with subjects taking concomitant LEV (16/ 231, 6.9%) (corresponding placebo groups: 7/79, 8.9% versus 11/346, 3.2%). Conclusion: Despite lacking statistical significance, the absolute and placebo-adjusted incidence of nonpsychotic behavioral TEAEs were found to be numerically lower for BRV compared with LEV.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

Medical Therapy and Pharmacology 6 Tuesday, 02 October 2012

Purpose: Despite the development of new compounds, more than 30% of patients with epilepsy are still resistant to antiepileptic drugs (AEDs). Pharmaceutical industry clearly needs new preclinical strategies to improve AED discovery and development. Accordingly, chronic animal models of epilepsy that are resistant to one or several AEDs appear of great interest. Method: Mesiotemporal lobe epilepsy (MTLE) is the most common form of epilepsy that is refractory to AEDs. During the past ten years, a model of MTLE in adult mice has emerged where spontaneous recurrent focal seizures with mild behavioral expression are observed. A unilateral

119 Abstracts
injection of kainate (KA) into the dorsal hippocampus induces an ipsilateral hippocampal sclerosis along with the occurrence of spontaneous recurrent hippocampal paroxysmal discharges (HPD). These HPD develop during the first 3 weeks post KA and then remain stable and stereotyped for the whole life of the animals and occur spontaneously about 45 times per hour. Result: By using this MTLE mouse model, SynapCell has developed a broad range of preclinical solutions to better identify promising drug candidates. First, the in vivo screening protocol allows testing of small libraries of compounds and relies on quantitative EEG evaluation of the efficacy of new AEDs on highly recurrent HPDs. Then, promising drug candidates can be further studied for their dose response or long lasting effects with acute or chronic treatments. Conclusion: Altogether, this chronic model of MTLE reproduces behavioral, electroclinical and histopathological features of human MTLE and represents a unique tool to identify new AEDs potentially efficient in drug-resistant MTLE patients.

*University of Porto, Porto, Portugal; 4Health Consulting, Cantanhede, Portugal; BIAL Portela & Ca. SA, So Mamede do Coronado, Portugal; and University of Aveiro, Aveiro,
Purpose: In a phase II placebo-controlled, adjunctive therapy study in adult patients with partial-onset seizures eslicarbazepine acetate (ESL) 800 and 1200 mg/day once-daily (QD) was found to be efficacious and well tolerated. However, the same dose given twice-daily (BID) was not significantly more efficacious than placebo (Epilepsia, 48, 497504, 2007). The present study investigated the steady-state pharmacokinetics of QD and BID regimens of ESL in healthy volunteers. Tolerability was also assessed. Method: Single centre, open-label, randomised, three-way crossover study in 12 healthy volunteers. The study consisted of two 8-day treatment periods separated by a washout period of 1015 days. In each treatment period the volunteers received a daily dose of either ESL (900 mg QD or 450 mg BID) or 450 mg of OXC BID (data not shown). Result: Eslicarbazepine was the major drug entity in plasma, accounting for 94.6% and 94.0% of total exposure with ESL QD and ESL BID, respectively. Eslicarbazepine (Cmax) was 34% higher with ESL QD in comparison with ESL BID; AUC024 was 1133.71 and 1101.16 mmol*h/ L, respectively. Trough plasma eslicarbazepine before the last dose was 24.2% lower in the ESL QD in relation to ESL BID (27.45 and 36.21 lmol/L, respectively). A total of 18 treatment-emergent adverse events were reported in each group. Conclusion: In comparison to ESL BID, administration of ESL QD resulted in 34% higher maximum concentration of eslicarbazepine with similar overall exposure, which may correlate with the efficacy profile reported with ESL.

p405 ESLICARBAZEPINE DOES NOT ALTER PROLIFERATION AND CELL CYCLE DISTRIBUTION OF NEURAL STEM CELLS ISOLATED FROM THE RAT SUBVENTRICULAR ZONE M. I. Morte*, B. P. Carreira*, P. Soares-Da-Silva, I. M. Arajo, and C. M. Carvalho* *University of Coimbra, Coimbra, Portugal; University of Porto, Porto, Portugal; and University of Algarve, Faro, Portugal
Purpose: The effect on the proliferation of cultured neural stem cells isolated from the rat subventricular zone by eslicarbazepine acetate (ESL) and its metabolites, eslicarbazepine, and R-licarbazepine (R-Lic), carbamazepine (CBZ), oxcarbazepine (OXC), lamotrigine (LTG) and valproic acid (VPA) was investigated. Method: Cell proliferation was determined by the incorporation of 5ethynyl-2-deoxyuridine (EdU) after exposure of the cells to AEDs for 24 h, analysed by flow cytometry, together with cell cycle analysis performed by quantitative fluorescence. Result: The number of EdU-positive cells, with a median of 11.52 cells (10.4712.62 cells) in basal conditions, was decreased by all the AEDs except eslicarbazepine (10300 lM). Number of cells was decreased by 60% after treatment with ESL (30 lM), by 40% after treatment with RLic (1 lM), between 6575% after treatment with CBZ (10300 lM), by 60% or 90% after treatment with OXC (30300 lM), by 30% after treatment with LTG (300 lM), and by 98% after treatment with VPA (13 mM). Cells in G0/G1 phase increased by 2% after treatment with LTG (10 lM) and by 13% after treatment with VPA (1 mM). The number of cells in S phase was unchanged by the AEDs [median of 3.4% (2.6 4.0%)]. However, the number of cells in G2/M phase was increased by 90% after exposure to OXC (300 lM), while VPA (13 mM) decreased the number of G2/M cells by 6570%. Conclusion: Eslicarbazepine does not alter the proliferation of neural stem cells, whereas CBZ, OXC and VPA impaired proliferation of neural stem cells.

p407 RETIGABINE IN CHILDREN AND ADOLESCENTS WITH PHARMACORESISTANT EPILEPSIES DOCUMENTATION WITH THE ELECTRONIC TREATMENT DIARY EPI-VISTA K. Groening*, C. Dreiwes, U. Stephani, and R. Boor *Klinik fr Neuropdiatrie, Kiel, Germany; and Norddeutsches Epilepsiezentraum, Schwentinental, Germany
Purpose: The anticonvulsant retigabine exhibits a novel mechanism of action opening neuronal KCNQ/Kv7 potassium channels. Investigations on effects and side-effects in children/adolescents are not available. We analysed results of individual treatment trials with retigabine in pharmacoresistant epilepsies, focussing on seizure frequency and tolerability. Method: 17 patients (1;1019 years) with pharmacoresistant epilepsies were treated with retigabine. 12 patients documented seizures, dose and side effects in EPI-Vista. We compared the number of seizures during the last 4 weeks before starting treatment (baseline) with 4 weeks after reaching 10 mg/kg body weight/day or after the patient became seizure free or had side-effects earlier during titration. Result: The patients were treated with 413 (median 6.5) anticonvulsants before starting retigabine, duration of epilepsy was 1;211;6 (median 8) years. The number of seizures at baseline were 8 -1045 (median 47), in the observation period 0 1216 (median 15). Three patients showed reduction of seizure frequency of more than 50%. The dose when side effects were present was 6.3 16.37 (median 10,2) mg/kg body weight. 2 patients did not have side effects. The side effects were fatigue (6), speech disorders (3), concentration disturbances (3), sleep disorder, hallucination, agitation, increase of seizures, personality changes, elevated lever values. All side effects vanished when reducing/ending treatment with retigabine. Conclusion: Retigabine is a novel anticonvulsant which showed reduction of seizures in 3/12 children with pharmacoresistant epilepsies. Side
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x


120 Abstracts
effects appeared in most cases but were reversible when withdrawing retigabine. Further studies are needed to define the group of children where retigabine is most powerful. (for early adverse effects in 8, non-compliance 3, and concomitant pseudoseizures 1). Among the 76 patients with informative trials, 15 (19.73%) became seizure-free for more than 12 months (mean: 17.67 months [SD: 3.67], range: 1224). The mean dose of lacosamide used in seizure-free patients was 246.66 mg. The mean number of previously failed AED trials, in the group of 76 patients, was 8 (SD: 3.51, range: 2 16). When the analysis was restricted to the 56 patients who had failed >6 AED trials, the number of seizure-free patients was 7 (12.5%). Conclusion: In our study, lacosamide showed a promising result when used as adjunctive therapy in patients with previously drug-resistant focal epilepsy, included those who had previously failed six or more AED trials.

p408 THE EFFECTS OF ESLICARBAZEPINE, R-LICARBAZEPINE, OXCARBAZEPINE, AND CARBAMAZEPINE ON SODIUM CURRENTS THROUGH NAV1.2 CHANNELS N. Pires*, K. Brady, S. Hebeisen, and P. Soares-Da-Silva *BIAL Portela & Ca. SA, So Mamede do Coronado, Portugal; BSYS GmbH, Witterswil; and University of Porto, Porto, Portugal
Purpose: Eslicarbazepine acetate (ESL) is a once-daily antiepileptic drug approved in Europe as adjunctive therapy for refractory partialonset seizures in adults. ESL undergoes rapid and extensive first pass metabolism via hydrolysis to eslicarbazepine, its major active metabolite. This study was aimed to determine the effects of eslicarbazepine, R-licarbazepine (minor metabolite of ESL), oxcarbazepine (OXC), and carbamazepine (CBZ) on the rat NaV1.2 sodium channel expressed in CHO cells. Method: About 2448 hours following transfection with rat NaV1.2 cDNA, cells were ready for electrophysiological experiments. The whole-cell patch-clamp technique was used to investigate the effects of eslicarbazepine, R-licarbazepine, OXC, and CBZ on NaV1.2 inward peak currents. These compounds were tested at various holding potentials ()80 mV and )70 mV). Result: With the exception of CBZ, the potency of inhibition was highly sensitive to the holding potential, increasing with depolarisation, but the affinity of eslicarbazepine was approximately 2- to 3-fold lower than that of OXC and CBZ in more depolarized conditions. CBZ was endowed with the potency to inhibit inward NaV1.2 sodium currents at )80 mV and )70 mV holding potentials. Conclusion: Eslicarbazepine demonstrated a greater selectivity for the inactive state of NaV1.2 sodium channels, which is the common feature of the rapidly firing neurons, over their resting state as compared to CBZ and OXC.

Purpose: The purpose of the study was to evaluate the prescription pattern of older and newer antiepileptic drugs (AEDs) in a representative population of patients with epilepsy in the tertiary care centre in India. Method: Prescription data of epilepsy patients attending outpatient department (OPD) of neurology, AIIMS, India was obtained. Demographic variables including age, sex, diagnosis, age at onset of seizures, frequency of seizures and use of all AEDs were noted. Descriptive analysis of the use of older and newer AEDs was done and their different combinations were studied. Result: The prescriptions of 1000 epileptic patients attending OPD from 1st October 2010 to 27th January 2012 were evaluated. The demography showed 63.8% males, 36.2% females; mean age 23.2 years (range: 4 months to 77 years). The cases of generalized and focal seizures were 50.9% and 49.1% respectively. A total of 14 AEDs were prescribed. The four most frequently prescribed AEDs were sodium valproate (46.6%), clobazam (40.4%), carbamazepine (31.2%), levetiracetam (30.1%). The 32.7% of the patients received monotherapy. The common AEDs used on monotherapy were sodium valproate (33.6%), carbamazepine (25.1%), phenytoin (23.5%). Of the 67.3% patients received polytherapy, the three most common AED combinations were phenytoin + clobazam (46), sodium valproate + clobazam (40), phenytoin/carbamazepine + sodium valproate + clobazam (27). The recent AED introduced in 2010 in India was lacosamide used in 25 patients as add on therapy. Conclusion: An increasing trend of use of newer AEDs needs careful scrutiny in terms of cost, efficacy and safety.

p409 EFFICACY OF LACOSAMIDE IN DRUG-RESISTANT FOCAL EPILEPSY P. Bellas-Lamas, A. Fraga-Bau, B. Rodriguez-Acevedo, E. Alvarez-Rodriguez, and J. Gomez-Alonso University Hospital Xeral-Cies, Vigo, Spain
Purpose: New antiepileptic drugs (AEDs) may offer some hope in refractory epilepsy, even in cases of absolute drug-resistance, or grade III drug-resistance, that had failed >6 AED trials. We analyzed our experience with lacosamide in refractory focal epilepsy. Method: We prospectively registered all patients treated with lacosamide, as adjunctive therapy, until December 2010, at the Epilepsy Clinic of a general hospital in NW Spain. In February 2012, we evaluated the outcomes of those trials following the standards of the International League Against Epilepsy. The daily dose of lacosamide usually prescribed was 50 mg for two weeks, 100 mg for another two weeks, and then 200 mg or more. Result: Although lacosamide was administered to 88 patients with focal epilepsy, 12 trials were excluded because their results were undetermined
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

p411 RUFINAMIDE'S EFFICACY AND SAFETY IN CHILDHOOD EPILEPSY SECONDARY TO BRAIN MALFORMATIONS R. Moavero*, F. Madeddu, D. Pruna, M. Balestri, L. Fusco, N. Specchio, A. Capuano, D. J. Claps, P. Curatolo*, F. Vigevano, and R. Cusmai *Tor Vergata University Hospital of Rome, Rome, Italy; Azienda Ospedaliero Universitaria of Cagliari, Cagliari, Italy; and Bambino Ges Children's Hospital of Rome, Rome, Italy
Purpose: Aim of this study was the evaluation of efficacy and tolerability of add-on Rufinamide in pediatric patients with focal symptomatic epilepsy due to brain malformations.

121 Abstracts
Method: We retrospectively reviewed the clinical and electroencephalographic data of 32 children with refractory seizures symptomatic of different brain malformations treated with Rufinamide. Rufinamide was slowly titrated up to 40 mg/Kg/day (range 1040 mg/Kg/day, mean 33 mg/Kg/day). All the patients have been followed-up for at least 12 months. Patients have been considered responders if seizure reduction was greater than 50%. Result: 46,9% of patients presented focal cortical dysplasia, 21,9% pachygyria, 12,5% lissencephaly, 6,2% polymicrogyria, 3,1% ulegyria, 3,1% tuberous sclerosis, 3,1% schizencephaly, and 3,1% Walker-Warburg syndrome. 81,2% of patients presented focal motor and complex partial seizures, 15,6% focal motor seizures and the last patient only complex partial seizures. At the final follow-up 50% of patients were responders; seizure reduction was greater than 90% in 9% of cases, between 75% and 90% in 19%, and ranging from 50 to 75% in 22%. All the non-responder patients (50%) discontinued Rufinamide. 31,2% of subjects presented mild and transient side effects; only in one case (3,1%) dosage reduction was necessary to control irritability. In another patient (3,1%) Rufinamide was discontinued because of persisting anorexia. Conclusion: Our results suggest that Rufinamide can be considered as a valuable adjunctive therapeutic option for children presenting refractory seizures symptomatic of brain malformations. Purpose: To demonstrate the bioequivalence (BE) between two active product ingredient (API) sources of eslicarbazepine acetate (ESL) [current API source marketed formulation (MF) versus new API source to-be-marketed (TBM)]. Method: Two-centre, open-label, randomized, gender-balanced, singledose, laboratory-blinded, two-period, two-sequence, crossover study in two groups of 20 healthy subjects. Subjects randomly received on period 1 and 2 either a single tablet of ESL (MF) or a single tablet of ESL (TBM), separated by a wash-out of at least seven days between doses. Two dosage strengths were studied 400 mg in one group and 800 mg in the other. For all subjects, blood samples (4 mL) were drawn for the assay of plasma ESL and its active metabolite eslicarbazepine at pre-dose and then 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose on each dosing period. Result: At the two studied dosage levels, 400 mg and 800 mg, the 90% back-transformed confidence intervals for Cmax, AUC0-t and AUC0- ratios of the Test formulation (TBM) and Reference (MF) formulation were all contained in the bioequivalence range of 0.8 1.25. Additionally, at both dose levels, no evidence of difference between Test and Reference products in tmax (p > 0.05) was found. Study treatments, whatever the dosage and formulation, were well tolerated. Conclusion: The oral formulations containing 400 mg or 800 mg of ESL of the TBM source are bioequivalent to the MF source for both 400 mg and 800 mg of ESL.

p412 ON THE USE OF INTRA RECTAL VALIUM IN PATIENTS WITH DRAVET SYNDROME: FAMILIES EXPERIENCE R. Nabbout*, N. Chemaly, and N. Coque *Hopital Necker-Enfants Malades, Paris, France; Paris, France; and Brest, France
Purpose: Intra rectal Diazepam (DZ) remains the first rescue medication for acute prolonged convulsive seizures in children. In this study, we aimed at assessing the experience of the families of patients presenting Dravet syndrome (DS) concerning DZ use. Method: We invited 53 families of patients with DS to complete an auto-administered on-line questionnaire. Questions addressed the different aspects of intra rectal DZ use: usual administrators, and time, easiness, and risk of errors in the preparation and administration. Parents were questioned about their feeling concerning efficacy, usefulness in emergency setting, facility of its administration, and possible refuse of care givers to use it. Result: 52 families answered the questionnaire. DZ was usually administered by mothers and less frequently by other care givers. Almost all parents (92%) agreed on its efficacy. However, 50% found that preparation and administration are affected by errors especially when carried out of the parents presence. Many educational and non-medical institutions refused to use DZ. Conclusion: Parents confirm the efficacy of intra rectal DZ and emphasized the need for a medication that is easier to prepare and administer.

Purpose: Although the cognitive side effects of AEDs are more or less known, the risk profiles of the respective drugs must be extrapolated from a plethora of studies with heterogeneous study designs, control conditions and assessments. In this regard, we aimed at a cross-sectional head-to-head comparison of the cognitive effects of common AEDs given in mono- or polytherapy and using the same screening test. Method: Using a cross-sectional controlled study design, 542 untreated epilepsy patients, 1074 patients on mono-, and 1357 patients on polytherapies were evaluated in regard to a set of executive functions. For this purpose, we applied a 12-minute tool (EpiTrack) which, in its second edition, had newly been standardized for an age range of 1687 years. in 689 healthy subjects. Result: In the off drug condition, 42% of the patients were impaired. Compared to this, the odds ratios increased from 1.4 with monotherapy to 7.8 with 4 drugs in polytherapy. Linear regression indicated worse EpiTrack performance with a higher number of AEDs, TPM, ZNS, or GBP and better performance with LEV or LTG. Education appeared to be a protective factor, female gender an additional risk factor. The regression model, however, only explains 23% of the observed variance. Following odds ratios, AEDs could be grouped into three classes with ratios of 1.9 2.6 (LTG, LEV, CBZ, OXC), 2.63.6 (VPA, PB, PGB, LCM, GBP, PHT) and 4.15.3 (ZNS, TPM, CLB). Conclusion: This is the first study, which, using a single assessment tool, models and replicates the known cognitive effects of common AEDs in a cross-sectional study design.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

p413 COMPARATIVE BIOAVAILABILITY STUDY OF TWO DIFFERENT SOURCES OF ESLICARBAZEPINE ACETATE IN HEALTHY SUBJECTS R. P. Sousa*, R. Lima*, T. Nunes*, and P. Soares-Da-Silva *BIAL Portela & Ca. SA, So Mamede do Coronado, Portugal; and University of Porto, Porto, Portugal

122 Abstracts

Medical Therapy and Pharmacology 7 Tuesday, 02 October 2012

p415 DESIGN OF A PHASE III, DOUBLE-DUMMY, ACTIVECONTROLLED, MULTI-NATIONAL NON-INFERIORITY MONOTHERAPY TRIAL OF ESLICARBAZEPINE ACETATE VERSUS CONTROLLED-RELEASE CARBAMAZEPINE IN ADULTS WITH PARTIAL-ONSET SEIZURES J. Moreira*, E. Trinka, F. Mota*, T. Nunes*, and P. Soares-DaSilva *BIAL Portela & Ca. SA, So Mamede do Coronado, Portugal; Paracelsus Medical University, Salzburg, Austria; and University of Porto, Porto, Portugal
Purpose: Eslicarbazepine acetate (ESL) was approved by the European Medicines Agency in 2009 as adjunctive therapy in adults with partialonset seizures, with or without secondary generalization. This phase-III, randomised, double-blind, active-controlled, non-inferiority study aims to demonstrate the efficacy and safety of once-daily ESL as monotherapy treatment for newly diagnosed adults with POS in comparison to twicedaily controlled-release carbamazepine (CBZ-CR). Method: Patients (>18 year) with >2 unprovoked seizures in the past year and >1 in the last 3-months will be randomised in a 1:1 ratio to receive ESL 800 mg once-daily or CBZ-CR 200 mg twice-daily during a 26-week evaluation-period. In case of seizure occurrence during the evaluation-period, subjects are titrated to dose-levels B (1200 mg once-daily/ 400 mg twice-daily) and C (1600 mg once-daily/600 mg twice-daily). To assess maintenance of effect over 1-year, a 26-week maintenance-period will follow. Exit criteria include seizures at dose-level C at evaluationperiod or at any dose-level in the maintenance-period. The primary endpoint is seizure-freedom in the 26-week evaluation-period at the last received dose level. The sample size was calculated to achieve a > 90% power to establish non-inferiority, using a )12% margin. Secondary endpoints include tolerability, QOLIE)31, sedation, and clinical laboratory assessments. Result: The study is expected to be completed by the end of 2013. Conclusion: The use of a non-inferiority design implies the pre-definition of a clinically relevant margin and adequate power to detect noninferiority versus a gold standard. To our knowledge this is the first pivotal study to fully achieve those requirements.

Method: Twelve patients affected by focal epilepsy underwent A-PSG, MSLT, and a subjective evaluation of nocturnal sleep by means of PSQI and daytime somnolence by means of the Epworth Sleepiness Scale (ESS), before and after 3 month treatment with ZNS. Recordings were evaluated in according to standard criteria. The study was single-blind. PSG data, MSLT, both PSQI and ESS scores were calculated before and after ZNS treatment. Statistical analysis was performed by means of the non-parametric Wilcoxon test. Bonferroni correction was applied when required. Result: ZNS induced a decrease of seizures >50% in 9 out of 12 patients (75%). ZNS did not induce any significant differences of nocturnal PSG parameters and mean sleep latency as measured by means of MSLT. No significant changes were detected in both PSQI e ESS scores after ZNS addition. Conclusion: To our knowledge this is first study focusing about the effects of ZNS on nocturnal sleep and diurnal sleepiness. Firstly ZNS adjuntive treatment seems to be effective in focal epilepsy in our narrow sample as reported in several clinical trials3. In addition ZNS does not induce negative effects on sleep-wake cycle and diurnal sleepiness as evaluated by means of a comprehensive objective e subjective evalution.

p417 EFFICACY OF PERAMPANEL, A SELECTIVE AMPA ANTAGONIST, IN COMPLEX PARTIAL AND SECONDARILY GENERALIZED SEIZURES: A POOLED ANALYSIS OF PHASE III STUDIES IN PATIENTS WITH TREATMENT-RESISTANT PARTIAL-ONSET SEIZURES B. J. Steinhoff*, H. Gauffin, P. Mckee, D. Squillacote, H. Yang, D. Kumar, and A. Laurenza *Epilepsiezentrum Kork, Kehl-Kork, Germany; Linkping University, Linkping, Sweden; The James Cook University Hospital, Middlesbrough, UK; and Eisai Neuroscience Product Creation Unit, Woodcliff Lake, NJ, USA
Purpose: In this sensitivity/subgroup analysis we summarize the efficacy of perampanel in both complex partial plus secondarily generalized seizures (CPS+SGS) and secondarily generalized seizures (SGS) across phase III studies according to actual doses of perampanel achieved. The randomized population, with prespecified endpoints, will be presented in the poster. Method: Following Baseline, patients were randomized to once-daily placebo, perampanel 2, 4, 8, or 12 mg. Endpoints included percent change in CPS+SGS and SGS frequency/28 days (vs Baseline), and CPS+SGS and SGS 50% responder rates. Analyses were based on last actual perampanel doses in patients completing 19 weeks treatment (excluding Central/South American patients due to significant treatmentby-region interactions). Result: Overall, 442, 180, 172, 431, and 254 patients were randomized to placebo, perampanel 2, 4, 8, 12 mg, respectively; 1264 patients completed the studies. The numbers of patients achieving each actual dose were: 348, 161, 159, 46, 287, 14, 114 for placebo, perampanel 2, 4, 6, 8, 10, 12 mg. Median percent changes in CPS+SGS frequency were )14.6% (n = 319), )26.6% (n = 150), )35.6% (n = 145), )35.9% (n = 267), )30.3% (n = 104) for placebo, perampanel 2, 4, 8, 12 mg actual doses. Responder rates were 21.9%, 29.3%, 37.9%, 40.1%, 39.4%. Median percent changes in SGS frequency were )19.5% (n = 133), )27.9% (n = 60), -54.6% (n = 66), )60.8% (n = 112), )56.0% (n = 43) for placebo, 2, 4, 8, 12 mg. Responder rates were 38.3%, 43.3%, 53.0%, 56.3%, 53.5%. Conclusion: In this sensitivity/subgroup analysis of phase III trials, perampanel decreased CPS+SGS and SGS frequency and increased responder rates, compared with placebo. Support: Eisai Inc.

p416 ZONISAMIDE AS ADD-ON TREATMENT DOES NOT AFFECT NOCTURNAL SLEEP AND VIGILANCE IN PATIENTS AFFECTED BY FOCAL EPILEPSY: A POLYSOMNOGRAPHIC STUDY A. Romigi, F. Izzi, F. Placidi, S. Zannino, E. Evangelista, C. Del Bianco, F. Cum, and M. G. Marciani University of Rome Tor Vergata, Rome, Italy
Purpose: Epilepsy are particularly sensitive to the sleep disruption induced by antiepileptic drugs (AEDs). AEDs have the potential to either improve or worsen sleep and sleep disorders in epileptic patients. Zonisamide (ZNS) is a new AED approved in USA and Europe as adjunctive therapy for focal epilepsy. To date the effects of ZNS on sleep and vigilance in focal epilepsy are not yet studied. The purpose of our study is to evaluate the effects of ZNS adjunctive therapy on nocturnal sleep by means of ambulatory polysomnography (A-PSG) and Pittsburgh Sleep Quality Index (PSQI) and on daytime somnolence by means of multiple sleep latency test (MSLT) and Epworth Sleepiness Scale (ESS) in focal epilepsy as standard methodology.
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

123 Abstracts
Purpose: So far the information on cognitive effects of antiepileptic treatment is based on short-term trials. The long-term effects have, as yet, not been studied. Mostly fluid cognitive functions are assessed as no changes are expected in higher-order function in such a short period. It is unknown whether higher functions are at risk with longer treatment intervals. In this open clinical cohort study the long-term cognitive effects of monotherapy carbamazepine and valproate were evaluated in children and adults with epilepsy. Method: Patients were only included when they had been on monotherapy CBZ or VPA from epilepsy onset without any switch to other medication. Outcome measures included WISC-III/WAIS-III1,2 and cognitive tests (FePsy)3. Result: Thirty-five children (average treatment length 3.8 years) and 22 adults (average treatment length 7.8 years) were included with CBZ. Forty-six children and 17 adult patients were included with VPA. Average length of treatment in both VPA-groups was 3.5 years. Signs for mild mental/psychomotor slowing without any differences between CBZ and VPA were found. Children on CBZ had lower intelligence scores than on VPA. However, this result was not found for adults. The two treatment groups did not differ in type of epilepsy. There is a high inverse correlation between length of treatment and IQ-scores only for children on CBZ. Conclusion: Our study shows evidence that at long-term CBZ may impact higher-order cognitive function and even intelligence in children. As this effect was not found for adults, this suggests that longterm treatment with CBZ may influence the maturation of the brain in children. in the first twenty-four hours following incubation regardless of drug loading percentage, and then demonstrated a steady release until eight weeks. We confirmed the neuronal loss in CA1 in the lesioned hippocampus of tetanus-treated rats. Spontaneous seizures which resemble human generalized tonic clonic seizures, absence and myoclonic seizures have been observed. The PHT-loaded microsphere implanted rats exhibited a reduced number of convulsive seizures as illustrated by attenuated seizure scores. Conclusion: This study demonstrates the efficacy of PHT-loaded PCL microspheres in attenuating generalized seizures in a rat model of temporal lobe epilepsy. This may warrant further studies for focal delivery of polymer-based anticonvulsants in treating partial and secondary generalized seizures.

p420 SEIZURE FREEDOM ON ANTIEPILEPTIC MONOTHERAPY L. J. Stephen, K. Kelly, O. Mcgowan, V. Politi, and M. Brodie Western Infirmary, Glasgow, UK
Purpose: The goal of antiepileptic drug (AED) treatment is sustained seizure freedom on monotherapy with no or acceptable side effects. This project examined characteristics of patients seizure-free on 1 AED for 1 year. Method: Data were acquired by Epilepsy Unit database and case sheet interrogation of 6821 patients registered between 1982 and 2011. Result: Seizure freedom was achieved on 17 different monotherapies in 1425 (20.9%) patients (687 men, 738 women, aged 1894 years [median 46 years]). Of these, 1131 (79.3%) had partial + secondary generalised tonic-clonic seizures [GTCS], 294 (20.7%) had idiopathic generalised epilepsies. First monotherapy produced complete seizure freedom in 866 (60.7%) patients; the remainder controlling on 2nd (n=309, 21.7%), 3rd (n=217, 15.2%), 4th (n= 31, 2.2%), or 5th (n=2, 0.2%) schedules. The commonest AEDs used were sodium valproate (n=443, 31.1%), carbamazepine (n=382, 26.8%), lamotrigine (n=318, 22.3%) and levetiracetam (n=82, 5.8%). Of patients receiving sodium valproate, 67% (n=298) took 1000mg/day (median 1000, range 4003000), 66% of carbamazepinetreated patients received 600mg/day (median 600, range 2002000), 75% of lamotrigine-treated patients received 200mg/day (median 200, range 25700), and 74% of levetiracetam-treated patients received 1000mg/day (median 1000, range 5003000). There was no relationship between AED dosing and schedule. Side effects (108 [81%] neurotoxicity, 26 [19%] other) were reported by 134 (9.4%) patients, particularly those taking carbamazepine (60 of 382, 16%; others 73 of 1043, 7%; p<0.001). Conclusion: Although the majority of patients became seizure-free on their first monotherapy, a substantial minority controlled on later schedules. Doses were often modest. Side effects were twice as likely with carbamazepine.

p419 IMPLANTATION OF PHENYTOIN-LOADED POLYCAPROLACTONE MICROSPHERES IN A RAT MODEL OF TEMPORAL LOBE EPILEPSY J. Sui*, A. Halliday, K. Mclean*, T. Wilson, S. Moulton, G. Wallace, R. Balson, A. Lai*, N. Beattie*, and M. Cook* *St Vincent's Hospital, Melbourne, Vic, Australia; University of Melbourne, St. Vincent's Hospital, Melbourne, Vic, Australia; St Vincent's Pathology, Melbourne, Vic, Australia; University of Wollongong, Wollongong, NSW, Australia; and Bionics Institute, Melbourne, Vic, Australia
Purpose: The main purpose of this study is to explore the potential therapeutic effects of intracerebral polymer-based anticonvulsant delivery in treating generalized and partial seizures. Method: Phenytoin (PHT)-loaded polycaprolactone (PCL) microspheres were produced by performing an emulsion process. The actual drug loading and releasing profile was determined using high performance liquid chromatography. Temporal lobe epilepsy model was established by unilateral injections of tetanus toxin into right hippocampus of adult male Sprague-Dawley rats. PHT PCL spheres were ipsilaterally injected in the adjacent region. Seizure phenotypes and cortico-electrical discharges were detected and recorded by a twenty-four hours video electroencephalography system equipped with ProFusion. Animals were killed eight weeks after toxin injection, and biocompatibility was assessed by immunohistochemistry. Result: The PCL microspheres were 3050 lm in diameter. In vitro study revealed PCL microspheres released a substantial amount of PHT

p421 ESLICARBAZEPINE ACETATE AND PLASMA LEVELS OF COMBINED ANTIEPILEPTIC DRUGS: A POPULATION PHARMACOKINETICS EVALUATION BASED ON DOUBLE-BLIND PHASE III CLINICAL STUDIES M. Bialer*, A. Falco, R. Costa, N. Lopes, T. Nunes, and P. Soares-Da-Silva *The Hebrew University of Jerusalem, Jerusalem, Israel; 4Health Consulting, Cantanhede, Portugal; BIAL - Portela & Ca. SA, So Mamede do Coronado, Portugal; and University of Porto, Porto, Portugal
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

124 Abstracts
Purpose: Eslicarbazepine acetate (ESL) is a once-daily voltage-gated sodium channel blocker approved in Europe for use in adults as adjunctive therapy for refractory partial-onset seizures (POS) with or without secondary generalisation. The variability of the population pharmacokinetics (PK) and systemic plasma exposure to concomitant antiepileptic drugs (AEDs) in treating patients with refractory POS were analysed to determine the potential influence of ESL on the metabolism and PK of concomitant AEDs. Method: Plasma concentrations of eslicarbazepine (main active metabolite of ESL) and other concomitant AEDs were obtained from 641 patients receiving ESL. Data were analysed using nonlinear mixed-effect modelling (NONMEM) methods. Plasma exposure PK parameters were calculated from individual parameters estimates derived from the model. A population PK model of trough (Cmin,ss) eslicarbazepine plasma concentrations at steady-state was fitted. Result: No clinically relevant changes in the mean end/initial Cmin,ss ratios of concomitant AEDs were calculated for placebo, ESL 400 mg and 800 mg dose groups. In ESL 1200 mg treated patients, mean end/ initial Cmin,ss ratios of carbamazepine (CBZ), lamotrigine (LTG), and topiramate (TPM) were reduced by 13%, 25% and 16%, respectively. ESL slightly increased the oral clearance (CL/F) of CBZ, LTG, and TPM up to 14%, 12%, and 16%, respectively, but did not affect that of clobazam, gabapentin, phenytoin, phenobarbital, levetiracetam and valproate. Conclusion: This pop-PK analysis based on integrated data from three phase III clinical studies suggests that the pharmacokinetic effect of eslicarbazepine acetate on the clearance of concomitant AEDs is unlikely to be clinically relevant in most cases.

p423 OUTCOMES IN NEWLY DIAGNOSED EPILEPSY WHY DO PATIENTS REMAIN UNCONTROLLED? M. Brodie*, D. Goldberg*, K. Kelly*, L. J. Stephen*, and P. Kwan *Western Infirmary, Glasgow, UK; and Prince of Wales Hospital, New Territories, Hong Kong
Purpose: More than 30% of a cohort of 1098 patients with newly diagnosed epilepsy followed for 226 years were uncontrolled at the time of analysis (Brodie et al. Neurology, in press). Their clinical details were examined to see how many fulfilled the ILAE criteria for drug-resistant epilepsy (Kwan et al, Epilepsia 2010; 10691077). Method: Casesheets from 361 patients were reviewed and data entered into a web-based drug response classifier programme (Hao et al. Epilepsy Behav 2011; 388390). Those that were categorised as undefined were investigated further. Result: Thirty-two patients had died and data were incomplete for 9 patients. A further nine had taken part in head-to-head placebo-controlled trials. Of the remaining 311 patients, 136 (43.7%) fulfilled the definition of drug-resistant epilepsy. The remaining 175 (56.3%) were classified as undefined. A number of reasons were identified, including trying one drug, inadequate dosing, intermittent compliance, adverse effects at minimal dosage, psychiatric problems affecting documentation, erratic attendance, social issues such as imprisonment, alcohol and recreational drug use, and patient choice (median reasons 2