INTENSIVE MANAGEMENT OF STATUS EPILEPTICUS

OBJECTIVES

 Current definition of status epilepticus

 Classification
 Epidemology
 Etiology
 Types of status epilepticus
 Clinical manefestations-convulsive/nonconvulsive
 Diagnosis
 Therapy

Current guidelines for the management of status epilepticus-Neurocritical care society guide lines-2013
DEFINITIONSTATUS EPILEPTICUS
 Conventional “textbook” definition of status epilepticus:
 Single seizure > 30 minutes
 Series of seizures > 30 minutes without full recovery

 Operational definition Generalized, convulsive status epilepticus in

children and adults refers to > 5 minutes of continuous seizure or >2 discrete
seizures with incomplete recovery of consciousness

Neurocritical care society Guidelines 2012

STATUS EPILEPTICUS-EPIDEMIOLOGY

 US-20-40/100 000
 Bimodal-< 1 year & >60 years
 25% have history of pre existing Epilepsy
 Status epilepticus with 14% mortality rate – 86/100,000 in elderly ,
with 38% mortality rate
Classification framework

Axis 1: Semiology Axis 2 : Etiology of status epilepticus

the clinical presentation of SE :
1.The presence or absence of prominent motor symptoms
2 The degree (qualitative or quantitative) of impaired con- sciousness
Known (i.e., symptomatic)
Acute (stroke, intoxication, malaria, encephalitis, etc.)
Remote (posttraumatic, postencephalitic, poststroke,
Progressive (e.g., brain tumor, Lafora’s disease and
other PMEs, dementias)
SE in defined electroclinical syndromes

Unknown (i.e., cryptogenic)

Axis 3: Electroencephalographic Axis 4:Age

 Location: generalized, lateralized, bilateral independent, multifocal. 1 Neonatal (0 to 30 days).
Name of the pattern
2 Infancy (1 month to 2 years).


 Morphology: sharpness, number of, absolute and relative amplitude,

3 Childhood (> 2 to 12 years).
polarity.
4 Adolescence and adulthood (> 12 to 59 years). 5 Elderly
 Time-related features
 Modulation: stimulus-induced vs. spontaneous. (≥ 60 years).
 Effectofintervention(medication)onEEG.
 STATUS EPILEPTICUS ETIOLOGY

 stroke,including haemorrhagic 20%

 low AED levels 35%
 alcohol withdrawal 15%
 anoxic brain injury 15%
 Metabolic disturbances 15%
 remote brain injury/congenital malformations 20%

 infections 5%
 brain neoplasms 5%
 Idiopathic 5%
 ETIOLOGICAL CLASSIFICATION OF SE:

• CRYPTOGENIC: SE in absence of an acute precipitating CNS insult or metabolic

dysfunction in a patient without a pre-existing neurologic abnormality.
• REMOTE SYMPTOMATIC: SE in a patient with a known history of a neurologic insult
asociated with an increased risk of seizures(Stroke,TBI,static encephalopathy).
• FEBRILE:THE MOST COMMON TYPE IN CHILDREN. SE provoked solely by fever
in a patient without a history of afebrile seizures.
• ACUTE SYMPTOMATIC: SE during an acute illness involving a known neurologic insult or
metabolic dysfunction.
• PROGRESSIVE ENCEPHALOPATHY: SE in a pt. with a progressive neurologic disease.
PATHOPHYSIOLOGY STATUS EPILEPTICUS

GABA A receptor
internalized in Clathrin
coated vesicle and
destroyed in Lysosome

NMDA synapses subunits

are mobilised to the
synaptic membrane

Chen,Wasterlain, Status epilepticus: pathophysiology and management in adults. Lancet Neurol 2006; 5: 246–56
POSTICTAL CELL CHANGES
SPROUTING / CHANGES OF THE NEURONAL FEEDBACK MECHANISM
Susceptibility to
seizures
Neuro- genesis
Neuronal cell death
Glial activation

Sprouting Protein
expression
Activation of kinases Early
gene activation

Calcium ion influx

1 sec. 1 min. 1h 1 day 1 wk 1 month 1 yeTaimr e

(logarithmic)
modified after Cole A.J. (2000) Epilepsia 41(S2):13-22
ASTROCYTES CHANGE THEIR MORPHOLOGY AND PROTEIN
EXPRESSION IN A PROCESS TERMED REACTIVE ASTROGLIOSIS

 As a consequence of SE and subsequent

inflammation, “Became hypertrophic, increase
expression of intermediate filament proteins
(for example, GFAP), and develop longer and
thicker processes”

 A number of molecules and signaling pathways

are known to trigger reactive Astrogliosis, such
as ATP and glutamate, inflammatory cytokines
such as TNF-α and Il1-β.
MICROGLIA MORPHOLOGICAL AND MOLECULAR
ACTIVATION AT DIFFERENT STAGES AFTER SEIZURES.
STATUS EPILEPTICUS : SYSTEMIC AND BRAIN METABOLISM

From Hirsch LJ, Gaspard N. Status epilepticus. Continuum 2013;19(3):767

Neuronal destruction occurs when cerebral metabolic requirements cannot be met by the available oxygen,
glucose and metabolic substrates.
Cerebral
Hypoxic/metabolic cerebral damage
Excitotoxic cerebral damage (seizure related) Cerebral oedema and raised intracranial pressure Cerebral venous
thrombosis
Cerebral haemorrhage and infarction
Cardiorespiratory and autonomic
Hypo- or hypertension
Cardiac failure
Tachy or bradyarrhythmias
Respiratory failure, Pulmonary oedema, hypertension, aspiration, pneumonia Hyperpyrexia ,
Hypersecretion, tracheobronchial obstruction
Metabolic and systemic
Dehydration, Electrolyte disturbances (especially hypoglycaemia, hyponatraemia and hypokalaemia) Acute renal
failure (acute tubular necrosis)
Acute hepatic failure, Acute pancreatitis Disseminated intravascular coagulation
Multiorgan failure, Rhabdomyolysis, Fractures or joint dislocations 13
APPROACH : DIAGNOSTIC WORKUP

All patients
• Obtain IV access
• Monitor vital signs (ABC).
• Head CT (appropriate for most cases)
• Labs: blood glucose, CBC, renal function tests, Calcium, Magnesium, electrolytes, AED
levels.

•cEEG monitoring (preferably)

Consider based on clinical presentation
• Brain MRI
• Lumbar puncture
• Toxicology panel (i.e. isoniazid, TCAs, theophylline, cocaine,
sympathomimetics,
organophosphates, cyclosporine)
• Other relevant investigations as per the need

Brophy G, Bell . Guidelines for the evaluation and management of status epilepticus. Neurocritical care
society. 2012; 17:3-2
 CONTINUOUS EEG MONITORING

 Continuous EEG monitoring should be initiated within 1 hour of SE onset if ongoing seizures are suspected. The
duration of cEEG monitoring should be at least 48 hours in comatose patients to evaluate for non-convulsive
seizures.

 Indication :

 Recent clinical seizure or SE without return to baseline > 10 min, Coma, including post-cardiac arrest,
Epileptiform activity or periodic discharges on initial 30 min EEG, Suspected non-convulsive seizures in
patients with altered mental status

• End point : Cessation of non-convulsive seizures, Diffuse beta activity, Burst suppression 8 – 20
seconds intervals, Complete suppression of EEG

Brophy G, Bell R, Claassen J,Alldredge B, Bleck T, Glauser T, et al. Guidelines for the evaluation and management of status
epilepticus. Neurocritical care society. 2012; 17:3-23
 MANAGEMENT STATUS EPILEPTICUS :
THINK TIME
 Time to treatment needs to be shorter.
 Response to treatment is time dependent.

 Morbidity and mortality are related to etiology and duration (time) of status epilepticus.

 Prolonged seizures predict future prolonged seizures.

1. Termination of Status Epilepticus

2. Prevention of Seizure Recurrence
3. Management of Precipitating cause
4. Management of complications
Brophy G, Bell R, Claassen J,Alldredge B, Bleck T, Glauser T, et al.
Guidelines for the evaluation and management of status epilepticus.
Neurocritical care society. 2012; 17:3-23
 ALGORITHM STATUS EPILEPTICUS

Glauser T, Shinnar S, Gloss D. Evidence-based guideline: treatment of convulsive status epilepticus in children and adults. American epilepsy society
guideline. Epilepsy Currents. 2016; 16:48-61
 PROPOSED ALGORITHM FOR STATUS EPILEPTICUS

Glauser T, Shinnar S, Gloss D. Evidence-based guideline: treatment of convulsive status epilepticus in children and adults. American epilepsy society
guideline. Epilepsy Currents. 2016; 16:48-61
EMERGING THERAPIES

 KETAMINE : An NMDA receptor antagonist, synergistic action of diazepam

in termination SE, Efficacy in extremely refractory SE
 PROPOFOL : Nonbarbiturate anesthetic, Highly lipid soluble with high volume
of distribution resulting in rapid and short lived action,Causes profound
respiratory and cerebral depression requiring assisted ventilation
 Inhalational Anaesthetic agents Isoflurane and Desflurane) Both drugs in endtidal
concentrations of 1.2-5%achieved an EEG burst suppression and termination of seizure
activity within minutes.

Mirsattari SM, Sharpe MD,Young GB. Treatment of refractory status epilepticus with inhalational anaesthetic agents : Isoflurane &
Desflurane.Arch Neurology. 2004; 61(8):1254-9
 NONPHARMACOLOGICAL TREATMENTS
IN STATUS EPILEPTICUS.
 Hypothermia-decrease brain metabolism which is neuroprotective,
 Resective surgery.
 Ketogenic diet.
 Vagal nerve stimulation.
 Resective surgery.1
 Electroconvulsive therapy (ECT)

1. Ng YT, Kerrigan JF, Rekate HL. Neurosurgical treatment of status epilepticus. J Neurosurg. 2006;105(Suppl 5):378–81.
2. Shahwan A, Bailey C, Maxiner W, Harvey AS. Vagus nerve stimulation for refractory epilepsy in children: more to VNS than seizure
frequency reduction. Epilepsia. 2009;50(5):1220–8.
3. Corry JJ, Dhar R, Murphy T, Diringer MN. Hypothermia for refractory status epilepticus. Neurocrit Care. 2008;9(2):189–97.
4. Kamel H, Cornes SB, Hegde M, Hall SE, Josephson SA. Electroconvulsive therapy for refractory status epilepticus: a case series. Neurocrit
Care. 2010;12(2):204–10.
 STEROIDS AND IMMUNOTHERAPY

 Rationale that refractory SE may be due to antibodies directed against neural

elements.
 Increasing recognition the role of inflammation in epileptogenesis.
 SE may be the initial presenting feature of some immune mediated encephalopathies.

Shorvon S, Ferlisi M.The treatment of super-refractory status epilepticus: a critical review of available therapies and a clinical treatment
protocol. Brain: a journal of neurology. 2011; 134:2802-18
STEROIDS AND IMMUNOTHERAPY (IVIG )
KETOGENIC DIET

Diet high in fat and low in

carbohydrates

Induces ketosis in body and

thought to suppress seizures
by release of Leptin.

Exact mechanism remains

unknown.
 SURGERY IN REFRACTORY SE

 Procedures based on standard

epilepsy surgery
 Success has been reported with
focal resections,subpial
transections,corpus
callosotomy,hemispherectomy
ELECTROCONVULSIVE THERAPY (ECT)

 dose-1 session daily for 3-8 days.

PROGNOSIS
 NEURONAL INJURY CORRELATED WITH STATUS DURATION
ELEVATION OF NSE FOLLOWING STATUS EPILEPTICUS
ipsilateral injury (score)

= Status duration
= NSE in serum
Seizure duration in min. DeGiorgio et al. Neurology 1999;52:746–749
Gruenthal, M., Epilepsy Res., 29 (1998) 221-232.
OUT COME

 Depends on age,etiology,degree of impairment of

consciousness
 Refractory & super refractory>>worse prognosis
 No irreversible brain damage>>Good recovery is possible even
after weeks of Status epilepticus
SUMMARY

 Status epilepticus (SE) is a relatively common medical emergency with high morbidity
and mortality.
 Stroke, hypoxic injury, low antiepileptic drug level, metabolic disorders, alcohol, trauma and brain
tumor are the most commonly reported underlying etiologies of SE.
 SE duration, age, level of consciousness and EEG patterns have also been found to
impact the outcomes of SE.
 Phenobarbital, valproic acid, levetiracetam, lacosamide and topiramate can serve as the third line of
treatment.
 General anesthesia is used commonly to treat refractory SE; however, specifics of treatment (i.e., the
anesthetic agent choice and dose, duration of treatment and EEG goal) are yet to be determined.
 Aggressive treatment is necessary and appropriate for all presentations of SE in order to maximize
the probability of a successful outcome, even when the etiology suggests a poor prognosis
THINK TIME - SAVE THE BRAIN
POTENTIAL SITES OF ACTION OF ATP RELEASED DURING STATUS EPILEPTICUS,
EXPRESSIONAL RESPONSES OF INDIVIDUAL P2X RECEPTORS,AND
CONSEQUENCES OF RECEPTOR ACTIVATION.
PATHOPHYSIOLOGY
 REFRACTORY STATUS EPILEPTICUS

•Refractory SE therapy recommendations should consist of continuous infusion AEDs,

but vary by the patient’s underlying condition

•Dosing of continuous infusion AEDs for RSE should be titrated to cessation of

electrographic seizures or burst suppression

•During the transition from continuous infusion AEDs in RSE, it is suggested to use
maintenance AEDs and monitor for recurrent seizures by cEEG during the titration
period.

•A period of 24–48 h of electrographic control is recommended prior to slow

withdrawal of continuous infusion AEDs for RSE
 Seizures continuing / Stage of Refractory Status

 -General anesthesia should be induced

 Propofol:- 2mg/kg IV bolus,Repeat if necessary, followed by infusion (2 – 10 mg/kg/hr)
 Thiopental:- 100-250mg IV bolus over 20 sec. with further 50mg bolus every 2-3
min.until seizure control followed by IV infusion(3-5mg/kg/hr)
 Midazolam:- 0.3mg/kg IV bolus dose at the rate of 4mg/min, rpt every 5 min 3 doses followed by
infusion(2 ug/kg/hr)
 Neuromuscular Blocking Agents :
If seizures have been controlled for 12hrs., reduce the dose over further 12hrs. If seizure
recurs again GA agent should be given
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