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J Neurol (2012) 259:653659 DOI 10.



FB 224j.1204

Ischemic stroke in young adults: classication and risk factors

Anastasios Chatzikonstantinou Marc E. Wolf Michael G. Hennerici

Received: 5 August 2011 / Revised: 26 August 2011 / Accepted: 30 August 2011 / Published online: 17 September 2011 Springer-Verlag 2011

Abstract Our aim was to analyze an important subgroup represented by young adult patients (1945 years) with acute ischemic stroke according to stroke classication (including the novel ASCO score), infarct types and risk factors. All patients up to 45 years of age with an acute ischemic stroke conrmed by MRI and treated in our stroke unit from 2006 to 2009 were recruited for this study. Patients were neurologically examined and underwent thorough stroke work-up. One hundred four patients (58 women, 46 men) with a mean age of 38 6.9 years were evaluated. The mean NIHSS score (SD) was 3 5 on admission and 1 4 on discharge. The classication using TOAST/ASCO (grade 1) was as follows: Macroangiopathic 10.6%/8.7%, cardiac origin 21.2%/10.6%, microangiopathic 9.6%/9.6%, other causes 19.2%/13.5% and undetermined 39.4%/19.2% (for A0S0C0O0). The most common risk factors were smoking (55.2%), hypertension (31.4%) and hyperlipidemia (27.6%). Twenty nine of 74 patients with TEE (39.2%) had a patent foramen ovale (PFO). Hypoplastic posterior circulation (21.9%) and migraine (21.0%) were also quite common. Young adult ischemic stroke patients share many of the characteristic risk factors with the general elderly ischemic stroke population. If regular work-up includes TEE, a high percentage of young patients reveal comorbidities with PFO, hypoplasia of the posterior circulation and migraine. The ASCO classication should be favored for a better classication of coexisting stroke subtypes and lower number of undetermined etiologies in this patient group.
A. Chatzikonstantinou (&) M. E. Wolf M. G. Hennerici tsMedizin Mannheim, Department of Neurology, Universita University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany e-mail:

Keywords Brain ischemia Stroke in young Risk factors ASCO TOAST

Introduction Ischemic stroke in young adult patients between 18 and 45 years is relatively rare (accounting for 212% of cerebral infarcts), but often poses a particular challenge with regard to the diagnosis of stroke subtypes [13]. This is not only important for best secondary prevention recommendations, but also because stroke etiologies and risk factors are generally considered to be very different from those of older patients [36]. Embolism due to cardiac abnormalities, arterial dissection, migraine and specic conditions of hypercoagulation rather than large or small atherosclerotic arteriopathies are thought to be the most common causes of stroke in the young population [57]. Although younger patients usually receive complete stroke work-up, the fact that a large number of strokes are of undetermined etiology (usually [1/3 of all cases) is alarming [2, 8, 9]. One possible explanation is the continuous use of an outdated stroke subtype classication, the Trial of Org 10172 in Acute Stroke Treatment (TOAST) score, which was introduced for a randomized acute stroke trial using heparin in 1993 [10]. The aim of our study was to reevaluate the actual risk factor pattern in young ischemic stroke patients and to compare their etiologies using the more descriptive ASCO score [11].

Patients and methods One hundred four patients (58 women and 46 men) ranging between 19 and 45 years of age (mean age 38 6.9 years)



J Neurol (2012) 259:653659 Table 1 Patient characteristics and risk factors (n = 104 total population) Parameter Age Mean (years SD) Range (years) Women [n (%)] Thrombolysed patients [n (%)] 3 h time window ECASS III time window DWI/PWI-Mismatch [4.5 h after symptom onset NIHSS score (median SD) On admission On discharge Work-up [n (%)] MRI (incl. MRA) Duplex vascular imaging ECG-Monitoring TEE Infarct type [n (%)] Territorial Lacunar Other (multiple territories, emboligenic distribution) Infarct territory (circulation) Anterior only Posterior only Both Risk factors [n (%)] Atrial brillation Coronary heart disease Peripheral artery disease Cerebral large artery disease Diabetes Arterial hypertension Hyperlipidemia 3 (2.9%) 1 (0.9%) 2 (1.9%) 14 (13.5%) 7 (6.7%) 33 (31.4%) 29 (27.6%) 8 (7.6%) 58 (55.2%) 22 (21.0%) 3 (2.9%)/10 (9.6%) 23 (21.9%) 6 (5.7%) 29 (27.9%) 16 (15.4%) 5 (4.8%) 9 (8.6%) 9 (8.6%) 70 (67.3%) 26 (25.0%) 8 (7.7%) 49 (47.1%) 14 (13.5%) 41 (39.4%) 104 (100%) 104 (100%) 104 (100%) 74 (71.2%) 3 (5) (range 025) 1 (4) (range 018) 38.4 6.9 1945 58 (55.8%) 23 (22.1%) 19 (18.3%) 3 (2.9%) 1 (0.9%) Value

and consecutively admitted to our stroke unit with the diagnosis of acute ischemic stroke were recruited for this study. The diagnosis of ischemic stroke was based on clinical features and MRI in all patients. Each patient underwent a clinical neurological examination [including National Institute of Health Stroke Scale (NIHSS) scores] and received a thorough stroke work-up according to the guidelines of the European Stroke Organization, which was documented in our stroke registry in detail: Brain MRI and MRA [including T1-, T2-, T2*-, FLAIR- and diffusionweighted images (DWI) and time-of-ight (TOF) angiography], extra- and intracranial ultrasound cerebrovascular imaging, ECG-monitoring and standard laboratory blood tests. Most of the patients (74/104; 71.2%) also received transesophageal echocardiograms (TEE). The rest refused to undergo TEE or could not be examined during the period of hospitalization. In patients with no obvious stroke etiology or risk factors, thorough coagulation and vasculitis tests were performed. Infarct types and localization on MRI were recorded, as well as history of stroke and/or older cerebral ischemia visible on MRI. Furthermore, patients characteristics and risk factors [patent foramen ovale (PFO), mitral valve prolapse (MVP), atrial brillation, history of coronary and/or peripheral artery diseases, arterial hypertension (history/treatment or hypertensive blood pressure on admission), hyperlipidemia (history/ treatment or high fasting cholesterol levels), diabetes mellitus (history/treatment or high fasting glucose levels and elevated HbA1c), obesity, smoking, history of migraine and positive stroke family history] were recorded in our Stroke Unit database and analyzed. As an additional parameter, we chose to include hypoplastic vertebral arteries (dened as lumen diameter B2 mm in MR-TOF) in the analysis [12]. To classify ischemic strokes according to etiology, we used both the TOAST [10] and ASCO [11] scores and compared their results.

Results Patient characteristics and ischemia types The patient characteristics are summarized in Table 1. There were slightly more women [58 (55.2%)] than men [46 (43.8%)]. We were able to apply thrombolytic treatment to 23 (22.1%) patients, the majority of them (19/23; 82.6%) in the standard 3-h-window, the rest (3/23; 13%) received thrombolytic treatment in the extended 34.5-hwindow (according to the results and recommendations of the ECASS III study [13]) and in 1/23 (4.3%) using mismatch of DWI and perfusion-weighted images (PWI)

Obesity Smoking Migraine Previous stroke: symptomatic/asymptomatic Hypoplastic vertebral artery Stroke family history Patent foramen ovale (all) Arterial dissection (carotid/vertebral artery) Other cardiac disease Hypercoagulable state Other (e.g., drugs, antiphospholipid syndrome, vasculitis)


J Neurol (2012) 259:653659 Fig. 1 Risk factors in all patients (orange, n = 104) and in patients with non-cardiac stroke (blue, n = 83). AF atrial brillation, CHD coronary heart disease, PAD peripheral artery disease, VA vertebral artery


Fig. 2 Patent foramen ovale. Pie chart: distribution of different PFO grades (ASD aortic septal defect). Tables: the frequency of PFO in the different etiology stroke subtype groups using TOAST (LA large artery, CO cardiac origin, SV small vessel, OD other determined, UD

undetermined) and ASCO (A atherothrombosis, S small vessel, C cardiac origin, O other). On the right side are the results only for the patients who received TEE

([4.5 h after onset of symptoms) [14]. The median NIHSS score on admission was 3 5 (range 025) and on discharge 1 4 (range 018). Most of the patients (49/104; 47.1%) suffered a territorial and 14/104 (13.5%) a lacunar stroke, while 41/104 (39.4%) had other stroke morphologies, mostly of emboligenic distribution. In 70/104 patients (67.3%), ischemia was located in the anterior circulation only, in 26/104 patients (25.0%) in the posterior circulation, while in 8/104 cases (7.7%) both vascular territories were simultaneously affected. Risk factors Risk factors are presented in Table 1 and are visualized in Fig. 1, which also shows the frequency of risk factors in all patients compared to patients with non-cardiac stroke, in which cardioembolic risk factors such as atrial brillation are usually absent. Results were similar for these two groups; the following numbers refer to the whole population. Smoking (58; 55.8%) was the most common risk factor in our population, followed by arterial hypertension (33; 31.7%), hyperlipidemia (29; 27.9%) and cerebral artery

atherosclerosis (14; 13.5%). Classic atherosclerotic risk factors (apart from smoking) were found in 59/104 (56.7%) patients. While not being among the classic stroke risk factors and not considered by the TOAST or ASCO criteria, migraine (22; 21.2%) was quite commonly found among our young stroke patients. Hypoplastic vertebral arteries were also a common nding (23; 22.1%). Atrial brillation was found only in three patients (2.9%), all of whom had suffered cardioembolic stroke. Arterial dissection was relatively common and found in 16 (15.4%) of patients. Patent foramen ovale PFO was the particular focus of our attention, as most of our patients were also examined using TEE, in which PFOs are easy to detect. Figure 2 shows the corresponding results. PFO was identied in 29/74 (27.9%) patients. Most commonly (18/29; 62%), it was a PFO III with or without atrial septal defect (ASD). If we only consider patients with TEE (74), which denitely reveals PFO, the percentage of PFO increases to 39.2%. Three quarters of patients (15 of 20; 75%) with a cardioembolic stroke according to the



J Neurol (2012) 259:653659

Fig. 3 Comparison of ASCO and TOAST classication results. Comparison of TOAST and ASCO results for the different etiology groups. A atherothrombosis/large artery, S small vessel disease, C cardioembolic/cardiac origin, O other (determined). The numbers

1, 2 refer to the corresponding grade in ASCO [11]. The ASCO score A0S0C0O0 was taken as the corresponding TOAST category undetermined

TOAST classication and a TEE showed a PFO. Using the ASCO classication, patients with certain (C1, n = 8) or possible (C2; n = 11) cardioembolic stroke and TEE had a PFO in a similarly high percentage (63.2%). A combination of PFO and other possible stroke etiologies was present in 11/29 (37.9%) cases. ASCO and TOAST comparison We also compared how the two stroke etiology scores (TOAST and the newer ASCO) classify strokes in this young population. Figure 3 shows the comparison of the two scores. In greater detail, the classication using TOAST/ASCO (only grade 1) was as follows: Atherothrombotic (large artery) 10.6%/8.7%, cardiac origin 21.2%/10.6%, small vessel disease 9.6%/9.6% and other causes 19.2%/13.5%. The TOAST score delivered the result undetermined in 41 cases (39.4%). The corresponding score in ASCO would be A0S0C0O0, because it delivers no additional information, like the last TOAST category. Only 20 patients (19.2%) received this classication, about half as many as in TOAST.

be more sensitive and better informed than older ones. On the other hand, thrombolysis rate is generally high in our region, due to optimization of publicity, informing of the general population and training of emergency personnel [17]. In addition to this, many of the patients had no, or only minor, neurological decits on admission, thus not requiring thrombolysis (58.7% of patients had a NIHSS score \3 on admission). Our young stroke population received a very thorough work-up. In addition to MRI, MRA, vascular duplex imaging and ECG monitoring, which are standard in acute stroke management, TEE was also performed in over 70% of our patients. This is considerably more than in most other studies (560%) which have investigated stroke causes and risk factors in young ischemic stroke patients and may subsequently have inuenced our results, especially concerning PFO [5, 7, 9, 15]. Risk factors Cerebrovascular risk factors are generally thought to be less important in younger patients than in older ones [3]. In our population, the most common risk factor was smoking (55.2%). Other studies on young stroke patients have also found a high percentage of smokers; however, not as high as in our study (3744%), with the exception of the study performed by Spengos et al., who found almost 60% of smokers in their population of Greek stroke patients [5, 9, 15, 18, 19]. Hypertension and hyperlipidemia were also quite common in these studies (2256 and 1759%, respectively), in approximately the same levels as in our study (31.4 and 27.6%, respectively). Diabetes was found in 6.7% of our patients, i.e., with a similar frequency as in other comparable studies (517%) [5, 9, 15, 18, 19]. Overall, 58.7% patients had one or more atherosclerotic risk factors (not counting smoking), which is close to what

Discussion In this study, we describe the risk factors and etiopathogenetic classication in 104 young adult patients with ischemic stroke aged up to and including 45 years. Age range (1945 years) and mean age (38.4 6.9 years) were very similar to other recent studies on young stroke patients [5, 7, 9, 15, 16]. The rate of thrombolytic treatment was about 22% and thus did not substantially differ from the rate in the general ischemic stroke population in our stroke center. This seems surprising at rst, as one might expect younger patients to


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one might have expected from an elderly population. Surprisingly, we found a high number of patients with silent previous strokes as evidenced on MRI (10/104; 9.6%) and there were three patients (2.9%) with previous, symptomatic strokes. This parameter was not always included in previous studies. Putaala et al. [5], in their study with 1008 young stroke patients with rst-ever ischemic stroke, found a similar percentage (12.5%) of patients with previous silent infarcts. Spengos et al. [19] found 13.4% of patients with a history of previous cerebrovascular events in their population of 253 young stroke patients, including, however, transient ischemic attacks. Janssen et al. [18] found a very high percentage (47.9%) with a history of vascular events; this, however, included cardiovascular events as well. Migraine may be a less-well documented and even controversial risk factor for stroke, but an association between migraine and stroke, especially in young patients, has indeed been shown in the literature [6, 2022]. Quite a large percentage of our patients had a history of migraine (21%). In studies with similar populations, percentages varied between 13 and 20% [5, 18, 19]. The role of hypoplastic posterior circulation, in particular affecting both vertebral and the basilar arteries, in ischemic stroke is not clear, whereas unilateral and sometimes bilateral vertebral artery hypoplasia is not rare in the general population [23]. Since this anomaly is probably congenital, it may play an underestimated role in a population of younger patients than in a general stroke population. Not many studies have investigated this topic. A study by Park et al. [23] found approximately 35% of a general ischemic stroke population (n = 529) and 26.5% of 303 healthy people to have hypoplastic vertebral arteries. We had 23 (21.9%) patients with hypoplasia of either or, less frequently, both vertebral arteries, which would signify that this feature does not seem to be of particular importance in young stroke patients. PFO is present in about 25% of the general population and many casecontrol studies have shown a statistical association between PFO and stroke [6, 24]. Numbers on the frequency of PFO in young ischemic stroke patients vary in the literature. In the largest series with 1,008 patients, Putaala et al. found PFO in 10.5% of all patients, while Spengos et al. in 8.3% and Janssen et al. in only 6.4% [5, 18, 19]. However, in the last two studies, the minority of patients received a TEE, which is the most sensitive diagnostic test for the detection of PFO. The study with the highest percentage of PFO (Putaala et al.) also had the higher percentage of TEEs performed (60%). We found 27.9% of our population to have a PFO, which would be about the same as the general population. However, most (but not all) of our patients received a TEE. If we consider only the 74 (71.2%) patients with TEE, the percentage of

PFO increases to 39.2%, which is surprisingly high. Perhaps less surprising, the frequency of PFO is even higher in patients with stroke of cardiac origin (63.275%, according to the classication of stroke usedA1 and A2 grades in ASCO and cardiac origin in TOAST). Of course, the high percentage of PFO in cardiac origin strokes as dened by TOAST is at least partially explained by the fact that TOAST considers the presence of PFO as a criterion for the cardiac origin classication, whereas ASCO requires PFO to be associated with in situ thrombosis or pulmonary embolism or deep vein thrombosis preceding the brain infarction to classify the stroke as denitely cardioembolic (grade 1). These ndings suggest that PFO may play a more important role in young stroke adults than previously thought, although the mechanism of stroke in patients with PFO, as well as its signicance, are not always clear. Further studies with larger patient numbers and more complete cardiac work-up will be needed to clarify this issue. Stroke classication Most studies on ischemic stroke in young adults have used the TOAST classication of stroke subtype [6]. While this classication has some benets and is quite simple, it does not include risk factors in its criteria and in some cases leaves much room for different interpretations. Furthermore, its last category undetermined offers no more information apart from the fact that the cause of stroke could not be determined with certainty. Our results concerning the etiology of stroke using TOAST were similar to other studies performed on young stroke adults [57, 9, 19, 25, 26]. We found 10.6% of patients to be in the large-vessel disease category (6.726.7% in the literature), 21.2% in the cardiac origin category (5.225% in the literature), 9.6% in the smallvessel disease category (1.717.4% in the literature), 19.2% in the category of other dened causes (2935% in the literature) and 39.4% of undetermined etiology (13.362.4% in the literature). As previously observed, variations in the classication among these studies is mainly explained by the different criteria used and by the grade of completeness of stroke work-up [6]. The new ASCO classication was created with risk factors in mind and with the aim of offering more information in the appointed stroke subtypes [11]. To our knowledge, this is the rst series of young adults with ischemic stroke to apply and compare both stroke subtype classication systems. In the category of macroangiopathy and other determined causes, both classication methods delivered similar results. In the cardiac origin category, the percentage of patients using ASCO grade 1 was about half



J Neurol (2012) 259:653659 Northern Portugal: incidence and case fatality in rural and urban populations. Stroke 35(9):20482053 Kristensen B, Malm J, Carlberg B, Stegmayr B, Backman C, Fagerlund M, Olsson T (1997) Epidemiology and etiology of ischemic stroke in young adults aged 18 to 44 years in northern Sweden. Stroke 28(9):17021709 Bogousslavsky J, Pierre P (1992) Ischemic stroke in patients under age 45. Neurol Clin 10(1):113124 Lee TH, Hsu WC, Chen CJ, Chen ST (2002) Etiologic study of young ischemic stroke in Taiwan. Stroke 33(8):19501955 Putaala J, Metso AJ, Metso TM, Konkola N, Kraemer Y, Haapaniemi E, Kaste M, Tatlisumak T (2009) Analysis of 1008 consecutive patients aged 15 to 49 with rst-ever ischemic stroke: the Helsinki young stroke registry. Stroke 40(4):11951203 Ferro JM, Massaro AR, Mas JL (2010) Aetiological diagnosis of ischaemic stroke in young adults. Lancet Neurol 9(11):10851096 Varona JF, Guerra JM, Bermejo F, Molina JA, Gomez de la Camara A (2007) Causes of ischemic stroke in young adults, and evolution of the etiological diagnosis over the long term. Eur Neurol 57(4):212218 Carolei A, Marini C, Ferranti E, Frontoni M, Prencipe M, Fieschi C (1993) A prospective study of cerebral ischemia in the young. Analysis of pathogenic determinants. The national research council study group. Stroke 24(3):362367 Cerrato P, Grasso M, Imperiale D, Priano L, Baima C, Giraudo M, Rizzuto A, Azzaro C, Lentini A, Bergamasco B (2004) Stroke in young patients: etiopathogenesis and risk factors in different age classes. Cerebrovasc Dis 18(2):154159 Adams HPJ, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, EEr Marsh (1993) Classication of subtype of acute ischemic stroke. Denitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 24(1):3541 Amarenco P, Bogousslavsky J, Caplan LR, Donnan GA, Hennerici MG (2009) New approach to stroke subtyping: the A-S-C-O (phenotypic) classication of stroke. Cerebrovasc Dis 27(5):502508 Chaturvedi S, Lukovits TG, Chen W, Gorelick PB (1999) Ischemia in the territory of a hypoplastic vertebrobasilar system. Neurology 52(5):980983 Hacke W, Kaste M, Bluhmki E, Brozman M, Davalos A, Guidetti D, Larrue V, Lees KR, Medeghri Z, Machnig T, Schneider D, von Kummer R, Wahlgren N, Toni D (2008) Thrombolysis with alteplase 3 to 4.5 h after acute ischemic stroke. N Engl J Med 359(13):13171329 Kane I, Sandercock P, Wardlaw J (2007) Magnetic resonance perfusion diffusion mismatch and thrombolysis in acute ischaemic stroke: a systematic review of the evidence to date. J Neurol Neurosurg Psychiatry 78(5):485491 Balci K, Utku U, Asil T, Celik Y (2011) Ischemic stroke in young adults: risk factors, subtypes, and prognosis. Neurologist 17(1):1620 Spengos K, Vemmos KN (2010) Etiology and outcome of cardioembolic stroke in young adults in Greece. Hellenic J Cardiol 51(2):127132 Ellinger K, Koch C, Daffertshofer M, Behrens S, Luiz T (1999) Das Mannheimer Schlaganfallprojekt. Eine Initiative zur Optimierung der Versorgungsstrategie. Notfall and Rettungsmedizin 2:428433 Janssen AW, de Leeuw FE, Janssen MC (2010) Risk factors for ischemic stroke and transient ischemic attack in patients under age 50. J Thromb Thrombolysis 31(1):8591 Spengos K, Vemmos K (2010) Risk factors, etiology, and outcome of rst-ever ischemic stroke in young adults aged 15 to 45the Athens young stroke registry. Eur J Neurol 17(11):1358 1364

that of those using TOAST, but exactly the same in both systems when including both grade 1 and 2 of ASCO. The opposite was true in the category of microangiopathic strokes, where TOAST and ASCO grade 1 delivered exactly the same percentage of patients, whereas ASCO grade 1 ? 2 showed a much higher result. These effects may be explained by the very detailed and strict criteria used in ASCO, as opposed to TOAST, at least in some cases. The last category undetermined cause was particularly interesting, as cryptogenic strokes pose a particular challenge, especially regarding the choice of secondary prevention. As already mentioned, most studies found about one-third of strokes to be of undetermined cause (2436%), with some exceptions, e.g., Musolino et al. (13.3%) and Leys et al. (62.4%), obviously depending on the completeness of investigations [5, 7, 9, 19, 25, 26]. In our study, this percentage was 39.4%, slightly more than one-third of the patients, despite quite a broad work-up. However, during these extensive examinations, data pertaining to risk factors and possible stroke causes were collected which are not reected in the TOAST classication. This data, however, are found in the ASCO score. Even the score A0S0C3O0, for example, contains information (in this case that cardiac problems exist), even if the cause of stroke is uncertain. Therefore, we chose the score A0S0C0O0 as the best corresponding category to TOASTs undetermined cause. Only about half of strokes then remained completely undetermined as compared to using TOAST (A0S0C0O0: 19.2%, TOAST undetermined cause: 39.4%). The limitations of our study are the relatively small patient number and the fact that most, but not all, patients received a complete work-up including TEE, something our study has in common with previous ones. However, we believe we could demonstrate that young ischemic stroke patients share some of the classic risk factors with elderly stroke patients. In addition, provided corresponding investigations including TEE studies are regularly performed, a signicantly increased percentage of young stroke patients reveal comorbidities with PFO, migraine and previous, usually asymptomatic, cerebrovascular events. There are also arguments (more contained information, less undetermined strokes) for preferring the ASCO classication over the TOAST one for a better classication of stroke subtypes in this patient group.
Conict of interest None.


3. 4. 5.

6. 7.












1. Correia M, Silva MR, Matos I, Magalhaes R, Lopes JC, Ferro JM, Silva MC (2004) Prospective community-based study of stroke in



J Neurol (2012) 259:653659 20. Camerlingo M, Romorini A, Ferrante C, Valente L, Moschini L (2010) Migraine and cerebral infarction in young people. Neurol Sci 31(3):293297 21. Kurth T (2007) Migraine and ischaemic vascular events. Cephalalgia 27(8):965975 22. Wolf ME, Szabo K, Griebe M, Forster A, Gass A, Hennerici MG, Kern R (2011) Clinical and MRI characteristics of acute migrainous infarction. Neurology 76(22):19111917 23. Park JH, Kim JM, Roh JK (2007) Hypoplastic vertebral artery: frequency and associations with ischaemic stroke territory. J Neurol Neurosurg Psychiatry 78(9):954958

659 24. Alsheikh-Ali AA, Thaler DE, Kent DM (2009) Patent foramen ovale in cryptogenic stroke: incidental or pathogenic? Stroke 40(7):23492355 25. Leys D, Bandu L, Henon H, Lucas C, Mounier-Vehier F, Rondepierre P, Godefroy O (2002) Clinical outcome in 287 consecutive young adults (15 to 45 years) with ischemic stroke. Neurology 59(1):2633 26. Musolino R, La Spina P, Granata A, Gallitto G, Leggiadro N, Carerj S, Manganaro A, Tripodi F, Epifanio A, Gangemi S, Di Perri R (2003) Ischaemic stroke in young people: a prospective and longterm follow-up study. Cerebrovasc Dis 15(12):121128