Post-Stroke Seizures and Epilepsy: Risk factors and Outcome.

Introduction: Cerebrovascular disease is considered to be the most common cause of epilepsy in the elderly. However, information pertaining to incidence of post-stroke seizures and epilepsy, factors influencing occurrence of seizures in patients with stroke, management and their influence on overcome are noted to be very variable in the literature, and not extensively explored. Aim: This study aims to explore the prevalence of seizures and epilepsy among patients with stroke, risk factors associated with their occurrence and their influence on outcome.Patients and methods: Adult patients with acute stroke ?either ischemic or hemorrhagic, occurring new or over the last three years will be recruited. Demographic data; type of stroke (based on TOAST classification); nature and severity of neurologic deficits (on NIH Stroke Scale); risk factors for stroke (including Hypertension, Diabetes mellitus, Hyperlipidemia, smoking, alcohol abuse); imaging observations including: location(s) of infarct or hemorrhage, presence of periventricular or cortical changes, microbleeds (on MRI imaging), mass effect; changes in electrolytes, renal and liver functions; evidence of intercurrent infection; - will be documented. Occurrence of seizures in the acute phase of stroke or later over a period of 1 year ? occurring spontaneously or in relation to systemic crises (eg.infection, electrolyte disorders, etc) will be noted. Occurrence of Epilepsy, defined as the occurrence of recurrent seizures will be documented, along with anticonvulsant medication used and their efficacy in control. Outcome at the end of 1 year of follow up will be recorded using modified Rankin Score (scale of 0-6). Quality of life will be documented using Stroke Specific Quality of Life scale. Analysis: Univariate and multivariate methods of analysis will be applied to explore factors associated with the post-stroke seizures/epilepsy, and outcome.

Introduction: Cerebrovascular disease is considered to be the most common cause of epilepsy in the elderly. However, information pertaining to incidence of post-stroke seizures and epilepsy, factors influencing occurrence of seizures in patients with stroke, management and their influence on overcome are noted to be very variable in the literature, and not extensively explored. Aim: This study aims to explore the prevalence of seizures and epilepsy among patients with stroke, risk factors associated with their occurrence and their influence on outcome.Patients and methods: Adult patients with acute stroke ?either ischemic or hemorrhagic, occurring new or over the last three years will be recruited. Demographic data; type of stroke (based on TOAST classification); nature and severity of neurologic deficits (on NIH Stroke Scale); risk factors for stroke (including Hypertension, Diabetes mellitus, Hyperlipidemia, smoking, alcohol abuse); imaging observations including: location(s) of infarct or hemorrhage, presence of periventricular or cortical changes, microbleeds (on MRI imaging), mass effect; changes in electrolytes, renal and liver functions; evidence of intercurrent infection; - will be documented. Occurrence of seizures in the acute phase of stroke or later over a period of 1 year ? occurring spontaneously or in relation to systemic crises (eg.infection, electrolyte disorders, etc) will be noted. Occurrence of Epilepsy, defined as the occurrence of recurrent seizures will be documented, along with anticonvulsant medication used and their efficacy in control. Outcome at the end of 1 year of follow up will be recorded using modified Rankin Score (scale of 0-6). Quality of life will be documented using Stroke Specific Quality of Life scale. Analysis: Univariate and multivariate methods of analysis will be applied to explore factors associated with the post-stroke seizures/epilepsy, and outcome.

Proposed research outline must include a literature review, long and short term goals, protocol, practical significance of outcome and pertinent references. Maximum of 3 pages of at least 10 point font, single spaced, Times Roman.Stroke and Epilepsy are two of the commonest neurologic disorders. Cerebro-vascular disease is considered to be the most common cause of epilepsy in the elderly, accounting for 35% of all cases (Menon et al, 2009). This observation has been the reason for the recommendation that investigations for cerebrovascular disease should be a part of the work-up in all adult and elderly patients with seizures or epilepsy. However, the relation between stroke and post-stroke seizures or epilepsy, despite being the focus of several studies, has been poorly understood in terms of incidence, risk factors, pathophysiology, influence on outcome or management. In patients with a history of stroke Li et al (1997) reported a life time risk of epilepsy of 3.3 (odds ratio, OR) (95% CI 1.3 ? 8.5). Among 13 hospital based studies reviewed by Menon et al (2013), the overall frequency of seizures following stroke ranged from 2.4% to 14%. About half of these (2.4% ? 5%) are noted to occur in the early phase after stroke (early onset seizures ? up to 2 to 4 weeks), while the remaining half occur later (Menon et al, 2009; Lossiusa et al, 2002). The relation between early and late onset seizures and the occurrence of epilepsy is also unclear. Studies report a higher incidence of progression to epilepsy with either of these. Overall, about 35% of patients with either early or late onset of post-stroke seizures are reported to progress to epilepsy, though late onset seizures are believed to have a stronger association with long term epilepsy (Oxforshire study; Burn et al, 1997). In a hospital based study of post stroke epilepsy from Taiwan, 35% of patients with early onset seizures and 90% of late onset seizures progressed to epilepsy (Sung et al, 1990). Studies have also observed seizures to occur at onset of stroke (ie. as the presenting manifestation of stroke) as well as to precede stroke. Giroud et al (1994) reported seizures to be the presenting manifestation of stroke among 89% of 90 patients experiencing early onset seizures. SQU-PSR-1 The pathophysiologic changes leading from brain ischemia to seizures is poorly understood, though several hypothesis has been proposed to explain their relation. In the post-stroke phase, neuronal hyper-excitable in the ischemic zone; selective neuronal death or apoptosis, mitochondrial changes; changes in the balance of excitatory (eg. Glutamate) and inhibitor (eg.GABA) neurotransmittors; membrane injury; release of calcium or free fatty acids; etc. have been proposed as possible mechanisms. In later stages, similar changes together with mechanisms such as axonal sprouting by intact neurons to occupy synapses vacated by injured neurons; gliotic scars; deafferentation of the cortex, etc may contribute to epileptogenesis to varying extant (Luhmann et al, 1995; Buchkremer-Ratzmann et al., 1998; Stroemer et al., 1995).Are any particular types of stroke or locations of injury associated with post-stroke seizures? Several studies have attempted to explore factors influencing with post-stroke seizures, though with varied conclusions. Several studies (eg. six of 13 studies reviewed by Menon et al, 2009) have recognized cortical location of infarction as a risk factor for seizures; few studies recognize this to be an independent risk factor (Bladin et al., 2000; Cheung et al., 2003). Raak et al., 1996 recognized posterior central or supramarginal gyrus to be associated with seizures following cardioembolism. (There are however reports of post stroke seizures in the context fo lacunar or subcortical infarcts). Hemorrhage is also a well recognized risk factor: Davalos et al (1992) reported hemorrhagic infarcts to be more commonly associated (19.2%) with early post-stroke seizures in contrast to hemorrhage (15.6%) or ischemic infarction (6.2%). Among 368 patients with ischemic stroke followed prospectively, hemorrhagic transformation was noted to be an independent risk factor for developing seizures with an odds ratio of 6.58 (95% CI: 1.4?1.61; p = 0.001) as well as adverse outcome (OR 8.45; 95% CI: 1.72?41.20; p = 0.008) (Alberti et al., 2008). Other associated risk factors have included large infarction, cardiembolism, severe stroke, altered mental status, etc. However, as yet, many factors such as MRI observations (eg. Microhemorrhages, residual brain connectivity), cerebrovascular status (eg.collateral flow), etc have not been explored and may be potentially significant.Seizures in post-stroke period do have an influence both in the short and long term. Few studies however have explored this relation specifically. In the acute phase of stroke, seizures may increase the cerebral oxygen utilization significantly and greatly stress a already compromised cerebrovascular supply, resulting in potential worsening of stroke (eg. extension of infarction into penumbra). This may translate to worsening of stroke outcomes, as recognized by Bladin et al (2000). However, contrary to this, better outcomes in stroke patients with seizures have also been reported (Reith et al., 1997). Mortality may also be influenced by post-stroke seizures, though at varied rates. Arboix et al (1997) observed a mortality of 37.9% in patients with post stroke seizures compared to 14.4% in those without. Bladin et al (2000) reported mortality to be significantly higher (p 0.001)at 30 days as well as 1 year among those with seizures than those without. Reith et al (1997) reported a 2.5 fold higher mortaliy among patients with seizures on univariate analysis; however, this was attributed exclusively to initial severity of stroke. In a recent systematic review of 25 studies addressing post-stroke seizures/epilepsy, Zhang et al (2014) concluded that stroke severity, intracerebral hemorrhage, cortical infarcts and hemorrhagic transformation of stroke are predictors of seizures; and that intracerebral hemorrhage and infarction could contribute equally to single late post stroke seizure. There are no clear guidelines yet as to how to optimally manage post stroke seizures and epilepsy. While commonly used medications are indeed effective in controlling seizures, drug interactions (eg.phenytoin, carbamazepine), sedation (eg.clobazam), cardiac adverse effects (eg.phenytoin, carbamazepine), etc may be issues of concern. Drugs such as benzodiazepines and phenytoin, following prolonged use, may adversely influence recovery from stroke. A recent case series reported favourable experience in treating post-stroke epilepsy with levetiracetam. However, further studies are indicated.