European Journal of Cardiovascular Medicine

Seizures are a common phenomenon following a stroke. Many questions about seizures in stroke remain unanswered, despite the fact that they were first recognised more than a century ago. As on today, stroke has been considered as one of the   most important causes of epilepsy in the elderly.¹ Stroke-related seizures are a neglected topic that is generally regarded as a benign complication that occurs during the course of a progressive and long-term cerebrovascular disease. Differences in study design, definition of late or early seizures, target population, inclusion and exclusion criteria, and imaging data limit direct comparison of seizures and may explain conflicting results in the literature.

Seizures that occur at the onset, or after a period of time after occurrence of stroke are termed as post stroke seizures. Time cut off for early versus late seizures is arbitrary and varies among different studies between 1 to 2 weeks. For our study we took 2 weeks as cut off. Post- stroke Seizures occur within 2 weeks of stroke onset (as early onset seizures) or 2 weeks after stroke (as late onset seizures). Seizures are classified as 'immediate' if they occur within 24 hours of the onset of the stroke. Recurrent seizures are defined as those that occur at least two weeks after the initial seizure. If the patient has two or more seizures, they are considered multiple.²

From stroke registry data, about 5% to 20% of all individual who have a stroke will have subsequent seizures.² Incidence of post-stroke seizures according to Seizures after stroke study (SASS) group³ and Oxfordshire community stroke project (OCSP)⁴ were 8.9% and 11.6% respectively.

In India, the prevalence of post-stroke seizures is estimated to be 13%.³ Every year around 5 lakh cases of stroke, with about 1,75,000 fatalities from this cause. Since the active early detection and management of hypertension, there has been a great reduction in the frequency of stroke. So this world witnessed a gross reduction in cerebral infarct about 40% and haemorrhage 30% in between 1950-54. This reduction shared both sexes. There has been no change in the frequency of aneurysmal rupture.⁵

Cerebral embolism is one of the important causes of stroke particularly in young patients. The incidence of cardiac embolism varies in several studies. It is as low as 3% in community studies and as high as 30% in referral centers and 15% of patients with stroke. Intra cerebral haemorrhage accounts for approximately 10-15% of stroke. The commonest risk factor being hypertension.⁶

Reports on the frequency of seizures following stroke vary quite widely because of, differing stroke patient populations, sample sizes studies, varying follow up periods, definitions used for stroke and seizures, use of investigation such as CT and MRI and type of statistical analysis. In most studies to date the follow-up period was less than a few weeks, so the documentation of late-onset or recurring seizures is limited.⁷ There have been very few studies in the Indian subcontinent on post-stroke seizures. The purpose of this study is to determine the onset time, semiology and anatomical location of stroke in relation to seizure.

This observational cross-sectional study was conducted at the inpatient clinics of the Neurology Department, St. Stephen’s Hospital, Tis Hazari, Delhi, over a 19-month period from April 1, 2021, to October 31, 2022. A sample size of 149 was calculated based on Kamble S et al.’s findings; however, 60 patients were included due to logistical constraints. Patients aged 18 years or older with a first episode of post-stroke seizure were included. Exclusion criteria comprised patients with prior seizure history, neurosurgical conditions mimicking stroke, CNS infections, cortical venous thrombosis, drug-related strokes, pregnancy-related complications, or those unwilling to participate.

Following consent, each patient underwent a complete medical history review, neurological examination, and baseline investigations, including MRI/CT scans and EEG. Clinical history emphasized seizure details, including the time of onset relative to stroke, seizure semiology, and stroke type (ischemic or hemorrhagic). Seizure semiology was classified following the 2017 ILAE guidelines into focal, generalized, and unknown onset types, with status epilepticus noted.⁸

Radiological assessments included stroke type and lesion characteristics (location, depth, and volume for hemorrhagic cases). Ischemic strokes were classified per the Oxfordshire classification, and intracerebral hemorrhage (ICH) was assessed using the ABC/2 method to categorize volume. Stroke severity was evaluated using the NIH Stroke Scale (NIHSS).

EEG findings were categorized from normal to periodic lateralized epileptiform discharges (PLEDS). Data were analyzed in SPSS (v25) with qualitative data presented as frequencies and percentages, and quantitative data as means with standard deviations or medians with IQRs. Statistical tests included Chi-square, t-test, and Mann-Whitney test, with significance at p<0.05.

Informed consent was obtained, and ethical approval was granted by the Institutional Ethics Committee. No additional costs were incurred by patients. 

Males comprised 61.7% of the sample, with a male-to-female ratio of approximately 1.6:1. The majority (81.7%) of patients were aged over 50, with the highest representation in the 61-70 years age group (30%). [Table 1]

Table 2 presents data on the stroke subtype among the study participants, with 85% experiencing ischemic stroke and 15% experiencing intracerebral hemorrhage (ICH). Among the ischemic strokes, 64.7% were classified as partial anterior circulation infarcts (PACI), while total anterior circulation infarcts (TACI), posterior circulation infarcts (POCI), and lacunar infarcts (LACI) were less common.

Table 3 displays the distribution of EEG findings and anatomical lesion sites. The most frequent EEG pattern was focal slowing (45%), followed by diffuse slowing (31.7%). No PLEDS (Periodic Lateralized Epileptiform Discharges) were observed. Lesions were predominantly cortical (65%), with cortical-subcortical involvement seen in 23.3% of cases.

Table 4 provides correlations between seizure semiology, EEG patterns, NIHSS severity, and stroke subtype. Focal seizures were slightly more common in thrombotic strokes, and generalized seizures had a higher occurrence in cardio-embolic strokes. Type III EEG patterns (focal slowing) were most frequent across stroke subtypes. A significant correlation was observed between NIHSS severity and stroke subtype, with severe NIHSS scores predominantly in ICH patients.

Table 5 describes correlations between anatomical lesion location (cortical, subcortical, and combined) and side (left, right, bilateral) with stroke subtypes. Cortical lesions were more prevalent across all stroke types, particularly thrombotic. Although left-sided lesions were slightly more common, no statistically significant correlation was found between lesion location, side, and stroke subtype.

Table 1: Demographic Profile of Study Patients

Table 2: Stroke Subtype and Classification

Table 3: EEG Findings and Anatomical Site of Lesion

Table 4: Correlation of Seizure Semiology, EEG Findings, and NIHSS Severity with Stroke Subtype

Table 5: Correlation of Anatomical Site and Side of Lesion with Stroke Subtype

Cerebrovascular diseases are a significant cause of disability worldwide and represent the most common etiology of seizures among the elderly. This relationship is particularly noteworthy, given that stroke accounts for a substantial portion of newly diagnosed epilepsy cases.⁹ This correlation between stroke and seizure development necessitates further investigation, as the interaction remains poorly understood, despite its high clinical importance. A major obstacle in understanding this comorbidity lies in the varied incidence rates of post-stroke seizures reported across studies, ranging widely from 2% to 20%.¹⁰ This variability may stem from differences in stroke etiologies, inconsistencies in defining stroke-related seizures, variations in follow-up duration, and a lack of standardized protocols.^11-12

In our study of 60 patients presenting with seizures post-stroke, there was a male predominance, with 62% males and 38% females, though this difference was not statistically significant. Dhanuka et al.’s study also reported a similar distribution with 57% male participants.³ This finding aligns with other studies, including Burn et al., who observed a male-to-female ratio close to 1:1 in a larger cohort of 675 stroke patients.¹³ The current study also showed a higher rate of post-stroke seizures in patients over 50, a finding consistent with the reports of Forsgren et al.¹⁴ and Yang et al.¹⁵, who noted that stroke accounts for a high percentage of newly diagnosed seizures in individuals aged 60 and older.

In terms of stroke subtype, ischemic stroke accounted for 85% of cases, with 15% classified as ICH. Within the ischemic group, 15.6% were cardio-embolic (CE), while the remaining cases had a thrombotic etiology. This distribution is comparable to previous studies. Dhanuka et al. reported that ischemic strokes comprised 57% of cases in their study, with 25% of ischemic patients having a cardio-embolic source.³ Similarly, Giroud et al. found that cardio-embolic sources accounted for 16.6% of cases, highlighting a somewhat consistent distribution of stroke subtypes across studies.¹⁷

Regarding Oxfordshire classification, 64% of patients in the current study had partial anterior circulation infarcts (PACI), followed by 16% with total anterior circulation infarcts (TACI). Our findings align with previous research, such as Bamford et al., who observed PACI as the most common classification in stroke patients with seizures.¹⁸ Additionally, other studies by De Reuck et al.¹⁹ Cheung et al.²⁰, reported similar findings, indicating that certain stroke classifications, particularly PACI, may carry a higher risk for seizure development.

Our study also showed that hematoma volume plays a role in seizure risk, with larger hematomas (over 30 ml) associated with a higher likelihood of post-stroke seizures, consistent with findings by Dhanuka et al., who similarly found that larger hematoma volumes increased seizure risk.³ The association between hematoma size and seizure risk further emphasizes the need for careful monitoring in patients with substantial ICH.

In terms of seizure semiology, 56.7% of patients presented with focal seizures, while 38.3% experienced generalized seizures. This distribution closely resembles other studies, including Bladin et al. and Giroud et al., who observed focal seizures as the most common seizure type following a stroke.^2,17 In contrast, Arboix et al. reported a higher frequency of generalized seizures, with focal seizures being less prevalent in their study.²³ This variation may stem from differences in patient demographics and stroke characteristics across studies. In our study, generalized seizures were slightly more frequent in CE strokes, though this trend did not reach statistical significance.

Our study also examined the role of lesion location in seizure occurrence. Cortical involvement was present in 70% of thrombotic, 50% of CE, and 55% of ICH cases, supporting the hypothesis that cortical sites are more epileptogenic than subcortical regions. This finding aligns with previous research by Dhanuka et al., which reported a high rate of cortical involvement in post-stroke seizures.³ Other studies, such as De Reuck et al., have similarly observed that cortical and large cortical infarcts in particular, located in parietal and temporal regions, are associated with a higher seizure risk.¹⁹ Our data suggest that cortical lesions are indeed more susceptible to seizure development post-stroke, particularly in the frontal lobe.

EEG findings in this study were also consistent with previous research. The most common EEG finding was Type III (focal slowing), observed in 45% of patients, a result comparable to studies by Dhanuka et al³. and Gupta et al²¹., where focal slowing was also predominant. Our study found no cases of PLEDS (Periodic Lateralized Epileptiform Discharges), However, other studies, such as that by De Reuck, have reported PLEDS in a subset of post-stroke seizure patients.¹⁹ These findings suggest that while focal slowing is commonly observed, PLEDS may be less prevalent and vary based on the study population and methodology.

The severity of stroke, as assessed by the NIHSS, was positively correlated with post-stroke seizure risk in our study. Moderate and moderate-to-severe NIHSS categories accounted for 38% and 34% of post-stroke seizures, respectively, with a significant association between NIHSS severity and stroke subtype (P = 0.0001). This finding supports previous research by Bladin et al². and Lamy et al²²., who noted that stroke severity is a major risk factor for post-stroke seizures.

Finally, our study assessed the role of hemispheric lesion side in seizure occurrence. Left-sided lesions (55%) were more common than right-sided (40%) or bilateral lesions (5%). Previous studies, including those by Gupta et al²¹. and Sitajeyalakshmi et al²³., have reported a similar trend, where left-sided lesions are more likely to induce seizures post-stroke, although the underlying reasons remain unclear. Our study did not find a statistically significant correlation between lesion side and stroke subtype.

Overall, this study contributes to the growing body of literature on post-stroke seizures by corroborating existing findings and identifying patterns consistent with prior research. Our results reinforce the importance of factors such as age, stroke severity, lesion location, and cortical involvement in determining post-stroke seizure risk. Moreover, the findings underscore the need for close monitoring of older stroke patients, particularly those with cortical or left-sided lesions, as they are at higher risk for seizure development. The complex interplay between stroke characteristics and seizure risk highlights the necessity of continued research to enhance our understanding of this significant post-stroke complication and improve patient outcomes.

The high incidence of stroke makes post-stroke seizures one of the most common causes of epilepsy, despite the relatively low incidence of seizures following a stroke. To fully comprehend the societal effects of post-stroke seizures, their prevention, and efficient management, much more research is needed. Future studies on seizures in stroke should examine the delayed patient outcomes and create novel antiepileptic medications with greater neuroprotective properties. Post-stroke seizure patients may potentially serve as a fundamental model in studies aimed at preventing the development of an epileptic focus in the damaged brain cells. Extensive research is needed at the community level with large sample sizes and multi- center RCTs are needed to determine the correlation of stroke and seizures.

1. Lühdorf K, Jensen LK, Plesner AM. Etiology of seizures in the elderly. Epilepsia. 1986 Aug;27(4):458-63.
2. Bladin CF, Alexandrov AV, Bellavance A, Bornstein N, Chambers B, Coté R, Lebrun L, Pirisi A, Norris JW, Seizures After Stroke Study Group. Seizures after stroke: a prospective multicenter Archives of neurology. 2000 Nov 1;57(11):1617-22.
3. Dhanuka AK, Misra UK, Kalita J. Seizures after stroke: a prospective clinical Neurology India. 2001 Mar 1;49(1):33-6.
4. Andrade JB, Mohr JP, Timbó FB, Nepomuceno CR, Moreira JV, Timbó ID, Lima FO, Silva GS, Bamford Oxfordshire Community Stroke Project Classification: A proposed automated algorithm. European Stroke Journal. 2021 Jun;6(2):160-7.
5. Pandian JD, Sudhan P. Stroke epidemiology and stroke care services in India. Journal of stroke. 2013 Sep;15(3):128.
6. Smajlović D. Strokes in young adults: epidemiology and prevention. Vascular health and risk management. 2015; 11:157.
7. Lackland DT, Roccella EJ, Deutsch AF, Fornage M, George MG, Howard G et al. Factors influencing the decline in stroke mortality: a statement from the American Heart Association/American Stroke Stroke. 2014 Jan;45(1):315-53.
8. Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, et al. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58:512–21.
9. Tomari S, Tanaka T, Ihara M, Matsuki T, Fukuma K, Matsubara S et al. Risk factors for post-stroke seizure recurrence after the first episode. 2017 Nov 1;52:22-6.
10. Wang JZ, Vyas MV, Saposnik G, Burneo JG. Incidence and management of seizures after ischemic stroke: systematic review and meta-analysis. Neurology. 2017 Sep 19;89(12):1220-8.
11. Stefanidou M, Das RR, Beiser AS, Sundar B, Kelly-Hayes M, Kase CS, Devinsky O, Seshadri S, Friedman D. Incidence of seizures following initial ischemic stroke in a community-based cohort: the Framingham Heart Study. Seizure. 2017 Apr 1;47:105-10.
12. Zhao Y, Li X, Zhang K, Tong T, Cui R. The progress of epilepsy after stroke. Current 2018 Jan 1;16(1):71-8.
13. Burn J, Dennis M, Bamford J, Sandercock P, Wade D, Warlow C. Epileptic seizures after a first stroke: the Oxfordshire Community Stroke Project. Bmj. 1997 Dec 13;315(7122):1582-7.
14. Forsgren L, Bucht G, Eriksson S, Bergmark Incidence and clinical characterization of unprovoked seizures in adults: a prospective population‐based study. Epilepsia. 1996 Mar;37(3):224-9.
15. Yang H, Rajah G, Guo A, Wang Y, Wang Q. Pathogenesis of epileptic seizures and epilepsy after stroke. Neurol Res. 2018 Jun;40(6):426-432.
16. Hauser WA, Annegers JF, Kurland LT. Incidence of epilepsy and unprovoked seizures in Rochester, Minnesota: 1935–1984. 1993 May;34(3):453-8.
17. Giroud M, Gras P, Fayolle H, Andre N, Soichot P, Dumas Early seizures after acute stroke: a study of 1,640 cases. Epilepsia. 1994 Sep;35(5):959-64.
18. Bamford J, Sandercock P, Dennis M, Warlow C, Burn JJ. Classification and natural history of clinically identifiable subtypes of cerebral The Lancet. 1991 Jun 22;337(8756):1521-6.
19. De Reuck JL, Stroke related seizures and epilepsy; Neurol Neurochirn 2007Mar-Apr;41(2):144-9.
20. Cheung CM, Tsoi TH, Au-Yeung M, Tang AS. Epileptic seizure after stroke in Chinese Journal of neurology. 2003 Jul;250(7):839-43.
21. Gupta SR, Naheedy MH, Elias D, Rubino FA. Postinfarction seizures. A clinical Stroke. 1988 Dec;19(12):1477-81.
22. Lamy C, Domigo V, Semah F, Arquizan C, Trystram D, Coste J, Mas JL. Early and late seizures after cryptogenic ischemic stroke in young adults. Neurology. 2003 Feb 11;60(3):400-4.
23. Sitajayalakshmi S, Mani J, Borgohain R, Mohandas Post stroke epilepsy. Neurol india. 2002 Dec;50(1 Suppl):S78-84.