Risk Of Poststroke Epilepsy Research Articles

Risk Factors and Temporal Patterns of Poststroke Epilepsy across Stroke Subtypes: Insights from a Nationwide Cohort Study in Korea

Introduction: We aimed to investigate the risk factors associated with poststroke epilepsy (PSE) among patients with different subtypes of stroke, focusing on age-related risk and time-varying effects of stroke subtypes on PSE development. Methods: A retrospective, nationwide, population-based cohort study was conducted using Korean National Health Insurance Service–National Sample Cohort data. Patients hospitalized with newly diagnosed stroke from 2005 to 2015 were included and followed up for up to 10 years. The primary outcome was the development of PSE, defined as having a diagnostic code and a prescription for anti-seizure medication. Multivariable Cox proportional hazard models were used to estimate PSE hazard ratios (HRs), and time-varying effects were also assessed. Results: A total of 8,305 patients with ischemic stroke, 1,563 with intracerebral hemorrhage (ICH), and 931 with subarachnoid hemorrhage (SAH) were included. During 10 years of follow-up, 4.6% of patients developed PSE. Among patients with ischemic stroke, significant risk factors for PSE were younger age (HR = 1.47), living in rural areas (HR = 1.35), admission through the emergency room (HR = 1.33), and longer duration of hospital stay (HR = 1.45). Time-varying analysis revealed elevated HRs for ICH and SAH, particularly in the first 2 years following the stroke. The age-specific HRs also showed an increased risk for those under the age of 65, with a noticeable decrease in risk beyond that age. Conclusion: The risk of developing PSE varies according to stroke subtype, age, and other demographic factors. These findings underscore the importance of tailored poststroke monitoring and management strategies to mitigate the risk of PSE.

To Select or Not to Select: Evaluating the Effectiveness of the SeLECT Score in Predicting the Risk of Post-stroke Epilepsy: A Systematic Review (P6-1.002)

To Select or Not to Select: Evaluating the Effectiveness of the SeLECT Score in Predicting the Risk of Post-stroke Epilepsy: A Systematic Review (P6-1.002)

Exploratory study of blood biomarkers in patients with post-stroke epilepsy.

In addition to clinical factors, blood-based biomarkers can provide useful information on the risk of developing post-stroke epilepsy (PSE). Our aim was to identify serum biomarkers at stroke onset that could contribute to predicting patients at higher risk of PSE. From a previous study in which 895 acute stroke patients were followed-up, 51 patients developed PSE. We selected 15 patients with PSE and 15 controls without epilepsy. In a biomarker discovery setting, 5 Olink panels of 96 proteins each, were used to determine protein levels. Biomarkers that were down-regulated and overexpressed in PSE patients, and those that showed the strongest interactions with other proteins were validated using an enzyme-linked immunosorbent assay in samples from 50 PSE patients and 50 controls. A ROC curve analysis was used to evaluate the predictive ability of significant biomarkers to develop PSE. Mean age of the PSE discovery cohort was 68.56 ± 15.1, 40% women and baseline NIHSS 12 [IQR 1-25]. Nine proteins were down-expressed: CASP-8, TNFSF-14, STAMBP, ENRAGE, EDA2R, SIRT2, TGF-alpha, OSM and CLEC1B. VEGFa, CD40 and CCL4 showed greatest interactions with the remaining proteins. In the validation analysis, TNFSF-14 was the single biomarker showing statistically significant downregulated levels in PSE patients (p = 0.006) and it showed a good predictive capability to develop PSE (AUC 0.733, 95% CI 0.601-0.865). Protein expression in PSE patients differs from that of non-epileptic stroke patients, suggesting the involvement of several different proteins in post-stroke epileptogenesis. TNFSF-14 emerges as a potential biomarker for predicting PSE.

The added value of risk assessment and subsequent targeted treatment for epileptic seizures after stroke: An early-HTA analysis

IntroductionThe development of post-stroke epilepsy (PSE) is related to a worse clinical outcome in stroke patients. Adding a biomarker to the clinical diagnostic process for the prediction of PSE may help to establish targeted and personalized treatment for high-risk patients, which could lead to improved patient outcomes. We assessed the added value of a risk assessment and subsequent targeted treatment by conducting an early Health Technology Assessment. MethodsInterviews were conducted with four relevant stakeholders in the field of PSE to obtain a realistic view of the current healthcare and their opinions on the potential value of a PSE risk assessment and subsequent targeted treatment. The consequences on quality of life and costs of current care of a hypothetical care pathway with perfect risk assessment were modeled based on information from a literature review and the input from the stakeholders. Subsequently, the maximum added value (the headroom) was calculated. Sensitivity analyses were performed to test the robustness of this result to variation in assumed input parameters, i.e. the accuracy of the risk assessment, the efficacy of anti-seizure medication (ASM), and the probability of patients expected to develop PSE. ResultsAll stakeholders considered the addition of a predictive biomarker for the risk assessment of PSE to be of value. The headroom amounted to €12,983. The sensitivity analyses demonstrated that the headroom remained beneficial when varying the accuracy of the risk assessment, the ASM efficacy, and the number of patients expected to develop PSE. DiscussionWe showed that a risk assessment for PSE development is potentially valuable. This work demonstrates that it is worthwhile to undertake clinical studies to evaluate biomarkers for the prediction of patients at high risk for PSE and to assess the value of targeted prophylactic treatment.

Post-stroke Epilepsy and its Association with Stroke Location - Meta-analysis (P3-1.004)

<h3>Objective:</h3> The objective of this study was to review the association between stroke location and post-stroke epilepsy (PSE). <h3>Background:</h3> There have been several meta-analytic studies that investigated potential risk factors for PSE^1,2. Cortical location is known to be associated with increased risk of PSE. However, relationship between the involvement of specific lobe with stroke and PSE has not been evaluated in a meta-analysis due to availability of relevant data. To the best of our knowledge, this is the first meta-analysis on this subject matter. <h3>Design/Methods:</h3> The PubMed and Embase databases were comprehensively assessed and searched for studies that evaluated the association between the involvement of different lobes with PSE. Studies that evaluated post-stroke epilepsy or recurrent post-stroke seizure were included, and acute symptomatic seizure was excluded. Following search strategy was used, “post-stroke” OR “stroke” OR “intracerebral hemorrhage” AND “epilepsy” OR “seizure” AND “lobe” OR “territory” OR “location”. A random effects model was used to estimate pooled odds ratio of the selected outcomes with 95 percent confidence intervals (CIs), and the study heterogeneity was analyzed. <h3>Results:</h3> Nine studies^3–11 were identified with 1328 stroke patients. 9/9 studies showed association of frontal lobe involvement with higher likelihood of PSE (OR=2.10, 95% CI=1.37–3.21, p-value=0.0007). All studies showed association of parietal stroke with increased likelihood of PSE (OR=2.85, 95% CI=1.93–4.22, p-value &lt;0.00001). Previous temporal lobe stroke was associated with increased risk of PSE (OR=3.55, 95% CI=1.95–6.45, p-value &lt;0.00001). In contrast, association between occipital lobe involvement and PSE was not statistically significant (OR=1.37, 95% CI=0.95–1.96, p-value &lt;0.09). <h3>Conclusions:</h3> Our meta-analysis shows that PSE is associated with frontal, parietal, and temporal involvement of previous stroke. There was no statistically significant association between occipital lobe involvement and PSE. Further high quality studies are needed to investigate if stroke in one lobe/territory can be more epileptogenic than those in others. <b>Disclosure:</b> Dr. Park has nothing to disclose. Dr. Esengul has nothing to disclose. Dr. Sheikh has nothing to disclose. Dr. Gharaibeh has nothing to disclose.

Risk of poststroke epilepsy after reperfusion therapies: Anational cohort study.

The risk of poststroke epilepsy (PSE) after endovascular treatment (EVT) is not well characterized. In this nationwide study, we assessed the risk of PSE after EVT and identified associated predictors. We included all individuals (n= 3319) treated with EVT (±intravenous thrombolysis [IVT]) between 2015 and 2019 in the Swedish National Quality Register for EVT. Two control groups were identified from the Swedish Stroke Register: the first treated with IVT alone (n= 3132) and the second with no treatment (n= 3184), both matched for age, sex, stroke severity, and time of stroke. PSE developed in 7.9% (n= 410). The survival-adjusted 2-year risk was 6.5% (95% confidence interval [CI] = 5.28-7.70) after EVT, 10.0% (95% CI=8.25-11.75) after IVT, and 12.3% after no revascularization (95% CI=10.33-14.25). The hazard ratio (HR) of PSE after EVT was almost half compared to no treatment (HR=0.51, 95% CI=0.41-0.64). The risk of PSE after EVT was lower compared to no treatment in a multivariable Cox model that adjusted for age, sex, hemicraniectomy, and stroke severity (HR=0.76, 95% CI=0.60-0.96). Multivariable predictors of PSE after EVT were large infarction on computed tomography Day 1, high posttreatment National Institutes of Health Stroke Scale score, and need of assistance 3months after stroke. IVT before EVT was associated with a lower risk of PSE (HR=0.66, 95% CI=0.46-0.94). This nationwide study identified a reduced risk of PSE after EVT. Markers of severe infarction after EVT were associated with PSE, whereas IVT given before EVT was protective.

Development and validation of a novel radiomics-clinical model for predicting post-stroke epilepsy after first-ever intracerebral haemorrhage.

Post-stroke epilepsy (PSE) is associated with increased morbidity and mortality. This study aimed to develop and validate a novel prediction model combining clinical factors and radiomics features to accurately identify patients at high risk of developing PSE after intracerebral haemorrhage (ICH). Researchers performed a retrospective medical chart review to extract derivation and validation cohorts of patients with first-ever ICH that attended two tertiary hospitals in China between 2010 and 2020. Clinical data were extracted from electronic medical records and supplemented by tele-interview. Predictive clinical variables were selected by multivariable logistic regression to build the clinical model. Predictive radiomics features were identified, and a Rad-score was calculated according to the coefficient of the selected feature. Both clinical variables and radiomic features were combined to build the radiomics-clinical model. Performances of the clinical, Rad-score, and combined models were compared. A total of 1571 patients were included in the analysis. Cortical involvement, early seizures within 7days of ICH, NIHSS score, and ICH volume were included in the clinical model. Rad-score, instead of ICH volume, was included in the combined model. The combined model exhibited better discrimination ability and achieved an overall better benefit against threshold probability than the clinical model in the decision curve analysis (DCA). The combined radiomics-clinical model was better able to predict ICH-associated PSE compared to the clinical model. This can help clinicians better predict an individual patient's risk of PSE following a first-ever ICH and facilitate earlier PSE diagnosis and treatment. • Radiomics has not been used in predicting the risk of developing PSE. • Higher Rad-scores were associated with higher risk of developing PSE. • The combined model showed better performance of PSE prediction ability.

Abstract TP229: Impact Of Genetic Polymorphisms On The Risk Of Epilepsy Amongst Patients With Acute Brain Injury: A Systematic Review

Introduction: Stroke and traumatic brain injury (TBI) accounts for 70% of secondary epilepsy in the adult population. The genetic architecture of epilepsy secondary to TBI or stroke is poorly understood. Objective: We undertook a systematic review to test the association of single nucleotide polymorphisms (SNPs) with the risk of posttraumatic epilepsy (PTE) and post-stroke epilepsy (PSE). Methods: We conducted a comprehensive literature search until 5 July 2022 in PubMed, Embase, PsycINFO, Web of Science, and Google Scholar. We preregistered the protocol of this systematic review on PROSPERO (CRD42022325617). We collated the association statistics from the articles to assess the association of SNPs with the risk of epilepsy amongst TBI or stroke patients. We assessed the study quality using the Quality of Genetic Association (Q-Genie) tool. We report Odds Ratio (OR) and Hazard Ratio (HR) with a 95% confidence interval (CI), including combined OR where a meta-analysis was possible. Results: The literature search yielded 420 articles, of which 16 were included in our systematic review. Q-Genie-based assessment of the literature found that 58% of the included studies were of poor quality. We examined published data on 127 SNPs from 32 genes identified in PTE and PSE patients. Twelve studies reported that 718 TBI patients (21%) suffered from PTE. Four studies reported PSE in 1192 stroke patients (50%). Eleven SNPs were associated with an increased risk of PTE. Three SNPs, TRMP6 rs2274924, ALDH2 rs671, CD40 -1C/T, were significantly associated with an increased risk of PSE, while two SNPs, AT1R rs12721273 and rs55707609, were significantly associated with reduced risk. Only two studies tested the association of APOE E4 with PTE; no other studies validated previously reported genetic association data. Hence, the limited data precluded meta-analysis of all but one SNP, i.e., the APOE E4 allele. The meta-analysis for the association of the APOE E4 allele with PTE was non-significant (OR 1.8, CI 0.6-5.6). Conclusions: The current evidence on the association of genetic polymorphisms in epilepsy secondary to TBI or stroke is of low quality and lacks validation. A collaborative effort to pool genetic data linked to epileptogenesis in stroke and TBI patients is warranted.

Predictive factors for the development of epilepsy after ischemic stroke

ObjectivesIschemic stroke is one of the most common causes of epilepsy in adults. The incidence of post-stroke epilepsy (PSE) is approximately 7%. Risk factors are higher stroke severity, cortical localization, higher National Institute of Health Stroke Scale (NIHSS) upon admission and acute symptomatic seizures. We analyzed the predictive factors of PSE development in our population. Materials and methodsRetrospective observational cohort of adult patients (age ≥ 18 years) with ischemic stroke assessed between January 2012 and June 2020. Patients with personal history of epilepsy and potentially epileptogenic structural injury other than acute or chronic stroke were excluded. Demographic, clinical and imaging variables were evaluated in a multivariate analysis for independent risk factors associated with PSE. ResultsMedical records of 1586 stroke patients were reviewed, 691 met the inclusion criteria and had at least one year of follow-up. Of them, 428 (61.9%) were males. During follow-up, 6.2% had diagnosis of PSE (42/691) with a higher frequency of: previous ischemic stroke, higher NIHSS upon admission, treatment with rt-PA, higher Fazekas scale grade, cortical involvement, hemorrhagic transformation, acute symptomatic seizures, longer hospitalization and higher modified Rankin Scale (mRS) at discharge compared to the group without PSE. In a multivariate analysis, acute symptomatic seizures (OR=3.22, p: 0.033), cortical involvement (OR=0.274, p < 0.05), Fazekas scale score (OR=0.519, p < 0.05) and mRS at discharge (OR=1.33, p: 0.043) were independent risk factors. ConclusionsThe variables related to higher risk of PSE were similar to those reported in the literature, highlighting the importance of neuroimaging findings, acute symptomatic seizures during hospitalization and neurological deficit at discharge. The data obtained will serve as the basis for construction of predictive models, allowing to individualize PSE probability in our population.

Association of Cortical Superficial Siderosis with Post-Stroke Epilepsy.

To assess whether post-stroke epilepsy (PSE) is associated with neuroimaging findings of hemosiderin in a case-control study, and whether the addition of hemosiderin markers improves the risk stratification models of PSE. We performed a post-hoc analysis of the PROgnosis of POST-Stroke Epilepsy study enrolling PSE patients at National Cerebral and Cardiovascular Center, Osaka, Japan, from November 2014 to September 2019. PSE was diagnosed when one unprovoked seizure was experienced >7 days after the index stroke, as proposed by the International League Against Epilepsy. As controls, consecutive acute stroke patients with no history or absence of any late seizure or continuing antiseizure medications at least 3 months after stroke were retrospectively enrolled during the same study period. We examined cortical microbleeds and cortical superficial siderosis (cSS) using gradient-echo T2*-weighted images. A logistic regression model with ridge penalties was tuned using 10-fold cross-validation. We added the item of cSS to the existing models (SeLECT and CAVE) for predicting PSE and evaluated performance of new models. The study included 180 patients with PSE (67 women; median age 74 years) and 1,183 controls (440 women; median age 74 years). The cSS frequency was higher in PSE than control groups (48.9% vs 5.7%, p < 0.0001). Compared with the existing models, the new models with cSS (SeLECT-S and CAVE-S) demonstrated significantly better predictive performance of PSE (net reclassification improvement 0.63 [p=0.004] for SeLECT-S and 0.88 [p=0.001] for CAVE-S at the testing data). Cortical superficial siderosis was associated with PSE, stratifying stroke survivors at high risk of PSE. ANN NEUROL 2023;93:357-370.

Risk Factors for Postischemic Stroke Epilepsy in Young Adults: A Nationwide Population-Based Study in Taiwan.

BackgroundThe incidence of ischemic stroke has been increasing in the young population over the past 20 years. Poststroke epilepsy (PSE) is a common complication after stroke. However, few population-based studies with sufficient follow-up have investigated factors associated with PSE, especially factors related to comorbidities and unhealthy lifestyles in the modern young population. Accordingly, this study aimed to determine the long-term incidence and these risk factors for PSE young adults.MethodsThis cohort study was conducted using data from the Taiwan National Health Insurance Research Database (NHIRD) from 2002 to 2018. All patients aged between 19 and 44 years and diagnosed with ischemic stroke from 2002 to 2015 were retrospectively enrolled with a follow-up of at least 3 years. Multivariable Cox regression models were performed to identify predictors of PSE, including patients' demographics, baseline conditions, stroke severity, etiologies, comorbidities, and unhealthy behaviors.ResultsAmong 6,512 ischemic stroke patients, 402 cases (6.2%) developed PSE who were with a mean follow-up period of 8.3 years (SD = 4.3 years). During the overall follow-up, stroke severity and manifestations were associated with PSE, including National Institutes of Health Stroke Scale (NIHSS) score ≥10 (aHR, 1.98; 95% CI, 1.50–2.61), seizure at first stroke admission [adjusted hazard ratio (aHR), 57.39; 95% confidence interval (CI), 43.02–76.55], length of hospital stay ≥14 days (aHR, 1.60; 95% CI, 1.26–2.02), recurrent stroke (aHR, 2.32; 95% CI, 1.85–2.90), aphasia (aHR, 1.77; 95% CI, 1.20–2.60), and malignancy (aHR, 2.05; 95% CI, 1.30–3.24). Furthermore, stroke patients with drug abuse were 2.90 times more likely to develop PSE than those without (aHR, 2.90; 95% CI, 1.53–5.50). By contrast, statin use (aHR, 0.62; 95% CI, 0.48–0.80) was associated with a lower risk of PSE. The risk factors at 1-year and 5-year PSE were similar to that of an overall follow-up.ConclusionsStroke severity, aphasia, malignancy, and drug abuse were associated increased risk of PSE and statin use may protect against PSE in young adults. Reducing the severity of stroke, statin use and controlling unhealthy behaviors might be able to decrease the development of PSE. Since PSE is associated with poor outcomes, early identification or intervention of PSE based on the risk factors might reduce the harmful effects of PSE.

Risk of Incident Epilepsy After a Middle Cerebral Artery Territory Infarction.

BackgroundAmong poststroke morbidities, poststroke epilepsy (PSE) has been identified as a significant clinical issue. Although middle cerebral artery (MCA) infarct is the most common type of stroke among all vascular territories, very few studies specifically focused on the risk factors leading to PSE in patients with MCA infarct.MethodsA population study in Taiwan has been conducted, linking the National Health Insurance Research Database and Hospital Stroke Registry, from 2001 to 2015 and 2006 to 2010, respectively. Patients were divided into MCA and non-MCA groups, and the diagnosis of incident epilepsy between the groups has been compared. The multivariable Cox proportional hazard model was used to identify the risk factors for developing PSE. The distribution of time to PSE was estimated using the Kaplan–Meier method.ResultsIn total, 1,838 patients were recruited, with 774 and 1,064 in the MCA and non-MCA groups, respectively. PSE incidence in the MCA group was 15.5% vs. 6.2% in the non-MCA group, with a hazard ratio of (95% CI) 2.06 (1.33–3.19). Factors significantly associated with PSE included atrial fibrillation, depression, National Institutes of Health Stroke Scale (NIHSS) scores of ≥ 16, and alert on arrival. For patients with MCA infarct, higher NIHSS and Glasgow coma scale scores, the presence of visual field defects and weakness, urination control impairment, and complications during hospitalization were associated with a higher risk for PSE development.ConclusionsThis study established the conditions leading to a higher risk of PSE and identified the important clinical risk factors in patients experiencing MCA infarct. Efforts to manage these risk factors may be important in preventing PSE in patients with MCA infarct.

Seizures after Ischemic Stroke: A Matched Multicenter Study.

ObjectiveThe purpose of this study was to identify risk factors for acute symptomatic seizures and post‐stroke epilepsy after acute ischemic stroke and evaluate the effects of reperfusion treatment.MethodsWe assessed the risk factors for post‐stroke seizures using logistic or Cox regression in a multicenter study, including adults from 8 European referral centers with neuroimaging‐confirmed ischemic stroke. We compared the risk of post‐stroke seizures between participants with or without reperfusion treatment following propensity score matching to reduce confounding due to treatment selection.ResultsIn the overall cohort of 4,229 participants (mean age 71 years, 57% men), a higher risk of acute symptomatic seizures was observed in those with more severe strokes, infarcts located in the posterior cerebral artery territory, and strokes caused by large‐artery atherosclerosis. Strokes caused by small‐vessel occlusion carried a small risk of acute symptomatic seizures. 6% developed post‐stroke epilepsy. Risk factors for post‐stroke epilepsy were acute symptomatic seizures, more severe strokes, infarcts involving the cerebral cortex, and strokes caused by large‐artery atherosclerosis. Electroencephalography findings within 7 days of stroke onset were not independently associated with the risk of post‐stroke epilepsy. There was no association between reperfusion treatments in general or only intravenous thrombolysis or mechanical thrombectomy with the time to post‐stroke epilepsy or the risk of acute symptomatic seizures.InterpretationPost‐stroke seizures are related to stroke severity, etiology, and location, whereas an early electroencephalogram was not predictive of epilepsy. We did not find an association of reperfusion treatment with risks of acute symptomatic seizures or post‐stroke epilepsy. ANN NEUROL 2021;90:808–820

Risk of Post-stroke Epilepsy Following Stroke-Associated Acute Symptomatic Seizures.

Objective: Post-stroke epilepsy (PSE) is associated with increased morbidity and mortality. Stroke-associated acute symptomatic seizures are an important risk factor: 20.8–34.3% of these patients will go on to develop PSE. Identifying these “high risk” individuals may result in earlier PSE diagnosis, treatment, and avoidance of seizure-related morbidity. This study was to identify predictors of PSE development in patients with stroke-associated acute symptomatic seizures.Participants and Methods: This was a retrospective cohort study of 167 patients with stroke-associated acute symptomatic seizures admitted to the Neurology Department of a tertiary Hospital of China, from 1 May 2006 to 30 January 2020. Both those with primary ischemic stroke and intracerebral hemorrhage were included in the study. Patient demographics, medical history, stroke-associated, and seizure-related variables were evaluated with univariable analysis and multivariable Cox regression analysis. PSE was defined as unprovoked seizures occurring > 7 days post-stroke. Data points were extracted from medical records and supplemented by tele-interview.Results: Of the 167 patients with stroke-associated acute symptomatic seizures, 49 (29.3%) developed PSE. NIHSS score > 14 [hazard ratio (HR) 2.98, 95% CI 1.57–5.67], longer interval from stroke to acute symptomatic seizures (days 4–7 post-stroke) (HR 2.51, 95% CI 1.37–4.59) and multiple acute symptomatic seizures (HR 5.08, 95% CI 2.58–9.99) were independently associated with PSE development. This association remained in the sub-analysis within the ischemic stroke cohort. In the sub-analysis of the hemorrhagic stroke cohort, multilobar involvement (HR 4.80, 95% CI 1.49–15.39) was also independently associated with development of PSE. Further, we developed a nomogram to predict individual risk of developing PSE following stroke-associated acute symptomatic seizures. The nomogram showed a C-index of 0.73.Conclusion: More severe neurofunctional deficits (NIHSS score > 14), longer interval from stroke to acute symptomatic seizures (days 4–7 post-stroke), and multiple acute symptomatic seizures were independently associated with development of PSE in patients with stroke-associated acute symptomatic seizures. This knowledge may increase clinical vigilance for development of PSE, facilitating rapid diagnosis and treatment initiation, and subsequently reduce seizure-related morbidity.

Effects of atorvastatin and aspirin on post-stroke epilepsy and usage of levetiracetam.

Objective:Atorvastatin and aspirin have been used in treating different forms of epilepsy. However, their effect on post-stroke epilepsy (PSE) still needs to be validated by large-scale clinical studies. In addition, their impact on the use of the antiepileptic drug levetiracetam for post-stroke epilepsy remains to be explored. Thus, the aim of this study was to further evaluate the effect of atorvastatin and aspirin on PSE and their effect on the usage of the antiepileptic drug levetiracetam in PSE patients.Methods:Patients, aged 65 to 85 years, with newly diagnosed post-ischemic stroke epilepsy from August 30, 2014 to August 30, 2018 were included in the study, with the exclusion of those with coexisting conditions.Results:Initially, 1321 patients were included, and 780 remained in the study at the 1-year follow-up. During the study, atorvastatin treatment with or without aspirin reduced the number of clinical epileptic episodes in PSE patients. It also reduced the dosage of levetiracetam and achieved better control of epilepsy compared to levetiracetam mono-treatment. Aspirin co-treatment with levetiracetam did not result in a significant improvement. However, the combination of aspirin with atorvastatin significantly reduced the number of seizures compared to atorvastatin treatment alone.Conclusion:Atorvastatin and aspirin co-treatment with levetiracetam can reduce epilepsy in PSE patients and reduce the dosage of levetiracetam required for effective control of PSE.

The influence of statins on the risk of post-stroke epilepsy.

Currently, statins are widely used for secondary prevention of stroke due to their pleiotropic neuroprotective effects. Epilepsy is a common complication of cerebrovascular diseases. The purpose of this study was to evaluate the effect of statin therapy on the occurrence of post-stroke epilepsy (PSE). In this prospective cohort study, patients who suffered an ischemic stroke and without history of epilepsy before stroke were enrolled. At baseline, patients were classified according to the particularities of statin therapy. Statin use onset and adherence to treatment were registered as well. After a follow-up period of 1year, we assessed the occurrence of seizures and PSE. Among the 477 patients included in our cohort, there were 91 (19.1%) patients without statins, 160 (33.5%) with simvastatin 20mg, 180 (37.7%) with simvastatin 40mg, and 46 (9.6%) with high-potency statins. Overall, PSE emerged in 53 (11.1%) patients. PSE was significantly more prevalent among those who did not receive statins and those with lower doses of simvastatin. Acute onset of statin use was associated with reduced odds of having PSE. Adequate treatment with statins after stroke may lower the risk of PSE.

Abstract TP164: Statins for the Prevention of Post-Stroke Seizure and Epilepsy Development: A Systematic Review and Meta-Analysis

Introduction: Cerebrovascular disease is the leading cause of seizures and incident epilepsy of known etiology in older adults. As prophylactic use of antiepileptic drugs remains controversial, statins have garnered attention as an alternate preventive strategy due to pleiotropic effects, beyond lipid-lowering, which may include neuroprotective and anti-epileptogenic properties. Our objective was to assess the current evidence on statin use for prevention of post-stroke seizure and post-stroke epilepsy (PSE). Methods: We conducted a systematic review following PRISMA guidelines. Pubmed and Embase were searched from database inception to May 2019 for English-language, full-text experimental, observational analytic, or systematic reviews/meta-analytic studies examining the association between statin use in adults and development of early-onset seizures (ES; seizures ≤7 days after stroke) or PSE. Pooled analyses were based on random-effects models using the inverse-variance method. Results: Of 157 citations, 154 were excluded due to duplication or ineligibility, yielding 3 cohort studies from East Asia. Two studies reported on outcomes of ischemic stroke and 1 on hemorrhagic stroke. Only 1 study reported on ES, finding a significantly reduced risk following post-stroke statin use (OR 0.35, CI 0.20-0.60). Two studies reported on pre-stroke statin use, with findings demonstrating a lack of association with PSE (pooled OR 1.17, CI 0.93-1.48; Figure 1.1). However, post-stroke statin use was associated with less PSE (pooled OR 0.61, CI 0.50-0.74), without evidence of heterogeneity (Figure 1.2). Conclusions: Systematic review and meta-analysis of 3 high-quality cohort studies suggests post-stroke, but not pre-stroke, statin use may be associated with reduced risk of PSE. Further research is warranted to verify if these findings are replicable in other populations, as well as to explore the influence of timing and duration of statin use on outcomes.

Acute symptomatic seizures and epilepsy after mechanical thrombectomy

PurposeThe purpose of this study was to assess the incidence of acute symptomatic seizures and poststroke epilepsy (PSE) in a well-characterized cohort of patients treated with mechanical thrombectomy. In addition, we aimed to describe the dynamics of blood markers of brain injury in patients that developed PSE. MethodsParticipants of the prospective AnStroke Trial of anesthesia method during mechanical thrombectomy were included and acute symptomatic seizures and PSE ascertained by medical records review. Blood markers neurofilament light (NFL), tau, glial fibrillary acidic protein (GFAP), S100 calcium-binding protein B (S100B), and neuron-specific enolase (NSE) were assessed. ResultsA total of 90 patients with acute anterior ischemic stroke were included. Median National Institutes of Health Stroke Scale (NIHSS) at admission to hospital was 18 (IQR 15–22). Recanalization was achieved in 90%. No patients had epilepsy prior to the ischemic stroke. Four patients (4.4%) had acute symptomatic seizures and four patients (4.4%) developed PSE during the follow-up time (to death or last medical records review) of 0–4.5 years (median follow-up 1070 days IQR 777–1306), resulting in a two-year estimated PSE risk of 5.3% (95%CI: 0.2–10.4%). Blood markers of brain injury (NFL, tau, GFAP, S100B, and NSE) were generally above the cohort median in patients that developed PSE. ConclusionsThe incidence of PSE after mechanical thrombectomy was low in our cohort. All blood biomarkers displayed interesting sensitivity and specificity. However, the number of PSE cases was small and more studies are needed on risk factors for PSE after mechanical thrombectomy. The potential of blood markers of brain injury markers to contribute to assessment of PSE risk should be explored further.This article is part of the Special Issue "Seizures & Stroke".

Efficacy of Statin therapy in post-stroke seizure prophylaxis: Clues from an observational study of routine secondary prevention treatment

PurposeTo confirm that statin use can reduce the risk of post-stroke seizures (PSS), and to further investigate the association between the details of specific statin therapy, including the initial time, types, doses, courses, and the risk of PSS. MethodsPatients with newly-onset ischemic stroke and no history of epilepsy before stroke were enrolled. After an average of 2 years follow-up, with the aim of establishing a PSS diagnosis, logistic regression was utilized to assess the association between specific statin therapy and the risk of PSS. ResultsOf 1051 enrolled patients, 24 (2.3%) developed early-onset seizures (ES) and 38 (3.6%) had late-onset seizures (LS), 28 of whom had LS twice or more, and thus fell in the category of post-stroke epilepsy (PSE) patients. Statin therapy was associated with a lower risk of ES (P = 0.009), LS (P = 0.007), and PSE (P = 0.009), and this reduction was even more pronounced in patients using intensive-dose statins (ES [P = 0.003], LS [P = 0.004], PSE [P = 0.006]). In addition, the risk of PSE was significantly reduced in long-course statin therapy compared with short-course statin therapy (P = 0.015). However, no significant association was found between the initial time of treatment and PSS risk (ES [P = 0.321], LS [P = 0.050], PSE [P = 0.108]). ConclusionsStatin treatment, especially with intensive-dose statins, can reduce the risk of PSS. In addition, the risk of developing PSE appears to be significantly lower for prolonged statin treatment. However, due to the observational nature of this study, more investigations are warranted to confirm its findings.

Long-term epilepsy after early post-stroke status epilepticus

Purpose: The risk of developing epilepsy at long term after post-stroke status epilepticus (PSSE) is unknown. We aimed to evaluate post-stroke epilepsy (PSE) after early-onset PSSE and its associated factors.Method: All consecutive patients with early-onset PSSE and no history of epilepsy admitted to our hospital between February 2011 and April 2017 were included. We analysed status epilepticus (SE) and stroke-related factors in relation to the development of PSE.Results: Fifty patients with early-onset PSSE were analysed. Mean age was 74.8 ± 14.3 years and 22 (44%) were women. Median NIHSS at the onset of PSSE was 11 (IQR 4–16) and median PSSE duration was 12 h (IQR 4.69–57). Median follow-up was 214 days (IQR 7.5–747). Ten patients (20%) developed PSE at a median delay of 153 days (IQR 20–334). On multivariate analysis, NIHSS > 4 (p = 0.019; hazard ratio: 15.757; 95% CI, 1.564–158.799) and PSSE > 16 h (p = 0.023; hazard ratio: 7.483; 95% CI, 1.325–42.276) were independently associated with a greater risk of PSE. The mean time from PSSE to onset of recurrent seizures was 142 days (IQR 19–153) in patients with PSSE > 16 h and 310 days (IQR 147–480) in PSSE < 16 h (p = 0.094).Conclusions: NIHSS score >4 at the stroke presentation and PSSE duration >16 h may predict of PSE in patients with early-onset PSSE. Recurrence may develop earlier in PSSE patients with longer duration of the episode.