Poststroke epilepsy (PSE) is associated with higher mortality and poor functional and cognitive outcomes in patients with stroke. With the remarkable development of acute stroke treatment, there is a growing number of survivors with PSE. Although approximately 10% of patients with stroke develop PSE, given the significant burden of stroke worldwide, PSE is a significant problem in stroke survivors. Therefore, the attention of health policymakers and significant funding are required to promote PSE prevention research. The current PSE definition includes unprovoked seizures occurring more than 7 days after stroke onset, given the high recurrence risks of seizures. However, the pathologic cascade of stroke is not uniform, indicating the need for a tissue-based approach rather than a time-based one to distinguish early seizures from late seizures. EEG is a commonly used tool in the diagnostic work-up of PSE. EEG findings during the acute phase of stroke can potentially stratify the risk of subsequent seizures and predict the development of poststroke epileptogenesis. Recent reports suggest that cortical superficial siderosis, which may be involved in epileptogenesis, is a promising marker for PSE. By incorporating such markers, future risk-scoring models could guide treatment strategies, particularly for the primary prophylaxis of PSE. To date, drugs that prevent poststroke epileptogenesis are lacking. The primary challenge involves the substantial cost burden due to the difficulty of reliably enrolling patients who develop PSE. There is, therefore, a critical need to determine reliable biomarkers for PSE. The goal is to be able to use them for trial enrichment and as a surrogate outcome measure for epileptogenesis. Moreover, seizure prophylaxis is essential to prevent functional and cognitive decline in stroke survivors. Further elucidation of factors that contribute to poststroke epileptogenesis is eagerly awaited. Meanwhile, the regimen of antiseizure medications should be based on individual cardiovascular risk, psychosomatic comorbidities, and concomitant medications. This review summarizes the current understanding of poststroke epileptogenesis, its risks, prognostic models, prophylaxis, and strategies for secondary prevention of seizures and suggests strategies to advance research on PSE.

Background and purpose: The management of post‐stroke epilepsy (PSE) should ideally include prevention of both seizure and adverse effects; however, an optimal antiseizure medications (ASM) regimen has yet been established. The purpose of this study is to assess seizure recurrence, retention, and tolerability of older‐generation and newer‐generation ASM for PSE.Methods: This prospective multicenter cohort study (PROgnosis of Post‐Stroke Epilepsy [PROPOSE] study) was conducted from November 2014 to September 2019 at eight hospitals. A total of 372 patients admitted and treated with ASM at discharge were recruited. Due to the non‐interventional nature of the study, ASM regimen was not adjusted and followed standard hospital practices. The primary outcome was seizure recurrence in patients receiving older‐generation and newer‐generation ASM. The secondary outcomes were the retention and tolerability of ASM regimens.Results: Of the 372 PSE patients with ASM at discharge (median [IQR] age, 73 [64–81] years; 139 women [37.4%]), 36 were treated with older‐generation, 286 with newer‐generation, and 50 with mixed‐generation ASM. In older‐ and newer‐generation ASM groups (n = 322), 98 patients (30.4%) had recurrent seizures and 91 patients (28.3%) switched ASM regimen during the follow‐up (371 [347–420] days). Seizure recurrence was lower in newer‐generation, compared with the older‐generation, ASM (hazard ratio [HR], 0.42, 95%CI 0.27–0.70; p = .0013). ASM regimen withdrawal and change of dosages were lower in newer‐generation ASM (HR, 0.34, 95% CI 0.21–0.56, p < .0001).Conclusions: Newer‐generation ASM possess advantages over older‐generation ASM for secondary prophylaxis of post‐stroke seizures in clinical practice.

The most effective antiseizure medications (ASMs) for poststroke seizures (PSSs) remain unclear. We aimed to determine outcomes associated with ASMs in people with PSS. We systematically searched electronic databases for studies on patients with PSS on ASMs. Our outcomes were seizure recurrence, adverse events, drug discontinuation rate, and mortality. We assessed the risk of bias using Cochrane Risk of Bias tool for randomized controlled trials and Risk Of Bias In Non-randomized Studies of Interventions tools. Using levetiracetam as the reference treatment, we conducted a frequentist network meta-analysis and determined the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Our search yielded 15 studies (3 randomized, 12 nonrandomized, N = 18,676 patients (121 early and 18,547 late seizures), 60% male, mean age 69 years) comparing 13 ASMs. Three studies had moderate and 12 had high risk of bias. Seizure recurrence was 24.8%. Compared with levetiracetam, very low-certainty evidence suggested that phenytoin was associated with higher seizure recurrences (odds ratio [OR] 7.3, 95% CI 3.7-14.5) and more adverse events (OR 5.2, 95% CI 1.2-22.9). Low-certainty evidence suggested that carbamazepine (OR 1.8, 95% CI 1.5-2.2) and phenytoin (OR 1.9, 95% CI 1.4-2.8) were associated with high drug discontinuation rates. Moderate to high-certainty evidence suggested that valproic acid (OR 4.7, 95% CI 3.6-6.3) and phenytoin (OR 8.3, 95% CI 5.7-11.9) were associated with higher mortality rates. Considering all treatments and using the GRADE approach for treatment ranking, very low-certainty evidence suggested that eslicarbazepine, lacosamide, and levetiracetam had the fewest seizure recurrences. Low to very low-certainty evidence suggested that lamotrigine had the fewest adverse events and drug discontinuations, whereas lamotrigine and levetiracetam exhibited low mortality rates with moderate-certainty evidence. We found that levetiracetam and lamotrigine may be safe and tolerable ASMs for PSS. Despite ASM use, the seizure recurrence rate remains high in the PSS population. Owing to bias and confounding risks, these findings should be interpreted cautiously. PROSPERO: CRD42022363844.

Objective: 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.Methods: 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.Results: 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).Interpretation: Cortical superficial siderosis was associated with PSE, stratifying stroke survivors at high risk of PSE. ANN NEUROL 2023;93:357–370