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.

Efficacy of rTMS for poststroke epilepsy and its effects on patients' cognitive function and depressive status.

OBJECTIVE: This study aimed to investigate the efficacy of rTMS in the treatment of poststroke epilepsy and the effect of rTMS on patients' cognitive function and depressive status. METHODS: One hundred and twenty-one poststroke epilepsy patients with mild cognitive impairment and depressive status admitted to the Department of Neurology of the Second People's Hospital of Nanning from January 1, 2017, to April 31, 2023, were selected and divided into the rTMS treatment group (treated group) and the control group. MMSE scores and HAMD scores were recorded before and after treatment. The frequency of EEG spiky waves recorded before and after treatment within 24 h and the frequency of any clinical seizure form (the number of clinical seizures within 1 month after treatment) and changes in observed indices before and after treatment were calculated. The differences between the data of the two groups were analyzed, to further assess the efficacy of rTMS in the treatment of poststroke epilepsy and the rTMS' effects on cognition and depression. RESULTS: Compared with drug treatment alone, rTMS significantly decreased clinical seizures and epileptiform discharges after stroke, especially in patients with lesions in the frontal, temporal, and parietal lobes. Compared with drug treatment alone, rTMS treatment can effectively reduce cognitive impairment and mood disorders, such as depression, especially for patients with lesions in the frontal and temporal lobes. The results of this experiment suggest that rTMS treatment does not increase adverse effects. CONCLUSION: rTMS reduces clinical seizures while improving cognitive impairment and depression in patients with epilepsy. Therefore, we suggest that low-frequency rTMS can be used as an adjunctive treatment for patients with epilepsy and provide some ideas and references for the treatment of epilepsy with cognitive impairment and depression.

Periodic discharges plus fast activity on electroencephalogram predict worse outcomes in poststroke epilepsy.

OBJECTIVE: Postseizure functional decline is a concern in poststroke epilepsy (PSE). However, data on electroencephalogram (EEG) markers associated with functional decline are scarce. Thus, we investigated whether periodic discharges (PDs) and their specific characteristics are associated with functional decline in patients with PSE. METHODS: In this observational study, patients admitted with seizures of PSE and who had scalp EEGs were included. The association between the presence or absence of PDs and postseizure short-term functional decline lasting 7 days after admission was investigated. In patients with PD, EEG markers were explored for risk stratification of short-term functional decline, according to the American Clinical Neurophysiology Society's Standardized Critical Care EEG Terminology. The association between EEG markers and imaging findings and long-term functional decline at discharge and 6 months after discharge, defined as an increase in the modified Rankin Scale score compared with the baseline, was evaluated. RESULTS: In this study, 307 patients with PSE (median age = 75 years, range = 35-97 years, 64% males; hemorrhagic stroke, 47%) were enrolled. Compared with 247 patients without PDs, 60 patients with PDs were more likely to have short-term functional decline (12 [20%] vs. 8 [3.2%], p < .001), with an adjusted odds ratio (OR) of 4.26 (95% confidence interval [CI] = 1.44-12.6, p = .009). Patients with superimposed fast-activity PDs (PDs+F) had significantly more localized (rather than widespread) lesions (87% vs. 58%, p = .003), prolonged hyperperfusion (100% vs. 62%, p = .023), and a significantly higher risk of short-term functional decline than those with PDs without fast activity (adjusted OR = 22.0, 95% CI = 1.87-259.4, p = .014). Six months after discharge, PDs+F were significantly associated with long-term functional decline (adjusted OR = 4.21, 95% CI = 1.27-13.88, p = .018). SIGNIFICANCE: In PSE, PDs+F are associated with sustained neuronal excitation and hyperperfusion, which may be a predictor of postseizure short- and long-term functional decline.

Clinical and imaging features of nonmotor onset seizure in poststroke epilepsy.

OBJECTIVE: Motivated by the challenges raised by diagnosing poststroke epilepsy (PSE), especially in nonmotor onset seizure (non-MOS), we aimed to investigate the features of non-MOS, including seizure sequences, patient characteristics, and electrophysiological and imaging findings in PSE. METHODS: This observational cohort study enrolled patients with PSE whose seizure onset was witnessed. According to the International League Against Epilepsy (ILAE) 2017 seizure classification, we classified seizure-onset symptoms into the non-MOS and MOS groups. We compared the different clinical characteristics between the two groups. RESULTS: Between 2011 and 2018, we enrolled 225 patients with PSE (median age, 75 years), consisting of 97 (43%) with non-MOS and 128 (57%) with MOS. Overall, 65 (67%) of the patients without MOS had no subsequent convulsions. Multivariable logistic regression analysis showed significant associations of non-MOS with absence of poststroke hemiparesis (adjusted odds ratio [OR], 1.88; 95% confidence interval [CI], 1.03-3.42), frontal stroke lobe lesions (OR, 2.11; 95% CI, 1.14-3.91), and putaminal stroke lesions (OR, 2.51; 95% CI, 1.22-5.18) as negative indicators. Postictal single-photon emission computed tomography (SPECT) detected prolonged hyperperfusion in the temporal lobe more frequently in the non-MOS than in the MOS group (48% vs 31%; p = .02). The detection rate was higher than spikes/sharp waves in scalp electroencephalography, both in the non-MOS group (72% vs 33%; p < .001) and the MOS group (68% vs 29%; p < .001). SIGNIFICANCE: This study provides the clinical features of non-MOS in patients with PSE. Compared with the patients with MOS, patients with non-MOS showed less likely subsequent convulsive seizures, highlighting the clinical challenges. Postictal perfusion imaging and negative indicators of the non-MOS type may help diagnose and stratify PSE.

Blood biomarkers predictive of epilepsy after an acute stroke event.

OBJECTIVE: Blood biomarkers have not been widely investigated in poststroke epilepsy. In this study, we aimed to describe clinical factors and biomarkers present during acute stroke and analyze their association with the development of epilepsy at long term. METHODS: A panel of 14 blood biomarkers was evaluated in patients with ischemic and hemorrhagic stroke. Biomarkers were normalized and standardized using Z-scores. Stroke and epilepsy-related variables were also assessed: stroke severity, determined by National Institutes of Health Stroke Scale (NIHSS) score, stroke type and cause, time from stroke to onset of late seizures, and type of seizure. Multiple Cox regression models were used to identify clinical variables and biomarkers independently associated with epilepsy. RESULTS: From a cohort of 1115 patients, 895 patients were included. Mean ± standard deviation (SD) age was 72.0 ± 13.1 years, and 57.8% of patients were men. Fifty-one patients (5.7%) developed late seizures, with a median time to onset of 232 days (interquartile range [IQR] 86-491). NIHSS score ≥8 (P < .001, hazard ratio [HR] 4.013, 95% confidence interval [CI] 2.123-7.586) and a history of early onset seizures (P < .001, HR 4.038, 95% CI 1.802-9.045) were factors independently associated with a risk of developing epilepsy. Independent blood biomarkers predictive of epilepsy were high endostatin levels >1.203 (P = .046, HR 4.300, 95% CI 1.028-17.996) and low levels of heat shock 70 kDa protein-8 (Hsc70) <2.496 (P = .006, HR 3.795, 95% CI 1.476-9.760) and S100B <1.364 (P = .001, HR 2.955, 95% CI 1.534-5.491). The risk of epilepsy when these biomarkers were combined increased to 17%. The area under the receiver-operating characteristic (ROC) curve of the predictive model was stronger when clinical variables were combined with blood biomarkers (74.3%, 95% CI 65.2%-83.3%) than when they were used alone (68.9%, 95% CI 60.3%-77.6%). SIGNIFICANCE: Downregulated S100B and Hsc70 and upregulated endostatin may assist in prediction of poststroke epilepsy and may provide additional information to clinical risk factors. In addition, these data are hypothesis-generating for the epileptogenic process.

Medication use in poststroke epilepsy: A descriptive study on switching of antiepileptic drug treatment.

OBJECTIVE: Currently, as evidence-based guidelines are lacking, in patients with poststroke epilepsy (PSE), the choice of the first antiepileptic drug (AED) is left over to shared decision by the treating physician and patient. Although, it is not uncommon that patients with PSE subsequently switch their first prescribed AED to another AED, reasons for those switches are not reported yet. In the present study, we therefore assessed the reasons for switching the first prescribed AED in patients with PSE. METHOD: We gathered a hospital-based case series of 53 adult patients with poststroke epilepsy and assessed the use of AEDs, comedication, and the reasons for switches between AEDs during treatment. We also determined the daily drug dose (DDD) at the switching moment. RESULTS: During a median follow-up of 62 months (Interquartile range [IQR] 69 months), 21 patients (40%) switched their first prescribed AED. Seven patients switched AED at least once because of ineffectivity only or a combination of ineffectivity and side effects, whereas 14 patients switched AED at least once because of side effects only. The DDD was significantly (p < 0.001) higher in case of medication switches due to ineffectivity (median 1.20, IQR 0.33) compared to switching due to side effects (median 0.67, IQR 0.07). There was no difference in the use of comedication between the group that switched because of ineffectivity compared to the group that switched because of side effects. CONCLUSION: In our case series, up to 40% of patients with epilepsy after stroke needed to switch their first prescribed AED, mostly because of side effects in lower dosage ranges.

Statins in primary prevention of poststroke seizures and epilepsy: A systematic review.

INTRODUCTION: Cerebrovascular disease is the most common cause of seizures in adults and the elderly. So far, no drug is recommended as primary prevention of acute symptomatic poststroke seizures (ASPSS) or poststroke epilepsy (PSE). This systematic review aimed to evaluate the association between the use of statins after stroke and the risk of developing ASPSS or PSE following cerebral infarct or hemorrhage (primary prevention). METHODS: We included studies evaluating the poststroke use of statins as primary prevention of ASPSS or PSE, irrespective of stroke type. We excluded uncontrolled studies and studies with prestroke statin use. The main outcome included the occurrence of ASPSS or PSE and the effect of statins by type and dose. The odds ratios (ORs) or hazard ratios (HR) with 95% confidence intervals (CIs) were used as the measures of association between treatment and outcome. RESULTS: Four studies were included. One study showed a reduced risk of ASPSS after ischemic stroke (OR: 0.25; 95% CI: 0.10-0.59; p = 0.0016). Three studies consistently reported a reduced risk of PSE after ischemic stroke, and one study a reduced risk of PSE after hemorrhagic stroke (HR: 0.62; 95% CI: 0.42-0.90; p = 0.01). CONCLUSIONS: Data from the literature suggest an association between statin use and a reduced risk of ASPSS after ischemic stroke and a reduced risk of PSE after ischemic and hemorrhagic stroke. Although the certainty of the evidence is low, these findings appear promising and worthy of further investigation.

Predictive value of acute EEG measurements for seizures and epilepsy after stroke using a dry cap electrode EEG system - Study design and proof of concept.

The development of seizures is a common complication in patients with stroke. A recent study suggests that electroencephalography (EEG) could be useful to predict the occurrence of seizures after stroke. However, EEG is not routinely performed in the follow-up after stroke. We present the design and proof of concept of a large prospective cohort study in which we seek to evaluate the predictive usefulness of a single dry cap EEG measurement in the acute phase after stroke or transient ischemic attack (TIA) with respect to the development of poststroke epilepsy (PSE). In patients with ischemic stroke (IS), TIA, or intracerebral hemorrhage (ICH), an acute EEG measurement using a dry cap electrode EEG (dEEG) system is performed within 7 days of symptom onset. Electroencephalography data will be analyzed quantitatively and qualitatively looking for background asymmetry, different band power ratios, and epileptiform activity. The development of seizures will be assessed repeatedly during the first 2 years after stroke or TIA using a validated questionnaire. Results from the pilot phase of 11 patients showed that the dry cap EEG measurements in patients with acute stroke and TIA are feasible. In comparison with conventional EEG, a higher proportion of noise and artifacts was detected. This article is part of the Special Issue "Seizure & Stroke".

Cognition and quality of life in patients with poststroke epilepsy: A case-control study.

INTRODUCTION: Though seizures are a common complication after stroke, only little scientific evidence is available about the impact of epilepsy on cognitive functioning and quality of life in patients who have had a stroke. Therefore, we assessed these items in a case-control study. METHODS: We studied 36 patients with poststroke epilepsy (PSE) and 36 matched patients who have had a stroke without epilepsy using parts of the FePsy (the computerized visual searching task (CVST) for central information processing speed and a reaction time test), the mini-mental-state examination (MMSE), the EuroQol, the stroke-adapted Sickness Impact Profile questionnaire (SA-SIP-30), the Barthel index, the modified Rankin scale, and the National Institutes of Health stroke scale (NIHSS). RESULTS: Patients with PSE had significantly lower scores on the CVST and MMSE. Generic quality of life was the same in patients with poststroke epilepsy and patients with stroke only, however, the SA-SIP-30 showed a lower disease-specific quality of life in patients with poststroke epilepsy. The Barthel index showed no difference between both groups, but both the modified Rankin scale and the NIHSS were significantly higher in patients with poststroke epilepsy, indicating more disability and neurological impairment in patients with PSE. CONCLUSIONS: We found that PSE relates to impaired cognitive functioning, a lower disease-specific quality of life and more disability and neurological impairment. This underlines the importance of further clinical research in this field. This article is part of the Special Issue "Seizures & Stroke".

Status epilepticus mimicking stroke recurrence.

AIM OF THE STUDY: The aim of the study was to evaluate the clinical characteristics of patients with previous stroke (either ischemic or hemorrhagic), who developed status epilepticus (SE) mimicking a stroke relapse. MATERIALS AND METHODS: We performed a retrospective cohort study of patients brought to hospital by the emergency service between December 2016 and January 2018 with a stroke code as possible candidates for intravenous thrombolysis and who had already have a previous stroke. Among them, patients admitted for negative symptoms and finally discharged with a diagnosis of SE mimicking stroke were selected and their clinical characteristics collected. All patients underwent routine blood sample analysis, head computed tomography (CT) scan and, when indicated, CT angiography and CT-perfusion imaging of the head. After admission in our stroke unit, an Electroencephalogram (EEG) was performed within 3 h in patients suspected with SE, then classified according to International League Against Epilepsy (ILAE) classification (2015). Outcome measures were SE duration, antiepileptic drugs (AEDs) administered, mortality at 12 months, Engel scale, and modified Rankin scale (m-RS) at 6 months. A second cohort included those consecutive patients discharged with a true stroke relapse in the same considered time span. Clinical characteristics of these two cohorts were compared using Mann-Whitney test or Student t-test (Confidence Interval (C.I.) 95%, p < 0.05) for continuous variable and Fisher exact test or Pearson-Chi test for dichotomic variables (p < 0.05). Survival rates were calculated, and a Log-Rank test was performed to evaluate differences in survival distribution. Only in the group with SE, m-RS at 6 months and recurrence of SE were also evaluated. RESULTS: Eleven patients were discharged with a diagnosis of SE mimicking stroke and 65 patients with stroke relapse. Temporal lobe localization was significantly more represented in group with SE (p = 0.036) while there was no difference regarding age, sex, and National Institutes of Health Stroke Scale (NIHSS). The m-RS was significantly higher in patients with hemorrhage relapse, mainly due to the high incidence of amyloid angiopathy in this subgroup. Status epilepticus recurred in 36.4% of patients, presenting with the same clinical features, and most patients (62.5%) achieved a good seizure control at 6 months (Engel scale = 1). A difference in mortality at 12 months (all cause considered) appeared only when distinguishing strokes between ischemic and hemorrhagic (Chi-Square: 10.711, p < 0.005). DISCUSSION AND CONCLUSION: Status epilepticus is not infrequent in patients with previous stroke and may present with negative neurological symptoms, thus mimicking a stroke recurrence. EEG should be considered as a potential diagnostic tool in the acute stroke setting, at least in patients with previous stroke. This article is part of the Special Issue "Seizures & Stroke".

Modeling poststroke epilepsy and preclinical development of drugs for poststroke epilepsy.

Stroke is a severe clinical issue for global public health, representing the third leading cause of death and a major cause of disability in developed countries. Progresses in the pharmacological treatment of the acute stroke have given rise to a significant decrease in its mortality rate. However, as a result, there has been an increasing number of stroke survivors living with disability worldwide. Poststroke epilepsy (PSE) is a common clinical complication following stroke. Seizures can arise in close temporal association with stroke damage and/or after a variably longer interval. Overall, PSE have a good prognosis; in fact, its responding rate to antiepileptic drugs (AEDs) is higher than other types of epilepsy. However, regarding pharmacological treatment, some issues are still unresolved. To this aim, a deeper understanding of mechanisms underlying the transformation of infarcted tissue into an epileptic focus or better from a nonepileptic brain to an epileptic brain is also mandatory for PSE. However, studying epileptogenesis in patients with PSE clearly has several limitations and difficulties; therefore, modeling PSE is crucial. Until now, different experimental models have been used to study the etiopathology of cerebrovascular stroke with or without infarction, but few studies focused on poststroke epileptogenesis and PSE. In this review, we show a brief overview on the features emerging from preclinical research into experimental PSE, which could affect the discovery of biomarkers and therapy strategies for poststroke epileptogenesis. This article is part of the Special Issue "Seizures & Stroke".

Association between hemorrhagic transformation after endovascular therapy and poststroke seizures.

OBJECTIVE: Endovascular therapy has recently become standard therapy for select patients with acute ischemic stroke. Infarcted brain tissue may undergo hemorrhagic transformation (HT) after endovascular therapy. We investigated the association between HT and occurrence of poststroke seizures in patients treated with endovascular therapy. METHODS: Consecutive patients treated with endovascular therapy for acute anterior circulation ischemic stroke were included. HT was assessed with computed tomography/magnetic resonance imaging (CT/MRI) at 24 h after stroke onset. Patients were followed for up to 2 years for seizure occurrence. RESULTS: A total of 205 (57.1% male) patients were analyzed. Median age was 69 years (interquartile range [IQR] 57-78). Among patients with HT, 17.9% (10/56) developed poststroke seizures compared with 4.0% (6/149) among those without HT (hazard ratio [HR] 5.52; 95% confidence interval [CI] 2.00-15.22; P = .001). The association remained significant after adjustment for cortical involvement, baseline National Institutes of Health Stroke Scale score, age and use of intravenous tissue plasminogen activator and clot retrieval (HR 4.85; 95% CI 1.60-14.76; P = .005). In patients who developed seizures within the follow-up period, median time to first seizure was 111 days (IQR 28-369) in patients with HT and 36 days (IQR 0.5-183) in patients without HT. SIGNIFICANCE: A patient who develops HT following endovascular therapy for acute ischemic stroke had a nearly 5 times higher rate of developing poststroke seizures within 2 years. HT may be used as an imaging biomarker for poststroke seizures.

Health-related quality of life in patients with poststroke epilepsy.

BACKGROUND: Lesional epilepsy is an important long-term sequela of stroke. Data on health-related quality of life (HrQoL) in patients with poststroke epilepsy are limited. We investigated HrQoL in patients with epilepsy after ischemic stroke and identified independent HrQoL-determinants. METHODS AND PATIENTS: All patients with acute ischemic stroke, who were permanent residents in the district Marburg-Biedenkopf (Hessia, Germany, reference population 240,000 inhabitants) were recruited within 12months in the population-based Marburg Stroke Register (MARSTREG). Follow-up visits were performed after 6, 12, and 24months, and patients who developed poststroke epilepsy were identified. Data on demographics, antiepileptic drugs (AEDs), stroke severity (National Institute of Heath Stroke Scale (NIHSS), Barthel-Index, modified Rankin Scale), depression (Geriatric Depression Scale), and HrQoL (EQ-5D and EQ VAS) were collected. A multiple regression analysis was performed to identify HrQoL-determinants. RESULTS: Among the study participants (n=374), 23 (6.1%) developed poststroke epilepsy. The HrQoL of patients with poststroke epilepsy was reduced in comparison with patients without seizures (24-month follow-up: EuroQol Visual Analogue Scale (EuroQol-VAS): 55.3±10.7 versus 64.2±11.4, p=0.03). Seizure frequency, depression, and functional impairment (Barthel-Index) were identified as independent determinants of HrQoL. The adjustment of AEDs between 6-month and 24-month follow-ups resulted in decrease of seizure frequency by 40% and reduction of complications (dizziness by 27.8%, nausea by 52.2%, fatigue by 84.2%). CONCLUSION: Lesional epilepsy is associated with decreased HrQoL in patients with stroke. We identified HrQoL-determinants, which would improve the management of patients with poststroke epilepsy. These determinants include proper adjustment of AEDs with reduction of seizure frequency, treatment of depression, and focused rehabilitation programs for poststroke epilepsy.

Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Is Associated With a Reduced Risk of Poststroke Epilepsy in Patients With Ischemic Stroke.

BACKGROUND: Poststroke epilepsy (PSE) is a common complication after ischemic stroke. This study investigates the association between the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) and the risk of PSE in patients with ischemic stroke. METHODS AND RESULTS: A population-based retrospective cohort study was conducted using Taiwan's National Health Insurance Research Database between 2000 and 2015. Patients with hypertension with a history of ischemic stroke were classified into prevalent, new, and nonusers according to their use of ACEIs/ARBs. Prevalent ACEI/ARB users were further classified into continuing or discontinued users, based on their poststroke medication adherence. We used multivariate Cox regression models, adjusted for demographics and comorbidities, to assess the risk of PSE among different ACEI/ARB user groups. There were 182 983 ACEI/ARB users and 38 365 nonusers included. There were 7387 patients diagnosed with PSE, whereas 213 961 were not. Nonusers exhibited a higher risk of PSE (adjusted hazard ratio [aHR], 1.72 [95% CI, 1.63-1.82]). Both prevalent and nonusers had higher risks compared with new ACEI/ARB users, with respective aHRs of 1.33 (95% CI, 1.25-1.41) and 2.00 (95% CI, 1.87-2.14). Discontinued ACEI/ARB users showed the highest risk of PSE (aHR, 2.34 [95% CI, 2.15-2.54]), suggesting the importance of continuing ACEI/ARB use after stroke. Treatment-by-age interaction was significant among patients with or without ACEI/ARB use before stroke (P value for interaction 0.004 and <0.001, respectively), suggesting a stronger beneficial association in younger patients. CONCLUSIONS: The use of ACEIs/ARBs after ischemic stroke in patients with hypertension is associated with a reduced risk of PSE, especially among younger patients.

Eslicarbazepine acetate for the treatment of status epilepticus.

OBJECTIVE: Due to the high mortality of patients with refractory status epilepticus (SE), new antiseizure medications (ASMs) are needed to improve long-term outcomes. In this study, we evaluated the efficacy and safety of eslicarbazepine acetate (ESL), a new sodium channel blocker, based on the data from a large epilepsy register. METHODS: Data on the efficacy and safety of ESL for the treatment of refractory SE were gathered from the Mainz Epilepsy Registry (MAINZ-EPIREG). Logistic regression was applied to identify predictors of status interruption. RESULTS: In total, 64 patients with remote symptomatic refractory SE were treated with ESL. No cases of idiopathic generalized epilepsy were included. The average age was 61.4 ± 11.0 years. The median number of administered ASMs before the start of ESL was three. On average, 2 days had elapsed since the onset of SE before the administration of ESL. The initial dose of 800 mg/day was increased up to a maximum daily dose of 1600 mg in case of nonresponse. In 29 of 64 patients (45.3%), the SE could be interrupted within 48 h of ESL therapy. In patients with poststroke epilepsy, the control of SE was achieved in 62% of patients (15/23). The earlier initiation of ESL therapy was an independent predictor of control of SE. Hyponatraemia occurred in five patients (7.8%). Other side effects were not observed. SIGNIFICANCE: Based on these data, ESL may be used as an adjunct therapy for the treatment of refractory SE. The best response was found in patients with poststroke epilepsy. In addition, early initiation of ESL therapy appears to result in better control of SE. Besides a few cases of hyponatraemia, no other adverse events were detected.

Incidence, temporal profile and neuroanatomic correlates of poststroke epilepsy.

BACKGROUND AND PURPOSE: The relationship between ischemic stroke site and occurrence of poststroke epilepsy (PSE) is incompletely understood. This study intended to evaluate incidence and temporal profiles of seizures and to correlate ischemic lesion sites with PSE using voxel-based lesion symptom mapping (VLSM). METHODS: Patients with imaging-confirmed first-ever ischemic stroke without prior history of epilepsy were prospectively included. Demographic data, cardiovascular risk factors, and National Institute of Health Stroke Scale (NIHSS) scores were assessed. Data on seizures and modified Rankin scale scores were determined within a 90-day period after stroke onset. Ischemic lesion sites were correlated voxel wise with occurrence of PSE using nonparametric permutation test. Age- and sex-matched patients with first-ever ischemic strokes without PSE after 90 days served as controls for the VLSM analysis. RESULTS: The stroke database contained 809 patients (mean age: 68.4 ± 14.2 years) with first-ever imaging-confirmed ischemic strokes without history of epilep. Incidence of PSE after 90-day follow-up was 2.8%. Five additional patients were admitted to the emergency department with a seizure after 90-day follow-up. Fifty percent of the seizures occurred in the acute phase after stroke. PSE patients had higher NIHSS scores and infarct volumes compared to controls without PSE (p < .05). PSE patients had infarcts predominantly involving the cerebral cortex. The hemisphere-specific VLSM analysis shows associations between PSE and damaged voxels in the left-hemispheric temporo-occipital transition zone. CONCLUSIONS: The data indicate that PSE occurs in a small proportion of patients with rather large ischemic strokes predominantly involving the cerebral cortex. Especially patients with ischemic lesions in the temporo-occipital cortex are vulnerable to develop PSE.

Frequency and predictors of poststroke epilepsy after mechanical thrombectomy for large vessel occlusion stroke: results from a multicenter cohort study.

BACKGROUND: Poststroke epilepsy (PSE) represents an important complication of stroke. Data regarding the frequency and predictors of PSE in patients with large-vessel occlusion stroke receiving mechanical thrombectomy (MT) are scarce. Furthermore, information on acute and preexisting lesion characteristics on brain MRI has not yet been systematically considered in risk prediction of PSE. This study thus aims to assess PSE risk after acute ischemic stroke treated with MT, based on clinical and MRI features. METHODS: In this multicenter study from two tertiary stroke centers, we included consecutive acute ischemic stroke patients who had received MT for acute intracranial large vessel occlusion (LVO) between 2011 and 2017, in whom post-interventional brain MRI and long term-follow-up data were available. Infarct size, affected cerebrovascular territory, hemorrhagic complications and chronic cerebrovascular disease features were assessed on MRI (blinded to clinical information). The primary outcome was the occurrence of PSE (> 7 days after stroke onset) assessed by systematic follow-up via phone interview or electronic records. RESULTS: Our final study cohort comprised 348 thrombectomy patients (median age: 67 years, 45% women) with a median long-term follow-up of 78 months (range 0-125). 32 patients (9%) developed PSE after a median of 477 days (range 9-2577 days). In univariable analyses, larger postinterventional infarct size, infarct location in the parietal, frontal or temporal lobes and cerebral microbleeds were associated with PSE. Multivariable Cox regression analysis confirmed larger infarct size (HR 3.49; 95% CI 1.67-7.30) and presence of cerebral microbleeds (HR 2.56; 95% CI 1.18-5.56) as independent predictors of PSE. CONCLUSION: In our study, patients with large vessel occlusion stroke receiving MT had a 9% prevalence of PSE over a median follow-up period of 6.5 years. Besides larger infarct size, presence of cerebral microbleeds on brain MRI predicted PSE occurrence.

Identification of disordered profiles of gut microbiota and functional component in stroke and poststroke epilepsy.

AIMS: It is estimated that 11.5% of patients with stroke (STR) were at risk of suffering poststroke epilepsy (PSE) within 5 years. Gut microbiota is shown to affect health in humans by producing metabolites. The association between dysregulation of gut microbiota and STR/PSE remains unclear. The aim of this study was to identify potential gut microbiota and functional component in STR and PSE, which may provide a theoretical foundation for diagnosis and treatment of STR and PSE. METHODS: The fresh stool samples were collected from 19 healthy controls, 27 STR patients, and 20 PSE patients for 16S rRNA gene sequencing. Analysis of amplicon sequence variant and community diversity was performed, followed by the identification of dominant species, species differences analysis, diagnostic, and functional analysis of species in STR and PSE. RESULTS: Community diversity was decreased in STR and PSE. Some disordered profiles of gut microbiota in STR and PSE were identified, such as the increase of Enterococcus and the decrease of butyricicoccus in STR, the increase of Escherichia Shigella and Clostridium innocuum-group and the decrease of Faecalibacterium in PSE, and the decrease of Anaerostipes in both STR and PSE. Moreover, potential diagnostic biomarkers for STR (butyricicoccus), PSE (Faecalibacterium), STR, and PSE (NK4A214_group and Veillonella) were identified. Several significantly dysfunctional components were identified, including l-tryptophan biosynthesis in STR, fatty acid biosynthesis in PSE, and Stress_Tolerant and anaerobic in both STR and PSE. CONCLUSION: The disturbed gut microbiota and related dysfunctional components are closely associated with the progression of STR and PSE.

The Primary Prevention of Poststroke Epilepsy in Patients With Middle Cerebral Artery Infarct: Protocol for a Randomized Controlled Trial.

BACKGROUND: Poststroke epilepsy poses a significant clinical challenge for individuals recovering from strokes, leading to a less favorable long-term outlook and increased mortality rates. Existing studies have primarily concentrated on administering antiseizure or anticonvulsant treatments only after the onset of late-onset seizures, without intervening during the epileptogenesis phase following a stroke. OBJECTIVE: This research protocol is designed to conduct a randomized controlled trial to assess whether the early, preventive introduction of low-dose antiepileptic drug therapy (levetiracetam [LEV] or perampanel [PER]) in patients who have experienced middle cerebral artery (MCA) infarction can reduce the risk of developing poststroke epilepsy (primary prevention). METHODS: Participants with MCA infarction, either with or without reperfusion treatments, will be recruited and promptly receive preventive intervention within 72 hours of the stroke occurrence. These participants will be randomly assigned to receive either PER (4 mg per day), LEV (1000 mg per day), or a placebo that matches the active drugs. This treatment will continue for 12 weeks after allocation. Brain magnetic resonance imaging will be used to confirm the presence of MCA territory infarction, and an electroencephalography will be used to ensure the absence of epileptiform discharges or electrographic seizures at the time of the stroke. All participants will undergo follow-up assessments for 72 weeks after allocation. RESULTS: The primary outcome under evaluation will be the incidence of poststroke epilepsy in the 3 groups following the 18-month study period. Secondary outcomes will encompass the time to the occurrence of the first seizure, the severity of seizures, any treatment-related adverse events, and the modified Rankin scale score at 3 and 18 months. Exploratory outcomes will involve comparing the effectiveness and safety of PER and LEV. CONCLUSIONS: We anticipate that the intervention groups will experience a lower incidence and reduced severity of poststroke epilepsy compared to the control group after 18 months. We aim to establish evidence supporting the potential preventive effects of LEV and PER on poststroke seizures and epilepsy in patients with MCA infarction, as well as to explore the antiepileptogenic potential of both LEV and PER in patients with major ischemic strokes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04858841; https://clinicaltrials.gov/study/NCT04858841. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49412.

Interictal epileptiform discharges as a predictive biomarker for recurrence of poststroke epilepsy.

Poststroke epilepsy is a major ischaemic/haemorrhagic stroke complication. Seizure recurrence risk estimation and early therapeutic intervention are critical, given the association of poststroke epilepsy with worse functional outcomes, quality of life and greater mortality. Several studies have reported risk factors for seizure recurrence; however, in poststroke epilepsy, the role of EEG in predicting the risk of seizures remains unclear. This multicentre observational study aimed to clarify whether EEG findings constitute a risk factor for seizure recurrence in patients with poststroke epilepsy. Patients with poststroke epilepsy were recruited from the PROgnosis of POst-Stroke Epilepsy study, an observational multicentre cohort study. The enrolled patients with poststroke epilepsy were those admitted at selected hospitals between November 2014 and June 2017. All patients underwent EEG during the interictal period during admission to each hospital and were monitored for seizure recurrence over 1 year. Board-certified neurologists or epileptologists evaluated all EEG findings. We investigated the relationship between EEG findings and seizure recurrence. Among 187 patients with poststroke epilepsy (65 were women with a median age of 75 years) admitted to the lead hospital, 48 (25.7%) had interictal epileptiform discharges on EEG. During the follow-up period (median, 397 days; interquartile range, 337-450 days), interictal epileptiform discharges were positively correlated with seizure recurrence (hazard ratio, 3.82; 95% confidence interval, 2.09-6.97; P < 0.01). The correlation remained significant even after adjusting for age, sex, severity of stroke, type of stroke and generation of antiseizure medications. We detected periodic discharges in 39 patients (20.9%), and spiky/sharp periodic discharges were marginally associated with seizure recurrence (hazard ratio, 1.85; 95% confidence interval, 0.93-3.69; P = 0.08). Analysis of a validation cohort comprising 187 patients with poststroke epilepsy from seven other hospitals corroborated the association between interictal epileptiform discharges and seizure recurrence. We verified that interictal epileptiform discharges are a risk factor for seizure recurrence in patients with poststroke epilepsy. Routine EEG may facilitate the estimation of seizure recurrence risk and the development of therapeutic regimens for poststroke epilepsy.