Association of Cortical Superficial Siderosis with Post-Stroke Epilepsy.

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.

Nonconvulsive Status Epilepticus in Acute Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Patients with acute intracerebral hemorrhages (ICHs) often develop nonconvulsive status epilepticus (NCSE). We aimed to identify determinants and the prognostic significance of NCSE among patients with acute ICH. METHODS: Consecutive patients with acute spontaneous ICH who were admitted to a comprehensive stroke center were enrolled. We diagnosed NCSE using the modified Salzburg Consensus Criteria. Factors associated with NCSE and their significance in relation to clinical outcomes were assessed using multivariate logistic regression models. RESULTS: Of 228 patients (136 men; mean age, 68±14 years), 20 (8.8%) developed NCSE during their hospital stays. In logistic regression models, the adjusted odds ratios (95% confidence intervals) for NCSE were 3.5 (1.2-10.7) for craniotomy and 7.0 (2.2-31.2) for lobar involvement. The patients with NCSE had higher modified Rankin Scale scores at discharge, but NCSE was not independently associated with poor functional outcomes (modified Rankin Scale score, 4-5) or mortality after adjusting for confounders. CONCLUSIONS: NCSE is not a rare complication of acute ICH. Craniotomy and lobar involvement are independently associated with NCSE in patients with acute ICH.

Early Achievement of Blood Pressure Lowering and Hematoma Growth in Acute Intracerebral Hemorrhage: Stroke Acute Management with Urgent Risk-Factor Assessment and Improvement-Intracerebral Hemorrhage Study.

BACKGROUND: Previous studies have revealed that hematoma growth mainly occurs during the first 6 h after the onset of spontaneous intracerebral hemorrhage (ICH). Early lowering of blood pressure (BP) may be beneficial for preventing hematoma growth. However, relationships between timing of BP lowering and hematoma growth in ICH remain unclear. We investigated associations between timing of BP lowering and hematoma growth for ICH. METHODS: The Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI)-ICH Study was a multicenter, prospective, observational study investigating the safety and feasibility of early (within 3 h from onset) reduction of systolic BP (SBP) to < 160 mm Hg with intravenous nicardipine for acute hypertension in cases of spontaneous ICH. The present study was a post hoc analysis of the SAMURAI-ICH study. We examined relationships between time from onset, imaging, and initiation of treatment to target SBP achievement and hematoma growth (absolute growth ≥6 mL) in ICH patients. Target SBP achievement was defined as the time at which SBP first became < 160 mm Hg. RESULTS: Among 211 patients, hematoma growth was seen in 31 patients (14.7%). The time from imaging to target SBP and time from treatment to target SBP were significantly shorter in patients without hematoma growth than in those with (p = 0.043 and p = 0.032 respectively), whereas no significant difference was seen in time from onset to SBP < 160 mm Hg between groups (p = 0.177). Patients in the lower quartiles of time from imaging to target SBP and time from treatment to target SBP showed lower incidences of hematoma growth (p trend = 0.023 and 0.037 respectively). The lowest quartile of time from imaging to target SBP (< 38 min) was negatively associated with hematoma growth on multivariable logistic regression (OR 0.182; 95% CI 0.038-0.867; p = 0.032). CONCLUSIONS: Early achievement of target SBP < 160 mm Hg is associated with a lower risk of hematoma growth in ICH.

Two-Year Outcomes of Anticoagulation for Acute Ischemic Stroke With Nonvalvular Atrial Fibrillation　- SAMURAI-NVAF Study.

BACKGROUND: We determined the 2-year long-term risk-benefit profile in patients with stroke or transient ischemic attack (TIA) receiving warfarin or direct oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (NVAF) using a prospective, multicenter, observational registry in Japan.Methods and Results:NVAF patients within 7 days after onset of ischemic stroke/TIA were enrolled in 18 stroke centers. Outcome measures included ischemic and bleeding events and death in the 2-year follow-up period. We enrolled 1,116 patients taking either warfarin (650 patients) or DOACs (466 patients) at acute hospital discharge. DOAC users were younger and had lower National Institutes of Health Stroke Scale, CHADS2and discharge modified Rankin Scale scores than warfarin users (P<0.0001 each). Incidences of stroke/systemic embolism (adjusted hazard ratio, 1.07; 95% CI, 0.66-1.72), all ischemic events (1.13; 0.72-1.75), and ischemic stroke/TIA (1.58; 0.95-2.62) were similar between groups. Risks of intracranial hemorrhage (0.32; 0.09-0.97) and death (0.41; 0.26-0.63) were significantly lower for DOAC users. Infection was the leading cause of death, accounting for 40% of deaths among warfarin users. CONCLUSIONS: Stroke/TIA patients receiving DOACs for secondary prevention were younger and had lower stroke severity and risk indices than those receiving warfarin. Estimated cumulative incidences of stroke and systemic embolism within 2 years were similar between warfarin and DOACs users, but those of death and intracranial hemorrhage were significantly lower among DOAC users.

Risk Factors for Nonconvulsive Status Epilepticus after Stroke.

BACKGROUND: Status epilepticus (SE) sometimes occurs after stroke. SE is classified as convulsive SE (CSE) and nonconvulsive SE (NCSE). Clinical characteristics, outcomes, mortality, and recurrences of post-stroke NCSE are yet to be clarified. METHODS: We retrospectively identified post-stroke SE patients between April 2010 and September 2015, with follow-ups continued until March 2016. We compared baseline clinical characteristics (age, sex, past history of epilepsy, early seizure, stroke type, and localization) between the CSE and NCSE groups. We determined the Glasgow Outcome Scale (GOS) at discharge, along with the mortality and seizure recurrence rates for the two groups. RESULTS: We identified 300 consecutive post-stroke seizure patients admitted to our department. A total of 50 post-stroke SE patients (33 men; mean age, 71.6 ± 14.2 years; 38 CSE; 12 NCSE; 20 ischemic strokes; 23 intracerebral hemorrhages; 7 subarachnoid hemorrhages) were included. Multivariable analysis showed that cardioembolic stroke and frontal lesion were significant risk factors of NCSE after stroke. GOS (Scale 1/2/3/4/5) results at patient discharge showed there was no significant difference between the groups (CSE; 8/26.3/18.4/26.3/21%, NCSE; 0/25/33/25/17%). Follow-up in 31 patients (21 CSE, 10 NCSE, median 815 days, interquartile range 538-1,327 days), revealed that seizure recurred in 15 CSE patients (71%) and in 4 NCSE patients (40%). During the follow-up, 3 CSE patients (14%) and 2 NCSE patients (20%) died. Seizure recurrence and mortality were not significantly different between the 2 groups. CONCLUSION: Cardioembolic stroke and frontal lesion were significant risk factors of NCSE after stroke.

Urgent Detection of Acute Type A Aortic Dissection in Hyperacute Ischemic Stroke or Transient Ischemic Attack.

BACKGROUND AND PURPOSE: Urgent diagnosis of acute Stanford type A aortic dissection (AAD) in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) is sometimes challenging. We assessed predictive values for markers of AAD in patients with AIS or TIA. METHODS: Consecutive patients with AIS or TIA with AAD who presented to our emergency room within 4.5 hours of symptom onset between 2007 and 2014 were compared with patients without AAD seen between 2012 and 2014. RESULTS: Data were obtained for 24 patients with AIS or TIA with AAD (15 women; mean age, 75 ± 12 years) and 812 patients without AAD (305 women; mean age, 73 ± 12 years). Compared with patients without AAD, patients with AAD displayed significantly higher systolic blood pressure (SBP) laterality (30 ± 20 mm Hg versus 12 ± 11 mm Hg), initial D-dimer concentration (median 38.1 µg/mL versus 1.3 µg/mL), and mediastinal width-to-chest width (M/C) ratio on x-ray (.35 ± .05 versus .29 ± .05), and more frequently showed common carotid artery (CCA) dissection on carotid ultrasonography (84% versus 1%) and pericardial effusion on echocardiography (43% versus 0%). Sensitivity and specificity to identify AAD were 80% and 75% for SBP laterality 17 mm Hg or greater; 100% and 86% for D-dimer concentration 4.1 µg/mL or greater; 75% and 76% for M/C ratio .32 or greater; 84% and 99% for CCA dissection; and 43% and 100% for pericardial effusion, respectively. CONCLUSIONS: High D-dimer level may provide the most reliable screening test for AAD in patients with AIS or TIA. CCA dissection on ultrasonography appears to represent the most disease-specific finding and shows acceptable sensitivity.

Frequency and Detection of Stanford Type A Aortic Dissection in Hyperacute Stroke Management.

BACKGROUND AND PURPOSE: Acute Stanford type A aortic dissection (AAD) is a devastating aortic disease, and prompt diagnosis is sometimes difficult to make. Identification of AAD in suspected acute stroke patients is especially challenging. Nevertheless, the frequencies and predictive factors of AAD in suspected acute stroke patients have not been well investigated. The aim of this study was to elucidate the prevalence of and predictors for AAD in patients with suspected acute stroke. METHODS: From January 2012 through January 2013, consecutive patients who visited our emergency department (ED) due to suspected acute (<24 h from onset) stroke were retrospectively enrolled. Clinical parameters including systolic blood pressure (SBP) and laboratory data were collected. Frequency of AAD in suspected acute stroke patients and acute ischemic stroke (AIS) subjects were assessed, and factors associated with AAD among AIS patients were investigated. RESULTS: A total of 1,637 patients were included in this study. Five patients (0.31%, 95% CI 0.04-0.57) were diagnosed as having AAD. The prevalence of AAD in all AIS individuals during the study period was 1.09% (95% CI 0.14-2.05), and AAD accounted for 1.70% (95% CI 0.05-3.36) of AIS patients who appeared at the hospital within 4 h from onset. Most AAD patients presented with disturbed consciousness, and none of the AAD patients complained of chest pain. Neck ultrasonography detected an intimal flap in AAD patients. Two AAD cases died soon after ED arrival. The remaining 3 were promptly diagnosed as having AAD in the ED and underwent emergency surgery; all were discharged with only mild neurological symptoms. Low SBP in the right arm (cut-off value ≤110 mm Hg, sensitivity 100%, specificity 94.4%) and high D-dimer level (cut-off value ≥5.0 µg/ml, sensitivity 100%, specificity 91.7%) had high predictive values for detecting AAD in patients with AIS presenting within 4 h from onset. CONCLUSIONS: AAD was seen in 0.31% of suspected acute stroke patients and 1.70% of AIS patients presenting within 4 h from onset. AAD patients who were initially suspected as having acute stroke had severe neurological symptoms, including disturbance of consciousness, did not complain of typical chest pain, and when emergency surgery was performed, favorable neurological and survival outcomes were achieved. Low SBP in the right arm and high D-dimer level could predict AAD.

A Novel Mutation of VPS13D-related Disorders with Parkinsonism.

We herein report a case of VPS13D-related disorder with a novel homogeneous variant. A 58-year-old Japanese woman was referred to our hospital with slowly progressive gait disturbance and cognitive impairment. A neurological examination revealed decreased spontaneity, recent memory impairment, Parkinsonism, cerebellar ataxia, pyramidal signs, and autonomic dysfunction. Dopamine transporter single-photon-emission computed tomography showed a markedly reduced uptake in the striatum bilaterally. Whole-exome sequencing revealed a novel homozygous missense variant of the VPS13D gene (Arg3267Pro). Our case suggests that mutations in VPS13D may cause parkinsonism, in addition to the previously reported cerebellar ataxia and spastic paraplegia.

Impact of Seizure Recurrence on 1-Year Functional Outcome and Mortality in Patients With Poststroke Epilepsy.

BACKGROUND AND OBJECTIVES: The functional outcome and mortality of patients with poststroke epilepsy (PSE) have not been assessed in a prospective study. Previous reports have suggested that patients with PSE may suffer from prolonged functional deterioration after a seizure. In this study, we prospectively investigated the functional outcome and mortality of patients with PSE and analyzed the effect of seizure recurrence on the outcomes. METHODS: This is part of the Prognosis of Post-Stroke Epilepsy study, a multicenter, prospective observational cohort study, where 392 patients with PSE (at least 1 unprovoked seizure more than 7 days after the onset of the last symptomatic stroke) were followed for at least 1 year at 8 hospitals in Japan. This study included only PSE patients with a first-ever seizure and assessed their functional decline and mortality at 1 year. Functional decline was defined as an increase in modified Rankin Scale (mRS) score at 1 year compared with baseline, excluding death. The associations between the seizure recurrence and the outcomes were analyzed statistically. RESULTS: A total of 211 patients (median age of 75 years; median mRS score of 3) were identified. At 1 year, 50 patients (23.7%) experienced seizure recurrence. Regarding outcomes, 25 patients (11.8%) demonstrated functional decline and 20 (9.5%) had died. Most patients died of pneumonia or cardiac disease (7 patients each), and no known causes of death were directly related to recurrent seizures. Seizure recurrence was significantly associated with functional decline (odds ratio [OR] 2.96, 95% CI 1.25-7.03, p = 0.01), even after adjusting for potential confounders (adjusted OR 3.26, 95% CI 1.27-8.36, p = 0.01), but not with mortality (OR 0.79, 95% CI 0.25-2.48, p = 0.68). Moreover, there was a significant trend where patients with more recurrent seizures were more likely to have functional decline (8.7%, 20.6%, and 28.6% in none, 1, and 2 or more recurrent seizures, respectively; p = 0.006). DISCUSSION: One-year functional outcome and mortality of patients with PSE were poor. Seizure recurrence was significantly associated with functional outcome, but not with mortality. Further studies are needed to ascertain whether early and adequate antiseizure treatment can prevent the functional deterioration of patients with PSE.

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.

Antiseizure medications for post-stroke epilepsy: A real-world prospective cohort study.

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.

Statin treatment can reduce incidence of early seizure in acute ischemic stroke: A propensity score analysis.

A previous study showed early statin administration in patients with acute ischemic stroke (AIS) was associated with a lower risk of early-onset seizure (ES), which is a high risk of epilepsy, but this retrospective study design may not have eliminated confounding factor effects. We aimed to verify the determinants and prognostic significance of ES and clarify the effects of statin administration. Consecutive AIS patients without a history of epilepsy were enrolled. The relationship between ES (within 7 days of index-stroke) and statin treatment was assessed using multivariate and propensity scores (PS). Of 2,969 patients with AIS, 1,623 (54.6%) were treated with statin, and 66 (2.2%) developed ES. In logistic regression models, cortical stroke lesion [odds ratio (OR), 2.82; 95% confidence interval (CI), 1.29-7.28) and pre-morbid modified Rankin Scale (per 1 point) (OR, 1.39; 95% CI, 1.18-1.65) were higher risks for ES, while statin significantly reduced the risk of ES (OR, 0.44; 95% CI, 0.24-0.79). In accordance with PS-matching, statin treatment produced consistent results for ES after adjusting by inverse probability of treatment-weighting PS (OR, 0.41; 95% CI, 0.22-0.75). In conclusion, as previously, statin treatment was independently associated with a lower risk of ES in AIS.

Cerebrovascular imaging of cerebral ischemia in acute type A aortic dissection.

BACKGROUND AND PURPOSE: Stanford type A aortic dissection (AAD) sometimes causes acute ischemic stroke (AIS) or transient ischemic attack (TIA). There is little understanding of cerebrovascular imaging of AIS or TIA in patients with AAD. METHODS: Consecutive AIS/TIA patients with AAD who were admitted within 4.5 h of onset were reviewed. We compared findings of MRI/MRA between these and consecutive AIS/TIA patients without AAD within 4.5 h of onset. RESULTS: Seventeen AAD and 249 non-AAD patients were identified. Compared to non-AAD patients, AAD patients had infarcts more frequently in the right anterior cerebral artery (ACA) territory (18% vs. 2%, P = 0.007) and the right middle cerebral artery (MCA) territory (71% vs. 29%, P < 0.001). There was no difference between the groups regarding whether it was perforator or cortical infarct, single or multiple infarcts, unilateral or bilateral infarcts, or ischemic change extension. On the MRA imaging, the AAD patients more frequently had poor visualization of the right internal carotid artery (ICA) (47% vs. 6%, P < 0.001). After adjustment for sex, age and confounding factors, the right ACA territory infarct [odds ratio (OR), 12.2; 95% confidence interval (CI), 1.4-119.4], the MCA territory infarct (OR, 4.9; 95% CI, 1.0-25.0) and poor visualization of the right ICA (OR, 18.1; 95% CI, 4.0-101.9) were independently associated with AAD. CONCLUSION: In emergency AIS/TIA patients, right anterior circulation infarct and poor visualization of the right ICA on cerebrovascular imaging are potential imaging markers of AAD.

Risk factors for post-stroke seizure recurrence after the first episode.

PURPOSE: Seizure is a common complication after stroke. However, the clinical characteristics, treatment, and recurrence rates in patients with the first episode of post-stroke seizure remain unclarified. The aim of this study was to identify the predictors of seizure recurrence in those patients. METHOD: We retrospectively identified patients admitted to our hospital between July 2010 and June 2014 and followed-up until June 2015 because of the first episode of post-stroke seizure. We classified post-stroke seizure as early (within one week after stroke) or late (in the second week or later). We compared the baseline clinical characteristics and treatment between the groups and investigated the factors that determined seizure recurrence by Cox proportional hazards model. RESULTS: A total of 153 patients (84 men; mean age, 73.7±12.3years; 73 hemorrhagic and 80 ischemic strokes; 63 early and 90 late seizure) were included. Compared with the late seizure group, the early seizure group more frequently manifested with status epilepticus; tended to less often undergo stereotactic aspiration of hematoma; and less frequently used anti-epileptic drugs. During the observation period (median 364days, IQR 124-680days), 40 patients were lost to follow-up; subsequently, 113 patients were included in the analysis. The early seizure group had lower survival and seizure recurrence rates than the late seizure group. The factors significantly associated with seizure recurrence were presence of status epilepticus in the early group (HR 4.75, 95% CI 1.28-17.62) and younger age in the late seizure group (HR 0.95, 95% CI 0.93-0.99). CONCLUSIONS: In patients with post-stroke seizure, status epilepticus and younger age were the predictors of recurrence after early and late seizure, respectively.

[Angiographically documented hemorrhagic transformation of embolic stroke: A case report].

A 81-year-old man with rheumatoid vasculitis presented with total aphasia followed by right hemiplegia. The NIHSS score was 24. Diffusion weighted magnetic resonance imaging (DWI) demonstrated an acute infarct in the left middle cerebral artery (MCA) territory, and magnetic resonance angiogram (MRA) revealed left MCA M1 occlusion. We administrated recombinant tissue plasminogen activator (rt-PA) at 132 min after symptom onset, but symptom was not improved. Emergency neuroendovascular recanalization was conducted with Penumbra(®) system. After MCA was recanalized partially, extravasations appeared on left lenticulostriate arteries territory at 376 min from symptom onset. Multiple extravasations spread over perforating branches, and ventricular rupture recognized angiographically. After the procedure, head CT demonstrated hematoma on left basal ganglia territory with intraventricular bleeding. Rheumatoid vasculitis might affect hemorrhagic infarction in emergency neuroendovascular recanalization procedure, and careful choice of treatment would be required.