Thrombolysis for Wake-Up Stroke Versus Non-Wake-Up Unwitnessed Stroke: EOS Individual Patient Data Meta-Analysis.

BACKGROUND: Stroke with unknown time of onset can be categorized into 2 groups; wake-up stroke (WUS) and unwitnessed stroke with an onset time unavailable for reasons other than wake-up (non-wake-up unwitnessed stroke, non-WUS). We aimed to assess potential differences in the efficacy and safety of intravenous thrombolysis (IVT) between these subgroups. METHODS: Patients with an unknown-onset stroke were evaluated using individual patient-level data of 2 randomized controlled trials (WAKE-UP [Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke], THAWS [Thrombolysis for Acute Wake-Up and Unclear-Onset Strokes With Alteplase at 0.6 mg/kg]) comparing IVT with placebo or standard treatment from the EOS (Evaluation of Unknown-Onset Stroke Thrombolysis trial) data set. A favorable outcome was prespecified as a modified Rankin Scale score of 0 to 1 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage at 22 to 36 hours and 90-day mortality. The IVT effect was compared between the treatment groups in the WUS and non-WUS with multivariable logistic regression analysis. RESULTS: Six hundred thirty-four patients from 2 trials were analyzed; 542 had WUS (191 women, 272 receiving alteplase), and 92 had non-WUS (42 women, 43 receiving alteplase). Overall, no significant interaction was noted between the mode of onset and treatment effect (P value for interaction=0.796). In patients with WUS, the frequencies of favorable outcomes were 54.8% and 45.5% in the IVT and control groups, respectively (adjusted odds ratio, 1.47 [95% CI, 1.01-2.16]). Death occurred in 4.0% and 1.9%, respectively (P=0.162), and symptomatic intracranial hemorrhage in 1.8% and 0.3%, respectively (P=0.194). In patients with non-WUS, no significant difference was observed in favorable outcomes relative to the control (37.2% versus 29.2%; adjusted odds ratio, 1.76 [0.58-5.37]). One death and one symptomatic intracranial hemorrhage were reported in the IVT group, but none in the control. CONCLUSIONS: There was no difference in the effect of IVT between patients with WUS and non-WUS. IVT showed a significant benefit in patients with WUS, while there was insufficient statistical power to detect a substantial benefit in the non-WUS subgroup. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: CRD42020166903.

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.

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.

Tmax Mismatch Ratio to Identify Intracranial Atherosclerotic Stenosis-Related Large-Vessel Occlusion Before Endovascular Therapy.

Background We aimed to clarify which time-to-maximum of the tissue residue function (Tmax) mismatch ratio is useful in predicting anterior intracranial atherosclerotic stenosis (ICAS)-related large-vessel occlusion (LVO) before endovascular therapy. Methods and Results Patients with ischemic stroke who underwent perfusion-weighted imaging before endovascular therapy for anterior intracranial LVO were divided into those with ICAS-related LVO and those with embolic LVO. Tmax ratios of >10 s/>8 s, >10 s/>6 s, >10 s/>4 s, >8 s/>6 s, >8 s/>4 s, and >6 s/>4 s were considered Tmax mismatch ratios. Binominal logistic regression was used to identify ICAS-related LVO, and the adjusted odds ratio (aOR) and 95% CI for each Tmax mismatch ratio increase of 0.1 were calculated. A similar analysis was performed for ICAS-related LVO with and without embolic sources, using embolic LVO as the reference. Of 213 patients (90 women [42.0%]; median age, 79 years), 39 (18.3%) had ICAS-related LVO. The aOR (95% CI) per 0.1 increase in Tmax mismatch ratio in ICAS-related LVO with embolic LVO as reference was lowest with Tmax mismatch ratio >10 s/>6 s (0.56 [0.43-0.73]). Multinomial logistic regression analysis also showed the lowest aOR (95% CI) per 0.1 increase in Tmax mismatch ratio with Tmax >10 s/>6 s (ICAS-related LVO without embolic source: 0.60 [0.42-0.85]; ICAS-related LVO with embolic source: 0.55 [0.38-0.79]). Conclusions A Tmax mismatch ratio of >10 s/>6 s was the optimal predictor of ICAS-related LVO compared with other Tmax profiles, with or without an embolic source before endovascular therapy. Registration clinicaltrials.gov. Identifier NCT02251665.

[Cerebral venous sinus thrombosis presenting transient ischemic attack after recovery from COVID-19 with Graves' disease and IgG4-related ophthalmic disease: a case report].

A 57-year-old man presented with headache, transient right upper extremity weakness and numbness one month after recovery from coronavirus disease 2019 (COVID-19). His medical history included Graves' disease and IgG4-related ophthalmic disease. He had been administered prednisolone. His weakness and numbness were transient and not present on admission. Contrast-enhanced CT and MRI of the head showed thrombi in the superior sagittal sinus, right transverse sinus, sigmoid sinus, and the right internal jugular vein. Digital subtraction angiography showed occlusion at the same sites and mild perfusion delay in the left frontoparietal lobe. We diagnosed the patient with cerebral venous sinus thrombosis and treated him with anticoagulation. The thrombi partially regressed three months later, and perfusion delay became less noticeable. Cerebral venous sinus thrombosis is an important complication of COVID-19. Patients with predisposing factors, including Graves' disease and IgG4-related ophthalmic disease, may be at increased risk of developing cerebral venous sinus thrombosis even after recovery from COVID-19.

Identifying large ischemic core volume ranges in acute stroke that can benefit from mechanical thrombectomy.

BACKGROUND: We aimed to identify the large ischemic core (LIC) volume ranges in acute ischemic stroke patients that can benefit from mechanical thrombectomy (MT). METHODS: Consecutive patients within 24 hours of onset of anterior circulation ischemic stroke with large vessel occlusion and ischemic core volumes of 70-300 mL were included from our single-center prospective database from March 2014 to December 2019. Subjects were divided into three groups by baseline ischemic core volume (A: 70-100 mL; B: 101-130 mL; C: >130 mL). We compared modified Rankin Scale (mRS) score 0-2 at 3 months and parenchymal hematoma between patients receiving MT and standard medical treatment (SMT), and determined clinically treatable core volume ranges for MT. RESULTS: Of 157 patients (86 women; median age, 81 years; median ischemic core volume, 123 mL), 49 patients underwent MT. In Group A (n=52), MT patients (n=31) showed a higher proportion of mRS 0-2 at 3 months (52% vs 5%, P<0.05) versus SMT, respectively. Group B (n=36) MT patients (n=14) also had a higher proportion of mRS 0-2 at 3 months (29% vs 9%, P=0.13) versus SMT, respectively. In Group C (n=69), only four patients received MT. The 95% confidence intervals for the probability of mRS 0-2 at 3 months in patients with MT (n=49) versus SMT (n=108) intersected at 120-130 mL. CONCLUSIONS: Ischemic core volumes between 70 and 100 mL may benefit from MT. The treatable upper core limit is approximately 120 mL in selected patients with LIC of 70-300 mL.

Blind Exchange With Mini-Pinning Technique Using the Tron Stent Retriever for Middle Cerebral Artery M2 Occlusion Thrombectomy in Acute Ischemic Stroke.

Introduction: The usefulness of the blind exchange with mini-pinning (BEMP) technique has recently been reported for mechanical thrombectomy in patients with stroke owing to medium vessel occlusion (MeVO). The Tron stent retriever can be delivered and deployed through a 0.0165-inch microcatheter. This retriever has potential as an effective and safe treatment for acute ischemic stroke (AIS) due to occlusion of the M2 segment of the middle cerebral artery (MCA). Here, we report the outcomes of the BEMP technique using Tron stent retrievers for M2 occlusion thrombectomy. Methods: Consecutive patients with AIS owing to M2 occlusion who underwent the BEMP technique using 2 × 15-mm or 4 × 20-mm Tron stent retrievers were included. The technique involves deploying a Tron stent retriever through a 0.0165-inch microcatheter, followed by microcatheter removal and blind navigation of a 3MAX or 4MAX aspiration catheter over the bare Tron delivery wire until the aspiration catheter reaches the clot. A Tron stent retriever is inserted into the aspiration catheter like a cork and subsequently pulled as a unit. We assessed procedural outcomes [first-pass expanded thrombolysis in cerebral infarction (eTICI) score 2c/3 and 2b/2c/3], safety outcomes [symptomatic intracranial hemorrhage (sICH)], and clinical outcomes (good outcome rate defined as modified Rankin Scale score 0-2 at 90 days and mortality at 90 days). Results: Eighteen M2 vessels were treated in 15 patients (six female, median age: 80 years, and median National Institutes of Health Stroke Scale score: 18). The BEMP technique was performed successfully in all cases. Whether to use a 3MAX or 4MAX catheter was determined by considering one of the following target vessels: dominant, non-dominant, or co-dominant M2 (3MAX, n = 9; 4MAX, n = 9). The first-pass eTICI 2c/3 and 2b/2c/3 rates were 47 (7/15) and 60% (9/15), respectively; sICH was not observed. Seven patients (47%) achieved good outcomes, and one patient (7%) died within 90 days. Conclusions: The Tron stent retriever was safely and effectively used in the BEMP technique for acute MCA M2 occlusion and can be combined with a 0.0165-inch microcatheter, which may be useful for treating MeVO, in general.

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.

[MRI and intravenous thrombolysis for unclear-onset stroke during the COVID-19 pandemic: a case report].

During the COVID-19 pandemic in 2020, an 81-year-old afebrile woman was transported to our institute at 44 minutes after she was found to have global aphasia and weakness of the right extremities. The onset time was unclear. CT showed an occlusion of the left middle cerebral artery without early ischemic changes. MRI revealed a negative fluid-attenuated inversion recovery (FLAIR) pattern, in which several small acute infarcts were seen in diffusion-weighted images with no corresponding hyperintensity lesions on FLAIR. Accordingly, intravenous thrombolysis with alteplase (0.6 mg/kg, the dose approved in Japan) was administered at 1,660 minutes after the last known well and 116 minutes after the symptom recognition. An immediate internal carotid angiogram showed severe stenosis at the distal end of the horizontal portion of the left middle cerebral artery. In the follow-up angiogram at 164 minutes after the symptom recognition, the stenotic lesion almost resolved with the restoration of quick and nearly complete antegrade flow. Her symptoms also resolved promptly. Although the use of MRI is recommended to be minimized in the emergency stroke management during the COVID-19 pandemic, MRI is occasionally mandatory for patient selection, such as cases with unclear onset to perform intravenous thrombolysis. The individualized protected code stroke is essential and must be well considered by each institute for diagnosing patients by selecting appropriate modalities.

Use of Diffusion-Weighted Imaging-Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS) and Ischemic Core Volume to Determine the Malignant Profile in Acute Stroke.

Background Malignant profiles were identified by imaging profiles and unfavorable outcomes that have poor response to reperfusion therapy. Many trials have used this profile in their inclusion criteria including large-vessel occlusion acute ischemic stroke trials. We aimed to redefine the cutoff values for malignant profile in acute ischemic stroke patients with large-vessel occlusion regardless of reperfusion therapy. Methods and Results Consecutive acute ischemic stroke patients with anterior large-vessel occlusion were prospectively extracted from the National Cerebral and Cardiovascular Center Stroke Registry between March 2014 and December 2017. Diffusion-Weighted Imaging-Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS) and diffusion-weighted imaging lesion ischemic core volume (VolDWI) were measured in acute ischemic stroke patients with large-vessel occlusion with or without treatment. Unfavorable outcome was defined as a modified Rankin Scale score 5 to 6 at 3 months, and optimal DWI-ASPECTS and VolDWI for unfavorable outcome were assessed. In total, 198 patients (111 men, 77±13 years old) were enrolled. Median DWI-ASPECTS was 7 (5-9), and median VolDWI was 55 (6-134) mL. Among the patients, 72 (36%) patients underwent reperfusion therapy, and 83 (42%) had unfavorable outcomes. The threshold values for a malignant profile on receiver operating characteristic curve analysis for DWI-ASPECTS and VolDWI were 4 (area under the curve 0.78, P<0.01; sensitivity 0.71, specificity 0.75) and 71 mL (area under the curve 0.80, P<0.01; sensitivity 0.76, specificity 0.77), respectively. Conclusions The cutoff values for our redefined malignant profile were DWI-ASPECTS 4 and VolDWI 71 mL with no selection bias for reperfusion therapy in the real-world clinical practice. Clinical Trial Registration URL: http://www.clinicaltrials.gov Unique identifier: NCT02251665.