Thrombolysis for Acute Wake-Up and Unclear-Onset Strokes with Alteplase at 0.6 mg/kg in Clinical Practice: THAWS2 Study.

INTRODUCTION: The aim of this study was to determine the safety and efficacy of intravenous (IV) alteplase at 0.6 mg/kg for patients with acute wake-up or unclear-onset strokes in clinical practice. METHODS: This multicenter observational study enrolled acute ischemic stroke patients with last-known-well time >4.5 h who had mismatch between DWI and FLAIR and were treated with IV alteplase. The safety outcomes were symptomatic intracranial hemorrhage (sICH) after thrombolysis, all-cause deaths, and all adverse events. The efficacy outcomes were favorable outcome defined as an mRS score of 0-1 or recovery to the same mRS score as the premorbid score, complete independence defined as an mRS score of 0-1 at 90 days, and change in NIHSS at 24 h from baseline. RESULTS: Sixty-six patients (35 females; mean age, 74 ± 11 years; premorbid complete independence, 54 [82%]; median NIHSS on admission, 11) were enrolled at 15 hospitals. Two patients (3%) had sICH. Median NIHSS changed from 11 (IQR, 6.75-16.25) at baseline to 5 (3-12.25) at 24 h after alteplase initiation (change, -4.8 ± 8.1). At discharge, 31 patients (47%) had favorable outcome and 29 (44%) had complete independence. None died within 90 days. Twenty-three (35%) also underwent mechanical thrombectomy (no sICH, NIHSS change of -8.5 ± 7.3), of whom 11 (48%) were completely independent at discharge. CONCLUSIONS: In real-world clinical practice, IV alteplase for unclear-onset stroke patients with DWI-FLAIR mismatch provided safe and efficacious outcomes comparable to those in previous trials. Additional mechanical thrombectomy was performed safely in them.

Study Protocol for LOMCAD Trial: Effect of Lomerizine Hydrochloride to Prevent Recurrence of Cerebral Ischemic Events in CADASIL Patients.

OBJECTIVES: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is one of the most common monogenic cerebral small vessel diseases. Our previous observational study suggested that lomerizine hydrochloride, a calcium channel blocker approved in Japan in 1999 for the prevention of migraine headaches, is also effective for preventing recurrent ischemic stroke in CADASIL patients. The aim of this study (LOMCAD trial) is to verify the efficacy of lomerizine hydrochloride. MATERIALS AND METHODS: This is a multicenter, prospective, single-arm trial, using a historical control for comparison. CADASIL patients with a history of two or more cerebral ischemic events within the last two years will be administered lomerizine hydrochloride (5-mg tablet twice daily) for 24 months. The primary endpoint is symptomatic cerebral ischemic events during the 24-month period. Using our historical data and Bayesian sample size calculation based on a prior predictive distribution, the planned sample size was determined as 20 subjects. CONCLUSION: We have planned a clinical trial to verify the effectiveness of lomerizine hydrochloride as prophylaxis to prevent recurrent cerebral ischemic events in CADASIL patients. REGISTRATION: The LOMCAD trial has been registered in the Japan Registry of Clinical Trials (jRCTs051220072, https://jrct.niph.go.jp/latest-detail/jRCTs051220072).

Absence of the Susceptibility Vessel Sign with Cancer-Associated Hypercoagulability-Related Stroke.

BACKGROUND AND PURPOSE: The susceptibility vessel sign, a hypointense signal on MR T2-weighted gradient-recalled echo images, is associated with erythrocyte-predominant thrombi, which are often present in cardioembolism. In contrast, cancer-associated hypercoagulability (CAH)-related stroke, which is presumably caused by fibrin-predominant thrombi, is associated with the absence of the susceptibility vessel sign. We hypothesized that the prevalence of the susceptibility vessel sign may be helpful in distinguishing CAH-related stroke from cardioembolism. This study attempted to validate this hypothesis and investigated the usefulness of the susceptibility vessel sign in differentiating CAH-related stroke from cardioembolism. MATERIALS AND METHODS: We retrospectively studied patients with both CAH-related stroke (CAH group) and cardioembolism (cardioembolism group) who had major cerebral artery occlusion on MRA that was performed within 6 hours of stroke onset. All patients visited our department from 2015 to 2021. CAH-related stroke was defined as the following: 1) complication of active cancer, 2) pretreatment D-dimer value of >3 µg/mL, 3) multiple vascular territory infarctions, and 4) lack of any other specifically identified causes of stroke. We compared susceptibility vessel sign positivity rates within each group. Multivariable logistic regression analysis was used to assess the association between the absence of the susceptibility vessel sign and CAH-related stroke. RESULTS: Of 691 patients with CAH-related stroke or cardioembolism, major cerebral artery occlusion was observed in 10 patients in the CAH group and 198 patients in the cardioembolism group. The absence of the susceptibility vessel sign was identified in 55 of 208 patients and was significantly more frequent in the CAH group versus the cardioembolism group (90% versus 24%, P < .05). For predicting CAH-related stroke, the absence of the susceptibility vessel sign demonstrated a sensitivity of 90% (95% CI, 59%-99%), specificity of 78% (95% CI, 71%-83%), a positive predictive value of 18% (95% CI, 10-31), a negative predictive value of 99% (95% CI, 96%-99%), and a likelihood ratio of 4.06. Multivariable logistic regression analysis revealed that the absence of the susceptibility vessel sign was independently associated with CAH-related stroke (OR, 43; 95% CI, 6.8-863; P < .01). CONCLUSIONS: The absence of the susceptibility vessel sign was more frequent in CAH-related stroke than in cardioembolism. These findings could potentially be helpful for clinical management and differentiating cardioembolism and CAH-related stroke.

Magnetic resonance imaging features and stroke etiology of ischemic stroke in essential thrombocythemia.

BACKGROUND: Various essential thrombocythemia (ET)-related stroke mechanisms have been proposed, including microcirculatory disturbance due to coagulopathy, vasculitis, and embolism due to thrombus formation in large vessels. However, the stroke mechanism in ET remains largely unexplored. The purpose of this study was to evaluate magnetic resonance image (MRI) features of ischemic stroke in ET and determine the potential stroke mechanism. METHODS: We retrospectively collected data from 21 acute ischemic stroke patients with ET who were admitted to two stroke centers between 2010 and 2023. ET was diagnosed according to the World Health Organization criteria. We evaluated MRI features including the diffusion-weighted image (DWI) lesion pattern, and the presence of hemorrhagic transformation and intracranial artery steno-occlusive lesion, as well as other etiological workup results. RESULTS: Of 21 patients, 20 exhibited multiple ischemic lesions on DWI, mainly within a single vascular territory. Cortical infarcts were observed in 19 patients. Hemorrhagic transformation occurred in 15 patients. Additionally, 15 patients had intracranial steno-occlusive arteries, which regressed to normal in 11 patients during follow-up. Out of all patients, only 2 had potential causes of stroke other than ET (1 with atrial fibrillation and 1 with intracranial atherosclerotic stenosis). The remaining 19 patients had ET as the only identified potential cause. CONCLUSIONS: MRI features, including DWI lesion pattern in ischemic stroke patients with ET, suggested embolic etiology despite the absence of major embolic sources. Intra-arterial thrombus appears to be part of the stroke mechanism related to ET and may contribute to ischemic stroke in ET.