Yusuke Inoue

Background/Objectives: Subarachnoid hemorrhage (SAH) is a life-threatening condition frequently complicated by cerebral vasospasm (VS). Clazosentan has been shown to reduce the incidence of VS and improve outcomes in Japanese studies, and it has been available in Japan since January 2022. However, clazosentan has been associated with systemic adverse events, sometimes leading to discontinuation. This retrospective observational study investigated clinical variables associated with clazosentan discontinuation. Methods: We analyzed data from the multicenter “Database of Cohort Study for Outcome of SAH in Japan” (DCI Japan), prospectively collected from 2020 to 2024. Patients with aneurysmal SAH who underwent surgical clipping or endovascular coiling less than 4 days from onset were included. Multivariable logistic regression was used to investigate variables associated with clazosentan discontinuation. Secondary exploratory analyses examined clinical variables associated with poor functional outcomes (modified Rankin Scale [mRS] 3–6) at discharge and 6 months. Results: Among 372 patients treated with clazosentan (mean age 64.2 ± 14.3 years; 72.6% female), 91.7% (341/372) completed clazosentan during the VS phase, while 8.3% (31/372) discontinued clazosentan prematurely, mainly due to pulmonary complications. Overall, 8.9% (31/350) developed symptomatic VS, and 46.0% (171/372) had poor outcomes (modified Rankin Scale 3–6) at discharge and 31.4% (106/338) at 6 months. Clazosentan discontinuation was associated with age ≥ 76 years (OR for discontinuation: 2.33, 95% CI 1.03–5.28), World Federation of Neurosurgical Societies Grade V (OR 6.52 [2.70–15.78]), larger aneurysm size (OR 1.15 [1.03–1.29]), Fisher computed tomography group 4 (OR 2.61 [1.08–6.30]), and Fasudil hydrochloride hydrate use (OR 3.96 [1.77–8.87]). Poor functional outcome was more frequent in the discontinuation group than in the completion group both at discharge (83.9% vs. 42.5%, p < 0.001) and at 6 months (82.8% vs. 26.5%, p < 0.001). Clazosentan discontinuation was associated with poor outcome at discharge and at 6 months, although the latter was attenuated in sensitivity analysis. Conclusions: Some factors were associated with clazosentan discontinuation, highlighting the clinical relevance of careful systemic monitoring during clazosentan therapy, particularly in patient populations underrepresented in prior trials.

Background/Objectives: Subarachnoid hemorrhage (SAH) is frequently complicated by cerebral vasospasm (VS). Clazosentan reduces VS, and fasudil hydrochloride hydrate (Fasudil) is widely used for VS prevention in Japan. However, the benefit of adding Fasudil to clazosentan remains unclear. We investigated whether adjunctive Fasudil was associated with VS-related and functional outcomes in clazosentan-treated aneurysmal SAH. Methods: We retrospectively analyzed data from the multicenter “Database of Cohort Study for Outcome of SAH in Japan,” collected from 2020 to 2024. Patients with aneurysmal SAH who underwent surgical clipping or endovascular coiling within 4 days of onset and completed 14 days of clazosentan treatment were included. Outcomes were compared between clazosentan plus Fasudil and clazosentan alone. Multivariable logistic regression assessed factors associated with angiographic vasospasm (AVS), cerebral infarction, and poor functional outcome (modified Rankin Scale 3–6) at discharge and 6 months. Results: Among 341 patients, 100 (29.3%) received adjunctive Fasudil and 241 (70.7%) clazosentan alone. AVS occurred in 58/329 (17.6%), cerebral infarction in 58/327 (17.7%), poor functional outcome at discharge in 142/341 (41.6%), and poor functional outcome at 6 months in 82/325 (25.2%). Adjunctive Fasudil was independently associated with higher odds of AVS (adjusted odds ratio [aOR] 2.41, 95% confidence interval [CI] 1.21–4.81), cerebral infarction (aOR 2.10, 95% CI 1.08–4.09), and poor 6-month outcome (aOR 2.88, 95% CI 1.08–7.71), but not with poor functional outcome at discharge (aOR 1.37, 95% CI 0.62–3.03). Conclusions: In clazosentan-treated aneurysmal SAH, adjunctive Fasudil use was not associated with additional benefit and was associated with higher odds of AVS, cerebral infarction, and poor functional outcome at 6 months.

Background/Objectives: Subarachnoid hemorrhage (SAH) is frequently complicated by cerebral vasospasm (VS). Clazosentan has reduced VS in Japanese studies but shown inconsistent efficacy in Western trials. We hypothesized that clinical and pharmacologic interactions may influence its effectiveness. Methods: We analyzed the multicenter “Database of Cohort Study for Outcome of SAH In Japan” (DCI Japan) registry, prospectively collected from 2020 to 2023, to assess associations between clazosentan use, VS prevention, functional outcomes, and potential interactions in adults with aneurysmal SAH (aSAH) treated by surgical clipping or endovascular coiling within 4 days of onset. Outcomes included angiographic VS (AVS), symptomatic VS (SVS), cerebral infarction, and modified Rankin Scale (mRS) scores at discharge and at 6 months. Predictors and interactions were first screened using univariable analysis and Light Gradient Boosting Machine, then evaluated via multivariable logistic regression. Results: Among 544 patients (mean age 65.2 ± 14.2 years; 71.5% female), 34.0% received clazosentan. AVS, SVS, and cerebral infarction occurred in 20.6%, 16.0%, and 22.4%, respectively. Poor outcomes (mRS 3–6) were observed in 48.8% at discharge and 33.7% (137/406) at 6 months. Clazosentan use was associated with reduced odds of AVS (OR 0.27, 95% CI [0.11–0.69]), SVS (OR 0.15 [0.04–0.64]), and poor 6-month outcome (OR 0.08 [0.01–0.68]). A potential interaction with nicardipine was linked to higher odds of AVS (OR 1.85 [1.43–2.65]). Conclusions: Clazosentan was associated with reduced VS and improved 6-month outcomes after aSAH, although concomitant nicardipine may attenuate its prophylactic effectiveness against AVS.

Background/Objectives: The accurate evaluation of stroke etiology in basilar artery occlusion (BAO) remains underexplored. This study aimed to explore a simple and practical method for predicting the in situ atherosclerotic thrombosis (ISAT) subtype of BAO. Methods: We retrospectively analyzed patients diagnosed with BAO at our institution between April 2015 and April 2025. ISAT was characterized by moderate-to-severe stenosis (>50%) at the occlusion site on angiography, while the cardioembolism (CE) subtype was defined as sudden-onset arterial occlusion with evidence of a cardiac source of embolism. The location of BAO was classified based on cerebral angiography findings as proximal, middle, or distal. Clinical and imaging characteristics were compared between CE and ISAT subtypes. Results: Among 33 patients, 8 (24%) were classified as having the ISAT subtype. Multivariable analyses revealed that the presence of atrial fibrillation (AF) (OR 0.03; 95% CI, 0.00–0.56) and a non-proximal occlusion site (i.e., middle or distal) (OR 0.02; 95% CI, 0.00–0.27) were independently associated with ISAT. Patients were stratified into four groups based on the presence or absence of proximal occlusion and AF. CE subtypes predominated in groups with either AF or no proximal occlusion (25/27, 93%), whereas ISAT was present in all patients with both proximal occlusion and absence of AF (6/6, 100%). The area under the curve for this classification was 0.955. The sensitivity, specificity, positive predictive value, and negative predictive value for diagnosing ISAT were 75%, 100%, 100%, and 93%, respectively. Conclusions: A simple classification based on the presence of proximal occlusion and AF status suggested the potential to facilitate preprocedural differentiation of ISAT subtype in BAO.

Background: Since clazosentan was approved for insurance coverage in Japan, the postoperative management of delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) has changed as each facility gains experience. Here, we investigate the prevention, treatment, and management of DCI after SAH throughout Japan in 2023. Methods: In 2024, we conducted an anonymous questionnaire survey—emailed to certified neurosurgeons in hospitals across Japan—regarding management for preventing DCI after aneurysmal SAH. Of them, 78 hospitals responded and were included in this study. These results were compared with the findings of a survey conducted prior to the approval of clazosentan in Japan (2022). Results: The proportion of institutions with a standardized protocol for DCI after aneurysmal SAH at a level of ≥50% was 93.0%. For both craniotomy and endovascular surgery, clazosentan was used most frequently, followed by cilostazol, fasudil, and statins. The most common drug for both direct and endovascular procedures was clazosentan. The predominant reason for discontinuing clazosentan was respiratory complications—such as pulmonary edema—followed by cardiac complications. However, 62.1% of facilities felt that the number of cases wherein clazosentan was discontinued was deceasing. While 77.5% of respondents felt that clazosentan was effective for preventing DCI after aneurysmal SAH, only 49.3% felt that it improved outcomes. Conclusions: Since its approval, clazosentan has been the most common treatment for DCI prevention after aneurysmal SAH. The impression of the effectiveness in preventing DCI and the outcomes of clazosentan have been mixed. As data accumulate, clazosentan use and management protocols will be refined and developed.