Ichiro Nakahara

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: Poor-grade aneurysmal subarachnoid hemorrhage (SAH; WFNS grades 4–5) carries a historically dismal prognosis, driven by early brain injury and delayed cerebral ischemia (DCI). Despite advances in neurocritical care, effective pharmacological strategies for this vulnerable population remain limited. This multicenter study investigated prognostic factors for functional recovery, with particular emphasis on the potential benefit of adjunctive cilostazol, a phosphodiesterase-3 inhibitor with vasodilatory and antiplatelet properties. Methods: This multicenter retrospective cohort study analyzed 394 patients with WFNS grade 4–5 aneurysmal SAH treated at 10 institutions between 2018 and 2024. The primary outcome was favorable functional status (modified Rankin Scale 0–2) at 6 months. Multivariable logistic regression was performed to identify independent predictors of outcome. Sensitivity analyses were also performed to assess the potential influence of missing 6-month outcome data. Results: Six-month outcomes were available for 318 patients (80.7%), of whom 107 (33.6%) achieved favorable recovery. Patients with favorable outcomes were significantly more likely to have received cilostazol than those with unfavorable outcomes (70.1% vs. 55.5%; p = 0.016). In multivariable logistic regression, cilostazol use remained associated with a favorable outcome (odds ratio [OR] 2.29; 95% confidence interval [CI] 1.01–5.22; p = 0.048) after adjustment for age (OR 0.95; p < 0.001), WFNS grade 5 (OR 0.46; p = 0.012), ventricular drainage, and cerebral infarction. Sensitivity analyses, including propensity score–weighted and missing-outcome analyses, yielded directionally favorable estimates but were not statistically significant. Conclusions: Despite the severity of the initial insult, one-third of patients with available 6-month follow-up achieved functional independence. Cilostazol use was associated with favorable functional outcome in the primary analysis, although statistical significance was not retained in sensitivity analyses addressing missing outcomes. These findings suggest a potential therapeutic signal of cilostazol in poor-grade aneurysmal SAH, warranting prospective validation.

Intraprocedural rupture during Woven EndoBridge (WEB) treatment is most commonly reported in the early deployment phase, whereas rebleeding after substantial deployment is considered rare. We report a patient in their early 90s with poor-grade subarachnoid hemorrhage caused by a large ruptured internal carotid artery aneurysm with a fetal-type posterior communicating artery. After initial deployment, the bleb was already covered by the lateral surface of the device. During partial resheathing and repositioning to preserve the branch, the WEB rotated slightly, altering the configuration of the device relative to the bleb and thereby changing device–aneurysm wall interaction. Retrospective assessment of the procedural recording later suggested minimal contrast leakage just above the bleb, although massive hemorrhage became evident only during the final angiographic runs after detachment. Rescue treatment with balloon occlusion and n-butyl cyanoacrylate embolization achieved hemostasis; however, postprocedural cone-beam computed tomography revealed a massive intracerebral hematoma, and the patient died 3 days later despite supportive care. This case underscores that even after substantial deployment, repositioning maneuvers may carry a risk under specific high-risk conditions.

Contrast-induced encephalopathy (CIE) is a rare adverse complication of various diagnostic and therapeutic angiographic procedures following iodinated contrast media administration. Disruption of the blood–brain barrier is the center point of underlying mechanism. It mimics subarachnoid hemorrhage (SAH) on computed tomography (CT) scan. Patient usually present early with wide range of symptoms of neurological deficit; however, late presentations have been documented in literatures. Most of these cases are transient resolving within 48 hours but fatal outcomes have been reported. The purpose of this article was to report three cases who underwent endovascular intervention at our center and developed CIE. All these three patients had untreated hypertension. Iopamidol as contrast agent was used in all these cases. All three patients developed stroke-like symptoms in the postoperative period and radiological investigations revealed a picture of SAH with dual-energy iodinated CT confirming CIE. All patients were managed according to our institutional protocol and made recovery. It is paramount to recognize this potentially devastating complication early after carefully excluding thromboembolic and hemorrhagic causes. Once diagnosed, early initiation of conservative treatment include hydration therapy, anticonvulsants, institute selective use of steroids, and osmotherapy such as mannitol. Adequate preoperative management of hypertension may play an important role in the prevention of CIE. Future use of contrast should include meticulous risk assessment and exhaustive patient and relatives counseling.

Background: Sphenoidal diploic arteriovenous fistulas (AVFs) are exceptionally rare. When accompanied by cortical venous reflux (CVR), they are considered high-risk lesions with a potential for intracranial hemorrhage, warranting prompt treatment. Endovascular management is challenging in the sphenoidal region because arterial feeders often harbor extracranial–intracranial anastomoses. Case Description: A 67-year-old woman presented with chronic left temporal headache and tinnitus. Cerebral angiography revealed a sphenoidal diploic AVF with CVR. The shunt was located in the lateral sphenoid diploe and was supplied by branches of the external carotid system, including the anterior deep temporal artery and the middle meningeal artery. Venous drainage occurred through an ascending diploic vein into a parasagittal meningeal sinus (venous lacuna) with reflux into an adjacent cortical vein. The lesion was treated by transarterial Onyx embolization with balloon assistance for flow control. Careful feeder selection was essential to avoid high-risk anastomoses, particularly meningo-ophthalmic connections. Complete angiographic obliteration was achieved without complications, with immediate symptom resolution. No recurrence was observed during 4 years of follow-up. Conclusion: Transarterial Onyx embolization with appropriate flow-control techniques can be a safe and effective option for sphenoidal diploic AVFs with CVR. This case underscores that the presence of CVR itself is the key indication for treatment, irrespective of whether the venous reflux pathway is direct or indirect, and that meticulous angiographic assessment and feeder selection are critical for procedural safety.

Ruptured dissecting aneurysms (DAs) of the anterior cerebral artery (ACA), particularly at the A1–A2 junction, are rare and diagnostically challenging, especially in young patients. Conventional treatment options may be limited due to anatomical constraints and the lesion's fragility. We report the case of a 23-year-old male who presented with diffuse subarachnoid hemorrhage and seizure. Initial imaging failed to identify the bleeding source. On follow-up, computed tomography angiography revealed subtle findings suggestive of a dissection at the right A1–A2 junction, which was subsequently confirmed by digital subtraction angiography. Considering the lesion's morphology and location, the aneurysm was treated with a flow diverter (Pipeline Flex with Shield Technology) following clinical stabilization. The patient recovered without neurological deficits and was discharged in good functional condition. This case highlights the potential of flow diversion as an effective treatment strategy for ruptured DAs in the distal ACA. Early recognition through repeat imaging and individualized multidisciplinary planning may contribute to favorable outcomes in anatomically complex lesions.

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.

Objective: Cavernous dural arteriovenous fistula (dAVF) is often treated by transvenous embolization through percutaneous routes. However, it is sometimes difficult when venous drainage flows only into leptomeningeal venous reflux. Here, we present a case of cavernous dAVF draining predominantly into the superficial middle cerebral vein (SMCV), through which endovascular coil embolization was successfully performed by direct surgical exposure.Case Presentation: A 62-year-old woman presented with left hemiparesis. Head CT revealed a right frontoparietal subcortical hematoma. Cerebral angiography showed retrograde leptomeningeal venous drainage (RLVD) caused by a right cavernous dAVF. Despite multiple percutaneous transvenous attempts, the cavernous sinus could not be accessed; therefore, a combined open surgical and endovascular approach was selected. After right frontotemporal craniotomy, the temporal cortical vein arising from a common trunk with the SMCV was preserved to reduce intra-sinus pressure and confirm fistula obliteration, with the puncture performed distal to this branch. The other drainage pathway, the SMCV, was cut down for sheath placement to secure stable access and minimize bleeding risk. A microcatheter was looped within the cavernous sinus for stability. Coil embolization was successfully completed under intraoperative digital subtraction angiography. After disappearance of shunt flow and RLVD, both the SMCV and the temporal cortical vein were coagulated and clipped.Conclusion: A hybrid surgical and endovascular approach can be an alternative method in cases when percutaneous transvenous embolization is not feasible. We review the combined surgical and endovascular approach and discuss the key technical considerations for successful implementation, including indications for the hybrid approach, operating room setup, craniotomy, sheath placement, coil embolization strategies, and closure.