Motohiro Morioka

Introduction: Pulmonary pleomorphic carcinoma is a rare, highly aggressive subtype of lung cancer with frequent early multiple-organ metastases including to the brain. However, brain metastases that precede detection of a primary lung lesion are exceedingly rare. We report a case of pulmonary pleomorphic carcinoma with brain metastasis that was initially diagnosed and treated as glioblastoma. Case Presentation: A 69-year-old man presented with left-sided spatial neglect and abnormal behaviors. Brain computed tomography revealed a right temporal-subcortical hemorrhage. The patient subsequently underwent right temporal craniotomy and hematoma evacuation surgery. Histopathological examination revealed markedly large atypical cells with necrosis. Immunohistochemistry revealed focal GFAP positivity. As no primary lesion was detected on systemic computed tomography, the patient was diagnosed with glioblastoma, IDH-wildtype, and temozolomide was initiated. Without a significant recurrence of the brain lesion, the patient’s condition deteriorated. Follow-up computed tomography revealed new mass lesions in the lungs and small intestine. The patient died of peritonitis secondary to small intestinal perforation. Autopsy revealed a large mass in the right lung that extended to the mediastinum and small daughter lesions in multiple organs, including the small intestinal mesentery. The known brain tumor and trunk tumors showed similar histology and strong immunohistochemical positivity for cytokeratin 7. Conclusion: This case illustrates that metastatic pulmonary pleomorphic carcinoma may mimic glioblastoma both radiologically and histopathologically, particularly when the primary tumor remains undetected. When brain metastasis cannot be confidently excluded during the evaluation of a brain tumor, re-evaluation of histopathological and neuroimaging findings, together with repeated systemic evaluation at short intervals, is important for establishing an accurate diagnosis.

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.

Glioblastoma is the most common primary malignant central nervous system (CNS) tumor; however, its microenvironment, including tumor‐associated microglia/macrophages (TAMs), is not fully understood. Although ionized calcium‐binding adaptor molecule 1 (IBA‐1) is expressed in various microglial phenotypes in the healthy human brain, CD163 is a marker of activated/phagocytic microglia. Tissues from 34 patients with glioblastoma were analyzed, and 17.6% of cases were CD163‐dominant. CD163‐dominant patients showed better overall survival than IBA‐1‐dominant patients ( p = 0.019). CD163 dominance was identified as an independent prognostic factor for overall survival (hazard ratio [HR], 0.17; p = 0.011). Compared with the IBA‐1‐dominant group, CD163‐dominant tumors showed more CD4‐positive cell infiltration ( p = 0.005), fewer ameboid TAMs ( p = 0.021), and fewer non‐microvascular proliferation (non‐MVP) vessels ( p = 0.012). No significant differences were found in patient characteristics, such as age, sex, tumor location, or extent of resection. The CD163‐to‐IBA‐1 ratio of TAMs is a significant independent prognostic factor in glioblastoma, suggesting that the activation status of these cells and their interactions with the vascular endothelium and T cells influence tumor progression. These findings highlight TAMs as potential therapeutic targets for glioblastoma.

BACKGROUND: Compared to dural arteriovenous fistulas (AVFs), the pathogenesis of extradural AVFs is unclear. Furthermore, the outcomes of surgical and endovascular treatments are inferior to those of dural AVFs, and in some cases, there are reports of poor outcomes. OBSERVATIONS: A 74-year-old male hemodialysis patient presented with gradually progressive gait disturbance. MRI showed high T2 signal intensity in the lower spinal cord, and angiography revealed a dural AVF. The patient was referred to the authors’ hospital. Multiple small arteries were found to have refluxing veins in the dura at T12–L1 on the right side, and a diagnosis of epidural AVF was made, leading to direct surgery. During exoscopic microsurgery, the venous pouch located on the lateral ventral side was exposed, and intradural and extradural hemodynamics were confirmed using indocyanine green (ICG) videoangiograhy, followed by complete coagulated occlusion. Postoperatively, the patient’s symptoms improved. LESSONS: There have been few cases of epidural AVF treated with exoscopic ICG videoangiography for intradural and extradural observation and healing. https://thejns.org/doi/10.3171/CASE25865

Compared to dural arteriovenous fistulas (AVFs), the pathogenesis of extradural AVFs is unclear. Furthermore, the outcomes of surgical and endovascular treatments are inferior to those of dural AVFs, and in some cases, there are reports of poor outcomes. A 74-year-old male hemodialysis patient presented with gradually progressive gait disturbance. MRI showed high T2 signal intensity in the lower spinal cord, and angiography revealed a dural AVF. The patient was referred to the authors’ hospital. Multiple small arteries were found to have refluxing veins in the dura at T12–L1 on the right side, and a diagnosis of epidural AVF was made, leading to direct surgery. During exoscopic microsurgery, the venous pouch located on the lateral ventral side was exposed, and intradural and extradural hemodynamics were confirmed using indocyanine green (ICG) videoangiograhy, followed by complete coagulated occlusion. Postoperatively, the patient’s symptoms improved. There have been few cases of epidural AVF treated with exoscopic ICG videoangiography for intradural and extradural observation and healing. https://thejns.org/doi/10.3171/CASE25865

Background: Giant thrombosed aneurysms of the M1 segment of the middle cerebral artery (MCA) are rare and technically demanding lesions. Surgical management is particularly challenging when the lenticulostriate arteries (LSAs) are involved, as their preservation is often difficult and the risk of ischemic complications is substantial. Case Description: A 15-year-old boy presented with seizures, and neuroimaging revealed a partially thrombosed giant aneurysm measuring 55 mm involving the entire M1 segment. Digital subtraction angiography demonstrated severe flow stagnation within the aneurysm, associated with reduced cerebral blood flow (CBF) and the development of collateral circulation. No LSAs or other perforating arteries arising from the M1 trunk were identified angiographically. The patient was initially managed conservatively; however, progressive aneurysm enlargement resulted in neurological deterioration, cerebral edema, and infarction of the caudate head. Surgical intervention consisting of superficial temporal artery–MCA bypass, complete M1 trapping, and aneurysm excision was subsequently performed. Postoperative imaging showed no additional ischemic lesions, and postoperative CBF increased with clinical improvement. The unexpectedly favorable course following complete M1 trapping may have been influenced by preexisting collateral circulation, including leptomeningeal pathways; however, the precise contribution of perforator-related collateral flow could not be determined. Conclusion: This case illustrates an uncommon clinical course following complete M1 trapping for a thrombosed giant aneurysm. Although preservation of LSAs is generally considered critical, this experience suggests that bypass-assisted trapping may be feasible in carefully selected cases with well-developed collateral circulation, highlighting the complexity of cerebral collateral pathways and the difficulty of predicting ischemic risk.

Intracerebral hemorrhage is frequently complicated by hematoma expansion, which is a major determinant of poor outcomes. Leakage sign, defined as progressive contrast extravasation on delayed computed tomography after angiography, has been proposed as a predictor of hematoma expansion. However, the relationship between onset-to-imaging time, hemorrhage location, and leakage sign positivity remains unclear. Data from 144 patients with primary supratentorial intracerebral hemorrhage were retrospectively collected and divided into 2 groups: leakage sign-positive (n = 58) and leakage sign-negative (n = 86) groups. Clinical characteristics, radiological findings, and outcomes were compared, and correlations between hematoma size, onset-to-imaging time, and blood pressure at admission were assessed. Leakage sign-positive patients were significantly older, more frequently underwent antithrombotic therapy, and exhibited larger hematomas, a higher incidence of spot sign(s), a greater need for surgical intervention, and worse outcomes than their leakage sign-negative counterparts. Leakage sign was detectable within 5 hours of onset. In putaminal hemorrhage, hematoma size demonstrated a significant time-dependent increase, particularly in patients who were leakage sign-positive. Moreover, in leakage sign-positive putaminal hemorrhage, admission systolic blood pressure was strongly correlated with hematoma size, suggesting a synergistic effect between hypertension and ongoing bleeding. In contrast, there was no significant correlation between time and hematoma size in thalamic or subcortical hemorrhages, although trends were noted in subcortical cases. These findings indicate that leakage sign positivity reflects ongoing hyperacute bleeding, with diagnostic validity limited to within 5 hours of onset. Early detection of leakage sign, especially in cases of putaminal hemorrhage, may help identify high-risk patients who could benefit from aggressive interventions to mitigate hematoma expansion and improve outcomes.

The leakage sign (LS), defined as contrast medium extravasation on the 5-minute delayed phase after computed tomography (CT) angiography, has been reported as a predictive imaging marker for hematoma expansion in acute subdural hematoma (ASDH). We recently identified two different patterns of LS: local and diffuse. This study aimed to evaluate the clinical importance of these LS types in predicting brain swelling and determining the appropriate surgical intervention. We retrospectively reviewed 98 patients with LS-positive ASDH on contrast-enhanced CT between January 2013 and September 2024. LS was classified as local-type when one or two positive areas were observed and as diffuse-type when three or more positive areas were present and/or when contrast medium extended along the brain surface. Brain swelling was defined based on radiological findings and the requirement for decompressive craniectomy. Clinical data, treatment modalities, and outcomes were analyzed in both groups. Among the 98 LS-positive patients, 40 were classified as having local-type and 58 as having diffuse-type. The diffuse-type LS group had a significantly greater proportion of patients in severe admission Glasgow Coma Scale category ( p = 0.027), underwent decompressive craniectomy more frequently ( p = 0.04), and had higher indicators of coagulopathy, including elevated activated partial thromboplastin time, prothrombin time-international normalized ratio, and D-dimer levels (all p < 0.05). Brain swelling occurred in 70.7% of patients in the diffuse-type group compared with 17.5% in the local-type group ( p < 0.001). Poor outcomes were significantly more common in the diffuse-type group (67.2% vs. 32.5%, p = 0.001), along with a higher mortality rate (56.9% vs. 22.5%, p < 0.001). Diffuse-type LS was independently associated with poor outcomes and was associated with clinical severity, coagulopathy, and brain swelling. Conversely, local-type LS was associated with favorable outcomes and a low rate of brain swelling. Because most patients with LS-positive ASDH show progressive ASDH, emergency hematoma evacuation is generally required. Patients with diffuse-type LS may be more likely to require decompressive craniectomy, whereas endoscopic hematoma removal via a small craniotomy may be a feasible option for local-type LS, where the bleeding point can be detected using the LS-positive area.