Ohkawara Neurosurgical Hospital

Moyamoya disease (MMD) has a strong genetic basis, with the rare RNF213 p.Arg4810Lys variant (rs112735431) representing a major risk factor, while the broader genetic architecture and disease-relevant vascular cell types remain incompletely understood. We conducted a genome-wide association study in Japanese individuals (n=47 656; 401 MMD cases and 47 255 controls). Population-level features at MMD risk loci were examined by regional allele frequency and haplotype analyses. We performed single-nucleus RNA-seq of superficial temporal arteries from patients with MMD (n=3). Cell type-specific enrichment of genome-wide association study signals was assessed using the Single-Cell Disease Relevance Score. Endothelial signatures were validated by integration with publicly available single-cell data sets from controls (n=5) and immunohistochemistry for candidate markers (n=1). Beyond rs112735431, we identified a genome-wide significant signal in the HDAC9-TWIST1 region (rs12530920; P=3.3×10-14; odds ratio, 1.77). Conditional analysis on rs112735431 revealed a protective RNF213 missense variant, p.Asp1331Gly (rs8074015; P=3.7×10-9; odds ratio, 0.53), whose minor allele was mutually exclusive with rs112735431-A on haplotypes. Population analysis revealed geographic variation and extended haplotype structure of the rs112735431-A allele in Japan. Single-nucleus RNA-seq identified a mesenchymal-like endothelial cell (MEC) population with selective FN1 expression. Genome-wide association study-prioritized disease genes were strongly enriched in MECs. MECs showed mesenchymal pathway activation with a regulatory program distinct from canonical endothelial states. The proportion of MECs was markedly increased in MMD (72% versus 28% in controls), and fibronectin 1 (FN1) expression in endothelial regions was confirmed by immunohistochemistry. Our findings identify a protective RNF213 p.Asp1331Gly variant (rs8074015) that is mutually exclusive with the known rs112735431-A allele. Genetic risk converges on an MEC state markedly expanded in MMD.

Large anterior skull base meningiomas with sinonasal invasion pose a challenge not only for safe resection but also for tackling reconstruction of the anterior skull base. Here, in this video, the authors present the case of a 35-year-old female with a biopsy-proven WHO grade II meningioma who required a combined transcranial and endoscopic endonasal approach. This combined approach allowed for excellent tumor exposure, complete safe resection, and, importantly, durable and appropriate skull base reconstruction.The video can be found here: https://stream.cadmore.media/r10.3171/2025.10.FOCVID25157

The therapeutic time window for endovascular therapy in acute stroke patients with large-vessel occlusion was extended to 24 hours from onset. Although a retrospective study showed the efficacy of endovascular therapy beyond 24 hours from the last known well, it remains unclear whether endovascular therapy is effective. Extending the time window of Endovascular therapy in the Triage of Late Presenting Strokes beyond 24 h (SKIP-EXTEND trial) aimed to clarify the efficacy of endovascular therapy compared to the best medical management. This is an investigator-initiated, multicenter, prospective, randomized, open-label, blinded end-point clinical trial. Eligibility criteria included adults and pre-stroke modified Rankin scale score ≤2 with internal carotid artery or M1 (horizontal or sphenoidal segment) occlusion beyond 24 to 72 hours of the last known well. The target enrollment is 260 patients, with 130 reeiving endovascular therapy and 130 receiving the best medical treatment. The primary outcome is the rate of favorable outcome defined as a modified Rankin scale score ≤2 at 90 days. The secondary outcomes are the ordinal logistic regression analysis of the modified Rankin scale score and the rate of recanalization at 48 hours. As safety outcomes, the rate of any and symptomatic intracranial hemorrhage at 24 hours and the rate of mortality at 90 days are assessed. This is the first randomized controlled trial to focus on the efficacy of endovascular therapy beyond 24 hours. Our results will not only benefit patients but also reduce healthcare costs. We believe that this novel study will be useful in clinical practice.

Amino acid (AA) substitutions in the fusion (F) protein of respiratory syncytial virus (RSV) and their effects on antibody susceptibility remain unclear. We analyzed AA substitutions in the main neutralizing epitopes of the F protein. We analyzed F protein genes of 236 RSV strains isolated from children hospitalized with RSV infection in Fukushima, Japan (June 2008-February 2023). AA substitutions in antigenic sites II, V, and Ø were detected, and their effects on antibody susceptibility and viral replication were evaluated. Site II: The K272M (RSV-A) and the K272E (RSV-B) substitutions in strains from palivizumab-treated children reduced antibody susceptibility. Site V: In RSV-A, >50% of strains isolated since 2022 harbored the V178I substitution; however, this did not change antibody susceptibility. In RSV-B, L172Q/S173L mutant strains became predominant around 2016, leading to reduced antibody susceptibility. Site Ø: No AA substitutions were detected in RSV-A. In RSV-B, the I206M/Q209R mutant strain became predominant around 2018, leading to improved antibody susceptibility and replicative ability. However, none of the substitutions reduced antibody susceptibility. The RSV F protein in Fukushima has naturally undergone AA substitutions with corresponding changes in antibody susceptibility, including unique regional patterns. Monitoring substitutions and antibody susceptibility is essential.

Abstract Background Spinal chronic subdural hematoma (sCSDH) is a rare condition whereas intracranial chronic subdural hematoma (iCSDH) is well-recognised and documented in clinical settings. Despite various theories have been proposed, the exact pathogenesis of sCSDH remains to be elucidated. Herein, we report a rare case of sCSDH with co-existing iCSDH and deduce its etiology using histopathological findings. Case presentation A 76-year-old Japanese man with slight hemiparesis due to iCSDH underwent burr hole surgery with successful drainage of the hematoma. The patient could not walk unassisted after the surgery. Spinal magnetic resonance imaging (MRI) was performed, revealing a subdural hematoma extending from the T11 to S2 levels. The patient decided to undergo hematoma evacuation via a hemilaminectomy. Intraoperatively, we identified a dark liquefied hematoma with its capsule, which closely resembled an iCSDH. Histological examination of the resected capsule revealed loose fibrovascular tissues comprising capillaries, collagen fibres, small number of macrophages, and hemosiderin deposits. These findings were very similar to those for iCSDH, such that the pathogenesis of sCSDH was considered identical to that of iCSDH. The patient was transferred to a rehabilitation hospital, and 4 months after the lumbar surgery, no recurrence was observed in MRI examination. Conclusions sCSDH may result from various potential pathogeneses, that clinicians should consider for correct diagnosis and appropriate management. Our case provides valuable insights into the pathogenesis of sCSDH.

Since zinc is involved in many aspects of the hematopoietic process, zinc supplementation can reduce erythropoiesis-stimulating agents (ESAs) in patients undergoing hemodialysis. However, it remains unclear whether hypoxia-inducible factor–prolyl hydroxylase inhibitors (HIF-PHIs) have similar reduction effects. HIF-PHI stabilizes HIF, which promotes hematopoiesis, although HIF-1α levels are downregulated by zinc. This study aimed to investigate the effect of zinc supplementation on the hematopoietic effect of HIF-PHI in patients undergoing hemodialysis. Thirty patients undergoing maintenance hemodialysis who underwent periods of treatment with roxadustat or darbepoetin alfa during the past 3 years were retrospectively observed. Participants who underwent periods with and without zinc supplementation were selected, with nine treated with darbepoetin alfa and nine treated with roxadustat. Similarly to the ESA responsiveness index (ERI), the hematopoietic effect of zinc supplementation was determined by the HIF-PHI responsiveness index (HRI), which was calculated by dividing the HIF-PHI dose (mg/week) by the patient’s dry weight (kg) and hemoglobin level (g/L). Zinc supplementation significantly increased ERI (p < 0.05), but no significant change was observed (p = 0.931) in HRI. Although zinc supplementation did not significantly affect HRI, adequate zinc supplementation is required to alleviate concerns such as vascular calcification and increased serum copper during the use of HIF-PHI.

BackgroundThe optimal duration of dual antiplatelet therapy (DAPT) after stent-assisted coil embolization (SACE) for cerebral aneurysm remains uncertain. This randomized trial of short- versus long-term Dual AntiPlatelet Therapy for Stent-Assisted treatment of CErebral aneurysm (DAPTS ACE) aimed to clarify whether long-term DAPT can reduce the occurrence of ischemic stroke in patients with cerebral aneurysms treated by SACE compared with short-term DAPT.MethodsPatients treated for cerebral aneurysm with SACE were enrolled from 17 hospitals in Japan. Patients were enrolled within 30 days after SACE and assigned in a 1:1 ratio to receive long-term (12 months) or short-term (3 months) DAPT with aspirin and clopidogrel. Randomization was performed centrally through a web-based system. The primary outcome was the time to ischemic stroke event during 3 to 12 months after SACE. This trial was registered with the Japan Registry of Clinical Trials (jRCTs051180141).ResultsA total of 142 patients were recruited from November 4, 2016 to January 7, 2019. Among them, 65 and 68 patients assigned to the long- and short-term DAPT groups, respectively, were included in the full analysis set. Ischemic stroke occurred in no patients in the long-term DAPT group and in one patient in the short-term DAPT group. The incidence rate did not differ between the groups (0.0 vs 2.1/100 person-years; log rank test, P=0.33).ConclusionsIn this multicenter randomized controlled trial, there was not a statistically significant difference in the rate of ischemic strokes between long- and short-term DAPT.

AbstractsBACKGROUNDFaster recanalization for acute large vessel occlusion is associated with better clinical outcome. The aim of this study was to identify patient characteristics that require puncture-to-recanalization (P-R) time within 30 min for good clinical outcome.METHODSWe evaluated the patients from K-NET Registry, which is a prospective, multicenter, observational registry of acute ischemic stroke patients. The present analysis included patients who met the following criteria: (1) treated with endovascular therapy for ICA or MCA M1 occlusion; and (2) achieved successful recanalization (mTICI 2b or more). Patients were divided into subgroups according to pre-treatment patients’ characteristics; DWI ASPECTS, age, NIHSS, occlusion site and symptom recognition to puncture time. In each subgroup, the frequency of good clinical outcomes was compared between P-R time &lt;30min and &gt;30min. We entered interaction terms into the models to evaluate the correlation between each patient characteristic and P-R time.RESULTS1053 patients were included in this study. Overall, P-R &lt;30min was significantly associated with good outcome. Univariate analysis in each subgroup revealed a significant association between P-R &lt;30min and good outcomes in the patients with DWI ASPECTS ≤6, age &gt;85 and NIHSS ≥16. In multivariable analysis, NIHSS, age, symptom recognition to puncture time, DWI ASPECTS and P-R &lt;30 minutes were significant independent predictors of good outcomes; however, only DWI ASPECTS had interaction terms with P-R &lt;30 minutes. Multivariable analysis showed P-R &lt;30min was an independent predictor for good outcome in patients with DWI ASPECTS ≤6, whereas P-R&lt;30min was not in patients with DWI ≥7.CONCLUSIONSP-R&lt;30 min is a predictor of good clinical outcome, however, the effect depends on DWI ASPECTS. A target P-R time of less than 30 minutes is appropriate for patients with DWI ASPECTS scores of 0-6, whereas 30 minutes or longer is reasonable for patients with DWI ASPECTS 7 or higher.