桒原 聖典

Karnofsky Performance Status (KPS) is a widely used scale to assess performance status. KPS ≥ 50% implies that patients can live at home. Therefore, maintaining KPS ≥ 50% is important to improve the quality of life of patients with glioblastoma, whose median survival is less than 2 years. This study aimed to identify the factors associated with survival time with maintenance of KPS ≥ 50% (survival with KPS ≥ 50%) in patients with glioblastoma, IDH-wildtype. Ninety-eight patients with glioblastomas, IDH-wildtype, who were treated with concomitant radiotherapy (RT) and temozolomide (TMZ) followed by maintenance TMZ therapy, and whose KPS at the start of RT was ≥ 50%, were included. The median survival with KPS ≥ 50% was 13.3 months. In univariate analysis, preoperative KPS (≥ 80%), KPS at the start of RT (≥ 80%), residual tumor size (< 2 cm3), methylated MGMT promotor, and implantation of BCNU wafer were associated with survival with KPS ≥ 50%. In multivariate analysis, KPS at the start of RT (≥ 80%), methylated MGMT promotor, and residual tumor size (< 2 cm3) were significantly associated with increased survival with KPS ≥ 50%. A strategy of maximum possible tumor resection without compromising KPS is desirable to prolong the survival time with KPS ≥ 50%.

BACKGROUND <p lang="en">Reperfusion therapy for acute ischemic stroke efficacy is highly time dependent; therefore, stroke centers are required to further reduce the delays from hospital arrival to treatment efficiently. We developed a visual task management application, Task Calculation Stroke (Task Calc. Stroke: TCS), to facilitate hospital acute ischemic stroke treatment by supporting parallel staff task completion. We evaluated TCS for the reduction of reperfusion therapy delays and improvement of clinical outcomes. </p> METHODS <p lang="en">In this multicenter cohort study, patients were directly admitted to 4 comprehensive stroke centers in Japan and given intravenous tissue plasminogen activator and/or mechanical thrombectomy from June 2018 to December 2020. The research team visited each facility and instructed the staff on TCS use for acute ischemic stroke (training stage), after which the staff used TCS independently (TCS stage). We then compared door‐to‐needle time for intravenous tissue plasminogen activator, door‐to‐puncture time for mechanical thrombectomy, and clinical outcomes at discharge according to the modified Rankin Scale among patients treated before training (original stage), during the training stage, or the TCS stage. </p> RESULTS <p lang="en"> During the study period, 316 patients with acute ischemic stroke received reperfusion therapy; of these, 246 received intravenous tissue plasminogen activator and 162 mechanical thrombectomy (including 92 receiving both the treatments). The mean door‐to‐needle time was significantly reduced from 58.0 minutes in the original stage to 54.6 minutes in the training stage ( P =0.049) and 47.8 minutes in the TCS stage ( P &lt;0.001). The door‐to‐puncture time did not change during the training stage; however, in the TCS stage, it significantly reduced from 93.8 minutes in the original stage to 88.5 minutes ( P =0.004). The distribution of modified Rankin Scale scores at discharge significantly shifted favorably at the TCS stage ( P =0.003). </p> CONCLUSION <p lang="en">In this study, TCS application could reduce workflow time for reperfusion therapy and might have led to improved clinical outcomes. </p>

OBJECTIVES: The benefit of mechanical thrombectomy for acute ischemic stroke is highly time dependent. However, time to treatment is longer for in-hospital stroke patients than community-onset stroke patients. This study aimed to clarify the cause of this difference. METHODS: A retrospective single-center study was performed to analyze patients with large vessel occlusion who underwent mechanical thrombectomy between January 2017 and December 2019. Patients were divided into in-hospital stroke and community-onset stroke groups. Clinical characteristics and treatment time intervals were compared between groups. RESULTS: One hundred four patients were analyzed: 17 with in-hospital stroke and 87 with community-onset stroke. Patient characteristics did not significantly differ between groups. Median door (stroke recognition)-to-computed tomography time (36 min vs. 14 min, P<0.01) and door-to-puncture time (135 min vs. 117 min, P=0.02) were significantly longer in the in-hospital stroke group than the community-onset stroke group. However, median computed tomography-to-puncture time (104 min vs. 104 min, P=0.47) and puncture-to-reperfusion time (53 min vs. 38 min, P=0.17) did not significantly differ. CONCLUSIONS: Longer door-to-puncture time in in-hospital stroke patients was mostly caused by longer door-to-computed tomography time, which is the initial part of the workflow. An in-hospital stroke protocol that places importance on early stroke specialist consultation and prompt transportation to the computed tomography scanner might hasten treatment and improve outcomes in patients with in-hospital stroke.

Cyst formation in the third ventricle and the histopathological findings were rarely reported. We report a similar case of late-onset aqueductal membranous occlusion (LAMO) caused by a thin gliotic cyst and a review of related literature. A 28-year-old woman with enlarged lateral ventricles was referred to our hospital with complaints of headache and dizziness. In our hospital, the obvious cause of the hydrocephalus was unknown on any examination and we decided performing endoscopic third ventriculostomy for hydrocephalus. A thin cyst covering the entrance of the aqueduct was identified and we perforated it. Histopathological finding of the cyst wall was gliosis and our case was similar to LAMO, although not typical. The postoperative symptoms and ventricle size improved for 4 years. When suspecting cases similar to definition of LAMO, neuroendoscopic surgery would be the first-choice treatment and might detect causes undetectable on preoperative imaging such as our thin membrane.

PURPOSE: The Flow Re-direction Endoluminal Device (FRED) has recently become available for flow diversion in Japan. We have encountered cases that failed to deploy the FRED. In this study, we report our initial experience with the FRED for cerebral aneurysms and clarify the causes of failed FRED deployment. METHODS: A retrospective data analysis was performed to identify patients treated with the FRED between June 2020 and March 2021. Follow-up digital subtraction angiography was performed at 3 and 6 months and assessed using the O'Kelly-Marotta (OKM) grading scale. RESULTS: Thirty-nine aneurysms in 36 patients (average age: 54.4 years) were treated with the FRED. The average sizes of the dome and neck were 9.9 mm and 5.2 mm, respectively. In nine patients, additional coiling was performed. In one patient (2.6%), proximal vessel injury caused direct carotid-cavernous fistula during deployment. Ischaemic complications were encountered in one patient (2.6%) with transient symptoms. Angiographic follow-up at 6 months revealed OKM grade C or D in 86.6% of patients. FRED deployment was successful in 35 (92.1%) procedures. In the failure group, the differences between the FRED and the minimum vessel diameter (P = 0.04) and the rate of the parent vessel having an S-shaped curve (P = 0.04) were greater than those in the success group. CONCLUSIONS: Flow diversion using the FRED is effective and safe for treating cerebral aneurysms. The use of the FRED for patients with an S-shaped curve in the parent vessel and oversizing of more than 2 mm should be considered carefully.

We report a case of vertebral artery dissecting aneurysm (VADA) that developed with subarachnoid hemorrhage and was found to be occluded based on subsequent digital subtraction angiography. Few reports have been published on ruptured VADA in which ipsilateral vertebral arteries are occluded. The proper management of this type of aneurysm is controversial. A 44-year-old woman developed a sudden onset headache. Computed tomography and three-dimensional computed tomography were immediately performed and showed subarachnoid hemorrhage and VADA distal to the right posterior inferior cerebellar artery bifurcation. We decided to treat the VADA immediately and performed digital subtraction angiography but found the VADA had spontaneously occluded. We performed coil embolization, including the aneurysm and the parent artery, with reference to the findings of three-dimensional computed tomography. On Day 16, recurrence was considered due to the finding of dilation of the distal end where the coil was embolized. An additional embolization was performed via the posterior communicating artery. No cases of endovascular treatment have been reported in VADA cases in which the rupture site is spontaneously occluded. In such cases, the treatment may be incomplete, so strict follow-up is required.

The PulseRider (Cerenovus, Johnson & Johnson Medical Devices, New Brunswick, NJ, USA) is a neck reconstruction device that is used for the treatment of unruptured wide-necked bifurcation aneurysms. Herein, we describe the case of a 51-year-old male patient with a basilar apex aneurysm who was treated with PulseRider but had post-procedural brainstem infarctions caused by one of the proximal markers covering the origin of a perforator. In such cases, repositioning of the PulseRider should be performed to avoid infarctions.

Background: Cerebral amyloid angiopathy-related inflammation (CAA-I) presents with slowly progressive nonspecific neurological symptoms, such as headache, cognitive function disorder, and seizures. Pathologically, the deposition of amyloid-β proteins at the cortical vascular wall is a characteristic and definitive finding. Differential diagnoses include infectious encephalitis, neurosarcoidosis, primary central nervous system lymphoma, and glioma. Here, we report a case of CAA-I showing acute progression, suggesting a glioma without enhancement, in which a radiological diagnosis was difficult using standard magnetic resonance imaging. Case Description: An 80-year-old woman was admitted due to transient abnormal behavior. Her initial imaging findings were similar to those of a glioma. She presented with rapid progression of the left hemiplegia and disturbance of consciousness for 6 days after admission and underwent emergent biopsy with a targeted small craniotomy under general anesthesia despite her old age. Intraoperative macroscopic findings followed by a pathological study revealed CAA-I as the definitive diagnosis. Steroid pulse therapy with methylprednisolone followed by oral prednisolone markedly improved both the clinical symptoms and imaging findings. Conclusion: Differential diagnosis between CAA-I and nonenhancing gliomas may be difficult using standard imaging studies in cases presenting with acute progression. A pathological diagnosis under minimally invasive small craniotomy may be an option, even for elderly patients.

PURPOSE: Endovascular treatment of posterior communicating artery aneurysms with fetal-type posterior communicating artery originating from the aneurysm dome is often challenging because, with conventional techniques, dense packing of aneurysms for posterior communicating artery preservation is difficult; moreover, flow-diversion devices are reportedly less effective. Herein, we describe a novel method called the λ stenting technique that involves deploying stents into the internal carotid artery and posterior communicating artery. METHODS: Between January 2018 and September 2020, the λ stenting technique was performed to treat eight consecutive cases of aneurysms. All target aneurysms had a wide neck (dome/neck ratio < 2), a fetal-type posterior communicating artery with hypoplastic P1, and a posterior communicating artery originating from the aneurysm dome. The origin of the posterior communicating artery from the aneurysm, relative to the internal carotid artery, was steep (< 90°: V shape). RESULTS: The maximum aneurysm size was 8.0 ± 1.9 mm (6-12 mm). The average packing density (excluding one regrowth case) was 32.7 ± 4.2% (26.8-39.1%). Initial occlusion was complete occlusion in 6 (75.0%) patients and neck remnants in 2 (25.0%) patients. Follow-up angiography was performed at 18.4 ± 11.6 months (3-38 months). There were no perioperative complications or reinterventions required during the study period. CONCLUSION: The λ stenting technique enabled dense coil packing and preservation of the posterior communicating artery. This technique enabled safe and stable coil embolization. Thus, it could become an alternative treatment option for this sub-type of intracranial aneurysms.

BACKGROUND: Recurrent complex middle cerebral artery (MCA) aneurysms after combined clipping and endovascular surgery are challenging, and if conventional techniques are adapted, advanced surgical, endovascular, and a combination of both techniques are often required. For such complex aneurysms, safe and effective straightforward techniques for all neurovascular surgeons are warranted. We describe the details of staged hybrid techniques with straightforward bypass surgery followed by flow diverter deployment in a patient with complex MCA aneurysm. ILLUSTRATIVE CASE: A 69-year-old woman presented with left recurrent large MCA aneurysm enlargement 25 years after direct surgery and coil embolization for ruptured aneurysm. The recurrent MCA aneurysm had large and complex morphology and was adhering to the brain tissues. Therefore, it was unsuitable to treat such aneurysm with conventional surgical and endovascular techniques with a high risk of morbidity. We performed (1) M2 ligation following superficial temporal artery-M2 bypass and (2) flow diverter deployment assisted with coil packing in two sessions. Three months after the second session, the aneurysm was completely occluded with endothelialization of the neck. Angiographic findings revealed no recurrence 12 months after the treatment. CONCLUSIONS: Staged hybrid techniques with straightforward bypass surgery followed by flow diverter deployment may be a safe and effective treatment for complex recurrent MCA aneurysms.

Seizures are common in patients with gliomas; however, the mechanisms of epileptogenesis in gliomas have not been fully understood. This study hypothesized that analyzing quantified metabolites using magnetic resonance spectroscopy (MRS) might provide novel insights to better understand the epileptogenesis in gliomas, and specific metabolites might be indicators of preoperative seizures in gliomas. We retrospectively investigated patient information (gender, age at diagnosis of tumor, their survival time) and tumor information (location, histology, genetic features, and metabolites according to MRS) in patients with gliomas. The data were correlated with the incidence of seizure and analyzed statistically. Of 146 adult supratentorial gliomas, isocitrate dehydrogenase (IDH) mutant tumors significantly indicated higher incidence of preoperative seizures than IDH wild-type gliomas. However, MRS study indicated that glutamate concentration in IDH wild-type gliomas was higher than that in IDH mutant gliomas. Glutamate was not associated with high frequency of preoperative seizures in patients with gliomas. Instead, increased total N-acetyl-L-aspartate (tNAA) was significantly associated with them. Moreover, multivariable analysis indicated that increased level of tNAA was an independent predictor of preoperative seizures. According to MRS analysis, tNAA, rather than glutamate, might be a useful to detect preoperative seizures in patient with supratentorial gliomas.

BACKGROUND: The extent of resection has been reported to be associated with overall survival in gliomas. The use of 5-aminolevulinic acid (5-ALA) has been recognized to increase the extent of tumor resection. OBJECTIVE: To evaluate what factors affect the intraoperative fluorescence after administration of 5-ALA in gliomas. METHODS: Correlation of intraoperative fluorescence and several clinical, radiographic, molecular biologic, and histopathologic characters was retrospectively evaluated in 104 patients (53 males and 51 females; mean age 54.2 yr) with gliomas at our institution. To clarify the mechanisms that mutant isocitrate dehydrogenase (IDH) affect the intraoperative fluorescence, in Vitro experiments using genetically engineered glioma cells harboring mutant IDH1 were performed. RESULTS: Intraoperative fluorescence was observed in 82 patients (78.8%). In addition to age, magnetic resonance imaging enhancement, World Health Organization grades, and MIB-1 index, the status of IDH was revealed to be correlated with intraoperative fluorescence. In Vitro assay revealed that mutant IDH indirectly reduced the amount of exogenous 5-ALA-derived protoporphyrinogen IX in glioma cells by increasing activity of ferrochelatase and heme oxygenase 1. CONCLUSION: Mutant IDH1/2-induced metabolite changes of exogenous 5-ALA were suggested to contribute to the lesser intraoperative fluorescence in gliomas with mutant IDH1/2 than in those without.

According to the 2016 World Health Organization (WHO) classification of central nervous system tumors, diffuse astrocytic and oligodendroglial tumors are differentiated by the presence of isocitrate dehydrogenase 1 or 2 (IDH1/2) mutation and the combined loss of the short arm of chromosome 1 and the long arm of chromosome 19 (1p/19q co-deletion). IDH-mutant astrocytoma often has p53 and alpha-thalassemia/mental retardation syndrome X-linked (ATRX) mutation, showing the alternative lengthening of telomeres (ALT) phenotype, while IDH-mutant and 1p/19q-co-deleted oligodendroglioma often have wild-type p53 and telomerase reverse transcriptase (TERT) promoter mutation, showing telomerase activation. This study analyzed IDH, ATRX, and TERT promoter mutations, and the correlation between them. Immortalized cells overcome the telomere-related crisis by activating telomerase or ALT. In glioma, telomerase is mainly activated by TERT promoter mutation, while ALT is usually associated with ATRX mutation. Although the mechanism of how ATRX mutation induces ALT remains unclear, ATRX loss alone is believed to be insufficient to induce ALT. Treatments targeting telomere maintenance are promising.

<p>Objective: A case of cerebral embolism due to left atrial myxoma successfully treated using a direct aspiration first pass technique (ADAPT) is reported with a review of the literature.</p><p>Case Presentation: The patient was a 31-year-old male who developed left hemiparesis and dysarthria and was transported to our hospital. Based on MRI and MRA findings, a diagnosis of acute cerebral infarction due to occlusion of the distal part of M1 of the right middle cerebral artery, and transthoracic echocardiography suggested left atrial myxoma. Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) and mechanical thrombectomy were carried out, and complete recanalization could be achieved 196 minutes after the onset. The symptoms were resolved, and the embolus was pathologically confirmed to be left atrial myxoma.</p><p>Conclusion: ADAPT using Penumbra was suggested to be useful for the treatment of cardiogenic cerebral embolism due to left atrial myxoma.</p>