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Background: Quality indicators (QIs) are an accepted tool for measuring a hospital’s performance in routine care. We examined national trends in adherence to the QIs developed by the Close The Gap-Stroke program by combining data from the health insurance claims database and electronic medical records, and the association between adherence to these QIs and early outcomes in patients with acute ischemic stroke in Japan. Methods: In the present study, patients with acute ischemic stroke who received acute reperfusion therapy in 351 Close The Gap-Stroke-participating hospitals were analyzed retrospectively. The primary outcomes were changes in trends for adherence to the defined QIs by difference-in-difference analysis and the effects of adherence to distinct QIs on in-hospital outcomes at the individual level. A mixed logistic regression model was adjusted for patient and hospital characteristics (eg, age, sex, number of beds) and hospital units as random effects. Results: Between 2013 and 2017, 21 651 patients (median age, 77 years; 43.0% female) were assessed. Of the 25 defined measures, marked and sustainable improvement in the adherence rates was observed for door-to-needle time, door-to-puncture time, proper use of endovascular thrombectomy, and successful revascularization. The in-hospital mortality rate was 11.6%. Adherence to 14 QIs lowered the odds of in-hospital mortality (odds ratio [95% CI], door-to-needle Conclusions: We demonstrated national marked and sustainable improvement in adherence to door-to-needle time, door-to-puncture time, and successful reperfusion from 2013 to 2017 in Japan in patients with acute ischemic stroke. Adhering to the key QIs substantially affected in-hospital outcomes, underlining the importance of monitoring the quality of care using evidence-based QIs and the nationwide Close The Gap-Stroke program.

OBJECTIVEImproved outcomes in patients with subarachnoid hemorrhage (SAH) treated at high-volume centers have been reported. The authors sought to examine whether hospital case volume and comprehensive stroke center (CSC) capabilities affect outcomes in patients treated with clipping or coiling for SAH.METHODSThe authors conducted a nationwide retrospective cohort study in 27,490 SAH patients who underwent clipping or coiling in 621 institutions between 2010 and 2015 and whose data were collected from the Japanese nationwide J-ASPECT Diagnosis Procedure Combination database. The CSC capabilities of each hospital were assessed by use of a validated scoring system based on answers to a previously reported 25-item questionnaire (CSC score 1–25 points). Hospitals were classified into quartiles based on CSC scores and case volumes of clipping or coiling for SAH.RESULTSOverall, the absolute risk reductions associated with high versus low case volumes and high versus low CSC scores were relatively small. Nevertheless, in patients who underwent clipping, a high case volume (> 14 cases/yr) was significantly associated with reduced in-hospital mortality (Q1 as control, Q4 OR 0.71, 95% CI 0.55–0.90) but not with short-term poor outcome. In patients who underwent coiling, a high case volume (> 9 cases/yr) was associated with reduced in-hospital mortality (Q4 OR 0.69, 95% CI 0.53–0.90) and short-term poor outcomes (Q3 [> 5 cases/yr] OR 0.75, 95% CI 0.59–0.96 vs Q4 OR 0.65, 95% CI 0.51–0.82). A high CSC score (> 19 points) was significantly associated with reduced in-hospital mortality for clipping (OR 0.68, 95% CI 0.54–0.86) but not coiling treatment. There was no association between CSC capabilities and short-term poor outcomes.CONCLUSIONSThe effects of case volume and CSC capabilities on in-hospital mortality and short-term functional outcomes in SAH patients differed between patients undergoing clipping and those undergoing coiling. In the modern endovascular era, better outcomes of clipping may be achieved in facilities with high CSC capabilities.

Background: Postoperative cerebral hyperperfusion syndrome (CHS) may occur after superficial temporal artery (STA)-middle cerebral artery (MCA) bypass for moyamoya disease (MMD). Predicting postoperative CHS is challenging; however, we previously reported the feasibility of using a hyperspectral camera (HSC) for monitoring intraoperative changes in brain surface hemodynamics during STA-MCA bypass. Objective: To investigate the utility of HSC to predict postoperative CHS during STA-MCA bypass for patients with MMD. Methods: Hyperspectral images of the cerebral cortex of 29 patients with MMD who underwent STA-MCA bypass were acquired by using an HSC before and after anastomosis. We then analyzed the changes in oxygen saturation after anastomosis and assessed its correlation with CHS. Results: Five patients experienced transient neurological deterioration several days after surgery. 123I-N-Isopropyl-iodoamphetamine single-photon emission computed tomography scan results revealed an intense, focal increase in cerebral blood flow at the site of anastomosis without any cerebral infarction. Patients with CHS showed significantly increased oxygen saturation (SO2) in the cerebral cortex after anastomosis relative to those without CHS (33 ± 28 vs. 8 ± 14%, p < 0.0001). Receiver operating characteristic analysis results show that postoperative CHS likely occurs when the increase rate of cortical SO2 value is >15% (sensitivity, 85.0%; specificity, 81.3%; area under curve, 0.871). Conclusions: This study indicates that hyperspectral imaging of the cerebral cortex may be used to predict postoperative CHS in patients with MMD undergoing STA-MCA bypass.

Objectives To examine the utility of FDG-PET/MRI in patients with epilepsy by comparing the diagnostic accuracy of PET/MRI and PET/CT in epileptogenic zone (EZ) detection. Methods This prospective study included 31 patients (17 males, 14 females) who underwent surgical resection for EZ. All patients were first scanned using FDG-PET/CT followed immediately with FDG-PET/MRI. Two series of PET plus standalone MR images were interpreted independently by five board-certified radiologists. A 4-point visual score was used to assess image quality. Sensitivities and visual scores from both PETs and standalone MRI were compared using the McNemar test with Bonferroni correction and Dunn’s multiple comparisons test. Results The EZs were confirmed histopathologically via resection as hippocampal sclerosis (n = 11, 35.5%), gliosis (n = 8, 25.8%), focal cortical dysplasia (n = 6, 19.4%), and brain tumours (n = 6, 19.4%) including cavernous haemangioma (n = 3), dysembryoplastic neuroepithelial tumour (n = 1), ganglioglioma (n = 1), and polymorphous low-grade neuroepithelial tumour of the young (n = 1). The sensitivity of FDG-PET/MRI was significantly higher than that of FDG-PET/CT and standalone MRI (FDG-PET/MRI vs. FDG-PET/CT vs. standalone MRI; 77.4–90.3% vs. 58.1–64.5% vs. 45.2–80.6%, p p Conclusions The diagnostic accuracy for the EZ detection in focal epilepsy could be higher in FDG-PET/MRI than in FDG-PET/CT. Key Points • Sensitivity of FDG-PET/MRI was significantly higher than that of FDG-PET/CT and standalone MRI (FDG-PET/MRI vs. FDG-PET/CT vs. standalone MRI; 77.4–90.3% vs. 58.1–64.5% vs. 45.2–80.6%, p • Visual scores derived from FDG-PET/MRI were significantly higher than those of FDG-PET/CT and standalone MRI (2.8 ± 1.2 vs. 2.0 ± 1.1 vs. 2.1 ± 1.2, p • Compared to FDG-PET/CT, FDG-PET/MRI increased the visual score (51.9%, increased visual scores of 2 and 3).

BACKGROUND AND PURPOSE: Recanalization after coil embolization is widely studied. However, there are limited data on how recanalized aneurysms rupture. Herein, we describe our experience with the rupture of recanalized aneurysms and discuss the type of recanalized aneurysms at greatest rupture risk. MATERIALS AND METHODS: A total of 426 unruptured aneurysms and 169 ruptured aneurysms underwent coil embolization in our institution between January 2009 and December 2017. Recanalization occurred in 38 (8.9%) of 426 unruptured aneurysms (unruptured group) and 37 (21.9%) of 169 ruptured aneurysms (ruptured group). The Modified Raymond-Roy classification on DSA was used to categorize the recanalization type. Follow-up DSA was scheduled until 6 months after treatment, and follow-up MRA was scheduled yearly. If recanalization was suspected on MRA, DSA was performed. RESULTS: In the unruptured group, the median follow-up term was 74.0 months. Retreatment for recanalization was performed in 18 aneurysms. Four of 20 untreated recanalized aneurysms (0.94% of total coiled aneurysms) ruptured. In untreated recanalized aneurysms, class IIIb aneurysms ruptured significantly more frequently than class II and IIIa (P = .025). In the ruptured group, the median follow-up term was 28.0 months. Retreatment for recanalization was performed in 16 aneurysms. Four of 21 untreated recanalized aneurysms (2.37% of total coiled aneurysms) ruptured. Class IIIb aneurysms ruptured significantly more frequently than class II and IIIa (P = .02). CONCLUSIONS: The types of recanalization after coil embolization may be predictors of rupture. Coiled aneurysms with class IIIb recanalization should undergo early retreatment because of an increased rupture risk.

Purpose Diffusion-weighted imaging (DWI) plays an important role in the preoperative assessment of gliomas; however, the diagnostic performance of histogram-derived parameters from mono-, bi-, and stretched-exponential DWI models in the grading of gliomas has not been fully investigated. Therefore, we compared these models’ ability to differentiate between high-grade and low-grade gliomas. Methods This retrospective study included 22 patients with diffuse gliomas (age, 23–74 years; 12 males; 11 high-grade and 11 low-grade gliomas) who underwent preoperative 3 T-magnetic resonance imaging from October 2014 to August 2019. The apparent diffusion coefficient was calculated from the mono-exponential model. Using 13 b-values, the true-diffusion coefficient, pseudo-diffusion coefficient, and perfusion fraction were obtained from the bi-exponential model, and the distributed-diffusion coefficient and heterogeneity index were obtained from the stretched-exponential model. Region-of-interests were drawn on each imaging parameter map for subsequent histogram analyses. Results The skewness of the apparent diffusion, true-diffusion, and distributed-diffusion coefficients was significantly higher in high-grade than in low-grade gliomas (0.67 ± 0.67 vs. − 0.18 ± 0.63, 0.68 ± 0.74 vs. − 0.08 ± 0.66, 0.63 ± 0.72 vs. − 0.15 ± 0.73; P = 0.0066, 0.0192, and 0.0128, respectively). The 10th percentile of the heterogeneity index was significantly lower (0.77 ± 0.08 vs. 0.88 ± 0.04; P = 0.0004), and the 90th percentile of the perfusion fraction was significantly higher (12.64 ± 3.44 vs. 7.14 ± 1.70%: P Conclusion The bi-exponential model exhibited the best diagnostic performance for differentiating high-grade from low-grade gliomas.

Background and Purpose— The treatment and prognosis of acute large vessel occlusion with mild symptoms have not been sufficiently studied. The present study aimed to investigate the clinical or radiological predictors of clinical outcome in patients with stroke with mild symptoms due to acute large vessel occlusion. Methods— Of 2420 patients with acute large vessel occlusion in the RESCUE-Japan Registry 2 (Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism-Japan Registry 2), a multicenter prospective registry in Japan, patients with modified Rankin Scale scores of 0 to 2 before onset and initial National Institutes of Health Stroke Scale (NIHSS) scores of 0 to 5 were examined in post hoc analysis. We examined the clinical and radiological characteristics associated with a favorable outcome (modified Rankin Scale score, 0–2 at 90 days) using multivariate analysis, as well as the factors associated with a favorable outcome in patients treated with endovascular therapy. Results— We analyzed 272 patients (median age, 73 years; median NIHSS score on admission, 3). Eighty-six (31.6%) patients were treated with intravenous recombinant tissue-type plasminogen activator, 54 (19.9%) underwent endovascular therapy, and 208 (76.5%) showed a favorable outcome. In multivariate analysis, age P Conclusions— Younger age, lower initial NIHSS score, intravenous recombinant tissue-type plasminogen activator, and absence of hyperglycemia were independently associated with a favorable outcome in patients with acute large vessel occlusion with low NIHSS scores. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02419794.

This study aimed to compare the functional outcome at discharge for unruptured cerebral aneurysms (UCAs) between surgical clipping and endovascular coiling in total, nonelderly (65 years), and elderly (≥65 years) patients by nonbiased analysis based on a national database in Japan.A total of 15,671 patients with UCA were registered in the Diagnosis Procedure Combination, the nationwide database, from 2010 to 2015 in Japan. The outcome of the Barthel Index (BI) at discharge was investigated, and propensity score-matched analysis was conducted in total, nonelderly, and elderly patient groups.Propensity score-matched analysis found no significant difference for in-hospital mortality between the 2 treatment methods in the total and both age-groups. The rate of morbidity of BI90 at discharge was higher after surgical clipping than after endovascular coiling in the total (4.9% vs. 3.9%; P = 0.040; risk difference, -1.0%; 95% confidence interval, -3.6 to 2.3%) and the elderly age-group (8.1% vs. 5.0%; P0.001; risk difference, -3.1%; -4.8% to 1.5%), however, no significant association between the 2 treatment methods (2.4% vs. 2.6%; P = 0.67; risk difference, 0.22%; -0.79 to 1.22%) was found in the nonelderly group.In elderly patients with UCA, a better outcome at discharge after endovascular coiling was found. However, no significantly different functional outcome at discharge between surgical clipping and endovascular coiling for UCA in nonelderly patients was confirmed by propensity score-matched analysis from a nationwide database in Japan.

BACKGROUND AND PURPOSE: Embolization is widely performed to treat brain arteriovenous malformations, but little has been reported on factors contributing to complications. We retrospectively reviewed a nationwide surveillance to identify risk factors contributing to complications and short-term clinical outcomes in the endovascular treatment of brain arteriovenous malformations. MATERIALS AND METHODS: Data for endovascular treatment of brain arteriovenous malformations were extracted from the Japanese nationwide surveillance. Patient characteristics, brain arteriovenous malformation features, procedures, angiographic results, complications, and clinical outcomes at 30 days postprocedure were analyzed. RESULTS: A total of 1042 endovascular procedures (788 patients; mean, 1.43 ± 0.85 procedures per patient) performed in 111 institutions from 2010 to 2014 were reviewed. Liquid materials were used in 976 procedures (93.7%): to perform presurgical embolization in 638 procedures (61.2%), preradiosurgical embolization in 160 (15.4%), and as sole endovascular treatment in 231 (22.2%). Complete or near-complete obliteration of brain arteriovenous malformations was obtained in 386 procedures (37.0%). Procedure-related complications occurred in 136 procedures (13.1%), including hemorrhagic complications in 59 (5.7%) and ischemic complications in 57 (5.5%). Univariate analysis identified deep venous drainage, associated aneurysms, infratentorial location, and preradiosurgical embolization as statistically significant risk factors for complications. Multivariate analysis showed that embolization of brain arteriovenous malformations in the infratentorial location was significantly associated with complications. Patients with complications due to endovascular procedures had worse clinical outcomes 30 days after the procedures than those without complications. CONCLUSIONS: Complications arising after endovascular treatment of brain arteriovenous malformations are not negligible even though they may play a role in adjunctive therapy, especially in the management of infratentorial brain arteriovenous malformations.

The long-term outcomes of patients with intraprocedural aneurysm rupture (IPR) during endovascular coiling of unruptured intracranial aneurysms (UIAs) remain unclear. We investigated the long-term outcomes and predictors of neurological outcomes in patients who sustained IPR during coil embolization of UIAs.We retrospectively analyzed the medical record of 312 untreated UIAs in 284 patients who underwent endovascular coiling between April 2013 and July 2018.The mean follow-up period for the entire cohort was 25.6 months. Twelve patients (3.8%) experienced IPR. The mean aneurysm size in the IPR cohort was significantly smaller than that in the no-IPR cohort (P = 0.045). The IPR cohort had a higher percentage of earlier subarachnoid hemorrhage from another aneurysm (P = 0.019), anterior communicating artery (AComA) aneurysm (P0.001), and basilar artery (BA) aneurysm (P = 0.022) than the no-IPR cohort. Neurologic deterioration was observed in 3 patients. The morbidity and mortality rates of the IPR cohort were 25% and 8.3%, respectively. Patients with IPR during coil embolization for AComA aneurysm did not develop neurological deterioration. Two of the 3 patients (66.7%) with a BA aneurysm had neurological deterioration. The proportion of patients with an mRS score of 0-2 at the last follow-up did not differ between the 2 cohorts (P = 0.608).The proportion of functionally independent patients did not differ between patients with and without IPR. Patients with BA aneurysms who developed an IPR tended to exhibit more unfavorable clinical courses than patients with AcomA aneurysms.

A total of 907 patients enrolled in the Japanese Registry of Neuroendovascular Therapy (JR-NET)3, a surveillance study in Japan, who underwent intracranial percutaneous transluminal angioplasty (PTA)/stenting for intracranial stenosis during the period from 2010 to 2014 were investigated. Technical success was achieved in 97.5% of the patients, and 6.8% had a residual stenosis of ≥50%. The incidence rates of ischemic and hemorrhagic complications were as low as 5.3% and 3.1%, respectively, and the mortality rate was 1.9%. However, the mortality rate of cases with either complications was higher at 10.7%. About half of the treatment cases were performed between 24 h and 14 days after onset, and the incidence of perioperative complications was similar to that after at least 15 days. Although it is necessary to verify the effectiveness of PTA/stenting within 14 days, the results of this treatment were stable regardless of the intervention period.

Endosaccular coiling is recognized as a feasible method for treating unruptured intracranial aneurysms (UIAs). We retrospectively reviewed cases of UIAs treated by coiling in the Japanese Registry of Neuroendovascular Therapy (JR-NET) 3, a nationwide survey of NET between 2010 and 2014, the beginning period of intracranial stents in Japan. Data were extracted for 6844 UIAs (6619 procedures) from 40,169 registered records of all NETs in the JR-NET 3 databases. The features of the aneurysms and procedures, immediate radiographic findings, procedure-related complications, and clinical outcomes at 30 days after the procedures were assessed. Of 6844 UIAs, 81.8% were located in the anterior circulation. The mean patient age was 61.3 years (72.4% females). Compared with the preceding JR-NET 1 and 2, there were significant increases (P 2) from 2.1% to 2.8%. In conclusion, introduction of neck-bridge stent was associated with an increase in cases of wide-necked aneurysms. However, the ischemic complication rate increased despite the greater use of periprocedural antiplatelet therapy.

IntroductionIn our institute, most cases of carotid artery stenosis are treated by carotid artery stenting (CAS) with an open-cell stent and double-balloon protection, even if plaques are unstable. This study was performed to examine the outcome of CAS with an open-cell stent and double-balloon protection for unstable plaques.MethodsA total of 184 CAS procedures in our institute between October 2010 and February 2018 were assessed. Ultrasonography findings of low-echo plaques, plaque ulceration, or both were defined as unstable plaques. A plaque-to-muscle ratio (PMR) of >1.8 on T1-weighted black blood imaging using spin-echo was also defined as an unstable plaque. Seventy-four unstable plaques on ultrasonography and 86 unstable plaques evaluated by PMR were included. Open-cell stents and double-balloon protection (proximal balloon protection during lesion crossing and distal balloon protection after lesion crossing) were used in all cases.ResultsOn ultrasonography, perioperative asymptomatic thromboembolization was significantly more frequent in the unstable plaque group (39/74, 52.7%) than in the stable plaque group (41/110, 37.3%, p=0.0384). Asymptomatic thromboembolization was also significantly more frequent in the PMR >1.8 group (44/86, 51.2%) than in the PMR ConclusionsThe outcomes of CAS with an open-cell stent and double-balloon protection are acceptable. This method is effective and safe, even if carotid artery stenosis comprises unstable plaques.

BACKGROUND: The Japanese Registry of NeuroEndovascular Therapy 2 (JR-NET2) and 3 (JR-NET3) were nationwide surveys that evaluated clinical outcomes after neuroendovascular therapy in Japan. The aim of this study was to compare the prevalence and risk factors of complications of intracranial tumor embolization between JR-NET2 and JR-NET3. METHODS: A total of 1018 and 1545 consecutive patients with intracranial tumors treated with embolization were enrolled in JR-NET2 and JR-NET3, respectively. The prevalence of complications in intracranial tumor embolization and related risk factors were compared between JR-NET2 and JR-NET3. RESULTS: The prevalence of complications in JR-NET3 (3.69%) was significantly higher than that in JR-NET2 (1.48%) (p = 0.002). The multivariate analysis in JR-NET2 showed that embolization for tumors other than meningioma was the only significant risk factor for complication (odds ratio [OR], 3.88; 95% confidence interval [CI], 1.13-12.10; p = 0.032), and that in JR-NET3 revealed that embolization for feeders other than external carotid artery (ECA) (OR, 3.56; 95% CI, 2.03-6.25; p CONCLUSIONS: Embolization for feeders other than ECA and use of liquid materials could increase the complication rate in intracranial tumor embolization.

Japan has a rapidly aging population and the application of neuroendovascular therapy (NET) for cerebrovascular diseases among elderly patients has increased, but feasibility and safety of NET for elderly patients are still debated. Therefore, this study aimed to elucidate feasibility and safety of NET by analyzing the Japanese nationwide database, the Japanese Registry of Neuroendovascular Therapy 3 (JR-NET 3). In total, 35,972 patients in the JR-NET 3 were analyzed retrospectively. "Elderly patients" were defined as those aged ≥75 years. Approximately one-quarter of patients who received NET were elderly patients. The proportion of patients with modified Rankin Scale (mRS) 0-2 before treatment and 30 days after NET was significantly low across all diseases in the elderly patients. Technical success rates were generally high across all procedures, but complication rate was significantly higher among elderly patients; ischemic complications were significantly higher with NET for unruptured aneurysms (UA) and carotid artery stenosis (CAS). Multivariate analysis revealed that mRS 0-2 before treatment [odds ratio (OR): 0.56, 95% confidence interval (CI): 0.34-0.94, P = 0.03], middle cerebral artery aneurysm (OR: 0.33, 95% CI: 0.12-0.92, P = 0.04), and complete obliteration (OR: 0.66, 95% CI: 0.44-0.97, P = 0.03) were associated with ischemic complications with NET for UA. Moreover, mRS 0-2 before treatment (OR: 0.55, 95% CI: 0.36-0.86, P < 0.01), high intensity with time-of-flight magnetic resonance angiography (OR: 1.55, 95% CI: 1.03-2.32, P = 0.04), open-cell stent (OR: 2.20, 95% CI: 1.50-3.22, P

To evaluate the performance of acceleration-selective arterial spin labeling (AccASL) MR angiography in the visualization of brain arteriovenous malformations (AVMs) in comparison with digital subtraction angiography (DSA) and time-of-flight (TOF) MR angiography. Twenty-one patients with brain AVM (mean age 31.1 ± 18.6 years; 11 males, 10 females) underwent TOF and AccASL MR angiography and DSA. Two neuroradiologists conducted an observer study for detection, nidus size, eloquence, venous drainage pattern, and Spetzler-Martin (SM) grade. The evaluations included the visualization of each AVM component with reference to DSA and assessments of contrast-to-noise ratio (CNR). The kappa statistic, repeated measures analysis of variance, Wilcoxon matched pairs test, and paired t test were used. Both observers detected more AVMs with AccASL (95.2%, 90.5% for Observers 1 and 2) than with TOF (76.2% and 71.4%, respectively). The inter-modality agreement between AccASL and DSA was almost perfect for the eloquence, venous drainage pattern, and SM grade for Observer 1 and moderate for the venous drainage pattern and substantial for the eloquence and SM grade for Observer 2. The visualization scores were higher with AccASL than with TOF for the feeding artery (AccASL, 4.5 ± 1.0 vs. TOF, 3.9 ± 1.5, p = 0.0214), nidus (4.6 ± 1.1 vs. 3.2 ± 1.5, p = 0.0006), and draining vein (4.6 ± 1.0 vs. 2.2 ± 1.1, p

BackgroundThe efficacy of combined stent retriever (SR) and aspiration catheter (AC; combined technique: CBT) use for acute ischemic stroke (AIS) is unclear. We investigated the safety and efficacy of single-unit CBT (SCBT)—retrieving the thrombus as a single unit with SR and AC into the guide catheter—compared with single use of either SR or contact aspiration (CA).MethodsWe analysed 763 consecutive patients who underwent mechanical thrombectomy for AIS between January 2013 and January 2020, at six comprehensive stroke centers. Patients were divided into SCBT and single device (SR/CA) groups. The successful recanalization with first pass (SRFP) and other procedural outcomes were compared between groups.ResultsOverall, 240 SCBT and 301 SR/CA (SR 128, CA 173) patients were analyzed. SRFP (modified Thrombolysis In Cerebral Infarction (mTICI) ≥2c, 43.3% vs 27.9%, pConclusionsSCBT increases the SRFP rate and shortens the puncture-to-reperfusion time without increasing procedural complications.

Targeting the unique glioma immune microenvironment is a promising approach in developing breakthrough immunotherapy treatments. However, recent advances in immunotherapy, including the development of immune checkpoint inhibitors, have not improved the outcomes of patients with glioma. A way of monitoring biological activity of immune cells in neural tissues affected by glioma should be developed to address this lack of sensitivity to immunotherapy. Thus, in this study, we sought to examine the feasibility of non-invasive monitoring of glioma-associated microglia/macrophages (GAM) by utilizing our previously developed induced microglia-like (iMG) cells. Primary microglia (pMG) were isolated from surgically obtained brain tissues of 22 patients with neurological diseases. iMG cells were produced from monocytes extracted from the patients’ peripheral blood. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) revealed a significant correlation of the expression levels of representative markers for M1 and M2 microglia phenotypes between pMG and the corresponding iMG cells in each patient (Spearman’s correlation coefficient = 0.5225, P <0.0001). Synchronous upregulation of CD206 expression levels was observed in most patients with glioma (6/9, 66.7%) and almost all patients with glioblastoma (4/5, 80%). Therefore, iMG cells can be used as a minimally invasive tool for monitoring the disease-related immunological state of GAM in various brain diseases, including glioma. CD206 upregulation detected in iMG cells can be used as a surrogate biomarker of glioma.

Objective Aneurysm recurrence after coiling is a major complication in some cases, including cases of repeated recurrences. In this study, we identified a relationship between the recurrence of a coiled aneurysm and angle change of the parent artery. Methods From April 2008 to December 2019, we performed 283 coil embolizations to treat 256 aneurysms in 251 patients. Among these, 21 cases of recurrent saccular aneurysms were selected. The parent artery angle changes between the initial treatment and the first re-treatment were compared between those who underwent single re-treatment and showed no recurrence after the first re-treatment (Group SR, n = 14) and those who required multiple re-treatments (Group MR, n = 7). Results The parent artery angles at the first treatment [medians (interquartile ranges)] were 121.6° (109.3–135.6°) in Group SR and 104.9° (89.9–131.0°) in Group MR; at the second treatment, these angles were 121.2° (105.5–132.7°) and 81.9° (67.0–111.4°), respectively, revealing angle changes of -2.2° (−4.0 to −0.4°) and −16.4° (−30.1 to −8.6°) in Groups SR and MR between the first and second treatments. The between-group differences in the parent artery angles at the second treatment and the changes in the parent artery angle between the first and second treatments were statistically significant. Conclusion In patients with recurrent aneurysms, simple aneurysm coiling is not effective when the angle of the parent artery becomes narrower after treatment, relative to that before treatment. Stent placement should be considered for straightening the parent artery or diverting blood flow.

Objective We devised a new surgical alternative to the conventional nasoseptal flap, a pedicled posterior septal–nasal floor flap that we named the Kegon flap. We evaluated the effectiveness of this flap for skull base reconstruction in patients with high-flow cerebrospinal fluid (CSF) leakage after sellar/parasellar tumor resection. Methods The Kegon flap with a novel rescue flap was designed to preserve blood flow and mucosa anterior to the nasal septum and to avoid flap damage during surgery. We retrospectively evaluated postoperative flap perfusion with T1-weighted contrast-enhanced magnetic resonance imaging and characterized complications and wound healing in 5 patients who experienced high-flow CSF leakage after sellar/parasellar tumor resection requiring reconstruction. Results Postoperative T1-weighted contrast-enhanced magnetic resonance imaging demonstrated good flap perfusion in all patients. The area reconstructed with the Kegon flap healed within the first month following surgery. No postoperative CSF leakage or nasal hemorrhage was observed. There was no perforation of the anterior nasal septum after surgery. The mucosal defect had completely epithelialized in all patients by 3 months after surgery. There were no instances of prolonged nasal crusting or any subjective decrease in olfactory function 3 months after surgery. Conclusions The use of a Kegon flap with a novel rescue flap was effective and helped preserve nasal structure and function in patients undergoing skull base reconstruction after sellar/parasellar tumor resection associated with high-flow CSF leakage.

The preoperative imaging-based differentiation of primary central nervous system lymphomas (PCNSLs) and glioblastomas (GBs) is of high importance since the therapeutic strategies differ substantially between these tumors. In this study, we investigate whether the gamma distribution (GD) model is useful in this differentiation of PNCSLs and GBs. Twenty-seven patients with PCNSLs and 57 patients with GBs were imaged with diffusion-weighted imaging using 13 b-values ranging from 0 to 1000 sec/mm2. The shape parameter (κ) and scale parameter (θ) were obtained with the GD model. Fractions of three different areas under the probability density function curve (f1, f2, f3) were defined as follows: f1, diffusion coefficient (D) −3 mm2/sec; f2, D >1.0×10−3 and −3 mm2/sec; f3, D >3.0 × 10−3 mm2/sec. The GD model-derived parameters were compared between PCNSLs and GBs. Receiver operating characteristic (ROC) curve analyses were performed to assess diagnostic performance. The correlations with intravoxel incoherent motion (IVIM)-derived parameters were evaluated. The PCNSL group's κ (2.26 ± 1.00) was significantly smaller than the GB group's (3.62 ± 2.01, p = 0.0004). The PCNSL group's f1 (0.542 ± 0.107) was significantly larger than the GB group's (0.348 ± 0.132, p

Background Statins have been associated with reduced recurrence and better functional outcomes in patients with acute ischemic stroke. However, the effect of statins in patients with acute large vessel occlusion (LVO) is not well scrutinized. Methods and Results RESCUE (Recovery by Endovascular Salvage for Cerebral Ultra‐Acute Embolism)‐Japan Registry 2, a physician‐initiated registry, enrolled 2420 consecutive patients with acute LVO who were admitted to 46 centers across Japan within 24 hours of onset. We compared patients with and without statin use after acute LVO onset (statin group and nonstatin group, respectively) in terms of the modified Rankin scale at 90 days. We estimated that the odds ratios for the primary outcome was modified Rankin scale and we estimated the odds ratios for a 1‐scale lower modified Rankin scale adjusting for confounders. After excluding 12 patients without LVO and 9 patients without follow‐up, the mean age of 2399 patients was 75.9 years; men accounted for 55% of patients. Statins were administered to 447 (19%) patients after acute LVO onset. Patients in the statin group had more atherothrombotic cerebral infarctions (34.2% versus 12.1%, P P P P =0.02). The mortality at 90 days was lower in the statin group (4.7%) than the nonstatin group (12.5%; P P =0.02). Conclusions Statin administration after acute LVO onset is significantly associated with better functional outcome and mortality at 90 days.

Purpose Conventional genetic analyzers require surgically obtained tumor tissues to confirm the molecular diagnosis of diffuse glioma. Recent technical breakthroughs have enabled increased utilization of cell-free tumor DNA (ctDNA) in body fluids as a reliable resource for molecular diagnosis in various cancers. Here, we tested the application of a chip-based digital PCR system for the less invasive diagnosis (i.e., liquid biopsy) of diffuse glioma using the cerebrospinal fluid (CSF). Methods CSF samples from 34 patients with diffuse glioma were collected from the surgical field during craniotomy. Preoperative lumbar CSF collection was also performed in 11 patients. Extracted ctDNA was used to analyze diagnostic point mutations in IDH1 R132H, TERT promoter (C228T and C250T), and H3F3A (K27M) on the QuantStudio® 3D Digital PCR System. These results were compared with their corresponding tumor DNA samples. Results We detected either of the diagnostic mutations in tumor DNA samples from 28 of 34 patients. Among them, we achieved precise molecular diagnoses using intracranial CSF in 20 (71%). Univariate analyses revealed that the World Health Organization (WHO) grade (p = 0.0034), radiographic enhancement (p = 0.0006), and Mib1 index (p = 0.01) were significant predictors of precise CSF-based molecular diagnosis. We precisely diagnosed WHO grade III or IV diffuse gliomas using lumbar CSF obtained from 6 (87%) of 7 patients with tumors harboring any mutation. Conclusion We established a novel, non-invasive molecular diagnostic method using a chip-based digital PCR system targeting ctDNA derived from CSF with high sensitivity and specificity, especially for high-grade gliomas.

Background Recent prospective registration studies of transient ischemic attack in Western countries demonstrated that large artery atherosclerosis is the highest risk etiology for early stroke recurrence under urgent evaluation and treatment. On the other hand, some limited transient ischemic attack studies from East Asian countries showed transient ischemic attack patients due to small vessel occlusion were at a higher early stroke risk. Aims We aimed to assess the risk for early stroke in small vessel occlusion-transient ischemic attack patients in a Japanese large transient ischemic attack registry. Methods We analyzed the data of a prospective Japanese transient ischemic attack registry including 1320 transient ischemic attack patients within seven days after onset. Small vessel occlusion-transient ischemic attack was defined as the presence of lacunar transient ischemic attack syndrome, without other etiologies. The outcome measure was recurrent stroke within 30 days after transient ischemic attack. The predictors of 30-day recurrent stroke were estimated using the Cox proportional hazards model. Results The study population had a mean age of 69 ± 12 years and 470 were women. Recurrent stroke was observed in 61 patients (4.6%), and the highest rate was observed with small vessel occlusion-transient ischemic attack (7.8%), followed by large artery atherosclerosis (5.4%). In multivariate analysis, recurrent stroke was independently associated with small vessel occlusion-transient ischemic attack (hazard ratio (HR): 2.01, 95% confidence interval (CI): 1.19–3.35), higher systolic blood pressure (HR: 1.18, 95% CI: 1.08–1.28), and presentation within 3 h after onset (HR: 2.21, 95% CI: 1.27–4.04). Furthermore, small vessel occlusion-transient ischemic attack with acute small deep infarct on diffusion-weighted imaging was a stronger predictor of recurrent stroke (HR: 4.87, 95% CI: 2.09–10.0). Conclusion Small vessel occlusion-transient ischemic attack, especially with acute small deep infarct, had a higher early stroke risk compared with other etiologies in Japanese transient ischemic attack patients who received early management.

A subgroup analysis of spinal vascular lesions registered in the Japanese Registry of Neuroendovascular Therapy 2 (JR-NET2) and JR-NET3 was performed. About 172 analyzable cases of spinal dural arteriovenous fistula (SDAVF) were assessed, including the characteristics, treatment strategy, and treatment outcome. SDAVF was more common in middle-aged and older males. The most commonly affected area was the thoracolumbosacral region (83.7%), and most cases had a non-hemorrhagic onset (89.0%). Complete obliteration was achieved in 54.7%. Treatment-related complications occurred in three patients (7.0%). Post-treatment neurological improvement was achieved in 48.3%. The primary endpoint [modified Rankin Scale (mRS) score of 0-2 on postoperative day 30] was achieved in 60.5% of the cases. As a new discovery, the incidence of cervical SDAVF increased from 1.8% in JR-NET2 to 19.7% in JR-NET3. Compared with non-cervical SDAVF, cervical SDAVF was characterized by a higher proportion of hemorrhagic onset (P

Endovascular treatments for vasospasm after subarachnoid hemorrhage are typically performed for patients who are refractory to recommended medical therapies. We analyzed the current status of endovascular treatments based on the data of Japanese Registry of Neuroendovascular Therapy (JR-NET)3, and evaluated factors related to improvement of imaging findings and neurological condition, and to mechanical hemorrhage complications. We collected data of 1211 treatments performed from 2010 to 2014. Target vessels for treatments were anterior circulation (n = 1079), posterior circulation (n = 91), and both (n = 32); the distribution of vasospasm was the proximal vessel (n = 754) to the Circle of Willis, distal vessel (n = 329), and both (n = 119). Of the treatments, 948 cases (78.3%) were intra-arterial administration of vasodilators and 259 (21.4%) were percutaneous transluminal angioplasty (PTA); 879 cases were the first intervention. The treatment time from onset was within 3 h in 378 (31.2%) cases, between 3 and 6 h in 349 (28.8%) cases, and over 6 h in 245 (20.2%) cases. The statistically significant factors associated with improvement on imaging findings was the first treatment, and treatment within 3 h from onset compared with that after 6 h. Additionally, the first and early treatments after the symptoms were associated with significantly improved neurological condition. All complications of mechanical hemorrhage occurred along with PTA. The findings show that endovascular treatment for vasospasm was effective, especially for cases who suffered from symptomatic vasospasm with a short interval after onset.

Limited dorsal myeloschisis (LDM) is characterized by two invariable features: a focal closed neural tube defect and a fibroneural stalk linking the skin lesion to the underlying spinal cord. Although detailed histopathological findings of the LDM stalk were originally described by Pang et al., the precise relationship between the histopathological findings and clinical manifestations including intraoperative findings has not been fully determined. We retrospectively analyzed the histopathological findings of the almost entire stalk and their relevance to the clinical manifestations in six Japanese LDM patients with flat skin lesions. Glial fibrillary acidic protein (GFAP)-immunopositive neuroglial tissues were observed in three of the six patients. Unlike neuroglial tissues, peripheral nerve fibers were observed in every stalk. In four patients, dermal melanocytosis, “Mongolian spot,” was seen surrounding the cigarette-burn lesion. In three of these four patients, numerous melanocytes were distributed linearly along the long axis of the LDM stalk, which might represent migration of melanocytes from trunk neural crest cells during formation of the LDM stalk. Immunopositivity for GFAP in the LDM stalk was observed in as few as 50% of our patients, despite the relatively extensive histopathological examination. We confirm that the clinical diagnosis of LDM should be made based on comprehensive histopathological examination as well as clinical manifestations. The profuse network of peripheral nerve fibers in every stalk and the high incidence of melanocyte accumulation associated with dermal melanocytosis might assist the histopathological diagnosis of LDM.

Background We previously reported a favorable outcome in a case series of patients with oligodendrogliomas treated with upfront chemotherapy; however, their progression-free survival (PFS) was relatively short considering their long-term overall survival (OS). This suggests that salvage treatments after progression were effective. However, the clinical impact of salvage treatments on outcomes of patients with recurrent oligodendrogliomas has not been precisely investigated. Methods Our case series included 28 patients with newly diagnosed isocitrate dehydrogenase–mutant and 1p/19q-codeleted oligodendroglial tumors treated with upfront procarbazine, nimustine, and vincristine. Clinical outcomes and patterns of recurrence were reviewed retrospectively. Results The median follow-up period of enrolled patients was 90.2 months. Disease progression occurred in 15 patients (53.6%), whereas the cancer appeared as local relapse alone in 14 (93.3%) patients. Salvage treatments were performed for all local relapses; thereafter, most of the subsequent progressions also appeared as resectable local relapses. The 5-year PFS and OS rates from the first progression were 30.3% and 92.9%, respectively. These relatively short PFS and favorable OS indicated the effectiveness of salvage treatment even after multiple progression. Thus far, 9 (60%) of 15 patients are deterioration-free with locally controlled lesions or complete remission; however, clinical deterioration was observed in 6 patients, and 4 of them experienced dissemination. Conclusions In isocitrate dehydrogenase–mutant and 1p/19q-codeleted oligodendrogliomas, most of the tumors that demonstrated early progression appeared as local, nonlethal lesions, which have been well-controlled by salvage treatments. A precise diagnosis of oligodendrogliomas using molecular parameters is crucial to receive the best benefit from salvage treatment.

Objective This study aims to determine whether the line between the digastric point and posterior edge of the occipital condyle (DC line) could be a new surface landmark for the posterior margin of the horizontal part of the sigmoid sinus. Methods Cadaveric specimens were used to show the relationship between the DC line and retrosigmoid craniotomy. Three-dimensional computed tomography angiography images of adult heads (56 sides) were analyzed to measure the distance between the DC line and the horizontal part of the sigmoid sinus at the digastric point, posterior edge of the condyle, and midpoint of the line. Results The DC line was roughly parallel and posterior to the posterior margin of the sigmoid sinus. The distance between the DC line and the posterior edge of the sigmoid sinus at the digastric point, condyle, and midpoint of the line measured 4.7 ± 3.3 mm, 5.9 ± 2.6 mm, and 1.3 ± 2.2 mm, respectively. All sigmoid sinuses coursed anterior to the digastric point and condyle but in 17.9% (10/56 sides) the posterior edge of the sigmoid sinus extended a maximum of 4.1 mm posterior to the midpoint of the DC line. Conclusions The DC line can be used as a new surface landmark for estimating the position of the horizontal part of the sigmoid sinus. The posterior edge of the sinus may extend posterior to the line at the midpoint; thus, care should be taken to prevent sinus injury when drilling around the midpoint of the line.

To evaluate the performance of four-dimensional pseudo-continuous arterial spin labeling (4D-pCASL)-based angiography using CENTRA-keyhole and view sharing (4D-PACK) in the visualization of flow dynamics in distal cerebral arteries and leptomeningeal anastomosis (LMA) collaterals in moyamoya disease in comparison with contrast inherent inflow-enhanced multiphase angiography (CINEMA), with reference to digital subtraction angiography (DSA). Thirty-two cerebral hemispheres from 19 patients with moyamoya disease (mean age, 29.7 ± 19.6 years; five males, 14 females) underwent both 4D-MR angiography and DSA. Qualitative evaluations included the visualization of anterograde middle cerebral artery (MCA) flow and retrograde flow via LMA collaterals with reference to DSA. Quantitative evaluations included assessments of the contrast-to-noise ratio (CNR) on these vessels. The linear mixed-effect model was used to compare the 4D-PACK and CINEMA methods. The vessel visualization scores were significantly higher with 4D-PACK than with CINEMA in the visualization of anterograde flow for both Observer 1 (CINEMA, 3.53 ± 1.39; 4D-PACK, 4.53 ± 0.80; p < 0.0001) and Observer 2 (CINEMA, 3.50±1.39; 4D-PACK, 4.31 ± 0.86; p = 0.0009). The scores were higher with 4D-PACK than with CINEMA in the visualization of retrograde flow for both Observer 1 (CINEMA, 3.44 ± 1.05; 4D-PACK, 4.47 ± 0.88; p < 0.0001) and Observer 2 (CINEMA, 3.19 ± 1.20; 4D-PACK, 4.38 ± 0.91; p < 0.0001). The maximum CNR in the anterograde flow was higher in 4D-PACK (40.1 ± 16.1, p = 0.0001) than in CINEMA (27.0 ± 16.6). The maximum CNR in the retrograde flow was higher in 4D-PACK (36.1 ± 10.0, p < 0.0001) than in CINEMA (15.4 ± 8.0). The 4D-PACK provided better visualization and higher CNRs in distal cerebral arteries and LMA collaterals compared with CINEMA in patients with this disease. • The 4D-PACK enables good visualization of distal cerebral arteries in moyamoya disease. • The 4D-PACK enables direct visualization of leptomeningeal collateral vessels in moyamoya disease. • Vessel visualization by 4D-PACK can be useful in assessing cerebral hemodynamics.

OBJECTIVEAlthough heterogeneity in patient outcomes following subarachnoid hemorrhage (SAH) has been observed across different centers, the relative merits of clipping and coiling for SAH remain unknown. The authors sought to compare the patient outcomes between these therapeutic modalities using a large nationwide discharge database encompassing hospitals with different comprehensive stroke center (CSC) capabilities.METHODSThey analyzed data from 5214 patients with SAH (clipping 3624, coiling 1590) who had been urgently hospitalized at 393 institutions in Japan in the period from April 2012 to March 2013. In-hospital mortality, modified Rankin Scale (mRS) score, cerebral infarction, complications, hospital length of stay, and medical costs were compared between the clipping and coiling groups after adjustment for patient-level and hospital-level characteristics by using mixed-model analysis.RESULTSPatients who had undergone coiling had significantly higher in-hospital mortality (12.4% vs 8.7%, OR 1.3) and a shorter median hospital stay (32.0 vs 37.0 days, p < 0.001) than those who had undergone clipping. The respective proportions of patients discharged with mRS scores of 3–6 (46.4% and 42.9%) and median medical costs (thousands US$, 35.7 and 36.7) were not significantly different between the groups. These results remained robust after further adjustment for CSC capabilities as a hospital-related covariate.CONCLUSIONSDespite the increasing use of coiling, clipping remains the mainstay treatment for SAH. Regardless of CSC capabilities, clipping was associated with reduced in-hospital mortality, similar unfavorable functional outcomes and medical costs, and a longer hospital stay as compared with coiling in 2012 in Japan. Further study is required to determine the influence of unmeasured confounders.

ASL is useful in evaluating tumour blood flow and in detecting hypervascular tumours. The purpose of this study was to assess the additive value of ASL to non-contrast and contrast-enhanced (NC/CE)-T1WI for diagnosing residual or recurrent meningiomas. This retrospective study included 25 postoperative patients (20 women, 5 men; median age, 65 [32–85] years) with and 25 gender- and age-matched postoperative patients without residual or recurrent meningiomas. ASL was performed using a pseudocontinuous method. Seven independent observers (two radiology residents, two general radiologists and three neuroradiologists) participated in two reading sessions consisting of only NC/CE-T1WI (first session) or NC/CE-T1WI with ASL (second session). We evaluated the sensitivity and diagnostic performance for the detection of residual or recurrent meningiomas. The diagnostic performance was assessed using a figure of merit (FOM) calculated via jackknife free-response receiver-operating characteristics. Statistical analysis was performed with paired t tests, with a significance level of p < .05. The sensitivities were as follows (NC/CE-T1WI vs. NC/CE-T1WI with ASL): residents (62.1% vs. 70.7%), general radiologists (75.9% vs. 87.9%), neuroradiologists (97.7% vs. 100%) and all observers (81.3% vs. 88.2%). The FOMs were as follows (NC/CE-T1WI vs. NC/CE-T1WI with ASL): residents (0.76 vs. 0.83), general radiologists (0.83 vs. 0.93), neuroradiologists (0.95 vs. 0.99) and all observers (0.86 vs. 0.93). The addition of ASL significantly improved the diagnostic parameters for all observers except neuroradiologists (p

ObjectivesThis cross-sectional survey explored the characteristics and outcomes of direct oral anticoagulant (DOAC)–associated nontraumatic intracerebral hemorrhages (ICHs) by analyzing a large nationwide Japanese discharge database.MethodsWe analyzed data from 2,245 patients who experienced ICHs while taking anticoagulants (DOAC: 227; warfarin: 2,018) and were urgently hospitalized at 621 institutions in Japan between April 2010 and March 2015. We compared the DOAC- and warfarin-treated patients based on their backgrounds, ICH severities, antiplatelet therapies at admission, hematoma removal surgeries, reversal agents, mortality rates, and modified Rankin Scale scores at discharge.ResultsDOAC-associated ICHs were less likely to cause moderately or severely impaired consciousness (DOAC-associated ICHs: 31.3%; warfarin-associated ICHs: 39.4%; p = 0.002) or require surgical removal (DOAC-associated ICHs: 5.3%; warfarin-associated ICHs: 9.9%; p = 0.024) in the univariate analysis. Propensity score analysis revealed that patients with DOAC-associated ICHs also exhibited lower mortality rates within 1 day (odds ratio [OR] 4.96, p = 0.005), within 7 days (OR 2.29, p = 0.037), and during hospitalization (OR 1.96, p = 0.039).ConclusionsThis nationwide study revealed that DOAC-treated patients had less severe ICHs and lower mortality rates than did warfarin-treated patients, probably due to milder hemorrhages at admission and lower hematoma expansion frequencies.

Purpose To evaluate and compare the performance of acceleration-selective arterial spin labeling (AccASL) magnetic resonance (MR) angiography in the visualization of cerebral arteries and collateral vessels in patients with Moyamoya disease with that of time-of-flight (TOF) MR angiography, with digital subtraction angiography (DSA) as the reference standard. Materials and Methods Thirty-six cerebral hemispheres from 22 patients with Moyamoya disease underwent TOF and AccASL MR angiography and DSA. Qualitative evaluations included imaging of the terminal internal carotid artery (ICA), distal middle cerebral arteries (MCAs), Moyamoya vessels, and leptomeningeal anastomosis (LMA) collaterals with reference to DSA. Quantitative evaluations included assessment of contrast-to-noise ratio (CNR) and number of vessels in MCA branches. The linear mixed-effect model was used to compare the two methods. Results Mean scores for qualitative evaluation were significantly higher with AccASL angiography than with TOF angiography for imaging distal MCAs (3.9 ± 0.3 [standard deviation] vs 2.9 ± 1.1; P.001), Moyamoya vessels (3.6 ± 0.6 vs 2.7 ± 0.9, P.001), and LMA collaterals (3.8 ± 0.6 vs 1.8 ± 0.7, P.001). Scores for steno-occlusive degree around the terminal ICAs were better with TOF angiography than with AccASL angiography (2.6 ± 0.5 vs 2.4 ± 0.6, P = .023). CNRs in the M4 segment were significantly higher with AccASL angiography (11.9 ± 12.9, P.001) than with TOF angiography (4.1 ± 7.9). The number of vessels was significantly higher with AccASL angiography (18.3 ± 5.0, P.001) than with TOF angiography (8.9 ± 4.9). The increase in the number of vessels from TOF angiography to AccASL angiography was greater in patients with severe ICA steno-occlusion (late ICA stage group, 11.4 ± 4.5; early ICA stage group, 6.8 ± 4.0; P = .007) and well-developed leptomeningeal anastomosis (mildly developed LMA group, 7.1 ± 4.3; well-developed LMA group, 11.3 ± 4.5; P = .011). Conclusion AccASL MR angiography enables better visualization of distal cerebral arteries and collateral vessels in patients with Moyamoya disease than does TOF MR angiography, while TOF MR angiography enables better visualization of stenosis of proximal arteries. Both methods work in a mutually beneficial manner in the assessment of cerebral arteries.

Background: An ependyma-lined canal with surrounding neuroglial tissues can be present in lumbosacral lipomatous malformations; however, the precise embryological significance is still unclear. Method: Six out of 50 patients with lipomatous malformations had ependymal structures. We retrospectively analyzed the clinical, neuroradiological, and histological findings of these patients to demonstrate the relationship with the embryological background of the retained medullary cord (RMC), which normally regresses, but was retained here because of late arrest of secondary neurulation. Results: Five (13.9%) of 36 patients with filar and caudal types and 1 of 3 lipomyelomeningoceles had ependymal structures, while none with dorsal and transitional types had these tissues. Histologically, the ependymal structures surrounded by neuroglial tissue and containing various amounts of adipose tissue bear a striking resemblance to the ependymal structures in RMC. Conclusion: The 13.9% incidence of association between the ependymal structures and filar and caudal types is thought to be because of second ary neurulation failure with the same embryological background as that of RMC. Dorsal and transitional types, resulting from primary neurulation failure, therefore, did not have ependymal structures.

Purpose: It is well known that bony and cartilaginous tissues can be present in lumbosacral lipomas; however, the relationship between their presence and clinical features has not been demonstrated. Methods: Five (10.4%) out of 48 patients had osteochondral tissues in lipomas. We retrospectively analyzed the clinical, neuroradiological, and histological findings of these patients. Results: Five (45.5%) of 11 patients with dorsal and transitional type lipomas had osteochondral tissues, while none with caudal and filar type lipomas had these tissues. Presurgical imaging demonstrated that the osteochondral tissue was located in a large subcutaneous lipoma dorsal to the bifid vertebral column. Histologically, mature bone with hematopoietic marrow and hyaline cartilage were observed in 3 and 2 patients, respectively. Conclusions: The high incidence of association of osteochondral tissues with dorsal and transitional type lipomas is thought to be the result of primary neurulation failure with invasion of mesenchymal tissues. Caudal and filar type lipomas, resulting from secondary neurulation failure, thus did not have osteochondral tissue.

A retained medullary cord (RMC) is a rare closed spinal dysraphism with a robust elongated neural structure continuous from the conus and extending to the dural cul-de-sac. One case extending down to the base of a subcutaneous meningocele at the sacral level has been reported. We report on three cases of closed spinal dysraphism, in which a spinal cord-like tethering structure extended out from the dural cul-de-sac and terminated at a skin-covered meningocele sac in the sacrococcygeal region, which was well delineated in curvilinear coronal reconstructed images of 3D-heavily T2-weighted images (3D-hT2WI). Intraoperative neurophysiology revealed the spinal cord-like tethering structure was nonfunctional, and histopathology showed that it consisted of central nervous system tissue, consistent with RMC. The tethering structure histologically contained a glioneuronal core with an ependymal-like lumen and smooth muscle, which may indicate developmental failure during secondary neurulation. When the RMC extending to a meningocele is demonstrated with the detailed magnet resonance imaging including 3D-hT2WI, decision to cut the cord-like structure for untethering of the nervous tissue should be made under careful intraoperative neurophysiological monitoring.

A recurrent glycine-to-arginine/valine alteration at codon 34 (G34R/V) within H3F3A, a gene that encodes the replication-independent histone variant H3.3, reportedly occurs exclusively in pediatric glioblastomas. However, the clinicopathological and biological significances of this mutation have not been completely elucidated; especially, no such data exist for tumor samples from Japanese patients. We analyzed 411 consecutive glioma cases representing patients of all ages. Our results demonstrated that 14 patients (3.4%) harbored H3F3A mutations, of which four had G34R mutations and 10 had K27M mutations. G34R-mutant tumors were located in the parietal region in two patients and the basal ganglia in one patient. One patient showed multi-lobular extension similar to the pattern observed in gliomatosis cerebri. Regarding neuroradiological features, intratumoral calcification was evident in two cases and all cases showed no or scarce contrast enhancement on MRI. Histopathologically, the four G34R-mutant cases included three glioblastomas and one astroblastoma. We have also investigated alterations in histone methylation including H3K27me3, H3K9me3, and H3K4me3 in G34R-mutant samples by immunohistochemistry. These results indicate that G34R-mutant tumors are likely to show extensive infiltration and alterations in global histone trimethylation might also play an important role in G34R mutant tumors.

To evaluate the usefulness of 4D-MR angiography based on super-selective pseudo-continuous ASL combined with keyhole and view-sharing (4D-S-PACK) for vessel-selective visualization and to examine the ability of this technique to visualize brain arteriovenous malformations (AVMs). In this retrospective study, 15 patients (ten men and five women, mean age 44.0 ± 16.9 years) with brain AVMs were enrolled. All patients were imaged with 4D-PACK (non-selective), 4D-S-PACK, and digital subtraction angiography (DSA). Observers evaluated vessel selectivity, identification of feeding arteries and venous drainage patterns, visualization scores, and contrast-to-noise ratio (CNR) for each AVM component. Measurements were compared between the MR methods. Vessel selectivity was graded 4 in 43/45 (95.6%, observer 1) and 42/45 (93.3%, observer 2) territories and graded 3 in two (observer 1) and three (observer 2) territories. The sensitivity and specificity for identification of feeding arteries for both observers was 88.9% and 100% on 4D-PACK, and 100% and 100% on 4D-S-PACK, respectively. For venous drainage, the sensitivity and specificity was 100% on both methods for observer 1. The sensitivity and specificity for observer 2 was 94.4% and 83.3% on 4D-PACK, and 94.4% and 91.7% on 4D-S-PACK, respectively. The CNRs at the timepoint of 1600 ms were slightly lower in 4D-S-PACK than in 4D-PACK for all AVM components (Feeding artery, p = .02; nidus, p = .001; and draining artery, p = .02). The visualization scores for both observers were not significantly different between 4D-PACK and 4D-S-PACK for all components. 4D-S-PACK could be a useful non-invasive clinical tool for assessing hemodynamics in brain AVMs. • The 4D-MR angiography based on super-selective pseudo-continuous arterial spin labeling combined with CENTRA-keyhole and view-sharing (4D-S-PACK) enabled excellent vessel selectivity. • The 4D-S-PACK enabled the perfect identification of feeding arteries of brain arteriovenous malformation (AVM). • 4D-S-PACK could be a non-invasive clinical tool for assessing hemodynamics in brain AVMs.

Objective We sought to examine whether the effect of treatment modality and drugs for cerebral vasospasm on clinical outcomes differs between elderly and non-elderly subarachnoid hemorrhage (SAH) patients in Japan. Methods We analyzed the J-ASPECT Study Diagnosis Procedure Combination database (n = 17,343) that underwent clipping or coiling between 2010 and 2014 in 579 hospitals. We stratified patients into two groups according to their age (elderly [≥75 years old], n = 3,885; non-elderly, n = 13,458). We analyzed the effect of treatment modality and anti-vasospasm agents (fasudil hydrochloride, ozagrel sodium, cilostazol, statin, eicosapentaenoic acid [EPA], and edaravone) on in-hospital poor outcomes (mRS 3–6 at discharge) and mortality using multivariable analysis. Results The elderly patients were more likely to be female, have impaired levels of consciousness and comorbidity, and less likely to be treated with clipping and anti-vasospasm agents, except for ozagrel sodium and statin. In-hospital mortality and poor outcomes were higher in the elderly (15.8% vs. 8.5%, 71.7% vs. 36.5%). Coiling was associated with higher mortality (odds ratio 1.43, 95% confidence interval 1.2–1.7) despite a lower proportion of poor outcomes (0.84, 0.75–0.94) in the non-elderly, in contrast to no effect on clinical outcomes in the elderly. A comparable effect of anti-vasospasm agents on mortality was observed between non-elderly and elderly for fasudil hydrochloride (non-elderly: 0.20, 0.17–0.24), statin (0.63, 0.50–0.79), ozagrel sodium (0.72, 0.60–0.86), and cilostazol (0.63, 0.51–0.77). Poor outcomes were inversely associated with fasudil hydrochloride (0.59, 0.51–0.68), statin (0.84, 0.75–0.94), and EPA (0.83, 0.72–0.94) use in the non-elderly. No effect of these agents on poor outcomes was observed in the elderly. Conclusions In contrast to the non-elderly, no effect of treatment modality on clinical outcomes were observed in the elderly. A comparable effect of anti-vasospasm agents was observed on mortality, but not on functional outcomes, between the non-elderly and elderly.

Endovascular treatment of extracranial steno-occlusive lesions is an alternative to direct surgery. There is no consensus regarding the natural course and standard treatment of these lesions. The aim of this study was to identify the current status of endovascular treatment for extracranial steno-occlusive lesions. A total of 1154 procedures for extracranial steno-occlusive lesions, except for internal carotid artery stenosis, were collected from the Japanese Registry of Neuroendovascular Therapy 3 (JR-NET3). Atherosclerotic lesions were most frequent (1021 patients, 88.5%). Endovascular treatment was performed for 456 (39.5%) patients with subclavian artery, 349 (30.2%) with extracranial vertebral artery, 172 (14.9%) with the origin of common carotid artery, and 38 (3.3%) with innominate artery stenosis; the overall technical success rate was 98.0%. Percutaneous transluminal angioplasty was performed in 307 patients (26.6%) and stenting in 838 (72.6%). An embolic protection device (EPD) was used in 571 patients (49.5%), and procedure under general anesthesia was performed in 168 (14.6%). Preoperative antiplatelet therapy was administered in 1091 procedures (94.5%). A good outcome was obtained for 962 patients (83.4%). Complications were observed in 89 patients (7.7%). The procedure under general anesthesia was statistically significant factors (P

OBJECTIVEJapan has been reported to have the highest (and increasing) incidence of subarachnoid hemorrhage (SAH) in the world. However, there has never been a report on the nationwide incidence rate and recent trends for SAH in Japan. In this register-based study, the authors aimed to clarify the estimated nationwide SAH incidence rate and the recent trend in SAH incidence in Japan and the reasons for any changes in this trend.METHODSThe authors compiled data from the Japanese Ministry of Health, Labour and Welfare and from the records of the Japan Neurosurgical Society. They reviewed the age-standardized nationwide SAH mortality rate, the estimated age-standardized SAH incidence rate according to the age-standardized SAH mortality rate, and the estimated crude SAH incidence rate, including the 95% confidence intervals, from 2003 to 2015. The trends in the number of treatments for unruptured and ruptured cerebral aneurysms, as well as the prevalence of hypertension, current smoking status, and use of cholesterol-lowering drugs, were assessed. The estimated treatment rate for unruptured cerebral aneurysms (UCAs) was also calculated along with the 95% confidence interval.RESULTSThe estimated age-standardized nationwide SAH incidence rate significantly declined from 31.34 cases (95% CI 31.32–31.34) to 27.63 (95% CI 27.59–27.63; decrease by 11.8%) per 100,000 person-years. This decline was based on the 2010 population as the reference from 2003 through 2015 and a case-fatality rate of SAH that was assumed to decrease by 1% annually from 44% in 2003 to 32% in 2015. According to sensitivity analysis, the change rate of the estimated age-standardized SAH incidence rate ranged from −56.69% to 23.27%, with a mean of −30.91% (SD 20.52%), and there were decline trends in 92% of all trends. The estimated nationwide crude SAH incidence rate also showed a significant decline from 23.79 (95% CI 23.78–23.79) to 20.25 (95% CI 20.24–20.25; decrease by 14.9%) per 100,000 person-years. The trend in treatment numbers for UCAs increased significantly (p < 0.0001) from 2003 through 2015; however, the estimated treatment rate for UCAs was only 0.19 (95% CI 0.19–0.20) to 0.51 (95% CI 0.50–0.51) among all UCA patients. The prevalence of hypertension (males, p = 0.0003; females, p < 0.0001) and current smoking status (males, p < 0.0001; females, p = 0.0002) declined significantly from 2003 through 2015, while the use of cholesterol-lowering drugs increased significantly (males, p < 0.0001; females, p = 0.0005) during the same period.CONCLUSIONSThe estimated nationwide SAH incidence rate in Japan was higher than rates in other countries, although it has declined recently. An improving lifestyle may have contributed to the declining rate of SAH incidence in Japan.

Background Various radiologic patterns of posterior reversible encephalopathy syndrome (PRES) have been reported. Among them, PRES involving brainstem, thalamus, or deep white matter and lacking parieto-occipital edema is rare. Although PRES in general has a benign course, PRES-related intracranial hemorrhage has been associated with a poor prognosis. We report a case of variant type of PRES associated with deep brain hemorrhage and discuss the characteristics of PRES-related intracranial hemorrhage via a literature review. Case Description A woman aged 41 years with a history of untreated hypertension presented to our hospital complaining of severe headache and with an elevated blood pressure of 237/142 mmHg. Computed tomography revealed a hemorrhage in the left thalamus and basal ganglia. Magnetic resonance imaging revealed remarkable hyperintensity in the left cerebellum, pons, bilateral temporal lobes, bilateral basal ganglia, and bilateral cerebral white matter on fluid-attenuated inversion recovery imaging, which represented vasogenic edema. The parieto-occipital regions were unremarkable. Given this clinical presentation, PRES associated with deep brain hemorrhage was suspected. The patient received strict blood pressure control treatment, which resulted in gradual symptom improvement. Magnetic resonance images obtained 1 month after admission demonstrated an almost complete resolution of the edema. Conclusions Although hemorrhage in the thalamus, basal ganglia, or brainstem is uncommon in patients with PRES, it may occur in patients with variant type of PRES involving these lesions. It is important to recognize the presence of variant patterns of clinical features and radiologic findings of PRES to allow for early identification and appropriate treatment.

Stroke is one of the major causes of maternal death. This study aimed to analyze the maternal and fetal outcomes of stroke occurred during pregnancy and puerperium.We conducted a retrospective analysis of patients admitted to our perinatology center between 1982 and 2012 with a diagnosis of acute cerebral stroke during pregnancy or within 6 weeks postpartum.Thirty-four patients were registered and all the patients had never been diagnosed as stroke nor detected cerebrovascular abnormalities before the current pregnancies. They were divided into 8 ischemic strokes (ISs) and 26 intracranial hemorrhage group. In the hemorrhage group, there was a spontaneous abortion and two patients chose artificial abortions to avoid rehemorrhage, and there were another three intrauterine fetal deaths (IUFDs) in the acute stage of maternal stroke. More patients in hemorrhage group delivered in preterm than in IS group for the treatment of stroke, 10/23 (43%)Hemorrhagic stroke was more common etiology of stroke related to pregnancy than IS in this study. Intensive and multidisciplinary care was needed especially in hemorrhagic stroke related to pregnancy as in the hemorrhagic stroke the fetal survival rate was lower, and maternal conscious levels at the onset of the stroke and neurological outcomes in the chronic stage were worse than IS.

Background We aimed to develop quality indicators (QIs) related to primary and comprehensive stroke care and examine the feasibility of their measurement using the existing Diagnosis Procedure Combination (DPC) database. Methods and results We conducted a systematic review of domestic and international studies using the modified Delphi method. Feasibility of measuring the QI adherence rates was examined using a DPC-based nationwide stroke database (396,350 patients admitted during 2013-2015 to 558 hospitals participating in the J-ASPECT study). Associations between adherence rates of these QIs and hospital characteristics were analyzed using hierarchical logistic regression analysis. We developed 17 and 12 measures as QIs for primary and comprehensive stroke care, respectively. We found that measurement of the adherence rates of the developed QIs using the existing DPC database was feasible for the 6 QIs (primary stroke care: early and discharge antithrombotic drugs, mean 54.6% and 58.7%; discharge anticoagulation for atrial fibrillation, 64.4%; discharge antihypertensive agents, 51.7%; comprehensive stroke care: fasudil hydrochloride or ozagrel sodium for vasospasm prevention, 86.9%; death complications of diagnostic neuroangiography, 0.4%). We found wide inter-hospital variation in QI adherence rates based on hospital characteristics. Conclusions We developed QIs for primary and comprehensive stroke care. The DPC database may allow efficient data collection at low cost and decreased burden to evaluate the developed QIs.

First-line bevacizumab (BEV) is now available as a treatment option for glioblastoma patients with severe clinical conditions in Japan. However, the survival benefits remain controversial. To elucidate these potential survival benefits, we retrospectively analyzed survival in glioblastoma patients receiving BEV. We analyzed survival in 120 patients with IDH-wild type glioblastoma treated from 2002 to 2018. Overall survival (OS) was assessed in three treatment era subgroups [pre-temozolomide (TMZ), TMZ, and TMZ–BEV], and the correlations of prognostic factors with survival were evaluated. An improvement in survival was observed after BEV approval (median OS in the pre-TMZ, TMZ, and TMZ–BEV eras: 14.6, 14.9, and 22.1 months, respectively). A Cox proportional hazards model identified extent of resection and MGMT methylation status as significant prognostic factors in the TMZ era; however, these factors were not significant in the TMZ–BEV era. In subgroup analyses, patients with MGMT methylation had improved OS after TMZ introduction (pre-TMZ vs. TMZ, 18.5 vs. 28.1 months; P = 0.13), and those without MGMT methylation had significantly increased OS after BEV approval (TMZ vs. TMZ–BEV, 12.2 vs. 16.7 months; P = 0.04). Our findings imply that optional first-line administration of BEV can overcome the impact of conventional risk factors and prolong survival complementary to TMZ. The patient subgroups benefitting from TMZ and BEV did not seem to overlap, and stratification based on risk factors, including MGMT methylation status, might be effective for selecting patients in whom BEV should be preferentially used as a first-line therapy.

The characteristics of cerebral aneurysms in Japan differ from other countries in the higher incidence of unruptured cerebral aneurysm detected by brain check-up screening, higher rupture rate of unruptured cerebral aneurysm, higher incidence of subarachnoid hemorrhage, and superior outcome after subarachnoid hemorrhage based on meta-analysis. Head shape, genetic features, environmental factors, demographics, and medical system in Japan are also different from other countries. Unruptured cerebral aneurysms are 2.8 times more likely to rupture in Japanese than western aneurysms, resulting in the highest incidence of subarachnoid hemorrhage in the world. The exact and specific mechanisms of de novo, growth, and rupture of cerebral aneurysms have not been elucidated. Investigations will contribute to the understanding of cerebral aneurysms and subarachnoid hemorrhage worldwide. Some features of cerebral aneurysm in Japan are discussed for possible research guidance in the elucidation of the predominance of subarachnoid hemorrhage in Japan.

There has been no precise guide for treatment management of aneurysmal subarachnoid hemorrhage (aSAH) based on the patient's age and treatment method. This study clarifies each risk management for aSAH according to age and treatment method listed in a nationwide database.We compared 2 groups of patients (nonelderly,65 years; elderly, ≥65 years) who underwent surgical clipping or endovascular coiling and were registered in a nationwide database in Japan from 2010 to 2015. The odds ratio (OR) and 95% confidence interval (CI) of each risk factor were calculated through multivariate logistic regression analysis for poor outcome according to a modified Rankin Scale score2 at discharge for each group.In all groups, the risk factors for poor outcome were older age, male sex, neurologic grade on admission, diabetes mellitus, and use of anticoagulation drugs. Inverse risk factors were a high-volume hospital, academic hospital, hypertension, and use of an antiplatelet drug (OR, 0.63-0.81; 95% CI, 0.56-0.88). Chronic heart disease was also a risk factor, but use of a statin drug (OR, 0.85-0.87; 95% CI, 0.76-0.97) and location other than on the anterior communicating artery (OR, 0.74-0.80; 95% CI, 0.67-0.91) were inverse risks in both the elderly and the endovascular coiling groups.Management for patients with aneurysmal subarachnoid hemorrhage was recommended in high-volume and academic institutes with the administration of antiplatelet drugs and consideration of several risk factors. Elderly patients undergoing endovascular coiling might be better given a statin drug, and patients with chronic heart failure or an anterior communicating artery aneurysm should be treated more carefully.

This study aimed to clarify the risk factors of treatment for unruptured cerebral aneurysms (UCAs) in elderly patients by comparing the morbidity at discharge between surgical clipping and endovascular coiling in nonelderly (65 years) and elderly (≥65 years) patients based on a national database in Japan.A total of 36,017, including 15,671 patients with UCA after exclusion of unknown location, were registered in the Diagnosis Procedure Combination, the nationwide database, from 2010 to 2015 in Japan. Outcome of Barthel Index at discharge was investigated and multivariate logistic regression analysis identified risk factors for morbidity of Barthel Index90 at discharge in nonelderly and elderly patient groups.Risk factors for morbidity at discharge were basilar artery aneurysm compared with internal carotid artery (ICA), diabetes mellitus (odds ratio [OR], 2.0-2.5; 95% confidence interval [CI], 1.6-3.7), antiplatelet drug, and anticoagulation drug; however, highest hospital volume compared with lowest was an inverse risk factor in both age groups. Endovascular coiling (OR, 0.4; 95% CI, 0.3-0.5) was a significantly inverse risk in the elderly group. Anterior communicating artery aneurysm compared with ICA was a significant risk (OR, 1.6; 95% CI, 1.0-2.6) in the nonelderly group; on the other hand, anterior communicating artery aneurysm (OR, 0.7; 95% CI, 0.5-0.95) and middle cerebral artery aneurysm (OR, 0.6; 95% CI, 0.5-0.8) compared with ICA were significantly inverse risks in the elderly group.Endovascular coiling after control of diabetes mellitus was recommended for the treatment of UCA in elderly patients. The ICA location of aneurysm in the elderly should be paid attention as the treatment risk.

Background We aimed to improve the assessment quality of plaque vulnerability with combined use of magnetic resonance imaging and contrast‐enhanced ultrasound ( CEUS ). Methods and Results We prospectively enrolled 71 patients with internal carotid artery stenosis who underwent carotid endarterectomy and performed preoperative CEUS and magnetic resonance plaque imaging. We distinguished high–signal‐intensity plaques ( HIP s) and non‐ HIP s based on magnetization‐prepared rapid acquisition with gradient echo images. We graded them according to the CEUS contrast effect and compared the CEUS images with the carotid endarterectomy specimens. Among the 70 plaques, except 1 carotid endarterectomy tissue sample failure, 59 were classified as HIP s (43 symptomatic) and 11 were classified as non‐ HIP s (5 symptomatic). Although the magnetization‐prepared rapid acquisition with gradient echo findings alone had no significant correlation with symptoms ( P =0.07), concomitant use of magnetization‐prepared rapid acquisition with gradient echo and CEUS findings did show a significant correlation ( P CEUS showed that all 5 symptomatic non‐ HIP s had a high‐contrast effect. These 5 plaques were histopathologically confirmed as vulnerable, with extensive neovascularization but only a small amount of intraplaque hemorrhage. Conclusions Complementary use of magnetic resonance imaging and CEUS to detect intraplaque hemorrhage and neovascularization in plaques can be useful for evaluating plaque vulnerability, consistent with the destabilization process associated with neovessel formation and subsequent intraplaque hemorrhage.