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Moyamoya disease (MMD) is characterized by progressive arterial occlusion, causing chronic hemodynamic impairment, which can reduce brain volume. A novel quantitative technique, synthetic magnetic resonance imaging (SyMRI), can evaluate brain volume. This study aimed to investigate whether brain volume measured with SyMRI correlated with cerebral blood flow (CBF) and brain function in adult MMD. In this retrospective study, 18 adult patients with MMD were included. CBF was measured using iodine-123-N-isopropyl-p-iodoamphetamine single photon emission computed tomography. Cerebrovascular reactivity (CVR) to acetazolamide challenge was also evaluated. Brain function was measured using the Wechsler Adult Intelligence Scales (WAIS)-III/IV and the WAIS-R tests. Gray matter (GM), white matter, and myelin-correlated volumes were evaluated in six areas. Resting CBF was positively correlated with GM fractions in the right anterior cerebral arterial and right middle cerebral arterial (MCA) territories. CVR was positively correlated with GM fraction in the right posterior cerebral arterial (PCA) territory. Full-Scale Intelligence Quotient and Verbal Comprehension Index scores were marginally positively correlated with GM fractions in the left PCA territory. Processing Speed Index score was marginally positively correlated with GM fraction in the right MCA territory. The SyMRI-measured territorial GM fraction correlated with CBF and brain function in patients with MMD.

ObjectivesTo 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).MethodsIn 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.ResultsVessel 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.Conclusions4D-S-PACK could be a useful non-invasive clinical tool for assessing hemodynamics in brain AVMs.Key Points• 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.

ObjectivesTo 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).MethodsThirty-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.ResultsThe 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).ConclusionsThe 4D-PACK provided better visualization and higher CNRs in distal cerebral arteries and LMA collaterals compared with CINEMA in patients with this disease.Key Points• 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.

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. 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. 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. 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.

Angiogenic factors associated with Moyamoya disease (MMD) are overexpressed in M2 polarized microglia in ischemic stroke, suggesting that microglia may be involved in the pathophysiology of MMD; however, existing approaches are not applicable to explore this hypothesis. Herein we applied blood induced microglial-like (iMG) cells. We recruited 25 adult patients with MMD and 24 healthy volunteers. Patients with MMD were subdivided into progressive (N = 7) or stable (N = 18) group whether novel symptoms or radiographic advancement of Suzuki stage within 1 year was observed or not. We produced 3 types of iMG cells; resting, M1-, and M2-induced cells from monocytes, then RNA sequencing followed by GO and KEGG pathway enrichment analysis and qPCR assay were performed. RNA sequencing of M2-induced iMG cells revealed that 600 genes were significantly upregulated (338) or downregulated (262) in patients with MMD. Inflammation and immune-related factors and angiogenesis-related factors were specifically associated with MMD in GO analysis. qPCR for MMP9 , VEGFA , and TGFB1 expression validated these findings. This study is the first to demonstrate that M2 microglia may be involved in the angiogenic process of MMD. The iMG technique provides a promising approach to explore the bioactivity of microglia in cerebrovascular diseases.

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%, p<0.001; mTICI 3, 35.8% vs 25.5%, p=0.009) and final mTICI ≥2b recanalization (89.1% vs 82.0%, p=0.020) rates were significantly higher, puncture-to-reperfusion time was shorter (median (IQR) 43 (31.5–69) vs 55 (38–82.2) min, p<0.001), and the number of passes were fewer (mean±SD 1.72±0.92 vs 1.99±1.01, p<0.001) in the SCBT group. Procedural complications were similar between the groups. In subgroup analysis, SCBT was more effective in women, cardioembolic stroke patients, and internal carotid artery and M2 occlusions.ConclusionsSCBT increases the SRFP rate and shortens the puncture-to-reperfusion time without increasing procedural complications.

Background: Pericytes are multifunctional cells surrounding capillaries and postcapillary venules. In brain microvasculature, pericytes play a pivotal role under physiological and pathological conditions by producing reactive oxygen species (ROS). The aims of this study were to elucidate the source of ROS and its regulation in human brain pericytes. Methods: The expression of Nox enzymes in the cells was evaluated using RT-PCR and western blot. Superoxide production was determined by superoxide dismutase-inhibitable chemiluminescence. Silencing of Nox4 was performed using RNAi, and cell proliferation was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Results: Nox4 was predominant among the Nox family in human brain pericytes. Membrane fractions of cells produced superoxide in the presence of NAD(P)H. Superoxide production was almost abolished with diphenileneiodonium, a Nox inhibitor; however, inhibitors of other possible superoxide-producing enzymes had no effect on NAD(P)H-dependent superoxide production. Pericytes expressed angiotensin II (Ang II) receptors, and Ang II upregulated Nox4 expression. Hypoxic conditions also increased the Nox4 expression. Silencing of Nox4 significantly reduced ROS production and attenuated cell proliferation. Conclusion: Our study showed that Nox4 is a major superoxide-producing enzyme and that its expression is regulated by Ang II and hypoxic stress in human brain pericytes. In addition, Nox4 may promote cell growth.

Purpose 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. Methods 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. Results 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  < 0.0001), respectively. The CNRs in the nidus were higher in AccASL than in TOF (29.9 ± 16.7 vs. 20.8 ± 16.5, p  = 0.0002), as in the draining vein (23.2 ± 13.0 vs. 12.6 ± 12.0, p  = 0.0010), respectively. Conclusions AccASL better visualized brain AVMs compared with TOF and was useful for grading without the use of contrast agents.

ObjectivesComprehensive stroke centre (CSC) capabilities are associated with reduced in-hospital mortality due to acute stroke. However, it remains unclear whether there are improving trends in the CSC capabilities or how hospital-related factors determine quality improvement. This study examined whether CSC capabilities changed in Japan between 2010 and 2018 and and whether any changes were influenced by hospital characteristics.DesignA hospital-based cross-sectional study.SettingWe sent out questionnaires to the training institutions of the Japan Neurosurgical Society and Japan Stroke Society in 2010, 2014 and 2018.Participants749 hospitals in 2010, 532 hospitals in 2014 and 786 hospitals in 2018 participated in the J-ASPECT study, a nationwide survey of acute stroke care capacity for proper designation of a comprehensive stroke centre in Japan.Main outcome measuresCSC capabilities were assessed using the validated scoring system (CSC score: 1–25 points) in 2010, 2014 and 2018 survey. The effect of hospital characteristics was examined using multiple logistic regression analysis.ResultsAmong the 323 hospitals that responded to all surveys, the implementation of 13 recommended items increased. The CSC score (median and IQR) was 16 (13–19), 18 (14–20) and 19 (15–21) for 2010, 2014 and 2018, respectively (p<0.001). There was a ≥20% increase in six items (eg, endovascular physicians, stroke unit and interventional coverage 24/7), and a ≤20% decrease in community education. A lower baseline CSC score (OR: 0.82, 95% CI 0.75 to 0.9), the number of beds≥500 (OR: 3.9, 95% CI 1.2 to 13.0) and the number of stroke physicians (7–9) (OR: 2.6, 95% CI 1.1 to 6.3) were associated with improved CSC capabilities, independent of geographical location.ConclusionsThere was a significant improvement in CSC capabilities between 2010 and 2018, which was mainly related to the availability of endovascular treatment and multidisciplinary care. Our findings may be useful to determine which hospitals should be targeted to improve CSC capabilities in a defined area.

This study aimed to elucidate the anatomical characteristics of the ascending pharyngeal artery (APhA) using three-dimensional rotational angiography (3D-RA) and its role in preventing complications during carotid endarterectomy (CEA). Data from 279 primary CEAs (259 patients; median age, 73 years; male/female ratio, 6.2:1) conducted between 2006 and 2022 at a single center were retrospectively analyzed. The APhA anatomy was evaluated using carotid 3D-RA. The APhA was identified on 3D-RA in 277 of 279 carotid arteries (99.3%), with 98.6% showing a single APhA and 1.4% duplication. Among single APhAs, 60.1% arose from the external carotid artery (ECA), 34.8% from the occipital artery, 3.3% from the internal carotid artery, and 1.5% from the carotid bifurcation. Of the 170 APhAs directly arising from the ECA, 64.1% originated from the medial wall and 35.9% from the posterior wall. A higher carotid bifurcation level significantly correlated with a shorter distance between the APhA origin and carotid bifurcation (Spearman’s rho = − 0.583; p  < 0.001). During CEA, APhA manipulation with cross-clamping was required in 15.8% (44/279) of cases, and no unexpected back-bleeding occurred. The incidence of cranial nerve injury (CNI) was 1.4% (4/279), with a trend toward higher risk when the APhA was manipulated (odds ratio, 5.70; p  = 0.086). The APhA typically originates medially or posteriorly from the carotid artery. In standard antero-lateral CEA approaches, this places the APhA on the obscured backside of the artery, emphasizing the importance of preoperative identification and intraoperative management to prevent back-bleeding and CNI.