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Background: Long-term outcomes are unknown in patients with asymptomatic moyamoya disease. In this report, we aimed to clarify their 5-year risk of stroke and its predictors. Methods: We are conducting a multicenter, prospective cohort study (Asymptomatic Moyamoya Registry) in Japan. Participants were eligible if they were 20 to 70 years, had bilateral or unilateral moyamoya disease, experienced no episodes suggestive of TIA and stroke; and were functionally independent (modified Rankin Scale score 0–1). Demographic and radiological information was collected at enrollment. In this study, they are still followed up for 10 years. In this interim analysis, we defined the primary end point as a stroke occurring during a 5-year follow-up period. Independent predictors for stroke were also determined, using a stratification analysis method. Results: Between 2012 and 2015, we enrolled 109 patients, of whom 103 patients with 182 involved hemispheres completed the 5-year follow-up. According to the findings on DSA and MRA, 143 hemispheres were judged as moyamoya disease and 39 hemispheres as questionable manifestations (isolated middle cerebral artery stenosis). The patients with questionable hemispheres were significantly older, more often male, and more frequently had hypertension than those with moyamoya hemisphere. Moyamoya hemispheres developed 7 strokes, including 6 hemorrhagic and 1 ischemic stroke, during the first 5 years. The annual risk of stroke was 1.4% per person, 0.8% per hemisphere, and 1.0% per moyamoya hemisphere. Independent predictor for stroke was Grade-2 choroidal anastomosis (hazard ratio, 5.05 [95% CI, 1.24–20.6]; P =0.023). Furthermore, microbleeds (hazard ratio, 4.89 [95% CI, 1.13-21.3]; P =0.0342) and Grade-2 choroidal anastomosis (hazard ratio, 7.05 [95% CI, 1.62–30.7]; P =0.0093) significantly predicted hemorrhagic stroke. No questionable hemispheres developed any stroke. Conclusions: The hemispheres with asymptomatic moyamoya disease may carry a 1.0% annual risk of stroke during the first 5 years, the majority of which are hemorrhagic stroke. Grade-2 choroidal anastomosis may predict stroke, and the microbleeds and Grade-2 choroidal anastomosis may carry the risk for hemorrhagic stroke. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: UMIN000006640.

Neuroimaging using the 7-Tesla (7T) human magnetic resonance (MR) system is rapidly gaining popularity after being approved for clinical use in the European Union and the USA. This trend is the same for functional MR imaging (MRI). The primary advantages of 7T over lower magnetic fields are its higher signal-to-noise and contrast-to-noise ratios, which provide high-resolution acquisitions and better contrast, making it easier to detect lesions and structural changes in brain disorders. Another advantage is the capability to measure a greater number of neurochemicals by virtue of the increased spectral resolution. Many structural and functional studies using 7T have been conducted to visualize details in the white matter and layers of the cortex and hippocampus, the subnucleus or regions of the putamen, the globus pallidus, thalamus and substantia nigra, and in small structures, such as the subthalamic nucleus, habenula, perforating arteries, and the perivascular space, that are difficult to observe at lower magnetic field strengths. The target disorders for 7T neuroimaging range from tumoral diseases to vascular, neurodegenerative, and psychiatric disorders, including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, epilepsy, major depressive disorder, and schizophrenia. MR spectroscopy has also been used for research because of its increased chemical shift that separates overlapping peaks and resolves neurochemicals more effectively at 7T than a lower magnetic field. This paper presents a narrative review of these topics and an illustrative presentation of images obtained at 7T. We expect 7T neuroimaging to provide a new imaging biomarker of various brain disorders.

Purpose Diffusion-weighted MRI (DWI) is an essential sequence for evaluating pediatric patients with moyamoya disease (MMD); however, acoustic noise associated with DWI may lead to motion artifact. Compared with conventional DWI (cDWI), quiet DWI (qDWI) is considered less noisy and able to keep children more relaxed and stable. This study aimed to evaluate the suitability of qDWI compared with cDWI for pediatric patients with MMD. Methods In this observational study, MR examinations of the brain were performed either with or without sedation in pediatric patients with MMD between September 2017 and August 2018. Three neuroradiologists independently evaluated the images for artifacts and restricted diffusion in the brain. The differences between qDWI and cDWI were compared statistically using a chi-square test. Results One-hundred and six MR scans of 56 patients with MMD (38 scans of 15 sedated patients: 6 boys and 9 girls; mean age, 5.2 years; range, 1-9 years; and 68 scans of 42 unsedated patients: 19 boys and 23 girls; mean age, 10.7 years; range, 7-16 years) were evaluated. MR examinations were performed either with or without sedation (except in one patient). In sedated patients, no artifact other than susceptibility was observed on qDWI, whereas four artifacts were observed on cDWI (P = .04). One patient awoke from sedation during cDWI scanning, while no patient awoke from sedation during qDWI acquisition. For unsedated patients, three scans showed artifacts on qDWI, whereas two scans showed artifacts on cDWI (P = .65). Regarding restricted diffusion, qDWI revealed three cases, while two cases were found on cDWI (P = .66). Conclusion qDWI induced fewer artifacts compared with cDWI in sedated patients, and similar frequencies of artifacts were induced by qDWI and by cDWI in unsedated patients. qDWI showed restricted diffusion comparable to cDWI.

BACKGROUND AND PURPOSE: Collateral vessels in Moyamoya disease represent potential sources of bleeding. To test whether these cortical distributions vary among subtypes, we investigated cortical terminations using both standardized MR imaging and MRA. MATERIALS AND METHODS: Patients with Moyamoya disease who underwent MR imaging with MRA in our institution were enrolled in this study. MRA was spatially normalized to the Montreal Neurological Institute space; then, collateral vessels were measured on MRA and classified into 3 types of anastomosis according to the parent artery: lenticulostriate, thalamic, and choroidal. We also obtained the coordinates of collateral vessel outflow to the cortex. Differences in cortical terminations were compared among the 3 types of anastomosis. RESULTS: We investigated 219 patients with Moyamoya disease, and a total of 190 collateral vessels (lenticulostriate anastomosis, n = 72; thalamic anastomosis, n = 21; choroidal anastomosis, n = 97) in 46 patients met the inclusion criteria. We classified the distribution patterns of collateral anastomosis as follows: lenticulostriate collaterals outflowing anteriorly (P

OBJECTIVEAccumulated findings in the pathophysiology of atherosclerosis have demonstrated that not only luminal narrowing but also plaque characteristics influence the risk of future ischemic events. The morphology of the carotid artery (CA) changes in response to atherosclerotic development by expansive remodeling (ER), the clinical significance of which remains unclear. This study aimed to define associations between ER and local risk factors, including CA geometry and traditional systemic risk factors for ischemic events, to determine whether ER could serve as a clinical marker of carotid vulnerable plaque.METHODSThe authors retrospectively analyzed 66 patients with CA stenosis who were scheduled to undergo carotid endarterectomy or CA stenting. They calculated ER ratios in the internal CA (ICA) from long-axis MR images and as the maximal distance between the lumen and the outer borders of the plaque perpendicular to the axis of the ICA/the maximal luminal diameter of the distal ICA at a region unaffected by atherosclerosis. Relative overall signal intensity (roSI) was calculated to assess intraplaque hemorrhage and defined as the signal intensity of plaque on an axial T1-weighted image with maximal stenosis relative to that of the adjacent sternocleidomastoid muscle. The authors evaluated CA geometry by calculating the angles between the common CA (CCA) and ICA, and between the CCA and external CA (ECA) using digital subtraction angiography. The ER ratios, age, sex, percentage of stenosis, roSI, hypertension, hyperlipidemia, low-density lipoprotein, statin medication, diabetes, smoking habit, and ischemic heart disease were compared between 33 symptomatic and 33 asymptomatic patients. The authors also compared symptomatic status, age, sex, percentage of stenosis, ICA angle, ECA angle, roSI, and other traditional atherosclerotic risk factors between groups with extensive and slight ER.RESULTSThe ER ratio was significantly greater in symptomatic than in asymptomatic patients (1.91 ± 0.46 vs 1.68 ± 0.40, p < 0.05). The ICA angle was significantly larger in the group with extensive ER than in those with slight ER (33.9° ± 20.2° vs 21.7° ± 13.8°, p < 0.01). The roSI, ECA angle, percentage stenosis, or any other traditional vascular risk factors were not associated with ER.CONCLUSIONSCarotid ER might be an independent indicator of carotid vulnerable plaque, which should be validated in a longitudinal study of patients with carotid atherosclerosis, including those with nonstenotic to moderate stenosis.

[Purpose] The aim of this study was to examine the evaluation of ultra-high-resolution computed tomography angiography (UHR CTA) images in moyamoya disease (MMD) reconstructed with hybrid iterative reconstruction (Hybrid-IR), model-based iterative reconstruction (MBIR), and deep learning reconstruction (DLR). [Methods] This retrospective study with institutional review board approval included patients with clinically suspected MMD who underwent UHR CTA between January 2018 and July 2020. CTA images were reconstructed with three reconstruction methods. Qualitative visualization was evaluated in comparison with digital subtraction angiography. Quantitative evaluation included assessment of edge sharpness, full width at half maximum (FWHM), vessel contrast, and tissue signal-to-noise ratio (SNR[tissue]). One-way analysis of variance was used to analyze differences. In addition, reconstruction time were assessed. [Results] Qualitative evaluation of CTA for 33 sides did not differ significantly between reconstruction methods. In quantitative evaluation for 54 patients, edge sharpness for right and left cortical segments of the middle cerebral artery was significantly higher for Hybrid-IR than for other reconstructions. No significant difference was seen between MBIR and DLR. Edge sharpness for STA-MCA bypass was significantly higher for Hybrid-IR than for MBIR, but no significant difference was seen between Hybrid-IR and DLR. FWHM for STA-MCA showed no significant difference between the three reconstruction methods. DLR displayed the highest SNR[tissue]. The time required for reconstruction was 40 s for Hybrid-IR, 2580 s for MBIR, and 180 s for DLR. [Conclusion] UHR CTA with DLR adequately visualized vessels in patients with MMD within a clinically feasible reconstruction time.

BACKGROUND Selecting therapeutic options for moyamoya disease (MMD)-associated anterior communicating artery (ACoA) aneurysm, a rare pathology in children, is challenging because its natural course remains unclear. OBSERVATIONS A 4-year-old boy exhibiting transient ischemic attacks was diagnosed with unilateral MMD accompanied by an unruptured ACoA aneurysm. Although superficial temporal artery to middle cerebral artery anastomosis eliminated his symptoms, the aneurysm continued to grow after surgery. Since a previous craniotomy and narrow endovascular access at the ACoA precluded both aneurysmal clipping and coil embolization, the patient underwent a surgical anastomosis incorporating an occipital artery graft between the bilateral cortical anterior cerebral arteries (ACAs). This was intended to augment blood flow in the ipsilateral ACA territory and to reduce the hemodynamic burden on the ACoA complex. The postoperative course was uneventful, and radiological images obtained 12 months after surgery revealed good patency of the bypass and marked shrinkage of the aneurysm in spite of the intact contralateral internal carotid artery. LESSONS Various clinical scenarios should be assessed carefully with regard to this pathology. Bypass surgery aimed at reducing flow to the aneurysm might be an alternative therapeutic option when neither coiling nor clipping is feasible.

OBJECTIVEHere, the authors aimed to determine whether the presence of cerebral hemodynamic failure predicts subsequent bleeding attacks and how it correlates with the effect of direct bypass surgery in hemorrhagic moyamoya disease.METHODSData from the Japanese Adult Moyamoya (JAM) Trial were used in this study: 158 hemispheres in 79 patients. A newly formed expert panel evaluated the SPECT results submitted at trial enrollment and classified the cortical hemodynamic state of the middle cerebral artery territory of each hemisphere into one of the following three groups: SPECT stage (SS) 0 as normal, SS1 as decreased cerebrovascular reserve (CVR), and SS2 as decreased CVR with decreased baseline blood flow. In the nonsurgical cohort of the JAM Trial, the subsequent hemorrhage rate during the 5-year follow-up was compared between the SS0 (hemodynamic failure negative) and SS1+2 (hemodynamic failure positive) groups. The effect of direct or combined direct/indirect bypass surgery on hemorrhage prevention was examined in each subgroup.RESULTSThe hemodynamic grade was SS0 in 59 (37.3%) hemispheres, SS1 in 87 (55.1%), and SS2 in 12 (7.6%). In the nonsurgical cohort, subsequent hemorrhage rates in the SS0 and SS1+2 groups were 12 cases per 1000 person-years and 67 cases per 1000 person-years, respectively. Kaplan-Meier analysis revealed that hemorrhagic events were significantly more common in the SS1+2 group (p = 0.019, log-rank test). Cox regression analysis showed that hemodynamic failure was an independent risk factor for subsequent hemorrhage (HR 5.37, 95% CI 1.07–27.02). In the SS1+2 subgroup, bypass surgery significantly suppressed hemorrhagic events during 5 years (p = 0.001, HR 0.16, 95% CI 0.04–0.57), with no significant effect in the SS0 group (p = 0.655, HR 1.56, 95% CI 0.22–11.10). Examination of effect modification revealed that the effect of surgery tended to differ nonsignificantly between these two subgroups (p = 0.056).CONCLUSIONSHemodynamic failure is an independent risk factor for subsequent hemorrhage in hemorrhagic moyamoya disease. Direct bypass surgery showed a significant preventive effect in the hemodynamically impaired hemispheres. Thus, hemodynamic failure, as well as previously proposed factors such as choroidal anastomosis, should be considered for the surgical indication in hemorrhagic moyamoya disease.Clinical trial registration no.: C000000166 (umin.ac.jp)

Background The clinical significance of asymptomatic microbleeds in moyamoya disease remains unclear. The purpose of this study was to clarify the relationship between bypass surgery and the incidence of asymptomatic microbleeds. Methods This retrospective study included 142 adult patients (mean age, 37.7 ± 13.5 years) with moyamoya disease, 36 of whom (25.3%) underwent bypass surgery in childhood. Hemorrhagic onset was diagnosed in 31 patients (21.8%). The incidence of microbleeds was evaluated on T2*-weighted or susceptibility-weighted imaging from 3-T magnetic resonance imaging. The patients were subsequently categorized into MBs (microbleeds) or non-MBs groups. Because previous microbleeds potentially lead to hemorrhage, the MBs group was defined as patients with radiographic evidence of bleeding, including asymptomatic microbleeds and/or hemorrhagic onset. The association of baseline characteristics was evaluated. Results Asymptomatic microbleeds were detected in 38 patients (26.8%). Of 31 patients with hemorrhagic onset, 18 had microbleeds, whereas 13 had no microbleeds. Therefore, 51 patients (35.9%) were classified into the MBs group. Bypass surgery in childhood (MBs, 7.8% vs. non-MBs, 35.2%; P Conclusions This study shows the clinical significance of revascularization surgery in childhood associated with a low incidence of asymptomatic microbleeds in adult patients with moyamoya disease. This finding indicates that a newly established bypass can reduce hemodynamic overstress.

Although cognitive impairment is well-documented in children with moyamoya disease (MMD), selective decline in specific neurocognitive domains remains controversial. The purpose of this study was to characterize the neurocognitive profile of children with MMD using the Das Naglieri Cognitive Assessment System (CAS) and the Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV). We analyzed the neurocognitive data of 30 children (median age, 7 years) with MMD who were assessed with the CAS and the WISC-IV before surgery. We focused on the comparison of standard scores and intraindividual differences across domains. The CAS scores significantly varied across four measures (standard scores, p p

[Objectives] Although the association between genetic factors, such as RNF213 mutations, and moyamoya disease (MMD) has been well investigated, environmental factors are largely undetermined. Thus, we aimed to examine whether viral infection increases the risk of MMD. [Materials and Methods] To eliminate the effect of presence or absence of the RNF213 p.R4810K mutation, the entire study population was positive for this mutation. We collected whole blood from 111 patients with MMD (45 familial and 66 sporadic cases) and 67 healthy volunteers, and we measured the immunoglobulin G titer of 11 viruses (cytomegalovirus, varicella-zoster virus, measles virus, rubella virus, herpes simplex virus, mumps virus, Epstein–Barr virus, human parvovirus B19, human herpesvirus 6 [HHV6], human herpesvirus 8, and John Cunningham virus) that were presumed to be associated with vasculopathy using the enzyme-linked immunosorbent assay. Positivity for past viral infection was determined by cut-off values obtained from previous reports and the manufacturer's instructions, and the positive rate was compared between cases and age- and sex-matched controls. We performed familial case-specific and sporadic case-specific analyses, as well as a case–control analysis. [Results] There was no significant difference in the positive rate between the case group and the control group in any of the analyses. A significant difference was only observed in the combined case–control analysis for HHV6 (p = 0.046), but the viral antibody-positive rate in control individuals was higher than in MMD cases. [Conclusions] Our cross-sectional study suggest that the investigated 11 viruses including HHV6 are unlikely to have an impact on MMD development.

In this educational article for young neurosurgeons, the author highlights the characteristic CT and MRI findings for diagnosing moyamoya disease. The author also provides guidelines for the systematic interpretation of angiographic findings in patients with moyamoya disease.

The Japan Adult Moyamoya (JAM) Trial was a unique randomized controlled trial demonstrating the effectiveness of direct bypass surgery for hemorrhagic moyamoya disease. Prespecified subgroup analysis undertaken as part of the trial demonstrated that posterior-dominant initial hemorrhage is a significant predictor of rebleeding and an effect modifier for surgery. Periventricular anastomosis—fragile collaterals formed by the lenticulostriate arteries, thalamic perforators, and choroidal arteries—might present a clue to the mechanism of high rebleeding risk linked to posterior hemorrhage. Angiographic analyses of the JAM Trial revealed that choroidal collaterals and the involvement of the posterior cerebral artery are associated with posterior hemorrhage, and subsequent cohort analysis of the nonsurgical group has revealed that choroidal anastomosis is a strong predictor of rebleeding. A better understanding of periventricular anastomosis might contribute to further progress in the surgical treatment of hemorrhagic moyamoya disease.

Plaque characteristics play pivotal roles in ischemic events, but stenosis severity does not accurately reflect carotid plaque volume due to expansive remodeling in some patients with low-grade stenosis (LGS). This study aimed to assess the safety, efficacy, and durability of carotid endarterectomy (CEA) for symptomatic LGS.Study participants comprised 61 consecutive patients who underwent CEA for symptomatic carotid stenosis. Patients were divided into an LGS group (50%, n = 17) and a non-LGS group (≥50%, n = 44). Patient characteristics and short-term (within 30 days of CEA) and long-term outcomes were compared between groups for selective usage of internal shunt and known complications of CEA.Magnetic resonance imaging-detected intraplaque hemorrhage was more significant in LGS than in non-LGS (P = 0.04). For short-term outcomes, no symptomatic infarcts, hyperperfusion syndrome, or acute myocardial infarction was confirmed in either group. Internal shunts were used in 4 LGS (23.5%) and 6 non-LGS (13.6%). Asymptomatic diffusion-weighted imaging-positive lesions were confirmed in 2 LGS patients (11.8%) and 5 non-LGS patients (11.4%), neck hematoma in 1 LGS patient, and transient cranial nerve palsy in 1 LGS patient and 2 non-LGS patients, with no significant differences apparent between groups. For long-term outcomes, 5 non-LGS patients showed restenosis (P = 0.17). Hemorrhagic stroke was not observed in either group. No significant differences were seen for infarct in the ipsilateral carotid territory, any ischemic stroke, AMI, or mortality.CEA represents a safe and feasible therapeutic option for a subset of patients with symptomatic LGS.

An 82-year-old female suffered from head trauma, and developed acute consciousness disturbance 6 days after the event. Head CT showed the acute subdural hematoma in the left temporooccipital area and the patient underwent emergency hematoma evacuation and decompression. However, her consciousness disturbance became worse after surgery. Intermittent large negative infraslow shifts (lasting longer than 40 seconds) were recorded in the right posterior quadrant by scalp EEG with TC of 2 sec, that was defined as cortical spreading depolarizations (CSDs). Clinically consciousness disturbance sustained poor until 1 month after surgery in spite of treatment by anti-epileptic drugs. CSDs were observed on the right side where head injury most likely occurred. It may explain the sustained consciousness disturbance associated with significant prolonged ischemia. Once scalp EEG could record CSDs in this particular patient, the degree and its prognosis of traumatic head injury were estimated.

Although direct bypass is effective at preventing intracranial hemorrhage in moyamoya disease, the optimal strategy for achieving this purpose has rarely been addressed. The tailored targeting bypass strategy is a novel technical modification of direct bypass focused on hemorrhage prevention. The strategy is based on the promising theory of periventricular anastomosis, which explains the mechanism of hemorrhage in moyamoya disease. The strategy is defined as the use of multi-imaging modalities to predetermine in a tailored manner a target vessel at the point at which the medullary artery directly extends from the periventricular anastomosis of interest. Direct bypass with a wide craniotomy was performed on 13 hemispheres in eight patients according to this strategy. Marked shrinkage of the periventricular anastomosis of interest was observed in all but one hemisphere after surgery, and no new hemorrhages have occurred as of this writing. The present case series illustrates the technical aspects and preliminary results of the tailored targeting bypass strategy, an approach that might expand the potential of direct bypass in preventing hemorrhage.

[Objectives] It is sometimes difficult to differentiate middle cerebral artery disease from moyamoya disease because the two can present similarly yet have different treatment strategies. We investigated whether the presence of a narrow carotid canal and the RNF213 mutation can help differentiate between the two phenotypes. [Population and Methods] We analyzed 78 patients with moyamoya disease, 27 patients with middle cerebral artery disease, and 79 controls from 2 facilities. The carotid canal diameter was measured using computed tomography. The p.R4810K mutation was genotyped by TaqMan assay. A receiver operating characteristics analysis was performed to assess the significance of the carotid canal diameter for the accurate diagnosis of moyamoya disease. [Results] The carotid canal diameter was significantly narrower in patients with moyamoya disease than in controls. The optimal cutoff values were 5.0 mm for adult males and 4.5 mm for adult females and children (sensitivity: 0.82; specificity: 0.92). Among the patients with middle cerebral artery disease, 18.5% and 25.0% of the affected hemispheres had the p.R4810K mutation and narrow canal (i.e., below the cutoff), respectively, whereas only 3.1% of those had both. Contrastingly, 68.8% of the affected hemispheres in patients with moyamoya disease had both these characteristics. Among the patients with moyamoya disease, those with the p.R4810K mutation tended to have narrower carotid canals. [Conclusions] Although the presence of a narrow carotid canal or the p.R4810K mutation alone could not be used to distinguish those with moyamoya disease from those with middle cerebral artery disease, the combination of these factors could better characterize the two phenotypes.

OBJECTIVE Although many studies have analyzed risk factors for contralateral progression in unilateral moyamoya disease, they have not been fully elucidated. The aim of this study was to examine whether genetic factors as well as nongenetic factors are involved in the contralateral progression. METHODS The authors performed a multicenter cohort study in which 93 cases with unilateral moyamoya disease were retrospectively reviewed. The demographic features, RNF213 R4810K mutation, lifestyle factors such as smoking and drinking, past medical history, and angiographic findings were analyzed. A Cox proportional hazards model was used to find risk factors for contralateral progression. RESULTS Contralateral progression was observed in 24.7% of cases during a mean follow-up period of 72.2 months. Clinical characteristics were not significantly different between 67 patients with the R4810K mutation and those without it. Cox regression analysis showed that the R4810K mutation (hazard ratio [HR] 4.64, p = 0.044), childhood onset (HR 7.21, p < 0.001), male sex (HR 2.85, p = 0.023), and daily alcohol drinking (HR 4.25, p = 0.034) were independent risk factors for contralateral progression. CONCLUSIONS These results indicate that both genetic and nongenetic factors are associated with contralateral progression of unilateral moyamoya disease. The findings would serve to help us better understand the pathophysiology of moyamoya disease and to manage patients more appropriately.

BACKGROUND The development of noninvasive approaches for identifying hypoperfused brain tissue at risk is of major interest. Recently, the temporal-shift (TS) maps estimated from resting-state blood oxygenation level-dependent (BOLD) signals have been proposed for determining hemodynamic state. OBJECTIVE To examine the equivalency of the TS map and the cerebrovascular reactivity (CVR) map derived from acetazolamide-challenged single-photon emission computed tomography (SPECT) in identifying hemodynamic impairment in patients with arterial occlusive diseases. METHODS Twenty-three patients with arterial occlusive diseases who underwent SPECT were studied. With a recursive TS analysis of low-frequency fluctuation of the BOLD signal, a TS map relative to the global signal was created for each patient. The voxel-by-voxel correlation coefficient was calculated to examine the image similarity between TS and SPECT-based cerebral blood flow (CBF) or CVR maps in each patient. Furthermore, simple linear regression analyses were performed to examine the quantitative relationship between the TS of BOLD signals and CVR in each cerebrovascular territory. RESULTS The within-patient, voxel-by-voxel comparison revealed that the TS map was more closely correlated with SPECT-CVR map ([Z(r)] = 0.42 ± 0.18) than SPECT-CBF map ([Z(r)] = 0.058 ± 0.11; P

Background This study aimed to determine the effectiveness of genetic testing for the p.R4810K variant (rs112735431) of the Mysterin/RNF213 gene, which is associated with moyamoya disease and other intracranial vascular diseases, in the family members of patients with moyamoya disease. Methods We performed genotyping of the RNF213 p.R4810K polymorphism and magnetic resonance angiography on 59 relatives of 18 index patients with moyamoya disease. Nineteen individuals had follow-up magnetic resonance angiography with a mean follow-up period of 7.2 years. Results Six of the 34 individuals with the GA genotype (heterozygotes for p.R4810K) showed intracranial steno-occlusive lesions in the magnetic resonance angiography, whereas none of the 25 individuals with the GG genotype (wild type) showed any abnormalities. Follow-up magnetic resonance angiography revealed de novo lesions in 2 and disease progression in 1 of the 11 individuals with the GA genotype, despite none of the 8 individuals with the GG genotype showing any changes. Accordingly, 8 individuals had steno-occlusive lesions at the last follow-up, and all had the p.R4810K risk variant. The prevalence of steno-occlusive intracranial arterial diseases in family members with the p.R4810K variant was 23.5% (95% confidence interval: 9.27%-37.78%), which was significantly higher than in those without the variant (0%, P = .0160). Conclusions Genotyping of the p.R4810K missense variant is useful for identifying individuals with an elevated risk for steno-occlusive intracranial arterial diseases in the family members of patients with moyamoya disease.

BACKGROUND AND PURPOSE: The location of intracerebral hemorrhage in Moyamoya disease is a prognostic factor for rebleeding and the degree of preventive effects obtainable with bypass surgery. We evaluated whether the bleeding point and responsible vessel were detectable using fusion images of SWI and time-of-flight MRA performed during chronic-phase hemorrhage. MATERIALS AND METHODS: We retrospectively enrolled 42 patients with hemorrhagic Moyamoya disease (48 hemorrhagic events). Fusion images of SWI and MRA were made using workstations, and we defined the bleeding point as the point at which the signal of an abnormally extended artery on MRA overlapped the hypointense area on SWI. Two independent raters identified the bleeding point, and classified the location and responsible vessels. RESULTS: The bleeding point was detectable at a frequency of 79.2% by rater 1. Agreement for the presence of a bleeding point was high (interrater κ = 0.83; 95% CI, 0.65–1; intrarater κ = 0.86; 95% CI, 0.68–1). The frequency of a periventricular location of the bleeding point was 65.8% by rater 1, and agreement on the location was again high (interrater κ = 0.92; 95% CI, 0.82–1; intrarater κ = 0.85; 95% CI, 0.72–0.99). The choroidal artery was the most frequent responsible vessel (57.9% by rater 1), and agreement on the responsible vessel was high (interrater κ = 0.84; 95% CI, 0.69–1; intrarater κ = 0.90; 95% CI, 0.78–1). CONCLUSIONS: Detection of the bleeding point in hemorrhagic Moyamoya disease using SWI and MRA fusion images offers highly reproducible results.

Intracranial germ cell tumor is sometimes associated with Down syndrome; however, no optimal treatment has been developed due to the high risk of recurrence and treatment-related mortality. Here, we report on a patient with an intracranial germinoma in the bilateral basal ganglia. The patient received 3 courses of ifosfamide-cisplatin-etoposide in combination with whole-brain irradiation (24 Gy), with no serious complications. The patient is alive and disease free 16 months after the initial diagnosis. This regimen is a feasible treatment for intracranial germ cell tumor associated with Down syndrome, although careful attention must be paid to the increased risk for severe infection.

Background Quasi-moyamoya disease is an angiographical moyamoya disease equivalent accompanied by known underlying diseases. Mysterin/RNF213 is a major susceptibility gene for moyamoya disease, of which the p.R4810K variant is a founder polymorphism. The genetics of quasi-moyamoya disease is poorly understood, therefore, this study investigated a potential association between the p.R4810K polymorphism and quasi-moyamoya disease. Methods Genotyping of the p.R4810K variant was performed on 18 quasi-moyamoya disease cases and 91 controls, who visited Kyoto University Hospital or Kobe City Medical Center, Japan, between 2006 and 2015. Results The p.R4810K variant was found in 12 of 18 quasi-moyamoya disease patients. The frequency of p.R4810K carriers was significantly higher in quasi-moyamoya disease cases than in controls (66.7% versus 2.2%, odds ratio 89.0, 95% confidence interval: 19.2-669.4). Conclusions Our data showed that the RNF213 p.R4810K polymorphism was significantly associated with quasi-moyamoya disease.

Ventriculitis is an uncommon condition with a poor prognosis, especially when complicated by brain abscess. We compared the therapeutic efficacy of neuroendoscopic ventricular irrigation with those of conventional treatments such as ventricular drainage and continuous irrigation via a ventricular drain.We retrospectively analyzed 14 consecutive patients treated for ventriculitis at our institution between 2001 and 2015. Included were the six patients treated with neuroendoscopic (NE) irrigation (NE group), which we adopted in 2011, and the eight patients treated before 2011 with conventional treatments (non-NE group). We compared mortality, modified Rankin Scale (mRS) score 6 months postoperatively, and duration of ventricular/spinal drainage-catheter placement between groups.Mean age at onset was 49.3 years (range, 32-68 years) in the NE group and 50.3 years (range, 8-78 years) in the non-NE group. At 6-month follow-up, good clinical outcome (mRS≤3) was observed in 66.7% of the NE group, whereas it was observed in 25.0% of the non-NE group. There were three deaths (37.5%) in the non-NE group but none in the NE group. Duration of drainage-catheter placement was significantly shorter in the NE group than in the non-NE group (19.8days vs. 70.9days, p0.001). Among patients in the NE group, only those who underwent irrigation on the day of diagnosis maintained a low mRS score.Neuroendoscopic ventricular irrigation was safe and effective in the treatment of ventriculitis. Immediate intervention after diagnosis may lead to an improved prognosis.

The pathophysiological mechanism of chorea as a presentation of pediatric moyamoya disease remains unknown, although ischemia is suspected as a likely cause. The authors describe two cases of pediatric moyamoya disease, both of which presented with hemichorea in the stable phase after successful bypass surgery. Cerebral blood flow was almost normal in one case and decreased in the basal ganglia and watershed area in the other case due to infarcts occurring before surgery. In both cases, 18F-fluorodeoxyglucose positron emission tomography revealed elevated glucose metabolism in the corresponding side of the striatum, which reverted to normal after recovery from chorea. Magnetic resonance angiography revealed a dilated and extended lenticulostriate artery at the exact site of the hypermetabolic lesion.

Moyamoya disease (MMD) is a unique progressive steno-occlusive disease of the distal ends of bilateral internal arteries and their proximal branches. The difference in clinical symptoms between adult and children MMD patients has been well recognized. In this study, we sought to investigate the phenomenon through histopathological study. Fifty-one patients underwent surgical procedures for treatment of standard indications of MMD at Kyoto University Hospital. Fifty-nine specimens of MCA were obtained from MMD patients during the surgical procedures. Five MCA samples were also obtained in the same way from control patients. The samples were analyzed by histopathological methods. In this study, MCA specimens from MMD patients had significantly thinner media and thicker intima than control specimens. In subsequent analysis, adult (≥ 20 years) patients had thicker intima of MCA compared to pediatric (< 20 years) patients. There is no difference in internal elastic lamina pathology between adult and pediatric patients. Our results indicated that the pathological feature of MMD in tunica media occurs in both adult and pediatric patients. However, the MMD feature in tunica intima of MCA is more prominent in adult patients. Further analysis from MCA specimens and other researches are necessary to elucidate the pathophysiology of MMD.

Background Although superficial temporal artery (STA) to middle cerebral artery (MCA) anastomosis is a beneficial treatment for hemorrhagic moyamoya disease, indeterminate mechanisms can cause rebleeding even after successful bypass surgery. We describe a case with a prominent collateral from the lenticulostriate artery (LSA) causing multiple recurrent hemorrhages after successful STA-MCA anastomosis. Case Description A 49-year-old Japanese woman with moyamoya disease was referred to our institution after suffering intracranial hemorrhage on 2 occasions. Angiography revealed multiple anastomotic vessels branching from a prominent LSA to connect medullary arteries in the periventricular area corresponding to the location of the hemorrhage. She underwent STA-MCA anastomoses and the bypass widely perfused the MCA territory; however, intracranial hemorrhage recurred in the same hemisphere. Angiography revealed sustained dilatation of the medial anastomotic branches from the LSA with de novo pseudoaneurysm, whereas the lateral branches showed shrinkage. Subsequent surgical treatment included direct bypass targeting the medial hemispheric surface in which the medial branches were distributed; marked shrinkage of the branches and disappearance of the aneurysm were obtained without infarct. Conclusions Lenticulostriate anastomotic branches distributed medially to the anterior cerebral artery territory should be given more attention as an intractable cause of hemorrhage after successful STA-MCA anastomosis. Although challenging, direct bypass targeting the area reached by collateral vessels could be considered an alternative treatment strategy for this pathologic condition.

While periventricular anastomosis, a unique abnormal vasculature in moyamoya disease, has been studied in relation to intracranial hemorrhage, no study has addressed its change after bypass surgery. The authors sought to test whether direct bypass surgery could restore normal periventricular vasculature. Patients who had undergone direct bypass surgery for moyamoya disease at a single institution were eligible for the study. Baseline, postoperative, and follow-up magnetic resonance angiography (MRA) scans were scheduled before surgery, after the first surgery, and 3 to 6 months after contralateral second surgery, respectively. Sliding-thin-slab maximum-intensity-projection coronal MRA images of periventricular anastomoses were scored according to the three subtypes (lenticulostriate, thalamic, and choroidal anastomosis). Baseline and postoperative MRA images were compared to obtain a matched comparison of score changes in the surgical and nonsurgical hemispheres within individuals (intra-individual comparison). Of 110 patients, 42 were identified for intra-individual comparisons. The periventricular anastomosis score decreased significantly in the surgical hemispheres (median, 2 versus 1; p

In this article, the authors review the literature related to long-term outcome of pediatric moyamoya disease, focusing on late cerebrovascular events and social outcome of pediatric patients once they reach adulthood. Late-onset de novo hemorrhage is rare but more serious than recurrence of ischemic stroke. Long-term follow-up data on Asian populations suggest that the incidence of de novo hemorrhage might increase at age 20 or later, even more than 10 years after bypass surgery. Social adaptation difficulty, possibly related to cognitive impairment caused by frontal ischemia, continues in 10-20% of patients after they reach adulthood, even if no significant disability is present in daily life. A treatment strategy aimed at improving long-term outcome and careful follow-up might be required.

OBJECTIVEFollowing hemorrhagic stroke in moyamoya disease, de novo intracranial hemorrhage can occur in the previously unaffected nonhemorrhagic hemisphere. In the present analysis the authors intended to determine whether the presence in the nonhemorrhagic hemisphere of choroidal collateral vessels, which have been the focus of attention as a source of bleeding, affects the risk of de novo hemorrhage.METHODSThe subject of focus of the present cohort study was the nonhemorrhagic hemispheres of adult patients with hemorrhagic moyamoya disease enrolled in the Japan Adult Moyamoya Trial and allocated to the nonsurgical arm. The variable of interest was the presence of choroidal collaterals (also termed choroidal anastomoses), identified with baseline angiography and represented by a connection (anastomosis) between the anterior or posterior choroidal arteries and the medullary arteries. The outcome measure was de novo hemorrhage during the 5-year follow-up period, assessed in all nonhemorrhagic hemispheres. The incidence of de novo hemorrhage in the collateral-positive and -negative groups was compared.RESULTSChoroidal collaterals were present in 15 of 36 (41.7%) nonhemorrhagic hemispheres analyzed. The overall annual risk of de novo hemorrhage was 2.0%. Three de novo hemorrhages occurred in the collateral-positive group, whereas no hemorrhage occurred in the collateral-negative group. The annual risk of de novo hemorrhage was significantly higher in the collateral-positive group than in the collateral-negative group (5.8% per year vs 0% per year; p = 0.017). All hemorrhage sites corresponded to the distribution of choroidal collaterals.CONCLUSIONSThe present preliminary results suggest that the presence of choroidal collaterals affects the risk of de novo hemorrhage in the nonhemorrhagic hemisphere, subject to verification in larger studies. Further studies are needed to determine the optimal treatment strategy for nonhemorrhagic hemispheres and asymptomatic patients.