Search

Background RNF213 is a major susceptibility gene for moyamoya disease (MMD), characterized by chronic progressive steno-occlusion of the intracranial arteries. However, coincidental extracranial arteriopathy is sporadically described in a few cases and in children with MMD. Methods and Results This study prospectively enrolled 63 young adults (aged 20-49 years) without a known history of systemic vascular diseases who were confirmed to have definite (bilateral, n=54) or probable (unilateral, n=9) MMD, as per typical angiographic findings. Coronary and aorta computed tomography angiography was performed to characterize extracranial arteriopathy and investigate its correlation with clinical characteristics and MMD status, including the RNF213 p.Arg4810Lys variation (c.14429G>A, rs112735431). Altogether, 11 of 63 patients (17%) had significant (>50%) stenosis in the coronary (n=6), superior mesenteric (n=2), celiac (n=2), renal (n=1), and/or internal iliac artery (n=1). One patient showed both mesenteric and iliac artery stenosis. Patients with extracranial arteriopathy were more likely to have diabetes mellitus and posterior cerebral artery involvement. Moreover, a higher prevalence of extracranial arteriopathy was observed in the presence of the RNF213 p.Arg4810Lys variant (67% in homozygotes). After controlling for diabetes mellitus and posterior cerebral artery involvement, the p.Arg4810Lys variant was independently associated with extracranial arteriopathy (additive model; P =0.035; adjusted odds ratio, 4.57; 95% CI, 1.11-27.20). Conclusions Young adults with MMD may have concomitant extracranial arteriopathy in various locations. Patients with RNF213 variants, especially the p.Arg4810Lys homozygous variant, should be screened for systemic arteriopathy.

Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by progressive stenosis of large intracranial arteries and a hazy network of basal collaterals called moyamoya vessels. A polymorphism (R4810K) in the Ring Finger Protein 213 (RNF213) gene, at chromosome 17q25.3, is the strongest genetic susceptibility factor for MMD in East Asian populations. MMD was regarded prevalent in childhood and in East Asian populations. However, the so-called MMD could represent only the tip of the iceberg. MMD is increasingly reported in adult patients and in Western populations. Moreover, the RNF213 variant was recently reported to be associated with non-MMD disorders, such as intracranial atherosclerosis and systemic vasculopathy (e.g., peripheral pulmonary artery stenosis and renal artery stenosis). In this review, we summarize the spectrums of RNF213 vasculopathy in terms of clinical and genetic phenotypes. Continuous efforts are required for pathophysiology-based diagnoses and treatment, which will benefit from collaboration between clinicians and researchers, and between stroke and vascular physicians.

Background and Purpose- Hemodynamic compromise has been implicated in moyamoya disease (MMD) with transient ischemic attacks or ischemic stroke. However, increasing evidence supports the notion that artery-to-artery embolism may also contribute to ischemic events based on microembolic signal (MES) monitoring. Methods- A total of 48 patients aged between 20 and 60 years with newly diagnosed MMD were enrolled and angiographically classified according to the Suzuki staging system. For detection of MESs, transcranial Doppler was performed at the middle cerebral artery bilaterally for a 30-minute period. Mean flow velocities in the middle cerebral artery were also evaluated and categorized into low (<40 cm/s), normal (40-80 cm/s), and high (>80 cm/s). Clinical characteristics, cerebral angiography findings, recent ischemic events within 3 months, and antiplatelet medication were correlated with transcranial Doppler findings. Results- MESs were detected in 11 of the 48 patients (23%), with a frequency of 11 of 89 (12%) examined hemispheres. The mean number of MESs was 2 (range, 1-6). Six of the 11 hemispheres (55%) presented with ischemic strokes or transient ischemic attacks, and 2 (18%) presented with hemorrhagic strokes. The presence of MESs was associated with recent ischemic events ( P=0.024) and high mean flow velocities ( P=0.016), which was usually observed in Suzuki stage I and II (early-stage MMD). After controlling for age, sex, and antiplatelet medication, both recent ischemic events (odds ratio, 6.294; 95% CI, 1.345-29.457; P=0.019) and high mean flow velocities (odds ratio, 6.172; 95% CI, 1.235-31.25; P=0.027) were found to be independent predictors of MESs. Conclusions- MESs were observed in patients with high mean flow velocities, particularly early-stage MMD, and clinically associated with recent ischemic events. A randomized controlled study is necessary to determine the efficacy of antiplatelet agents in the treatment of MES-positive MMD.

Background and Purpose- Moyamoya disease (MMD) is a unique cerebrovascular occlusive disease characterized by progressive stenosis and negative remodeling of the distal internal carotid artery (ICA). We hypothesized that cav-1 (caveolin-1)-a protein that controls the regulation of endothelial vesicular trafficking and signal transduction-is associated with negative remodeling in MMD. Methods- We prospectively recruited 77 consecutive patients with MMD diagnosed via conventional angiography. Seventeen patients with intracranial atherosclerotic stroke and no RNF213 mutation served as controls. The outer distal ICA diameters were examined using high-resolution magnetic resonance imaging. We evaluated whether the degree of negative remodeling in the patients with MMD was associated with RNF213 polymorphism, cav-1 levels, or various clinical and vascular risk factors. We also investigated whether the derived factor was associated with negative remodeling at the cellular level using the tube formation and apoptosis assays. Results- The serum cav-1 level was lower in the patients with MMD than in the controls (0.47±0.29 versus 0.86±0.68 ng/mL; P=0.034). The mean ICA diameter was 2.48±0.98 mm for the 126 affected distal ICAs in patients with MMD and 3.84±0.42 mm for the asymptomatic ICAs in the controls ( P<0.001). After adjusting for confounders, cav-1 levels (coefficient, 1.018; P<0.001) were independently associated with the distal ICA diameter in patients with MMD. In vitro analysis showed that cav-1 downregulation suppressed angiogenesis in the endothelial cells and induced apoptosis in the smooth muscle cells. Conclusions- Our findings suggest that cav-1 may play a major role in negative arterial remodeling in MMD.

Purpose: Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by stenosis of the internal carotid arteries with compensatory development of collateral vessels. Although a founder variant of RNF213, p.Arg4810Lys (c.14429G>A, rs112735431), is a major genetic risk factor for MMD in East Asians, the frequency and disease susceptibility of other variants in this gene remain largely unknown. In the present study, we investigated the association of RNF213 variants with MMD in Korean patients and population controls., Methods: For all RNF213 variants listed in the Human Gene Mutation Database (HGMD) as disease-causing or likely disease-causing mutations for MMD, genotyping was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Genetic data from 264 adult patients with MMD were analyzed and compared with two control populations comprised of 622 and 1,100 Korean individuals, respectively., Results: Among the 30 RNF213 variants that were listed in the HGMD, p.Arg4810Lys was identified in 67.4% (178/264) of patients with MMD and showed a significantly higher allele frequency than in the controls, giving an odds ratio of 63.29 (95% confidence interval, 33.11-120.98) for the 622 controls and 48.55 (95% confidence interval, 31.00-76.03) for the 1100 controls. One additional variant, p.Ala5021Val (c.15062C>T, rs138130613), was identified in 0.8% (2/264) of patients; however, the allele frequencies were not significantly different from those in the controls., Conclusions: These results suggest that, in our cohort of Korean patients, the p.Arg4810Lys is the only variant that is strongly associated with MMD among the 30 RNF213 variants listed in the HGMD.

OBJECTIVE Direct and indirect bypass surgeries are recognized as the most effective treatments for preventing further stroke in adults with moyamoya disease (MMD). However, the risk factors for postoperative infarction after bypass surgery for MMD are not well established. Therefore, the objective of this study was to investigate the risk factors for postoperative infarction. In particular, the authors sought to determine whether transcranial Doppler (TCD) ultrasonography measurements of mean flow velocity (MFV) in the middle cerebral artery (MCA) could predict postrevascularization infarction. METHODS The medical records of patients with MMD who underwent direct bypass surgery at the authors' institution between July 2012 and April 2015 were reviewed. The MFV in the MCA was measured with TCD ultrasonography and categorized as high (> 80 cm/sec), medium (40-80 cm/sec), and low (< 40 cm/sec). Postoperative MRI, including diffusion-weighted imaging, was performed for all patients within a week of their surgery. Angiographic findings were classified according to the Suzuki scale. Postrevascularization infarction was defined as any diffusion restriction on postoperative MRI scans. Postoperative neurological status was assessed through a clinical chart review, and the modified Rankin Scale was used to evaluate clinical outcomes. RESULTS Of 43 hemispheres in which bypass surgery for MMD was performed, 11 showed postrevascularization infarction. Ten of these hemispheres had low MFV and 1 had medium MFV in the ipsilateral MCA. In both univariate and multivariate analyses, a low MFV was associated with postrevascularization infarction (adjusted OR 109.2, 95% CI 1.9-6245.3). A low MFV was also statistically significantly associated with more advanced MMD stage (p = 0.02). CONCLUSIONS A low MFV in the ipsilateral MCA may predict postrevascularization infarction. Bypass surgery for MMD appears to be safe in early-stage MMD. Results of TCD ultrasonography provide clinical data on the hemodynamics in MMD patients before and after revascularization.

Background and Purpose: Moyamoya disease (MMD) is a unique cerebrovascular disease characterized by the progressive stenosis of large intracranial arteries and a hazy network of basal collaterals, called moyamoya vessels. Although hemodynamic studies have been applied in MMD patients, the mechanisms of stroke in MMD are still unclear. The present study evaluated the infarct pattern and collateral status using multimodal magnetic resonance imaging in MMD patients., Methods: Adult MMD patients with acute ischemic stroke were prospectively recruited, and infarct pattern on diffusion-weighted imaging was evaluated. A collateral flow map, derived from magnetic resonance perfusion-weighted imaging data, was generated through automatic postprocessing, and collateral status was assigned into 3 grades. Transcranial Doppler monitoring was performed to detect microembolic signals in selected patients., Results: A total of 67 hemispheres (31 patients with bilateral and 5 patients with unilateral MMD) were analyzed. Most patients (83.7%) showed embolic pattern and rarely deep (9.3%) or hemodynamic infarct pattern (7.0%) on diffusion-weighted imaging. Most cases (86%) showed good collateral status, and few patients with acute infarcts of embolic pattern showed poor collateral status (n=7). One third (31.6%) of patients who underwent transcranial Doppler monitoring showed microembolic signals., Conclusions: In the studied population of adult MMD patients, embolic phenomenon played an important role in ischemic stroke. Therapeutic strategies against thromboembolism, as well as collateral enhancing strategies targeting improvement of hemodynamic status or increased washout of emboli, are warranted., (© 2016 American Heart Association, Inc.)

Background: Moyamoya disease is a unique cerebrovascular occlusive disease of unknown etiology. Ring finger protein 213 (RNF213) was identified as a susceptibility gene for Moyamoya disease in East Asian countries. However, the pathogenesis of Moyamoya disease remains unclear., Methods: We prospectively analyzed clinical data for 139 patients with Moyamoya disease (108 bilateral Moyamoya disease, 31 unilateral Moyamoya disease), 61 patients with intracranial atherosclerotic stroke, and 68 healthy subjects. We compared the genetic (RNF213 variant) and protein biomarkers for caveolae (caveolin-1), angiogenesis (vascular endothelial growth factor (VEGF) and receptor (VEGFR2), and antagonizing cytokine (endostatin)) and endothelial dysfunction (asymmetric dimethylarginine (ADMA), and nitric oxide and its metabolites (nitrite and nitrate)) between patients with Moyamoya disease and intracranial atherosclerotic stroke. We then performed path analysis to evaluate whether a certain protein biomarker mediates the association between genes and Moyamoya disease., Results: Caveolin-1 level was decreased in patients with Moyamoya disease and markedly decreased in RNF213 variant carriers. Circulating factors such as VEGF and VEGFR2 did not differ among the groups. Markers for endothelial dysfunction were significantly higher in patients with intracranial atherosclerotic stroke but normal in those with Moyamoya disease. Path analysis showed that the presence of the RNF213 variant was associated with caveolin-1 levels that could lead to Moyamoya disease. The level of combined marker of Moyamoya disease (caveolin-1) and intracranial atherosclerotic stroke (ADMA, an endothelial dysfunction marker) predicted Moyamoya disease with good sensitivity and specificity., Conclusion: Our results suggest that Moyamoya disease is a caveolae disorder but is not related to endothelial dysfunction or dysregulation of circulating cytokines., (© 2016 World Stroke Organization.)

Background/aims: To enable the diagnosis of moyamoya disease (MMD), detection of distal internal carotid artery stenosis and hazy network of basal collaterals (BCs) are required. This study aimed at evaluating the factors that could determine the degree of BCs in patients with angiographically confirmed MMD., Methods: We analyzed 146 consecutive patients with MMD (age 26.2 ± 19.6, range 1-75). The degree of BCs (%) was measured based on conventional angiography. Factors associated with the degree of BCs, including clinico-radiological and genetic factors (p.Arg4810Lys variant), were analyzed., Results: The degree of BCs varied among MMD patients and significantly decreased with an increase in the age of diagnosis of MMD (coefficient -1.55; p < 0.001). Although the degree of BC development depends on the MMD stage (Suzuki stage), it is less prominent in adult-onset (>18 years) MMD compared to childhood MMD. The presence of p.Arg4810Lys variant, types of MMD (bilateral vs. unilateral) and stroke (ischemic, hemorrhagic, or asymptomatic), shrinkage (outer diameter) of intracranial vessels, external carotid collateral status, and cortical neovascularization were not associated with the degree of BCs., Conclusion: Although prominent BCs are required for diagnosis of MMD, BCs are decreased with aging, suggesting that angiogenic capacity is altered in adult onset MMD compared to childhood MMD., (© 2016 S. Karger AG, Basel.)

Objective: We sought to identify the clinical outcome and predictors for ischemic stroke recurrence in adults with symptomatic moyamoya disease (MMD)., Methods: We analyzed 104 adult MMD patients with ischemic stroke or TIA registered at our institution. All patients underwent digital subtraction angiography and single photon emission computed tomography to measure disease severity and cerebral vascular reserve (CVR). A Cox regression model was used to identify predictors of recurrent ischemic stroke., Results: Fifty-nine patients were non-surgically treated and 45 patients were surgically treated. In the non-surgical group, the Kaplan-Meier estimate of ischemic stroke recurrence was 1.6% in the first year and 11.8% in the 5th year. Hypertension (hazard ratio [HR]=0.07, 95% confidence interval [CI] 0.01-0.99), diabetes (HR=35.16, 95% CI 2.61-474.16), presence of steno-occlusive lesion in posterior cerebral arteries (HR=17.53, 95% CI 2.02-152.43), and extended or global decreased CVR (HR=13.62, 95% CI 1.55-119.84) were independent predictors of recurrence. In the surgical group, the Kaplan-Meier estimate of ischemic stroke recurrence was 24.4% in the first year and 24.4% in the 5th year. Half of the recurred patients experienced recurrent ischemic strokes postoperatively. Diabetes was the only predictor of recurrent ischemic stroke (HR=6.17, 95% CI 1.31-29.14)., Conclusions: In non-surgically treated MMD, PCA stenosis and CVR were identified as predictors of ischemic stroke recurrence. Diabetes was an independent predictor of recurrent ischemic stroke in both non-surgical and surgically treated MMD groups., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Both Moyamoya disease (MMD) and intracranial atherosclerotic stenosis (ICAS) are more prevalent in Asians than in Westerners. We hypothesized that a substantial proportion of patients with adult-onset MMD were misclassified as having ICAS, which may in part explain the high prevalence of intracranial atherosclerotic stroke in Asians., Method: We analyzed 352 consecutive patients with ischemic events within the MCA distribution and relevant intracranial arterial stenosis, but no demonstrable carotid or cardiac embolism sources. Conventional angiography was performed in 249 (70.7%) patients, and the remains underwent MRA. The occurrence of the c.14429G>A (p.Arg4810Lys) variant in ring finger protein 213 (RNF213) was analyzed. This gene was recently identified as a susceptibility gene for MMD in East Asians., Results: The p.Arg4810Lys variant was observed in half of patients with intracranial stenosis (176 of 352, 50.0%), in no healthy control subjects (n = 51), and in 3.2% of stroke control subjects (4 of 124 patients with other etiologies). The presence of basal collaterals, bilateral involvement on angiography, and absence of diabetes were independently associated with the presence of the RNF213 variant. Among 131 patients who met all three diagnostic criteria and were diagnosed with MMD, three-fourths (75.6%) had this variant. However, a significant proportion of patients who met two criteria (57.7%), one criterion (28.6%), or no criteria (20.0%) also had this variant. Some of them developed typical angiographic findings of MMD on follow-up angiography., Conclusions: Careful consideration of MMD is needed when diagnosing ICAS because differential therapeutic strategies are required for these diseases and due to the limitations of the current diagnostic criteria for MMD.

The purpose of this study was to determine the prevalence and characteristics of symptomatic coronary heart disease (CHD) in patients with moyamoya disease (MMD). This retrospective study evaluated 456 patients who received examination for MMD between 1995 and 2012. We reviewed the patients' medical history and coronary imaging, including conventional coronary angiography and coronary computed tomography angiogram (CTA). Among 456 patients with MMD, 21 (4.6%) patients were found to have symptomatic CHD. Ten patients were treated with coronary artery bypass graft or percutaneous coronary intervention for unstable angina or myocardial infarction. Eleven were treated with medication for stable angina (n = 6) and variant angina with mild degree of stenosis (n = 5).The median age of these patients was 44 yr (range, 27-59). The median Framingham score at diagnosing MMD was < 1% (range, < 1%-16%). The old age was associated with CHD in uni- and multivariate analyses (P = 0.021, OR, 1.053; 95% CI, 1.008-1.110). Considering low age of onset and low stroke risk factor, CHD might be a systemic manifestation that is clinically relevant to MMD.

Background and Purpose: Diagnosis of Moyamoya disease (MMD) is based on the characteristic angiographic findings. However, differentiating MMD from intracranial atherosclerotic disease (ICAD) is difficult. We compared vessel wall imaging findings on high-resolution magnetic resonance imaging between MMD and ICAD., Methods: High-resolution magnetic resonance imaging was performed on 32 patients with angiographically proven MMD and 16 patients with acute infarcts because of ICAD. Bilateral internal carotid arteries and steno-occlusive middle cerebral artery were analyzed for wall enhancement and remodeling., Results: Enhancement patterns and distribution were different. Most patients with MMD (90.6%) showed concentric enhancement on distal internal carotid arteries and middle cerebral arteries, whereas focal eccentric enhancement was observed on the symptomatic segment in ICAD. MMD was characterized by middle cerebral artery shrinkage; the remodeling index and wall area were lower in MMD than in ICAD (remodeling index, 0.19±0.11 versus 1.00±0.43; wall area, 0.32±0.22 versus 6.00±2.72; P<0.001)., Conclusions: MMD was characterized by concentric enhancement on bilateral distal internal carotid arteries and shrinkage of middle cerebral artery, regardless of symptoms., (© 2014 American Heart Association, Inc.)

Background: As regular medical check-ups are becoming more common, the prevalence of asymptomatic moyamoya disease (MMD) is increasing. However, the definition and clinical features are still unclear. The lack of precision has hampered the establishment of guidelines for the management of asymptomatic MMD. The purpose of this study was to define and clarify the clinical characteristics of asymptomatic MMD in adults., Methods: We identified all adults (aged ≥18 years) with MMD who underwent digital subtraction angiography or magnetic resonance angiography at our institution from 1995 through 2010. The authors defined asymptomatic MMD as asymptomatic or nonspecific symptom without any infarction or ischemia on magnetic resonance imaging. In our MMD registry, 40 patients (74 hemispheres) were identified and enrolled in this retrospective cohort study. Their demographic, radiological and clinical findings were evaluated. The log-rank test was used to assess prognostic factors. Pearson's correlation test and the Mann-Whitney U test were used to identify correlation angiographic staging and age or perfusion status., Results: Overall, 6 patients underwent indirect bypass surgery and 36 received antiplatelet medication. On initial single positron emission tomography (35 patients, 67 affected hemispheres), basal and acetazolamide stress brain perfusion were decreased in 19 (28.4%) and 22 (32.8%) hemispheres, respectively. Among 70 angiographically evaluated hemispheres, 6 were unilateral MMD; 27 of 64 affected hemispheres (42.2%) had transdural collateral at evaluation. Age (p = 0.309, Pearson's correlation test) and hemodynamic impairment (p = 0.614, Mann-Whitney U test) did not correlate with angiographic staging. During a median 32-month (range 6-203) clinical follow-up, 3 nonsurgically treated patients had a transient ischemic attack, which was associated with decreased vascular reserve (p < 0.001, log-rank test) and smoking (p = 0.017). Other variables did not show a significant association with clinical progression. During a median 24-month (range 12-108) radiological follow-up, 3 patients displayed angiographic progression and 3 displayed new hemodynamic abnormalities. Radiological progressions were related to hypertension only (p = 0.022). In this case series, there was no case of ischemic or hemorrhagic stroke., Conclusion: The findings suggest that asymptomatic MMD in adults is not a stable disease in our definition. However, stroke rate (0%) was lower than previous reports. Lifestyle modification, stroke risk factor control and/or antiplatelet medication seem to be appropriate initial treatments for patients with normal cerebrovascular reserve. A clear definition of asymptomatic MMD and further clarification of its clinical course are needed to set precise treatment guidelines.

Background: Both basal collaterals (BC) and cortical microvascularization (CM) on angiography have been suggested as moyamoya disease (MMD)-specific findings; however, it is unknown whether the vascular network represents compensatory mechanisms for vascular occlusion or aberrant active neovascularization., Methods: We investigated the grade of antegrade MCA flow, the degree of BC, and the presence of CM on conventional angiography in relation to disease severity in pediatric MMD. CM was defined as enlarged and winding distal cortical arteries and categorized into anterior or posterior CM depending on their sources. Findings from basal and acetazolamide stress brain perfusion SPECT studies were also evaluated., Results: A total of 172 pediatric patients with MMD were enrolled in this study. As the severity of MMD increased, the grade of antegrade MCA flow gradually diminished. While the degree of BC peaked at Suzuki stage 3-4, CM was frequently observed at early MMD stages. About two-thirds of hemispheres with normal antegrade MCA flow on angiography and normal perfusion status on SPECT had anterior and/or posterior CM. Both anterior and posterior CM gradually decreased with the advancement of MMD., Conclusion: Our findings from a large cohort of angiographically confirmed pediatric MMD patients indicate that neovascularization may occur before significant hemodynamic impairment in MMD., (© 2014 S. Karger AG, Basel.)

Background and Purpose: To evaluate the factors predictive of contralateral progression in children and adolescents with unilateral moyamoya disease (MMD), the authors retrospectively analyzed clinicoradiological findings., Methods: The records of 394 consecutive patients with MMD aged 0 to 17 years were reviewed. Unilateral MMD was defined based on the typical angiographic findings of MMD in 1 hemisphere and no abnormality in the contralateral internal carotid artery and the middle cerebral artery. Of the 394 patients with MMD, 45 (11.4%) had unilateral MMD and the prevalence increased with age. Untreated contralateral hemispheres were followed by serial MR angiography. Follow-up angiography was performed if contralateral progression, defined as any noticeable change in the contralateral internal carotid artery and/or middle cerebral artery, was suggested by MR angiography., Results: Eight of the 45 (17.8%) had angiographically documented progression over a mean follow-up of 53.4 months. Mean time to contralateral progression was 27 months (range, 21 to 37 months). An age at diagnosis of <9 years was found to be the only independent predictor of contralateral progression (P=0.025), which persisted despite adjustment for sex and ipsilateral Suzuki stage (hazard ratio, 8.26; 95% CI, 1.01 to 67.94). Other factors, including abnormalities in the contralateral anterior cerebral artery, were not found to be predictive of progression to bilateral MMD., Conclusions: The incidence of contralateral progression in our cohort of children and adolescents with unilateral MMD appears to be lower than those previously reported. Furthermore, contralateral progression tended to occur in children aged <9 years within 3 years of initial diagnosis (32%).

Background: Major artery aneurysms may be found incidentally while evaluating moyamoya disease (MMD). The purpose of this study was to delineate the prevalence and characteristics of these uncommon aneurysms with a brief mention of their management and outcomes., Methods: We conducted a retrospective review of 249 adult patients who were diagnosed with non-hemorrhagic MMD. Cerebral angiograms obtained at the time of initial diagnosis were carefully reviewed to identify incidental aneurysms located on a major intracranial artery or near its tributaries. Aneurysms originating from distal peripheral arteries or moyamoya vessels were ineligible for this study., Results: Nine patients (3.6%) were found to have 13 major artery aneurysms, 7 (54%) of which were located in the posterior circulation, especially in older patients with bilateral MMD. The sizes of all aneurysms were less than 10 mm. Surgical clipping was performed on two aneurysms, and endovascular coiling on six (five posterior circulation aneurysms). Ischemic complications occurred in two patients after clipping of an anterior communicating artery aneurysm and in one patient after the second coiling of a recanalized basilar tip aneurysm., Conclusions: Incidental major artery aneurysms can be found in 3.6% of adult patients with non-hemorrhagic MMD, an observed frequency that increases with age. About half of these aneurysms are located in the posterior circulation, particularly in older patients with bilateral MMD. Considering the risks of treatment-related complications, more information about the natural course of these aneurysms is needed to design proper management strategies both for the aneurysms and MMD.

Background: To clarify the risk factors associated with perioperative ischemic complications in adult-onset moyamoya disease., Material and Methods: The incidence and causes of perioperative ischemic complications in adult-onset moyamoya disease were retrospectively examined by reviewing 165 surgically treated adult patients. Two hundred forty-six revascularization procedures were performed in these patients., Results: There were 19 (7.7%) perioperative ischemic complications (four infarctions with neurological sequelae and 15 reversible ischemic neurological deficits with a new lesion). The complications occurred in the initially affected hemispheres in 17 (89.4%) of the 19 ischemic complications, regardless of the side of the operation. Multiple ischemic episodes (defined as over four-symptom episodes before treatment), the presence of a preoperative low density area (LDA) on computed tomographic (CT) scanning, and a high signal intensity on diffusion-weighted magnetic resonance (MR) imaging were significantly correlated with perioperative ischemic complications (p < 0.05, p < 0.05, and p < 0.01, respectively). Non-surgical hemodynamic risk factors, i.e., hypercapnia, hypocapnia, or hypotension/hypovolemia, were noted in all of the 19 cases. None of the surgical factors evaluated were associated with the complications identified., Conclusions: Avoidance of non-surgical hemodynamic risk factors as well as maintaining vital collateral vessels is essential for the prevention of perioperative hemodynamic brain damage in patients with adult-onset moyamoya disease. In addition, very close monitoring of the perioperative care of patients with preoperative multiple ischemic episodes and an LDA or high signal intensity on preoperative CT or diffusion-weighted MR imaging is extremely important.

Background and Purpose: To investigate the association between thyroid autoantibodies and moyamoya disease (MMD) in patients with an apparent euthyroid state., Methods: We prospectively studied angiographically diagnosed patients with MMD. We compared demographic profiles, thyroid function test, and thyroid autoantibody status between MMD and control groups., Results: A total of 63 patients with MMD, 71 patients with non-MMD stroke, and 200 healthy control subjects were included. The prevalence of elevated thyroid autoantibodies was higher in the MMD group than in other groups (P<0.01 for MMD versus non-MMD; P<0.001 for MMD versus control subjects). After adjusting for covariates, the elevated thyroid autoantibodies (OR, 4.871; 95% CI, 1.588 to 15.277) and smoking habits (OR, 0.206 for current smoker; 95% CI, 0.054 to 0.786) were independently associated with MMD versus non-MMD stroke., Conclusions: Elevated thyroid autoantibodies were frequently observed in patients with MMD. The results of the present study suggest that immune aberrancies associated with or underlying thyroid autoimmunity are also playing a role in developing MMD.

Background: Both intracranial atherosclerotic stenosis (ICAS) and moyamoya disease (MMD) are prevalent in Asians. We hypothesized that the Ring Finger protein 213 gene polymorphism (RNF213), a susceptibility locus for MMD in East Asians, is also a susceptibility gene for ICAS in patients whose diagnosis had been confirmed by conventional angiography (absence of basal collaterals) and high-resolution MRI (HR-MRI, presence of plaque). Methods: We analyzed 532 consecutive patients with ischemic events in the middle cerebral artery (MCA) distribution and relevant stenotic lesion on the distal internal carotid artery or proximal MCA, but no demonstrable carotid or cardiac embolism sources. Additional angiography was performed on 370 (69.5%) patients and HR-MRI on 283 (53.2%) patients. Results: Based on angiographic and HR-MRI findings, 234 patients were diagnosed with ICAS and 288 with MMD. The RNF213 variant was observed in 50 (21.4%) ICAS patients and in 119 (69.1%) MMD patients. The variant was observed in 25.2% of patients with HR-MRI-confirmed ICAS. Similarly, 15.8% of ICAS patients in whom MMD was excluded by angiography had this variant. Among the ICAS patients, RNF213 variant carriers were younger and more likely to have a family history of MMD than non-carriers were. Multivariate testing showed that only the age of ICAS onset was independently associated with the RNF213 variant (odds ratio, 0.97; 95% CI, 0.944–0.99). Conclusions: RNF213 is a susceptibility gene not only for MMD but also for ICAS in East Asians. Further studies are needed on RNF213 variants in ICAS patients outside East Asian populations. [ABSTRACT FROM AUTHOR]