Unilateral Moyamoya Disease Research Articles

Disease progression, transient ischemic attack, and de novo parenchymal lesions in asymptomatic moyamoya disease: results of a 5-year interim analysis of the AMORE study

OBJECTIVE Recently, the authors have reported the 5-year risk of stroke in patients with asymptomatic moyamoya disease (MMD). In this report, the aim was to clarify patients’ 5-year risk of disease progression, transient ischemic attack (TIA), and de novo parenchymal lesions and to identify their predictors. METHODS This multicenter, prospective cohort study (Asymptomatic Moyamoya Registry [AMORE]) in Japan is still ongoing. Participants were enrolled if they were 20–70 years of age, had bilateral or unilateral MMD, experienced no episodes suggestive of TIA and stroke, were functionally independent (modified Rankin Scale score of 0 or 1), and had been followed up for 10 years. Clinical and radiological data were obtained at enrollment and annually thereafter for 5 years. In this 5-year interim analysis, the authors defined disease progression, TIA, and de novo parenchymal lesions as the secondary endpoints. The predictors for these events were identified, using a stratification analysis method. RESULTS A total of 103 patients were enrolled and prospectively followed up for 5 years. On annual MRA examinations, disease progression occurred in 39 hemispheres in 26 patients. The incidence of disease progression was 5.9% per patient-year, and the predictors included younger age (OR 5.72, 95% CI 1.28–25.56; p = 0.0223) and hypercholesterolemia (OR 5.41, 95% CI 1.37–21.28; p = 0.0158). TIA occurred in 12 hemispheres in 10 patients, for an incidence of 2.3% per patient-year. The disease progression prior to TIA was a significant predictor for TIA (OR 5.00, 95% CI 1.31–19.0; p = 0.0184). De novo microbleeds were found in 11 hemispheres in 10 patients (2.3% per patient-year). The presence of microbleeds at enrollment was a significant predictor for de novo microbleeds (OR 5.53, 95% CI 1.17–26.13; p = 0.0309). CONCLUSIONS Patients with asymptomatic MMD may carry a significant risk of disease progression, TIA, and de novo microbleeds during the first 5 years after initial diagnosis. Practitioners should very carefully follow up with them to improve their outcome, using MRI and MRA at regular intervals. Clinical trial registration no.: UMIN000006640 (https://www.umin.ac.jp).

FOXM1 c.1205C > A mutation is associated with unilateral Moyamoya disease and inhibits angiogenesis in human brain endothelial cells.

Unilateral moyamoya disease (MMD) represents a distinct subtype characterised by occlusive changes in the circle of Willis and abnormal vascular network formation. However, the aetiology and pathogenesis of unilateral MMD remain unclear. In this study, genetic screening of a family with unilateral MMD using whole-genome sequencing helped identify the c.1205C > A variant of FOXM1, which encodes the transcription factor FOXM1 and plays a crucial role in angiogenesis and cell proliferation, as a susceptibility gene mutation. We demonstrated that this mutation significantly attenuated the proangiogenic effects of FOXM1 in human brain endothelial cells, leading to reduced proliferation, migration, and tube formation. Furthermore, FOXM1 c.1205C > A results in increased apoptosis of human brain endothelial cells, mediated by the downregulation of the transcription of the apoptosis-inhibiting protein BCL2. These results suggest a potential role for the FOXM1 c.1205C > A mutation in the pathogenesis of unilateral MMD and may contribute to the understanding and treatment of this condition.

405 The Impact of Cerebral Revascularization on Pial Collateral Flow in Patients With Moyamoya Disease Using Quantitative Magnetic Resonance Angiography

INTRODUCTION: Moyamoya disease (MMD) is a chronic steno-occlusive disease primarily of the anterior circulation leading to significant pial collateralization. Changes in the distribution of intracranial blood flow after revascularization surgery are not well understood. METHODS: We conducted a retrospective chart review of 46 patients with unilateral MMD who underwent cerebral revascularization from 2011-2019. Patients who underwent pre- and post- QMRA NOVA were included in the study. Flow was measured at the M1 segment of the middle cerebral artery (MCA), P2 segment of the posterior cerebral artery (PCA), and A2 segment of the anterior cerebral artery (ACA). Pial collaterals were defined as the sum of (A2+P2) flow. Total hemispheric flow was calculated as (M1+PCA+A2) pre-operatively and (M1+PCA+A2+Bypass) post-operatively, with the incorporation of the bypass graft. RESULTS: A total of 46 patients with unilateral MMD underwent revascularization with pre and post QMRA. Total intracranial flow at baseline prior to revascularization was lower in the side of disease (214.9 ml/min vs. 269.1 ml/min). Total intracranial flow at baseline after revascularization remained lower on the ipsilateral side of disease with an increased flow in the contralateral healthy side (211.7 ml/min vs 286.1 ml/min). Pre-bypass there was a higher flow through pial collaterals on the ipsilateral diseased side (183 ml/min) than the contralateral healthy side (135 ml/min). Post-bypass this difference in pial flow between ipsilateral and contralateral sides decreased from 48 ml/min to 22 ml/min (p = 0.02). Collateral ratio decreased significantly (0.46 preoperatively vs. 0.18 postoperatively) (P < 0.01). CONCLUSIONS: The results of this study quantitatively confirm that direct cerebral revascularization decreases collateral stress in patients with moyamoya disease.

Impact of Cerebral Revascularization on Pial Collateral Flow in Patients With Unilateral Moyamoya Disease Using Quantitative Magnetic Resonance Angiography.

Moyamoya disease (MMD) is a chronic steno-occlusive disease of the intracranial circulation that depends on neoangiogenesis of collateral vessels to maintain cerebral perfusion and is primarily managed with cerebral revascularization surgery. A quantitative assessment of preoperative and postoperative collateral flow using quantitative magnetic resonance angiography with noninvasive optimal vessel analysis (NOVA) was used to illustrate the impact of revascularization on cerebral flow distribution. A retrospective review of patients with unilateral MMD who underwent direct, indirect, or combined direct/indirect cerebral revascularization surgery was conducted between 2011 and 2020. Using NOVA, flow was measured at the anterior cerebral artery (ACA), ACA distal to the anterior communicating artery (A2), middle cerebral artery (MCA), posterior cerebral artery (PCA), and PCA distal to the posterior communicating artery (P2). Pial flow (A2 + P2) and collateral flow (ipsilateral [A2 + P2])-(contralateral [A2 + P2]) were measured and compared before and after revascularization surgery. Total hemispheric flow (MCA + A2 + P2) with the addition of the bypass graft flow postoperatively was likewise measured. Thirty-four patients with unilateral MMD underwent cerebral revascularization. Median collateral flow significantly decreased from 68 to 39.5 mL/min ( P = .007) after bypass. Hemispheres with maintained measurable bypass signal on postoperative NOVA demonstrated significant reduction in median collateral flow after bypass ( P = .002). Median total hemispheric flow significantly increased from 227 mL/min to 247 mL/min ( P = .007) after bypass. Only one patient suffered an ipsilateral ischemic stroke, and no patients suffered a hemorrhage during follow-up. NOVA measurements demonstrate a reduction in pial collateral flow and an increase in total hemispheric flow after bypass for MMD, likely representing a decrease in leptomeningeal collateral stress on the distal ACA and PCA territories. Further studies with these measures in larger cohorts may elucidate a role for NOVA in predicting the risk of ischemic and hemorrhagic events in MMD.

Long-term outcomes after conservative and EDAS treatment for 111 elderly patients with moyamoya disease: longitudinal and cross-sectional study.

This study aimed to explore the clinical features of moyamoya disease (MMD) and the efficacy of encephaloduroarteriosynangiosis (EDAS) in elderly patients with MMD and to identify the risk factors for long-term stroke events. Clinical data were retrospectively collected on elderly patients with MMD (age ≥ 60 years) who had been treated at the authors' center from May 2007 to December 2017. Clinical features, angiographic findings, and long-term outcomes (> 5-year follow-up) were analyzed. Cox regression analysis was performed to determine the risk factors for postoperative stroke events. Long-term stroke events were analyzed using Kaplan-Meier curves. The mean age at symptom onset was 62.9 ± 3.0 years among 111 elderly patients with MMD. Vascular comorbidities were present in 80 (72.1%) patients. The ratio of female to male patients was 1:1.2. Familial MMD was found in 7 (6.3%) patients. Cerebral ischemia was the most common clinical manifestation observed in 82 (73.9%) patients. Most patients (59.5%) presented with Suzuki stages 5 and 6 MMD, and 29 (26.1%) patients presented with stenosis or occlusion of the posterior circulation. Unilateral MMD was present in 17 (15.3%) patients. Among the 58 (52.3%) patients who underwent EDAS, 28 (48.3%) and 30 (51.7%) underwent bilateral and unilateral surgeries, respectively. Overall, 53 (47.7%) patients were treated conservatively using internal medicine. After a median follow-up duration of 8.2 years, stroke incidence in the EDAS and conservative treatment groups was respectively 17.2% (7 and 3 cases of cerebral infarction and hemorrhage, respectively) and 49.1% (22 and 4 cases of cerebral infarction and hemorrhage, respectively). The stroke incidence rate was higher in the conservative group than in the EDAS group, with a statistically significant difference (p = 0.001) according to results of the Kaplan-Meier analysis. The identified predictor of postoperative stroke events was initial hemorrhage in the EDAS group and advanced age, aneurysm, and initial ischemia in the conservative treatment group. The postoperative long-term stroke rate among elderly patients with MMD was lower in the EDAS group than in the conservative treatment group. Long-term stroke events were associated with advanced age, aneurysm, and initial ischemia after conservative treatment and only initial hemorrhage after EDAS.

Clinical and genetic factors associated with contralateral progression in unilateral moyamoya disease: Longitudinal and Cross-Sectional Study

ObjectiveThis study aimed to explore the long-term outcome of unilateral moyamoya disease and predict the clinical and genetic factors associated with contralateral progression in unilateral moyamoya disease. MethodsWe retrospectively recruited unilateral moyamoya disease patients with available genetic data who underwent encephaloduroarteriosynangiosis (EDAS) surgery at our institution from January 2009 to November 2017. Long-term follow-up data, including clinical outcomes, angiographic features, and genetic information, were analyzed. ResultsA total of 83 unilateral moyamoya disease patients with available genetic data were enrolled in our study. The mean duration of clinical follow-up was 7.9 ± 2.0 years. Among all patients, 19 patients demonstrated contralateral progression to bilateral disease. Heterozygous Ring Finger Protein 213 p.R4810K mutations occurred significantly more frequently in unilateral moyamoya disease patients with contralateral progression. Furthermore, patients with contralateral progression typically demonstrated an earlier age of onset than those with non-progressing unilateral moyamoya disease. In the contralateral progression group, posterior circulation involvement was observed in 11 (11/19, 57.9%) patients compared to 12 (12/64, 18.8%) in the non-contralateral progression group (P = 0.001). The time to peak of cerebral perfusion and neurological status showed significant postoperative improvement. ConclusionLong-term follow-up revealed that the EDAS procedure might provide benefits for unilateral moyamoya disease patients. Ring Finger Protein 213 p.R4810K mutations, younger age, and posterior circulation involvement might predict the contralateral progression of unilateral moyamoya disease.

Posterior cerebral artery involvement in unilateral moyamoya disease is exclusively ipsilateral and influenced by RNF213 mutation gene dose: The SUPRA Japan study: PCA involvement in unilateral moyamoya

ObjectivesThe characteristics and clinical implications of posterior cerebral artery (PCA) involvement in unilateral moyamoya disease (U-MMD), such as laterality, frequency of the RNF213 p.R4810K mutation, and clinical outcomes, have not been well studied. Population and methodsWe analyzed a cohort of 93 patients with U-MMD who participated in the SUPRA Japan study. Clinical characteristics and radiological examinations were collected from medical records. The presence of the p.R4810K mutation was determined using a TaqMan assay. The clinical outcome was assessed using the modified Rankin Scale (mRS). Univariate and multivariate logistic regression analyses were performed to assess the associations. ResultsAmong the patients with U-MMD, PCA involvement was observed in 60.0 % (3/5) of patients with homozygous mutation, 11.3 % (7/62) of those with heterozygous mutation, and 3.8 % (1/26) of those with wild type, showing a significant linear trend (p < 0.001 for trend). PCA involvement was observed exclusively on the same side as the affected anterior circulation. Dyslipidemia and cerebral infarction at initial onset were independently associated with mRS ≥1. Hypertension was associated with mRS ≥1 and it was also linked to infarction at initial onset, suggesting a potential confounding effect. Although PCA involvement showed a trend for higher mRS, it was not statistically significant. ConclusionsOur findings indicate a gene dose effect of the p.R4810K mutation on PCA involvement, with the homozygous state showing the most significant effect. Both genetic and modifiable factors such as dyslipidemia may influence the progression of U-MMD.

Effect of cerebral oxygen saturation monitoring in patients undergoing superficial temporal anterior-middle cerebral artery anastomosis for ischemic Moyamoya disease: a prospective cohort study.

Regional cerebral oxygen saturation (rSO2) is linked with blood pressure. This study evaluated the influence of perioperative rSO2 monitoring on the prognosis of ischemic Moyamoya disease (MMD) patients undergoing anastomosis surgery. In this prospective cohort, patients with unilateral ischemic MMD of Suzuki stage ≥3 were included. The decision of rSO2 was made by the clinician and the patient. The rSO2 group maintained intraoperative rSO2 levels through the modulation of blood pressure, inhaled oxygen concentration, carbon dioxide in arterial blood, and red blood cell transfusion. The non-rSO2 group used conventional anesthesia practices. Perioperative mean arterial pressure (MAP), rSO2 values, neurological complications, and postoperative results were assessed. A total of 75 eligible patients were categorized into a rSO2 monitoring group (n = 30) and a non-rSO2 monitoring group (n = 45). For the rSO2 group, the preoperative rSO2 was significantly lower on the affected side (P < 0.05). After anastomosis, this value notably increased (P = 0.01). A moderate relationship was observed between perioperative rSO2 and MAP before, during, and after surgery, with correlation coefficients (r) of 0.536, 0.502, and 0.592 (P < 0.05). Post-surgery MAP levels differed between the groups, with the rSO2 group showing decreased levels compared to pre-surgery and the non-rOS2 group displaying elevated levels. Notably, the rSO2 group reported shorter hospitalizations and decreased neurological complications. Patients with a hypertension history found postoperative MAP influencing hospital stay duration. Perioperative rSO2 surveillance enhanced cerebral perfusion and minimized postoperative complications in ischemic MMD patients. Thus, rSO2 monitoring is advocated for MMD patients undergoing vascular anastomosis.

Ruptured basilar artery perforator aneurysm: a novel mechanism of pure subarachnoid hemorrhage in moyamoya disease. Illustrative case.

Pure subarachnoid hemorrhage (SAH) in patients with moyamoya disease is a rare occurrence. Three underlying mechanisms have been described previously, except for ruptured aneurysm of the circle of Willis. Herein, the authors describe a novel mechanism: rupture of a perforator aneurysm in moyamoya disease. A 51-year-old man experienced sudden onset of severe headache and vomiting. Computed tomography showed diffuse SAH. Digital subtraction angiography (DSA) showed unilateral moyamoya disease without remarkable etiology of SAH. The patient underwent conservative management with antihypertensive agents. The second DSA on day 17 revealed a slow-filling aneurysm emerging from the basilar top perforating artery. The diagnosis of SAH due to unknown origin was changed to ruptured basilar artery perforator aneurysm (BAPA). The third follow-up DSA on day 159 revealed the resolution of BAPA. In the case of pure SAH, it is crucial to consider the possibility of perforator aneurysms due to hemodynamic stress caused by moyamoya disease. Repeated DSA is essential for detecting the lesion.

RNF213 R4810K Variant in Suspected Unilateral Moyamoya Disease Predicts Contralateral Progression.

BackgroundEarly‐stage unilateral moyamoya disease (MMD) is difficult to discriminate from isolated intracranial atherosclerotic stenosis, and identification of contralateral progression may aid in the diagnosis of MMD. The RNF213 (ring finger protein 213) R4810K variant is a strong genetic susceptibility factor for MMD; however, the role of contralateral progression in unilateral MMD is unknown.Methods and ResultsPatients who had undergone RNF213 R4810K genotyping with suspected unilateral MMD between January 2017 and August 2021 from 2 tertiary university hospitals were retrospectively reviewed. We compared the clinical features and radiographic outcomes of patients with and without this variant. The risk factors of contralateral progression in patients with suspected unilateral MMD were evaluated. The RNF213 R4810K variant was observed in 72 of 123 patients with suspected unilateral MMD, all of which were heterozygous. The allele frequency of the R4810K variant was significantly higher in the suspected unilateral MMD group compared with the historical control group (29.3% versus 1.2%; P<0.0001). Family history of MMD was significantly more common in patients with the variant than in those without (17% versus 4%; P=0.003). Eleven of 72 patients with the variant developed contralateral progression, whereas only 1 of 51 patients without the variant developed contralateral progression during a median follow‐up period of 28 months (log‐rank test; P=0.03). The presence of the RNF213 R4810K variant significantly correlated with contralateral progression (adjusted odds ratio, 6.39 [95% CI, 1.11–36.63]; P=0.04).ConclusionsContralateral progression is more likely to occur in patients with suspected unilateral MMD with the RNF213 R4810K variant than in those without the variant. However, because our study used a small sample size, this finding should be carefully interpreted and requires further studies with more patients and longer follow‐up periods.

Angiographic Characteristics of Cerebral Perfusion and Hemodynamics of the Bridging Artery After Surgical Treatment of Unilateral Moyamoya Disease.

PurposeTo investigate the characteristics of cerebral perfusion and hemodynamics of bypass grafting in the treatment of moyamoya disease (MMD) using the iFlow color-coded flow map in comparison with magnetic resonance imaging–perfusion-weighted imaging (MRI–PWI) and computational fluid dynamic (CFD) analysis.Materials and MethodsPatients with MMD treated with bypass grafting who had undergone MRI PWI and digital subtraction angiography for iFlow color-coded map was retrospectively enrolled and CFD was performed for calculating the hemodynamic stresses around the bypass grafting.ResultsForty-five patients with unilateral MMD treated with bypass surgery were enrolled. The bypass surgery was successful in all patients, with no severe neurological complications during the periprocedural period. Followed up for 4–12 months (median 5.5), the neurological function was good in all patients. The cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and time to peak (TTP) were significantly (p < 0.05) improved in the middle cerebral artery distribution area on the surgical side before and after vascular bypass, and the difference of TTP (s) measured from the proximal bifurcation of common carotid artery to the confluence of sinus was also significant (p < 0.05). A significant (p < 0.05) positive correlation existed in the perfusion parameters between the iFlow blood perfusion and the MRI–PWI perfusion, with r-value for TTP of 0.765 (p < 0.01). The iFlow color-coded blood flow map showed warm color changes on the diseased side, similar to those on the contralateral side. In CFD analysis, the hemodynamic stresses were all improved, in and around the bypass grafting and distal vessels, which were beneficial to blood flow entering distal arterial branches.ConclusionThe iFlow color-coded flow map can be used to analyze cerebral perfusion after bypass grafting for MMD, similar to MRI–PWI, and CFD can be used to analyze the hemodynamics after bypass grafting, revealing improved hemodynamics to promote blood flow entering distal arteries.

Pediatric moyamoya disease associated with ipsilateral internal carotid artery agenesis: illustrative case

BACKGROUNDAlthough most cases of internal carotid artery (ICA) agenesis are clinically silent due to a well-developed collateral pathway, some cases may develop ischemic symptoms when they are associated with other occlusive cerebrovascular disorders. The authors describe herein the first case with ICA agenesis that developed ischemic attack because of coincidence with moyamoya disease.OBSERVATIONSA 3-year-old girl was admitted to the authors’ hospital due to sudden onset of right arm weakness followed by clonic convulsion. Skull computed tomography could not identify the carotid canal on the left side. Simultaneously, magnetic resonance (MR) imaging and MR angiography demonstrated the luminal stenosis and outer diameter reduction of the carotid fork and posterior cerebral artery on the left side. She was diagnosed with unilateral moyamoya disease associated with ipsilateral ICA agenesis. She successfully underwent combined bypass surgery on the left side and has been free from any cerebrovascular events during a follow-up period of 6 months.LESSONSWhen patients with ICA agenesis develop ischemic symptoms, careful investigation of the cause and appropriate care, including surgical treatment, are required.

Genetic and nongenetic factors for contralateral progression of unilateral moyamoya disease: the first report from the SUPRA Japan Study Group.

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. 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. 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. 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.

Erratum. Genetic and nongenetic factors for contralateral progression of unilateral moyamoya disease: the first report from the SUPRA Japan Study Group.

"Erratum. Genetic and nongenetic factors for contralateral progression of unilateral moyamoya disease: the first report from the SUPRA Japan Study Group" published on 29 Oct 2021 by American Association of Neurological Surgeons.

The contralateral progression in a cohort of Chinese adult patients with unilateral moyamoya disease after revascularization: a single-center long-term retrospective study

BackgroundMoyamoya disease (MMD) is a chronic progressive cerebrovascular disease mainly existing in the Asian population, which can be divided into unilateral and bilateral types. Contralateral progression has been reported in pediatric patients with unilateral MMD, while large series about contralateral progression in Chinese adult patients were rare. The goal of this study is to elucidate the clinical features and incidence of contralateral progression in Chinese MMD adult patients.MethodsOne hundred one Chinese adult patients with unilateral MMD who received surgery treatments between January 2015 and January 2017 in our hospital were enrolled in this study. This study contained 89 patients. Digital subtraction angiography was performed in all patients for initial diagnosis, and magnetic resonance angiography was repeated 6 months from the initial operation and then annually. Clinical characteristics, contralateral progression, and risk factors were studied. Previous related studies were also reviewed and meta-analyzed.ResultsOf these 89 patients, contralateral progression was identified in 8 patients (9.0%) within a median follow-up period of 63 months, which was lower than that in previous studies (25.9%). Single-factor analysis and multivariate analysis did not reveal significant risk factors related to the contralateral progression.ConclusionThe progress rate in this cohort of Chinese adult patients with unilateral MMD after revascularization was 9.0%, which indicates that some of the unilateral MMD were an early form of bilateral MMD rather than a separate condition.Trial registration.This work was approved by the Medical Ethics Committee of Zhongnan Hospital of Wuhan University (approval number: Kelun-2017005).

Patient-Specific Modeling Could Predict Occurrence of Pediatric Stroke.

Moyamoya disease (MMD) is a progressive steno-occlusive cerebrovascular disease leading to recurrent stroke. There is a lack of reliable biomarkers to identify unilateral stroke MMD patients who are likely to progress to bilateral disease and experience subsequent contralateral stroke(s). We hypothesized that local hemodynamics are predictive of future stroke and set out to noninvasively assess this stroke risk in pediatric MMD patients. MR and X-ray angiography imaging were utilized to reconstruct patient-specific models of the circle of Willis of six pediatric MMD patients who had previous strokes, along with a control subject. Blood flow simulations were performed by using a Navier–Stokes solver within an isogeometric analysis framework. Vascular regions with a wall shear rate (WSR) above the coagulation limit (>5,000 s−1) were identified to have a higher probability of thrombus formation, potentially leading to ischemic stroke(s). Two metrics, namely, “critical WSR coverage” and “WSR score,” were derived to assess contralateral stroke risk and compared with clinical follow-up data. In two patients that suffered a contralateral stroke within 2 months of the primary stroke, critical WSR coverages exceeding 50% of vessel surface and WSR scores greater than 6× the control were present in multiple contralateral vessels. These metrics were not as clearly indicative of stroke in two additional patients with 3–5 year gaps between primary and contralateral strokes. However, a longitudinal study of one of these two cases, where a subsequent timepoint was analyzed, suggested disease stabilization on the primary stroke side and an elevated contralateral stroke risk, which was confirmed by patient outcome data. This indicates that post-stroke follow-up at regular intervals might be warranted for secondary stroke prevention. The findings of this study suggest that WSR-based metrics could be predictive of future stroke risk after an initial stroke in pediatric MMD patients. In addition, better predictions may be possible by performing patient-specific hemodynamic analysis at multiple timepoints during patient follow-up to monitor changes in the WSR-based metrics.

Asymptomatic Moyamoya Disease in a North American Adult Cohort

The natural history of asymptomatic adult moyamoya disease (MMD) is unclear, and the benefit of treatment remains controversial. This study aimed to investigate the natural history of asymptomatic MMD in a North American cohort and to evaluate risk factors associated with and the effects of treatment on disease progression. Medical records from 3 institutions of consecutive adult patients with MMD diagnosed between 1984 and 2018 were retrospectively reviewed. Patients with unilateral or bilateral asymptomatic MMD were evaluated for subsequent development of infarction or hemorrhage. Multivariate Cox proportional hazards regression assessed risk factors associated with infarction or hemorrhage, adjusting for age, sex, race, initial Suzuki grade, hypertension, hyperlipidemia, diabetes, obesity, presence of aneurysms, smoking status, aspirin, and statin use at diagnosis. We identified 106 hemispheres with asymptomatic MMD in 97 patients with mean 5.1 years (interquartile range, 1.0-7.9 years) of follow-up. Of 106 hemispheres, 59 were treated medically, and 47 were treated with revascularization with direct or indirect bypasses. The medical and surgical cohorts had a 1.9% and 1.3% annual rate of radiographic infarction or hemorrhage per hemisphere, respectively. Cox regression for radiographic events, including early postoperative events, showed no significant difference between the treatment groups (adjusted hazard ratio 0.34 [95% confidence interval 0.05-2.5]). We found an overall 1.7% annual rate of radiographic infarction or hemorrhage in asymptomatic MMD hemispheres. Although we did not find a benefit to surgical treatment within the study period, asymptomatic patients with expected long-term survival may benefit from surgery given the sustained long-term benefits after surgery despite an initial postoperative risk.

Clinical Course of Unilateral Moyamoya Disease

Church, Ephraim W MD; Bell-Stephens, Teresa E BSN, RN; Bigder, Mark G MD; Gummidipundi, Santosh MS; Han, Summer S PhD; Steinberg, Gary K MD, PhD

Angiographic and Hemodynamic Features in Asymptomatic Hemispheres of Patients With Moyamoya Disease.

There is also a risk of stroke in the asymptomatic hemispheres of moyamoya disease (MMD), but it does not draw enough attention. The study investigated the differences between the three types of asymptomatic hemispheres in MMD and their associations with the two types of symptomatic hemispheres, respectively. Retrospectively reviewed clinical and imaging characteristics of asymptomatic and symptomatic hemispheres in consecutive cases of single-center MMD patients, with an emphasis on imaging characterization regarding vascular morphology and cerebral perfusion. MMD hemispheres were categorized into 5 types: hemorrhagic hemispheres, ischemic hemispheres, asymptomatic hemispheres in unilateral hemorrhagic MMD, asymptomatic hemispheres in unilateral ischemic MMD, and bilateral asymptomatic hemispheres in MMD. Angiographic feature was assessed by Suzuki's angiographic stage, while hemodynamic feature was assessed by preinfarction period stage. One hundred ninety-four MMD patients with 388 hemispheres were enrolled. Asymptomatic hemispheres in unilateral hemorrhagic MMD were largely similar to hemorrhagic hemispheres, both had more advanced Suzuki's angiographic stage and lower degree of hemodynamic failure compared with bilateral asymptomatic hemispheres in MMD and asymptomatic hemispheres in unilateral ischemic MMD. Asymptomatic hemispheres in unilateral ischemic MMD were similar to ischemic hemispheres, both had less advanced Suzuki's angiographic stage and higher degree of hemodynamic failure compared with bilateral asymptomatic hemispheres in MMD and asymptomatic hemispheres in unilateral hemorrhagic MMD. Bilateral asymptomatic hemispheres in MMD were different from the other hemispheres and had less advanced Suzuki's angiographic stage and lower degree of hemodynamic failure. The three types of asymptomatic hemispheres in MMD are defined and have unique angiographic and hemodynamic features. Different combinations of the two features can reflect the tendency of pathological evolution in these different asymptomatic hemispheres.

Clinical Course of Unilateral Moyamoya Disease.

The natural history of unilateral moyamoya disease (MMD) progressing to bilateral MMD remains an enigma in modern vascular neurosurgery. Few, small series with limited follow-up have reported relatively high rates of contralateral stenosis progression. To review our large series of unilateral MMD patients and evaluate radiographic and surgical progression rates, and identify any factors associated with progression. We included all unilateral MMD cases treated from 1991 to 2017 in an observational study. We examined time to contralateral radiographic progression and contralateral progression requiring surgery. Using Cox regression analysis, we evaluated factors potentially associated with contralateral progression. There were 217 patients treated for unilateral MMD. About 71% were female, and the average age at first surgery was 33.8 yr. Average follow-up was 5.8 yr (range 1-22 yr). A total of 18 patients (8.3%) developed contralateral progression. And 8 of these (3.7%) developed progression requiring bypass surgery. Baseline stenosis and hyperlipidemia (HLD) were significantly associated with radiographic progression (hazard ratio [HR] = 9.7, P=.006; HR=4.0, P=.024). Baseline stenosis was associated with surgical progression (HR=44.2, P=.002). Results were similar when controlling for possible confounders using multivariate regression. Previous series showed relatively high rates of progression in unilateral MMD (15%-30%), but these studies were small and long-term follow-up was rarely available. Our large series indicates that the rate of progression is lower than previously reported but still warrants yearly noninvasive screening. These data may provide indirect support for statin therapy in MMD.