Stroke Events and Risk Factors in Older Patients with Moyamoya Disease.

BACKGROUND: We aimed to comprehensively analyze the epidemiology, natural history, stroke events and their risk factors, and the RNF213 p.Arg4810Lys variant in older patients with moyamoya disease (MMD). METHODS: We enrolled patients with MMD followed-up at our hospital between 2000 and 2023. Those who developed MMD at age ≥60 years or were diagnosed at a younger age and followed-up after age 60 years were included. Baseline characteristics, onset type, radiologic features, and RNF213 p.Arg4810Lys variant status were investigated. RESULTS: Among 56 patients with 100 affected hemispheres, 62 were asymptomatic, 26 experienced ischemic onset, and 12 had hemorrhagic onset. A higher incidence of anterior choroidal artery (AchA) dilatation and lower proportion of favorable modified Rankin scale scores were detected in hemorrhagic onset, whereas greater prevalence of bypass surgery in ischemic onset. Of 76 asymptomatic hemispheres at the age of 60 years, subsequent stroke events occurred in 10 hemispheres, comprising 8 hemorrhages and 2 ischemias. Risk factors for de novo hemorrhage in asymptomatic hemispheres included AchA dilatation and choroidal anastomosis. Comparison of the RNF213 p.Arg4810Lys variant status showed no significant differences in baseline characteristics, onset types, or imaging findings, except for a higher percentage of patients in the GA group with a family history of MMD. CONCLUSIONS: Hemorrhagic events were the most prevalent and prognostically deteriorating factors in older patients with MMD aged ≥60 years. AchA dilatation and choroidal anastomosis were predictors of de novo hemorrhage in asymptomatic nonsurgical hemispheres in older patients with MMD.

Risk factors associated with in-hospital complications for pediatric sickle-cell disease-associated moyamoya syndrome: a nationwide cross-sectional study.

PURPOSE: Sickle-cell disease-associated moyamoya syndrome (SCD-MMS) carries a high risk for recurrent strokes and cerebrovascular morbidity in children. However, few data are available about complications that occur in children hospitalized with SCD-MMS. The purpose of this analysis was to determine the risk factors for in-hospital complications in pediatric SCD-MMS admissions, and thus aid physicians in optimizing future treatment plans. METHODS: A national database of pediatric hospital admissions was examined across the years 2003-2019. ICD-9 and ICD-10 diagnosis codes were analyzed to identify discharges with a primary diagnosis of SCD-MMS and identify in-hospital complications, defined as complication-associated diagnostic codes logged during the same admission. Patient demographics, comorbidities, and hospital characteristics were examined using univariate and multivariate logistic regression analyses to determine associations with in-hospital complications. RESULTS: In total, 274 admissions with a primary diagnosis of SCD-MMS were identified. During 64 (23.4%) admissions, transfusion therapy was given, and in 86 admissions (31.4%), surgical revascularization was performed. In 10 admissions (3.6%), a total of 11 in-hospital complications were identified. After multivariate regression, both comorbid chronic lung disease (adjusted OR 5.3 [1.1, 26.9], P = 0.04) and surgical revascularization (adjusted OR 10.2 [2.0, 52.4], P = 0.006) were associated with development of complications. CONCLUSIONS: In this nationwide database of pediatric SCD-MMS hospitalizations, comorbid chronic lung disease and surgical revascularization were associated with development of in-hospital complications. Patients with comorbid chronic lung disease or who are admitted for revascularization may warrant closer monitoring and greater medical optimization during the hospitalization.

Comparison between moyamoya disease and moyamoya syndrome in Israel.

BACKGROUND AND AIMS: Moyamoya is a chronic brain vasculopathy involving the distal intracranial internal carotid artery (ICA) or proximal middle cerebral artery (MCA). Moyamoya patients can be divided into those with primary moyamoya disease (MMD) and those with moyamoya secondary to other known causes such as intracranial atherosclerosis (moymoya syndrome [MMS]). Our aim was to compare the characteristics of MMD patients to those of MMS patients in a sample of Israeli patients seen over the course of 20 years at a tertiary referral center. METHODS: Included patients were diagnosed with either MMD or MMS based on typical imaging findings and the presence or absence of known concomitant vascular risk factors or associated disorders and vascular disease. Patients with MMS were compared to those with MMD. Demographics, symptoms, signs, and radiological data were compared between the groups. Treatment options and long-term rates of recurrent stroke and functional outcome were also studied. RESULTS: Overall, 64 patients were included (25 MMD, 39 MMS). Patients with MMD were significantly younger (median IQR 20 (7-32) vs. 40 (19-52); p=0.035). Patients with MMS more often had vascular risk factors but there were no significant differences in clinical presentations or long-term disability rates between the groups and a similar proportion of patients underwent surgical interventions to restore hemispheric perfusion in both groups (48% vs. 44% MMS vs. MMD; p=0.7). Almost one in four patient had a recurrent stroke after the initial diagnosis in both groups. Most recurrences occurred in the pre-surgery period in the MMS group and in the post-surgery period in the MMD group. CONCLUSIONS: There were no statistically significant differences in clinical or radiological presentations between the MMS and MMD patients. The course is not benign with recurrent stroke occurring in as many as 25%. More data is needed in order to identify those at high risk for stroke occurrence and recurrence.

Arg4810Lys mutation in RNF213 among Eastern Indian non-MMD ischemic stroke patients: a genotype-phenotype correlation.

INTRODUCTION: RNF213 mutations have been reported mostly in moyamoya disease (MMD) with varying frequencies across different ethnicities. However, its prevalence in non-MMD adult-onset ischemic stroke is still not well explored. AIMS AND OBJECTIVES: This present study thus aims to screen the most common RNF213 variant (Arg4810Lys, among East Asians) in the Eastern Indian non-MMD ischemic stroke patients and correlate it with long-term progression and prognosis of the patients. The subjects were analyzed for this variant using PCR-RFLP and confirmed using Sanger sequencing method. RESULT AND CONCLUSION: We have identified Arg4810Lys variant among eleven young-onset familial ischemic stroke patients in heterozygous manner. A positive correlation of the variant with positive family history (P = 0.001), earlier age at onset (P = 0.002), and history of recurrent stroke (P = 0.015) was observed. However, the carriers showed better cognitive performances in memory (P = 0.042) and executive function (P = 0.004). Therefore, we can conclude that Arg4810Lys/RNF213 - a pathogenic variant for young-onset familial ischemic stroke with higher incidence of recurrent events unlike in MMD cases, have no additional impact on cognition among Eastern Indians.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Long-term stroke risk in Moyamoya disease.

BACKGROUND: Moyamoya disease (MMD) is considered a progressive disease with an ongoing risk of recurrent stroke. However, there is a lack of long-term observational data to quantify the extent of the stroke risk. METHODS: This study aimed to provide insight into the long-term stroke risk in MMD and explore possible risk factors for stroke. Records from all patients diagnosed with MMD in 13 clinical departments from 6 different Danish hospitals between 1994 and 2017 were retrospectively reviewed until 2021. RESULTS: The cohort comprised 50 patients (33 females and 17 males). Patients were followed up for a median of 9.4 years, with more than 10 years of follow-up for 24 patients. Ten patients had 11 new stroke events-6 ischemic strokes and 5 brain hemorrhages. Events occurred at a median of 7 years and up to 25 years after diagnosis. The overall Kaplan-Meier 5-year stroke risk was 10%. Patients with bypass performed had significantly fewer events than conservatively treated patients (HR 0.25, 95% confidence interval (CI) 0.07-0.91, p < 0.05). All but one event occurred in females, a difference that reached statistical significance. CONCLUSIONS: The study provides data on the extent of the risk of recurrent stroke in MMD. Bypass surgery patients had fewer stroke events than those treated conservatively. There was a trend toward a higher stroke risk in females. DATA ACCESS STATEMENT: The data supporting this study's findings are available from the corresponding author upon reasonable request.

Prevalence and Associations of Cognitive Impairment in Adult Patients with Moyamoya Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Cognitive impairment, and in the long term Alzheimer's disease, vascular, or mixed dementia, are potential complications of moyamoya disease (MMD), of which the prevalence and associations are not well established. OBJECTIVE: We performed a systematic review and meta-analysis to investigate the prevalence of cognitive impairment in adult patients with MMD as well as its clinical and demographic correlates. METHODS: We performed a systematic search of four electronic databases: PubMed (MEDLINE), EMBASE, Scopus, and Cochrane Library, profiling studies from inception until 7 May 2023. Clinical data consisting of population characteristics, comorbidities, cognitive assessment tools used, and prevalence of cognitive impairment was extracted. RESULTS: Seventeen studies were included in the meta-analysis, with a total study population of 1,190 patients. All studies assessed cognition, and the overall prevalence of cognitive impairment in MMD patients was 54.59%. A subgroup analysis identified that the prevalence of executive dysfunction in MMD patients was 31.55%. We performed a meta-regression analysis which identified that cognitive impairment was not associated with age, education level, or a history of ischemic or hemorrhagic stroke. CONCLUSIONS: A substantial proportion of MMD patients have cognitive impairment, and cognitive impairment was found to have no association with a history of stroke. Further research is necessary to investigate the longitudinal relationship of MMD and cognitive impairment, and the impact of bypass surgery on cognitive impairment.

Safe delivery planning of patients with moyamoya disease in pregnancy: Case series of a single center.

OBJECTIVE: Moyamoya disease (MMD) is a rare cerebral vascular disease and there is limited clinical experience for pregnant women. Cerebrovascular condition might deteriorated during pregnancy. Management and mode of delivery is challenging for obstetrics specialist. CASE REPORT: Three cases of parturients with moyamoya disease delivered in National Taiwan University Hospital are presented. All were previously diagnosed and one had stroke incidence before current pregnancy course. Two delivered with Cesarean section and one with vaginal delivery, and all delivered at term without maternal or neonatal complication. CONCLUSION: Although delivery method of parturients with MMD has been debating, vaginal delivery may be suitable for certain cases under adequate monitoring and case selection.

Clinical features, surgical treatment, and long-term outcomes of moyamoya disease in a single institution of Fujian, Southeast China: A retrospective study.

At present, detailed demographic and clinical data of moyamoya disease (MMD) in the population of Southeast China are lacking. Therefore, this study aimed to evaluate the epidemiological and clinical features of MMD in Southeast China. Our cohort included 170 patients diagnosed with MMD over the preceding 5 years. Clinical characteristics were obtained through a retrospective chart review, while follow-up information and outcomes were obtained through clinical visits and imaging. The median age at symptom onset was 49 years (range 4-73), with a peak in the age distribution observed at 41 to 60 years. The female-to-male ratio was 1.125 (90/80), and the ratio of the ischemic type to the hemorrhagic type was 2.33 (119/50). The most common initial symptom was an ischemic event. The 5-year Kaplan-Meier risk of stroke was 4.9% for all patients treated with surgical revascularization. Of all patients, 83.9% were able to live independently with no significant disability, and 89.8% showed improved cerebral hemodynamics. Our study provided detailed demographic and clinical data on Southeastern Chinese patients with MMD, which was consistent with findings in other parts of China. Raising clinical awareness of MMD in primary hospitals is important to facilitate early diagnosis and timely treatment of MMD patients.

Association of moyamoya vasculopathy with autoimmune disease: a systematic review and pooled analysis.

Despite more than six decades of extensive research, the etiology of moyamoya disease (MMD) remains unknown. Inflammatory or autoimmune (AI) processes have been suggested to instigate or exacerbate the condition, but the data remains mixed. The objective of the present systematic review was to summarize the available literature investigating the association of MMD and AI conditions as a means of highlighting potential treatment strategies for this subset of moyamoya patients. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the PubMed, Embase, Scopus, Web of Science, and Cochrane databases were queried to identify studies describing patients with concurrent diagnoses of MMD and AI disease. Data were extracted on patient demographics, clinical outcomes, and treatment. Stable or improved symptoms were considered favorable outcomes, while worsening symptoms and death were considered unfavorable. Quantitative pooled analysis was performed with individual patient-level data. Of 739 unique studies identified, 103 comprising 205 unique patients (80.2% female) were included in the pooled analysis. Most patients (75.8%) identified as Asian/Pacific Islanders, and the most commonly reported AI condition was Graves' disease (57.6%), with 55.9% of these patients presenting in a thyrotoxic state. Of the 148 patients who presented with stroke, 88.5% of cases (n = 131) were ischemic. Outcomes data was available in 152 cases. There were no significant baseline differences between patients treated with supportive therapy alone and those receiving targeted immunosuppressant therapy. Univariable logistic regression showed that surgery plus medical therapy was more likely than medical therapy alone to result in a favorable outcome. On subanalysis of operated patients, 94.1% of patients who underwent combined direct and indirect bypass reported favorable outcomes, relative to 76.2% of patients who underwent indirect bypass and 82% who underwent direct bypass (p < 0.05). On univariable analysis, the presence of multiple AI disorders was associated with worse outcomes relative to having a single AI disorder. Autoimmune diseases have been uncommonly reported in patients with MMD, but the presence of multiple AI comorbidities portends poorer prognosis. The addition of surgical intervention appears to improve outcomes and for patients deemed surgical candidates, combined direct and indirect bypass appears to offer better outcomes that direct or indirect bypass alone.

Adult Moyamoya Disease and Syndrome: Current Perspectives and Future Directions: A Scientific Statement From the American Heart Association/American Stroke Association.

Adult moyamoya disease and syndrome are rare disorders with significant morbidity and mortality. A writing group of experts was selected to conduct a literature search, summarize the current knowledge on the topic, and provide a road map for future investigation. The document presents an update in the definitions of moyamoya disease and syndrome, modern methods for diagnosis, and updated information on pathophysiology, epidemiology, and both medical and surgical treatment. Despite recent advancements, there are still many unresolved questions about moyamoya disease and syndrome, including lack of unified diagnostic criteria, reliable biomarkers, better understanding of the underlying pathophysiology, and stronger evidence for treatment guidelines. To advance progress in this area, it is crucial to acknowledge the limitations and weaknesses of current studies and explore new approaches, which are outlined in this scientific statement for future research strategies.

[Moyamoya disease and syndrome]. / Bolezn' i sindrom moyamoya.

Moyamoya disease (MMD) is a rare disease characterized by progressive stenosis of the terminal part of the internal carotid arteries (ICA) and the proximal part of their branches, which is accompanied by the formation of collateral network that look like smoke clouds on angiography (Japanese terminology - moyamoya). If the disease is comorbid to other diseases, usually associated with acute or chronic inflammation, including autoimmune processes, it is designated as moyamoy syndrome (MMS). MMD and MMS are one of the causes of ischemic stroke and chronic cerebrovascular insufficiency in young and middle age, less often they lead to hemorrhages. The review presents data on epidemiology, morphology, pathogenesis (the role of genetic predisposition, inflammation, proangiogenic factors and immune disorders), clinical manifestations, instrumental diagnostics and treatment.

Seizures in Pediatric Moyamoya: Risk Factors and Functional Outcomes.

BACKGROUND: Children with moyamoya arteriopathy are at high risk for stroke and seizures. Risk factors for seizures and the impact of seizures on neurological outcomes in children with moyamoya are unknown. METHODS: This is a single-center retrospective cohort study of children with moyamoya evaluated between 2003 and 2021. Functional outcome was assessed using the Pediatric Stroke Outcome Measure (PSOM). Associations between clinical variables and seizure occurrence were assessed using univariate and multivariable logistic regression. Associations between clinical variables and final PSOM score were assessed using ordinal logistic regression. RESULTS: Eighty-four patients met inclusion criteria, and 34 (40%) children experienced seizure. Factors associated with seizures included moyamoya disease (vs syndrome; odds ratio [OR] 3.43, P = 0.008) and the presence of infarcts on baseline neuroimaging (OR 5.80, P = 0.002). Factors associated with decreased likelihood of experiencing seizures included older age at initial presentation (OR 0.82, P = 0.002) and asymptomatic (radiographic) presentation (OR 0.05, P = 0.006). Both older age at presentation (adjusted OR [AOR] 0.80, P = 0.004) and incidental radiographic presentation (AOR 0.06, P = 0.022) remained significant after adjusting for potential confounders. Seizures were associated with worse functional outcomes as assessed by the PSOM (regression coefficient 2.03, P < 0.001). This association remained significant after adjusting for potential confounders (adjusted regression coefficient 1.54, P = 0.025). CONCLUSIONS: Younger age and symptomatic presentation are associated with increased likelihood of seizures among children with moyamoya. Seizures are associated with worse functional outcomes. Prospective studies should clarify how seizures impact outcomes and how effective seizure treatment modifies this relationship.

The incidence of radiation-induced moyamoya among pediatric brain tumor patients who received photon radiation versus those who received proton beam therapy: a systematic review.

Cranial irradiation is associated with several adverse events such as endocrinopathy, growth retardation, neurocognitive impairment, secondary malignancies, cerebral vasculopathy, and potential stroke. The better side effects profile of proton beam therapy compared with that of photon radiation therapy is due to its physical properties, mainly the sharp dose fall-off after energy deposition in the Bragg peak. Despite the better toxicity profile of proton beam therapy, the risk of  moyamoya syndrome still exists. We conducted a systematic review of the existing literature on moyamoya syndrome after receiving cranial radiation therapy for pediatric brain tumors to investigate the incidence of moyamoya syndrome after receiving photon versus proton radiation therapy. In this review, we report that the incidence of moyamoya syndrome after receiving proton beam therapy is almost double that of photon-induced moyamoya syndrome. Patients who received proton beam therapy for the management of pediatric brain tumors are more likely to develop moyamoya syndrome at the age of less than 5 years. Meanwhile, most patients with proton-induced moyamoya are more likely to be diagnosed within the first 2 years after the completion of their proton beam therapy.

Increase in age at onset of moyamoya disease in China over 25 years.

BACKGROUND: To explore whether the age at onset (AAO) of Chinese patients with moyamoya disease (MMD) increased over time due to a reduced exposure to leptospiral infection. METHODS: We performed an independent, multicenter, retrospective study based on data from patients with MMD who initially attended four tertiary hospitals in Hubei, China, from 1996 to 2020. After stratifying the year of MMD onset into five periods (1996-2000, 2001-2005, 2006-2010, 2011-2015, and 2016-2020), we analyzed the temporal trends in AAO and compared different classes of AAO (early-onset, < 20 years; intermediate-onset, 20-49 years; late-onset, ≥ 50 years) in each period. RESULTS: We included 1858 patients in this study, with 878 women and 980 men. Their median (IQR) AAO was 47 (39-55) years. The case AAO significantly increased at the rate of 0.94 years per year (r = 0.406, p < .0001), while no trend was observed in birth years through time (p = .512). The birth cohorts who grew up in the leptospirosis epidemic years was stably susceptible to MMD. The median (IQR) AAO has increased significantly from 26 (14-37) years (1996-2000) to 51 (43-57) years (2016-2020) (p < .0001). The proportion of early-onset MMD was significantly higher in 1996-2000 (33.3%, p < .0001) and 2001-2005 (10.4%, p < .001). The AAO shows an aging trend that the proportion of late-onset MMD went from 4.5% (2001-2005) to 54.5% (2016-2020) (p < .0001). CONCLUSIONS: The AAO of MMD was increasing during a recent 25-year period in China, which may reflect a birth cohort effect that resulted from environmental changes. The disparity risk of birth cohorts with MMD changed with leptospirosis epidemics, suggesting leptospiral exposure might be a potential risk factor.

Integrated analysis of the association between methionine cycle and risk of moyamoya disease.

OBJECTIVE: The role of methionine (Met) cycle in the pathogenesis and progression of cardiovascular and cerebrovascular diseases has been established, but its association with moyamoya disease (MMD) has rarely been studied. This study aimed to analyze the levels of Met cycle-related metabolites and constructed a risk model to explore its association with the risk of MMD. METHODS: In this prospective study, a total of 302 adult MMD patients and 88 age-matched healthy individuals were consecutively recruited. The serum levels of Met cycle-related metabolites were quantified by liquid chromatography-mass spectrometry (LC-MS). Participants were randomly divided into training set and testing set at a ratio of 1:1. The training set was used to construct the risk score model by LASSO regression. The association between Met cycle-related risk score and the risk of MMD was analyzed using logistic regression and assessed by ROC curves. The testing set was used for validation. RESULTS: The levels of methionine sulfoxide and homocysteine were significantly increased, while the levels of betaine and choline were significantly decreased in MMD and its subtypes compared to healthy controls (p < 0.05 for all). The training set was used to construct the risk model and the risk score of each participant has been calculated. After adjusting for potential confounders, the risk score was independently associated with the risk of MMD and its subtypes (p < 0.05 for all). We then divided the participants into low-risk and high-risk groups, the high-risk score was significantly associated with the risk of MMD and its subtypes (p < 0.05 for all). The risk scores were further assessed as tertiles, the highest tertile was significantly associated with a higher risk of MMD and its subtypes compared to the lowest (p < 0.05 for all). The results were validated in the testing set. CONCLUSION: This study has constructed and validated a risk model based on Met cycle-related metabolites, which was independently associated with the risk of MMD and its subtypes. The findings provided a new perspective on the risk evaluation and prevention of MMD.

Five-Year Stroke Risk and Its Predictors in Asymptomatic Moyamoya Disease: Asymptomatic Moyamoya Registry (AMORE).

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.

Development of a mobile application based on the salutogenic model for self-management in adolescents with Moyamoya disease.

PURPOSE: Moyamoya disease (MMD) is a rare disease which has a high incidence of onset in adolescence. Disease self-management skills are imperative for adolescents with MMD. This study aimed to describe the systematic development, content, and usability of the Moyamoya Healthy Youth application (app), which was developed to enhance self-management skills for adolescents with MMD. DESIGN AND METHODS: The theoretical grounding for the app was salutogenic model and the development process of the app was guided by the intervention mapping (IM) protocol. Results of each IM step were applied to the next step leading to the design of the app. Additionally, a pilot test was conducted to determine the usability of the app. RESULTS: Following the salutogenic model, we identified the stressors, behaviors, and resources regarding managing symptoms of MMD by interviewing adolescents with MMD, their parents, and healthcare providers. Based on the findings of the interviews, we determined the program outcomes and performance objectives to improve the self-management of MMD in adolescents. The app was developed by translating the theoretical methods to achieve the performance objectives into practical strategies for delivering the program. A pilot test with eight participants showed satisfaction with the app in terms of its usefulness and ease of use. CONCLUSION: We delineated the development process of the Moyamoya Healthy Youth. Additionally, we presented the positive outcomes regarding the usability of the app. PRACTICE IMPLICATIONS: The Moyamoya Healthy Youth app could benefit adolescents with MMD, by improving their self-management skills which are crucial for their health.

Long-term outcomes of moyamoya disease versus atherosclerosis-associated moyamoya vasculopathy using high-resolution MR vessel wall imaging.

OBJECTIVES: We aimed to compare the long-term outcomes and surgical benefits between moyamoya disease (MMD) and atherosclerosis-associated moyamoya vasculopathy (AS-MMV) using high-resolution MRI (HRMRI). METHODS: MMV patients were retrospectively included and divided into the MMD and AS-MMV groups according to vessel wall features on HRMRI. Kaplan-Meier survival and Cox regression were performed to compare the incidence of cerebrovascular events and prognosis of encephaloduroarteriosynangiosis (EDAS) treatment between MMD and AS-MMV. RESULTS: Of the 1173 patients (mean age: 42.4±11.0 years; male: 51.0%) included in the study, 881 were classified into the MMD group and 292 into the AS-MMV group. During the average follow-up of 46.0±24.7 months, the incidence of cerebrovascular events in the MMD group was higher compared with that in the AS-MMV group before (13.7% vs 7.2%; HR 1.86; 95% CI 1.17 to 2.96; p=0.008) and after propensity score matching (6.1% vs 7.3%; HR 2.24; 95% CI 1.34 to 3.76; p=0.002). Additionally, patients treated with EDAS had a lower incidence of events than those not treated with EDAS, regardless of whether they were in the MMD (HR 0.65; 95% CI 0.42 to 0.97; p=0.043) or AS-MMV group (HR 0.49; 95% CI 0.51 to 0.98; p=0.048). CONCLUSIONS: Patients with MMD had a higher risk of ischaemic stroke than those with AS-MMV, and patients with both MMD and AS-MMV could benefit from EDAS. Our findings suggest that HRMRI could be used to identify those who are at a higher risk of future cerebrovascular events.

Changes in the clinical spectrum of pediatric moyamoya disease over 40 years.

OBJECTIVE: To investigate the chronological changes in the clinical presentation and long-term prognosis of pediatric-onset moyamoya disease in our institute over 40 years. METHODS: We evaluated 282 pediatric-onset (≤ 15 years old) moyamoya disease patients who visited our institute from 1981 to 2020 (divided into the former period, 1981-2000, and the latter period, 2001-2020). Differences in the clinical presentation and the long-term outcome were compared between the periods. Multivariate analysis was also performed to reveal the risk factors for poor long-term outcomes. RESULTS: Compared to the former period, the total number of patients, the onset age and both the number of patients with family history and relatively older patients without symptoms or with headache were greater in the latter period (p < 0.05). The number of patients with poor long-term outcomes was significantly lower in the latter period (24.9% vs. 6.7%, p < 0.01). Multivariate analysis revealed that stroke onset, late cerebrovascular events and postoperative complications were independent risk factors for poor long-term outcomes (odds ratio = 31.4, 40.8 and 5.4, respectively). CONCLUSIONS: Over the last 40 years, the number of pediatric moyamoya disease patients has increased, especially in relatively older patients with mild presentation and favorable long-term outcomes. In clinical studies, these chronological changes and the inclusion period of the participants need to be accounted for. Whether the increased diagnostic rate in the recent era has led to a decrease in late cerebrovascular events and favorable outcomes throughout life remains unknown and should be evaluated in the future.