Clinical Presentation and Stroke Incidence Differ by Moyamoya Etiology

Abstract

Introduction: Moyamoya arteriopathy, which can be idiopathic or associated with sickle cell disease, neurofibromatosis, Down syndrome, or cranial radiation therapy, is a progressive cerebral arteriopathy associated with high rates of incident and recurrent stroke. Little is known about how these subgroups differ with respect to clinical presentation, radiographic findings, stroke risk, and functional outcomes. Methods: Using ICD codes, we identified children ages 28 days to 18 years treated for moyamoya arteriopathy at our tertiary care center between 2003 and 2019. Demographic, clinical, and radiographic data were extracted from the medical record. The Pediatric Stroke Recurrence and Recovery Questionnaire was administered to consenting participants. Results: Sixty-nine patients met inclusion criteria (33 idiopathic, 18 sickle cell disease, 11 neurofibromatosis, 6 Down syndrome, 1 cranial radiation therapy). Median follow-up time was 7.7 years; 24 patients had at least 5 years of follow-up data. Frequency of stroke at presentation differed by subgroup ( P < .001). Of patients with at least 2 years of follow-up, 33 (55%) experienced stroke. The proportion of patients experiencing stroke differed by subgroup (50% of idiopathic cases, 72% of sickle cell disease, 11% of neurofibromatosis, and 100% of Down syndrome, P = .003). The frequency of bilateral versus unilateral disease ( P = .001) and stroke-free survival following presentation ( P = .01) also differed by subgroup. Conclusions: In this single-center cohort, moyamoya subgroups differed with respect to clinical and radiographic characteristics, with neurofibromatosis-associated moyamoya syndrome having a milder phenotype and Down syndrome–associated moyamoya portending a more aggressive course. These findings need confirmation in a larger, multi-center cohort with longer duration of follow-up.

A new syndrome of moyamoya disease, kidney dysplasia, aminotransferase elevation, and skin disease associated with de novo variants in RNF213

“…The genetics of MMD are incompletely understood. Moyamoya physiology can occur as a consequence of several genetic syndromes including sickle cell disease, Alagille Syndrome, rasopathy and neurofibromatosis, so called moyamoya syndrome (Gatti, Torriente, & Sun, 2020 ); however, can also occur in the absence of underlying syndrome, albeit by a different mechanism. The complex environmental and genetic factors that confer risk for steno‐occlusive arteriopathy are poorly understood (Miyatake et al, 2012 ; Research Committee on the Pathology and Treatment of Spontaneous Occlusion of the Circle of Willis,, & Health Labour Sciences Research Grant for Research on Measures for Infractable Diseases, 2012 ).…”

Nonischemic Presentations of Pediatric Moyamoya Arteriopathy: A Natural History Study

“…Clinical and neuroimaging data, including mode of presentation (ischemic versus nonischemic) were extracted from the records of pediatric patients with MMA seen at our center. 1 Pediatric stroke outcome measure scores were stratified as previously described. 3 Differences in stroke-free survival are represented using Kaplan-Meier survival curves and analyzed using Cox Proportional hazard models.…”

“…Most children with moyamoya arteriopathy (MMA) present with ischemic stroke or transient ischemic attack, but many present with nonischemic symptoms or increasingly via incidental radiographic finding, especially with advancing imaging capabilities. 1,2 We describe the natural history of children with nonischemic MMA presentations to characterize long-term stroke risk and optimize management strategies in this unique group.…”

Stroke in Children

“…Two retrospective studies differentiated phenotypes of moyamoya, demonstrating that patients with neurofibromatosis type 1 had a more benign course, presenting with unilateral disease and fewer strokes compared with other types of moyamoya. 24,25 Geraldo et al 26 expanded the radiological phenotype of adenosine deaminase 2 deficiency beyond lacunar infarcts and hemorrhage to include enhancement of cerebral perivascular tissue, a specific finding which may prove useful in suggesting this diagnosis. 26 Deaminase 2 deficiency is treatable, with evidence that anti-TNF (tumor necrosis factor) therapy decreases ischemic events.…”