Clinical and Angiographic Features of Patients with Moyamoya Disease and the p.R4810K Heterozygous Variant

World Neurosurg. 2016 Jun:90:530-538.e3. doi: 10.1016/j.wneu.2015.12.093. Epub 2016 Jan 12.

Abstract

Objective: To elucidate the clinical and angiographic features in patients with moyamoya disease (MMD) and the p.R4810K heterozygous variant and present an angiographic grading system to evaluate disease severity.

Methods: We retrospectively reviewed 87 patients with MMD and the p.R4810K variant treated at Beijing Tiantan Hospital. Clinical features, stroke subtype, and angiographic characteristics were analyzed.

Results: The median age at diagnosis was 25 years (range, 3-59). The ratio of women to men was 1.2:1. The familial occurrence of MMD was 14.9%. The primary symptom at diagnosis was ischemia, hemorrhage, or other in 67, 16, and 4 patients, respectively. Angiographic features correlating with ischemic stroke or stroke, including Suzuki grade, external carotid artery collaterals, leptomeningeal collaterals, and Mugikura grade, were identified. A binary logistic regression model demonstrated a significant correlation of Suzuki grade (P = 0.008) and posterior cerebral artery grade (P = 0.029) with ischemic stroke (142 hemispheres). A modified Suzuki-Mugikura grading system was developed. The areas under the receiver operating characteristic curves used to predict ischemic stroke based on the Suzuki grading, Mugikura grading, and modified Suzuki-Mugikura grading systems were 0.736, 0.69, and 0.741, respectively. Furthermore, the modified Suzuki-Mugikura grades were significantly correlated with infarction in posterior circulation and the number of infarcted regions.

Conclusions: The clinical and angiographic features of a Chinese MMD population with the p.R4810K variant were similar to those of a Japanese MMD population; they might be a distinct cerebrovascular disease entity and represent a separate subgroup. A modified Suzuki-Mugikura grading system was valuable for predicting stroke and evaluating disease severity.

Keywords: Angiographic characteristics; Clinical features; moyamoya disease; p.R4810K variant.

MeSH terms

  • Adenosine Triphosphatases / genetics*
  • Adolescent
  • Adult
  • Cerebral Angiography / statistics & numerical data*
  • Child
  • Child, Preschool
  • China / epidemiology
  • Comorbidity
  • Female
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Loss of Heterozygosity / genetics
  • Male
  • Middle Aged
  • Moyamoya Disease / diagnosis*
  • Moyamoya Disease / epidemiology
  • Moyamoya Disease / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Prevalence
  • Risk Factors
  • Severity of Illness Index
  • Stroke / diagnosis*
  • Stroke / epidemiology
  • Stroke / genetics*
  • Ubiquitin-Protein Ligases / genetics*
  • Young Adult

Substances

  • RNF213 protein, human
  • Ubiquitin-Protein Ligases
  • Adenosine Triphosphatases