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

Yohei Mineharu MD, PhD1, Yasushi Takagi MD, PhD2, Akio Koizumi MD, PhD3, Takaaki Morimoto MD, PhD4, Takeshi Funaki MD, PhD1, Tomohito Hishikawa MD, PhD5, Yoshio Araki MD, PhD6, Hitoshi Hasegawa MD, PhD7, Jun C. Takahashi MD, PhD8, Satoshi Kuroda MD, PhD9, Kiyohiro Houkin MD, PhD10, and Susumu Miyamoto MD, PhD1
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  • 1 Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto;
  • | 2 Department of Neurosurgery, Tokushima University Graduate School of Medicine, Tokushima;
  • | 3 Social Health Welfare Medicine Laboratory, Kyoto;
  • | 4 Department of Neurosurgery, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki;
  • | 5 Okayama University Graduate School of Medicine, Okayama;
  • | 6 Department of Neurosurgery, Nagoya University Graduate School of Medicine, Nagoya;
  • | 7 Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata;
  • | 8 Department of Neurosurgery, National Cerebral and Cardiovascular Center, Suita;
  • | 9 Department of Neurosurgery, Toyama University Graduate School of Medicine, Toyama; and
  • | 10 Department of Neurological Cell Therapy, Hokkaido University Graduate School of Medicine, Sapporo, Japan
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OBJECTIVE

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

ABBREVIATIONS

ACA = anterior cerebral artery; AUC = area under the curve; CI = confidence interval; ICA = internal carotid artery; MCA = middle cerebral artery; OR = odds ratio; PCA = posterior cerebral artery; ROC = receiver operating characteristic; SUPRA = Study of Unilateral Moyamoya Disease Progression and Associated-Gene in Japan; TIA = transient ischemic attack.

Supplementary Materials

    • Supplemental Tables 1 and 2 (PDF 439 KB)

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