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Impact of RNF213 founder polymorphism (p.R4810K) on the postoperative development of indirect pial synangiosis after direct/indirect combined revascularization surgery for adult Moyamoya disease

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Abstract

Direct superficial temporal artery (STA) to middle cerebral artery (MCA) anastomosis combined with indirect pial synangiosis provides favorable surgical collaterals for Moyamoya disease (MMD), especially in adults; however, factors leading to the development of each direct and indirect collateral are not well documented.

We aimed to investigate the association between RNF213 founder polymorphism (p.R4810K) and each direct and indirect collateral development. By qualitative and quantitative evaluations of direct and indirect surgical collaterals using time-of-flight MR angiography, postoperative development of each type of bypass was evaluated independently into two categories. Multivariate logistic regression analysis was performed to study the contributing factors for the development of each surgical collateral.

Excellent development of postoperative direct and indirect bypass was observed in 65 hemispheres (70%) by qualitative evaluation, which was confirmed by quantitative evaluation. Multivariate logistic regression analysis of excellent indirect bypass development revealed a significant positive correlation with the p.R4810K (odds ratio, OR4.0; 95%-confidence interval, CI 1.2–16), advanced MR angiographic stage (OR9.5; 95%CI 1.7–73), and preoperative middle meningeal artery caliber (OR6.8; 95%CI 1.8–35), but a significant negative correlation was found with the excellent direct bypass development (OR0.17; 95%CI 0.03–0.75). No significant correlation was observed between excellent direct bypass development and the p.R4810K (OR0.95; 95%CI 0.37–2.4).

In conclusion, excellent development of indirect collaterals after STA-MCA anastomosis combined with indirect pial synangiosis occurs more frequently in adult MMD with the RNF213 founder polymorphism, suggesting a role of the p.R4810K variant for marked in-growth of indirect collaterals and the utility of preoperative genetic analysis.

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Fig. 1

source image (C) depicted the left superficial temporal artery (STA, double arrows) and middle meningeal artery (MMA, dotted arrows), whereas the deep temporal artery (DTA) was hardly seen in MIP or its source images preoperatively. (D, E) Follow-up MRA obtained 6 months after left STA-MCA anastomosis combined with encephalo-duro-myo-arterio-pericranio-synangiosis demonstrated excellent development of postoperative direct (STA) and indirect (DTA) surgical collaterals. The caliber of the STA and DTA were markedly increased after surgery (STA: pre: 1.54 mm; post: 1.99 mm, DTA: pre: 0.53 mm; post: 2.34 mm, MMA: pre: 1.18 mm; post: 1.23 mm) as shown in panel (C) and (E)

Fig. 2

source images of MR angiography before and after combined bypass in adult MMD. ns, not significant; ***P < 0.001, two-way ANOVA followed by Bonferroni multiple comparison

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Availability of data and material

Data supporting the findings of this study are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to acknowledge Ms. Rika Nagashima and Ms. Ikuyo Hata for their administrative assistance. We also thank Dr. Hiroyuki Kohno, Dr Kanako Hatanaka, and Ms. Miyuki Kasegai for their technical support in the genetic analysis.

Funding

This study was partially supported by Japanese Society for the Promotion of Science KAKENHI grant number 19H03765 (M.I.) and 20K09362 (M.F.). All authors declare that there is no personal or institutional financial interest in drugs, materials, or devices described in this article.

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Authors and Affiliations

  1. Department of Neurosurgery, Hokkaido University Graduate School of Medicine, North 14, West 5, Sapporo, 060-8638, Japan

    Masaki Ito, Masahito Kawabori, Taku Sugiyama, Kikutaro Tokairin, Ryota Tatezawa, Haruto Uchino, Ken Kazumata, Kiyohiro Houkin & Miki Fujimura

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  1. Masaki Ito
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  2. Masahito Kawabori
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Contributions

Conception and design: Fujimura M, Ito M, and Kawabori M. Acquisition of data: Ito M., Sugiyama T, Tokairin K, Tatezawa R. Analysis and interpretation of data: Ito M, Kawabori M, Sugiyama T, Tokairin K, Tatezawa R, Uchino H, and Fujimura M. Drafting the article: Ito M. Critically revising the article: Kazumata K, and Fujimura M. Statistical analysis: Ito M. Study supervision: Kazumata K and Houkin K.

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Correspondence to Masaki Ito.

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The present study was approved by the Hokkaido University Graduate School of Medicine medical ethics committee on human experimentation, including genetic analysis (14–053). Written informed consent was obtained from all participants (or guardians) to participate in this study.

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Ito, M., Kawabori, M., Sugiyama, T. et al. Impact of RNF213 founder polymorphism (p.R4810K) on the postoperative development of indirect pial synangiosis after direct/indirect combined revascularization surgery for adult Moyamoya disease. Neurosurg Rev 45, 2305–2313 (2022). https://doi.org/10.1007/s10143-022-01749-9

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