Neurological Surgery 脳神経外科50巻1号

2022年01月発行

特集 Precision Medicine—個別化医療を目指した遺伝子診断と新治療の知見 Ⅲ脳血管障害

もやもや病—病態研究の現状と個別化医療への道程

著者： 藤村幹¹

所属機関： ¹北海道大学大学院医学研究院脳神経外科学教室

ページ範囲：P.216 - P.221

Point
・もやもや病は東アジアに多い原因不明の頭蓋内動脈狭窄症であるが，近年，疾患感受性遺伝子RNF213が発見され研究が進んでいる．
・RNF213遺伝子多型は，もやもや病の発症年齢，臨床的重症度，バイパス術後急性期の脳循環動態や治療予後との関連が報告されている．
・今後，RNF213遺伝子多型からもやもや病発症に至る機序を解明することにより，個別化医療の実現が期待されている．

参考文献

1）Suzuki J, Takaku A：Cerebrovascular ‘moyamoya’ disease. Disease showing abnormal net-like vessels in base of brain. Arch Neurol 20：288-299, 1969

2）冨永悌二，他：もやもや病（ウイリス動脈輪閉塞症）診断・治療ガイドライン（改訂版）．脳卒中の外科 46：1-24, 2018

3）Fujimura M, Tominaga T：Lessons learned from moyamoya disease：outcome of direct/indirect revascularization surgery for 150 affected hemispheres. Neurol Med Chir（Tokyo） 52：327-332, 2012

4）Jeon JP, et al：Meta-analysis of the surgical outcomes of symptomatic moyamoya disease in adults. J Neurosurg 128：793-799, 2018［Online publication date：05 May 2017］

5）Miyamoto S, et al；JAM Trial Investigators：Effects of extracranial-intracranial bypass for patients with hemorrhagic moyamoya disease：results of the Japan Adult Moyamoya Trial. Stroke 45：1415-1421, 2014

6）Takahashi JC, et al；JAM Trial Investigators：Significance of the hemorrhagic site for recurrent bleeding：prespecified analysis in the Japan Adult Moyamoya Trial. Stroke 47：37-43, 2016

7）Fujimura M, Tominaga T：Current status of revascularization surgery for moyamoya disease：special consideration for its ‘internal carotid-external carotid（IC-EC）conversion’ as the physiological reorganization system. Tohoku J Exp Med 236：45-53, 2015

8）Kamada F, et al：A genome-wide association study identifies RNF213 as the first moyamoya disease gene. J Hum Genet 56：34-40, 2011

9）Fujimura M, et al：Genetics and biomarkers of moyamoya disease. Significance of RNF213 as a susceptibility gene. J Stroke 16：65-72, 2014

10）Fukui M：Guidelines for the diagnosis and treatment of spontaneous occlusion of the circle of Willis（‘moyamoya’ disease）. Research Committee on Spontaneous Occlusion of the Circle of Willis（Moyamoya Disease）of the Ministry of Health and Welfare, Japan. Clin Neurol Neurosurg 99（Suppl 2）：S238-S240, 1997

11）Takagi Y, et al：Histological features of middle cerebral arteries from patients treated for moyamoya disease. Neurol Med Chir（Tokyo）47：1-4, 2007

12）Kaku Y, et al：Outer-diameter narrowing of the internal carotid and middle cerebral arteries in moyamoya disease detected on 3D constructive interference in steady-state MR image：is arterial constrictive remodeling a major pathogenesis? Acta Neurochir（Wien）154：2151-2157, 2012

13）Ryoo S, et al：High-resolution magnetic resonance wall imaging findings of Moyamoya disease. Stroke 45：2457-2460, 2014

14）Kuriyama S, et al：Prevalence and clinicoepidemiological features of moyamoya disease in Japan：findings from a nationwide epidemiological survey. Stroke 39：42-47, 2008

15）Miyatake S, et al：Homozygous c.14576G＞A variant of RNF213 predicts early-onset and severe form of moyamoya disease. Neurology 78：803-810, 2012

16）Tashiro R, et al：Prolonged/delayed cerebral hyperperfusion in adult patients with moyamoya disease with RNF213 gene polymorphism c.14576G＞A（rs112735431）after superficial temporal artery-middle cerebral artery anastomosis. J Neurosurg, 2020［Online ahead of print］doi：10.3171/2020.6. JNS201037

17）Zhang Q, et al：Clinical features and surgical outcomes of patients with moyamoya disease and the homozygous RNF213 p.R4810K variant. J Child Neurol 34：793-800, 2019

18）Sonobe S, et al：Temporal profile of the vascular anatomy evaluated by 9.4-T magnetic resonance angiography and histopathological analysis in mice lacking RNF213：a susceptibility gene for moyamoya disease. Brain Res 1552：64-71, 2014

19）Kanoke A, et al：Temporal profile of the vascular anatomy evaluated by 9.4-tesla magnetic resonance angiography and histological analysis in mice with the R4859K mutation of RNF213, the susceptibility gene for moyamoya disease. Brain Res 1624：497-505, 2015

20）Choi EH, et al：Ring finger protein 213 variant and plaque characteristics, vascular remodeling, and hemodynamics in patients with intracranial atherosclerotic stroke：a high-resolution magnetic resonance imaging and hemodynamic study. J Am Heart Assoc 8：e011996, 2019

21）Kang HS, et al：Plasma matrix metalloproteinases, cytokines and angiogenic factors in moyamoya disease. J Neurol Neurosurg Psychiatry 81：673-678, 2010

22）Fujimura M, et al：Increased expression of serum matrix metalloproteinase-9 in patients with moyamoya disease. Surg Neurol 72：476-480, 2009

23）Chung JW, et al：Cav-1（caveolin-1）and arterial remodeling in adult moyamoya disease. Stroke 49：2597-2604, 2018

24）Funaki T, et al：High rebleeding risk associated with choroidal collateral vessels in hemorrhagic moyamoya disease：analysis of a nonsurgical cohort in the Japan Adult Moyamoya Trial. J Neurosurg 130：525-530, 2019［Online publication date：2 March 2018］

25）Funaki T, et al：Effect of choroidal collateral vessels on de novo hemorrhage in moyamoya disease：analysis of nonhemorrhagic hemispheres in the Japan Adult Moyamoya Trial. J Neurosurg 132：408-414, 2020［Online publication date：8 Feb 2019］