In this retrospective study, we compared hemorrhagic sites and collateral vessels between the matched groups. We found that lenticulostriate anastomosis were associated with p.R4810K variant. Whereas hemorrhagic sites, thalamic anastomosis, and choroidal anastomosis were not correlated with p.R4810K variant.
The p.R4810K variant in RNF213 was identified as a founder variant with a strong susceptibility in MMD patients [15]. The p.R4810K mutation was found in 31.4% MMD patients in China [14], 75.8% MMD patients in Korea [16], and 95.1% MMD patients in Japan [10]. In present study, the incidence of p.R4810K variant in hemorrhagic MMD was 19.2%, which was much lower than the overall incidence. The p.R4810K variant was correlated with phenotype in MMD [10, 14, 16, 17]. Previous study showed that patients with GA or homozygous variant (AA) may have a younger age onset, higher prevalence of family history, more cerebral infarction, and more PCA involvement. The p.R4810K variant may not relate to clinical outcomes in MMD [17, 18]. Although our previous study revealed that patients with GA might associate with better postoperative collateral formation than patients with GG [12], Nomura et al found that there was no difference in recurrent strokes and functional conditions[18], our previous study also had come to the same conclusion [17]. Recently, we investigated the whether the p.R4810K variant was associated with angiographic characteristics in MMD, the results revealed that patients in GA group may have a different collateral circulation from patients in GG group [11].
In this study, hemorrhagic sites were not correlated with p.R4810K variant. Our previous study showed that anterior hemorrhage may relate to better postoperative collateral formation [19]. And Takahashi et al found that posterior hemorrhage was associated with a higher rate of recurrent bleeding [7]. Nevertheless, the p.R4810K variant was not associated with clinical outcomes in MMD in previous studies [18]. In present study, no difference was observed in hemorrhagic sites between two matched groups. It might mean that there was no difference in clinical outcomes, which was similar with the previous studies.
Lenticulostriate anastomosis were associated with p.R4810K variant. Whereas thalamic anastomosis, and choroidal anastomosis were not correlated with p.R4810K variant.
The dilation and abnormal branching of the anterior choroidal artery was associated with hemorrhagic presentation and the risk of de novo hemorrhage [20–22]. A supplementary analysis of the JAM Trial showed that choroidal anastomosis was associated with posterior hemorrhage and might be a potential source of posterior hemorrhage [8]. In addition, a case control study of the JAM trial showed that different collateral vessels were observed between hemorrhagic and ischemic MMD [23], the thalamic and choroidal anastomosis was more prominent developed in hemorrhagic MMD. The results revealed that direct bypass could reduce the hemodynamic stress to the choroidal and thalamic collaterals[23, 24]. In this study, we found that no difference was observed in thalamic and choroidal anastomosis between two matched groups. It might mean direct bypass may have a role in both patients with GA and GG. Whereas patients with GA had more lenticulostriate anastomosis, recent study showed that lenticulostriate anastomosis in hemorrhagic MMD was less likely to diminish than other collaterals after successful direct bypass [25]. It suggested that patients with GA variants should be given more attention to surgical planning, and the bypass surgery should target the area reached by collateral vessels.
The present study has several limitations. First, although 1:1 PSM was conducted to minimize the effects of heterogeneity in the two groups, potential selection bias might still occur in this retrospective study. Second, the number of matched groups was small, this study was only enrolled patients with GG and GA, hemorrhagic MMD patients with AA variant was not found. Third, only p.R4810K variant in RNF 213 was sequenced, and the effect of the rare variants in RNF213 in hemorrhagic sites and collateral vessels remains unknown.