The effect of indirect revascularization on MMD relied on the neoangiogenesis from the vascularized donator into the cortical brain, which might act the same role in prefusion improvement and prevention in recurrence stroke as direct or combined bypass18, 19. Previous reports investigated that effect in neovascularization was associated with favorable long-term outcome for patients with MMD, and potential predictors for postoperative neovascularization was of great value to provide standard for elective surgical procedure before surgery20. Thus far, few studies had reported potential risk factors for neovascularization after indirect bypass. In this research, we attempted to investigate the relationship between postoperative neovascularization and a variety of possible factors.
Our findings showed that good neovascularization was achieved in 56 (57.7%) hemispheres after indirect bypass. The presence of preoperative collateral circulation system acted as independent risk factor for postsurgical neovascularization (P<0.001, OR [95%CI], 2.984 [2.031–5.437]). Preoperative intracerebral anastomosis predicted good neovascularization after surgery, whereas leptomeningeal anastomosis was a predictor of poor neovascularization. As it is known that cerebral ischemia indicated a potential signal for triggering moyamoya vessels and collateral growth in the progress of MMD21. As intracerebral anastomosis directly connects striate arteries with the medullary arteries, the main source of blood perfusion in cerebral cortex was leptomeningeal collateral, such as the anastomosis of the PCA-ACA branches and PCA-MCA branches at the watershed zones. Piao reported the hemisphere with extensive basal moyamoya vessels exhibited impaired perfusion and metabolism in cerebral cortex22. Takahashi et al. also reported that severe ischemia was essential for the formation of new vessels23. The transdural anastomosis developed in the advanced Suzuki stage, such as meningeal middle artery, ethmoid moyamoya and vault moyamoya vessels24–26. Thus, we hypothesized that hemisphere with intracerebral anastomosis was more likely to suffer cerebral ischemia than those with leptomeningeal collateral, stimulating the development of collateral development after surgical revascularization. Our study was a practical interpretation of association between preoperative collateral anastomosis and postoperative neovascularization, and the mechanisms behind this phenomenon remain to be clarified by future studies.
Previous studies demonstrated that indirect bypass was more effective for patients with young age and ischemic onset symptom 4, 27. In the study, 34 (60.7%) cases younger than 25 years had good neovascularization compared to 22 (39.3%) cases older than 25 years (P< 0.001, OR [95%CI], 0.827 [0.793–0.916]), indicating age might be a relatively significant predictor. Previous literature reported that hemisphere in young age was associated with better cerebrovascular reactivity and higher secretion of angiogenic peptides, vascular endothelial growth factor (VEGF) stimulating collateral growth than in old age when suffering from cerebral ischemia 28–30. However, Zhao reported that age was not an independent predictor for neovascularization after indirect bypass in the entire series, but the predictor of MMD patients in the hemorrhagic-onset type, which differed from our results15. As for age was not the most influential predictor affecting surgical effect, it still needed to explore further.
In addition, in our series, 41.5% hemispheres in the hemorrhagic had poorer neovascularization than 7.1% in the ischemic (P<0.001, OR [95%CI], 0.138 [0.054–0.353]). Previous reports demonstrated that hemorrhagic onset type was a potential predictor for neovascularization after indirect bypass15, 31. As is known the hemispheres with normal perfusion in the hemorrhagic were more common than the ischemic group. The MMD patients with hemorrhage tended to be diagnosed in early stage of the disease due to abrupt presence of brain hemorrhage, whereas the ischemic tended to be in the advanced stage32. We hypothesized that cerebral revascularization itself might be a destruction to the vulnerable blood supply from extracranial arteries for hemorrhagic MMD patient receiving surgery treatment too early, which could cause an adverse effect on postoperative neovascularization. Hence, the general superiority of direct bypass over indirect bypass for MMD patients should not be ignored, especially for the MMD patients with hemorrhage.
According to previous reports, good neovascularization was associated with better long-term outcomes33, 34. Better neurological status and more improved outcomes were observed in hemispheres with good neovascularization, suggesting the effect of revascularization was crucial to the long-term outcome for adult MMD patients (improvement: 94.6% vs 80.5%, P=0.014; deterioration: 1.8% vs 12.2%, P=0.036). However, there was no significant difference in recurrent ischemia, rehemorrhage and seizure between hemispheres with poor and good neovascularization (P>0.05). This finding was different from results reported by Arias et al35., due to the comparatively larger sample size of the study
The current study had a few limitations as follow. First, our study was a retrospective research in a single center, and selection bias might exist. The conclusion needed a multicenter research for further verification. Second, sample size of the study was small, which need more patients enrolled to confirm the conclusion. Third, the current study did not elucidate the potential pathophysiology, and future studies were needed to further address this issue. Fourth, the main indirect bypass included in the study is EDAS, so there was no basis for the evaluation of the other indirect bypass surgery. Fifth, the study lacked data on cerebral perfusion, and radiological brain perfusion examination would be the next.