Risk factors for postoperative stroke in adults patients with moyamoya disease: a systematic review with meta-analysis

Moyamoya disease (MMD) is an abnormal cerebrovascular characterized by progressive stenosis or occlusion of the intracranial vessels, resulting in the formation of a fine vascular network (the “moyamoya” vessels) at the base of the brain [1]. The current concept is to prevent cerebral ischemia and avoid cerebral hemorrhage [2]. And revascularization surgery is the most effective treatment for MMD. Surgical revascularization can be mainly divided into indirect bypass, direct bypass and combined bypass [3]. However, the incidence of postoperative complications, such as postoperative ischemic or hemorrhagic events and cerebral hyperperfusion syndrome (CHS), has been increasingly reported. These procedure-related complications can seriously affect the prognosis [4].

Previous studies have attempted to determine risk factors that would predict postoperative complications [5‐12]. To identify the clinical factors can be more useful in preventing postoperative complications. And, this information regarding the management of adult onset MMD is important [13]. However, the risk factors of postoperative complications were still unclear. Therefore, it is particularly important to identify these risk factors so as to ensure the efficacy of surgical treatment. Thus we conducted this systematic review with meta-analysis to clarify the risk factors for postoperative stroke in adult patients with MMD.

This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) criteria [14]. Ethical approval is not required by our institution for secondary research using published scientific studies.

There were 8 studies [5‐12] encompassing 1649 patients who underwent surgery with MMD were selected for analysis. The detailed study selection progress was shown in Fig. 1. The main characteristics of included studies are summarized in Table 1. The included studies were consisted of 3 prospective studies [6, 11, 12] and 5 retrospective studies [5, 7‐10].

MMD is a chronic cerebrovascular disorder. With recent advances in neuroradiological diagnostic modalities, the diagnosis of adult onset MMD has become more frequent than in the past. Postoperative stroke was common complication in patients with MMD. The previously reported rate of postoperative ischemia in MMD patients after revascularization varies from 1.5 to 11.4% [16‐19]. Some preoperative factors have been previously reported to be associated with increase of postoperative ischemic complications in MMD patients [5‐12, 16, 20‐25]. Controversy still remains in the literature regarding which contribute as risk factors.

In this meta-analysis, preoperative ischemic event, PCA involvement, presence of diabetes and surgical type of IB and CB were verified to be independent risk factors associated with postoperative stroke. Preoperative ischemic event was likely to be an indicator of the instability of cerebral hemodynamics before surgical revascularization [8]. Previous studies had reported that frequent occurrence of preoperative TIAs was an important indicator of a risk for perioperative ischemic [22] and stroke [26] complications. Our results showed that preoperative ischemic event had a significant increase in risk for postoperative stroke. Interestingly, in the subgroup analysis, this association only exit in Caucasian, but not in Asian. That may be due to our study results included not only TIAs but also symptomatic infarction. Our findings suggested that PCA involvement was an independent risk factor, possibly because patients with advanced stage MMD, the leptomeningeal collateral from the PCA was significantly important collateral blood flow source [8]. Thus, PCA impaired may seriously affect cerebral hemodynamics, which may lead to postoperative cerebral ischemia. Besides, Jung et al. [17] reported that direct bypass may result in cerebral infarction of contralateral hemisphere in patients with PCA involvement. In the past medical history of patients, several previous reports suggested that diabetes as a predictor of recurrent stroke [27‐29]. A recent meta-analysis reported that diabetes is an independent risk factor for stroke recurrence [30]. In context of MMD, patients with diabetes may elevate expression of growth factors and cytokines, such as hepatocyte growth factor, transforming growth factor-β, vascular endothelial growth factor, and nitrotyrosine, which could lead to more collateral angiogenesis [31]. Though our results support this hypothesis, it should be noted that only three included studies considered diabetes as a risk factor. For surgery types, a recent meta-analysis proves that direct bypass could reduce the risk of perioperative stroke than indirect bypass in MMD [32]. Notably, we also found that the risk of postoperative stroke is higher in MMD patients who underwent indirect bypass and combined bypass compared with direct bypass. However, due to sensitivity analysis unstable (the result become insignificant when excluded Wonhyoung et al. [8]), that conclusion should be interpreted cautiously.

Patients with higher Suzuki stage probably had poor collateralization pathways to compensate for the hemodynamic impairment [5]. However, in the current study, sensitivity analysis of the association between Suzuki stage and recurrent stroke was instable, the result become significant after exclude the Xiangyang et al. [12] We also found that older age of symptom onset was identified as a possible predictor of postoperative strokes. This may be because older patients are often accompanied by some underlying diseases, such as diabetes, arteriosclerosis, and hypertension and so on, these may aggravate postoperative complications. Therefore, further studies with a large sample size are still needed to confirm these factors.

There are some limitations in this meta-analysis. First, our research included three prospective studies, which reported HR value of different preoperative risk factors. Thus, pooled HR value of risk factors for postoperative stroke could not be obtained. Second, among different ethnic groups, there may be differences in postoperative stroke [33], so racial differences may exist. However, in the current study, there is not enough data to explore the racial differences in other risk factors. Third, heterogeneity exists in the meta-analysis results of ischemic events and PCA involvement, it could be inter-institutional differences, such as clinical experience, diagnostic standard, operative techniques, and surgeon’s preferences, however, we did not find the cause of heterogeneity. Fourth, due to the limitation of data included in the studies, we only compared between DB and IB/CB (DB as a reference), so further research is still needed to determine the results with IB and CB. In addition, hyperperfusion syndrome was barely mentioned in the included studies, so it is impossible to analyze the influence of factors on hyperperfusion syndrome. Lastly, sensitivity analysis of surgery types and Suzuki stage are instable. Wonhyoung et al. [8] and Xiangyang et al. [12] have a serious impact on the results, respectively.

This systematic review and meta-analysis indicated that preoperative ischemic events, PCA involvement and diabetes were independent risk factors for postoperative stroke in MMD patients. Therefore, in order to ensure the curative effect of patients with MMD, it is very necessary to detect these risk factors and prevent postoperative complications in time.