A meta‐analysis of comparisons of various surgical treatments for moyamoya diseases

Abstract Purpose Ischemia is one of the most familiar complications in the different procedures for moyamoya disease (MMD), but the optimal surgical approaches for MMD remain unknown. We aimed to evaluate the efficiency of various surgical treatments. Methods A literature search word was performed through four databases such as Cochrane Library, Web of Science, PubMed, and EMBASE for the literature published until May 2021. The I 2 statistic was used to assess heterogeneity. A random/fixed‐effects model was used to pool. Results There are a total of 18 studies including three surgical treatments such as including indirect, direct, and combined bypass in this study. The result revealed that indirect bypass was related to a higher incidence of recurrence stroke compared to the direct and combined bypass treatment (p = .001). Furthermore, the cases undergoing direct bypass were associated with a better angiographic change than the indirect bypass (OR = 3.254, p = .013). Conclusion This meta‐analysis demonstrated a positive effect of using the direct and combined bypass to treat MMD compared to indirect bypass due to their lower rates of recurrence stroke.

absence of supporting evidence from large randomized prospective clinical trials, there is growing scientific evidence and acceptance that surgery revascularization is the most effective treatment for patients with MMD (Guzman et al., 2009;Kuroda & Houkin, 2008). Different revascularization strategies are available which can conceptionally be divided into three main categories, namely direct bypass (DB), indirect bypass (IB), and combined bypass (CB) (Kuroda & Houkin, 2008). To date, this has not been studied systematically whether direct, indirect, or combined procedures of revascularization will result in a best extensive collateral blood supply, and therefore provide better protection for the ischemic brain. Therefore, this systematic review and meta-analysis aimed to summarize and critically appraise all existing evidence on the clinical outcome for the treatment of MMD in a large series of patients who underwent various types of surgical procedures.

METHODS
This study was based on the acknowledged PRISMA guidelines (the prioritized reported items for systematic review and meta-analysis).

ETHICAL REVIEW
All analyses were conducted according to the available published literature; thus, no ethical approval or patient consent was required.

Literature and search strategy
The electronic databases, including Cochrane Library, Web of Science,

Inclusion and exclusion criteria
If the article met the following criteria following PICOS, the article was considered to be included in the current meta-analysis: (I) patients with MMD; (II) surgical revascularizations; (III) DB, IB, and CB surgery; (IV) one or more of the preplanned outcomes were reported; (V) an official published full-text English-written article. Case reports, animal studies, comments, letters, editorials, protocols, guidelines, and review papers were excluded.

Data extraction
Two of the authors independently extracted data from all the included studies. The following essential information was captured: the first author's name, publication year, sample size, study design, and outcomes. Other relevant data such as patient characteristics and literature quality scores were also extracted from individual studies.

Data synthesis and analysis
All meta-analyses of eligible results were conducted using the STATA version 12.0 (Stata Corporation, College Station, Texas, USA). Heterogeneity among studies was estimated using a χ 2 test, and the I 2 value was identified to describe the percentage variance in trials attributable to heterogeneity. I 2 > 50% was deemed as the high heterogeneity, and a random-effect model was applied. Otherwise, the fixed-effect model was chosen. The odds ratios (ORs) or rate differences (RDs) with 95% confidence intervals (CIs) were applied for the evaluation of binary variables, and p-value < 0.05 was regarded as statistically significant.

Search results
The selection process is illustrated in Figure 1, and 1536 articles were searched in the original databases. Of these records, 1110 publications were removed owing to duplication. Meanwhile, 304 publications were eliminated due to different reasons. Full-text of the remaining 122 publications were assessed for eligibility. Three articles were excluded since they did not compare one or more of the preplanned outcomes.

Quality assessment
The Newcastle-Ottawa Scale (NOS) was taken to evaluate the quality of included studies. Two authors have appraised the quality of all involved studies. The differences that arose in the process were solved by discussing. More details about the specific scores are shown in Table 2.

Study characteristics
Demographic characteristics concerning the included studies are summarized in   Table 3.

DISCUSSION
MMD is a unique clinical entity, which is characterized by the progressive occlusion of the bilateral supraglenoid ICA. Despite MMD is firstly found in Japan, more and more patients with MMD have been found in China recently (Bao et al., 2015;X. J. Liu et al., 2015). To date, the most adopted revascularizations for MMD include DB, IB, and CB (Zhao et al. 2019), while the treatment prospects are limited since there is no known medical therapy that has been proven to be effective (Moussouttas & Rybinnik, 2020). DB seems to reduce the risk of stroke more than IB. Some studies supported using the CB strategy as the best alternative, employing both a direct STA-MCA bypass and an IB such as EDAS or EDAMS (Amin-Hanjani et al., 2013;Aoun et al., 2015).
This study investigated the effects of various surgical treatments for MMD.

F I G U R E 2 Forest plot for recurrence stroke between the indirect and direct bypass
In the analysis, we compared the effects and safety of DB and IB for MMD and showed the DB group had a lower rate of recurrence stroke. Considering recurrent stroke prevention, DB has a huge advantage compared to IB. About angiographic change, we investigated that DB surgical treatment was better. Matsushima et al. did a retrospective study including 40 children who underwent either EDAS or STA-MCA anastomosis with EMS. They reported that the DB resulted in better angiographic collateral filling and improved clinical outcomes (Matsushima et al., 1992). In another study conducted by Kawaguchi et al. comparing the outcomes between the two groups, the extent of revascularization was highest after DB than after only IB (Kawaguchi et al., 2000), and this study supported our angiographic finding.
Then, we compared the efficiency between CB and IB in patients with MMD. Despite the result indicated the patients in the IB surgery group did not have a higher postoperative complication rate, as for recurrence stroke, the IB group had a higher recurrence stroke rate.
Previous studies indicated that IB can lead to surgical collaterals in about 40%−50% of adult patients, which may develop 3−4 months after surgery. CB has been found to have a better effect on revascularization compared with IB (Kuroda & Houkin, 2008). Kim et al. (2012) showed that CB was slightly superior to IB based on the extent of postoperative angiographic revascularization. Similarly, Noh et al.
also revealed a favor of CB over IB (Noh et al., 2015). Those results supported the advantages of CB over IB, which is consistent with our research (Cho et al., 2014).
DB and CB surgery was reported to be more effective than IB in preventing rebleeding; however, the effect and superiority between DB and CB for MMD had barely been investigated yet (Y. Zhao et al., 2018). Therefore, this study was also concerned about the comparisons between CB and DB and revealed that there was no significant difference between CB and DB based on the aforementioned outcomes. It was noteworthy that these results were similar to those reported recently by Y. Zhao et al. (2018).
Their results showed that CB did not bring additional risks during the postoperative period even though operation time was longer than DB.
This study had the following limitations: First, there were only seven factors used to analyze the effects and safety of different surgical revascularization of MMD may lead to unequal operation quality comparison. Second, some pieces of literature included in this meta-analysis had a relatively small sample size. Finally, the focus of this meta-analysis was to provide a short-term outcome to clarify the value of DB, IB, and CB. Therefore, further attention should be paid to the long-term efficacy of randomized controlled trials (RCTs) to determine the potential advantages of DB. Abbreviations: CB, combined direct and indirect bypass; CI, confidence interval; mRS, modified Rankin Scale; OR, odds ratio; RD, rate difference. The bold value refers to p < 0.05.

CONCLUSION
This meta-analysis demonstrated a positive effect of using the direct and combined bypass to treat MMD compared to indirect bypass due to their lower rates of recurrence stroke.

CONFLICT OF INTEREST
The authors declare no conflict of interest.

DATA AVAILABILITY STATEMENT
The datasets used and/or analyzed during this study are available from the corresponding author upon reasonable request.