Cortical Microvascularization in Moyamoya Disease: Characteristics and the Relations with Surgical Outcomes of Encephaloduroarteriosynangiosis

Moyamoya disease (MMD) is a progressive occlusive cerebrovascular disorder of the internal carotid arteries or their branches, with compensatory development of an abnormal basal collateral vascular network [1]. Surgical revascularization has been proposed as effective in preventing clinical events, via either a direct or indirect procedure [2,3]. As a commonly used indirect revascularization method, encephaloduroarteriosynangiosis (EDAS) is considered easier and safer than direct bypass [4]. However, its effectiveness remains controversial [3,4]. Therefore, it is important to identify whether a patient is suitable for EDAS to determine the best surgical approach. Increased and dilated cortical microvasculature is considered a MMD-specific alteration, and it might represent a compensatory mechanism for reduced cerebral blood flow [5,6]. According to our surgical experience in the treatment of MMD, there seems to be a correlation between the cortical microvascular density and the effect of EDAS. Therefore, we sought to verify this hypothesis in this study. We identified all consecutive patients with MMD treated by EDAS at our department from October 2011 to October 2014. The diagnosis of MMDwas made according to the guidelines published in 2012 [2]. All EDAS surgeries were performed on the middle cerebral artery (MCA) territory, and the parietal branch of the superficial temporal artery (STA) was used. General anesthesia was maintained using sevoflurane in oxygen and air, combined infusions of propofol and remifentanil. End-tidal carbon dioxide (ETCO2) was maintained at 38–42 mmHg in all patients during surgery. For the analysis of cortical vascularization, we took photographs of the cerebral cortex during surgery. Postoperatively, we analyzed two suitable regions of interest (ROIs) per cortex image. ROIs were characterized as an area of 5 9 5 or 10 9 10 mm grids without obvious arteries and veins [5]. A microvascular density (MD) was calculated as the percentage of visible microvessel grids and total grids per analyzed ROI, and the final MD scores were represented as the means of the two ROIs in each image. The cases were divided into three groups with the following cutoff points: “low,” MD less than 33%; “medium,” MD between 33% and 66%; and “high,” MD higher than 66% [7] (Figure 1). Postoperative cerebral digital subtraction angiography (DSA) was routinely performed 6–8 months after surgery. The development of collateral circulation through the bypass was graded according to the system described by Matsushima et al. [8]: Grade I, revascularization of less than 1/3 of the MCA distribution; Grade II, between 1/3 and 2/3; and Grade III over 2/3. The extent of collateral formation was dichotomized into favorable (Grade II and Grade III) and unfavorable (Grade I). The long-term outcomes were ascertained during clinical visits and telephone interviews. The overall clinical outcomes were divided into four grades [9]: (1) excellent, preoperative symptoms had totally disappeared without fixed neurological deficits; (2) good, symptoms had markedly decreased, but mild neurological deficits remained; (3) fair, symptoms persisted albeit less frequently; and (4) poor, preoperative symptoms remained unchanged or worsened and with the appearance of new