Moyamoya Disease Group Research Articles

Association of Thyroid Autoantibodies With Moyamoya-Type Cerebrovascular Disease

To investigate the association between thyroid autoantibodies and moyamoya disease (MMD) in patients with an apparent euthyroid state. We prospectively studied angiographically diagnosed patients with MMD. We compared demographic profiles, thyroid function test, and thyroid autoantibody status between MMD and control groups. A total of 63 patients with MMD, 71 patients with non-MMD stroke, and 200 healthy control subjects were included. The prevalence of elevated thyroid autoantibodies was higher in the MMD group than in other groups (P<0.01 for MMD versus non-MMD; P<0.001 for MMD versus control subjects). After adjusting for covariates, the elevated thyroid autoantibodies (OR, 4.871; 95% CI, 1.588 to 15.277) and smoking habits (OR, 0.206 for current smoker; 95% CI, 0.054 to 0.786) were independently associated with MMD versus non-MMD stroke. Elevated thyroid autoantibodies were frequently observed in patients with MMD. The results of the present study suggest that immune aberrancies associated with or underlying thyroid autoimmunity are also playing a role in developing MMD.

Increased Levels of Circulating Endothelial Progenitor Cells in Patients With Moyamoya Disease

Chronic cerebral ischemia leads to higher risk for strokes attributable to insufficient collateralization, resulting from inadequate capacity for arteriogenesis and angiogenesis. Patients with Moyamoya disease (MMD) have similar transient ischemic attack frequencies compared to patients with chronic cerebral ischemia with other etiologies, but a strong capacity for arteriogenesis and angiogenesis. The mechanisms involved in the upregulation of the arteriogenesis and angiogenesis in MMD still remain unknown. In the present study we investigated if circulating endothelial progenitor cells are increasingly mobilized during MMD. Twenty MMD patients, 8 patients with atherosclerotic cerebrovascular disease, and 15 healthy individuals were included in this study. Peripheral blood mononuclear cells were isolated by Ficoll density gradient centrifugation and circulating endothelial progenitor cells were characterized by triple staining using antibodies against CD133, CD34, and vascular endothelial growth factor receptor-2. Serum concentrations of vascular endothelial growth factor and granulocyte-macrophage colony-stimulating factor were determined by enzyme-linked immunosorbent assay. In MMD patients the number of circulating endothelial progenitor cells was significantly higher than in atherosclerotic cerebrovascular disease patients (P<0.002) and healthy controls (P<0.0001). Serum vascular endothelial growth factor concentrations in MMD patients and in atherosclerotic cerebrovascular disease patients were significantly higher compared to those in healthy controls (P<0.0001). Similar findings were observed for granulocyte-macrophage colony-stimulating factor. An inverse correlation between circulating endothelial progenitor cell numbers and serum levels of vascular endothelial growth factor (r=-0.53; P<0,02) was found in the MMD group. Our results show increased circulating endothelial progenitor cell numbers in MMD, which may play a role in the increased arteriogenesis and angiogenesis in MMD. Moreover, our results suggest that increased circulating endothelial progenitor cell mobilization in MMD may not be entirely mediated by vascular endothelial growth factor or granulocyte-macrophage colony-stimulating factor.

Reduced hypercapnic vasoreactivity in moyamoya disease.

We measured cerebral perfusion at rest and in response to CO2 in eight patients with moyamoya disease (MMD), using the 133xenon inhalation method to determine the effect of large-vessel occlusive disease on vasoreactivity. We studied three other groups for comparison, including four with bilateral internal carotid artery occlusions (BICAO), 11 with unilateral carotid occlusion (UICAO), and six with unilateral middle cerebral artery stem occlusion (UMCAO). Resting flows appeared to correlate with the severity of occlusive disease overall. Normocapnic perfusion was lowest in the group with BICAO and decreased in proportion to the degree of contralateral stenosis in the group with UICAO. Hypercapnic perfusion correlated with the apparent adequacy of angiographic collaterals. Reactivity was lowest in the MMD group (0.79%/mm Hg) whose collateral supply was limited to leptomeningeal anastomosis from the posterior cerebral artery, but highest in the patients with BICAO (2.72%/mm Hg), each of whom showed excellent posterior communicating artery flow. The clinical course of the MMD group was compatible with the syndrome of perfusion insufficiency with repeated ischemic attacks or a saltatory progression of an ischemic deficit; CT showed infarction in the borderzone territory. These results suggest that a severely reduced hypercapnic response may help to identify patients with ischemic syndromes due to perfusion failure in the borderzones, as in MMD.