Moyamoya and Inflammation

Mejia-Munne, Juan C.; Ellis, Jason A.; Feldstein, Neil A.; Meyers, Philip M.; Connolly, E. Sander

doi:10.1016/j.wneu.2017.01.012

Cited by 25 publications

(25 citation statements)

References 17 publications

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“…The purpose of this study was to assess the admission rates and features of patients exhibiting moyamoya within our region. As observed in previous analyses, our cohort demonstrated a predominance of female patients [8] but differed significantly with respect to race. While Asian descent is recognized to have a significant association with the development of moyamoya [1], this study involved a predominantly white patient group reflective of the regional population.…”

Section: Discussionsupporting

confidence: 83%

High Prevalence of Moyamoya Syndrome in Appalachia

Nisiewicz

Roberts

Dobbs³

et al. 2020

Cerebrovasc Dis

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Introduction: Moyamoya is a chronic cerebrovascular condition of unclear etiology characterized by progressive occlusion of 1 or both internal carotid arteries with neovascular collateral formation. With both an idiopathic form (moyamoya disease) and congenital condition-associated form (moyamoya syndrome), it can cause ischemic and hemorrhagic stroke. Recent findings in Kentucky have challenged traditional estimates of its incidence in US populations. Using the Kentucky Appalachian Stroke Registry (KApSR), our aim was to further characterize its incidence as a cause of stroke and to understand the patient population in Appalachia. Methods: A retrospective review of moyamoya patients was performed using the KApSR database. Data collected included demographics, county location, risk factors, comorbidities, and health-care encounters from January 1, 2012, to December 31, 2016. Results: Sixty-seven patients were identified; 36 (53.7%) resided in Appalachian counties. The cohort accounted for 125 of 6,305 stroke admissions, representing an incidence of 1,983 per 100,000 stroke admissions. Patients presented with ischemic strokes rather than hemorrhagic strokes (odds ratio 5.50, 95% CI: 2.74–11.04, p < 0.01). Eleven patients (16.4%) exhibited autoimmune disorders. Compared to the general population with autoimmune disorder prevalence of 4.5%, the presence of autoimmunity within the cohort was significantly higher (p < 0.01). Compared to non-Appalachian patients, Appalachian patients tended to present with lower frequencies of tobacco use (p = 0.08), diabetes mellitus (p = 0.13), and hypertension (p = 0.16). Conclusions: Moyamoya accounts for a substantial number of stroke admissions in Kentucky; these patients were more likely to develop an ischemic stroke rather than a hemorrhagic stroke. Autoimmune disorders were more prevalent in moyamoya patients than in the general population. The reduced frequency of traditional stroke risk factors within the Appalachian group suggests an etiology distinct to the population.

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Section: Discussionsupporting

confidence: 83%

High Prevalence of Moyamoya Syndrome in Appalachia

Nisiewicz

Roberts

Dobbs³

et al. 2020

Cerebrovasc Dis

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“…Besides genetic aspect, environmental factors could also play a key role in the pathogenesis of MMD. On one hand, an increasing number of studies have revealed a significant association between MMD and immunological diseases, implying a potential immune component in the pathogenesis of MMD[13–16]. On the other hand, many recent studies have also focused on abnormal revascularization in MMD patients, which is probably a protective response to the ischemic and hypoxia cerebral environment[17].…”

Section: Introductionmentioning

confidence: 99%

Gene dysregulation in peripheral blood of moyamoya disease and comparison with other vascular disorders

Xing

Zhang

et al. 2019

PLoS ONE

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ObjectiveMoyamoya disease (MMD) is a chronic occlusive cerebrovascular disease with unknown etiology, sharing many similar clinical symptoms with other vascular disorders. This study aimed to investigate gene dysregulation in peripheral blood of MMD and compare it with other vascular disorders.MethodsTranscriptomic profiles of 12 MMD patients and 8 healthy controls were obtained using RNA sequencing. Differentially expressed genes (DEGs) were identified and several were validated by quantitative real-time PCR in independent samples. Biological pathway enrichment analysis of DEGs and deconvolution of leukocyte subsets in peripheral blood were performed. Expression profiles for other vascular diseases were downloaded from public database and consistent DEGs were calculated. Gene set enrichment analysis (GSEA) was conducted to compare gene dysregulation pattern between MMD and other vascular diseases.ResultsA total of 533 DEGs were identified for MMD. Up-regulated genes were mainly involved in extracellular matrix (ECM) organization, whereas down-regulated genes were primarily associated with inflammatory and immune responses. As for cell populations, significantly increased naïve B cells and naïve CD4 cells as well as obviously decreased resting natural killer cells were observed in peripheral blood of MMD patients. GSEA analysis indicated that only up-regulated genes of ischemic stroke and down-regulated genes of coronary artery disease and myocardial infarction were enriched in up-regulated and down-regulated genes of MMD, respectively.ConclusionDysregulated genes in peripheral blood of MMD mainly played key roles in ECM organization, inflammatory and immune responses. This gene dysregulation pattern was specific compared with other vascular diseases. Besides, naïve B cells, naïve CD4 cells and resting natural killer cells were aberrantly disrupted in peripheral blood of MMD patients. These results will help elucidate the complicated pathogenic mechanism of MMD.

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“…Mutation or polymorphism in TGFß pathway genes, TGFB1, TGFBR1 and TGFBR2 are associated with vascular disorders that have high stroke risk and inflammation such as Loeys Dietz syndrome 6,38 , Kawasaki disease 39,40 , and Moyamoya disease 41,42 . Tgfbr2 polymorphism is also associated with intracerebral hemorrhage 43 .…”

Section: Discussionmentioning

confidence: 99%

Attenuation of Myeloid-Specific TGFβ Signaling Induces Inflammatory Cerebrovascular Disease and Stroke

Hollander

Latour

Yang

et al. 2017

Circulation Research

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Rationale Cryptogenic strokes, those of unknown cause, have been estimated as high as 30–40% of strokes. Inflammation has been suggested as a critical etiological factor. However, there is lack of experimental evidence. Objective In this study, we investigated inflammation associated stroke etiology using a mouse model that developed spontaneous stroke due to myeloid deficiency of TGFβ signaling. Methods and Results We report that mice with deletion of Tgfbr2 in myeloid cells (Tgfbr2Myeko) developed cerebrovascular inflammation in the absence of significant pathology in other tissues, culminating in stroke and severe neurological deficits with 100% penetrance. The stroke phenotype can be transferred to syngeneic wild type mice via Tgfbr2Myeko bone marrow transplant, and can be rescued in Tgfbr2Myeko mice with wild-type bone marrow. The underlying mechanisms involved an increased type 1 inflammation, and cerebral endotheliopathy, characterized by elevated NFκB activation and TNF production by myeloid cells. A high fat diet accelerated stroke incidence. Anti-TNF treatment, as well as metformin and methotrexate, which are associated with decreased stroke risk in population studies, delayed stroke occurrence. Conclusions Our studies show that TGFβ signaling in myeloid cells is required for maintenance of vascular health, and provide insight into inflammation-mediated cerebrovascular disease and stroke.

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Moyamoya and Inflammation

Cited by 25 publications

References 17 publications

High Prevalence of Moyamoya Syndrome in Appalachia

High Prevalence of Moyamoya Syndrome in Appalachia

Gene dysregulation in peripheral blood of moyamoya disease and comparison with other vascular disorders

Attenuation of Myeloid-Specific TGFβ Signaling Induces Inflammatory Cerebrovascular Disease and Stroke

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