Association of moyamoya vasculopathy with autoimmune disease: a systematic review and pooled analysis

Despite more than six decades of extensive research, the etiology of moyamoya disease (MMD) remains unknown. Inflammatory or autoimmune (AI) processes have been suggested to instigate or exacerbate the condition, but the data remains mixed. The objective of the present systematic review was to summarize the available literature investigating the association of MMD and AI conditions as a means of highlighting potential treatment strategies for this subset of moyamoya patients. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the PubMed, Embase, Scopus, Web of Science, and Cochrane databases were queried to identify studies describing patients with concurrent diagnoses of MMD and AI disease. Data were extracted on patient demographics, clinical outcomes, and treatment. Stable or improved symptoms were considered favorable outcomes, while worsening symptoms and death were considered unfavorable. Quantitative pooled analysis was performed with individual patient-level data. Of 739 unique studies identified, 103 comprising 205 unique patients (80.2% female) were included in the pooled analysis. Most patients (75.8%) identified as Asian/Pacific Islanders, and the most commonly reported AI condition was Graves' disease (57.6%), with 55.9% of these patients presenting in a thyrotoxic state. Of the 148 patients who presented with stroke, 88.5% of cases (n = 131) were ischemic. Outcomes data was available in 152 cases. There were no significant baseline differences between patients treated with supportive therapy alone and those receiving targeted immunosuppressant therapy. Univariable logistic regression showed that surgery plus medical therapy was more likely than medical therapy alone to result in a favorable outcome. On subanalysis of operated patients, 94.1% of patients who underwent combined direct and indirect bypass reported favorable outcomes, relative to 76.2% of patients who underwent indirect bypass and 82% who underwent direct bypass (p < 0.05). On univariable analysis, the presence of multiple AI disorders was associated with worse outcomes relative to having a single AI disorder. Autoimmune diseases have been uncommonly reported in patients with MMD, but the presence of multiple AI comorbidities portends poorer prognosis. The addition of surgical intervention appears to improve outcomes and for patients deemed surgical candidates, combined direct and indirect bypass appears to offer better outcomes that direct or indirect bypass alone.