Abstract
BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) may be triggered by environmental risk factors. OBJECTIVES: We aimed to explore and integrate the recent research advances in this field. Here we describe relevant studies and summarize current knowledge on non-genetic factors that influence the onset of the disease. DESIGN: Systematic review. METHODS: We performed a systematic review up to May 21, 2024, following preferred reporting items for systematic reviews and meta-analyses guidelines. Two independent reviewers evaluated the quality of the included studies using the Joanna Briggs Institute checklist for risk of bias assessment. DATA SOURCES: MEDLINE, EMBASE, Scopus, and Web of Science databases. RESULTS: A total of 15,869 articles were evaluated. Of those 50 studies met the eligibility criteria. A total of 21,410 NMOSD patients were included in the studies; 17,080 patients were females. Totally, 14 risk factors, including vitamin D deficiency, vaccination, virus infections, lifestyle, and dietary factors, were assessed. A total of 37% of the included articles were conducted in East Asia, mainly focusing on the effects of infection and vitamin D deficiency. These studies suggested vitamin D deficiency as a possible NMOSD risk factor. A total of 25% of the studies included Caucasian populations from Western countries. They showed that smoking decreased the odds of NMOSD, in contrast to observations from Eastern studies. Few cases reported NMOSD onset after COVID-19 vaccination. Antibodies against Epstein-Barr virus, Mycobacterium paratuberculosis, and Helicobacter pylori were observed to be more frequently positive in the serum of NMOSD patients. Lower protein and fat and higher carbohydrate intakes were correlated with NMOSD development. CONCLUSION: Vitamin D deficiency, cigarette smoking, Mycobacterium avium subspecies paratuberculosis infection, and diet were reported as environmental risk factors for NMOSD. The difference in the onset of NMOSD between Asian and Caucasian populations could be affected by smoking and vitamin D deficiency. Knowledge of modifiable risk factors for NMOSD may be beneficial in preventing and improving disease outcomes.