Study Identifies Environmental Risk Factors Significantly Associated With Neuromyelitis Optica Spectrum Disorder

In a newly published review in Therapeutic Advances in Neurological Disorders, researchers observed that vitamin D deficiency, cigarette smoking, Mycobacterium avium subspecies paratuberculosis infection, and diet were environmental risk factors that were all significantly associated with neuromyelitis optica spectrum disorder (NMOSD). These findings suggest that understanding modifiable risk factors for NMOSD help prevent disease onset and improve outcomes.¹

Among 15,869 articles identified through MEDLINE, EMBASE, Scopus, and Web of Science databases up to May 21, 2024, 50 studies met eligibility criteria (NMOSD, n = 21,410; women, n = 17,080). The included studies assessed 14 risk factors including vitamin D deficiency, smoking, substance and alcohol abuse, vaccination, infection, diet, hormonal factors, seasonality, month of birth, latitude, sun exposure and physical activity and weight, stressful life events, and socioeconomic status. Quality assessment of these studies was performed by 2 independent researchers using the Newcastle-Ottawa tool.²

“Even though the exact pathogenesis of the disease is yet to be understood, addressing triggers might help reach a prompt and accurate diagnosis. Besides individual factors such as age, gender, education, and ethnicity, studies indicate an environmental involvement in the onset of NMOSD. Environmental factors with seasonal variation influence the development of neurological conditions related to NMOSD,” lead author Mohammad Ali Sahraian, MD, neurologist and professor of neurology at Tehran University of Medical Sciences, and colleagues wrote.¹ “Environmental risk factors in this study have mainly focused on vitamin D deficiency, smoking, infection, and diet."

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Of the included studies, authors noted that 37% were conducted in East Asia, which assessed infection and vitamin D deficiency. Among these, 31% originated from non-East Asian countries, including Iran, where the studies evaluated environmental risk factors such as diet, smoking, hormonal factors, and socioeconomic status, history of oral contraceptive pills use, month of birth, sun exposure and physical activity, and socioeconomic factors. An additional 25% of studies involved predominantly Caucasian populations, focusing mainly on smoking and infections.

All told, few cases reported onset of NMOSD following COVID-19 vaccination. Researchers also observed that antibodies against Epstein-Barr virus, Mycobacterium paratuberculosis, and Helicobacter pylori were to be more frequently positive in the serum of patients with NMOSD. In addition, results showed that lower protein and fat and higher carbohydrate intakes were associated with the development of the disease. The authors noted that a limitation of the review is potential publication bias and heterogeneity among studies, which may complicate interpretation of the findings. Additionally, few studies evaluated environmental risk factors for NMOSD, particularly in African populations.

“The review of 50 environmental risk factors in the current study showed that vitamin D deficiency, cigarette smoking, MAP infection, and diet had a significant association with NMOSD. In East Asians, vitamin D deficiency contributed to increased risk of NMOSD. Controversial results were reported regarding the effect of smoking among Caucasians and other races,” Sahraian et al noted.¹ “Further studies are required to elucidate the findings presented in this review study."

REFERENCES
1. Mohammadi Lapevandani M, Bazmi E, Jahani S, Asgari N, Sahraian MA. Environmental risk factors of neuromyelitis optica spectrum disorder: a systematic review. Ther Adv Neurol Disord. 2025;18:17562864251363293. Published 2025 Oct 8. doi:10.1177/17562864251363293
2. Lo CK, Mertz D, Loeb M. Newcastle-Ottawa Scale: comparing reviewers' to authors' assessments. BMC Med Res Methodol. 2014;14:45. Published 2014 Apr 1. doi:10.1186/1471-2288-14-45