A national case-control study investigating demographic and environmental factors associated with NMOSD

Dalia L Rotstein; Christina Wolfson; Robert Carruthers; Mark S Freedman; Sarah A Morrow; Liesly Lee; Jodie M Burton; Rosane Nisenbaum; Andrea Konig; Sandra Magalhaes; Ruth Ann Marrie

doi:10.1177/13524585231151953

A national case-control study investigating demographic and environmental factors associated with NMOSD

Mult Scler. 2023 Apr;29(4-5):521-529. doi: 10.1177/13524585231151953. Epub 2023 Feb 18.

Authors

Affiliations

¹ Department of Medicine, University of Toronto, Toronto, ON, Canada/MS Clinic, St. Michael's Hospital, Toronto, ON, Canada.
² Departments of Epidemiology, Biostatistics and Occupational Health and Medicine, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada/Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
³ Division of Neurology, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
⁴ Department of Medicine, University of Ottawa, Ottawa, ON, Canada/Ottawa Hospital Research Institute, Ottawa, ON, Canada.
⁵ Western University, London, ON, Canada/London Health Sciences Centre, London, ON, Canada.
⁶ Department of Medicine, University of Toronto, Toronto, ON, Canada/Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
⁷ Departments of Clinical Neurosciences and Community Health Sciences, University of Calgary, Calgary, AB, Canada.
⁸ St. Michael's Hospital, Toronto, ON, Canada/Applied Health Research Centre and MAP Centre for Urban Health Solutions, Li Ka Shing Knowledge Institute, St Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada/Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
⁹ St. Michael's Hospital, Toronto, ON, Canada.
¹⁰ Department of Sociology, University of New Brunswick, Fredericton, NB, Canada.
¹¹ Departments of Medicine and Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.

Abstract

Background: Risk factors for aquaporin-4 (AQP4+) antibody neuromyelitis optica spectrum disorder (NMOSD) are not well-established.

Objective: To investigate demographic and environmental factors associated with NMOSD using a validated questionnaire and case-control design.

Methods: We enrolled patients with AQP4 + NMOSD through six Canadian Multiple Sclerosis Clinics. Participants completed the validated Environmental Risk Factors in Multiple Sclerosis Study (EnvIMS) questionnaire. Their responses were compared to those of 956 unaffected controls from the Canadian arm of EnvIMS. We calculated odds ratios (ORs) for the association between each variable and NMOSD using logistic regression and Firth's procedure for rare events.

Results: In 122 participants (87.7% female) with NMOSD, odds of NMOSD in East Asian and Black participants were ⩾8 times that observed in White participants. Birthplace outside Canada was associated with an increased risk of NMOSD (OR = 5.5, 95% confidence interval (CI) = 3.6-8.3) as were concomitant autoimmune diseases (OR = 2.7, 95% CI = 1.4-5.0). No association was observed with reproductive history or age at menarche.

Conclusion: In this case-control study, risk of NMOSD in East Asian and Black versus White individuals was greater than that observed in many previous studies. Despite the preponderance of affected women, we did not observe any association with hormonal factors such as reproductive history or age at menarche.

Keywords: NMOSD; aquaporin-4; epidemiology; risk factors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aquaporin 4
Autoantibodies
Canada / epidemiology
Case-Control Studies
Demography
Female
Humans
Male
Multiple Sclerosis* / complications
Neuromyelitis Optica*

Substances

Aquaporin 4
Autoantibodies