Patients Located Farther North Experience More Severe MS

In this Q&A, Tomas Kalincik, MD, PhD, Dame Kate Campbell Professorial Fellow, head of the Clinical Outcomes Research (CORe) Unite, University of Melbourne, head of the MS Centre at the Royal Melbourne Hospital, shared insights as corresponding author on a study recently published in Neurology that examined how geographic latitude affects the severity of multiple sclerosis (MS).

The first author of the study, “Associate of Latitutde and Exposure to Ultraviolet B Radiation With Severity of Multiple Sclerosis: An International Registry Study,” is Marianna Vitkova, MD, PhD, Faculty of Medicine, L. Pasteur University Hospital, Kosice, Slovakia.

Question: What led you and your colleagues to investigate link between geographic latitudes and severity of MS?

Professor Tomas Kalincik: Together with Dr Marianna Vitkova, who spent a year as a fellow with the CORe team in Melbourne, we were intrigued by the fact that while susceptibility to MS increases with higher latitude, no similar trend has been convincingly demonstrated for MS severity.

Q: Please briefly describe the study method and participants. 

Professor Kalincik: This study used MSBase, an international MS Registry from 157 participating centers in 40 countries, which currently holds longitudinal neurological data from over 80,000 patients. We have used the information about the latitude of the patients' treating centers, country of birth and place of residence, in conjunction with disability adjusted for disease duration (Multiple Sclerosis Severity Scale). We have assessed the associations between latitude and MS severity using multivariable mixed-effect models, allowing for nonlinear behavior of this association.

Q: Please briefly describe the most significant finding(s).  

Professor Kalincik: We have found that the association between latitude and MS severity is nonlinear. While above 40° of latitude, MS tends to assume more severe course closer to the poles (by 1.3 steps for every 15°of latitude) this relationship becomes saturated below 40 degrees of latitude and is no longer observed. Interestingly, this association is also carried over from early childhood.

Q: Were any outcomes different than you expected?  

Professor Kalincik:The fact that the association disappears in people living below 40º of latitude is intriguing. We may speculate that this could be due to the “saturation” of the effect of ultraviolet (UV) radiation on immune system, but also behavioral factors, diet, and other cultural differences. Genetic constitution of different populations may also play an interesting role. For example, melanocortin 1 receptor is associated with skin tone, response to UV radiation and modulation of the immune system, as shown last year by the group in Muenster.

Q: Are there any practical applications of your findings for clinicians treating patients with MS? And how can practitioners account for their geographic location when caring for MS patients?

Professor Kalincik: While we are still unsure about the causal role of UV radiation and vitamin D in the pathogenesis of MS, results of epidemiological studies suggest that patients with MS tend to be vitamin D–depleted. Therefore, substitution of vitamin D in moderation is an intuitive action, even though we are yet to see if this intervention may have any effect on the severity of MS course.

Professor Tomas Kalincik, MD, PhD, is Dame Kate Campbell Professorial Fellow, the head of the Clinical Outcomes Research (CORe) Unit at the University of Melbourne and of the MS Centre at the Royal Melbourne Hospital. Together with his research group, CORe, Tomas specialises in analytics of observational data in neurology. He has led a number of international collaborative research initiatives - including studies of comparative effectiveness of MS therapies, management of treatment failure and individual treatment response. He has published more than 150 articles in peer-reviewed journals, including JAMA, Lancet Neurology and Brain. His main research interests span treatment outcomes in MS and other neuroimmunological diseases, individualised therapy, prognostics (including emerging biomarkers), causal inference, epidemiology and utility of volumetric MRI. He chairs the Scientific Leadership Group of the MSBase collaboration and convenes the international CORe Advanced Statistics Course, endorsed by the European Committee for Treatment and Research in MS.

Marianna Vitkova, MD, PhD, is a neurologist and an assistant professor at the Faculty of Medicine, P.J. Safarik University in Kosice, L.Pasteur University Hospital in Kosice, Slovakia. Her clinical practice and research focuses on demyelinating diseases of central nervous system. She has published  18 publications in peer-reviewed journals.  In 2020, she completed Multiple sclerosis research fellowship at the Royal Melbourne Hospital where she spent a year with the Clinical Outcome Research team led by Professor Kalincik.