Higher Latitudes Linked to Earlier Age at MS Onset

Deborah Brauser

November 10, 2016

Latitude can influence the age at onset (AAO) of multiple sclerosis (MS) in young adults, suggests new research that used "one of the largest cohorts to date."

The study of more than 22,000 patients with MS from 21 countries showed that those who lived at higher latitudes (defined as 50.0 to 56.0 degrees) had symptom onset almost 2 years earlier than those living at latitudes between 19.0 and 39.9 degrees.

In addition, participants with higher levels of ambient ultraviolet radiation (UVR) exposure had a significantly higher AAO, and women had an AAO that was about 5 months earlier than that in men. Further, patients with "relapsing-onset" MS had an AAO that was almost 9 years earlier than that in their counterparts with progressive-onset MS.

"These results suggest that environmental factors which act at the population level may significantly influence disease severity characteristics in genetically susceptible populations," write the investigators, led by Chunrong Tao, PhD student, Menzies Institute for Medical Research, University of Tasmania, Australia.

Although past research has shown a link between latitude and MS prevalence, few data have assessed the association with AAO, write the researchers. But their study "confirms the presence of a significant inverse latitudinal gradient in the onset age of MS."

The findings were published online November 3 in the Journal of Neurology, Neurosurgery, and Psychiatry.

Prognostic Significance

The investigators note that AAO may have prognostic significance when it comes to patients with MS. "Understanding what factors can influence AAO may shed light on the etiology of this complex disease, and have applications in the diagnostic process."

They evaluated 22,162 patients (70.4% women) with clinically diagnosed MS (91.5% relapsing-remitting) who were at least 16 years of age and enrolled in the international MSBase registry.

The patients were enrolled at 52 centers in Europe, North and South America, Asia Minor and South Asia, and Australia. Google maps were used to determine each study center's latitude. On the basis of each center's latitude and longitude, an ultraviolet B (UVB) variable was created for each study participant.

In addition, "AAO was defined as the year of the first symptom suggestive of inflammatory central nervous system demyelination," report the researchers. The mean AAO for the total study population was 32.3 years.

In univariable analysis, "latitude as a continuous linear factor was significantly negatively associated with AAO" (P = .01). Each 10-degree increase in latitude was linked to a 0.3-year earlier AAO. And in multivariable analysis, every 10-degree increment was associated with a 0.82-year earlier onset.

A Role for UVR?

There was also a significant association between latitude and UVB (P < .001), with multivariable analysis showing a dose-dependent relationship. In fact, those in the lowest UVB category (0.8 - 2.1 Wh/m2) had an AAO nearly 2 years earlier than that in the participants in the highest category (5.1 - 14.3 Wh/m2).

The findings suggest that UVR exposure variation may play a role in the association between latitude and AAO, note the investigators. However, "other factors such as differential timing of EBV [Epstein-Barr virus] infection and genetic background may also have a role."

Although latitude did not significantly affect differences in AAO between women and men, the full group of women did have a significantly younger AAO than the full group of men (adjusted difference, 0.43 years; P = .002).

Interestingly, there was no significant association between season/month of birth and AAO (P = .52).

Study limitations cited include no data on individual diet, use of supplements such as vitamin D, and genetic characteristics.

"Additionally, our data are limited to those MS cases of European origin and adult onset and cannot be generalized to other non-European or paediatric onset cases," write the researchers.

Still, the study results "may lead to improved understanding of MS aetiopathogenesis."

The study was funded by the MSBase Foundation, a not-for-profit organization that receives support from Merck Serono, Biogen Idec, Novartis Pharma, Bayer-Schering, Sanofi-Aventis, and BioCSL. Tao has disclosed no relevant financial relationships. Disclosures for the coauthors are in the paper.

Neuro Neurosurg Psychiatry. Published online November 3, 2016. Abstract

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