Multiple sclerosis: Pinpointing risk factors

Image Credit: ZEISS Microscopy via Flickr.

Because Scotland is of the countries with the highest incidence of multiple sclerosis (MS) in the world, many Scottish researchers are trying to figure out how it develops and working towards new treatments. A research group based at the University of Edinburgh has just published a new Scottish Multiple Sclerosis Register (SMSR) in the Journal of Neurology, which may bring us a step closer to identifying environmental and lifestyle causes of this chronic and debilitating disease.

MS is caused by aberrant activation of the immune system, leading it to attack the cells that wrap around your nerve cells to provide support and electrical insulation. As a result of inflammation, these cells are stripped away, leaving your nerves bare (literally speaking) and as a consequence, MS can cause your nervous system to malfunction. Depending on the diseased area, patients can experience difficulty walking, tingling or numb sensations in limbs, visual impairments, memory problems, or bladder dysfunction, amongst many other symptoms. Typically, MS occurs in a waxing and waning manner and can be either relapsing (returning with the same disease severity) or progressive (gradually getting worse). However, it is a chronic condition that affects over 11,000 people in Scotland alone and so far, there is no cure. We can only treat the symptoms.

A big step in the identification of factors that underlie diseases is to study affected populations and identify common features, such as genetic heritage or environmental factors; this type of research is known as epidemiology. We know from previous research that MS is strongly linked to environmental factors; there is a global latitude gradient, with countries around the equator exhibiting lower MS diagnoses than northern countries. 

This latitude gradient has typically been ascribed to the decreased exposure to sunlight compared with more southern regions, resulting in a deficiency of vitamin D. It is not precisely known how vitamin D protects from MS, but recent research – also from the University of Edinburgh – showed that vitamin D can prevent excessive inflammation of cells involved in MS in cell culture. Interestingly, Northern Scandinavia and Greenland show an inverse gradient of MS compared to other Northern-region countries. This may be ascribed to a high percentage of indigenous Sami (Scandinavia) and Inuit (Greenland) people in these regions. While vitamin D is typically synthesised in the skin after UV light (i. e., sun) exposure, some people have evolved to substitute vitamin D through a diet rich in fish and liver oil. Also, vegetables (such as UV-irradiated mushrooms) contain slightly different versions of vitamin D, however it is less efficient to take up via this route. Sami and Inuit people have lower frequencies of vitamin D deficiency and have often been termed “resistant” to MS. Similarly, although there is an overall high incidence of MS in Norway, inland farming villages have a higher incidence than coastal fishing villages, which may again stem from the richer diet in vitamin D. Therefore, there seems to be a pretty clear link between vitamin D and the development of MS. 

Coming back to Scotland, the new SMSR published by Patrick Kearne and colleagues confirms the results of previous studies showing that Scotland has a high incidence of MS. Another aim of the study was to assess inter-regional variability in MS diagnoses; surprisingly, there was a large inter-regional variability partially counterintuitive when only factoring in the global latitude gradient. In other words, while it was expected that MS incidence would gradually increase the more North you look in Scotland, this was not strictly the case. For example, Orkney has a three times higher incidence of MS than the Scottish borders – in accordance with the latitude gradient, – but the more northern Shetland has a lower incidence than Orkney. This may stem from the fact that Shetland has distinct genetic (and partially different) cultural heritage. On the mainland, Tayside had the highest incidence of MS. Overall, the latitude gradient does not seem to explain all of the inter-regional variability in Scotland. Another factor that is known to be strongly linked to development of MS is gender. The new SMSR confirms that women have a higher incidence of developing MS, and in combination with inter-regional variability, this can account for substantially different risks of MS. For example, a woman on Orkney has a 19.9/1000 lifetime risk of getting MS, while a man from the borders has 1.6/1000 lifetime risk, translating to 1/50 risk for a woman from Orkney developing MS as opposed to 1/600 for a man from the Borders.

However, this MS register and many other studies show that we don’t know it all yet. Other (as of yet unknown) factors are probably also crucial for the development of MS. Recent studies found that smoking, adolescence obesity, night work, and previous Epstein-Barr virus (mono) infections all increase the risk for developing MS. Alcohol use and coffee consumption appear to lower the risk of MS, although we don’t know why. Interestingly, much research so far has previously shown that many risk factors predominantly influence one certain period in life: adolescence. Therefore, MS prevention may need to start at an early age to avoid risk factors such as vitamin D deficiency, smoking, and obesity. 
The new SMSR is an important dataset that future investigation of environmental and lifestyle factors contributing to MS development in Scotland can build on, and may ultimately lead to the identification of novel therapeutic or preventative strategies for MS. In the meantime, vitamin D supplements may benefit anyone in the northern latitudes, not only for lowering MS risk but also to target disorders such as seasonal depression. And, as usual, no smoking and regular exercise to prevent obesity is also a step in the right direction. Hopefully in the years to come, further research, possibly even from Scotland, may lead us from studying MS to curing it.

This article was written by Chiara Herzog and edited by Miles Martin.

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