MS outliers are pwMS that are different from all other people diagnosed with the disease. Being an outlier could go both ways. Some pwMS develop significant disability very short after being diagnosed while others live with the disease for decades and are still out and about. The problem is we cannot reliably predict the disability trajectory of pwMS at diagnosis. Observations in big groups of untreated pwMS have shown that male gender and older age at onset might be unmodifiable negative prognostic factors. Modifiable lifestyle factors such as smoking and obesity have also been associated with a more aggressive disease course. It’s no rocket science that people who are smoking and obese also very often do not sufficiently exercise. However, the ‘exercise’ factor has often been neglected in observational cohorts or experimental research.
Fortunately, Brian Lozinski and V Wee Yong have summarised what we do know about the effects of exercise on the MS brain in an enlightening review.
- The highlights of the review in the animal model of MS:
In a pivotal study, the spinal cords of mice were exposed to lysolecithin which causes acute toxic demyelination after which the brain repair mechanisms (= oligodendrocyte precursor cells) become active and induce remyelination. In these mice, running wheel activity (= a treadmill for mice) activated the PPAR gamma co-activator-1α (PGC1α) within oligodendrocyte progenitor cells and increased the number of remyelinated axons, along with thicker myelin sheaths, compared to sedentary controls. Furthermore, the therapeutic effect of exercise was facilitated by a remyelinating drug, clemastine. In mice following the “MedXercise” protocol (running wheel + clemastine), there were more surviving axons after lysolecithin demyelination compared to exercise or clemastine alone groups.
In addition, many other studies in MS animal models showed that exercise reduces clinical severity scores, renders immune cells less pro-inflammatory and improves the integrity of the blood-brain-barrier allowing for less pro-inflammatory cells to invade the brain. Potentially the timing of exercise could be important, with exercising soon after a demyelinating event having more impact in terms of remyelination than weeks later.
- The highlights of the review in pwMS:
The evidence in humans is more indirect and does not involve remyelinating agents. In healthy individuals, there was a compelling association between piano practice and the integrity of the white matter tracts translating into more high level performances. In pwMS, several studies documented an impact of exercise on MRI measures. For example, a 24-week randomised controlled cross-over trial comparing progressive resistance training (= e.g. lifting weights) and self-guided physical activity with no training showed that brain volume change differed between groups and there were higher absolute cortical thickness values in several brain regions in the exercise group. There was no consensus among the different studies regarding the type of exercise and the benefits of exercise are most likely transient if the program is not maintained.
In summary, we need more human data to link exercise, brain function and repair. Moreover, it would be very interesting to know how pwMS on treatments such as ocrelizumab do vs. pwMS on ocrelizumab + an exercising program. Of note, all this emerging evidence comes on top of the fact that exercise has been clearly linked with less fatigue, less depression and anxiety, better cognition and higher mobility, and thus becoming an MS outlier in the most positive sense. The official advise for pwMS is to engage in 150-300 minutes of medium-vigourous exercise per week (i.e. increased respiratory rate and perspiring). As we all know from last week, the doorstep mile is the most difficult one. For anyone struggling to metaphorically get out of the door, I wanted to add the following advice:
- Do something you like to do
- Create a facilitating micro-environment: Put exercising in your agenda? Schedule exercising the day beforehand? Put your hiking shoes already next to the door? Rise and shine in a new sports outfit? For people working from home: Feel free to wear your sports outfit all-day long until you take the doorstep mile (some sports gear looks very professional during zoom meetings ;-))
- Multitask: Watching your favourite Netflix show is definitely compatible with exercising on a stationary bike? Running with an audiobook (warning: only if you wear bone-conducting headphones!) Hiking and listening to your favourite podcast? Taking one stop earlier on the subway to work and walk the remainder of the trajectory? Commuting by bike?
- Make it social: Tell other people about your ambitions, you will notice you get a lot of support and some people might even join!
And remember: we are all outliers, and that’s a good thing!
Brian M Lozinski 1, V Wee Yong 1Affiliations expand
- PMID: 33124511
- DOI: 10.1177/1352458520969099
While people with multiple sclerosis (PwMS) historically were advised to avoid physical activity to reduce symptoms such as fatigue, they are now encouraged to remain active and to enlist in programs of exercise. However, despite an extensive current literature that exercise not only increases physical well-being but also their cognition and mental health, many PwMS are not meeting recommended levels of exercise. Here, we emphasize the impact and mechanisms of exercise on functional and structural changes to the brain, including improved connectome, neuroprotection, neurogenesis, oligodendrogenesis, and remyelination. We review evidence from animal models of multiple sclerosis (MS) that exercise protects and repairs the brain, and provide supportive data from clinical studies of PwMS. We introduce the concept of MedXercise, where exercise provides a brain milieu particularly conducive for a brain regenerative medication to act upon. The emphasis on exercise improving brain functions and repair should incentivize PwMS to remain physically active.
Keywords: Exercise; magnetic resonance imaging; neuroprotection; oligodendrocytes; remyelination; repair.