November 13, 2017
"We have shown that after just 3 months of including a moderate aerobic exercise program into their schedules, MS patients had both functional and structural reorganization of brain networks. This is supportive of the idea that there is a role for exercise as a therapeutic intervention in MS," lead study author, Jan-Patrick Stellmann, MD, University of Hamburg, Germany, told Medscape Medical News.
The study was presented at the 7th Joint European Committee for Treatment and Research in Multiple Sclerosis-Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2017 meeting.
"Our study is looking at how this may occur in the brain. We believe this is a feasible approach to monitor the effects of exercise and maybe other interventions on the brain. Changes in connectivity in brain networks might be a suitable surrogate endpoint for a clinical outcome."
He added: "This was a mechanistic study to investigate how far an exercise intervention might influence the organization of the brain network of MS patients. We found that just after 3 months the connectivity — how well the nodes of the brain network are connected to each other — increases, and this is observed for the structure as well as the function. The main conclusion is that exercise might repair or improve connectivity in brain of MS patients."
The study involved 57 patients with relapsing-remitting MS (RRMS) (69% female; mean age, 39 years; median Expanded Disability Status Scale score, 1.5) who were randomly assigned 1:1 to a waitlist control group (n = 27) or a supervised and individualized aerobic exercise program (n = 30). There was also a healthy controls reference group, but these persons did not participate in the exercise program.
The exercise group engaged in two or three weekly exercise sessions (a median of 22 sessions of 20 to 40 minutes' duration over 3 months) in the form of individualized training. All patients underwent baseline training with a fitness instructor, who developed a medium-intensity personal training plan for each patient to increase stepwise over the 3-month period.
The primary endpoint of the study was cognitive function, with patients undergoing cognitive testing at baseline and after 3 months. This testing showed no difference between the two groups.
Dr Stellmann pointed out that the patients included did not have much cognitive impairment at baseline, "so it was perhaps unrealistic to expect much change in just 3 months."
All patients also underwent regular and functional MRI of the brain at baseline and at 3 months, with particular focus on brain networks.
"We know the brain is organized as a network with different regions within the cortex or gray matter interconnected by fibers," Dr Stellmann explained. "We reconstructed a computational model of these structural networks to measure physical and structural connectivity showing how the regions work together."
This was done based on wavelet correlations from the BOLD time series, and mean fractional anisotropy of tracks derived from probabilistic tractography for structural networks was used.
"This is very preliminary research," he added. "This is the first time this model has been used in a randomized controlled trial. We need further data to see how specific and sensitive it is for changes, and if it is a marker for neurodegeneration or neurorepair."
The researchers' results showed that compared with healthy controls, "the brain network was heavily reorganized in MS patients, with a loss of structural connectivity in several regions of the brain, but increased functional connectivity," he said. "It appears that MS patients try to compensate for this structural reorganization by having higher functional connectivity — they work harder to try and make up for the structural changes."
After 3 months, the waiting group showed a decrease in functional connectivity (P = .018) pronounced in hubs, while functional connectivity increased in the exercise group globally (P = .002).
The researchers observed a similar effect in structural connectomes, Dr Stellman said. "The waiting group remained unchanged after 3 months and the exercise group showed a globally increased structural connectivity (P = .002)," he said. "Moreover, we observed an increased clustering (ie, higher local connectivity) in the exercise group within 3 months (P < .001), again predominantly in hub regions."
He said the next step is to investigate longitudinal changes for these networks: How do patients with MS behave over time? "We also need to establish links to clinical parameters, such as cognitive performance, real-life mobility, or quality of life."
The study was included in a summary of clinical highlights of the ECTRIMS/ACRTIMS meeting. In the summary, Robert Fox, MD, Cleveland Clinic, Ohio, said, "Unfortunately the primary outcome in this study was not met — there was no effect on learning and memory tests — but we did learn about some innovative imaging methodologies to try and understand how exercise may have an impact on the brain."
Dr Stellmann receives research funding from Deutsche Forschungsgemeinschaft and grants from Biogen outside the submitted work.