AAN 2026 | Baseline characteristics to predict response to aerobic training and physical rehabilitation in MS

We know that there is a certain heterogeneity in individual response to physical rehabilitation in MS, and this may be due to various factors regarding how rehabilitation is delivered, but it may also depend on baseline characteristics of MS patients. So in this study, our aim was to examine whether these baseline characteristics of MS patients, including demographic, clinical, and MRI variables, could predict response to aerobic training and to physical rehabilitation in general. So we had 88 MS patients, which were randomized into two groups. One performed a moderate-intensity aerobic training, while the other group performed another non-specific motor program, which included stretching, mobilization, and balanced exercises. Before all this, all patients underwent clinical assessment, which included rating of their EDSS score, calculation of their peak oxygen consumption, and also evaluation of walking speed, walking endurance, and fatigue. So all subjects also underwent MRI acquisition of flair, T1-weighted, diffusion-weighted, and functional MRI sequences, from which we extracted different metrics related to lesion volume, brain volumetrics, cortical thickness, diffusivity metrics, and resting state functional connectivity metrics. So for each of these categories, we focused on measures that could be related to motor function. So for example, those involving the primary motor cortex, the corticospinal tract, or the sensory motor network. But we also included some control measures unrelated to motor function to test whether the possible motor-related findings were specific or not. So after the two-month training period, patients were categorized in responders and non-responders based on the improvement on the six-minute walking test. And moving to the results, the aerobic group showed a higher response rate compared to the non-aerobic group, but the difference was not statistically significant. However, when looking at baseline predictors of response, among all the demographic, clinical, and various MRI variables, in both groups, the only significant predictors were measures of diffusivity, meaning that reflecting microstructural integrity of white matter tracts, and in particular, three specific white matter tracts, which were the corticospinal tract, the middle, and the superior cerebellum. Then given the lack of differences between the two groups, we also performed an additional analysis considering all MS patients as a combined group. And also in this case, all the significant predictors were measures of fractional anisotropy and mean diffusivity of these three white matter tracts. So in summary, we did not find differences between the two training strategies, but what we found is that the improvements following physical training in MS patients were always linked to baseline microstructural integrity in these specific white matter tracts involved in motor function, regardless of the rehabilitation strategy used. And this supports the idea that a less severe microstructural white matter damage may enable a greater brain plasticity and adaptive changes in response to exercise, and also highlights the importance of starting rehabilitation early in the disease, and it highlights also the potential of advanced neuroimaging techniques in helping to identify patients who are most likely to benefit from physical rehabilitation.

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