Background and purpose: Limited research has been dedicated to upper limb (UL) rehabilitation in progressive multiple sclerosis (PMS). The objective in this pilot study was to investigate the effect of task-oriented UL rehabilitation in PMS and to perform explorative analyses of the magnetic resonance imaging (MRI) correlates of changes in motor performance. Methods: Twenty-six PMS patients with mild UL impairment were prospectively enrolled and randomized into two groups: an active treatment group (ATG, n = 13) and a passive treatment group (PTG, n = 13). At baseline and after training, patients underwent MRI scans with structural and functional imaging and were evaluated with the action research arm test, the nine-hole peg test, the ABILHAND scale and the modified fatigue impact scale (MFIS). Measures of motor finger performance were obtained by engineered glove measuring. Results: After rehabilitation, the ATG improved in several finger motor tasks (0.001 ≤ P ≤ 0.03, 0.72 ≤ Cohen's d ≤ 1.22) and showed reduced MFIS scores compared with the PTG (P = 0.03). The ATG showed increased functional connectivity within the cerebellar and thalamic resting state networks compared with the PTG (P < 0.05). Correlations were found between several measures of motor improvement and thalamic and sensorimotor networks (0.87 ≤ r ≤ 0.93, 0.001 ≤ P ≤ 0.03). No changes in cerebral volumes and diffusion tensor imaging derived measures were detected. Conclusions: Progressive multiple sclerosis patients with mild UL dysfunction benefit from task-oriented UL rehabilitation, which seems to be more efficient than simple passive mobilization. Despite a high burden of disability and brain damage, functional adaptive capacities seem to be preserved, thus providing a rationale for the use of rehabilitative treatments in late PMS.
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