Upper limb motor rehabilitation impacts white matter microstructure in multiple sclerosis

Abstract

Upper limb impairments can occur in patients with multiple sclerosis, affecting daily living activities; however there is at present no definite agreement on the best rehabilitation treatment strategy to pursue. Moreover, motor training has been shown to induce changes in white matter architecture in healthy subjects. This study aimed at evaluating the motor behavioral and white matter microstructural changes following a 2-month upper limb motor rehabilitation treatment based on task-oriented exercises in patients with multiple sclerosis. Thirty patients (18 females and 12 males; age=43.3 ± 8.7 years) in a stable phase of the disease presenting with mild or moderate upper limb sensorimotor deficits were randomized into two groups of 15 patients each. Both groups underwent twenty 1-hour treatment sessions, three times a week. The "treatment group" received an active motor rehabilitation treatment, based on voluntary exercises including task-oriented exercises, while the "control group" underwent passive mobilization of the shoulder, elbow, wrist and fingers. Before and after the rehabilitation protocols, motor performance was evaluated in all patients with standard tests. Additionally, finger motor performance accuracy was assessed by an engineered glove. In the same sessions, every patient underwent diffusion tensor imaging to obtain parametric maps of fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. The mean value of each parameter was separately calculated within regions of interest including the fiber bundles connecting brain areas involved in voluntary movement control: the corpus callosum, the corticospinal tracts and the superior longitudinal fasciculi. The two rehabilitation protocols induced similar effects on unimanual motor performance, but the bimanual coordination task revealed that the residual coordination abilities were maintained in the treated patients while they significantly worsened in the control group (p=0.002). Further, in the treatment group white matter integrity in the corpus callosum and corticospinal tracts was preserved while a microstructural integrity worsening was found in the control group (fractional anisotropy of the corpus callosum and corticospinal tracts: p=0.033 and p=0.022; radial diffusivity of the corpus callosum and corticospinal tracts: p=0.004 and p=0.008). Conversely, a significant increase of radial diffusivity was observed in the superior longitudinal fasciculi in both groups (p=0.02), indicating lack of treatment effects on this structure, showing damage progression likely due to a demyelination process. All these findings indicate the importance of administering, when possible, a rehabilitation treatment consisting of voluntary movements. We also demonstrated that the beneficial effects of a rehabilitation treatment are task-dependent and selective in their target; this becomes crucial towards the implementation of tailored rehabilitative approaches.

Inpatient versus outpatient rehabilitation for multiple sclerosis patients: effects on disability and quality of life

“…To this aim, we believe that active rehabilitation, based on voluntary task-oriented exercises, could determine beneficial effects in terms of functional independence. In agreement with this assertion, Bonzano et al demonstrated that rehabilitation treatment based on voluntary movements may contribute to preserve the white matter integrity in the corpus callosum and corticospinal tracts and to maintain the coordination ability; such benefits were not observed in control group [27]. These findings confirms the hypothesis that the sensorimotor deficits observed in PwMS over the disease course could be mainly due to the progression of white matter damage and that neurorehabilitation may attenuate this neurodegenerative process [37,38].…”

“…The rehabilitative treatment was tailored to the specific individual needs and was planned on volitional tasks mainly focused on motor performances. We kept into account the assertion that potential changes are specific to a given task and not a general effect of any training [27,28]. PwMS were treated according to a protocol based on voluntary exercises for neuromuscular control, aimed to improve muscle strength of both upper and lower limbs, propioceptive sensibility, stability and coordination for balance.…”

Neurorehabilitation in Persons with Multiple Sclerosis: Scientific Basis and Options of Treatment

“…In active group the bimanual coordination task remained stable, while worsened in passive group. Accordingly in fMRI, passive group, but not active one, showed reduced fractional anisotropy and increased radial diffusivity of corticospinal tracts and corpus callosum [63].…”

Effect of Comorbidities on Outcomes of Neurorehabilitation Interventions in Multiple Sclerosis

“…Four of seven studies (57%) had active comparison groups, [19][20][21][22] and the remaining three had usual care 23,24 or no intervention control groups. 25 The number of intervention sessions ranged from 10 25 to 24 24 over 2 25 to 8 24 weeks.…”

“…20,21,24,25 The most commonly excluded comorbidities were cognitive impairment (n = 4, 57%) 20,21,24,25 and psychiatric disorders (n = 3, 43%) 20,21,24 (Figure 3). These psychiatric disorders were not identified.…”