title: 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.
authors.affiliation: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy; Magnetic Resonance Research Centre on Nervous System Diseases, University of Genoa, Genoa, Italy. Electronic address: laura.bonzano@unige.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Bonzano
authors.affiliation: Scientific Research Area, Italian Multiple Sclerosis Foundation (FISM), Genoa, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Tacchino
authors.affiliation: Scientific Research Area, Italian Multiple Sclerosis Foundation (FISM), Genoa, Italy.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Brichetto
authors.affiliation: Magnetic Resonance Research Centre on Nervous System Diseases, University of Genoa, Genoa, Italy; Department of Health Sciences, Biostatistics Unit, University of Genoa, Genoa, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Roccatagliata
authors.affiliation: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy; Department of Experimental Medicine, Section of Human Physiology and Centro Polifunzionale di Scienze Motorie, University of Genoa, Genoa, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Dessypris
authors.affiliation: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Feraco
authors.affiliation: AISM Rehabilitation Service, Italian Multiple Sclerosis Society, Genoa, Italy.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Lopes De Carvalho
authors.affiliation: Department of Physiopathology, Experimental Medicine and Public Health, University of Siena, Siena, Italy.
authors.forename: Mario A
authors.initials: MA
authors.lastname: Battaglia
authors.affiliation: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy; Magnetic Resonance Research Centre on Nervous System Diseases, University of Genoa, Genoa, Italy.
authors.forename: Giovanni L
authors.initials: GL
authors.lastname: Mancardi
authors.affiliation: Department of Experimental Medicine, Section of Human Physiology and Centro Polifunzionale di Scienze Motorie, University of Genoa, Genoa, Italy. Electronic address: marco.bove@unige.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Bove
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology* / Q000534:rehabilitation*; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D011597:Psychomotor Performance / Q000502:physiology*; D011712:Pyramidal Tracts / Q000473:pathology; D034941:Upper Extremity / Q000502:physiology
keywords: Diffusion tensor imaging; Motor rehabilitation; Multiple sclerosis; Upper limb; Voluntary movements; White matter