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Objectives: Skill acquisition after motor training involves synaptic long-term potentiation (LTP) in primary motor cortex (M1). In multiple sclerosis (MS), LTP failure ensuing from neuroinflammation could contribute to worsen clinical recovery. We therefore addressed whether practice-dependent plasticity is altered in MS., Methods: Eighteen relapsing-remitting (RR)-MS patients and eighteen healthy controls performed 600 fast abductions of index finger in 30 blocks of 20 movements. Before and after practice, transcranial magnetic stimulation (TMS) was delivered over the hot spot of the trained first dorsal interosseous muscle. Movements kinematics, measures of cortical excitability, and the input/output curves of motor evoked potentials (MEPs) were assessed., Results: Kinematic variables of movement improved with practice in patients and controls to a similar extent, although patients showed lower MEPs amplitude increase after practice. Practice did not change the difference in resting motor threshold values observed between patients and controls, nor did modulate short-interval intracortical inhibition. Clinical/radiological characteristics were not associated to practice-dependent effects., Conclusions: Practice-induced reorganization of M1 is altered in non-disabled RR-MS patients, as shown by impaired MEPs modulation after motor learning., Significance: These findings suggest that in RR-MS physiological mechanisms of practice-dependent plasticity are altered., (Copyright © 2019. Published by Elsevier B.V.)

Objective: we investigated the effect of anodal transcranial direct current stimulation (tDCS) applied over the pharyngeal motor area in dysphagia associated with multiple sclerosis (MS)., Methods: Eighteen MS patients with dysphagia associated with brainstem involvement were randomized to receive either "real" or "sham" tDCS., Primary Outcome: The Penetration/Aspiration Scale (PAS)., Secondary Outcomes: changes in electromyographic (EMG) parameters and pharyngeal cortical motor evoked potentials (MEPs). Patients were evaluated at baseline (T 0 ), at the end of 5-session cycle of tDCS stimulations (T 1 ), after two (T 2 ), and four (T 3 ) weeks., Results: the PAS values were significantly lower in the active group than in "sham" group at T 1 , and at T 3 . Over the post-stimulation periods, PAS significantly improved only in the "real" group. As regards the secondary outcomes, we observed a statistically significant difference between the 2 groups only in the MEPs amplitude at T 1 . The comparison between baseline and each of the post-stimulation times showed significant differences only of the "real" group across all the secondary parameters., Conclusions: Our findings support a beneficial effect of anodal tDCS applied to the pharyngeal motor cortex in MS-associated dysphagia., Significance: Considering its safety and efficacy, tDCS may represent an important resource in MS-associated dysphagia., (Copyright © 2019. Published by Elsevier B.V.)

Multiple sclerosis (MS) is an inflammatory immune-mediate disorder of the central nervous system (CNS), primarily affecting the myelin sheath and followed by neurodegeneration. Synaptic alterations are emerging as critical determinants of early neurodegeneration in MS. Inflammation-induced alterations of synaptic transmission and plasticity have been investigated in vitro and also in human MS using transcranial magnetic stimulation (TMS) techniques. Specific inflammatory cytokines alter glutamatergic and GABAergic transmission, resulting in synaptic hyperexcitability. In both experimental autoimmune encephalomyelitis (EAE) and MS, excitotoxic damage and neurodegeneration are found even in the early phases of disease, conversely inflammation persists in the progressive phases. Inflammatory cytokines also affect synaptic plasticity, as both long-term potentiation (LTP) and long-term depression (LTD) are altered in EAE and in MS patients. In particular, inflammation profoundly subverts plasticity and influence both clinical recovery after a relapse and disease course. Regulation of neuronal activity by cytokines plays important roles in the neuro-immune crosstalk involved in inflammation-associated excitotoxic neuronal damage, and in the chance of developing compensatory plasticity. Innate and adaptive immunity interact with the CNS in MS, in line with the concept that cytokines and chemokines, in concert with neurotransmitters and neuropeptides, represent a major communication system in the CNS., (Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)