Long-term changes in short-interval intracortical facilitation modulate motor cortex plasticity and L-dopa-induced dyskinesia in Parkinson's disease.

Andrea Guerra, Francesco Asci, Alessandro Zampogna, Valentina D'Onofrio, Antonio Suppa, Giovanni Fabbrini, Alfredo Berardelli

Brain stimulation 2022 Jan-Feb

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Abnormal glutamatergic neurotransmission in the primary motor cortex (M1) contributes to Parkinson's disease (PD) pathophysiology and is related to l-dopa-induced dyskinesia (LID). We previously showed that short-term treatment with safinamide, a monoamine oxidase type-B inhibitor with anti-glutamatergic properties, improves abnormally enhanced short-interval intracortical facilitation (SICF) in PD patients. To examine whether a long-term SICF modulation has beneficial effects on clinical measures, including LID severity, and whether these changes parallel improvement in cortical plasticity mechanisms in PD. We tested SICF in patients with and without LID before (S0) and after short- (14 days - S1) and long-term (12 months - S2) treatment with safinamide 100 mg/day. Possible changes in M1 plasticity were assessed using intermittent theta-burst stimulation (iTBS). Finally, we correlated safinamide-related neurophysiological changes with modifications in clinical scores. SICF was enhanced at S0, and prominently in patients with LID. Safinamide normalized SICF at S1, and this effect persisted at S2. Impaired iTBS-induced plasticity was present at S0 and safinamide restored this alteration at S2. There was a significant correlation between the degree of SICF and the amount of iTBS-induced plasticity at S0 and S2. In patients with LID, the degree of SICF at S0 and S2 correlated with long-term changes in LID severity. Altered SICF contributes to M1 plasticity impairment in PD. Both SICF and M1 plasticity improve after long-term treatment with safinamide. The abnormality in SICF-related glutamatergic circuits plays a role in LID pathophysiology, and its long-term modulation may prevent LID worsening over time. Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Andrea Guerra, Francesco Asci, Alessandro Zampogna, Valentina D'Onofrio, Antonio Suppa, Giovanni Fabbrini, Alfredo Berardelli. Long-term changes in short-interval intracortical facilitation modulate motor cortex plasticity and L-dopa-induced dyskinesia in Parkinson's disease. Brain stimulation. 2022 Jan-Feb;15(1):99-108