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

doi:10.1016/j.brs.2021.11.016

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

Brain Stimul. 2022 Jan-Feb;15(1):99-108. doi: 10.1016/j.brs.2021.11.016. Epub 2021 Nov 22.

Authors

Andrea Guerra¹, Francesco Asci¹, Alessandro Zampogna², Valentina D'Onofrio², Antonio Suppa³, Giovanni Fabbrini³, Alfredo Berardelli⁴

Affiliations

¹ IRCCS Neuromed, Pozzilli, IS, Italy.
² Department of Human Neurosciences, Sapienza University of Rome, Italy.
³ IRCCS Neuromed, Pozzilli, IS, Italy; Department of Human Neurosciences, Sapienza University of Rome, Italy.
⁴ IRCCS Neuromed, Pozzilli, IS, Italy; Department of Human Neurosciences, Sapienza University of Rome, Italy. Electronic address: alfredo.berardelli@uniroma1.it.

PMID: 34823038
DOI: 10.1016/j.brs.2021.11.016

Abstract

Background: 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.

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Glutamatergic transmission; Parkinson's disease; Plasticity; Safinamide; Short-interval intracortical facilitation; l-dopa-induced dyskinesias.

MeSH terms

Dyskinesias*
Evoked Potentials, Motor / physiology
Humans
Levodopa / adverse effects
Motor Cortex* / physiology
Parkinson Disease* / drug therapy
Transcranial Magnetic Stimulation

Substances

Levodopa