Abnormal cortical facilitation and L-dopa-induced dyskinesia in Parkinson's disease

Andrea Guerra, Antonio Suppa, Valentina D'Onofrio, Flavio Di Stasio, Francesco Asci, Giovanni Fabbrini, Alfredo Berardelli

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Animal models of Parkinson's Disease (PD) demonstrated increased facilitatory cortico-striatal activity, reflecting overactive glutamatergic neurotransmission and contributing to the pathophysiology of l-dopa induced dyskinesias (LIDs).

OBJECTIVE: To assess different facilitatory intracortical circuits in the primary motor cortex (M1) in patients with PD and LIDs by means of a combination of transcranial magnetic stimulation (TMS) protocols.

METHODS: We tested the Input/Output (I/O) curve, intracortical facilitation (ICF) and short-interval intracortical facilitation (SICF) at baseline (T0), 'OFF' and 'ON' state, in 20 PD patients with LIDs. The same parameters were examined after 2 weeks of chronic intake of 50 mg (T1) and 100 mg/day (T2) of safinamide. Finally, we tested SICF in a further group of patients without LIDs.

RESULTS: At T0, patients with LIDs showed increased I/O curve steepness, which was partly ameliorated by l-dopa. These patients also had normal ICF, and abnormally increased SICF, which did not change with l-dopa. Safinamide improved the I/O curve both at T1 and T2, it reduced SICF at T1 and normalized this measure at T2. In patients with PD and LIDs, SICF correlated with the severity of dyskinesia. In patients without LIDs, SICF was less prominently abnormal and responsive to l-dopa.

CONCLUSIONS: Patients with PD and LIDs have abnormal cortical facilitation, possibly suggesting overactive glutamatergic neurotransmission in specific circuits within M1. Although not responsive to l-dopa, this dysfunction is restored by the anti-glutamatergic properties of safinamide 100 mg. The results suggest that the abnormal cortical facilitation in M1 contributes to the pathophysiology of LIDs.

Original languageEnglish
Pages (from-to)1517-1525
Number of pages9
JournalBrain Stimulation
Volume12
Issue number6
DOIs
Publication statusPublished - Jun 21 2019

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