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.

Abnormal cortical facilitation and L-dopa-induced dyskinesia in Parkinson's disease / Guerra, Andrea; Suppa, Antonio; D'Onofrio, Valentina; DI STASIO, Flavio; Asci, Francesco; Fabbrini, Giovanni; Berardelli, Alfredo. - In: BRAIN STIMULATION. - ISSN 1935-861X. - (2019). [10.1016/j.brs.2019.06.012]

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

Andrea Guerra;Antonio Suppa;D'ONOFRIO, VALENTINA;Flavio Di Stasio;Francesco Asci;Giovanni Fabbrini;Alfredo Berardelli
2019

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.
Parkinson's disease, SICF, Glutamate, l-dopa-induced dyskinesia, TMS, Safinamide
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Abnormal cortical facilitation and L-dopa-induced dyskinesia in Parkinson's disease / Guerra, Andrea; Suppa, Antonio; D'Onofrio, Valentina; DI STASIO, Flavio; Asci, Francesco; Fabbrini, Giovanni; Berardelli, Alfredo. - In: BRAIN STIMULATION. - ISSN 1935-861X. - (2019). [10.1016/j.brs.2019.06.012]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1291192
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