Abnormal cortical facilitation and L-dopa-induced dyskinesia in Parkinson's disease.
Glutamate
Parkinson's disease
SICF
Safinamide
TMS
l-dopa-induced dyskinesia
Journal
Brain stimulation
ISSN: 1876-4754
Titre abrégé: Brain Stimul
Pays: United States
ID NLM: 101465726
Informations de publication
Date de publication:
Historique:
received:
20
03
2019
revised:
05
06
2019
accepted:
07
06
2019
pubmed:
21
6
2019
medline:
25
2
2020
entrez:
21
6
2019
Statut:
ppublish
Résumé
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). 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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 31217080
pii: S1935-861X(19)30263-3
doi: 10.1016/j.brs.2019.06.012
pii:
doi:
Substances chimiques
Benzylamines
0
Levodopa
46627O600J
safinamide
90ENL74SIG
Alanine
OF5P57N2ZX
Types de publication
Journal Article
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
1517-1525Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.