Neurophysiological Predictors of Response to Medication in Parkinson's Disease

Background: Although dopaminergic medication has been the foundation of Parkinson's disease (PD) therapy for decades, sensitive and specific therapeutic response biomarkers that allow for better treatment optimization are lacking.Objective: We tested whether the features of Transcranial Magneti...

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Autores principales:	Saša R. Filipović, Aleksandra Kačar, Sladjan Milanović, Miloš R. Ljubisavljević
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Parkinson's disease TMS paired pulse TMS cortical inhibition dopaminergic therapy personalized therapy Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/0a00036df85149208d1ed2b38c5519b9
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spelling	oai:doaj.org-article:0a00036df85149208d1ed2b38c5519b92021-11-16T06:17:15ZNeurophysiological Predictors of Response to Medication in Parkinson's Disease1664-229510.3389/fneur.2021.763911https://doaj.org/article/0a00036df85149208d1ed2b38c5519b92021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fneur.2021.763911/fullhttps://doaj.org/toc/1664-2295Background: Although dopaminergic medication has been the foundation of Parkinson's disease (PD) therapy for decades, sensitive and specific therapeutic response biomarkers that allow for better treatment optimization are lacking.Objective: We tested whether the features of Transcranial Magnetic Stimulation-based neurophysiological measures taken off-medication are associated with dopaminergic medication-induced clinical effects.Method: Motor cortex excitability [short-latency intracortical inhibition (SICI), intracortical facilitation (ICF), short-latency afferent inhibition (SAI), and input-output (IO) curve], and plasticity [paired associative stimulation (PAS) protocol] neurophysiological measures were examined in 23 PD patients off-medication. Clinical features were quantified by the motor section of the Unified Parkinson's Disease Scale (total score and lateralized total, bradykinesia, and rigidity sub-scores), and the differences between measures off-medication and on-medication (following the usual morning dose), were determined. Total daily dopaminergic medication dose (expressed as levodopa equivalent daily dose-LEDD), was also determined.Results: SICI significantly correlated with changes in lateralized UPDRS motor and bradykinesia sub-scores, suggesting that patients with stronger basal intracortical inhibition benefit more from dopaminergic treatment than patients with weaker intracortical inhibition. Also, ICF significantly negatively correlated with LEDD, suggesting that patients with stronger intracortical facilitation require less dopaminergic medication to achieve optimal therapeutic benefit. Both associations were independent of disease severity and duration.Conclusions: The results suggest variability of (patho) physiological phenotypes related to intracortical inhibitory and facilitatory mechanisms determining clinical response to dopaminergic medication in PD. Measures of intracortical excitability may help predict patients' response to dopaminergic therapy, thus potentially providing a background for developing personalized therapy in PD.Saša R. FilipovićAleksandra KačarAleksandra KačarSladjan MilanovićMiloš R. LjubisavljevićMiloš R. LjubisavljevićFrontiers Media S.A.articleParkinson's diseaseTMSpaired pulse TMScortical inhibitiondopaminergic therapypersonalized therapyNeurology. Diseases of the nervous systemRC346-429ENFrontiers in Neurology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Parkinson's disease TMS paired pulse TMS cortical inhibition dopaminergic therapy personalized therapy Neurology. Diseases of the nervous system RC346-429
spellingShingle	Parkinson's disease TMS paired pulse TMS cortical inhibition dopaminergic therapy personalized therapy Neurology. Diseases of the nervous system RC346-429 Saša R. Filipović Aleksandra Kačar Aleksandra Kačar Sladjan Milanović Miloš R. Ljubisavljević Miloš R. Ljubisavljević Neurophysiological Predictors of Response to Medication in Parkinson's Disease
description	Background: Although dopaminergic medication has been the foundation of Parkinson's disease (PD) therapy for decades, sensitive and specific therapeutic response biomarkers that allow for better treatment optimization are lacking.Objective: We tested whether the features of Transcranial Magnetic Stimulation-based neurophysiological measures taken off-medication are associated with dopaminergic medication-induced clinical effects.Method: Motor cortex excitability [short-latency intracortical inhibition (SICI), intracortical facilitation (ICF), short-latency afferent inhibition (SAI), and input-output (IO) curve], and plasticity [paired associative stimulation (PAS) protocol] neurophysiological measures were examined in 23 PD patients off-medication. Clinical features were quantified by the motor section of the Unified Parkinson's Disease Scale (total score and lateralized total, bradykinesia, and rigidity sub-scores), and the differences between measures off-medication and on-medication (following the usual morning dose), were determined. Total daily dopaminergic medication dose (expressed as levodopa equivalent daily dose-LEDD), was also determined.Results: SICI significantly correlated with changes in lateralized UPDRS motor and bradykinesia sub-scores, suggesting that patients with stronger basal intracortical inhibition benefit more from dopaminergic treatment than patients with weaker intracortical inhibition. Also, ICF significantly negatively correlated with LEDD, suggesting that patients with stronger intracortical facilitation require less dopaminergic medication to achieve optimal therapeutic benefit. Both associations were independent of disease severity and duration.Conclusions: The results suggest variability of (patho) physiological phenotypes related to intracortical inhibitory and facilitatory mechanisms determining clinical response to dopaminergic medication in PD. Measures of intracortical excitability may help predict patients' response to dopaminergic therapy, thus potentially providing a background for developing personalized therapy in PD.
format	article
author	Saša R. Filipović Aleksandra Kačar Aleksandra Kačar Sladjan Milanović Miloš R. Ljubisavljević Miloš R. Ljubisavljević
author_facet	Saša R. Filipović Aleksandra Kačar Aleksandra Kačar Sladjan Milanović Miloš R. Ljubisavljević Miloš R. Ljubisavljević
author_sort	Saša R. Filipović
title	Neurophysiological Predictors of Response to Medication in Parkinson's Disease
title_short	Neurophysiological Predictors of Response to Medication in Parkinson's Disease
title_full	Neurophysiological Predictors of Response to Medication in Parkinson's Disease
title_fullStr	Neurophysiological Predictors of Response to Medication in Parkinson's Disease
title_full_unstemmed	Neurophysiological Predictors of Response to Medication in Parkinson's Disease
title_sort	neurophysiological predictors of response to medication in parkinson's disease
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/0a00036df85149208d1ed2b38c5519b9
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Neurophysiological Predictors of Response to Medication in Parkinson's Disease

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