Objective: The aim of this study was to detect alterations within GABAergic, glutamatergic and cholinergic circuitries in Parkinson’s Disease (PD) patients, including de Novo PD (naïve), and prodromal Parkinson’s disease, namely rapid eye movement (REM) sleep behaviour disorder (iRBD) patients.

Background: Most of previous studies found changes of both SICI and ICF in patients with PD suggesting a disinhibition and hypofacilitation of the motor cortex [1-2]. To date, conversely very little is known on TMS studies [3] carried out in prodromal and de novo Parkinson disease patients. 

Method: The study enrolled consecutive patients with PD, polysomnography-confirmed RBD and age-matched healthy controls. Each subject underwent an extensive motor and cognitive assessment and a TMS paired-pulse protocol evaluating GABA_Aergic circuits (short interval intracortical inhibition, SICI), glutamatergic circuits (intracortical facilitation, ICF) and cholinergic circuits (short latency afferent inhibition, SAI).

Results: Ninety subjects entered the study, namely 60 PD patients (including 30 drug-naïve 30 treated PD), 12 iRBD and 18 age-matched healthy controls (HC). Compared to HC, SICI and ICF resulted significantly reduced in PD (both drug-naïve and treated). iRBD subjects exhibited impaired SICI, whereas ICF resulted decreased in 6 increased in 6 subjects. SAI showed significant reduction in iRBD compared to both PD patients and HC. No differences between HC and PD patients. ICF values in PD-naïve (and not in treated PD) correlated with rigidity subscore of UPDRS III (r=0.563, p=0.006) and total UPDRS III (r=0.482, p=0.011).

Conclusion: GABAergic and glutamatergic alterations are a prominent feature of PD from prodromal stages. The differences observed in ICF patterns and the cholinergic impairment in iRBD might indicate divergent risk of conversion to PD or dementia with Lewy bodies (DLB). The inverse correlation between glutamatergic alterations and motor severity in drug-naïve PD might indicate ongoing compensations mechanisms and should be evaluated in ongoing longitudinal studies.

References: [1] Leon-Sarmiento FE, et al. Novel mechanisms underlying inhibitory and facilitatory transcranial magnetic stimulation abnormalities in Parkinson’s disease. Arch Med Res. 2013;44(3):221–228.
[2] Lefaucheur JP. Motor cortex dysfunction revealed by cortical excitability studies in Parkinson’s disease: influence of antiparkinsonian treatment and cortical stimulation. Clin Neurophysiol. 2005;116(2):244–253.
[3] Nardone R, et al. Functional evaluation of central cholinergic circuits in patients with Parkinson’s disease and REM sleep behavior disorder: a TMS study. J Neural Transm (Vienna). 2013;120(3):413–422

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MDS Abstracts - https://www.mdsabstracts.org/abstract/inhibitory-and-facilitatory-alterations-in-prodromal-and-de-novo-parkinsons-disease/