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NEUROLOGY 2009;73:113-119
© 2009 American Academy of Neurology

Cerebellar magnetic stimulation decreases levodopa-induced dyskinesias in Parkinson disease

G. Koch, MD, PhD, L. Brusa, MD, PhD, F. Carrillo, MD, E. Lo Gerfo, PsyD, S. Torriero, PsyD, M. Oliveri, MD, PhD, P. Mir, MD, PhD, C. Caltagirone, MD and P. Stanzione, MD

From the Clinica Neurologica (G.K., M.O., C.C., P.S.), Dipartimento di Neuroscienze, Università di Tor Vergata, Rome, Italy; Fondazione Santa Lucia IRCCS (G.K., E.L.G., S.T., C.C., P.S.), Rome, Italy; UOC Neurologia (L.B.), Ospedale S. Eugenio, Rome, Italy; and Unidad de Trastornos del Movimiento (F.C., P.M.), Servicio de Neurología y Neurofisiología Clínica, Hospital Universitario Virgen del Rocío, CIBERNED, Seville, Spain.

Address correspondence and reprint requests to Dr. Giacomo Koch, Laboratorio di Neurologia Clinica e Comportamentale Fondazione Santa Lucia, IRCCS Via Ardeatina 306 00179 Roma, Italy g.koch{at}hsantalucia.it; giakoch{at}libero.it.

Background: The neural mechanisms and the circuitry involved in levodopa-induced dyskinesia (LID) are still partially obscure. LID can be considered the consequence of an abnormal pattern or code of activity that originates and is conveyed from the basal ganglia to the thalamus and the cortical motor areas. However, not only striatothalamocortical motor circuits but also other interconnected pathways could be implicated in its pathogenesis.

Methods: In a series of experiments, we applied repetitive transcranial magnetic stimulation (rTMS) over the lateral cerebellum in a group of patients with advanced Parkinson disease, to investigate whether modulation of cerebellothalamocortical circuits by means of rTMS may result in a modification of a dyskinetic state induced by levodopa ingestion.

Results: We found that a single session of cerebellar continuous theta burst stimulation (cTBS) was capable of transiently reducing LID. In the same patients, we observed that cerebellar cTBS changed the profile of activation of intracortical circuits in the contralateral primary motor cortex. Cerebellar cTBS reduced short intracortical inhibition and increased long intracortical inhibition, inducing a cortical reorganization that is associated with a reduction of LID. Furthermore, in another experiment, we observed that a 2-week course of bilateral cerebellar cTBS induced persistent clinical beneficial effects, reducing peak-dose LID for up to 4 weeks after the end of the daily stimulation period.

Conclusions: Our study demonstrates that cerebellar continuous theta burst stimulation has an antidyskinetic effect in Parkinson disease patients with levodopa-induced dyskinesia, possibly due to modulation of cerebellothalamocortical pathways.

Abbreviations: AMT = active motor threshold; ANOVA = analysis of variance; CAPSIT = Core Assessment Program for Surgical Interventional Therapies; CS = conditioning stimulus; cTBS = continuous theta burst stimulation; FDI = first dorsal interosseous muscle; GABAB = {gamma}-aminobutyric acid type B; ISI = interstimulus interval; LICI = long intracortical inhibition; LID = levodopa-induced dyskinesia; M1 = primary motor cortex; MEP = motor evoked potential; MSO = maximum stimulator output; PD = Parkinson disease; RMT = resting motor threshold; rTMS = repetitive transcranial magnetic stimulation; SICI = short intracortical inhibition; SMA = supplementary motor area; TBS = theta burst stimulation; TS = test stimulus; UPDRS = Unified Parkinson's Disease Rating Scale.

Supplemental data at www.neurology.org.

Disclosure: Author disclosures are provided at the end of the article.

Received October 14, 2008. Accepted in final form April 3, 2009.






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