Research Committee on rTMS Treatment of Parkinson’s Disease. Supplementary motor area stimulation for Parkinson disease: a randomized controlled study

Department of Neurology (H.E., Y.U.), School of Medicine, Fukushima Medical University
Neurology (Impact Factor: 8.29). 03/2013; 80(15). DOI: 10.1212/WNL.0b013e31828c2f66
Source: PubMed


OBJECTIVE: To explore the efficacy and stimulation frequency dependence of repetitive transcranial magnetic stimulation (rTMS) over the supplementary motor area (SMA) in Parkinson disease (PD). METHODS: In this randomized, double-blind, sham-controlled, multicenter study with a parallel design, a weekly intervention was performed 8 times. The effects were monitored up to 20 weeks. By central registration, participants were assigned to 1 of 3 arms of the study: low-frequency (1-Hz) rTMS, high-frequency (10-Hz) rTMS, and realistic sham stimulation. The primary end point was the score change of the Unified Parkinson's Disease Rating Scale (UPDRS) part III from the baseline. Several nonmotor symptom scales such as the Hamilton Rating Scale for Depression, apathy score, and nonmotor symptoms questionnaire were defined as secondary end points. RESULTS: Of the 106 patients enrolled, 36 were allocated to 1-Hz rTMS, 34 to 10-Hz rTMS, and 36 to realistic sham stimulation. Results show 6.84-point improvement of the UPDRS part III in the 1-Hz group at the last visit of the 20th week. Sham stimulation and 10-Hz rTMS improved motor symptoms transiently, but their effects disappeared in the observation period. Changes in nonmotor symptoms were not clear in any group. No severe adverse event was reported. CONCLUSIONS: The 1-Hz rTMS over the SMA was effective for motor, but not nonmotor, symptoms in PD. LEVEL OF EVIDENCE: This study provides Class I evidence that 1-Hz rTMS over the SMA is effective for motor symptoms in PD.

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    • "1994),whereaslowerfrequenciesrTMS(1Hzandlower) cantransientlydepresscorticalexcitability(Chenetal. 1997).StudiesperformedsofarusingrTMS(ElahiandChen 2009;Gonzalez-Garciaetal.2011)showedmixedresults, whichcanbeattributedtothevariabilityofpatients'profile, smallsamplesize,largeheterogeneityofcorticaltargets,and stimulation(Shirotaetal.2013).Theta-burststimulationisa novelformofrTMSwhichusesalowerstimulationintensity andashorterstimulationtimecomparedwithconventional rTMSprotocols.Theta-burststimulationappliedovertheM1 hasbeensuccessfullyusedtoinducechangesincortical excitabilityandthisstimulationparadigmisabletoproduce strongandlong-lastingeffects(Morganteetal.2006). "
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    ABSTRACT: Dopamine replacement therapy in Parkinson's disease is associated with several unwanted effects, of which dyskinesia is the most disabling. The development of new therapeutic interventions to reduce the impact of dyskinesia in Parkinson's disease is therefore a priority need. This review summarises the key molecular mechanisms that underlie dyskinesia. The role of dopamine receptors and their associated signaling mechanisms including DARPP-32, ERK, mTOR, MSK-1 and Histone H3 are summarised, along with an evaluation of the role of cannabinoid and nicotinic acetylcholine receptors. The role of synaptic plasticity, and animal behavioural results on dyskinesia are also evaluated. The most recent therapeutic advances to treat Parkinson's disease are discussed, with emphasis on the possibilities and limitations of non pharmacological interventions such as physical activity, deep brain stimulation, transcranial magnetic field stimulation and cell replacement therapy. The review suggests new prospects for the management of Parkinson's disease-associated motor symptoms, especially the development of dyskinesia.This article is protected by copyright. All rights reserved.
    Journal of Neurochemistry 04/2014; 130(4). DOI:10.1111/jnc.12751 · 4.28 Impact Factor
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    • "Similar inconsistency was also found in the therapeutic effect of rTMS on PD. Although quite a few studies have shown clinical benefits of rTMS on PD (Lefaucheur et al. 2004; Elahi and Chen 2009; Degardin et al. 2012), the results so far have been inconclusive (Benninger et al. 2011; Shirota et al. 2013). Such discrepancy between studies could be due to the clinical heterogeneity in patients, long-term pharmacological effects, different severity of the disease, and the variability of protocols (Muller-Dahlhaus et al. 2008; Bologna et al. 2012; Hamada et al. 2013). "
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    ABSTRACT: Repetitive magnetic stimulation (rTMS), including theta burst stimulation (TBS), is capable of modulating motor cortical excitability through plasticity-like mechanisms and might have therapeutic potential for Parkinson's disease (PD). An animal model would be helpful for elucidating the mechanism of rTMS that remain unclear and controversial. Here, we have established a TMS model in rat and applied this model to study the impact of substantia nigra dopamine neuron on TBS-induced motor plasticity in PD rats. In parallel with human results, continuous TBS (cTBS) successfully suppressed motor evoked potentials (MEPs), while MEPs increased after intermittent TBS (iTBS) in healthy rats. We then tested the effect of iTBS in early and advanced 6-hydroxydopamine (6-OHDA)-lesioned PD. Moreover, dopaminergic neurons in substantia nigra and rotation behavior were assessed to correlate with the amount of iTBS-induced plasticity. In results, iTBS-induced potentiation was reduced in early PD rats and was absent in advanced PD rats. Such reduction in plasticity strongly correlated with the dopaminergic cell loss and the count of rotation in PD rats. In conclusion, we have established a TMS PD rat model. With the help of this model, we confirmed the loss of domaninergic neurons in substantia nigra resulting in reduced rTMS-induced motor plasticity in PD. © 2014 The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: [email protected] /* */
    Cerebral Cortex 01/2014; 25(7). DOI:10.1093/cercor/bht421 · 8.67 Impact Factor
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    • "A recent multicenter trial confirmed that rTMS of SMA can have some clinical impact. The authors found an improvement on the UPDRS scores following a prolonged protocol of weekly performed LF rTMS of SMA on motor symptoms of PD (29), but not with HF rTMS. Interestingly, rTMS of the SMA has also been shown able to improve LID (43, 44). "
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    ABSTRACT: Animal models of Parkinson's disease (PD) have shown that key mechanisms of cortical plasticity such as long-term potentiation (LTP) and long-term depression (LTD) can be impaired by the PD pathology. In humans protocols of non-invasive brain stimulation, such as paired associative stimulation (PAS) and theta-burst stimulation (TBS), can be used to investigate cortical plasticity of the primary motor cortex. Through the amplitude of the motor evoked potential these transcranial magnetic stimulation methods allow to measure both LTP-like and LTD-like mechanisms of cortical plasticity. So far these protocols have reported some controversial findings when tested in PD patients. While various studies described evidence for reduced LTP- and LTD-like plasticity, others showed different results, demonstrating increased LTP-like and normal LTD-like plasticity. Recent evidence provided support to the hypothesis that these different patterns of cortical plasticity likely depend on the stage of the disease and on the concomitant administration of l-DOPA. However, it is still unclear how and if these altered mechanisms of cortical plasticity can be taken as a reliable model to build appropriate protocols aimed at treating PD symptoms by applying repetitive sessions of repetitive TMS (rTMS) or transcranial direct current stimulation (tDCS). The current article will provide an up-to-date overview of these issues together with some reflections on future studies in the field.
    Frontiers in Neurology 11/2013; 4:180. DOI:10.3389/fneur.2013.00180
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