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Controlled study of 50-Hz repetitive transcranial magnetic stimulation for the treatment of Parkinson disease.

ABSTRACT: OBJECTIVE:To investigate the safety and efficacy of 50-Hz repetitive transcranial magnetic stimulation (rTMS) in the treatment of motor symptoms in Parkinson disease (PD). BACKGROUND:Progression of PD is characterized by the emergence of motor deficits that gradually respond less to dopaminergic therapy. rTMS has shown promising results in improving gait, a major cause of disability, and may provide a therapeutic alternative. Prior controlled studies suggest that an increase in stimulation frequency might enhance therapeutic efficacy. METHODS:In this randomized, double blind, sham-controlled study, the authors investigated the safety and efficacy of 50-Hz rTMS of the motor cortices in 8 sessions over 2 weeks. Assessment of safety and clinical efficacy over a 1-month period included timed tests of gait and bradykinesia, Unified Parkinson's Disease Rating Scale (UPDRS), and additional clinical, neurophysiological, and neuropsychological parameters. In addition, the safety of 50-Hz rTMS was tested with electromyography-electroencephalogram (EMG-EEG) monitoring during and after stimulation. RESULTS:The authors investigated 26 patients with mild to moderate PD: 13 received 50-Hz rTMS and 13 sham stimulation. The 50-Hz rTMS did not improve gait, bradykinesia, and global and motor UPDRS, but there appeared a short-lived "on"-state improvement in activities of daily living (UPDRS II). The 50-Hz rTMS lengthened the cortical silent period, but other neurophysiological and neuropsychological measures remained unchanged. EMG/EEG recorded no pathological increase of cortical excitability or epileptic activity. There were no adverse effects. CONCLUSION:It appears that 50-Hz rTMS of the motor cortices is safe, but it fails to improve motor performance and functional status in PD. Prolonged stimulation or other techniques with rTMS might be more efficacious but need to be established in future research.

SUBMITTER: Benninger DH

PROVIDER: S-EPMC4169897 | biostudies-literature | 2012 Nov-Dec

REPOSITORIES: biostudies-literature

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Controlled study of 50-Hz repetitive transcranial magnetic stimulation for the treatment of Parkinson disease.

Benninger David H DH Iseki Kazumi K Kranick Sarah S Luckenbaugh David A DA Houdayer Elise E Hallett Mark M

Neurorehabilitation and neural repair 20120515 9

<h4>Objective</h4>To investigate the safety and efficacy of 50-Hz repetitive transcranial magnetic stimulation (rTMS) in the treatment of motor symptoms in Parkinson disease (PD).<h4>Background</h4>Progression of PD is characterized by the emergence of motor deficits that gradually respond less to dopaminergic therapy. rTMS has shown promising results in improving gait, a major cause of disability, and may provide a therapeutic alternative. Prior controlled studies suggest that an increase in st ...[more]

PMID: 22593114

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Project description:Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique that has been closely examined as a possible treatment for Parkinson disease (PD). However, results evaluating the effectiveness of rTMS in PD are mixed, mostly owing to low statistical power or variety in individual rTMS protocols.To determine the rTMS effects on motor dysfunction in patients with PD and to examine potential factors that modulate the rTMS effects.Databases searched included PubMed, EMBASE, Web of Knowledge, Scopus, and the Cochrane Library from inception to June 30, 2014.Eligible studies included sham-controlled, randomized clinical trials of rTMS intervention for motor dysfunction in patients with PD.Relevant measures were extracted independently by 2 investigators. Standardized mean differences (SMDs) were calculated with random-effects models.Motor examination of the Unified Parkinson's Disease Rating Scale.Twenty studies with a total of 470 patients were included. Random-effects analysis revealed a pooled SMD of 0.46 (95% CI, 0.29-0.64), indicating an overall medium effect size favoring active rTMS over sham rTMS in the reduction of motor symptoms (P<.001). Subgroup analysis showed that the effect sizes estimated from high-frequency rTMS targeting the primary motor cortex (SMD, 0.77; 95% CI, 0.46-1.08; P<.001) and low-frequency rTMS applied over other frontal regions (SMD, 0.50; 95% CI, 0.13-0.87; P=.008) were significant. The effect sizes obtained from the other 2 combinations of rTMS frequency and rTMS site (ie, high-frequency rTMS at other frontal regions: SMD, 0.23; 95% CI, -0.02 to 0.48, and low primary motor cortex: SMD, 0.28; 95% CI, -0.23 to 0.78) were not significant. Meta-regression revealed that a greater number of pulses per session or across sessions is associated with larger rTMS effects. Using the Grading of Recommendations, Assessment, Development, and Evaluation criteria, we characterized the quality of evidence presented in this meta-analysis as moderate quality.The pooled evidence suggests that rTMS improves motor symptoms for patients with PD. Combinations of rTMS site and frequency as well as the number of rTMS pulses are key modulators of rTMS effects. The findings of our meta-analysis may guide treatment decisions and inform future research.

Project description:BackgroundClinical symptoms of Parkinson disease (PD) included both motor and nonmotor symptoms. Previous studies indicated inconsistent results for the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) on motor and depression in PD. The study aimed to assess the therapeutic effect of rTMS with different mode on motor and depression in PD using a meta-analysis.MethodsArticles published before July 2019 were searched based on the following databases (PubMed, Web of Science, Medline, Embase, and Google Scholar). The therapeutic effects were assessed by computing the standard mean difference (SMD) and a 95% confidence interval (CI).ResultsThe present study indicated that rTMS showed significant therapeutic effects on motor in PD (SMD 2.05, 95% CI 1.57-2.53, I = 93.0%, P < .001). Both high-frequency (HF)-rTMS and low-frequency rTMS showed therapeutic effects on motor; stimulation over primary motor cortex (M1), supplementary motor area, dorsal lateral prefrontal cortex (DLPFC) or M1+DLPFC showed therapeutic effects; stimulation during "on" and "off" states showed therapeutic effects; the study showed long-term effect of rTMS on motor in PD. In addition, the study indicated that rTMS showed significant therapeutic effects on depression in PD (SMD 0.80, 95% CI 0.31-1.29, I = 89.1%, P < .001). Stimulation over left DLPFC showed significant therapeutic effects on depression in PD; only HF-rTMS showed therapeutic effects; ages, disease durations, numbers of pulses, and session durations displayed influence on the therapeutic effects of rTMS on depression in PD; the therapeutic effects on depression was long term. However, no significant difference in therapeutic effects on depression were showed between rTMS and oral Fluoxetine (SMD 0.74, 95% CI -0.83 to 2.31, I = 92.5%, P < .001).ConclusionThe rTMS showed significant therapeutic effects on motor in PD. HF-rTMS showed a significant positive antidepressive effect in PD only over DLPFC.

Project description:The treatment of depression remains a challenge since at least 40% of patients do not respond to initial antidepressant therapy and 20% present chronic symptoms (more than 2 years despite standard treatment administered correctly). Repetitive transcranial magnetic stimulation (rTMS) is an effective adjuvant therapy but still not ideal. Intermittent Theta Burst Stimulation (iTBS), which has only been used recently in clinical practice, could have a faster and more intense effect compared to conventional protocols, including 10-Hz high-frequency rTMS (HF-rTMS). However, no controlled study has so far highlighted the superiority of iTBS in resistant unipolar depression.This paper focuses on the design of a randomised, controlled, double-blind, single-centre study with two parallel arms, carried out in France, in an attempt to assess the efficacy of an iTBS protocol versus a standard HF- rTMS protocol. Sixty patients aged between 18 and 75 years of age will be enrolled. They must be diagnosed with major depressive disorder persisting despite treatment with two antidepressants at an effective dose over a period of 6 weeks during the current episode. The study will consist of two phases: a treatment phase comprising 20 sessions of rTMS to the left dorsolateral prefrontal cortex, localised via a neuronavigation system and a 6-month longitudinal follow-up. The primary endpoint will be the number of responders per group, defined by a decrease of at least 50% in the initial score on the Montgomery and Asberg Rating Scale (MADRS) at the end of rTMS sessions. The secondary endpoints will be: response rate 1 month after rTMS sessions; number of remissions defined by a MADRS score of <8 at the endpoint and 1 month after; the number of responses and remissions maintained over the next 6 months; quality of life; and the presence of predictive markers of the therapeutic response: clinical (dimensional scales), neuropsychological (evaluation of cognitive functions), motor (objective motor testing) and neurophysiological (cortical excitability measurements).The purpose of our study is to check the assumption of iTBS superiority in the management of unipolar depression and we will discuss its effect over time. In case of a significant increase in the number of therapeutic responses with a prolonged effect, the iTBS protocol could be considered a first-line protocol in resistant unipolar depression.ClinicalTrials.gov, Identifier NCT02376491 . Registered on 17 February 2015 at http://clinicaltrials.gov .

Project description:Background Cocaine use disorder (CUD) is a global health issue with no effective treatment. Repetitive Transcranial Magnetic Stimulation (rTMS) is a recently proposed therapy for CUD. Methods We conducted a single-center, randomised, sham-controlled, blinded, parallel-group research with patients randomly allocated to rTMS (15 Hz) or Sham group (1:1) using a computerised block randomisation process. We enrolled 62 of 81 CUD patients in two years. Patients were followed for eight weeks after receiving 15 15 Hz rTMS/sham sessions over the left dorsolateral prefrontal cortex (DLPFC) during the first three weeks of the study. We targeted the DLFPC following the 5 cm method. Cocaine lapses in twice a week urine tests were the primary outcome. The secondary outcomes were craving severity, cocaine use pattern, and psychometric assessments. Findings We randomly allocated patients to either an active rTMS group (32 subjects) or a sham treatment group (30 subjects). Thirteen (42%) and twelve (43.3%) of the subjects in rTMS and sham groups, respectively, completed the full trial regimen, displaying a high dropout rate. Ten/30 (33%) of rTMS-treated patients tested negative for cocaine in urine, in contrast to 4/27 of placebo controls (p = 0.18, odd ratio 2.88, CI 0.9–10). The Kaplan-Meier survival curve did not state a significant change between the treated and sham groups in the time of cocaine urine negativisation (p = 0.20). However, the severity of cocaine-related cues mediated craving (VAS peak) was substantially decreased in the rTMS treated group (p<0.03) after treatment at T1, corresponding to the end of rTMS treatment. Furthermore, in the rTMS and sham groups, self-reported days of cocaine use decreased significantly (p<0.03). Finally, psychometric impulsivity parameters improved in rTMS-treated patients, while depression scales improved in both groups. Conclusions In CUD, rTMS could be a useful tool for lowering cocaine craving and consumption. Trial registration The study number on clinicalTrials.gov is NCT03607591.

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Controlled study of 50-Hz repetitive transcranial magnetic stimulation for the treatment of Parkinson disease.

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Controlled study of 50-Hz repetitive transcranial magnetic stimulation for the treatment of Parkinson disease.

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