Repetitive transcranial magnetic stimulation of the primary motor cortex in the treatment of motor signs in Parkinson's disease: A quantitative review of the literature

Parkinson's disease (PD) is a progressive disorder characterized by the emergence of motor deficits. In light of the voluminous and conflicting findings in the literature, the aim of the present quantitative review was to examine the effects of repetitive transcranial magnetic stimulation (rTMS) targeting the primary motor cortex (M1) in the treatment of motor signs in PD. Studies meeting inclusion criteria were analyzed using meta‐analytic techniques and the Unified Parkinson's Disease Rating Scale (UPDRS) sections II and III were used as outcome measures. In order to determine the treatment effects of rTMS, the UPDRS II and III scores obtained at baseline, same day, to 1 day post rTMS treatment (short‐term follow‐up) and 1‐month post stimulation (long‐term follow‐up) were compared between the active and sham rTMS groups. Additionally, the placebo effect was evaluated as the changes in UPDRS III scores in the sham rTMS groups. A placebo effect was not demonstrated, because sham rTMS did not improve motor signs as measured by UPDRS III. Compared with sham rTMS, active rTMS targeting the M1 significantly improved UPDRS III scores at the short‐term follow‐up (Cohen's d of 0.27, UPDRS III score improvement of 3.8 points). When the long‐term follow‐up UPDRS III scores were compared with baseline scores, the standardized effect size between active and sham rTMS did not reach significance. However, this translated into a significant nonstandardized 6.3‐point improvement on the UPDRS III. No significant improvement in the UPDRS II was found. rTMS over the M1 may improve motor signs. Further studies are needed to provide a definite conclusion. © 2015 International Parkinson and Movement Disorder Society     

Effect of daily repetitive transcranial magnetic stimulation on motor performance in Parkinson's disease.

Previous studies in patients with Parkinson's disease have reported that a single session of repetitive transcranial magnetic stimulation (rTMS) can improve some or all of the motor symptoms for 30 to 60 minutes. A recent study suggested that repeated sessions of rTMS lead to effects that can last for at least 1 month. Here we report data that both confirm and extend this work. Fifty-five unmedicated PD patients were classified into four groups: two groups (early and late PD) received 25 Hz rTMS bilaterally on the motor arm and leg areas; other groups acted as control for frequency (10 Hz) and for site of stimulation (occipital stimulation). All patients received six consecutive daily sessions (3,000 pulses for each session). The first two groups then received a further three booster sessions (3 consecutive days of rTMS) after 1, 2, and 3 months, while the third group had only one additional session after the first month. Unified Parkinson's Disease Rating Scale (UPDRS), walking time, key-tapping speed, and self-assessment scale were measured for each patient before and after each rTMS session and before and after the monthly sessions. Compared to occipital stimulation, 25 Hz rTMS over motor areas improved all measures in both early and late groups; the group that received 10 Hz rTMS improved more than the occipital group but less than the 25 Hz groups. The effect built up gradually during the sessions and was maintained for 1 month after, with a slight reduction in efficacy. Interestingly, the effect was restored and maintained for the next month by the booster sessions. We conclude that 25 Hz rTMS can lead to cumulative and long-lasting effects on motor performance.     

The impact of left prefrontal repetitive transcranial magnetic stimulation on depression in Parkinson's disease: A randomized,double‐blind,placebo‐controlled study

Based on several open‐label and case studies, repetitive transcranial magnetic stimulation (rTMS) seems to have an antidepressive effect on patients with Parkinson's disease (PD). However, this hypothesis requires further confirmation. We conducted a randomized, double‐blind placebo‐controlled study to evaluate the effect of rTMS over the left dorsolateral prefrontal cortex (DLPFC) on depression and various motor and nonmotor features of PD. Twenty‐two PD patients with mild or moderate depressive episodes were assigned into two groups, one receiving real‐rTMS (90% of resting motor threshold, 5 Hz, 600 pulses‐a‐day for 10 days) over the left DLPFC, and another group receiving sham‐rTMS. An investigator blinded to the treatment performed three video‐taped examinations on each patient: before stimulation (baseline), 1 day (short term), and 30 days after treatment session ended (long‐term effect). Mini‐Mental State Examination, Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn‐Yahr, Epworth Sleepiness, Visual Analog and Montgomery‐Asberg Depression Rating Scales (MADRS), Beck Depression Inventory (BDI), and Trail making and Stroop tests were applied. In the actively treated group, not only depression rating scales showed significant improvement 30 days after treatment ended (BDI by 44.4% and MADRS by 26.1%), but also the accuracy of Stroop test (by 16%). We could also demonstrate an insignificant improvement in UPDRS‐III by 7.5 points (31.9%, P = 0.06). In the sham‐treated group none of the examined tests and scales improved significantly after sham stimulation. Our study demonstrated the beneficial effect of the left DLPFC rTMS on depression in PD lasting at least 30 days after treatment. However, this result should be confirmed in patients with severe depression by further clinical trials. © 2010 Movement Disorder Society     

Dopamine levels after repetitive transcranial magnetic stimulation of motor cortex in patients with Parkinson's disease: preliminary results.

BACKGROUND: Repeated session of repetitive transcranial magnetic stimulation (rTMS) over motor cortex have been reported to produce significant improvement of motor performance in patients with parkinson's disease (PD). In addition, it is known that a single session of rTMS over motor cortex transiently increases DA in striatum. Here, we test whether repeated sessions of rTMS increase serum dopamine in PD patients and whether this correlates with changes in clinical rating scales. MATERIAL AND METHODS: Twenty untreated PD patients with moderate to severe symptoms (Hoehn & Yahr state III-V 1967) were assessed on the Unified Parkinson's Disease Rating Scale (UPDRS), and with an enzyme immunoassay for quantitative determination of plasma dopamine before and after six daily sessions of 25 Hz rTMS with 3,000 stimuli over the right and left hand and leg motor cortex. RESULTS: There was significant improvement in UPDRS compared with the baseline. Serum dopamine level also was significantly elevated over the same interval. There was a significant correlation between UPDRS and serum dopamine level before and after treatment. CONCLUSION: Improved motor performance in PD after repeated session of rTMS may be related to an elevation of serum dopamine concentration.     

Clinical effects of repetitive transcranial magnetic stimulation versus acute levodopa challenge in Parkinson's disease

We studied the short-term clinical effects of 10-Hz repetitive transcranial magnetic stimulation (rTMS) of the motor hand area contralateral to the more affected limb in 12 non-fluctuating, for at least 12 hours drug free patients with Parkinson's disease (PD). We investigated the efficacy of rTMS in combination with a levodopa challenge test design under double-blind, placebo controlled conditions. Significant reductions of UPDRS III motor scores showed the treatment conditions: placebo/rTMS, levodopa/sham stimulation and levodopa/rTMS. A more detailed evaluation of arm symptoms contralateral to the stimulated brain region showed even more pronounced effects for the three conditions. There were significant differences between the mean response of the UPDRS III arm scores to the four test conditions. In conclusion our study demonstrates short-term beneficial effects of 10-Hz rTMS on motor symptoms in PD patients. A release of endogenous dopamine in subcortical structures, i.e. putamen, in response to rTMS is the most likely mechanism of action.     

High‐frequency rTMS over the supplementary motor area for treatment of Parkinson's disease

Dysfunction of the basal ganglia‐thalamocortical motor circuit is a fundamental model to account for motor symptoms in Parkinson's disease (PD). Using high‐frequency repetitive transcranial magnetic stimulation (rTMS) over the supplementary motor area (SMA), we investigated whether modulation of SMA excitability engenders therapeutic effects on motor symptoms in PD. In this double‐blind placebo‐controlled study, 99 patients were enrolled and assigned randomly to SMA‐stimulation and sham‐stimulation groups. For SMA stimulation, 20 trains of 50 transcranial magnetic stimuli at 5 Hz were delivered at an intensity of 110% active motor threshold for leg muscles in one session. The sham stimulation was 20 trains of electric stimuli given through electrodes fixed on the head to mimic the cutaneous sensation during rTMS. Each session of intervention was carried out once a week for the first 8 weeks. The SMA stimulation, in contrast to the sham stimulation, engendered significant improvements in total scores and motor scores of the Unified Parkinson's Disease Rating Scale. Mean improvements in motor scores were 4.5 points in the SMA‐stimulation group and ?0.1 points in the sham‐stimulation group. Results indicate that 5 Hz rTMS over SMA modestly improves motor symptoms in PD patients; SMA is a potential stimulation site for PD treatment. © 2008 Movement Disorder Society     

Effects of successive repetitive transcranial magnetic stimulation on motor performances and brain perfusion in idiopathic Parkinson's disease

We studied the effects of 0.2 Hz repetitive transcranial magnetic stimulation (rTMS) successively performed 6 times for 2 weeks in 12 patients with idiopathic Parkinson's disease (PD). Ten patients received rTMS to the bilateral frontal cortex (frontal rTMS) and six patients received rTMS to the bilateral occipital cortex (occipital rTMS). Before and after rTMS, we evaluated regional cerebral blood flow (rCBF) using 99m-Tc-ECD single photon emission computed tomography (SPECT) and clinical tests.In an analysis with statistic parametric mapping, both frontal and occipital rTMS reduced rCBF in the cortical areas around the stimulated site. The activities of daily living (ADL) and motor scores of Unified Parkinson's Disease Rating Scale (UPDRS), pronation-supination movements, and buttoning up significantly improved after frontal rTMS than before it, while occipital rTMS had no significant effects in clinical tests.The findings of the present study suggest that successive 0.2 Hz rTMS has outlasting inhibitory effects on neuronal activity around the stimulated cortical areas. Because there were no significant relations between improved clinical tests and reduced rCBF, we speculate that the indirect effects of 0.2 Hz rTMS on subcortical structures are related to improved parkinsonian symptoms. Further studies recruiting large numbers of subjects are required to confirm the efficacy of 0.2 Hz rTMS on PD.     

Therapeutic effect of repetitive transcranial magnetic stimulation on motor function in Parkinson''s disease patients

Cortical excitability of the primary motor cortex is altered in patients with Parkinson's disease (PD). Therefore, modulation of cortical excitability by high frequency repetitive transcranial magnetic stimulation (rTMS) of the motor cortex might result in beneficial effects on motor functions in PD. The present study aims to evaluate the effect of rTMS of the motor cortex on motor functions in patients with PD. Thirty-six unmedicated PD patients were included consecutively in this study. The patients were assigned in a randomized pattern to one of two groups, one group receiving real-rTMS (suprathreshold 5-Hz, 2000 pulses once a day for 10 consecutive days) and the second group receiving sham-rTMS using closed envelopes. Total motor section of Unified Parkinson's Disease Rating Scale (UPDRS), walking speed, and self-assessment scale were performed for each patient before rTMS and after the first, fifth, 10th sessions, and then after 1 month. Evaluation of these measures was performed blindly without knowing the type of rTMS. anova for repeated measurements revealed a significant time effect for the total motor UPDRS, walking speed and self-assessment scale during the course of the study in the group of patients receiving real-rTMS (P = 0.0001, 0.001, and 0.002), while no significant changes were observed in the group receiving sham-rTMS except in self-assessment scale (P = 0.019). A 10-day course of real-rTMS resulted in statistically significant long-term improvement of the motor functions in comparison with the sham-rTMS. The rTMS could have a therapeutic role of for PD patients.     

Left prefrontal transcranial magnetic stimulation (TMS) treatment of depression in bipolar affective disorder: a pilot study of acute safety and efficacy

Objectives:  Repetitive transcranial magnetic stimulation (rTMS) has been shown to improve depressive symptoms. We designed and carried out the following left prefrontal rTMS study to determine the safety, feasibility, and potential efficacy of using TMS to treat the depressive symptoms of bipolar affective disorder (BPAD).
Methods:  We recruited and enrolled 23 depressed BPAD patients (12 BPI depressed state, nine BPII depressed state, two BPI mixed state). Patients were randomly assigned to receive either daily left prefrontal rTMS (5 Hz, 110% motor threshold, 8 sec on, 22 sec off, over 20 min) or placebo each weekday morning for 2 weeks. Motor threshold and subjective rating scales were obtained daily, and blinded Hamilton Rating Scale for Depression (HRSD) and Young Mania Rating Scales (YMRS) were obtained weekly.
Results:  Stimulation was well tolerated with no significant adverse events and with no induction of mania. We failed to find a statistically significant difference between the two groups in the number of antidepressant responders (>50% decline in HRSD or HRSD <10 – 4 active and 4 sham) or the mean HRSD change from baseline over the 2 weeks ( t =−0.22, p=0.83). Active rTMS, compared with sham rTMS, produced a trend but not statistically significant greater improvement in daily subjective mood ratings post-treatment ( t =1.58, p=0.13). The motor threshold did not significantly change after 2 weeks of active treatment ( t =1.11, p=0.28).
Conclusions:  Daily left prefrontal rTMS appears safe in depressed BPAD subjects, and the risk of inducing mania in BPAD subjects on medications is small. We failed to find statistically significant TMS clinical antidepressant effects greater than sham. Further studies are needed to fully investigate the potential role, if any, of TMS in BPAD depression.     

Double-blind,randomized, placebo controlled trial on the effect of 10 days low-frequency rTMS over the vertex on sleep in Parkinson’s disease

ObjectiveA recent report indicates repetitive transcranial magnetic stimulation (rTMS) improves sleep in Parkinson’s disease (PD). The aim of this work is to evaluate the effect of 10 days rTMS on sleep parameters in PD patients.MethodsDouble-blind, placebo-controlled design. Eighteen idiopathic PD patients completed the study. Sleep parameters were evaluated through actigraphy and the Parkinson’s Disease Sleep Scale (PDSS), along with depression (Hamilton Depression Rating Scale, HDS), and the Unified Parkinson’s Disease Rating Scale (UPDRS). Evaluations were carried out before treatment with rTMS (pre-evaluation, PRE), after the rTMS treatment programme (post-evaluation, POST), and one week after POST (POST-2). Nine PD patients received real rTMS and the other 9 received sham rTMS daily for 10 days, (100 pulses at 1 Hz) applied with a large circular coil over the vertex.ResultsStimulation had no effect over actigraphic variables. Conversely PDSS, HDS, and UPDRS were significantly improved by the stimulation. Notably, however, these changes were found equally in groups receiving real or sham stimulation.ConclusionsrTMS, using our protocol, has no therapeutic value on the sleep of PD patients, when compared to appropriate sham controls. Future works assessing the possible therapeutic role of rTMS on sleep in PD should control the effect of placebo.     

A randomized controlled comparison of electroconvulsive therapy and repetitive transcranial magnetic stimulation in severe and resistant nonpsychotic major depression.

BACKGROUND: Studies published over the past few years suggest that transcranial magnetic stimulation (TMS) may have significant antidepressant actions. In a previous report, we compared electroconvulsive therapy (ECT) and repetitive TMS (rTMS) and found ECT to be superior for psychotic major depression (MD); however, ECT and rTMS had similar results in nonpsychotic MD. We now report on a controlled randomized comparison of ECT and rTMS in patients with nonpsychotic MD. METHODS: Forty patients with nonpsychotic MD referred for ECT were included. Electroconvulsive therapy was performed according to established protocols. Repetitive TMS was performed over the left dorsolateral prefrontal cortex at 90% motor threshold. Patients were treated with 20 sessions (five times per week for 4 weeks) of 10-Hz treatments (1200 pulses per treatment-day) at 90% motor threshold. Response to treatment was defined as a decrease of at least 50% in the Hamilton Rating Scale for Depression (HRSD) score, with a final HRSD equal or less than 10 points and a final Global Assessment of Function Scale rating of 60 or more points. RESULTS: The overall response rate was 58% (23 out of 40 patients responded to treatment). In the ECT group, 12 responded and eight did not; in the rTMS group, 11 responded and nine did not (chi2 =.10, ns). Thus, patients responded as well to either ECT or rTMS. CONCLUSIONS: This study adds to the growing literature supporting an antidepressant effect for rTMS. This study is particularly relevant because it suggests that rTMS and ECT reach similar results in nonpsychotic major depressive disorder.     

Repetitive transcranial magnetic stimulation to SMA worsens complex movements in Parkinson's disease.

OBJECTIVES: To evaluate the therapeutic potential of repetitive transcranial magnetic stimulation (rTMS) for Parkinson's disease (PD) by delivering stimulation at higher intensity and frequency over longer time than in previous research. Promising beneficial effects on movement during or after rTMS have been reported. METHODS: Ten patients with idiopathic PD were enrolled in a randomized crossover study comparing active versus sham rTMS to the supplementary motor area (SMA). Assessments included reaction and movement times (RT/MT), quantitative spiral analysis, timed motor performance tests, United Parkinson's Disease Rating Scale (UPDRS), patient self-report and guess as to stimulation condition. RESULTS: Two of 10 patients could not tolerate the protocol. Thirty to 45 min following stimulation, active rTMS as compared with sham stimulation worsened spiral drawing (P=0.001) and prolonged RT in the most affected limb (P=0.030). No other significant differences were detected. CONCLUSIONS: We sought clinically promising improvement in PD but found subclinical worsening of complex and preparatory movement following rTMS to SMA. These results raise safety concerns regarding the persistence of dysfunction induced by rTMS while supporting the value of rTMS as a research tool. Studies aimed at understanding basic mechanisms and timing of rTMS effects are needed.     

Transcranial magnetic stimulation over dorsolateral prefrontal cortex in Parkinson's disease.

OBJECTIVE: Several studies have shown that repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) is effective in the treatment of depression in patients with Parkinson disease (PD). However, since research into the effect of this type of rTMS regime on motor function is limited, we studied the effect of rTMS over the DLPFC on the motor functions in PD patients. METHODS: Thirteen patients were randomly assigned into 2 groups, one receiving real-rTMS (90% of resting motor threshold, 10 Hz, 450 pulses-day for 10 consecutive days) over the DLPFC contralateral to the more affected side, and the other group receiving sham-rTMS. Assessment included a clinical motor evaluation using part III of the Unified Parkinson's Disease Rating Scale (UPDRS), and several motor tasks. The UPDRS was applied before and after 10 days of rTMS. Finger tapping, reach movement, grip movement and gait were measured in each session before and after the rTMS over the 10 day period. RESULTS: Statistical analysis (ANOVA for repeated measures; group *day *side *rTMS) only showed a significant effect for finger tapping, reach movement and gait for the factor day. No significant change was reported for the UPDRS in any group. CONCLUSIONS: Application of rTMS over the DLPFC as a 10 day course had no significant effect on motor functions and clinical motor status, and the improvement in performance of motor tasks can be attributed to the effects of practice. SIGNIFICANCE: rTMS over the DLPFC did not lead to any motor improvement in PD patients.     

Repetitive transcranial magnetic stimulation is as effective as fluoxetine in the treatment of depression in patients with Parkinson's disease

OBJECTIVE: To study the efficacy of 15 Hz repetitive transcranial magnetic stimulation (rTMS) in treating depression in patients with Parkinson's disease. METHODS: 42 patients were enrolled into two groups: group 1, active rTMS (15 Hz rTMS for 10 days) and placebo drug treatment; group 2, sham rTMS and fluoxetine 20 mg/day. A specially designed sham coil was used for sham stimulation. The unified Parkinson's disease rating scale (UPDRS), activities of daily living (ADL), Hamilton rating scale for depression (HRSD), Beck depression inventory (BDI), and mini-mental state examination (MMSE) were assessed by a rater blinded to treatment arm. RESULTS: HRSD and BDI were improved to the same extent in both groups after two weeks of treatment (38% and 32% for group 1, 41% and 33% for group 2, respectively). At week 8 there was a tendency for worse motor UPDRS scores in group 2 (NS). ADL showed improvement at week 8 only in group 1. MMSE improved in both groups after treatment, but faster in group 1 than in group 2. There were fewer adverse effects in group 1 than in group 2. CONCLUSIONS: rTMS has the same antidepressant efficacy as fluoxetine and may have the additional advantage of some motor improvement and earlier cognitive improvement, with fewer adverse effects.     

帕金森病患者运动皮质兴奋性的经颅磁刺激研究

目的:本研究拟应用低频重复性经颅磁刺激(rTMS)分别刺激帕金森病(PD)患者M1手代表区(M1Hand)及运动前区(PMC),探讨不同干预手段对运动皮质兴奋性的影响,以及M1与PMC间的联系。方法:对18名确诊PD患者先后进行4种不同干预,即口服美多芭、低频rTMS刺激M1Hand(0.5Hz,100%静息阈值,共1600次脉冲)、低频rTMS刺激PMC(0.5Hz,100%静息阈值,共1600次脉冲)以及假刺激。于每次干预前后各进行临床评价并测定运动诱发电位(MEP)相关指标。结果:①口服美多芭后UPDRSⅢ(P=0.001)以及其中有关僵直(P=0.001)、运动迟缓(P<0.001)的评分均较服药前显著改善。三种不同磁刺激干预产生结果不同,M1Hand组UPDRSⅢ减低(P=0.015),僵直(P=0.010)、运动迟缓(P=0.004)亦有所改善;PMC组UPDRSⅢ较干预前减低(P=0.046),僵直评分亦减低,但无显著性意义(P=0.163);②口服美多芭1h后MEP120减低(P=0.002),CSP延长(P=0.006);M1Hand组MEP120无著变,而CSP延长(P=0.015);PMC组MEP120减低(P=0.004),而CSP无著变;假刺激组则均无显著性改变。结论:低频rTMS对不同脑区产生的效应不同:刺激M1可使CSP延长;而刺激PMC可使MEP波幅减低。     

Transcranial magnetic stimulation of the cerebellum in essential tremor: a controlled study

BACKGROUND: Growing evidence implicates an overactivity of the cerebellum in the pathophysiology of essential tremor. In a small series of patients, we explored the acute effects and therapeutic possibilities of low-frequency repetitive transcranial magnetic stimulation (rTMS) of the cerebellum in patients with essential tremor in a double-blind, crossover, placebo-controlled design. METHODS: Ten patients with essential tremor underwent an active and a sham rTMS session, at a 1-week interval. The rTMS was performed with a focal double 70-mm butterfly coil (maximum peak field of 2.2 T) applied 2 cm below the inion. Each session consisted of 30 trains of 10-second duration separated by 30-second pauses, at 100% of the maximum output intensity and at 1-Hz frequency. Major evaluation outcomes were the score on the Tremor Clinical Rating Scale and accelerometric recordings obtained before (-5 minutes), immediately after (+5 minutes), and 1 hour after (+60 minutes) each rTMS session. Both clinical and accelerometric measurements were obtained by a blinded neurologist. RESULTS: On the +5-minute assessment, active rTMS produced a notable tremor improvement compared with sham rTMS, as evidenced by a significant reduction in scores on the clinical rating scale and accelerometric values. At +60 minutes, no clinical or accelerometric benefit was evidenced. No adverse effects of rTMS were observed. CONCLUSIONS: This exploratory study of the potential therapeutic properties of rTMS on essential tremor showed an acute antitremor effect. Further investigation in search of a more lasting benefit is warranted.     

High-Frequency Repetitive Transcranial Magnetic Stimulation over the Primary Foot Motor Area in Parkinson's Disease

BackgroundRepetitive transcranial magnetic stimulation (rTMS) has been reported to be clinically effective for treating motor symptoms in Parkinson's disease (PD). Few studies have been performed reporting the effects of rTMS on non-motor symptoms such as depression and apathy in PD.ObjectiveWe assessed the effects of high-frequency (HF) rTMS over the primary motor (M1) foot area on motor symptoms, depression and apathy scales, and sensory symptoms in PD.MethodsWe investigated the efficacy of 3 consecutive days of HF-rTMS over the M1 foot area in 21 patients with PD using a randomized, double-blind cross-over trial compared with sham stimulation. Motor effects were evaluated using the Unified Parkinson's Disease Rating Scale part III (UPDRS-III), the self-assessment motor score, the visual analog scale (VAS), the 10-m walking test, and finger tapping. Non-motor effects were analyzed using the Montgomery Asberg Depression Rating Scale, the Apathy Scale, and quantitative sensory testing.ResultsHF-rTMS significantly improved UPDRS-III (P < 0.001), VAS (P < 0.001), the walking test (P = 0.014), self-assessment motor score (P = 0.010), and finger tapping measurement (P < 0.05) compared to sham stimulation. In contrast, no significant improvement was observed in depression and apathy scales. Consecutive days of rTMS did not significantly increase the improvement in motor symptoms. There were no adverse effects following rTMS on patients with PD.ConclusionsWe confirmed that HF-rTMS over the M1 foot area significantly improved motor symptoms in patients with PD. In addition, daily repeated stimulation was not significantly more effective than a single session of stimulation, but may be effective for maintaining the improvement in motor symptoms in patients with PD.     

Controlled trial on the effect of 10 days low‐frequency repetitive transcranial magnetic stimulation (rTMS) on motor signs in Parkinson's disease

We evaluated the effect of low‐frequency rTMS on motor signs in Parkinson's disease (PD), under a double‐blind placebo‐controlled trial design. PD patients were randomly assigned to received either real (n = 9) or sham (n = 9) rTMS for 10 days. Each session comprises two trains of 50 stimuli each delivered at 1 Hz and at 90% of daily rest motor threshold using a large circular coil over the vertex. The effect of the stimulation, delivered during the ON‐period, was evaluated during both ON and OFF periods. Tests were carried out before and after the stimulation period, and again 1 week after. The effect of the stimulation was evaluated through several gait variables (cadence, step amplitude, velocity, the CV_{stride‐time}, and the turn time), hand dexterity, and also the total and motor sections of the UPDRS. Only the total and motor section of the UPDRS and the turn time during gait were affected by the stimulation, the effect appearing during either ON or OFF evaluation, and most importantly, equally displayed in both real and sham group. The rest of the variables were not influenced. We conclude the protocol of stimulation used, different from most protocols that apply larger amount of stimuli, but very similar to some previously reported to have excellent results, has no therapeutic value and should be abandoned. This contrasts with the positive reported effects using higher frequency and focal coils. Our work also reinforces the need for sham stimulation when evaluating the therapeutic effect of rTMS. © 2010 Movement Disorder Society     

Repetitive transcranial magnetic stimulation for levodopa‐induced dyskinesias in Parkinson's disease

In a placebo‐controlled, single‐blinded, crossover study, we assessed the effect of “real” repetitive transcranial magnetic stimulation (rTMS) versus “sham” rTMS (placebo) on peak dose dyskinesias in patients with Parkinson's disease (PD). Ten patients with PD and prominent dyskinesias had rTMS (1,800 pulses; 1 Hz rate) delivered over the motor cortex for 4 consecutive days twice, once real stimuli and once sham stimulation were used; evaluations were done at the baseline and 1 day after the end of each of the treatment series. Direct comparison between sham and real rTMS effects showed no significant difference in clinician‐assessed dyskinesia severity. However, comparison with the baseline showed small but significant reduction in dyskinesia severity following real rTMS but not placebo. The major effect was on dystonia subscore. Similarly, in patient diaries, although both treatments caused reduction in subjective dyskinesia scores during the days of intervention, the effect was sustained for 3 days after the intervention for the real rTMS only. Following rTMS, no side effects and no adverse effects on motor function and PD symptoms were noted. The results suggest the existence of residual beneficial clinical aftereffects of consecutive daily applications of low‐frequency rTMS on dyskinesias in PD. The effects may be further exploited for potential therapeutic uses. © 2008 Movement Disorder Society     

Treatment of articulatory dysfunction in Parkinson's disease using repetitive transcranial magnetic stimulation

Background and purpose: Neuroimaging has demonstrated that improved speech outcomes in Parkinson’s Disease (PD) subsequent to behavioural treatment approaches are associated with increased activity in the motor and pre‐motor cortex. High‐frequency repetitive transcranial magnetic stimulation (rTMS) is capable of modulating cortical activity and has been reported to have significant benefit to general motor function in PD. It is possible that high‐frequency rTMS may also have beneficial outcomes on speech production in PD. Methods: High‐frequency (5 Hz) rTMS was applied to 10 active stimulation and 10 sham placebo patients for 10 min/day (3000 pulses), for 10 days and speech outcome measures and lingual kinematic parameters recorded at baseline and 1 week, 2 and 12 months post‐stimulation. Results: The findings demonstrated positive treatment‐related changes observed in the active rTMS group when compared to the sham placebo control group at 2 and 12 months post‐stimulation in speech intelligibility, communication efficiency ratio, maximum velocity of tongue movements and distance of tongue movements. Conclusion: The results support the use of high‐frequency rTMS as a therapeutic tool for the treatment of articulatory dysfunction in PD.