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Multifocal repetitive TMS for motor and mood symptoms of Parkinson disease: A randomized trial.

ABSTRACT: OBJECTIVE:To assess whether multifocal, high-frequency repetitive transcranial magnetic stimulation (rTMS) of motor and prefrontal cortex benefits motor and mood symptoms in patients with Parkinson disease (PD). METHODS:Patients with PD and depression were enrolled in this multicenter, double-blind, sham-controlled, parallel-group study of real or realistic (electric) sham rTMS. Patients were randomized to 1 of 4 groups: bilateral M1 ( + sham dorsolateral prefrontal cortex [DLPFC]), DLPFC ( + sham M1), M1 + DLPFC, or double sham. The TMS course consisted of 10 daily sessions of 2,000 stimuli for the left DLPFC and 1,000 stimuli for each M1 (50 × 4-second trains of 40 stimuli at 10 Hz). Patients were evaluated at baseline, at 1 week, and at 1, 3, and 6 months after treatment. Primary endpoints were changes in motor function assessed with the Unified Parkinson's Disease Rating Scale-III and in mood with the Hamilton Depression Rating Scale at 1 month. RESULTS:Of the 160 patients planned for recruitment, 85 were screened, 61 were randomized, and 50 completed all study visits. Real M1 rTMS resulted in greater improvement in motor function than sham at the primary endpoint (p < 0.05). There was no improvement in mood in the DLPFC group compared to the double-sham group, as well as no benefit to combining M1 and DLPFC stimulation for either motor or mood symptoms. CONCLUSIONS:In patients with PD with depression, M1 rTMS is an effective treatment of motor symptoms, while mood benefit after 2 weeks of DLPFC rTMS is not better than sham. Targeting both M1 and DLPFC in each rTMS session showed no evidence of synergistic effects. CLINICALTRIALSGOV IDENTIFIER:NCT01080794. CLASSIFICATION OF EVIDENCE:This study provides Class I evidence that in patients with PD with depression, M1 rTMS leads to improvement in motor function while DLPFC rTMS does not lead to improvement in depression compared to sham rTMS.

SUBMITTER: Brys M

PROVIDER: S-EPMC5100715 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Multifocal repetitive TMS for motor and mood symptoms of Parkinson disease: A randomized trial.

Brys Miroslaw M Fox Michael D MD Agarwal Shashank S Biagioni Milton M Dacpano Geraldine G Kumar Pawan P Pirraglia Elizabeth E Chen Robert R Wu Allan A Fernandez Hubert H Wagle Shukla Aparna A Lou Jau-Shin JS Gray Zachary Z Simon David K DK Di Rocco Alessandro A Pascual-Leone Alvaro A

Neurology 20161005 18

<h4>Objective</h4>To assess whether multifocal, high-frequency repetitive transcranial magnetic stimulation (rTMS) of motor and prefrontal cortex benefits motor and mood symptoms in patients with Parkinson disease (PD).<h4>Methods</h4>Patients with PD and depression were enrolled in this multicenter, double-blind, sham-controlled, parallel-group study of real or realistic (electric) sham rTMS. Patients were randomized to 1 of 4 groups: bilateral M1 ( + sham dorsolateral prefrontal cortex [DLPFC] ...[more]

PMID: 27708129

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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:Importance:Parkinson disease is a progressive neurologic disorder. Limited evidence suggests endurance exercise modifies disease severity, particularly high-intensity exercise. Objectives:To examine the feasibility and safety of high-intensity treadmill exercise in patients with de novo Parkinson disease who are not taking medication and whether the effect on motor symptoms warrants a phase 3 trial. Design, Setting, and Participants:The Study in Parkinson Disease of Exercise (SPARX) was a phase 2, multicenter randomized clinical trial with 3 groups and masked assessors. Individuals from outpatient and community-based clinics were enrolled from May 1, 2012, through November 30, 2015, with the primary end point at 6 months. Individuals with idiopathic Parkinson disease (Hoehn and Yahr stages 1 or 2) aged 40 to 80 years within 5 years of diagnosis who were not exercising at moderate intensity greater than 3 times per week and not expected to need dopaminergic medication within 6 months participated in this study. A total of 384 volunteers were screened by telephone; 128 were randomly assigned to 1 of 3 groups (high-intensity exercise, moderate-intensity exercise, or control). Interventions:High-intensity treadmill exercise (4 days per week, 80%-85% maximum heart rate [n = 43]), moderate-intensity treadmill exercise (4 days per week, 60%-65% maximum heart rate [n = 45]), or wait-list control (n = 40) for 6 months. Main Outcomes and Measures:Feasibility measures were adherence to prescribed heart rate and exercise frequency of 3 days per week and safety. The clinical outcome was 6-month change in Unified Parkinson's Disease Rating Scale motor score. Results:A total of 128 patients were included in the study (mean [SD] age, 64 [9] years; age range, 40-80 years; 73 [57.0%] male; and 108 [84.4%] non-Hispanic white). Exercise rates were 2.8 (95% CI, 2.4-3.2) days per week at 80.2% (95% CI, 78.8%-81.7%) maximum heart rate in the high-intensity group and 3.2 (95% CI, 2.8-3.6; P = .13) days per week at 65.9% (95% CI, 64.2%-67.7%) maximum heart rate in the moderate-intensity group (P < .001). The mean change in Unified Parkinson's Disease Rating Scale motor score in the high-intensity group was 0.3 (95% CI, -1.7 to 2.3) compared with 3.2 (95% CI, 1.4 to 5.1) in the usual care group (P = .03). The high-intensity group, but not the moderate-intensity group, reached the predefined nonfutility threshold compared with the control group. Anticipated adverse musculoskeletal events were not severe. Conclusions and Relevance:High-intensity treadmill exercise may be feasible and prescribed safely for patients with Parkinson disease. An efficacy trial is warranted to determine whether high-intensity treadmill exercise produces meaningful clinical benefits in de novo Parkinson disease. Trial Registration:clinicaltrials.gov Identifier: NCT01506479.

Project description:The clinical phenotype of Parkinson's disease (PD) encompasses a wide range of non-motor symptoms (NMS) compromising the quality of life of affected patients. Currently, information about NMS in PD is scarce among Hispanic populations. Furthermore, few studies have reported the temporal pattern of NMS presentation. We conducted a cross-sectional study aimed to describe the frequency and time of NMS occurrence in Hispanic patients with PD using the self-completed NMS questionnaire (NMSQuest). Participants were interrogated about the time of each NMS presentation respect to the onset of motor symptoms. The frequency of NMS was described according to gender, age at disease onset, disease duration and Hoehn and Yahr (H&Y) stage. We enrolled 120 patients, 73.33% males and 26.66% females, with a mean age of 63.33 ± 8.60 years. All the participants presented at least 1 NMS. The median number of NMS per patient was 12. The most frequent NMS domains were miscellaneous, urinary tract, sleep/fatigue, and gastrointestinal tract symptoms, with no significant gender differences. The most frequent individual NMS were nocturia, urinary urgency, feeling sadness, and constipation. Any patient reported NMS before the onset of motor manifestations. The pattern of occurrence of NMS domains in our population was as follows: attention/memory, cardiovascular, gastrointestinal tract, perceptual problems/hallucinations, mood/cognition, urinary, miscellaneous, sleep/fatigue, and sexual function. Nausea/vomiting was the earliest symptom observed in all patients, whereas sexual dysfunction and changes in interest for sex were the last symptoms to occur. We found no differences in the total number and frequency of NMS between participants grouped according to their age at disease onset. Conversely, patients with a duration of disease >10 years reported a higher frequency of NMS compared to participants with a duration of disease < 10 years. The total number of NMS per patient increased as the HY stage progressed. The proportion of patients presenting symptoms of the gastrointestinal tract, urinary tract, mood/cognition, cardiovascular, and sexual function domains was higher in the HY 4-5 group. Our study provides relevant data to improve our understanding of NMS in PD, which may contribute to anticipate and plan diagnostic and therapeutic strategies among Hispanic PD patients.

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:STUDY OBJECTIVES:Parkinson disease (PD) non-motor symptoms are associated with sleep disorders and impair quality of life. Our objective was to assess the effect of obstructive sleep apnea (OSA) treatment using continuous positive airway pressure (CPAP) on PD non-motor symptoms. METHODS:In this prospective observational study, 67 patients with idiopathic PD underwent polysomnography. Those with moderate-severe OSA were offered CPAP therapy. Subjects were divided into those without OSA (OSA-), and those with OSA (OSA+). Analyses were conducted for 6 and 12 months' follow-up data. At 6 months, those who had used CPAP at home for at least 1 month were considered CPAP users (OSA+CPAP+), whereas those who did not try it, or declined further treatment following a short trial were considered non-users (OSA+CPAP-). For the 12-month analysis, only those still actively using CPAP at 12 months were included in the OSA+CPAP+ group. Non-motor symptom measurements were: Epworth Sleepiness Scale, Montreal Cognitive Assessment (MoCA), Unified Parkinson's Disease Rating Scale part 1 (UPDRS1), Parkinson's Disease Sleep Scale (PDSS), Fatigue Severity Scale, Apathy Scale, Beck Depression Inventory, and Hospital Anxiety and Depression Scale (HADS). RESULTS:Sixty-five participants were re-assessed at least once. At 6 months, 30 participants were categorized as OSA+CPAP+, 11 OSA+CPAP-, and 18 OSA-. At 12 months, 21 were categorized as OSA+CPAP+, 21 OSA+CPAP-, and 17 OSA-. The UPDRS1 and PDSS improved from baseline in OSA+CPAP+ at 6 months (-2.7, standard deviation [SD] 4.0, P = .001, and 7.9, SD 19.0, P = .03, respectively) and 12 months (-4.1, SD 5.4, P = .002, and 11.4, SD 24.4, P = .04, respectively), but not in other groups. The MoCA and HADS-A improved in OSA+CPAP+ at 12 months (1.7, SD 3.5, P = .04, and -2.1, SD 3.8, P = .02, respectively). The MoCA improved in those with low baseline MoCA and those with REM sleep behavior disorder. Mean CPAP use in users at 12 months was 3 hours 36 minutes per night. CONCLUSIONS:CPAP treatment of OSA in PD is associated with improved overall non-motor symptoms, sleep quality, anxiety, and global cognitive function over a 12-month period.

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Multifocal repetitive TMS for motor and mood symptoms of Parkinson disease: A randomized trial.

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Multifocal repetitive TMS for motor and mood symptoms of Parkinson disease: A randomized trial.

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