TMS May Ease Bradykinesia, Rigidity in Parkinson's

Megan Brooks

October 04, 2016

New research shows that high-frequency repetitive transcranial magnetic stimulation (rTMS) over bilateral motor cortex improves symptoms of bradykinesia and rigidity in patients with Parkinson's disease (PD).

This finding highlights the potential for developing targeted rehabilitation for specific motor symptoms based on specific cortical regions, the investigators say.

"Stimulation of the motor area can help Parkinson's symptoms, and this can be sustained over time. Knowing which symptoms are helped by TMS may be important to define better the target area," study investigator Alessandro Di Rocco, MD, executive director, The Fresco Institute for Parkinson's & Movement Disorders at NYU Langone Medical Center in New York City, told Medscape Medical News.

The findings, from a secondary subset analysis of the Magnetic Stimulation for the Treatment of Motor and Mood Symptoms of Parkinson's Disease (MASTER-PD) study, were reported September 23 at the Fourth World Parkinson Congress in Portland, Oregon.

The MASTER-PD study was a multicenter, double-blind, sham-controlled study in patients with idiopathic PD and significant motor problems despite treatment with medications.

The results, soon to be published, confirmed that high-frequency bilateral M1 stimulation is beneficial in improving the motor symptoms of PD. However, which specific motor symptoms improve has been less clear.

To investigate, Dr Di Rocco and colleagues did a subset analysis of 29 patients with PD enrolled in the study. The TMS protocol consisted of daily sessions of 2000 stimuli (50 × 4-second trains of 40 stimuli at 10 Hz) for 10 days, Monday to Friday, for 2 consecutive weeks over bilateral motor cortex vs placebo.

Patients were evaluated off PD medications at baseline and 1 month after treatment. Baseline demographic and clinical variables were similar between the two groups.

Investigators report that the United Parkinson's Disease Rating Scale Part III (UPDRS III) total score decreased more in the TMS group than the sham group (change, –4.9 points vs –0.3 points; P < .05).

However, post hoc analysis revealed that only bradykinesia (–0.29 points vs –0.01 points; P = .045) and rigidity (–0.2 points vs. 0.24 points; P = .006) decreased more in the TMS group than in the sham group. Axial symptoms and tremor scores did not significantly differ between the two groups.

Benefit "Modest"

J. Eric Ahlskog, MD, PhD, from the Mayo Clinic, Rochester, Minnesota, who reviewed the analysis for Medscape Medical News, noted that rTMS for PD symptoms has been investigated in more than 15 clinical trials over the last 15 years and the reported benefits in these trials have been "modest."

"This poster-report similarly revealed modest improvement in the UPDRS score. The improvement vs the control group was 5 points on the 56-point Part III UPDRS motor battery," Dr Ahlskog said.

"This reported clinical trial result should be contrasted with the response to carbidopa/levodopa treatment, which is the conventional medical therapy of Parkinson's disease. Optimized carbidopa/levodopa medical treatment results in improved UPDRS (Part III) scores at least three to four times that reported in this rTMS trial," he commented.

In Dr Ahlskog's view, "rTMS is of practical utility only if it can improve Parkinson's disease symptoms that do not respond to fully optimized carbidopa/levodopa treatment. Note that Parkinson's disease symptoms do not all have a dopamine substrate (levodopa replenishes brain dopamine). The appropriate clinical trial to document rTMS usefulness would study Parkinson's disease patients with residual symptoms that are incompletely responsive to optimized carbidopa/levodopa therapy (eg, gait freezing)," he said.

Also commenting for Medscape Medical News was Norbert Kovacs, MD, PhD, tenured professor, Department of Neurology, University of Pécs, Hungary, who wasn't involved in the study.

"In my opinion, the most important finding is that rTMS could improve bradykinesia and rigidity," he said. "Since many patients suffer from slowness of movements despite optimal oral pharmacological treatment, this beneficial effect of rTMS can improve their experiences of daily living. Moreover, the amelioration of rigidity after rTMS might result in less pain due to muscle stiffness."

Dr Kovacs also noted that the findings support a single-center, randomized, double-blind, sham-controlled study his group did looking at the efficacy of bilateral motor cortex rTMS.

"In our study we utilized the recently developed, more responsive and reliable MDS-UPDRS [Movement Disorder Society-Unified Parkinson's Disease Rating Scale] to measure changes in both the motor and nonmotor symptoms of PD," he explained.

"We were able to demonstrate that not only the motor symptoms but also some nonmotor symptoms (including depression) could be improved by the bilateral high-frequency rTMS. Moreover, we also confirmed that the health-related quality of life can also be improved significantly measured by the PDQ-39 [PD Questionnaire-39]. As far as I am aware, our study was the first to investigate the impact of rTMS on health-related quality of life."

Dr Kovacs said, "I think the most important message is that a noninvasive, well-tolerated rTMS can improve many aspects of PD, including slowness of movements and rigidity. It is particularly important in a patient population receiving combination of oral medications and experiencing several medication-related side-effects."

The study had no commercial funding, and the authors have disclosed no relevant financial relationships.

Fourth World Parkinson Congress. Poster P33.67. Presented September 23, 2016.

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