Transcranial Stimulation Lacks Efficacy in Parkinson's

Emma Hitt, PhD

June 01, 2011

June 1, 2011 (Lisbon, Portugal) — Using an intensity level that ensures study blinding, researchers have found that high-frequency repetitive transcranial magnetic stimulation (rTMS) does not improve either motor or nonmotor symptoms in Parkinson's disease (PD).

"Because rTMS has associated with huge placebo effect, this is a very important concern to receive reliable data," lead study author Norbert Kovacs, MD, told Medscape Medical News.

Dr. Kovacs is with the Department of Neurology at the University of Pécs in Hungary and presented the findings here at the 21st Meeting of the European Neurological Society.

The researchers specifically used an intensity level that ensured the blinding of the study but applied the most common high-frequency stimulation over the most promising area, the motor cortex. "Most of the available studies applied quite different technical parameters, which make the comparison almost impossible," he said.

"Based on our study, 5-Hz high-frequency bilateral motor cortex rTMS is ineffective to improve the motor and nonmotor features of Parkinson’s disease, but we have to carry on further studies involving larger pool of patients to further clarify the role of rTMS in the treatment arsenal of Parkinson’s disease," Dr. Kovacs concluded.

rTMS and Motor Symptoms

According to the researchers, several open-label and case studies have shown that rTMS of the motor cortex may improve clinical symptoms of patients with PD. "However, this hypothesis requires further confirmation," the study authors note.

The current study evaluated rTMS in 22 patients with PD who were assigned to receive either actual rTMS (90% of resting motor threshold, 5 Hz, 600 pulses a day for 10 days) or sham rTMS over the motor cortex. Examinations were performed by an investigator blinded to study treatment at baseline, after 1 day, and 30 days after treatment had ended.

They report that a similar level of improvement occurred in both the treatment and sham groups 30 days after treatment ended as measured by the Unified Parkinson's Disease Rating Scale (UPDRS) III, with an 11-point increase in the stimulated group compared with 10 points in the sham-treated group.

No other significant differences were observed between the groups on other measures, including the Mini-Mental State Examination, UPDRS, Hoehn-Yahr scale, Epworth Sleepiness Scale, visual analog scale, Montgomery-Asberg Depression Rating Scale, Beck Depression Inventory, and Trail-Making and Stroop tests.

No adverse events were reported in either group.

"Both real and sham stimulation produced a considerable improvement in the UPDRS III," the study authors conclude. "Because we could not find any significant changes between the 2 groups, we might conclude that this improvement is probably due to the placebo effect of rTMS."

'Huge' Placebo Effect Confirmed

"There are many ways of using rTMS for Parkinson treatment," said independent commentator Mark Hallett, MD, senior investigator with the Human Motor Control Section, Division of Intramural Research, at the National Institutes of Health's National Institute of Neurological Disorders and Stroke.

However, "it appears that this particular set of stimulation parameters is not effective," he told Medscape Medical News. "It is well known that there is a large placebo effect in Parkinson’s disease, and this is confirmed in this study."

Dr. Hallett pointed out that the use of rTMS for Parkinson's disease remains fully experimental. "It is still not clear whether rTMS — or other forms of noninvasive brain stimulation method, like transcranial direct current stimulation — can be therapeutically useful," he said. "There are many possible parameters, and, unfortunately, it takes considerable effort to evaluate any 1 set.

"This result does not invalidate earlier studies that might have used different stimulation parameters. TMS still might be useful, and further studies are worthwhile," he added.

The study was not commercially funded. The study authors have disclosed no relevant financial relationships. The independent commentator, Dr. Hallett, reports that he is one of the inventors of the H-coil, a coil for use with TMS and patented by the National Institutes of Health, which is being used by the Brainsway Company for studies in depression and other neurologic disorders.

21st Meeting of the European Neurological Society (ENS): Abstract 291. Presented May 30, 2011.