COPENHAGEN, Denmark — Deep repetitive transcranial magnetic stimulation (TMS) of the motor cortex has the potential to reduce fatigue and depression in patients with multiple sclerosis (MS), a new study suggests.

The study was presented by Sven Schippling, University Medical Centre, Zurich, Switzerland, at the recent 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). 

He explained to Medscape Medical News that TMS is a noninvasive, safe technique for stimulation of brain regions that has been shown to be effective in major depression, autism, and schizophrenia but has not been investigated previously for fatigue and depression in MS. He noted that fatigue and depression are frequent symptoms in patients with MS, with two thirds of patients reporting fatigue as their most disabling symptom and depression occurring in more than half of patients.

Dr. Schippling and colleagues tested the TMS strategy on 2 different areas of the brain: the prefrontal cortex and the motor cortex. "We thought the prefrontal cortex would be the best area to target as it is more involved in depression, but to our surprise it turned out that the results for the motor cortex area were much better," Dr. Schippling commented.

He cautioned that this was a preliminary phase 1/2 study with small patient numbers, so any conclusions must be speculative but that the impressive results in the motor cortex group may be explained by easing the demands on that part of the brain when carrying out basic tasks.

"We know in MS patients, even from the earliest stages of the disease, recruit a much broader area of the brain than patients without the disease to achieve just a simple motor task," he said. "Giving exogenous stimulation to the key areas involved in motor tasks could reduce the area of the brain being taxed, so sparing energy."

The study involved 28 patients with stable MS and a score of 4 or more on the Fatigue Severity Scale (FSS) or a score of 12 or more on the Beck Depression Inventory (BDI).

They were randomly assigned to TMS of the prefrontal cortex or the motor cortex or to sham stimulation as control. The 2 treatment groups received 18 sessions of deep TMS over 6 weeks.

Those who were assigned to prefrontal treatment received 50 trains (2 seconds) at 18 Hz, repeating at 20-second intervals for 18 minutes. Those assigned to motor cortex treatment received 40 trains (4 seconds) at 5 Hz, repeating at 20-second intervals for 16 minutes.

The researchers used an H coil device, which allows direct stimulation of deeper brain regions as compared with the conventional figure of 8 coils.

Safety results showed no severe adverse events, such as seizure or relapse. Other adverse events occurred in about one third of patients and were similar across the 3 groups. The most common adverse effects were mild to moderate headache and paresthesia of the lower limbs.

Efficacy results showed no significant changes in fatigue as measured on the FSS or depression as measured on the BDI with the sham control groups or in patients receiving TMS to the prefrontal cortex.

However, in patients who received TMS to the motor cortex, there was a decrease in the fatigue score during the treatment period that reached significance in the follow-up phase (change, –26.72%; P = .001).

In addition, a significant decrease in the depression scores were seen with motor cortex stimulation, as early as 2 weeks after first stimulation (change, –25.74%; P = .013), reaching a maximum in the follow-up phase (change, –39.23%; P = .001).

Phase 2 trials are now planned with larger patient numbers using TMS targeted again to both the prefrontal and motor cortex areas.

Dr. Schippling has received speaker honoraria and travel grants from Bayer, Biogen Idec, Merck Serono, Novartis, TEVA, and Genzyme/Sanofi Aventis and research grants from Bayer, Biogen, and Merck Serono.

29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Abstract #165. Presented October 4, 2013.


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