Repetitive TMS May Improve Gait, Balance in MS-Related Ataxia

PARIS — High-frequency repetitive transcranial magnetic stimulation (rTMS) is safe and effective in managing ataxia in patients with relapsing-remitting multiple sclerosis (RRMS), new research suggests.

A randomized, single-blind, pilot study of almost 40 patients with both RRMS and truncal ataxia showed that those who received 12 sessions of rTMS over 4 weeks and attended an "intensive" rehabilitation program showed significantly greater improvements on gait and balance measures than those who received a sham procedure plus the rehab program.

Interestingly, adherence was 100% in the rTMS group; and reports of adverse events (AEs) were classified as "mild and transitory." This included two reports each of nausea and headache and one report of dizziness.

Hatem Samir Shehata, MD, professor of neurology at Cairo University School of Medicine, Egypt, presented the findings here at the 7th Joint European Committee for Treatment and Research in Multiple Sclerosis-Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2017 meeting.

"High-frequency rTMS over the cerebellum has a positive effect on walking speed over short distance; it can improve balance when combined with intensive rehab techniques; and adverse events are negligible," Dr Shehata told attendees.

Session co-chair Trevor Kilpatrick, MD, PhD, director of the Melbourne Neuroscience Institute at the University of Melbourne, Australia, told Medscape Medical News after the session that this was a "fascinating study and provides some really exciting possibilities."

"As the speaker indicated, it's early days and there are other groups doing similar things. But I think there's potentially something in this," said Dr Kilpatrick.

Ataxia Common in MS

"Decrements in balance and gait are common mobility limitations in persons with MS," said Dr Shehata.

He noted that research published in November 2016 in Multiple Sclerosis and 3 months ago in Neuropsychiatric Disease and Treatment showed that more than 40% of 1600 patients with MS in a registry in Egypt developed ataxia during their disease course (follow-up, 1 to 56 months). "So this is a common scenario," he said.

For the current study, the investigators started enrolling patients (mean age, 35.2 years) in May 2012, with an interim data lock in June 2015. The 43 participants had both RRMS (mean duration, 4.9 years) and truncal ataxia.

In addition, mean Expanded Disability Status Scale (EDSS) score was 4.0, and 22 of the patients reported having fallen more than twice in the previous 6 months.

All were randomly assigned to receive real (n = 22) or sham (n = 21) rTMS for 4 weeks. Two participants from each treatment group were excluded from the analysis: One developed a relapse before treatment, 2 declined to participate, and 1 didn't show up.

The 12 sessions of rTMS included "20 trains, 20 seconds apart of 50 stimuli (at 5 Hz of 80% of MT [motor threshold]) using a figure-of-8-shape coil" attached over the cerebellum, write the investigators.

Both treatment groups also went through a 45-minute rehab program scheduled 5 times a week. Aiming to increase muscle strength, decrease spasticity, and improve balance and gait, the program included balance exercises, lumbar stabilization exercises, gait training, and "motor relearning techniques." It also included moderately intense aerobic exercise training on a bicycle ergometer to improve cardiorespiratory fitness.

Outcome measures included the 10-meter walk test (10MWT), the Berg Balance Scale (BBS), and the Time Up and Go (TUG) test.

Significant Improvements

Results showed that the real rTMS group had significant improvements from baseline to 4 weeks on the 10MWT and TUG.

Table. Main Outcomes in Real rTMS Group

Outcome	At Baseline (s)	After Treatment (s)	Pre-Post Change (%)	P Value
10MWT	15.4	13.0	–10.1	.001
TUG	15.8	14.2	–5.4	.02

The rTMS group also had significant improvement on the BBS (from 39.3 to 46.5; P = .01), whereas the sham-treatment group did not (39.9 to 43.8; P = .12).

In addition, falling episodes decreased significantly after real rTMS sessions.

During his talk, Dr Shehata discussed a 27-year-old female study participant who had a baseline EDSS score of 5.5.

In the "before" video that was shown, she walked hesitantly and continuously reached out to steady herself. In the "after" video, which was taken just 2 months later, the smiling patient walked confidently down a hallway and only put a hand lightly on the wall when she turned around quickly at the end.

"She had had three falls just before the treatment sessions, but no falls occurred during the month of sessions; long-term follow-up of about 8 months also showed no falls," reported Dr Shehata.

Durability of Effect?

During the postpresentation question-and-answer session, Dr Shehata was asked, on the basis of his own experience, how long-lasting the effects have been.

"That's an important question," he said. "Some of our patients have needed to repeat the sessions after 6 months, while some of our patients have extended the effect of rTMS for a longer period. There are no solid data yet, but we are planning future studies."

After the session, Dr Kilpatrick told Medscape Medical News that durability of effect is the key issue for rTMS, as is the possibility "to learn from the use of the technique in other diseases, such as depression, where it is well validated."

The other main issue, he said, is whether rTMS needs to be combined with physical therapy for there to be an effect.

"If it had efficacy independently from intensive physical therapy, it would be an avenue for benefit without a lot of resource input from other modalities," said Dr Kilpatrick.

"I suspect it's going to require the physiotherapy, but I think it's interesting to try and dissect out the relative benefits of the two aspects of the approach."

He added that it would be interesting to see whether rTMS can work alone but is even better with the additional therapy, or whether both are needed to see any improvement at all.

"The first thing is to substantiate these results. If they are substantiated, then we need to dissect out what's necessary and what's sufficient," Dr Kilpatrick said. "This is a really difficult area, and there's a lot of question about what we can do for people with ataxia."

The study authors and Dr Kilpatrick have disclosed no relevant financial relationships.

7th Joint European Committee for Treatment and Research in Multiple Sclerosis-Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2017. Free Communications Session 3, oral presentation 194. Presented October 27, 2017.

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