Inhibitory Right-Brain TMS Improves Language After Stroke

July 11, 2013

Use of inhibitory transcranial magnetic stimulation (TMS) over the speech area in the right side of the brain significantly improved language recovery in patients with stroke, new research shows.

"The dominant language center is normally in the left hemisphere of the brain. After a stroke, when this area is damaged, similar regions in the right hemisphere take over, but this is not as effective as if the left side recovers. Brain imaging studies show that stroke patients with right hemisphere activation generally do worse. So we used TMS treatment to inhibit the right hemisphere area, so the left hemisphere area has to function," lead investigator Alexander Thiel, MD, McGill University, Montreal, Quebec, Canada, told Medscape Medical News.

The study was published online June 27 in Stroke.

First Proof-of-Concept Study

Dr. Thiel compared the strategy with treating someone who has paralysis on 1 side of their body.

"If someone has paralysis of one arm, if you immobilize the good arm, the patient is forced to use the paralyzed arm, which helps it recover."

The inhibitory TMS is carried out by positioning a hand-held electromagnetic coil over the appropriate part of the brain. The fluctuating magnetic field induces an electrical current that blocks normal function.

Dr. Thiel noted that a few single case reports and case series of this treatment have been published previously, but this is the first randomized proof-of-concept study.

The study involved 24 patients (all right-handed) with subacute post-stroke aphasia from the rehabilitation hospital RehaNova in Cologne, Germany. They were randomly assigned to a 10-day protocol of 20-minute inhibitory 1-Hz TMS over the right triangular part of the posterior inferior frontal gyrus or sham stimulation, followed by 45 minutes of speech and language therapy.

Activity in language networks was measured with O-15-water positron emission tomography before and after treatment, and language performance was assessed by using the Aachen Aphasia Test (AAT) battery.

Results showed that language performance was significantly improved in the TMS group. The largest improvements were seen in the subtest of naming objects, but comprehension, token test, and writing also all improved.

Table. Change in Scores for Active TMS vs Sham

Variable Difference in Scores Between Active and Sham Treatment P Value
Global AAT score 16.2 .003
Comprehension 2.9 .082
Token test 2.9 .078
Naming 5.2 .002
Writing 3.1 .065
Repetition 2.0 Not significant

 

Imaging results showed that patients in the TMS group also activated proportionally more voxels in the left hemisphere language center after treatment than before (difference in activation volume index) compared with sham-treated patients. There was a moderate but significant linear relationship between activation volume index change and global AAT score change.

"We found that patients who underwent the real TMS treatment had 2-3 times better recovery of their aphasia than patients who were given the sham treatment. The principal improvement was in the ability to name objects. This is very important — you cannot communicate if you can't name things," said Dr. Thiel.

Pronounced Effect

"This study is telling us that this therapy seems to work the way we think it should. We are very excited by these results. We were a little surprised by the magnitude of the effect. We didn't expect it to be so pronounced. But the fact that the imaging results showed a shift in brain activity from the right to the left, corresponding with the improvement in aphasia, is reassuring and supports that this model is pathophysiologically valid."

He noted that the effect was measured immediately after the treatment. "How long it will last we don't know. Some previous studies suggest it does last long-term, but we need to study this further."

The next step is to try reproducing these results in a larger study. Such a study — NORTHSTAR — is now planned to start in October. Funded by the Canadian Institutes of Health Research, it will involve 100 patients from Canada and Germany. Patients will be assessed at day 10, as in the current study, but also longer term — about a month after treatment stops.

In the current study, patients were treated within 3 months after stroke. In the next study they will be treated within 1 month.

"We think the earlier we perform this treatment the more likely it is to be effective, as we believe there is a window of a few weeks after stroke when the right side of the brain becomes very active.

"We have seen this in imaging studies. Eventually it shifts back to the left. But the more the left brain takes over again the better the recovery. This treatment is just trying to accelerate this naturally occurring pattern," said Dr. Thiel.

Asked about risks, Dr. Thiel reported that aphasia did not deteriorate with the treatment.

The main adverse effect is headaches because TMS can cause the scalp muscles to contract, but these are benign and respond to normal headache treatments, he said.

In rare cases TMS has been associated with seizures, but this did not occur in the current study.

"I would think seizures would be very unlikely as we are downregulating electrical activity and that should prevent seizures. TMS is inhibitory when used below 4 Hz and excitatory when used above 4 Hz. We used 1 Hz, so this will definitely be inhibitory," he said.

He noted that in theory it might be possible to use excitatory TMS on the damaged area of the left hemisphere, but this would be more difficult.

"As the infarct is there the primary language center is damaged and secondary language centers have taken over. We don't know exactly where these are, and the risks of inducing seizures would be greater from excitatory TMS."

The current study was funded by The Walter and Marga Boll and Wolf-Dieter-Heiss Foundations.

Stroke. Published online June 27, 2013. Abstract

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