Brain Stimulation May Significantly Improve Post-Stroke Aphasia

Transcranial direct current stimulation (tDCS) may significantly improve the speech of stroke patients with aphasia, new research shows.

Results of a randomized controlled trial show that patients who received active brain stimulation as an adjunct to speech therapy could correctly name a mean of 14 more words 1 week after treatment compared with baseline, for a relative 70% increase in correct naming, vs 8 more words for a controlled comparison group receiving sham stimulation.

Because aphasia is "pretty resistant" to speech therapy, "we were looking for ways to boost or enhance the outcome," Julius Fridriksson, PhD, Department of Communication Sciences and Disorders, Arnold School of Public Health, University of South Carolina in Columbia, told Medscape Medical News.

"I was surprised by the magnitude of the change in the active group compared to the controls. We had said ahead of time if we could achieve a 15% improvement, we would be happy and would continue studying this," Fridriksson said.

The study was published online August 20 in JAMA Neurology.

Room for Improvement

It is estimated that in the United States, at least 1 million people experience post-stroke aphasia.

Fridriksson noted that although speech therapy for aphasia is worthwhile, there is room for improvement. Many patients make only minimal gains, his previous research revealed.

tDCS delivers a 1- to 2-mA electrical current, typically between two electrodes placed on the scalp. Although the neural mechanism(s) underlying its efficacy is not fully understood, past research has shown that anodal tDCS (A-tDCS) generally enhances cortical activity.

The study’s primary endpoint was change in the number of common objects correctly named 1 week after stimulation compared with baseline using the Philadelphia Naming Test and the Naming80 instrument.

Investigators assessed 74 people with long-term aphasia, ranging from age 25 to 80 years, in an intent-to-treat analysis. Most were men (70%), and the majority was non-Hispanic white (84%).

The researchers enrolled participants from August 2012 to March 2017, at least 6 months after a single ischemic stroke in the left hemisphere. They confirmed aphasia by using the Western Aphasia Battery-Revised.

Broca aphasia affected 53% of participants. Another 18% experienced conduction aphasia, 15% had anomic aphasia, and 9% had Wernicke aphasia. The remaining patients had global or transcortical motor forms of aphasia.

Unique Design

All participants completed two MRI sessions at baseline, including a T1- and T2-weighted structural MRI and a picture-naming fMRI protocol. Thirty-four participants were randomly assigned to A-tDCS and the other 40 to a sham intervention (S-tDCS).

A constant current stimulator (Phoresor IIPM850, Iomed Inc) provided 1 mA of A-tDCS stimulation-induced between two 5 × 5-cm saline-soaked sponges serving as electrodes.

Patients were instructed to press a green button when the word they heard through headphones matched the picture of a common object on a computer screen or a red button if the objects did not match.

The investigators chose a unique futility study design — also known as a failure to reject a null hypothesis. This approach allowed them to enroll one-third fewer participants than a traditional superiority study would require.

Based on pilot data, they assumed that A-tCDS works and so only had to demonstrate there was no difference between active and sham interventions (their null hypothesis). By rejecting the lack of difference, they found a benefit to A-tCDS.

"Subsequently, we have done the superiority analyses," Fridriksson said. "They are not included in this paper, but they show that if we had just kept it as a regular clinical trial, it would have been positive either way.”

Baseline aphasia severity correlated with an overall significant improvement in naming at 1 week after treatment (Pearson ρ = 0.29; P = .01). Between the A-tCDS and S-tCDS groups, the mean increase in correctly named words was 5.7, favoring active stimulation (95% confidence interval [CI], −0.9 to 12.3).

Multiple Time Points

The investigators also assessed performance at two subsequent time points.

For example, 4 weeks after treatment, the adjusted mean change in correct naming again favored A-tDCS. Compared with baseline, participants who received active stimulation named 17 more words (95% CI, 11.3 - 22.4) vs an increase of 9 words in the S-tDCS group (95% CI, 4.4 - 14.5).

At 24 weeks after treatment, the adjusted mean change from baseline in correct naming was 15 words in the A-tCDS group (95% CI, 8.8 - 21.1) and 7 words (95% CI, 1.59 - 12.0) in the S-tDCS group.

Treatment was well tolerated, the investigators report. Two participants did not complete all 15 treatment sessions; one person randomly assigned to A-tDCS dropped out of the study after 11 sessions. The other discontinuation was a patient in the S-tCDS group who experienced a seizure during the trial.

Eight mild adverse events were reported, including two patients who experienced erythema in the A-tCDS group, as well as two reports of headache and two reports of dizziness in the S-tCDS group.

"Given that the total number of A-tDCS sessions administrated here was more than 500, the rate of adverse events shown in this study would have to be considered very low," the authors note.

Feasible for Clinical Practice

Beyond the research findings, tDCS is relatively inexpensive, at "about $500 to $700 to get the hardware for the setup," Fridriksson said. "So I would think this is very feasible for clinical practice."

In addition, the investigators specifically chose the number of treatment sessions that aligns with the average number of sessions that patients with aphasia typically receive in the United States.

A limitation of the study is how well a better performance on the object-naming exercise correlates to improved daily function among those with aphasia.

However, "we believe that even one to two words' improvement could be meaningful to some patients who have very limited speech output," the researchers write.

Rejection of their null hypothesis supports conducting a larger trial to further evaluate the effects of A-tDCS on aphasia treatment, they add.

The findings "give us hope that speech therapy will be quite a bit more potent if you can add the electrical brain stimulation," Fridriksson said.

He noted that the next step could be to investigate an ideal dose of A-tDCS or to assess the genetics behind treatment response.

"For this group we actually did genetic testing on response to treatment," he said. "So there is a specific gene we had in mind, the brain-derived neurotropic factor gene, and we found the treatment response is specific to genotype."

The genetic findings will be explained in a separate paper in Brain Stimulation.

"Clinically Important"

"What does the ability to name 13.9 more objects mean in real life? If you are trying to order lunch or select a grandchild’s birthday present, it can mean the world. If you are litigating a criminal case, it is likely insufficient," Steven C. Cramer, MD, Departments of Neurology, Anatomy, and Neurobiology and of Physical Medicine and Rehabilitation at the University of California-Irvine, notes in an accompanying editorial.

"For most patients, this improvement may be clinically important," Cramer adds.

"The authors conclude, rightly, that these data provide motivation to proceed with further study of the effect of this form of active tDCS combined with speech therapy on aphasia outcomes poststroke," he writes.

Cramer also notes a few unanswered questions for future trials: What population should be enrolled? Which dose should be studied? And for how long should patients be assessed after therapy?

The National Institute on Deafness and Other Communication Disorders funded the study. Fridriksson has disclosed no relevant financial relationships. Dr Cramer serves as a consultant for Microtransponder, Dart NeuroScience LLC, Roche, Neurolutions Inc, Regenera, AbbVie, SanBio, and TRCare.

JAMA Neurol. Published online August 20, 2018. Full text, Editorial

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