Transcranial Magnetic Stimulation Combined With Multimodality Aphasia Therapy for Chronic Poststroke Aphasia: A Randomized Clinical Trial

Abstract

Background and objectives: Intensive speech therapy may improve recovery from poststroke aphasia. Further evidence suggests that pairing repetitive transcranial magnetic stimulation (rTMS) with intensive speech therapy might augment outcomes. This sham-controlled randomized clinical trial evaluated the efficacy of 1-Hz rTMS over the right pars triangularis combined with multimodality aphasia therapy (M-MAT) in chronic poststroke aphasia.

Methods: A parallel-group, double-blind, sham-controlled randomized clinical trial was conducted between April 2021 and May 2023 at an outpatient neurorehabilitation clinic. Individuals with chronic nonfluent aphasia after left middle cerebral artery stroke (>6 months from stroke) were enrolled and randomly assigned to receive either rTMS or sham stimulation combined with 35 hours of M-MAT over 10 days. The primary outcome was the Western Aphasia Battery aphasia quotient (WAB-AQ) measured at 3 weeks and 15 weeks. Intention-to-treat analysis examined treatment effects over time using linear mixed models.

Results: A total of 44 participants were randomized. Forty-three (mean [SD] age, 63.4 [12.3] years; 14 women [32.6%]) completed the intervention. Overall, WAB-AQ scores improved from baseline to 15 weeks regardless of rTMS allocation (mean difference 5.33, 95% CI 2.9-7.8, p < 0.001). We observed a significant group-by-time interaction (β = 0.31, p = 0.024), suggesting that those who received rTMS combined with M-MAT improved more over time than those who received sham. At 15 weeks, the rTMS group demonstrated significantly less word-finding difficulties and more complete and longer sentences with fewer pauses compared with sham as indicated by higher WAB-AQ scores (mean difference 4.1 points, 95% CI 0.6-7.6, p = 0.022). The change from baseline at 15 weeks was greater in the rTMS group (7.6 points, 95% CI 4.1-11.1) compared with sham (3.0 points, 95% CI -0.3 to 5.2; mean difference 4.6 points, 95% CI 0.6-8.6, p = 0.024).

Discussion: Intensive administration of M-MAT alone improves speech production in patients with chronic poststroke aphasia. Combining 1-Hz rTMS with M-MAT is associated with supplemental improvements in aphasia severity at follow-up. rTMS is a promising candidate as an adjuvant therapy to M-MAT.

Trial registration information: ClinicalTrials.gov Identifier: NCT04102228.

Classification of evidence: This study provides Class III evidence that in patients with aphasia 6 or more months after a stroke, 1-Hz rTMS combined with intensive M-MAT improves WAB-AQ more than sham stimulation plus M-MAT.

Figure 1. Participant Flow Diagram

M-MAT = multimodality aphasia therapy; rTMS = repetitive TMS; TMS = transcranial magnetic stimulation; WAB = Western Aphasia Battery–Revised.

Figure 2. Lesion Overlap Image Showing the Number of Participants With a Lesion in Each Voxel Overlaid on an MNI Standard Template Image

MNI = Montreal Neurological Institute; rTMS = repetitive transcranial magnetic stimulation.

Figure 3. Changes in Primary Outcome Measures Over Time

(A) Adjusted mean aphasia severity (WAB-AQ) over time. The dashed vertical line indicates the upper bound of the Johnson-Neyman interval, which specifies the point in time where the group-by-time interaction is deemed to be significant. Colored ribbons indicate 95% confidence intervals. (B) Unadjusted change from baseline in WAB-AQ at 3 and 15 weeks in rTMS and sham groups. *Statistical significance at p < 0.05. rTMS = repetitive transcranial magnetic stimulation; WAB-AQ = Western Aphasia Battery–Revised aphasia quotient.