Clinical and neurophysiological determinants of response to contralesional low-frequency repetitive transcranial magnetic stimulation after stroke: A systematic review and meta-analysis
Discuss this preprint
Start a discussion What are Sciety discussions?Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Background
Low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) over the contralesional primary motor cortex is widely used for post-stroke upper-limb rehabilitation, but treatment response varies substantially. This systematic review and meta-analysis aimed to quantify the efficacy of contralesional LF-rTMS and to examine whether baseline motor impairment severity and corticospinal tract (CST) integrity modify treatment effects.
Methods
We searched seven databases from inception to July 2026 for randomized controlled trials of contralesional LF-rTMS (≤1 Hz) versus sham after stroke, with comparable rehabilitation in both arms. The primary outcome was the change in Fugl-Meyer Assessment for the upper extremity (FMA-UE) scores. Random-effects meta-analysis used restricted maximum likelihood estimation with Knapp–Hartung adjustment. Effect modification was examined through meta-regression and biomarker-stratified analyses, and neurophysiological outcomes were also synthesized.
Results
Thirty trials (33 comparisons, 1,668 participants) were included. LF-rTMS produced greater FMA-UE improvement than sham (mean difference 4.11 points, 95% CI 2.83–5.39; Hedges g 0.64, 95% CI 0.45–0.84), with substantial heterogeneity. Baseline severity did not significantly modify the effect in continuous meta-regression. However, exploratory within-trial biomarker-stratified analyses suggested larger effects in participants with preserved CST integrity or positive motor-evoked potential (MEP) status. LF-rTMS also shortened MEP latency and central motor conduction time, but these measures could not be validated as surrogate endpoints.
Conclusions
Contralesional LF-rTMS provides a statistically significant but modest improvement in post-stroke upper-limb motor recovery. Baseline clinical severity alone may not identify responders, whereas CST integrity is an exploratory, hypothesis-generating candidate biomarker. It requires confirmation in adequately powered biomarker-stratified trials before it can inform clinical decisions.
Trial Registration
The study was registered with the International Prospective Register of Systematic Reviews (PROSPERO: CRD420261441561).
