Stimulation Dose and Efficacy of Intermittent Theta-Burst Stimulation for Upper-Limb Motor Recovery After Stroke: A Systematic Review and Meta-Analysis
DOI: Pending DOI
Synopsis
This systematic review and meta-analysis evaluated the efficacy of iTBS for upper-limb stroke rehabilitation and explored whether clinical recovery depends on total pulse dose.
Searching PubMed for randomized sham-controlled trials using the Fugl-Meyer Assessment-Upper Extremity, seventeen trials were identified, with eight providing sufficient data for quantitative pooling. Results showed that iTBS moderately improved upper limb motor impairment compared to sham stimulation. However, meta-regression revealed no evidence that treatment effects increased with higher total pulse doses within conventional once-daily protocols.
In conclusion, while iTBs has proven to enhance upper limb motor recovery after stroke, a clear dose-response relationship remains unclear.
Background
Intermittent theta-burst stimulation is increasingly investigated as an adjunct to upper-limb rehabilitation after stroke. (1–4) Because some neurophysiologic studies suggest that iTBS-induced cortical excitability changes may vary with the number of pulses delivered (5,6) , stimulation dose is a plausible determinant of treatment response. However, rehabilitation trials vary in pulses per session, number of sessions, and total stimulation exposure, and the relationship between total pulse dose and clinical recovery has not been quantitatively examined.
Methods
PubMed was systematically searched for randomized sham-controlled trials of iTBS after stroke reporting Fugl-Meyer Assessment–Upper Extremity outcomes. (7) Records were screened against predefined criteria, and per-arm outcome and dosing data were extracted. Standardized effects were calculated as Hedges g and pooled using random-effects models, using change-from-baseline data when available and endpoint data otherwise. A study-level random-effects meta-regression examined the association between effect size and total pulse dose.
Results
Seventeen randomized controlled trials met inclusion criteria, of which eight provided data sufficient for quantitative analysis. iTBS was associated with a moderate improvement in FMA-UE compared with sham stimulation (Hedges g = 0.69; 95% CI, 0.29–1.08; p = 0.001; I² = 36%). A sensitivity analysis restricted to change-score data showed a similar direction of effect and lower heterogeneity (g = 1.07; 95% CI, 0.47–1.67; I² = 17%). In study-level meta-regression, there was no evidence that treatment effect increased with total pulse dose within the analyzable 6,000–18,000-pulse, once-daily treatment range (slope = +0.03 g per 1,000 pulses; 95% CI, −0.06 to +0.12; p = 0.47).
Discussion
Intermittent theta-burst stimulation is emerging as a non-invasive tool for upper limb rehabilitation post-stroke, yet its introduction into clinical practice remains limited by a lack of standardized protocols. This meta-analysis confirms a moderate beneficial effect on upper limb-motor impairment, supporting its potential as a supplement to conventional therapy. However, the absence of a clear dose-response relationship challenges the assumption that more pulses necessarily yield a greater recovery.
These findings suggest that conventional once-daily iTBS protocols may confer meaningful motor benefits, but current evidence is insufficient to recommend a specific total pulse dose. Individualized approaches accounting for stroke severity and time since stroke, may be more relevant than dose escalation alone.
This review highlights a clear need for prospective dose-finding trials with pre-registered protocols and standardized FMA-UE reporting to define the optimal stimulation schedule and total dose.
Disclosures
Nothing to disclose by any authors
References
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