Comparative efficacy and acceptability of non-invasive neuromodulation technologies and botulinum toxin injections for post-stroke spasticity and motor function: a network meta-analysis of randomised controlled trials.

[BACKGROUND] Non-invasive neuromodulation is a promising approach for improving spasticity and motor function after stroke. However, it is still unclear which type of non-invasive neuromodulation is effective and evidence of important differences between them and botulinum toxin (BoNT) injection is limited. We aimed to assess the comparative efficacy and acceptability of non-invasive neuromodulation technologies and BoNT for post-stroke spasticity and motor function.

[METHODS] In this network meta-analysis, Cochrane Library, EMBASE, MEDLINE, Web of Science, Scopus, CNKI, and Wan Fang Data were searched from the earliest records to 8 October 2024. Randomised controlled trials that compared any type of non-invasive neuromodulation therapies, BoNT, and control treatments (including sham or no stimulation/injection) for post-stroke spasticity measured by modified Ashworth scale (MAS) were included. MAS, motor function, and acceptability were pooled using random-effects model with summary weighted mean difference (WMD) or risk ratios (RR) alongside 95% confidence interval (CI). Ranking probabilities of the treatments were estimated. Clinical importance was categorized as definite, probable, possible, or definitely not, considering the relationship between effect measures (95% CI) and minimal clinically important difference (1, 6, and 1.5 points for MAS, motor function, and acceptability, respectively). The quality of evidence was assessed using CINeMA online web. PROSPERO registration CRD42024543494.

[FINDINGS] 6260 studies were identified and 185 trials (11,185 participants; 12 interventions) were included. Compared with control treatments, BoNT, high- and low-frequency repetitive transcranial magnetic stimulation (HFrTMS and LFrTMS), and anodal, cathodal, and dual transcranial direct current stimulation (atDCS, ctDCS, and dtDCS) significantly improved spasticity at short-term follow-up (WMD range -0.81 to -0.31), but did not achieve clinical importance. At mid-term, ctDCS (WMD = -2.00; 95% CI: -3.03, -0.97) and dtDCS (WMD = -1.62; 95% CI: -3.22, -0.02) were more efficacious than control treatments in reducing post-stroke spasticity with probable clinical importance. For motor function, atDCS, ctDCS, and dtDCS were more efficacious than control treatments (WMD range 6.29-13.00), with probable clinical importance, while BoNT, HFrTMS, and LFrTMS with possible clinical importance (WMD range 3.42-5.28). Various modalities have comparable acceptability to control treatments (RR range 0.48-1.46). Confidence in accordance with CINeMA ranged from high to low. Sensitivity and meta-regression analyses on limb measured, cointervention, and stroke stage confirmed the main findings of this study.

[INTERPRETATION] Taken together with clinical importance, evidence available supports three forms of tDCS as effective treatments for post-stroke spasticity and/or motor impairments, whereas BoNT, HFrTMS, and LFrTMS for motor impairments. These modalities could be considered alongside rehabilitation interventions as core treatments for post-stroke spasticity and motor impairments.

[FUNDING] China Postdoctoral Science Foundation (2024M752230).