The theurapeutic effect of neuronavigation in transcranial magnetic stimulation for stroke: A systematic review and meta-analysis of randomized controlled trials

Non-invasive brain stimulation (NIBS) is a promising new tool for rehabilitation in stroke patients. Repetitive transcranial magnetic stimulation (rTMS) is a subcategory of NIBS, used to modulate brain plasticity and improve post-stroke recovery. Neuronavigation is used in order to improve the accuracy of stimulation with the aim of achieving a superior clinical outcome than with conventional targeting.The objective of this review is to evaluate the efficacy of navigated rTMS in subacute and chronic stroke patients in comparison to sham stimulation. Motor performance, disability and quality of life outcomes will be assessed. A systematic-review and a random-effects meta-analysis are conducted comparing the 5 most common types of rTMS; high frequency rTMS, low frequency rTMS, intermittent theta burst stimulation, continuous theta burst stimulation and Hebbian type rTMS. Outcomes included in the meta-analysis are Fugl-Meyer Assessment - Upper Extremity (FMA-UE; primary outcome), Wolf Motor Function Test (WMFT) and Jebsen-Taylor Test (JTT) (secondary outcomes). The Cochrane’s Risk of Bias RoB2 tool is used for risk of bias assessment, funnel plot/Egger’s test for publication bias and GRADE for certainty of evidence assessment.13 randomized controlled trials (RCTs) were included after a thorough screening of 1905 studies across 3 databases, Pubmed, Scopus and Cochrane CENTRAL. They consisted of 606 patients receiving either active (n=360) or sham stimulation (n=246). The pooled standardized mean difference favored rTMS over sham (Hedges’ g = 0.45, 95% CI 0.14–0.76). Subgroup analyses by stimulation type showed cTBS to be the most effective modality. However, the differences between stimulation types were not statistically significant (p=0,082). Regarding the subgroup analyses by stroke chronicity, only subacute stroke patients improved significantly g=0,40 (96%CI: 0,11 to 0,7). When including only RCTs that assessed FMA-UE (n=9), the result was a significant pooled MD=4,2 (95%CI: 2,09 to 6,31). Heterogeneity was at I²=64,1% and GRADE assessment at low to moderate. In conclusion, navigated rTMS provided a small to moderate effect on motor rehabilitation in stroke patients compared to sham. The high heterogeneity and possible publication bias of small navigated rTMS RCTs, emphasize the need for large RCTs in this field of research. Comparative reviews between navigated and conventional rTMS RCTs will conclude whether neuronavigation provides a benefit in the clinical outcomes of patients.