Low-Frequency Repetitive Transcranial Magnetic Stimulation Over Contralesional Motor Cortex for Motor Recovery in Subacute Ischemic Stroke: A Randomized Sham-Controlled Trial

Abstract

Background Low-frequency repetitive transcranial magnetic stimulation (rTMS) over the contralesional motor cortex (M1) has demonstrated beneficial effects on motor recovery, but evidence among patients with subacute stroke is lacking. We aimed to investigate whether 1-Hz rTMS over the contralesional M1 versus sham rTMS could improve arm function in patients with subacute ischemic stroke when combined with rehabilitative motor training. Methods In total, 77 patients who were within 90 days after their first-ever ischemic stroke were enrolled and randomly allocated to either real (n = 40) or sham rTMS (n = 37). We delivered 1-Hz 30-minute active or sham rTMS before each daily 30-minute occupational therapy sessions over a 2-week period. The primary endpoint was changes in the Box and Block Test (BBT) score immediately after the end of treatment (EOT). Secondary analyses assessed changes in Fugl-Meyer assessment, Finger Tapping Test (FTT), Brunnstrom stage, and grip strength. Clinical Trial Registration ClinialTrials.gov (NCT02082015). Results Changes in BBT immediately after the end of treatment did not differ significantly between the 2 groups ( P = .267). Subgroup analysis according to cortical involvement revealed that real rTMS resulted in improvements in BBT at 1 month after EOT (17.4 ± 9.8 real vs 10.9 ± 10.3 sham; P = .023) and Brunnstrom stage of the hand immediately after EOT (0.6 ± 0.5 real vs 0.2 ± 0.5 sham; P = .023), only in the group without cortical involvement. Conclusion The effects of real and sham rTMS did not differ significantly among patients within 3 months poststroke. The location of stroke lesions should be considered for future clinical trials.

Predicting Individual Treatment Response to rTMS for Motor Recovery After Stroke: A Review and the CanStim Perspective

“…Eleven studies included a sham-control condition either in a crossover or parallel-group design (16,20,(33)(34)(35)(37)(38)(39)(40)(41)(42). Of the 11 shamcontrolled trials, only four were randomized, double-blind trials (19,20,35,38).…”

“…In terms of rTMS protocols, 10 studies used excitatory rTMS (17,21,22,33,34,36,39) or iTBS (18,37,38) targeting ipsilesional M1 (17,18,21,22,34,(36)(37)(38)(39) or ipsilesional S1 (33), with either a single session (18,33,34,36,37,39) or a total of 10 sessions (17,21,22,38) of intervention. A total of 13 studies used inhibitory rTMS over contralesional M1, with a range from 5 up to 30 intervention sessions (19,20,(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)41). Two studies used both inhibitory contralesional, as well as excitatory ipsilesional rTMS over M1 (35,40), and a single study measured the effects of a single session of excitatory contralesional rTMS on M1, dorsal premotor cortex (dPMC), and anterior intraparietal sulcus (aIPS) (16).…”

Low-Frequency rTMS over Contralesional M1 Increases Ipsilesional Cortical Excitability and Motor Function with Decreased Interhemispheric Asymmetry in Subacute Stroke: A Randomized Controlled Study

“…The site of location (i.e., cortical or subcortical) could also influence the treatment effects of rTMS. A recent study by Kim et al revealed that low-frequency rTMS applied to the contralesional hemisphere resulted in improvements in BBT and hand motor control only in the group without cortical involvement [ 54 ]. There are several potential explanations.…”

Neurostimulation for Stroke Rehabilitation

“…Although there is promise for rTMS and TBS to improve stroke recovery (Zhang et al, 2017), there are also a number of negative reports from gold-standard randomized control trials (RCTs) (Dionísio et al, 2018;Kim et al, 2020). Several factors likely contribute to this disparity.…”