Abstract
BackgroundRehabilitation is critical for reducing stroke-related disability and improving quality-of-life post-stroke. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique used as stand-alone or adjunct treatment to physiotherapy, may be of benefit for motor recovery in subgroups of stroke patients. The Canadian Platform for Trials in Non-Invasive Brain Stimulation (CanStim) seeks to advance the use of these techniques to improve post-stroke recovery through clinical trials and pre-clinical studies using standardized research protocols. Here, we review existing clinical trials for demographic, clinical, and neurobiological factors which may predict treatment response to identify knowledge gaps which need to be addressed before implementing these parameters for patient stratification in clinical trial protocols.ObjectiveTo provide a review of clinical rTMS trials of stroke recovery identifying factors associated with rTMS response in stroke patients with motor deficits and develop research perspectives for pre-clinical and clinical studies.MethodsA literature search was performed in PubMed, using the Boolean search terms stroke AND repetitive transcranial magnetic stimulation OR rTMS AND motor for studies investigating the use of rTMS for motor recovery in stroke patients at any recovery phase. A total of 1,676 articles were screened by two blinded raters, with 26 papers identified for inclusion in this review.ResultsMultiple possible factors associated with rTMS response were identified, including stroke location, cortical thickness, brain-derived neurotrophic factor (BDNF) genotype, initial stroke severity, and several imaging and clinical factors associated with a relatively preserved functional motor network of the ipsilesional hemisphere. Age, sex, and time post-stroke were generally not related to rTMS response. Factors associated with greater response were identified in studies of both excitatory ipsilesional and inhibitory contralesional rTMS. Heterogeneous study designs and contradictory data exemplify the need for greater protocol standardization and high-quality controlled trials.ConclusionClinical, brain structural and neurobiological factors have been identified as potential predictors for rTMS response in stroke patients with motor impairment. These factors can inform the design of future clinical trials, before being considered for optimization of individual rehabilitation therapy for stroke patients. Pre-clinical models for stroke recovery, specifically developed in a clinical context, may accelerate this process.
Highlights
Repetitive transcranial magnetic stimulation is a noninvasive neuromodulation technique with the potential to modify cortical excitability in localized brain regions directly under the stimulation coil, as well as in distal brain regions connected to the stimulation site (1)
Studies were included based on the following inclusion criteria: (1) diagnosis of ischemic or hemorrhagic stroke in human subjects, (2) patients are reported to suffer from upper or lower extremity deficits, (3) study assesses and reports upper or lower limb motor function or associated electrophysiological parameters before and after Repetitive transcranial magnetic stimulation (rTMS) intervention, and (4) study reports statistical analysis results (e.g., ANOVA, multivariate regression model, etc.) of patient factors associated with differential rTMS response
A total of 1,676 articles were identified, and with duplicates removed, 1,673 articles remained to be screened for inclusion by the two raters
Summary
Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique with the potential to modify cortical excitability in localized brain regions directly under the stimulation coil, as well as in distal brain regions connected to the stimulation site (1). Low-frequency pulse rates of ≤ 1 Hz have inhibitory effects on underlying brain tissue by reducing the excitability of neurons, whereas high-frequency pulse rates ≥5 Hz have excitatory effects [see Ridding and Rothwell (3) for a more detailed review]. Another rTMS protocol, thetaburst stimulation (TBS), uses multiple short bursts of 50 Hz pulses (4). Repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique used as stand-alone or adjunct treatment to physiotherapy, may be of benefit for motor recovery in subgroups of stroke patients. We review existing clinical trials for demographic, clinical, and neurobiological factors which may predict treatment response to identify knowledge gaps which need to be addressed before implementing these parameters for patient stratification in clinical trial protocols
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