Phenotype-associated efficacy of regression of post-stroke hand paresis immediately after a course of adjuvant repetitive transcranial magnetic stimulation in real clinical practice

BACKGROUND: To enhance post-stroke motor recovery, integrating proven noninvasive brain stimulation techniques into clinical practice is essential. An important translational limitation is that phenotypes of beneficial response to noninvasive brain stimulation remain underdetermined. AIM: This study aims to evaluate the strength of regression of post-stroke hand paresis following adjuvant treatment with repetitive transcranial magnetic stimulation in a real-world clinical setting, based on patient phenotype. MATERIALS AND METHODS: The retrospective observational study involved 1,295 subjects (age: 23–83; men: 52.4%) with post-stroke hand paresis. Patients were divided into four phenotypes based on the motor deficit grade (Medical Research Committee (MRC) Scale for Muscle Strength) and resting motor threshold of the cortical representation of m. Abductor pollicis brevis in the affected hemisphere. They are Phenotype 1 (MRC grade 4-3 w/o resting motor threshold increase); Phenotype 2 (MRC grade 4-3 with an increased resting motor threshold); Phenotype 3 (MRC grade 2-0 w/o resting motor threshold increase); Phenotype 4 (MRC grade 2-0 with an increased resting motor threshold). Phenotype 1 and 3 subjects received adjuvant treatment with high-frequency repetitive transcranial magnetic stimulation of the affected hemisphere; Phenotype 2 and 4 subjects received low-frequency repetitive transcranial magnetic stimulation of the unaffected hemisphere. In the comparator group of each phenotype, noninvasive brain stimulation was not performed. Clinical efficacy was assessed immediately after the treatment based on an increase in MRC score by ≥1. RESULTS: Increased clinical efficacy in repetitive transcranial magnetic stimulation groups was detected for Phenotypes 2 (p 0.022) and 4 (p 0.0002). An additional beneficial outcome is expected, on average, in every seventh (Phenotype 4) and ninth (Phenotype 2) treated patient. Phenotype 1 showed lower (p 0.031) clinical efficacy in the repetitive transcranial magnetic stimulation group versus the comparator group. Repetitive transcranial magnetic stimulation in Phenotype 3 subjects showed no adjuvant efficacy. CONCLUSION: The study showed an increased strength of muscle weakness regression after repetitive transcranial magnetic stimulation in Phenotype 2 and 4 patients. The study showed that rhythmic transcranial magnetic stimulation affected the sanogenetic process of motor recovery in Phenotype 1 subpopulation. The study outlined prerequisites to identifying phenotypes in patients with post-stroke, non-paretic motor deficit.