Intermittent theta burst stimulation over ipsilesional primary motor cortex of subacute ischemic stroke patients: A pilot study

Background: We demonstrated that prolonged transcranial magnetic intermittent theta burst stimulation (iTBS, 1200 pulses/session = iTBS1200) produces longer-lasting facilitation in corticospinal excitability than ordinary form of iTBS in healthy subjects. Objective: Here we show the safety and small-scale efficacy of iTBS1200 over ipsilesional primary motor cortex (M1) in subacute stroke patients. Methods: Twelve patients with first-time, subacute ischemic stroke of the middle cerebral artery were randomized into two groups that received 10 daily-sessions of either iTBS1200 or sham stimulation (n = 6/group) over ipsilesional M1 hand region in addition to medical and rehabilitation treatments. The primary outcome measures were safety and tolerability. The secondary outcome measures included the National Institute of Health Stroke Scale (NIHSS), Upper Extremity Fugl-Meyer Test (UE-FMT), Action Research Arm Test (ARAT), active motor thresholds (aMTs)/motor-evoked potentials (MEPs) from the extensor carpi radialis (ECR), and magnetoencephalography on post-intervention day 1 and post-stroke day 60. Results: iTBS or sham stimulation was well tolerated by all patients without seizures or significant adverse effects. Compared with the matched controls, the iTBS group showed measurable improvements in the NIHSS and the proximal UE-FMT scores on post-intervention day 1 and post-stroke day 60. Nevertheless, the hand ARAT scores, aMT and MEPs from the paretic ECR were not different between groups. Post-movement beta synchronization increased over iTBS-conditioned M1 on post-intervention day 1 in testable patients. Conclusions: Repetitive sessions of iTBS1200 over ipsilesional M1 of subacute stroke patients are safe and the potential benefits encourage a larger trial to determine the efficacy in stroke patients. (ClinicalTrials.gov: NCT-01323881).