Treatment of Persistent Postconcussion Syndrome With Repetitive Transcranial Magnetic Stimulation Using Functional Near-Infrared Spectroscopy as a Biomarker of Response: Protocol for a Randomized Controlled Clinical Trial

Abstract

Background Approximately one-third of all concussions lead to persistent postconcussion syndrome (PPCS). Repetitive transcranial magnetic stimulation (rTMS) is a form of noninvasive brain stimulation that has been extensively used to treat refractory major depressive disorder and has a strong potential to be used as a treatment for patients with PPCS. Functional near-infrared spectroscopy (fNIRS) has already been used as a tool to assess patients with PPCS and may provide insight into the pathophysiology of rTMS treatment in patients with PPCS. Objective The primary objective of this research is to determine whether rTMS treatment improves symptom burden in patients with PPCS compared to sham treatment using the Rivermead postconcussion symptom questionnaire. The secondary objective is to explore the neuropathophysiological changes that occur following rTMS in participants with PPCS using fNIRS. Exploratory objectives include determining whether rTMS treatment in participants with PPCS will also improve quality of life, anxiety, depressive symptoms, cognition, posttraumatic stress, and function secondary to headaches. Methods A total of 44 adults (18-65 years old) with PPCS (>3 months to 5 years) will participate in a double-blind, sham-controlled, concealed allocation, randomized clinical trial. The participants will engage in either a 4-week rTMS treatment protocol or sham rTMS protocol (20 treatments). The left dorsolateral prefrontal cortex will be located through Montreal Neurologic Institute coordinates. The intensity of the rTMS treatment over the left dorsolateral prefrontal cortex will be 120% of resting motor threshold, with a frequency of 10 Hz, 10 trains of 60 pulses per train (total of 600 pulses), and intertrain interval of 45 seconds. Prior to starting the rTMS treatment, participant and injury characteristics, questionnaires (symptom burden, quality of life, depression, anxiety, cognition, and headache), and fNIRS assessment will be collected. Repeat questionnaires and fNIRS will occur immediately after rTMS treatment and at 1 month and 3 months post rTMS. Outcome parameters will be analyzed by a 2-way (treatment × time) mixed analysis of variance. Results As of May 6, 2021, 5 participants have been recruited for the study, and 3 have completed the rTMS protocol. The estimated completion date of the trial is May 2022. Conclusions This trial will expand our knowledge of how rTMS can be used as a treatment option of PPCS and will explore the neuropathophysiological response of rTMS through fNIRS analysis. Trial Registration ClinicalTrials.gov NCT04568369; https://clinicaltrials.gov/ct2/show/NCT04568369 International Registered Report Identifier (IRRID) DERR1-10.2196/31308