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 (Preprint)

Abstract

BACKGROUND Approximately one-third of all concussions lead to persistent post-concussion syndrome (PPCS). Repetitive transcranial magnetic stimulation (rTMS) is a form of non-invasive brain stimulation that has been extensively used to treat refractory major depressive disorder and has 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 is to determine whether rTMS treatment improves symptom burden in patients with PPCS compared to sham using the Rivermead Post-concussion Symptom questionnaire as the primary outcome measure. The secondary objective is to explore the neuropathophysiological changes that occur following rTMS in patients with PPCS using fNIRS. Exploratory objectives include determining whether rTMS treatment in patients with PPCS will also improve quality of life, anxiety, depressive symptoms, cognition, post-traumatic stress and function secondary to headaches. METHODS Forty-four adults (18-65) with PPCS (>3 months-5 years) will participate in a double-blind, sham-controlled, concealed allocation, randomized clinical trial. Patients will engage in either a four-week rTMS treatment protocol or sham rTMS protocol (20 treatments). The left DLPFC will be located through Montreal Neurologic Institute (MNI) coordinates. The intensity of the rTMS will be 120% of the resting motor threshold, with a frequency of 10 Hz, 10 trains of 60 pulses/train (total of 600 pulses), and an inter-train interval of 45 seconds. Prior to starting the rTMS treatment, patient 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- and 3- month post-rTMS. Outcome parameters within each specific group (rTMS, sham) will be analyzed by a one-way repeated measures analysis of variance (RM-ANOVA). RESULTS To date, 5 patients have been recruited for the study and 3 have completed the rTMS protocol. The estimated completion date of the trial is April 2022. CONCLUSIONS This trial will expand our knowledge of how rTMS can be used as a treatment option of PPCS and explore the neuropathophysiological response of rTMS though fNIRS analysis. CLINICALTRIAL ClinicalTrials.gov - NCT04568369