Patient Outcomes in Disorders of Consciousness Following Transcranial Magnetic Stimulation: A Systematic Review and Meta-Analysis of Individual Patient Data

Background: There are few treatments with limited efficacy for patients with disorders of consciousness (DoC), such as minimally conscious and persistent vegetative state (MCS and PVS). Objective: In this meta-analysis of individual patient data (IPD), we examine studies utilizing transcranial magnetic stimulation (TMS) as a treatment in DoC to determine patient and protocol-specific factors associated with improved outcomes. Methods: We conducted a systematic review of PubMed, Ovid Medline, and Clinicaltrials.gov through April 2020 using the following terms: “minimally conscious state,” or “persistent vegetative state,” or “unresponsive wakefulness syndrome,” or “disorders of consciousness” and “transcranial magnetic stimulation.” Studies utilizing TMS as an intervention and reporting individual pre- and post-TMS Coma Recovery Scale-Revised (CRS-R) scores and subscores were included. Studies utilizing diagnostic TMS were excluded. We performed a meta-analysis at two time points to generate a pooled estimate for absolute change in CRS-R Index, and performed a second meta-analysis to determine the treatment effect of TMS using data from sham-controlled crossover studies. A linear regression model was also created using significant predictors of absolute CRS-R index change. Results: The search yielded 118 papers, of which 10 papers with 90 patients were included. Patients demonstrated a mean pooled absolute change in CRS-R Index of 2.74 (95% CI, 0.62–4.85) after one session of TMS and 5.88 (95% CI, 3.68–8.07) at last post-TMS CRS-R assessment. The standardized mean difference between real rTMS and sham was 2.82 (95% CI, −1.50 to 7.14), favoring rTMS. The linear regression model showed that patients had significantly greater CRS-R index changes if they were in MCS, had an etiology of stroke or intracranial hemorrhage, received 10 or more sessions of TMS, or if TMS was initiated within 3 months from injury. Conclusions: TMS may improve outcomes in MCS and PVS. Further evaluation with randomized, clinical trials is necessary to determine its efficacy in this patient population.