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

Abstract

Background: There are few treatments with limited efficacy for patients with disorders of consciousness (DoC). In this meta-analysis of individual patient data (IPD), we examine studies utilizing transcranial magnetic stimulation (TMS) 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 ‘disorders of consciousness’ and ‘transcranial magnetic stimulation.’ Studies reporting individual pre- and post-TMS Coma Recovery Scale-Revised (CRS-R) scores were included. A linear mixed-effects model was created using significant predictors of relative CRS-R score change. Findings: The search yielded 118 papers, of which 12 papers with 111 patients were included. No adverse effects to TMS were reported and post-TMS CRS-R scores were higher than pre-TMS scores (p < 0.0001), with a pooled mean relative change of 5.92 (95% CI, 2.55 to 9.29). TMS initiated within three months of initial injury and MCS diagnosis were associated with increased relative CRS-R score change. Despite not reaching statistical significance, PVS patients with TMS initiated within three months and protocols targeting the default mode network demonstrated greater relative score changes. Interpretation: TMS significantly improved post-TMS CRS-R scores with no reported adverse effects in DoC patients. Initiating TMS early in MCS and PVS may improve patient outcomes. Further evaluation of TMS with randomized, clinical trials is necessary to determine its efficacy in DoC patients and define a protocol that optimizes patient recovery. Funding Statement: Allison Wells and Dr. Sixia Chen was partially supported by the Oklahoma Shared Clinical and Translational Resources (U54GM104938) with an Institutional Development Award (IDeA) from National Institute of General Medical Sciences. Declaration of Interests: The authors report no disclosures.