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), 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.

Repetitive transcranial magnetic stimulation over the posterior parietal cortex improves functional recovery in nonresponsive patients: A crossover, randomized, double-blind, sham-controlled study

“…The crossover design has the advantage of eliminating individual subject differences from the overall treatment effect and is suitable for chronic diseases such as DoC. Therefore, this study's behavioristics and EEG results make a significant clinical observation, which helps explore the target selection of rTMS (even other NIBS treatments) for DoC and improve its clinical diagnosis and treatment ( 8 ).…”

“…Currently, the available treatments for patients with DoC are limited. However, neuromodulation technology, a non-pharmacological treatment, has been successfully applied to various neurological and psychiatric conditions and holds promise for the treatment of DoC ( 8 ).…”

“…Currently, rTMS can increase awareness levels in patients with DoC ( 38 ). However, the published results were based on a small sample size or pilot studies ( 8 , 12 , 39 ). In this study, we propose a crossover, randomized, double-blind, sham-controlled rTMS treatment study that uses the left PPC (P3 electrode site) as the target for an intervention program for patients in VS/UWS.…”

Repetitive Transcranial Magnetic Stimulation of the Primary Motor Cortex beyond Motor Rehabilitation: A Review of the Current Evidence

“…In a recent meta-analysis, O’Neal and colleagues reported that rTMS was utilized without any adverse effects in patients with disorders of consciousness, including minimally conscious state (MCS) and vegetative state/unresponsive wakefulness syndrome [ 164 ]. Based on the individual patient data involved in their meta-analysis, O’Neal et al reported a 30.4% response rate following high-frequency rTMS at M1, with the response being defined as any change in the Coma Recovery Scale-Revised (CRS-R) score above a patient’s baseline.…”

“…Based on the individual patient data involved in their meta-analysis, O’Neal et al reported a 30.4% response rate following high-frequency rTMS at M1, with the response being defined as any change in the Coma Recovery Scale-Revised (CRS-R) score above a patient’s baseline. The more remarkable improvement in CRS-R scores was associated with MCS diagnosis, an etiology of stroke or intracranial hemorrhage, receiving 10 or more sessions of rTMS, and if the rTMS treatment was initiated within the first three months from inciting injury [ 164 ].…”