Deep brain stimulation and spinal cord stimulation for chronic disorders of consciousness: a decade of clinical evidence, mechanistic insights, and critical appraisal

Abstract

Deep brain stimulation (DBS) and spinal cord stimulation (SCS) have been investigated for over four decades as neuromodulatory treatments for chronic disorders of consciousness (DOC), including the vegetative state/unresponsive wakefulness syndrome (VS/UWS) and the minimally conscious state (MCS), for which no disease-modifying pharmacological therapy exists. This narrative review synthesizes literature published between 2016 and 2026 on the neurobiological rationale, clinical evidence, neurophysiological biomarkers, and safety of DBS and SCS for chronic DOC. The ‘mesocircuit hypothesis’, supported by human intraoperative electrophysiology and nonhuman primate causal manipulation, provides a coherent rationale for central thalamic and centromedian-parafascicular targeting. Across case series, cohort studies, and individual patient data meta-analyses, both DBS and SCS produce clinically meaningful improvement in a minority of patients, consistently more often in MCS (63–74% response) than in VS/UWS (26–30% response), with younger age and shorter injury-to-treatment interval predicting better outcomes. However, the two largest individual patient data meta-analyses of DBS concur that current evidence is insufficient to conclude that stimulation alters the natural history of neurological recovery beyond what would be expected from patient selection and spontaneous recovery, and adverse event rates (8.1% for SCS, 18.2% for DBS) indicate non-trivial surgical risk in this vulnerable population. Neurophysiological and neuroimaging biomarkers derived from EEG, functional near-infrared spectroscopy, functional MRI, and FDG-PET show promise for objective outcome prediction but await prospective validation. We conclude that DBS and SCS remain experimental, mechanistically motivated but not yet definitively proven therapies for chronic DOC, and that adequately powered randomized controlled trials, biomarker-guided patient selection, and dedicated ethical frameworks are needed before either modality can be recommended outside of research settings.