Off-Label Applications of Epidural Spinal Cord Stimulation: A Scoping Review

Epidural spinal cord stimulation (SCS) is established for chronic pain and has been explored for applications beyond chronic neuropathic pain. We conducted a scoping review to map the clinical literature, temporal publication trends, summarize outcomes, and synthesize proposed mechanisms across these applications.

MEDLINE, EMBASE, CENTRAL, and the WHO trials registry were searched. Full-text English human studies of epidural SCS for applications beyond chronic neuropathic pain were included. Screening and extraction were performed in duplicate with adjudication by a third reviewer. Outcomes and mechanisms were extracted in detail for randomized controlled trials (RCTs) and prospective studies with >ten participants. Risk of bias was assessed for RCTs and prospective studies.

From 6815 records, 221 studies (1976-2025) were included (N = 5154). Indications were grouped as vascular and microcirculatory (n = 57), cardiovascular (n = 51), motor function and rehabilitation following spinal cord injury (n = 43), neurodegenerative and movement disorders (n = 33), disorders of consciousness and respiratory function (n = 21), and miscellaneous (n = 16); motor function and rehabilitation following SCI publications were concentrated in 2020-2025 (29/43, 67.4%). Study designs were predominantly small, although 17 RCTs and 60 prospective studies were identified. Evidence was most consistent for refractory angina and spasticity. In critical limb ischemia, prospective studies suggested benefit, but RCTs were neutral. Findings for disorders of consciousness and rehabilitation following SCI were favorable but remain early-phase and heterogeneous, whereas heart failure trials were negative and multiple sclerosis outcomes favored bladder function. Proposed mechanisms most commonly invoked autonomic and microvascular modulation and altered spinal network excitability.

Epidural SCS applications beyond chronic neuropathic pain have been applied across diverse conditions with uneven evidentiary strength. Mechanistic hypotheses were rarely tested prospectively. Future progress will require hypothesis-driven trials with standardized, clinically meaningful outcomes, validated predictors of response to improve patient selection, and comparative effectiveness designs to define the role of SCS within its evolving therapeutic landscape.