Effects of early photobiomodulation therapy on motor recovery in patients with incomplete acute cervical spinal cord injury: A multicenter randomized controlled trial

Early neurological recovery following acute incomplete cervical spinal cord injury (SCI) is associated with better long-term function. Photobiomodulation (PBM) has shown neuroprotective effects in preclinical studies, but multicenter clinical evidence remains limited. In this multicenter randomized controlled trial, adults (18–70 years) with American Spinal Injury Association (ASIA) grade C cervical SCI presenting within 24 h were enrolled at three tertiary hospitals and randomized to PBM or control. All patients underwent posterior decompression within 24 h. The PBM group received once-daily PBM for 7 consecutive days (810 nm, 300 mW, 30 min) via a diffusing fiber positioned approximately 1.0 cm above the exposed spinal cord. The control group received standard care without PBM. Co-primary outcomes were change in ASIA motor score and independent ambulation at 3, 6, and 12 months. Secondary outcomes included CSF biomarkers at day 7, SCIM-III, SF-36, EQ-5D, and complications. Of 66 randomized patients, 56 (84.8 %) completed the 12-month follow-up (PBM: n = 25; control: n = 31). PBM patients had significantly higher ASIA motor scores at 0.5 months (mean difference, 8.13; 95 % CI, 5.62 to 10.22; P < 0.001) and 3 months (13.33; 95 % CI, 11.01–15.26; P < 0.001), with no significant between-group difference at 6 or 12 months. The PBM group showed higher—but not statistically significant—independent ambulation rates at 3 and 6 months; rates were similar at 12 months. At day 7, CSF levels of GFAP, Tau, S100β, NSE, and NFH were lower with PBM; exploratory proteomics suggested enrichment of synaptic plasticity and repair-related pathways. Scores on SCIM, SF-36, and EQ-5D favored PBM at 3 and 6 months (all P < 0.001), converging by 12 months. Fewer complications occurred with PBM, and no device-related serious adverse events were observed. Early PBM adjunctive to decompression may improve short-term neurological and functional recovery and reduce CSF markers of neural injury in acute incomplete cervical SCI. Our findings suggest that PBM can be safely integrated into standard decompression surgery and may enhance early recovery, supporting further trials to optimize this approach and translate this adjunctive therapy into clinical practice. Chinese Clinical Trial Registry (ChiCTR2100042296). Schematic diagram: Schematic illustration showing photobiomodulation (PBM) therapy delivered following decompressive surgery in acute incomplete cervical spinal cord injury (SCI). PBM was delivered postoperatively using an 810-nm fiber-optic diffuser, directed at the decompressed spinal cord without tissue contact. This targeted approach modulates neuroinflammatory pathways, reduces cerebrospinal fluid (CSF) biomarkers of injury, and promotes neuronal survival and synaptic plasticity. The diagram depicts primary mechanisms—suppression of inflammation, enhancement of mitochondrial and cellular function, and promotion of tissue repair—that may facilitate early motor recovery and improved neurological outcomes.