Time Course of Motor Improvement by Epidural Stimulation After Spinal Cord Injury: An Interim Analysis of a Phase II Trial

Porceban Mm; Angelin Lg; Gabana E; Prota C; De Byase Mem; Ferreira Rjr; Marcon Rm; Cristante Af; Greve Jmd; Arévalo A; Sitthinamsunwan B; Majeed N; Jarernpratumdee K; Charles H; Lepski Ga

doi:10.1177/11795735251379220

Time Course of Motor Improvement by Epidural Stimulation After Spinal Cord Injury: An Interim Analysis of a Phase II Trial

J Cent Nerv Syst Dis. 2025 Sep 22:17:11795735251379220. doi: 10.1177/11795735251379220. eCollection 2025.

Authors

Porceban Mm¹, Angelin Lg², Gabana E³, Prota C⁴, De Byase Mem⁴, Ferreira Rjr³, Marcon Rm³, Cristante Af³, Greve Jmd⁴, Arévalo A², Sitthinamsunwan B⁵, Majeed N⁶, Jarernpratumdee K⁶, Charles H⁶, Lepski Ga^{1

2

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Affiliations

¹ Departments of Neurology and Psychiatry, Medical School, Universidade de São Paulo, Brazil.
² Laboratory of Experimental Surgery LIM26, Medical School, Universidade de São Paulo, Brazil.
³ Institute of Orthopedics, Hospital Das Clínicas, Medical School, Universidade de São Paulo, Brazil.
⁴ Laboratory for the Study of Movements, Institute of Orthopedics, Hospital Das Clínicas, Medical School, Universidade de São Paulo, Brazil.
⁵ Division of Neurosurgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
⁶ Verita Neuro, Verita Healthcare Group, Singapore.
⁷ Department of Neurosurgery, Eberhard Karls University in Tuebingen, Germany.

Abstract

Background: Epidural spinal cord stimulation (EES) is a promising intervention for motor rehabilitation after spinal cord injury (SCI), but the extent and trajectory of motor recovery remain unclear.

Objective: This phase II trial evaluates the acquisition of voluntary movements in paraplegic patients (ASIA A or B) following SCI, assessed by the Fugl-Meyer Lower Extremity (FMA-LE) score and electromyography (EMG).

Methods: This interim analysis includes five patients implanted with EES and followed for 12 months. The primary outcome was motor recovery, measured by FMA-LE and EMG. Secondary outcomes included balance (Berg Balance Scale), spasticity (Modified Ashworth Scale), pain, autonomic functions, mood, quality of life (WHO-QOL), and safety. Adverse events were monitored.

Results: The FMA-LE score improved from 36 ± 9 (SD) to 55 ± 2 at 3 months (P < 0.05), 59 ± 2 at 6 months (P < 0.05), and 64 ± 4 at 12 months (P < 0.05). EMG confirmed increased voluntary activation. Balance and spasticity improved, while pain and autonomic functions remained unchanged. Motor gains plateaued after 5 months, reaching 68% above baseline. No serious adverse events occurred, though minor complications included transient nociceptive pain and a self-resolving pressure ulcer.

Conclusions: These findings support the role of EES in facilitating early motor recovery in SCI patients, consistent with prior studies. However, the plateau effect suggests a limit to long-term gains. Future research should explore strategies to sustain improvements, including regenerative therapies or optimized neuromodulation protocols.Trial registration number: NCT06847295.

Keywords: epidural stimulation; neuroplasticity; rehabilitation; spinal cord injury; spinal cord stimulation.

Associated data

ClinicalTrials.gov/NCT06847295