Paired associative stimulation improves outcomes when applied at the subacute stage after incomplete cervical spinal cord injury

We conducted a randomized sham-controlled clinical trial from 2019 to 2024 to characterize the safety and efficacy of applying paired-associative stimulation (PAS), consisting of high-intensity transcranial magnetic stimulation and high-frequency peripheral nerve stimulation, at early stages after incomplete spinal cord injury (SCI) to enhance motor recovery. Patients with incomplete cervical SCI were randomized 1:1 within 1-4 months post-injury to receive 12 weeks of PAS or sham stimulation alongside conventional rehabilitation, which was not changed. Patients were followed up to 1.5 years after injury (about 1 year after end of stimulation). Seventeen patients (14 males, age 53 ​± ​16 years) participated. Manual Muscle Test revealed a significant effect of treatment in favor of active group (F (1, 470) ​= ​14.69; p ​< ​0.001) in muscles that had no antigravity activity before beginning of stimulation. Improvement from baseline was observed at the end of stimulation (active: 346 ​± ​53 ​%, sham: 215 ​± ​26 ​%), 1 year after injury (about 6 months after end of treatment; active: 389 ​± ​61 ​%, sham: 241 ​± ​39 ​%), and at 1.5 years after injury (about 12 months after end of treatment; active: 419 ​± ​73 ​%, sham: 210 ​± ​17 ​%). Greater improvement in fine motor skill tests was observed in the active group. Although the Spinal Cord Independence Measure showed no differences between groups (p ​= ​0.36-0.83), there was improvement in activity of daily living tests. The intervention was feasible and well-tolerated in both groups. PAS is a safe and feasible therapy that can be added to conventional rehabilitation even in early stages after SCI.