Long-Term Paired Associative Stimulation Enhances Motor Output of the Tetraplegic Hand

A large proportion of spinal cord injuries (SCI) are incomplete. Even in clinically complete injuries, silent non-functional connections can be present. Therapeutic approaches that can strengthen transmission in weak neural connections to improve motor performance are needed. Our aim was to determine whether long-term delivery of paired associative stimulation (PAS, a combination of transcranial magnetic stimulation [TMS] with peripheral nerve stimulation [PNS]) can enhance motor output in the hands of patients with chronic traumatic tetraplegia, and to compare this technique with long-term PNS. Five patients (4 males; age 38–68, mean 48) with no contraindications to TMS received 4 weeks (16 sessions) of stimulation. PAS was given to one hand and PNS combined with sham TMS to the other hand. Patients were blinded to the treatment. Hands were selected randomly. The patients were evaluated by a physiotherapist blinded to the treatment. The follow-up period was 1 month. Patients were evaluated with Daniels and Worthingham's Muscle Testing (0–5 scale) before the first stimulation session, after the last stimulation session, and 1 month after the last stimulation session. One month after the last stimulation session, the improvement in the PAS-treated hand was 1.02 ± 0.17 points (p < 0.0001, n = 100 muscles from 5 patients). The improvement was significantly higher in PAS-treated than in PNS-treated hands (176 ± 29%, p = 0.046, n = 5 patients). Long-term PAS might be an effective tool for improving motor performance in incomplete chronic SCI patients. Further studies on PAS in larger patient cohorts, with longer stimulation duration and at earlier stages after the injury, are warranted.