A novel paired associative stimulation protocol with a high-frequency peripheral component: A review on results in spinal cord injury rehabilitation

In recent decades, a multitude of therapeutic approaches has been developed for spinal cord injury (SCI), but few have progressed to regular clinical practice. Novel non-invasive, cost-effective, and feasible approaches to treat this challenging condition are needed. A novel variant of paired associative stimulation (PAS), high-PAS, consists of non-invasive high-intensity transcranial magnetic stimulation (TMS) and non-invasive high-frequency electrical peripheral nerve stimulation (PNS). We observed a therapeutic effect of high-PAS in 20 patients with incomplete SCI with wide range of injury severity, age, and time since injury. Tetraplegic and paraplegic, traumatic, and neurological SCI patients benefited from upper- or lower-limb high-PAS. We observed increases in manual motor scores (MMT) of upper and lower limbs, functional hand tests, walking tests, and measures of functional independence. We also optimized PAS settings in several studies in healthy subjects and began elucidating the mechanisms of therapeutic action. The scope of this review is to describe the clinical experience gained with this novel PAS approach. This review is focused on the summary of our results and observations and the methodological considerations for researchers and clinicians interested in adopting and further developing this new method.