Human Motor Endplate Survival after Chronic Peripheral Nerve Injury

Abstract

Objective: Degeneration of motor endplates (MEPs) in denervated muscle is thought to be a key factor limiting functional regeneration after peripheral nerve injury (PNI) in humans. However, there is currently no paradigm to determine MEP status in denervated human muscle to estimate likelihood of reinnervation success. Here, we present a quantitative analysis of MEP status in biopsies of denervated muscles taken during nerve repair surgery and ensuing functional recovery. Methods: This is a retrospective single-surgeon cohort study of patients (n=22) with upper extremity PNI confirmed with electromyography (EMG), treated with nerve transfers. Muscle biopsies were obtained intra-operatively from 10 patients for MEP morphometric analysis. Age at time of surgery ranged from 22-77 years and time from injury to surgery ranged from 2.5-163 months. Shoulder range of motion (ROM) and Medical Research Council (MRC) scores were recorded pre-op and at final follow-up. Results: Surviving MEPs were observed in biopsies of denervated muscles from all patients, even those greater than six months from injury. Average postoperative ROM improvement (assessed between 6-9 months post-surgery) was: forward flexion 84.3 ± 51.8°, abduction 62.5 ± 47.9°, and external rotation 25.3 ± 28.0°. Interpretation: While it is believed that MEP degeneration 6 months post-injury prevents reinnervation, this data details MEP persistence beyond this timepoint along with significant functional recovery after nerve surgery. Accordingly, persistence of MEPs in denervated muscles may predict the extent of functional recovery from nerve repair surgery.