Role of Polyethylene Glycol-Mediated Axonal Fusion in Early Recovery of Median and Ulnar Nerve Injury: A Pilot Double-Blind Randomized Clinical Trial

Background: Up to 40% of peripheral nerve repairs fail to achieve functional recovery. Polyethylene glycol (PEG) attenuates Wallerian degeneration (WD) by facilitating early axonal fusion, promoting improved functional recovery. This study is the first randomized clinical trial assessing PEG-mediated fusion of mixed motor-sensory nerves. Study Design: Patients aged 18-75 with Sunderland V upper extremity nerve injuries were randomized into PEG-mediated and standard neurorrhaphy groups. Michigan Hand Questionnaire (MHQ) and Medical Research Council Classification (MRCC) sensory/motor grading were conducted at 1—21, 22—40, 41—120, 121—210, and 211—390 days, and beyond 13 months post-operatively. Univariate analyses followed by mixed-effect linear regression model analyses were performed for statistical analyses. Results: Thirteen patients (8 PEG, 5 non-PEG; with 10 and 7 nerves, respectively) were analyzed. There were no statistically significant demographic or clinical differences between groups. Ulnar nerve injuries were 59% and median nerve injuries were 41% of the injuries in this study. Within 22 post-operative days, non-PEG patients remained ≤ S2/M2, while PEG patients achieved ≥ S3 and ≥ M3 recovery, and had significantly lower pain scores compared to non-PEG patients (10.7 vs. 14.5, p < 0.05). Using a mixed-effect linear regression model across all follow-up visits, PEG patients demonstrated significantly higher estimated MRCC sensory (+1.27 ± 0.522, p = 0.039), MRCC motor (+1.13 ± 0.381, p = 0.013), and mean MHQ scores (+3.3.8 ± 1.42, p = 0.046) compared to non-PEG patients. Conclusions: PEG-mediated axon fusion of median and ulnar nerves may contribute to early functional recovery and significantly improved early patient-reported outcome and quality of life. Validation of these findings in larger cohorts with adequately powered subgroup analyses is warranted.