PEG Fusion Significantly Improves Return of Function in a Median/Ulnar Nerve Denervation Model
Christopher M. Frost, MD1, Cameron Ghergherehchi2, George Bittner, PhD2, Gerald Brandacher, MD1, Jaimie Shores, MD1.
1Johns Hopkins Hospital, Baltimore, MD, USA, 2University of Texas, Austin, TX, USA.
Purpose: Peripheral nerve injury is a challenging clinical problem due to slow, incomplete regeneration that results in the poor return of function. Polyethylene glycol (PEG) has been studied in the rat sciatic nerve model to immediately restore nerve continuity and prevent Wallerian degeneration. PEG-fusion reestablishes axoplasmic continuity by nonspecifically fusing closely apposed severed axons at the lesion site. In this study we examine if PEG-fusion can improve nerve repair in a novel denervation model using serial grip strength testing (GST).
Methods: Sprague-dawley rats (n=10) were utilized comparing suture repair alone (n=5) to PEG fusion with suture repair (n=5). In both control and PEG-fusion groups baseline grip strength was first calculated using percutaneous electrical stimulation to the rat forearm followed by GST of the rat paw using a force transducer. Next, bilateral ulnar and median nerves were exposed and divided. In both groups the proximal ulnar nerve was sutured into adjacent bicep muscle. Total nerve discontinuity was confirmed with nerve conduction testing (NCT). In both control and PEG fusion groups the median nerve was repaired using 10-0 nylon sutures. In the PEG-fusion group the nerve ends were first washed with hypotonic Plasmalyte followed by methylene blue prior to neurorrhaphy. PEG was applied for 90 seconds followed by Lactated Ringers solution. Successful PEG-fusion was confirmed using NCT. Follow up GST testing was performed at 7, 14, 21, 28, 35, 42 days under sedation using percutaneous stimulation. Statistics were performed using 2-tailed t-test with Bonferroni correction for multiple comparisons.
Results: Nerve continuity was reestablished in all PEG-fusion animals with NCT demonstrating both restored compound action potentials (CAP) and compound muscle action potentials (CMAP). There was no measurable CAP or CMAP after suture repair alone (Figure 1). The PEG fusion group demonstrated significant (p<0.05) increase in grip strength compared to control at all time points (Figure 2). PEG fusion group showed an average of 54% return to baseline grip strength as early as POD 7. As expected, suture repair alone had minimal return of function at POD 7. Further histologic examination pending.
Conclusion: PEG fusion significantly improved return of function compared to standard neurorrhaphy in this ulnar and median nerve denervation model.
Figure 1: Nerve conduction testing. Top left: CAP median nerve after PEG fusion. Top right: CMAP in flexor compartment after PEG fusion. Bottom: NCT after suture repair alone with no measurable CAP or CMAP. Blue arrow represents a CAP, orange arrow shows a CMAP. * indicates stimulus artifact.
Figure 2: Grip strength testing comparing suture repair alone to PEG fusion across 6 weeks, demonstrating significantly increased grip strength with PEG fusion across all time groups (* p<0.05). Error bars represent +/- 1 SD
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