Preoperative Biopsy of Denervated Muscles May be a Predictor of Functional Recovery after Nerve Transfers
Justin P. Chan, BA1, Jennifer Uong, BS1, Winnie Palispis, MD1, Henry Hoang, BS1, James Clune, MD2, Ranjan Gupta1.
1University of California, Irvine, Irvine, CA, USA, 2Yale University, New Haven, CT, USA.
Purpose: The current dogma is that performing a nerve transfer greater than 6-months post-injury rarely results in meaningful recovery, even with distal nerve lesions. However, injuries that are actually an axonotmesis or neuronotmesis are often misdiagnosed as a simple neuropraxia. As such, these unrecognized severe injuries have a significant delay in presentation to the reconstructive microsurgeon well beyond this 6-month time-frame. For these patients, surgeons must weigh the decreased likelihood of functional recovery against the potential functionally catastrophic risks with donor site morbidity. There is currently no objective method to help predict regenerative potential for patients with axonotmesis or neuronotmesis who present in a delayed fashion. While animal models have shed some light on molecular changes to the muscle and motor endplate post-injury, the time course by which motor endplates degenerate at the neuromuscular junction (NMJ) in animal models is likely not the same as in humans. As such, this species-specific variation may lead to ill-informed surgical decision-making. With this study, we sought to provide novel data characterizing human motor endplate degradation at the NMJ following traumatic nerve injury with an attempt to correlate the persistence of motor endplates on muscle biopsy with successful nerve transfers and thereby aid in surgical decision-making. Methods: IRB approval was obtained to perform biopsies from denervated muscles in patients with traumatic nerve injuries ranging from complete pre-ganglionic C5-T1 branchial plexus injuries to isolated axillary nerve transections. Time from injury to surgical intervention ranged from 1-week to 6-years. Electrodiagnostic studies confirmed the absence of motor nerve action potentials, presence of fibrillation potentials, and positive sharp waves in all patients. A total of 13-deltoids, 2-biceps, and 2-first dorsal interossei biopsies were obtained from 14-patients. Specimens were processed for hematoxylin and eosin staining and immunohistochemistry with visualization by confocal and two-photon excitation microscopy. Results: Gross atrophy of denervated muscles was clinically apparent. Denervated muscle biopsies demonstrated histological changes including muscle atrophy and peri-fascicular fat accumulation (Figure 1). NMJs from acutely-denervated muscles demonstrated well preserved morphology while NMJs from more chronically-denervated muscles demonstrated plaque endplate morphology consistent with degeneration. Remarkably, innervated, morphologically preserved NMJs persisted in muscles that had been denervated for greater than 5-years. Surprisingly, three of the patients who presented greater than 6-months post-injury, including one patient presenting 6-years post-injury, demonstrated functional deltoid recovery and return of normal muscle bulk on follow-up physical examination after a partial radial to axillary nerve transfer. Conclusions: This study highlights that murine models sometimes provide species-specific findings and may have limited clinical relevance in providing guidance as to the appropriateness of performing nerve transfers after denervation injuries beyond the current 6-month clinical window for surgical intervention. This novel data suggests that there may be a role for a preoperative muscle biopsy in patients with traumatic nerve injury presenting in a delayed fashion to evaluate integrity of NMJs and determine surgical candidacy for nerve transfers.
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