Mechanisms and outcomes of the supercharged end-to-side nerve transfer: a review of preclinical and clinical studies

Abstract

<jats:p>Proximal peripheral nerve injuries often result in poor functional outcomes, chiefly because of the long time period between injury and the reinnervation of distal targets, which leads to muscle and Schwann cell atrophy. The supercharged end-to-side (SETS) nerve transfer is a recent technical innovation that introduces donor axons distally into the side of an injured nerve to rapidly innervate and support end organs while allowing for additional reinnervation after a proximal repair at the injury site. However, the mechanisms by which donor axons grow within the recipient nerve, contribute to muscle function, and impact the regeneration of native recipient axons are poorly understood. This uncertainty has slowed the transfer’s clinical adoption. The primary objective of this article is to comprehensively review the mechanisms underpinning axonal regeneration and functional recovery after a SETS nerve transfer. A secondary objective is to report current clinical applications in the upper limb and their functional outcomes. The authors also propose directions for future research with the aim of maximizing the clinical utility of the SETS transfer for peripheral nerve surgeons and their patients.</jats:p>

Preoperative Muscle Biopsy to Assess Motor End Plate Integrity as a Predictor for Successful Nerve Transfer

“…Because most current studies evaluating the outcomes of nerve transfers in humans rely on subjective measurements (such as ROM and Medical Research Council scores), our current understanding of target end-organ recovery after nerve transfer remains largely conjectural. Although previous studies have postulated that nerve transfers are able to regenerate damaged MEPs and restore lost axonal connections 18 , these speculations have largely been based on rodent models 19,20 with no evidence to verify proposed mechanisms in humans. In this case report, our patient offered a unique opportunity to assess the objective structural response of MEPs in the target end-organ muscle after a nerve transfer procedure.…”

Developing a Video-Based Learning Module to Teach Decision-Making for Cubital Tunnel Surgeries

“…67 Otherwise, reports of poor results attributable to inappropriate patient selection will discourage adoption among surgeons within their social systems and impede future applications in other nerve injuries. 49,61…”

“…67 Otherwise, reports of poor results attributable to inappropriate patient selection will discourage adoption among surgeons within their social systems and impede future applications in other nerve injuries. 49,61 Second, educators should consider cognitive theory when deciding what content to include and how to present it. For example, clinical decisionmaking relies on the interplay of two processes: system 1 thinking, which is fast and often subconscious; and system 2 thinking, which is slower and requires conscious effort.…”

Molecular Basis of Surgical Coaptation Techniques in Peripheral Nerve Injuries

“…SETS also induces a second site (the first being the primary repair site) for SC proliferation and upregulation of NGFs. This in turn prevents SC senescence since prolonged periods without axonal contact causes SC atrophy and cause them to lose their ability to maintain the bands of Büngner [ 49 , 50 ]. Preclinical models using histology, immunofluorescence and retrograde labeling, have demonstrated robust axonal regeneration across coaptation sites [ 50 , 51 ].…”

“…This in turn prevents SC senescence since prolonged periods without axonal contact causes SC atrophy and cause them to lose their ability to maintain the bands of Büngner [ 49 , 50 ]. Preclinical models using histology, immunofluorescence and retrograde labeling, have demonstrated robust axonal regeneration across coaptation sites [ 50 , 51 ]. Lieu et al demonstrated that an upregulation of Insulin-like growth factor (IGF-1) and its receptor (IGF-1R) is upregulated after SETS, and are critical for the survival, proliferation, and differentiation of sensory and motor axons [ 52 ].…”