Proof of concept for multiple nerve transfers to a single target muscle

Abstract

Surgical nerve transfers are used to efficiently treat peripheral nerve injuries, neuromas, phantom limb pain or improve bionic prosthetic control. Commonly, one donor nerve is transferred to one target muscle. However, the transfer of multiple nerves onto a single target muscle may increase the number of muscle signals for myoelectric prosthetic control and facilitate the treatment of multiple neuromas. Currently, no experimental models are available for multiple nerve transfers to a common target muscle in the upper extremity. This study describes a novel experimental model to investigate the neurophysiological effects of peripheral double nerve transfers. For this purpose, we developed a forelimb model to enable tension-free transfer of one or two donor nerves in the upper extremity. Anatomic dissections were performed to design the double nerve transfer model (n=8). In 62 male Sprague-Dawley rats the ulnar nerve of the antebrachium alone (n=30) or together with the anterior interosseus nerve (n=32) was transferred to reinnervate the long head of the biceps brachii. Before neurotization, the motor branch to the biceps’ long head was transected at the motor entry point and resected up to its original branch to prevent auto-reinnervation. In all animals, coaptation of both nerves to the motor entry point could be performed tension-free. Mean duration of the procedure was 49 ± 13 min for the single nerve transfer and 78 ± 20 min for the double nerve transfer. Twelve weeks after surgery, muscle response to neurotomy, behavioral testing, retrograde labeling and structural analyses were performed to assess reinnervation. These analyses indicated that all nerves successfully reinnervated the target muscle. No aberrant reinnervation was observed by the originally innervating nerve. Our observations suggest a minimal burden for the animal with no signs of functional deficit in daily activities or auto-mutilation in both procedures. Furthermore, standard neurophysiological analyses for nerve and muscle regeneration were applicable. This newly developed nerve transfer model allows for the reliable and standardized investigation of neural and functional changes following the transfer of multiple donor nerves to one target muscle.

Autonomic Nerve Fibers Aberrantly Reinnervate Denervated Facial Muscles and Alter Muscle Fiber Population

“…This phenomenon was originally demonstrated by Flourens in 1828, where upper and lower trunks of the brachial plexus in the rooster were crosscoaptated, resulting in functional cross-reinnervation of the wing muscles (Flourens, 1828). Subsequently, nerve transfer surgeries have become a feasible procedure in experimental and clinical settings because of plastic properties of the skeletal muscles (Oberlin et al, 1994;Bergmeister et al, 2019;Luft et al, 2021). Our findings, however, further expand the understanding of muscular plastic capacity, showing possible functional reinnervation via autonomic sources as well.…”

“…Pathologic conditions, however, may disrupt natural neural connections resulting in dysfunctional reinnervation (Gordon, 2020). The remodeling capacity of some target end organs (e.g., muscles, mechanoreceptors) allows for functional connections with axons from an alternate neuronal source but of the same neuronal quality (Bergmeister et al, 2019;Luft et al, 2021). Yet, the capability of a target organ being reinnervated by a foreign axon type remains largely unknown (Brunelli et al, 2005).…”

Selective Repair of Motor Branches in the Femoral Nerve by Transferring the Motor Branches of Obturator Nerve

“…5,21 However, nerve transfer has provided a novel alternative in recent years for high-level femoral nerve lesions. 8,9,[22][23][24] It is a well-established technique that involves the coaptation of a proximal stump of a functional but redundant donor nerve to the distal stump of the injured nerve. Obturator nerve is well suited to transfer on account of the sufficient length to tension-free neurorrhaphy, closing to the femoral nerve, and expandability.…”

“…5 However, in case of extensive nerve gaps or severe pelvic adhesion, when directly coaptation or nerve graft is impossible, nerve transfer has been reported to be a simple and valid therapeutic option, especially in upper limb nerve injuries. [6][7][8][9][10] Concerning femoral nerve lesions, the obturator nerve has been recommended as an ideal donor nerve by several pieces of literature recently for nerve transfer. Campbell et al 11 first described intropelvic obturator nerve transfer to the femoral nerve in a patient with a 15-cm nerve gap caused by resection of retroperitoneal Schwannoma and reported good outcomes with a nearly normal gait and grade 4 strength of the quadriceps 2 years postoperatively.…”

The Grasping Test Revisited: A Systematic Review of Functional Recovery in Rat Models of Median Nerve Injury

“…The surgical paradigm of nerve transfers has gained increasing popularity during the last two decades [ 43 ] with new concepts such as the “babysitter” [ 44 , 45 ] end-to-side nerve transfer or the “supercharge” [ 46 ] reverse end-to-side nerve transfer. Now, as ever, clinical and preclinical research on nerve transfers is a main area of interest within the scientific community of peripheral nerve researchers [ 47 , 48 ]. We, therefore, advise that preclinical researcher interested in this area should carefully consider the time period until first signs of functional recovery can be expected when the rat median nerve is used as an experimental model.…”