Testing the effectiveness and the contribution of experimental supercharge (reversed) end-to-side nerve transfer (original) (raw)
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Reverse End-to-Side Nerve Transfer: From Animal Model to Clinical Use
The Journal of Hand Surgery, 2011
Purpose Functional recovery after peripheral nerve injury is predominantly influenced by time to reinnervation and number of regenerated motor axons. For nerve injuries in which incomplete regeneration is anticipated, a reverse end-to-side (RETS) nerve transfer might be useful to augment the regenerating nerve with additional axons and to more quickly reinnervate target muscle. This study evaluates the ability of peripheral nerve axons to regenerate across an RETS nerve transfer. We present a case report demonstrating its potential clinical applicability. Methods Thirty-six Lewis rats were randomized into 3 groups. In group 1 (negative control), the tibial nerve was transected and prevented from regenerating. In group 2 (positive control), the tibial and peroneal nerves were transected, and an end-to-end (ETE) nerve transfer was performed. In group 3 (experimental model), the tibial nerve and peroneal nerves were transected, and an RETS nerve transfer was performed between the proximal end of the peroneal nerve and the side of the denervated distal tibial stump. Nerve histomorphometry and perfused muscle mass were evaluated. Six Thy1-GFP transgenic Sprague Dawley rats, expressing green fluorescent protein in their neural tissues, also had the RETS procedure for evaluation with confocal microscopy. Results Nerve histomorphometry showed little to no regeneration in chronic denervation animals but statistically similar regeneration in ETE and RETS animals at 5 and 10 weeks. Muscle mass preservation was similar between ETE and RETS groups by 10 weeks and significantly better than negative controls at both time points. Nerve regeneration was robust across the RETS coaptation of Thy1-GFP rats by 5 weeks. Conclusions Axonal regeneration occurs across an RETS coaptation. An RETS nerve transfer might augment motor recovery when less-than-optimal recovery is otherwise anticipated.
Neurosurgery, 2018
BACKGROUND Brief electrical stimulation (ES) therapy to the nerve may improve outcome in lacerated, repaired nerves. However, most human nerve injuries leave the nerve in continuity with variable and often poor functional recovery from incomplete axon regeneration and reinnervation. OBJECTIVE To evaluate the effect of brief ES in an experimental model for neuroma-in-continuity (NIC) injuries in rodents. METHODS Lewis rats were randomly assigned to 1 of 4 groups: NIC injury immediately followed by brief (1 h) ES; NIC injury without ES; sham-operated controls; sciatic nerve transection without repair. Outcome measures included serial behavioral evaluation and electrophysiology together with terminal retrograde spinal cord motor neuron labeling and histomorphological analysis for axonal regeneration. RESULTS Applying brief ES immediately after in-continuity nerve injury resulted in earlier recovery and significantly improved locomotion function at 4 and 6 wk. At 8 wk, brief ES resulted...
Journal of Neurosurgery, 2021
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.
International Journal of Sciences: Basic and Applied Research, 2017
To investigate the role of reverse end-to-side nerve transfer in delayed repair of peripheral nerve injury, a rat sciatic nerve injury model was used. The dynamic of SV2B mRNA expression was investigated. Sixteen Wistar rats were divided into four groups (four rats in each group). In Group I, the right tibial nerve was ligated 1 cm proximal to sciatic trifurcation, and the peroneal nerve was ligated distally at its entrance to peroneal tunnel. Two weeks later, the resulting neuroma was excised and the tibial nerve was repaired in end-to-end (ETE) fashion. The peroneal nerve was transferred to the distal stump of the tibial nerve in a reverse end-to-side fashion (RETS / axonal supercharging). In Group II, similar procedure to create the sciatic nerve injury was performed. Two weeks later, the tibial nerve was repaired in ETE fashion. No axonal supercharging procedure was added. In Group II, the sciatic nerve was exposed, and the wound was closed again (sham surgery / positive control...
The basis for diminished functional recovery after delayed peripheral nerve repair
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011
The postsurgical period during which neurons remain without target connections (chronic axotomy) and distal nerve stumps and target muscles are denervated (chronic denervation) deleteriously affects functional recovery. An autologous nerve graft and cross-suture paradigm in Sprague Dawley rats was used to systematically and independently control time of motoneuron axotomy, denervation of distal nerve sheaths, and muscle denervation to determine relative contributions of each factor to recovery failure. Tibial (TIB) nerve was cross-sutured to common peroneal (CP) nerve via a contralateral 15 mm nerve autograft to reinnervate the tibialis anterior (TA) muscle immediately or after prolonging TIB axotomy, CP autograft denervation, or TA muscle denervation. Numbers of motoneurons that reinnervated TA muscle declined exponentially from 99 ± 15 to asymptotic mean (± SE) values of 35 ± 1, 41 ± 10, and 13 ± 5, respectively. Enlarged reinnervated motor units fully compensated for reduced moto...
Quantification of Functional Recovery Following Rat Sciatic Nerve Transection
Experimental Neurology, 2001
Functional recovery following experimental nerve injury has been notoriously difficult to quantify precisely. The current gold standard in the rat sciatic nerve model involves analysis of footprints of the recovering animal, and computation of the sciatic function index (SFI). We performed transection injuries and measured recovery both by walking track analysis and by a newer, simpler, more quantitative test of motor recovery, the extensor postural thrust (EPT). We demonstrate a high correlation between both testing modalities and suggest a role for EPT measurements as an easier, more consistent measure of motor recovery following experimental rat sciatic nerve transection.
Functional reconstruction of lower extremity nerve injuries
Plastic and Aesthetic Research, 2022
Peripheral nerve injuries (PNI) in the lower extremity are an uncommon but highly morbid condition. Recent advances in our understanding of nerve physiology and microsurgical techniques have inspired renewed faith in nerve surgery and sparked a creative renaissance in the tools, approaches, and reconstructive schemas available to surgeons in the management of lower extremity PNIs. In this article, we review the literature and provide a principles-based approach for the surgical management of lower extremity PNIs with an emphasis on techniques for functional reconstruction after complete nerve injury. General principles in management include early diagnosis with electrodiagnostics and imaging, early surgical exploration, and opting for nerve and tendon transfers when primary reconstruction of the injured nerve is unfavorable (e.g., delayed reconstruction, unavailability of proximal or distal nerve stumps, or long regenerative distance). The goal of functional reconstruction should be to restore independent gait, so understanding the roles of major neuromuscular units during the gait cycle informs the selection of donor nerves and tendons for transfer. Based on these principles and literature to date, specific algorithms for surgical management are presented for femoral, sciatic, tibial, and common peroneal nerves. We recognize limitations of the current literature, namely the predominance of case series evidence, and call for the accrual of more patient data in surgical management of PNIs.
Motor Cortex Stimulation Regenerative Effects in Peripheral Nerve Injury: An Experimental Rat Model
World neurosurgery, 2018
Immediate microsurgical nerve suture remains the gold standard after peripheral nerve injuries. However, functional recovery is delayed, and it is satisfactory in only 2/3 of cases. Peripheral electrical nerve stimulation proximal to the lesion enhances nerve regeneration and muscle reinnervation. This study aims to evaluate the effects of the motor cortex electrical stimulation on peripheral nerve regeneration after injury. Eighty rats underwent right sciatic nerve section, followed by immediate microsurgical epineural sutures. Rats were divided into 4 groups: Group 1 (control, n = 20): no electrical stimulation; group 2 (n = 20): immediate stimulation of the sciatic nerve just proximal to the lesion; Group 3 (n = 20): motor cortex stimulation (MCS) for 15 minutes after nerve section and suture (MCSa); group 4 (n = 20): MCS performed over the course of two weeks after nerve suture (MCSc). Assessment included electrophysiology and motor functional score at day 0 (baseline value befo...
Nerve Transfers in the Treatment of Peripheral Nerve Injuries
Peripheral Nerve Regeneration - From Surgery to New Therapeutic Approaches Including Biomaterials and Cell-Based Therapies Development, 2017
Successful re-innervation of proximal limb peripheral nerve injuries is rare. Axons regenerate at ~1 mm/day, reaching hand muscles by 24 months, finding them atrophied and fibrosed. Peripheral nerve injury repair is often delayed waiting for spontaneous recovery. This waiting time should not be longer than 6 months as after 18 months reinnervation will not achieve effective muscular function. When spontaneous recovery is impossible, referral too late or damage too severe, other options like a transfer from a nearby healthy nerve to the injured one must be considered. They are very successful, and the deficit in the donor site is usually minimal. The most common nerve transfers are a branch of the spinal nerve to the trapezius muscle to the suprascapular nerve, a branch of the long head of the triceps to the axillary nerve, a fascicle of the ulnar nerve to the motor branch of the biceps muscle, two branches of the median nerve to the posterior interosseous nerve and the anterior interosseous nerve to the ulnar nerve. There are many more options that can suit particular cases. Introduced in brachial plexus injury repair, they are now also applied to lower limb, to stroke and to some spinal cord injuries.
Journal of Neurotrauma, 2002
Accuracy of reinnervation is one of the main factors conditioning functional recovery after brain, spinal, or peripheral axonal damage. Using the peripheral nerve as an experimental model, we studied the amount of inaccurate muscle reinnervation and its consequences on walking. Adult rats were submitted to an 8-mm resection of the sciatic nerve repaired by autograft (AG, n 5 9), silicone (SIL, n 5 13) or poly-L-lactate-«-caprolactone (PLC, n 5 11) single guides, and fascicular tubulization of peroneal and tibial branches with a dual silicone tube (FSIL, n 5 9). At the end of follow-up, the sciatic nerve and its tibial and peroneal fascicles were dissected and stimulated by means of a suction electrode. In control rats, gastrocnemius and plantar muscles are fully innervated by the tibial fascicle and the tibialis anterior muscle by the peroneal nerve. None of the groups had noticeable recovery of locomotion assessed by the walking track index (SFI around 270 in all groups). After resection, all animals of groups AG, SIL, and PLC showed aberrant muscle reinnervation by axons from a non-corresponding fascicle, whereas in group FSIL only one of six regenerated animals showed misdirected activity. The proportion of inaccurate muscle activation was similar in group AG (47% for gastrocnemius, 54% for tibialis anterior, and 44% for plantar muscles) and in group SIL (42%, 42%, and 42%), and reduced in group PLC (26%, 38%, and 27%). In conclusion, fascicular silicone tubulization allowed the highest degree of accuracy but the lowest recovery, whereas resorbable PLC guides provided for the best balance between amount and accuracy of reinnervation after nerve resection.