Testing the effectiveness and the contribution of experimental supercharge (reversed) end-to-side nerve transfer

Abstract

OBJECTIVE Supercharge end-to-side (SETS) transfer, also referred to as reverse end-to-side transfer, distal to severe nerve compression neuropathy or in-continuity nerve injury is gaining clinical popularity despite questions about its effectiveness. Here, the authors examined SETS distal to experimental neuroma in-continuity (NIC) injuries for efficacy in enhancing neuronal regeneration and functional outcome, and, for the first time, they definitively evaluated the degree of contribution of the native and donor motor neuron pools. METHODS This study was conducted in 2 phases. In phase I, rats (n = 35) were assigned to one of 5 groups for unilateral sciatic nerve surgeries: group 1, tibial NIC with distal peroneal-tibial SETS; group 2, tibial NIC without SETS; group 3, intact tibial and severed peroneal nerves; group 4, tibial transection with SETS; and group 5, severed tibial and peroneal nerves. Recovery was evaluated biweekly using electrophysiology and locomotion tasks. At the phase I end point, after retrograde labeling, the spinal cords were analyzed to assess the degree of neuronal regeneration. In phase II, 20 new animals underwent primary retrograde labeling of the tibial nerve, following which they were assigned to one of the following 3 groups: group 1, group 2, and group 4. Then, secondary retrograde labeling from the tibial nerve was performed at the study end point to quantify the native versus donor regenerated neuronal pool. RESULTS In phase I studies, a significantly increased neuronal regeneration in group 1 (SETS) compared with all other groups was observed, but with modest (nonsignificant) improvement in electrophysiological and behavioral outcomes. In phase II experiments, the authors discovered that secondary labeling in group 1 was predominantly contributed from the donor (peroneal) pool. Double-labeling counts were dramatically higher in group 2 than in group 1, suggestive of hampered regeneration from the native tibial motor neuron pool across the NIC segment in the presence of SETS. CONCLUSIONS SETS is indeed an effective strategy to enhance axonal regeneration, which is mainly contributed by the donor neuronal pool. Moreover, the presence of a distal SETS coaptation appears to negatively influence neuronal regeneration across the NIC segment. The clinical significance is that SETS should only employ synergistic donors, as the use of antagonistic donors can downgrade recovery.

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

“…The degree of connective tissue disruption in the recipient nerve at the site of a SETS coaptation that facilitates maximal regeneration across the coaptation is controversial. 7,12 Preclinical models have demonstrated robust axonal regeneration across the SETS coaptation with an epineurial window 6,[13][14][15][16] or a perineurial window. 9,17 The presence of donor axons in a recipient nerve distal to the SETS coaptation has been confirmed histologically using light microscopy, 6 immunofluorescence, 9,14 and retrograde labeling.…”

“…9,17 The presence of donor axons in a recipient nerve distal to the SETS coaptation has been confirmed histologically using light microscopy, 6 immunofluorescence, 9,14 and retrograde labeling. 13,14,16 In rodent models, the difficulty distinguishing epineurial from perineurial windows adds to the challenge of assessing the relative benefit of either window in the SETS transfer. The two tissue layers are often confluent, and performing a perineurial coaptation is technically challenging.…”

“…9,17 That group found a much higher myelinated axon count with a perineurial window (3127 axons, "Group 3 RETS") 9 than Nadi et al did after SETS transfer with an epineurial window (745 axons, "Group 4 SETS control"). 16 Animals in both of these experimental subgroups were subject to the same experimental conditions. No comparable functional data were available.…”

Efficacy evaluation of personalized coaptation in neurotization for motor deficit after peripheral nerve injury: A systematic review and meta‐analysis

“…However, owing to an oversize nerve defect, poor functional outcome frequently occurs postoperatively. As is well known, tension‐free coaptation can offer an opportunity for autonomous axonal arrangement and lead to maximal alignment of regenerating axons (Nadi et al, ).…”

Novel Uses of Nerve Transfers

“…This distance means that the hope for recovery is low. In these cases, a SETS transfer can be performed, coapting the distal anterior interosseous nerve (donor) to the side of the distal ulnar nerve [44][45][46][47]. The distal anterior interosseous nerve is followed to its point of branching within the pronator quadratus muscle and transected in that location.…”