Long-term follow-up of three different nerve repair strategies (repair, autografting and allografting) in one-stage replantation to treat upper extremity amputation

Objective To examine the efficacy of three different nerve repair methods for one-stage replantation to treat complete upper extremity amputation and long-term postoperative functional recovery. Methods Twenty-five patients underwent direct nerve anastomosis (Group A), for patients with nerve defects greater than 3 cm, nerve autograft transplantation be used (Group B), or patients with nerve defects less than 3 cm, nerve allograft transplantation be used (Group C) based on the severity of injury. The Disabilities of the Arm, Shoulder, and Hand (DASH) score (higher score means poorer function-less than 25 means good effect) and visual analogue scale (VAS) scores for pain at rest and under exertion were measured. Sensation recovery time and grip function were recorded. Results The mean follow-up time was 78 ± 29 months. Group A had the lowest DASH score, while Group C had the highest DASH score. DASH score differed significantly between the three groups (P < 0.001). Sensation was not restored in two patients in Group B and two patients in Group C, and there were significant between-group differences in sensation recovery (P = 0.001). Group C had the lowest VAS score, while Group A had the highest, and there were significant differences between groups (P = 0.044). Only one patient in Group C recovered grip function. Conclusion Direct nerve anastomosis should be performed whenever possible in replantation surgery for complete upper extremity amputation, as the nerve function recovery after direct nerve anastomosis is better than that after nerve autograft transplantation or nerve allograft transplantation. Two-stage nerve autograft transplantation can be performed in patients who do not achieve functional recovery long after nerve allograft transplantation.

Corneal neurotisation for neurotrophic keratopathy with a sural nerve autograft: a case report

Neurotrophic keratopathy is a corneal disease characterised by reduced corneal sensation. Corneal neurotization is the transfer of healthy donor nerve tissue to the cornea to restore sensation. An 11-year-old male presented with reduced Mackie Stage 1 neurotrophic keratopathy from de-bulking of a cerebellopontine angle arachnoid cyst. He underwent minimally invasive indirect corneal neurotization with a sural nerve autograft to ipsilateral supratrochlear nerve and cornea. Close and objective post-operative monitoring of donor sites, the cornea, visual acuity, and tear production clearly demonstrate the efficacy of this technique, and the timeline of clinical improvement.

Nerve grafts and transfers

Following Cruickshank’s (1795) ingenious (and at first disbelieved) demonstration of the regenerative capacity of mammalian nerves, the eighteenth and nineteenth centuries saw a pan-European enthusiasm to redress the nihilism surrounding nerve injury. The first recorded experimental nerve grafts were performed by Philipeaux and Vulpian who attempted both nerve autografting as well as allografting in dogs. At that time, and for many years, allografts were thought to behave similarly to autografts, a belief that persisted well into the twentieth century in some clinics and laboratories. These early attempts at nerve grafting yielded poor results and most surgeons aimed for primary nerve repair despite nerve gaps. Other techniques to allow direct repair involved alteration of position, transposition of the nerve, and even sometimes bone shortening. Although primary repair was frequently possible, after these measures the repair was under tension and mechanical failure was common. Spurling (1945), Whitcomb (1946), and Woodall (1956) showed failure rates of 4%, 7.5%, and 22.4% respectively. Some recovery of function following nerve grafting was documented by Sanders (1942), Seddon (1954), and Brooks (1955). Millesi subsequently published his results for nerve grafting for injuries to the upper limb in 1984. These papers demonstrated more significant recovery of function and highlighted the detriment of delay in treatment to final outcome. Microsurgical advances were central to Millesi’s results, and he emphasized atraumatic dissection and the deleterious effect of tension at the repair site resulting in fibrosis preventing axonal regrowth. Nerve autograft is now the standard for orthotopic nerve reconstruction when primary repair cannot be achieved.

‘EngNT’ — Engineering live neural tissue for nerve replacement

Peripheral nerve injury can result in severe long-term disability and current clinical approaches for repairing large gaps rely on the nerve autograft. Engineered Neural Tissue (EngNT) has been developed to provide living aligned therapeutic cells in a stabilised collagen hydrogel, mimicking the key features of the autograft. This Perspective article will introduce the field and discuss the current stage of translation, highlighting the key opportunities for commercial and clinical development.

A Technique to Reconstruct a Nerve Injured at Its Bifurcation Site Using Autograft and End-to-Side Neurorrhaphy

Peripheral nerves injuries are relatively frequent after high-energy trauma in both upper and lower limb. This case report describes the reconstruction of a 5-cm nerve defect involving the superficial peroneal nerve (SPN) where it divides into its two terminal branches. A 5-cm nerve graft was harvested from the proximal part of the medial dorsal cutaneous nerve (MDN) and interposed to fill the gap between the distal stump of the SPN and the intermediate dorsal cutaneous nerve (IDN). The stump of the MDN was then sutured with an end-to-side (ETS) technique to the IDN, distally to the nerve graft, by opening a window in the epineurium of IDN. The sensory restoration of the dorsal area of the foot after 8 months was evaluated satisfactory from the authors. Tenderness and Tinel’s sign at the lesion site were not present. The patient’s satisfaction was excellent. The results of this case may suggest that a nerve defect involving a bifurcation point can be treated with satisfactory results using one distal stump as donor nerve for a nerve autograft to bridge the nerve gap followed by an ETS neurorrhaphy of donor one on the other stump. In this way, it is possible to reconstruct a bifurcation point by creating a new division point with the same Y-shape in a more distal position, without adding morbidity due to the harvesting of a nerve graft from another area of the body.

Conditioning Electrical Stimulation Is Superior to Postoperative Electrical Stimulation in Enhanced Regeneration and Functional Recovery Following Nerve Graft Repair

Background. Autologous nerve graft is the most common clinical intervention for repairing a nerve gap. However, its regenerative capacity is decreased in part because, unlike a primary repair, the regenerating axons must traverse 2 repair sites. Means to promote nerve regeneration across a graft are needed. Postoperative electrical stimulation (PES) improves nerve growth by reducing staggered regeneration at the coaptation site whereas conditioning electrical stimulation (CES) accelerates axon extension. In this study, we directly compared these electrical stimulation paradigms in a model of nerve autograft repair. Methods. To lay the foundation for clinical translation, regeneration and reinnervation outcomes of CES and PES in a 5-mm nerve autograft model were compared. Sprague-Dawley rats were divided into: ( a) CES, ( b) PES, and ( c) no stimulation cohorts. CES was delivered 1 week prior to nerve cut/coaptation, and PES was delivered immediately following coaptation. Length of nerve regeneration (n = 6/cohort), and behavioral testing (n = 16/cohort) were performed at 14 days and 6 to 14 weeks post-coaptation, respectively. Results. CES treated axons extended 5.9 ± 0.2 mm, significantly longer than PES (3.8 ± 0.2 mm), or no stimulation (2.5 ± 0.2 mm) ( P < .01). Compared with PES animals, the CES animals had significantly improved sensory recovery (von Frey filament testing, intraepidermal nerve fiber reinnervation) ( P < .001) and motor reinnervation (horizontal ladder, gait analysis, nerve conduction studies, neuromuscular junction analysis) ( P < .01). Conclusion. CES resulted in faster regeneration through the nerve graft and improved sensorimotor recovery compared to all other cohorts. It is a promising treatment to improve outcomes in patients undergoing nerve autograft repair.

Doxorubicin-Immersed Skeletal Muscle Grafts Promote Peripheral Nerve Regeneration Across a 10-mm Defect in the Rat Sciatic Nerve

Background The treatment of peripheral nerve defects requires bridging materials. Skeletal muscle grafts have been studied as an alternative to nerve autografts because they contain longitudinally aligned basal laminar tubes that are similar to axons. Several pretreatment methods for muscle grafts have promoted axonal regeneration. Here, a new method of doxorubicin pretreatment was used, and the efficacy of the pretreated muscle graft was evaluated in a rat model of a sciatic nerve defect. Methods A rat model of a 10-mm sciatic nerve defect was analyzed in three settings: muscle grafts with and without doxorubicin pretreatment (M-graft-w-Dox and M-graft-w/o-Dox groups, respectively) and a nerve autograft group (N-graft) (n = 6/group). The M-graft-w-Dox group was immersed in a doxorubicin solution for 10 minutes and rinsed with saline. Analyses of target muscle atrophy, electrophysiology, and histology were performed 8 weeks after grafting. Results Electrophysiological parameters and target muscle atrophy were significantly superior in the M-graft-w-Dox group compared with the M-graft-w/o-Dox group. Histological assessment revealed the presence of a significantly greater number of regenerated axons in the M-graft-w-Dox group versus the M-graft-w/o-Dox group, while there were no significant differences between the M-graft-w-Dox and N-graft groups. The diameter of myelinated axons of the regenerated nerve in the M-graft-w-Dox group was significantly larger than that in the M-graft-w/o-Dox group, while it was not significantly different compared with the N-graft group. Conclusion Pretreatment of muscle grafts with doxorubicin promoted significant peripheral nerve regeneration. This method may represent a new option for the treatment of peripheral nerve defects.