Acellular Nerve Allografts in Major Peripheral Nerve Repairs: An Analysis of Cases Presenting With Limited Recovery

Hand ◽  
2021 ◽  
pp. 155894472110031
Author(s):  
Blair R. Peters ◽  
Matthew D. Wood ◽  
Daniel A. Hunter ◽  
Susan E. Mackinnon

Background: Acellular nerve allografts have been used successfully and with increasing frequency to reconstruct nerve injuries. As their use has been expanded to treat longer gap, larger diameter nerve injuries, some failed cases have been reported. We present the histomorphometry of 5 such cases illustrating these limitations and review the current literature of acellular nerve allografts. Methods: Between 2014 and 2019, 5 patients with iatrogenic nerve injuries to the median or ulnar nerve reconstructed with an AxoGen AVANCE nerve allograft at an outside hospital were treated in our center with allograft excision and alternative reconstruction. These patients had no clinical or electrophysiological evidence of recovery, and allograft specimens at the time of surgery were sent for histomorphological examination. Results: Three patients with a median and 2 with ulnar nerve injury were included. Histology demonstrated myelinated axons present in all proximal native nerve specimens. In 2 cases, axons failed to regenerate into the allograft and in 3 cases, axonal regeneration diminished or terminated within the allograft. Conclusions: The reported cases demonstrate the importance of evaluating the length and the function of nerves undergoing acellular nerve allograft repair. In long length, large-diameter nerves, the use of acellular nerve allografts should be carefully considered.

Author(s):  
Melanie D. Luikart ◽  
Justin M. Kistler ◽  
David Kahan ◽  
Richard McEntee ◽  
Asif M. Ilyas

Abstract Background There has been an increasing utilization of end-to-end (ETE) and reverse “supercharged” end-to-side (SETS) anterior interosseous nerve (AIN) to ulnar nerve transfers (NTs) for treatment of high ulnar nerve injury. This study aimed to review the potential indications for, and outcomes of, ETE and SETS AIN–ulnar NT. Methods A literature review was performed, and 10 articles with 156 patients who had sufficient follow-up to evaluate functional outcomes were included. English studies were included if they reported the outcome of patients with ulnar nerve injuries treated with AIN to ulnar motor NT. Outcomes were analyzed based on the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire scores, grip and key pinch strength, and interosseous Medical Research Council–graded motor strength. Comparisons were made using the independent t-test and the chi-square test. No nerve graft control group was required for eligibility. Ulnar nerve injury types varied. Results NT resulted in 77% of patients achieving M3+ recovery, 53.7 ± 19.8 lb grip strength recovery, 61 ± 21% key pinch recovery, and a mean DASH score of 33.4 ± 16. In this diverse group, NT resulted in significantly greater M3+ recovery and grip strength recovery measured in pounds than in the nerve graft/conventional treatment group, and ETE repairs had significantly better outcomes compared with SETS repairs for grip strength, key pinch strength, and DASH scores, but heterogeneity limits interpretation. Conclusion ETE and SETS AIN–ulnar NTs produce significant restoration of ulnar nerve motor function for high ulnar nerve injuries. For ulnar nerve transection injuries at or above the elbow, ETE NT results in superior motor recovery compared with nerve grafting/conventional repair. However, further research is needed to determine the best treatment for other types of ulnar nerve injury and the role of SETS NT.


2019 ◽  
Vol 28 (9-10) ◽  
pp. 1231-1241 ◽  
Author(s):  
Sadaki Mitsuzawa ◽  
Ryosuke Ikeguchi ◽  
Tomoki Aoyama ◽  
Hisataka Takeuchi ◽  
Hirofumi Yurie ◽  
...  

Autologous nerve grafting is widely accepted as the gold standard treatment for segmental nerve defects. To overcome the inevitable disadvantages of the original method, alternative methods such as the tubulization technique have been developed. Several studies have investigated the characteristics of an ideal nerve conduit in terms of supportive cells, scaffolds, growth factors, and vascularity. Previously, we confirmed that biological scaffold-free conduits fabricated from human dermal fibroblasts promote nerve regeneration in a rat sciatic nerve injury model. The purpose of this study is to evaluate the feasibility of biological scaffold-free conduits composed of autologous dermal fibroblasts using a large-animal model. Six male beagle dogs were used in this study. Eight weeks before surgery, dermal fibroblasts were harvested from their groin skin and grown in culture. Bio 3D conduits were assembled from proliferating dermal fibroblasts using a Bio 3D printer. The ulnar nerve in each dog’s forelimb was exposed under general anesthesia and sharply cut to create a 5 mm interstump gap, which was bridged by the prepared 8 mm Bio 3D conduit. Ten weeks after surgery, nerve regeneration was investigated. Electrophysiological studies detected compound muscle action potentials (CMAPs) of the hypothenar muscles and motor nerve conduction velocity (MNCV) in all animals. Macroscopic observation showed regenerated ulnar nerves. Low-level hypothenar muscle atrophy was confirmed. Immunohistochemical, histological, and morphometric studies confirmed the existence of many myelinated axons through the Bio 3D conduit. No severe adverse event was reported. Hypothenar muscles were re-innervated by regenerated nerve fibers through the Bio 3D conduit. The scaffold-free Bio 3D conduit fabricated from autologous dermal fibroblasts is effective for nerve regeneration in a canine ulnar nerve injury model. This technology was feasible as a treatment for peripheral nerve injury and segmental nerve defects in a preclinical setting.


2005 ◽  
Vol 30 (1) ◽  
pp. 35-39 ◽  
Author(s):  
H. E. ROSBERG ◽  
K. S. CARLSSON ◽  
S. HÖJGÅRD ◽  
B. LINDGREN ◽  
G. LUNDBORG ◽  
...  

This study analysed the costs of median and ulnar nerve injuries in the forearm in humans and factors affecting such costs. The costs within the health-care sector and costs of lost production were calculated in 69 patients with an injury to the median and/or ulnar nerve in the forearm, usually caused by glass, a knife, or a razorblade. Factors associated with the variation in costs and outcome were analysed. The total median costs for an employed person with a median and an ulnar nerve injury were EUR 51,238 and EUR 31,186, respectively, and 87% of the total costs were due to loss of production. All costs were higher for patients with concomitant tendon injuries (≥4 tendons). The costs within the health-care sector were also higher for patients who changed work after the injury and if both nerves were injured. Outcome was dependent on age and repair method.


2015 ◽  
Vol 30 (5) ◽  
pp. 490-496 ◽  
Author(s):  
Michael P. Willand ◽  
May-Anh Nguyen ◽  
Gregory H. Borschel ◽  
Tessa Gordon

Peripheral nerve injury afflicts individuals from all walks of life. Despite the peripheral nervous system’s intrinsic ability to regenerate, many patients experience incomplete functional recovery. Surgical repair aims to expedite this recovery process in the most thorough manner possible. However, full recovery is still rarely seen especially when nerve injury is compounded with polytrauma where surgical repair is delayed. Pharmaceutical strategies supplementary to nerve microsurgery have been investigated but surgery remains the only viable option. Brief low-frequency electrical stimulation of the proximal nerve stump after primary repair has been widely investigated. This article aims to review the currently known biological basis for the regenerative effects of acute brief low-frequency electrical stimulation on axonal regeneration and outline the recent clinical applications of the electrical stimulation protocol to demonstrate the significant translational potential of this modality for repairing peripheral nerve injuries. The review concludes with a discussion of emerging new advancements in this exciting area of research. The current literature indicates the imminent clinical applicability of acute brief low-frequency electrical stimulation after surgical repair to effectively promote axonal regeneration as the stimulation has yielded promising evidence to maximize functional recovery in diverse types of peripheral nerve injuries.


2020 ◽  
pp. 1-8
Author(s):  
Ranjan Gupta ◽  
Justin P. Chan ◽  
Jennifer Uong ◽  
Winnie A. Palispis ◽  
David J. Wright ◽  
...  

OBJECTIVECurrent management of traumatic peripheral nerve injuries is variable with operative decisions based on assumptions that irreversible degeneration of the human motor endplate (MEP) follows prolonged denervation and precludes reinnervation. However, the mechanism and time course of MEP changes after human peripheral nerve injury have not been investigated. Consequently, there are no objective measures by which to determine the probability of spontaneous recovery and the optimal timing of surgical intervention. To improve guidance for such decisions, the aim of this study was to characterize morphological changes at the human MEP following traumatic nerve injury.METHODSA prospective cohort (here analyzed retrospectively) of 18 patients with traumatic brachial plexus and axillary nerve injuries underwent biopsy of denervated muscles from the upper extremity from 3 days to 6 years after injury. Muscle specimens were processed for H & E staining and immunohistochemistry, with visualization via confocal and two-photon excitation microscopy.RESULTSImmunohistochemical analysis demonstrated varying degrees of fragmentation and acetylcholine receptor dispersion in denervated muscles. Comparison of denervated muscles at different times postinjury revealed progressively increasing degeneration. Linear regression analysis of 3D reconstructions revealed significant linear decreases in MEP volume (R = −0.92, R2 = 0.85, p = 0.001) and surface area (R = −0.75, R2 = 0.56, p = 0.032) as deltoid muscle denervation time increased. Surprisingly, innervated and structurally intact MEPs persisted in denervated muscle specimens from multiple patients 6 or more months after nerve injury, including 2 patients who had presented > 3 years after nerve injury.CONCLUSIONSThis study details novel and critically important data about the morphology and temporal sequence of events involved in human MEP degradation after traumatic nerve injuries. Surprisingly, human MEPs not only persisted, but also retained their structures beyond the assumed 6-month window for therapeutic surgical intervention based on previous clinical studies. Preoperative muscle biopsy in patients being considered for nerve transfer may be a useful prognostic tool to determine MEP viability in denervated muscle, with surviving MEPs also being targets for adjuvant therapy.


2021 ◽  
Vol 22 (3) ◽  
pp. 1401
Author(s):  
Rui D. Alvites ◽  
Mariana V. Branquinho ◽  
Ana C. Sousa ◽  
Federica Zen ◽  
Monica Maurina ◽  
...  

Thousands of people worldwide suffer from peripheral nerve injuries and must deal daily with the resulting physiological and functional deficits. Recent advances in this field are still insufficient to guarantee adequate outcomes, and the development of new and compelling therapeutic options require the use of valid preclinical models that effectively replicate the characteristics and challenges associated with these injuries in humans. In this study, we established a sheep model for common peroneal nerve injuries that can be applied in preclinical research with the advantages associated with the use of large animal models. The anatomy of the common peroneal nerve and topographically related nerves, the functional consequences of its injury and a neurological examination directed at this nerve have been described. Furthermore, the surgical protocol for accessing the common peroneal nerve, the induction of different types of nerve damage and the application of possible therapeutic options were described. Finally, a preliminary morphological and stereological study was carried out to establish control values for the healthy common peroneal nerves regarding this animal model and to identify preliminary differences between therapeutic methods. This study allowed to define the described lateral incision as the best to access the common peroneal nerve, besides establishing 12 and 24 weeks as the minimum periods to study lesions of axonotmesis and neurotmesis, respectively, in this specie. The post-mortem evaluation of the harvested nerves allowed to register stereological values for healthy common peroneal nerves to be used as controls in future studies, and to establish preliminary values associated with the therapeutic performance of the different applied options, although limited by a small sample size, thus requiring further validation studies. Finally, this study demonstrated that the sheep is a valid model of peripheral nerve injury to be used in pre-clinical and translational works and to evaluate the efficacy and safety of nerve injury therapeutic options before its clinical application in humans and veterinary patients.


1987 ◽  
Vol 10 (1) ◽  
pp. 37-39 ◽  
Author(s):  
L. Duinslaeger ◽  
A. DeBacker ◽  
L. Ceulemans ◽  
P. Wylock

2011 ◽  
Vol 106 (5) ◽  
pp. 2450-2470 ◽  
Author(s):  
Francisco J. Alvarez ◽  
Haley E. Titus-Mitchell ◽  
Katie L. Bullinger ◽  
Michal Kraszpulski ◽  
Paul Nardelli ◽  
...  

Motor and sensory proprioceptive axons reinnervate muscles after peripheral nerve transections followed by microsurgical reattachment; nevertheless, motor coordination remains abnormal and stretch reflexes absent. We analyzed the possibility that permanent losses of central IA afferent synapses, as a consequence of peripheral nerve injury, are responsible for this deficit. VGLUT1 was used as a marker of proprioceptive synapses on rat motoneurons. After nerve injuries synapses are stripped from motoneurons, but while other excitatory and inhibitory inputs eventually recover, VGLUT1 synapses are permanently lost on the cell body (75–95% synaptic losses) and on the proximal 100 μm of dendrite (50% loss). Lost VGLUT1 synapses did not recover, even many months after muscle reinnervation. Interestingly, VGLUT1 density in more distal dendrites did not change. To investigate whether losses are due to VGLUT1 downregulation in injured IA afferents or to complete synaptic disassembly and regression of IA ventral projections, we studied the central trajectories and synaptic varicosities of axon collaterals from control and regenerated afferents with IA-like responses to stretch that were intracellularly filled with neurobiotin. VGLUT1 was present in all synaptic varicosities, identified with the synaptic marker SV2, of control and regenerated afferents. However, regenerated afferents lacked axon collaterals and synapses in lamina IX. In conjunction with the companion electrophysiological study [Bullinger KL, Nardelli P, Pinter MJ, Alvarez FJ, Cope TC. J Neurophysiol (August 10, 2011). doi:10.1152/jn.01097.2010], we conclude that peripheral nerve injuries cause a permanent retraction of IA afferent synaptic varicosities from lamina IX and disconnection with motoneurons that is not recovered after peripheral regeneration and reinnervation of muscle by sensory and motor axons.


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