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Recovery of Motor Function after Mixed and Motor Nerve Repair with Processed Nerve Allograft.

ABSTRACT: Background:Severe trauma often results in the transection of major peripheral nerves. The RANGER Registry is an ongoing observational study on the use and outcomes of processed nerve allografts (PNAs; Avance Nerve Graft, AxoGen, Inc., Alachua, Fla.). Here, we report on motor recovery outcomes for nerve injuries repaired acutely or in a delayed fashion with PNA and comparisons to historical controls in the literature. Methods:The RANGER database was queried for mixed and motor nerve injuries in the upper extremities, head, and neck area having completed greater than 1 year of follow-up. All subjects with sufficient assessments to evaluate functional outcomes were included. Meaningful recovery was defined as ?M3 on the Medical Research Council scale. Demographics, outcomes, and covariate analysis were performed to further characterize this subgroup. Results:The subgroup included 20 subjects with 22 nerve repairs. The mean ± SD (minimum-maximum) age was 38?±?19 (16-77) years. The median repair time was 9 (0-133) days. The mean graft length was 33?±?17 (10-70) mm with a mean follow-up of 779?±?480 (371-2,423) days. Meaningful motor recovery was observed in 73%. Subgroup analysis showed no differences between gap lengths or mechanism of injury. There were no related adverse events. Conclusions:PNAs were safe and provided functional motor recovery in mixed and motor nerve repairs. Outcomes compare favorably to historical controls for nerve autograft and exceed those for hollow tube conduit. PNA may be considered as an option when reconstructing major peripheral nerve injuries.

SUBMITTER: Safa B

PROVIDER: S-EPMC6467606 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Recovery of Motor Function after Mixed and Motor Nerve Repair with Processed Nerve Allograft.

Safa Bauback B Shores Jaimie T JT Ingari John V JV Weber Renata V RV Cho Mickey M Zoldos Jozef J Niacaras Timothy R TR Nesti Leon J LJ Thayer Wesley P WP Buncke Gregory M GM

Plastic and reconstructive surgery. Global open 20190313 3

<h4>Background</h4>Severe trauma often results in the transection of major peripheral nerves. The RANGER Registry is an ongoing observational study on the use and outcomes of processed nerve allografts (PNAs; Avance Nerve Graft, AxoGen, Inc., Alachua, Fla.). Here, we report on motor recovery outcomes for nerve injuries repaired acutely or in a delayed fashion with PNA and comparisons to historical controls in the literature.<h4>Methods</h4>The RANGER database was queried for mixed and motor nerv ...[more]

PMID: 31044125

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Project description:BackgroundCurrent repair options for peripheral nerve injuries where tension-free gap closure is not possible include allograft, processed nerve allograft, and hollow tube conduit. Here we report on the outcomes from a multicenter prospective, randomized, patient- and evaluator-blinded, pilot study comparing processed nerve allograft and hollow conduit for digital nerve reconstructions in the hand.MethodsAcross 4 centers, consented participants meeting inclusion criteria while not meeting exclusion criteria were randomized intraoperatively to either processed nerve allograft or hollow conduit. Standard sensory and safety assessments were conducted at baseline, 1, 3, 6, 9, and 12 months after reconstruction. The primary outcome was static 2-point discrimination (s2PD) testing. Participants and assessors were blinded to treatment. The contralateral digit served as the control.ResultsWe randomized 23 participants with 31 digital nerve injuries. Sixteen participants with 20 repairs had at least 6 months of follow-up while 12-month follow-up was available for 15 repairs. There were no significant differences in participant and baseline characteristics between treatment groups. The predominant nerve injury was laceration/sharp transection. The mean ± SD length of the nerve gap prior to repair was 12 ± 4 mm (5-20 mm) for both groups. The average s2PD for processed allograft was 5 ± 1 mm (n = 6) compared with 8 ± 5 mm (n = 9) for hollow conduits. The average moving 2PD for processed allograft was 5 ± 1 mm compared with 7 ± 5 mm for hollow conduits. All injuries randomized to processed nerve allograft returned some degree of s2PD as compared with 75% of the repairs in the conduit group. Two hollow conduits and one allograft were lost due to infection during the study.ConclusionsIn this pilot study, patients whose digital nerve reconstructions were performed with processed nerve allografts had significantly improved and more consistent functional sensory outcomes compared with hollow conduits.

Project description:BackgroundThe functional deterioration and loss of motor neurons are tightly associated with degenerative motor neuron diseases and aging-related muscle wasting. Motor neuron diseases or aging-related muscle wasting in turn contribute to increased risk of adverse health outcomes in the elderly. Cdon (cell adhesion molecule-downregulated oncogene) belongs to the immunoglobulin superfamily of cell adhesion molecule and plays essential roles in multiple signalling pathways, including sonic hedgehog (Shh), netrin, and cadherin-mediated signalling. Cdon as a Shh coreceptor plays a critical role in motor neuron specification during embryonic development. However, its role in adult motor neuron function is unknown.MethodsHb9-Cre recombinase-driven motor neuron-specific Cdon deficient mice (mnKO) and a compound mutant mice (mnKO::SOD1G93A ) were generated to investigate the role of Cdon in motor neuron degeneration. Motor neuron regeneration was examined by using a sciatic nerve crush injury model. To investigate the phenotype, physical activity, compound muscle action potential, immunostaining, and transmission electron microscopy were carried out. In the mechanism study, RNA sequencing and RNA/protein analyses were employed.ResultsMice lacking Cdon in motor neurons exhibited middle age onset lethality and aging-related decline in motor function. In the sciatic nerve crush injury model, mnKO mice exhibited an impairment in motor function recovery evident by prolonged compound muscle action potential duration (4.63 ± 0.35 vs. 3.93 ± 0.22 s for f/f, P < 0.01) and physical activity. Consistently, neuromuscular junctions of mnKO muscles were incompletely occupied (49.79 ± 5.74 vs. 79.39 ± 3.77% fully occupied neuromuscular junctions for f/f, P < 0.0001), suggesting an impaired reinnervation. The transmission electron microscopy analysis revealed that mnKO sciatic nerves had smaller axon diameter (0.88 ± 0.13 vs. 1.43 ± 0.48 μm for f/f, P < 0.0001) and myelination defects. RNA sequencing of mnKO lumbar spinal cords showed alteration in genes related to neurogenesis, inflammation and cell death. Among the altered genes, ErbB4 and FgfR expressions were significantly altered in mnKO as well as in Cdon-depleted NSC34 motor neuron cells. Consistently, Cdon-depleted NSC34 cells exhibited elevated levels of cleaved Caspase3 and γH2AX proteins, as well as Bax transcription. Cdon-depleted NSC34 cells also exhibited impaired activation of Akt in response to neuregulin-1 (NRG1) treatment.ConclusionsOur current data demonstrate the functional importance of Cdon in motor neuron function and nerve repair. Cdon ablation causes alterations in neurotrophin signalling that leads to motor neuron degeneration.

Dataset Information

Recovery of Motor Function after Mixed and Motor Nerve Repair with Processed Nerve Allograft.

Publications

Recovery of Motor Function after Mixed and Motor Nerve Repair with Processed Nerve Allograft.

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