Recovery of Motor Function after Mixed and Motor Nerve Repair with Processed Nerve Allograft.
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ABSTRACT:
SUBMITTER: Safa B
PROVIDER: S-EPMC6467606 | biostudies-literature | 2019 Mar
REPOSITORIES: biostudies-literature
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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.
| S-EPMC4920529 | biostudies-literature
Project description:BackgroundNeuromas causing sensory disturbance can substantially affect nerve function and quality of life. Historically, passive termination of the nerve end and proximal relocation to muscle or bone has been performed after neuroma resection, but this method does not allow for neurologic recovery or prevent recurrent neuromas. The use of processed nerve allografts (PNAs) for intercalary reconstruction of nerve defects following neuroma resection is reasonable for neuroma management, although reported outcomes are limited. The purpose of this study was to assess the outcomes of pain reduction and functional recovery following neuroma resection and intercalary nerve reconstruction using PNA.MethodsData on outcomes of PNA use for peripheral nerve reconstruction were collected from a multicenter registry study. The registry database was queried for upper extremity nerve reconstruction with PNA after resection of symptomatic neuroma. Patients completing both pain and quantitative sensory assessments were included in the analysis. Improvement in pain-related symptoms was determined via patient self-reported outcomes and/or the visual analog scale. Meaningful sensory recovery was defined as a score of at least S3 on the Medical Research Council Classification scale.ResultsTwenty-five repairs involving 21 patients were included in this study. The median interval from injury to reconstruction was 386 days, and the average nerve defect length was 31 mm. Pain improved in 80% of repairs. Meaningful sensory recovery was achieved in 88% of repairs.ConclusionNeuroma resection and nerve reconstruction using PNA can reduce or eliminate chronic peripheral nerve pain and provide meaningful sensory recovery.
| S-EPMC8489892 | biostudies-literature
Project description:Brachial plexus lesion results in loss of motor and sensory function, being more harmful in the neonate. Therefore, this study evaluated neuroprotection and regeneration after neonatal peripheral nerve coaptation with fibrin sealant. Thus, P2 neonatal Lewis rats were divided into three groups: AX: sciatic nerve axotomy (SNA) without treatment; AX+FS: SNA followed by end-to-end coaptation with fibrin sealant derived from snake venom; AX+CFS: SNA followed by end-to-end coaptation with commercial fibrin sealant. Results were analyzed 4, 8, and 12 weeks after lesion. Astrogliosis, microglial reaction, and synapse preservation were evaluated by immunohistochemistry. Neuronal survival, axonal regeneration, and ultrastructural changes at ventral spinal cord were also investigated. Sensory-motor recovery was behaviorally studied. Coaptation preserved synaptic covering on lesioned motoneurons and led to neuronal survival. Reactive gliosis and microglial reaction decreased in the same groups (AX+FS, AX+CFS) at 4 weeks. Regarding axonal regeneration, coaptation allowed recovery of greater number of myelinated fibers, with improved morphometric parameters. Preservation of inhibitory synaptic terminals was accompanied by significant improvement in the motor as well as in the nociceptive recovery. Overall, the present data suggest that acute repair of neonatal peripheral nerves with fibrin sealant results in neuroprotection and regeneration of motor and sensory axons.
| S-EPMC4942656 | biostudies-literature
Project description:BackgroundNerve transection is the most common form of peripheral nerve injury. Treatment of peripheral nerve injury has primarily focused on stabilization and mechanical cues to guide extension of the regenerating growth cone across the site of transection. Here we investigate the effects of a peripheral nerve matrix (PNM) hydrogel on recovery following nerve transection.MethodsWe use rodent models to determine the effect of PNM on axon extension, electrophysiological nerve conduction, force generation and neuromuscular junction formation after nerve transection and repair. We complemented this work with in vivo and in vitro FACS and immunohistochemistry approaches to determine the effects of PN on critical cell populations early after repair.ResultsExtension of axons from the proximal stump and overall GFP+ axon volume within the regenerative bridge were increased in the presence of PNM compared with an empty conduit (p< 0.005) 21 days after repair. PNM increased electrophysiological conduction (CMAP amplitude) across the repair site (p<0.05) and neuromuscular junction formation (p=0.04) 56 days after repair. PNM produced a shift in macrophage phenotype in vitro and in vitro (p<0.05) and also promoted regeneration in a murine model used to characterize the early immune response to PNM (p<0.05).ConclusionsPNM, delivered by subepineural injection, promoted recovery following nerve transection with immediate repair, supporting a beneficial macrophage response, axon extension and downstream remodeling using a range of clinically relevant outcome measures.
| S-EPMC10461719 | biostudies-literature
Project description:BackgroundPeripheral nerve damage resulting in pain, loss of sensation, or motor function may necessitate a reconstruction with a bridging material. The RANGER® Registry was designed to evaluate outcomes following nerve repair with processed nerve allograft (Avance® Nerve Graft; Axogen; Alachua, FL). Here we report on the results from the largest peripheral nerve registry to-date.MethodsThis multicenter IRB-approved registry study collected data from patients repaired with processed nerve allograft (PNA). Sites followed their own standard of care for patient treatment and follow-up. Data were assessed for meaningful recovery, defined as ≥S3/M3 to remain consistent with previously published results, and comparisons were made to reference literature.ResultsThe study included 385 subjects and 624 nerve repairs. Overall, 82% meaningful recovery (MR) was achieved across sensory, mixed, and motor nerve repairs up to gaps of 70 mm. No related adverse events were reported. There were no significant differences in MR across the nerve type, age, time-to-repair, and smoking status subgroups in the upper extremity (p > .05). Significant differences were noted by the mechanism of injury subgroups between complex injures (74%) as compared to lacerations (85%) or neuroma resections (94%) (p = .03) and by gap length between the <15 mm and 50-70 mm gap subgroups, 91 and 69% MR, respectively (p = .01). Results were comparable to historical literature for nerve autograft and exceed that of conduit.ConclusionsThese findings provide clinical evidence to support the continued use of PNA up to 70 mm in sensory, mixed and motor nerve repair throughout the body and across a broad patient population.
| S-EPMC7496926 | biostudies-literature
Project description:Sirtuin-2 (Sirt2) is a member of the NAD (+)-dependent protein deacetylase family involved in neuroprotection, cellular metabolism, homeostasis, and stress responses after injury of the nervous system. So far, no data have been published describing the role of SIRT2 in motor functional recovery after damage. We found that SIRT2 expression and deacetylase activity were increased within motoneurons after axotomy. To shed light onto the biological relevance of this change, we combined in vitro and in vivo models with pharmacological and genetic ablation approaches. We found that SIRT2 KO (knockout) mice exhibited improved functional recovery after sciatic nerve crush. SIRT2 activity blockage, using AK7, increased neurite outgrowth and length in organotypic spinal cord cultures and human cell line models. SIRT2 blockage enhanced the acetyltransferase activity of p300, which in turn increased the levels of an acetylated form of p53 (Ac-p53 k373), histone 3 (Ac-H3K9), and expression of GAP43, a downstream marker of regeneration. Lastly, we verified that p300 acetyltransferase activity is essential for these effects. Our results suggest that bolstering an epigenetic shift that promotes SIRT2 inhibition can be an effective therapy to increase functional recovery after peripheral nerve injury.
| S-EPMC7609484 | biostudies-literature
Project description:Active pronation is important for many activities of daily living. Loss of median nerve function including pronation is a rare sequela of humerus fracture. Tendon transfers to restore pronation are reserved for the obstetrical brachial plexus palsy patient. Transfer of expendable motor nerves is a treatment modality that can be used to restore active pronation. Nerve transfers are advantageous in that they do not require prolonged immobilization postoperatively, avoid operating within the zone of injury, reinnervate muscles in their native location prior to degeneration of the motor end plates, and result in minimal donor deficit. We report a case of lost median nerve function after a humerus fracture. Pronation was restored with transfer of the extensor carpi radialis brevis branch of the radial nerve to the pronator teres branch of the median nerve. Anterior interosseous nerve function was restored with transfer of the supinator branch to the anterior interosseous nerve. Clinically evident motor function was seen at 4 months postoperatively and continued to improve for the following 18 months. The patient has 4+/5 pronator teres, 4+/5 flexor pollicis longus, and 4-/5 index finger flexor digitorum profundus function. The transfer of the extensor carpi radialis brevis branch of the radial nerve to the pronator teres and supinator branch of the radial nerve to the anterior interosseous nerve is a novel, previously unreported method to restore extrinsic median nerve function.
| S-EPMC2654949 | biostudies-other
Project description:Both intracellular sigma peptide (ISP) and phosphatase and tensin homolog agonist protein (PAP4) promote nerve regeneration and motor functional recovery after spinal cord injury. However, the role of these two small peptides in peripheral nerve injury remains unclear. A rat model of brachial plexus injury was established by crush of the C6 ventral root. The rats were then treated with subcutaneous injection of PAP4 (497 µg/d, twice per day) or ISP (11 µg/d, once per day) near the injury site for 21 successive days. After ISP and PAP treatment, the survival of motoneurons was increased, the number of regenerated axons and neuromuscular junctions was increased, muscle atrophy was reduced, the electrical response of the motor units was enhanced and the motor function of the injured upper limbs was greatly improved in rats with brachial plexus injury. These findings suggest that ISP and PAP4 promote the recovery of motor function after peripheral nerve injury in rats. The animal care and experimental procedures were approved by the Laboratory Animal Ethics Committee of Jinan University of China (approval No. 20111008001) in 2011.
| S-EPMC8323685 | biostudies-literature
Project description:Although peripheral nerves can regenerate after injury, proximal nerve injury in humans results in minimal restoration of motor function. One possible explanation for this is that injury-induced axonal growth is too slow. Heat shock protein 27 (Hsp27) is a regeneration-associated protein that accelerates axonal growth in vitro. Here, we have shown that it can also do this in mice after peripheral nerve injury. While rapid motor and sensory recovery occurred in mice after a sciatic nerve crush injury, there was little return of motor function after sciatic nerve transection, because of the delay in motor axons reaching their target. This was not due to a failure of axonal growth, because injured motor axons eventually fully re-extended into muscles and sensory function returned; rather, it resulted from a lack of motor end plate reinnervation. Tg mice expressing high levels of Hsp27 demonstrated enhanced restoration of motor function after nerve transection/resuture by enabling motor synapse reinnervation, but only within 5 weeks of injury. In humans with peripheral nerve injuries, shorter wait times to decompression surgery led to improved functional recovery, and, while a return of sensation occurred in all patients, motor recovery was limited. Thus, absence of motor recovery after nerve damage may result from a failure of synapse reformation after prolonged denervation rather than a failure of axonal growth.
| S-EPMC3223863 | biostudies-literature
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.
| S-EPMC10570074 | biostudies-literature