The Pathogenesis of Glenohumeral Deformity and Contracture Formation in Obstetric Brachial Plexus Palsy-A Review.

Contractures of the shoulder joint and glenohumeral joint dysplasia are well known complications to obstetrical brachial plexus palsy. Despite extensive description of these sequelae, the exact pathogenesis remains unknown. The prevailing theory to explain the contractures and glenohumeral joint dysplasia states that upper trunk injury leads to nonuniform muscle recovery and thus imbalance between internal and external rotators of the shoulder. More recently, another explanation has been proposed, hypothesizing that denervation leads to reduced growth of developing muscles and that reinnervation might suppress contracture formation. An understanding of the pathogenesis is desirable for development of effective prophylactic treatment. This article aims to describe the current state of knowledge regarding these important complications.

Effects of early nerve repair on experimental brachial plexus injury in neonatal rats.

Obstetrical brachial plexus injury refers to injury observed at the time of delivery, which may lead to major functional impairment in the upper limb. In this study, the neuroprotective effect of early nerve repair following complete brachial plexus injury in neonatal rats was examined. Brachial plexus injury induced 90% loss of spinal motoneurons and 70% decrease in biceps muscle weight at 28 days after injury. Retrograde degeneration in spinal cord was associated with decreased density of dendritic branches and presynaptic boutons and increased density of astrocytes and macrophages/microglial cells. Early repair of the injured brachial plexus significantly delayed retrograde degeneration of spinal motoneurons and reduced the degree of macrophage/microglial reaction but had no effect on muscle atrophy. The results demonstrate that early nerve repair of neonatal brachial plexus injury could promote survival of injured motoneurons and attenuate neuroinflammation in spinal cord.

Long-Term Effects of Fibrin Conduit with Human Mesenchymal Stem Cells and Immunosuppression after Peripheral Nerve Repair in a Xenogenic Model.

INTRODUCTION: Previously we showed that a fibrin glue conduit with human mesenchymal stem cells (hMSCs) and cyclosporine A (CsA) enhanced early nerve regeneration. In this study long term effects of this conduit are investigated. METHODS: In a rat model, the sciatic nerve was repaired with fibrin conduit containing fibrin matrix, fibrin conduit containing fibrin matrix with CsA treatment and fibrin conduit containing fibrin matrix with hMSCs and CsA treatment, and also with nerve graft as control. RESULTS: At 12 weeks 34% of motoneurons of the control group regenerated axons through the fibrin conduit. CsA treatment alone or with hMSCs resulted in axon regeneration of 67% and 64% motoneurons respectively. The gastrocnemius muscle weight was reduced in the conduit with fibrin matrix. The treatment with CsA or CsA with hMSCs induced recovery of the muscle weight and size of fast type fibers towards the levels of the nerve graft group. DISCUSSION: The transplantation of hMSCs for peripheral nerve injury should be optimized to demonstrate their beneficial effects. The CsA may have its own effect on nerve regeneration.

Proximal versus Distal Nerve Transfer for Biceps Reinnervation-A Comparative Study in a Rat's Brachial Plexus Injury Model.

BACKGROUND: The exact role of proximal and distal nerve transfers in reconstruction strategies of brachial plexus injury remains controversial. We compared proximal with distal nerve reconstruction strategies in a rat model of brachial plexus injury. METHODS: In rats, the C6 spinal nerve with a nerve graft (proximal nerve transfer model, n = 30, group A) and 50% of ulnar nerve (distal nerve transfer model, n = 30, group B) were used as the donor nerves. The targets were the musculocutaneous nerve and the biceps muscle. Outcomes were recorded at 4, 8, 12, and 16 weeks postoperatively. Outcome parameters included grooming test, biceps muscle weight, compound muscle action potentials, tetanic contraction force, and axonal morphology of the donor and target nerves. RESULTS: The axonal morphology of the 2 donor nerves revealed no significant difference. Time interval analysis in the proximal nerve transfer group showed peak axon counts at 12 weeks and a trend of improvement in all functional and physiologic parameters across all time points with statistically significant differences for grooming test, biceps compound action potentials, tetanic muscle contraction force, and muscle weight at 16 weeks. In contrast, in the distal nerve transfer group, the only statistically significant difference was observed between the 4 and 8 week time points, followed by a plateau from 8 to 16 weeks. CONCLUSIONS: Outcomes of proximal nerve transfers are ultimately superior to distal nerve transfers in our experimental model. Possible explanations for the superior results include a reduced need for cortical adaptation and higher proportions of motor units in the proximal nerve transfers.

A Simplified Lateral Hinge Approach to the Proximal Interphalangeal Joint.

Proximal interphalangeal joint replacement is an effective treatment for painful arthritis affecting the joint. However, the complication rate is relatively high, with many of these complications related to soft-tissue imbalance or instability. Volar, dorsal, and lateral approaches have all been described with varying results. We describe a new simplified lateral hinge approach that splits the collateral ligament to provide adequate exposure of the joint. Following insertion of the prosthesis the collateral ligament is simply repaired, side-to-side, which stabilizes the joint. As the central slip, opposite collateral ligament, flexor and extensor tendons have not been violated, early active mobilization without splinting is possible, and the risk of instability, swan-neck, and boutonniere deformity are reduced. The indications, contraindications, surgical technique, and rehabilitation protocol are described.

Effect of delayed peripheral nerve repair on nerve regeneration, Schwann cell function and target muscle recovery.

Despite advances in surgical techniques for peripheral nerve repair, functional restitution remains incomplete. The timing of surgery is one factor influencing the extent of recovery but it is not yet clearly defined how long a delay may be tolerated before repair becomes futile. In this study, rats underwent sciatic nerve transection before immediate (0) or 1, 3, or 6 months delayed repair with a nerve graft. Regeneration of spinal motoneurons, 13 weeks after nerve repair, was assessed using retrograde labeling. Nerve tissue was also collected from the proximal and distal stumps and from the nerve graft, together with the medial gastrocnemius (MG) muscles. A dramatic decline in the number of regenerating motoneurons and myelinated axons in the distal nerve stump was observed in the 3- and 6-months delayed groups. After 3 months delay, the axonal number in the proximal stump increased 2-3 folds, accompanied by a smaller axonal area. RT-PCR of distal nerve segments revealed a decline in Schwann cells (SC) markers, most notably in the 3 and 6 month delayed repair samples. There was also a progressive increase in fibrosis and proteoglycan scar markers in the distal nerve with increased delayed repair time. The yield of SC isolated from the distal nerve segments progressively fell with increased delay in repair time but cultured SC from all groups proliferated at similar rates. MG muscle at 3- and 6-months delay repair showed a significant decline in weight (61% and 27% compared with contra-lateral side). Muscle fiber atrophy and changes to neuromuscular junctions were observed with increased delayed repair time suggestive of progressively impaired reinnervation. This study demonstrates that one of the main limiting factors for nerve regeneration after delayed repair is the distal stump. The critical time point after which the outcome of regeneration becomes too poor appears to be 3-months.

Fibrin conduit supplemented with human mesenchymal stem cells and immunosuppressive treatment enhances regeneration after peripheral nerve injury.

To address the need for the development of bioengineered replacement of a nerve graft, a novel two component fibrin glue conduit was combined with human mesenchymal stem cells (MSC) and immunosupressive treatment with cyclosporine A. The effects of MSC on axonal regeneration in the conduit and reaction of activated macrophages were investigated using sciatic nerve injury model. A 10mm gap in the sciatic nerve of a rat was created and repaired either with fibrin glue conduit containing diluted fibrin matrix or fibrin glue conduit containing fibrin matrix with MSC at concentration of 80×10(6) cells/ml. Cells were labeled with PKH26 prior to transplantation. The animals received daily injections of cyclosporine A. After 3 weeks the distance of regeneration and area occupied by regenerating axons and ED1 positives macrophages was measured. MSC survived in the conduit and enhanced axonal regeneration only when transplantation was combined with cyclosporine A treatment. Moreover, addition of cyclosporine A to the conduits with transplanted MSC significantly reduced the ED1 macrophage reaction.

BD™ PuraMatrix™ peptide hydrogel seeded with Schwann cells for peripheral nerve regeneration.

This study investigated the effects of a membrane conduit filled with a synthetic matrix BD™ PuraMatrix™ peptide (BD) hydrogel and cultured Schwann cells on regeneration after peripheral nerve injury in adult rats. After sciatic axotomy, a 10mm gap between the nerve stumps was bridged using ultrafiltration membrane conduits filled with BD hydrogel or BD hydrogel containing Schwann cells. In control experiments, the nerve defect was bridged using either membrane conduits with alginate/fibronectin hydrogel or autologous nerve graft. Axonal regeneration within the conduit was assessed at 3 weeks and regeneration of spinal motoneurons and recovery of muscle weight evaluated at 16 weeks postoperatively. Schwann cells survived in the BD hydrogel both in culture and after transplantation into the nerve defect. Regenerating axons grew significantly longer distances within the conduits filled with BD hydrogel when compared with the alginate/fibronectin hydrogel and alginate/fibronectin with Schwann cells. Addition of Schwann cells to the BD hydrogel considerably increased regeneration distance with axons crossing the injury gap and entering into the distal nerve stump. The conduits with BD hydrogel showed a linear alignment of nerve fibers and Schwann cells. The number of regenerating motoneurons and recovery of the weight of the gastrocnemius muscle was inferior in BD hydrogel and alginate/fibronectin groups compared with nerve grafting. Addition of Schwann cells did not improve regeneration of motoneurons or muscle recovery. The present results suggest that BD hydrogel with Schwann cells could be used within biosynthetic conduits to increase the rate of axonal regeneration across a nerve defect.