Ida K. Fox

Effects of motor versus sensory nerve grafts on peripheral nerve regeneration.

Autologous nerve grafting is the current standard of care for nerve injuries resulting in a nerve gap. This treatment requires the use of sensory grafts to reconstruct motor defects, but the consequences of mismatches between graft and native nerve are unknown. Motor pathways have been shown to preferentially support motoneuron regeneration. Functional outcome of motor nerve reconstruction depends on the magnitude, rate, and precision of end organ reinnervation. This study examined the role of pathway type on regeneration across a mixed nerve defect. Thirty-six Lewis rats underwent tibial nerve transection and received isogeneic motor, sensory or mixed nerve grafts. Histomorphometry of the regenerating nerves at 3 weeks demonstrated robust nerve regeneration through both motor and mixed nerve grafts. In contrast, poor nerve regeneration was seen through sensory nerve grafts, with significantly decreased nerve fiber count, percent nerve, and nerve density when compared with mixed and motor groups (P < 0.05). These data suggest that use of motor or mixed nerve grafts, rather than sensory nerve grafts, will optimize regeneration across mixed nerve defects.

Choosing the correct functional assay: a comprehensive assessment of functional tests in the rat.

While there are several ways to quantify peripheral nerve regeneration; the true measure of successful outcome is functional recovery. Functional tests are relatively easily conducted in human subjects; however it is more difficult in a laboratory animal. The laboratory rat is an excellent animal model of peripheral nerve injury and has been used extensively in the field of peripheral nerve research. Due to the intense interest in the rat as an experimental model, functional assays have been reported. In an effort to provide a resource to which investigators can refer when considering the most appropriate functional assay for a given experiment, the authors have compiled and tabulated the available functional tests applicable to various models of rat nerve injury.

Use of cold-preserved allografts seeded with autologous Schwann cells in the treatment of a long-gap peripheral nerve injury.

Background: Limitations in autogenous tissue have inspired the study of alternative materials for repair of complex peripheral nerve injuries. Cadaveric allografts are one potential reconstructive material, but their use requires systemic immunosuppression. Cold preservation (≥7 weeks) renders allografts devoid of antigens, but these acellular substrates generally fail in supporting regeneration beyond 3 cm. In this study, the authors evaluated the reconstruction of extensive nonhuman primate peripheral nerve defects using 7-week cold-preserved allografts repopulated with cultured autologous Schwann cells. Methods: Ten outbred Macaca fascicularis primates were paired based on maximal genetic disparity as measured by similarity index assay. A total of 14 ulnar nerve defects measuring 6 cm were successfully reconstructed using autografts (n = 5), fresh allografts (n = 2), cold-preserved allografts (n = 3), or cold-preserved allografts seeded with autogenous Schwann cells (n = 4). Recipient immunoreactivity was evaluated by means of enzyme-linked immunosorbent spot assay, and nerves were harvested at 6 months for histologic and histomorphometric analysis. Results: Cytokine production in response to cold-preserved allografts and cold-preserved allografts seeded with autologous Schwann cells was similar to that observed for autografts. Schwann cell–repopulated cold-preserved grafts demonstrated significantly enhanced fiber counts, nerve density, and percentage nerve (p < 0.05) compared with unseeded cold-preserved grafts at 6 months after reconstruction. Conclusions: Cold-preserved allografts seeded with autologous Schwann cells were well-tolerated in unrelated recipients and supported significant regeneration across 6-cm peripheral nerve defects. Use of cold-preserved allogeneic nerve tissue supplemented with autogenous Schwann cells poses a potentially safe and effective alternative to the use of autologous tissue in the reconstruction of extensive nerve injuries.

PROLONGED COLD-PRESERVATION OF NERVE ALLOGRAFTS

The goal of this study was to determine the effect of varying durations of cold‐preservation on the immunogenicity of nerve allografts and their subsequent ability to facilitate neuroregeneration across a short nerve gap. Allografts preserved for 1, 4, and 7 weeks were compared to untreated allografts and isografts. There was a shift from an interferon‐γ–producing cellular response (untreated allografts) to an absence of response (7‐week cold‐preserved allografts and isografts). There were no detectable alloantibodies by flow cytometry. Histomorphometry distal to the graft showed robust regeneration in the isograft and 7‐week cold‐preserved groups when compared to the untreated allograft group. Increasing duration of cold‐preservation diminished the cellular immune response. This cold‐preservation does not preclude subsequent nerve regeneration across a short nerve graft. Prolonged cold‐preservation of nerve allograft tissue could serve as a means to produce unlimited graft material for use in peripheral nerve reconstruction. Muscle Nerve, 2005

Thoracodorsal vessels as recipient vessels for the free TRAM flap in delayed breast reconstruction

The internal mammary vessels have been recommended as the first choice recipient vessels for delayed breast reconstruction with the free TRAM flap. This approach has avoided surgery in the previously operated axilla, has required a shorter pedicle length, and has allowed for more medial placement of the TRAM tissue. Frequency of nonusable axillary vessels has been reported at 11 percent, with a 6 percent incidence of flap loss in the delayed reconstructive setting. We reviewed our experience with the thoracodorsal vessels as recipient vessels in delayed free TRAM breast reconstruction to assess more accurately the adequacy of these potential recipient vessels. All patients undergoing delayed TRAM reconstruction were reviewed. Forty-seven of 300 consecutive TRAM procedures were for planned delayed free reconstruction. In seven of the patients (15 percent), the thoracodorsal vessels were found to be inadequate for free reconstruction. A supercharged pedicled TRAM was used for reconstruction in each of these seven patients. Average operating room time was 7 hours. Mean follow-up time was 38 months. Nineteen percent of all patients developed at least one complication. Twelve percent of free TRAM patients developed a complication, whereas 57 percent of supercharged patients developed a postoperative complication. The difference in complication rates was statistically significant. The thoracodorsal vessels have provided an adequate recipient vessel in 85 percent of delayed free TRAM reconstructions, comparable to previous reports. Pedicling and supercharging the flap, in those situations in which the thoracodorsal vessels were inadequate, were associated with an increased incidence of postoperative complications. This suggests that in the delayed reconstructive setting, higher-risk patients benefit from free reconstruction over supercharged reconstructions. A second recipient vessel should be used when the thoracodorsal vessels are inadequate for planned free TRAM reconstruction. In these circumstances, we would recommend the use of the internal mammary vessels followed by the thoracoacromial vessels as reliable alternative recipient sites for delayed free TRAM reconstruction.

Effect of Upper Extremity Nerve Damage on Activity Participation, Pain, Depression, and Quality of Life

PURPOSE To explore the relationship between upper extremity nerve damage and activity participation, pain, depression, and perceived quality of life. METHODS A total of 49 patients with upper extremity nerve damage completed standardized measures of activity participation, pain, depression, and quality of life. We analyzed scores for all subjects and for 2 diagnostic groups: patients with compressive neuropathy and patients with nerve injury (laceration, tumor, and brachial plexus injury), and explored predictors of overall quality of life. RESULTS Participants had given up 21% of their previous daily activities; greater activity loss was reported in patients with nerve injury. Pain was moderate and 39% had signs of clinical depression. Physical and psychological quality of life ratings were below the norms. Activity loss was strongly associated with higher levels of depression and lower physical and psychological quality of life. Higher depression scores correlated strongly with lower overall quality of life. Greater pain correlated moderately with higher depression scores and weakly with quality of life; no statistical relationship was found between pain and physical quality of life. Activity participation and depression predicted 61% of the variance in overall quality of life in patients with nerve damage. CONCLUSIONS The results of this study suggest that hand surgeons and therapists caring for patients with nerve compression and nerve injury should discuss strategies to improve activity participation, and decrease pain and depression, to improve overall effect on quality of life throughout the recovery process. Depression screening and referral when indicated should be included in the overall treatment plan for patients with upper extremity nerve damage. TYPE OF STUDY/LEVEL OF EVIDENCE Prognostic IV.

Ropivacaine-induced peripheral nerve injection injury in the rodent model.

BACKGROUND: Intraneural administration of local anesthetics has been associated with nerve damage. We undertook the present study to investigate histological changes induced by ropivacaine injection into rat sciatic nerve. METHODS: Fifty-four adult male Lewis rats were randomly distributed into 9 groups, 6 animals per group. Fifty microliters of normal saline, 10% phenol, or 0.75% ropivacaine were administered by intrafascicular injection, extrafascicular injection, or extraneural (topical) placement. At 2 weeks, animals were killed and the sciatic nerve at the injection site was evaluated with light microscopy, quantitative histomorphometry, and electron microscopy. RESULTS: On cross-sectional evaluation, extrafascicular ropivacaine injection and extraneural placement of ropivacaine were both associated with damage to the perineurium, with focal demyelination surrounded by edematous endoneurium. Intrafascicular injection of ropivacaine resulted in a wedge-shaped region of demyelination and focal axonal loss with some regeneration, bordered by a region of normally myelinated axons in a background of edematous endoneurium. Extrafascicular injection resulted in more significant damage than extraneural placement of ropivacaine, but less than intrafascicular injection as shown with quantitative histomorphometry. Quantitatively, ropivacaine-injured specimens had significantly lower nerve density than saline-injured specimens. Wallerian degeneration and perineural edema were also demonstrated qualitatively with electron microscopy. CONCLUSIONS: This study demonstrates that, in the rat model, ropivacaine is associated with marked histological abnormality, including edema of the perineurium and axonal destruction with wallerian degeneration, when injected into or extraneurally placed onto a nerve. Extrafascicular injection and extraneural placement were associated with similar, although milder, histological damage than intrafascicular injection. Further work is needed to investigate the functional implications, if any, of the histological abnormalities observed in this study.

Adult Peripheral Nerve Disorders—Nerve Entrapment, Repair, Transfer and Brachial Plexus Disorders

LEARNING OBJECTIVES After reading this article, the participant should be able to: 1. Describe the pathophysiologic bases for nerve injury and how they apply to patient evaluation and management. 2. Recognize the wide variety of injury patterns and associated patient complaints and physical findings associated with peripheral nerve pathology. 3. Evaluate and recommend further tests to aid in defining the diagnosis. 4. Specify treatment options and potential risks and benefits. SUMMARY Peripheral nerve disorders comprise a gamut of problems, ranging from entrapment neuropathy to direct open traumatic injury and closed brachial plexus injury. The pathophysiology of injury defines the patients symptoms, examination findings, and treatment options and is critical to accurate diagnosis and treatment. The goals of treatment include management of the often associated pain and improvement of sensory and motor function. Understanding peripheral nerve anatomy is critical to adopting novel nerve transfer procedures, which may provide superior options for a variety of injury patterns.

Motor Nerve Transfers to Restore Extrinsic Median Nerve Function: Case Report

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.

Neuroregenerative effects of preinjury FK-506 administration.

Background: FK-506 is used in organ transplantation because it promotes neurite outgrowth in vitro and enhances neuroregeneration in peripheral nerve injury transection models. Immunosuppressive mechanisms of FK-506 are well defined, with demonstration of decreased neuroregenerative effects with delayed administration. The purpose of this study was to describe the effects of preinjury administration of FK-506 in rats with tibial nerve transection injury. Methods: Eight inbred male Lewis rats per group in three separate groups underwent tibial nerve transection with primary repair. Group I received placebo, group II received FK-506 treatment at 1 day before surgery, and group III received FK-506 preloading 3 days before surgery. Results: Histologic and histomorphometric results demonstrated the preload FK-506 group had superior results compared with the immediate FK-506 group. Both FK-506 groups were superior to the placebo group. The preload FK-506 demonstrated superior regeneration in mean total nerve fiber counts (p < 0.05), greater percentage neural tissue (p < 0.05), greater mean nerve fiber density (p < 0.05), and lower percentage of debris (p > 0.05). Mean nerve fiber widths were similar in the preload and immediate FK-506 groups but superior to the placebo group. Conclusion: These data suggest that enhancement of FK-506’s neuroregenerative effect is enhanced when administered before nerve injury such as when performing elective surgery.