Catherine A. Munro

Analysis of upper and lower extremity peripheral nerve injuries in a population of Patients with multiple injuries

BACKGROUND The purpose of this study was to determine the prevalence, cause, severity, and patterns of associated injuries of limb peripheral nerve injuries sustained by patients with multiple injuries seen at a regional Level 1 trauma center. METHODS Patients sustaining injuries to the radial, median, ulnar, sciatic, femoral, peroneal, or tibial nerves were identified using a prospectively collected computerized database, maintained by Sunnybrook Health Science Centre, and a detailed chart review was undertaken. RESULTS From a trauma population of 5,777 patients treated between January 1, 1986, and November 30, 1996, 162 patients were identified as having an injury to at least one of the peripheral nerves of interest, yielding a prevalence of 2.8%. These 162 patients sustained a total of 200 peripheral nerve injuries, 121 of which were in the upper extremity. The mean patient age was 34.6 years (SEM +/- 1.1 year), and 83% of patients were male. The mean injury severity score was 23.1 (+/-0.90), and the mean length of hospital stay was 28 days (+/-1.8). CONCLUSIONS Motor vehicles crashes predominated (46%) as the cause of injury. The most frequently injured nerve was the radial nerve (58 injuries), and in the lower limb, the peroneal nerve was most commonly injured (39 injuries). Diagnosis of a peripheral nerve injury was made within 4 days of admission to Sunnybrook Health Science Centre in 78% of the cases. Surgery was required to treat 54% of patients. Head injuries were the most common associated injury, occurring in 60% of patients. Other common associated injuries included fractures and dislocations. The present report aims to aid in identification and treatment of peripheral nerve injuries.

Chronic Schwann Cell Denervation and the Presence of a Sensory Nerve Reduce Motor Axonal Regeneration

Motor axonal regeneration is compromised by chronic distal nerve stump denervation, induced by delayed repair or prolonged regeneration distance, suggesting that the pathway for regeneration is progressively impaired with time and/or distance. In the present experiments, we tested the impacts of (i) chronic distal sensory nerve stump denervation on axonal regeneration and (ii) sensory or motor innervation of a nerve graft on the ability of motoneurons to regenerate their axons from the opposite end of the graft. Using the motor and sensory branches of rat femoral nerve and application of neuroanatomical tracers, we evaluated the numbers of regenerated femoral motoneurons and nerve fibers when motoneurons regenerated (i) into freshly cut and 2-month chronically denervated distal sensory nerve stump, (ii) alone into a 4-cm-long distally ligated sensory autograft (MGL) and, (iii) concurrently as sensory (MGS) or motor (MGM) nerves regenerated into the same autograft from the opposite end. We found that all (315 +/- 24: mean +/- SE) the femoral motoneurons regenerated into a freshly cut distal sensory nerve stump as compared to 254 +/- 20 after 2 months of chronic denervation. Under the MGL condition, 151 +/- 5 motoneurons regenerated, which was not significantly different from the MGM group (134 +/- 13) but was significantly reduced to 99 +/- 2 in the MGS group (P < 0.05). The number of regenerated nerve fibers was 1522 +/- 81 in the MGL group, 888 +/- 18 in the MGM group, and 516 +/- 44 in the MGS group, although the high number of nerve fibers in the MGL group was due partly to the elaboration of multiple sprouts. Nerve fiber number and myelination were reduced in the MGS group and increased in the MGM group. These results demonstrate that both chronic denervation and the presence of sensory nerve axons reduced desired motor axonal regeneration into sensory pathways. A common mechanism may involve reduced responsiveness of sensory Schwann cells within the nerve graft or chronically denervated distal nerve stump to regenerating motor axons. The findings confirm that motor regeneration is optimized by avoiding even short-term denervation. They also imply that repairing pure motor nerves (without their cutaneous sensory components) to distal nerve stumps should be considered clinically when motor recovery is the main desired outcome.

Tissue engineered alternatives to nerve transplantation for repair of peripheral nervous system injuries

To date the best regenerative strategies to repair peripheral nerve injuries (PNI) have used peripheral nerve grafts.[1] However, this strategy is inherently flawed, requiring that a second injury be created to harvest the tissue for the primary injury repair. A better strategy would be to prepare a synthetic graft that mimics the properties of a peripheral nerve graft. Non-nerve biologic tissue and synthetic biodegradable material as bridges for neural repair have been utilized for over a century (reviewed by Doolabh et al [2]). Although offering considerable promise, artificial conduits have had only limited success, possibly due to their simple design and the lack of multiple stimuli of regeneration. In developing a bioengineered nerve graft, we have been systematically investigating a number of strategies to optimize nerve regeneration through tubular devices. We report our initial results with the use of bioengineered nerve grafts for repair of PNI in a rat model.

Histological and magnetic resonance analysis of sciatic nerves in the tellurium model of neuropathy

Abstract  Ingestion of tellurium (Te), a toxic element, produces paralysis of the hind limbs in weanling rats that is due to temporary, segmental demyelination of the sciatic nerves bilaterally. Weanling rats were fed a 1.1% elemental Te diet and sacrificed at various time points for histological and magnetic resonance (MR) analysis of the sciatic nerves. No controls exhibited impairments of the hind limbs, whereas Te‐treated animals became progressively impaired with increased Te exposure. Toluidine blue‐stained nerve sections of Te‐treated animals showed widened endoneurial spaces, disrupted myelin sheaths, swollen Schwann cells, and a few instances of axonal degeneration. Te decreased healthy myelin by 68% and increased percent extracellular matrix by 45% on day 7. MR experiments showed a decrease in the area of the short T2 component, an increase in average T1, and an increase in the position of the intermediate T2 component in Te‐treated nerves. The correlation coefficient for healthy myelin and average T1 was 0.88 and that for healthy myelin and the area underneath the short T2 component was 0.77. The area of the short T2 component has been postulated as the best measure of the process of demyelination.

Chemokine expression in nerve allografts

OBJECTIVE:Chemokines (chemoattractant cytokines) play a major role in trafficking of cells to areas of inflammation. Infiltration of allograft tissues by immunocompetent cells is critical for rejection of donor tissues. The role of chemokines in nerve allograft rejection is not clear. We hypothesized that chemokines are responsible for attracting macrophages and T lymphocytes into nerve allograft tissue, initiating the graft rejection process. METHODS:Lewis rats received 4-cm-long peroneal nerve allografts and isografts from ACI and Lewis rats, respectively. Twelve hours to 10 days after transplantation, grafts were removed and total cellular ribonucleic acid was extracted. Intragraft gene expression of several chemokines (cytokine-induced neutrophil chemoattractant, macrophage inflammatory protein [MIP]-2, monocyte chemoattractant protein-1, MIP-1α, and regulated upon activation normal T-cell expressed and secreted [RANTES]) were analyzed by reverse transcription-polymerase chain reaction. RESULTS:The cytokine-induced neutrophil chemoattractant was expressed in allografts and isografts at early time points (12 h to 6 d). Monocyte chemoattractant protein-1 messenger ribonucleic acid expression was similarly high in both isografts and allografts from 12 hours until 8 days after transplantation. MIP-1α, MIP-2, and RANTES were expressed only in allografts. Kinetics of the neutrophil (MIP-2) and macrophage (MIP-1α) chemokines revealed an early onset (12–24 h), a plateau from 1 to 4 days, and expression abruptly declining by Day 6. The lymphocyte chemoattractant RANTES had delayed kinetics, with a rise at Day 3, a peak at Day 4, and a gradual decline. CONCLUSION:Induction of specific chemokine genes precedes nerve allograft infiltration by immunocompetent cells. MIP-1α, MIP-2, and RANTES may be responsible for recruiting macrophages, granulocytes, and lymphocytes, respectively, to the rejecting allograft. In future studies, blockade of these specific chemokines or their receptors may prove to delay or prevent nerve allograft rejection.