The success of a microneurosurgical intervention in leprous neuropathy (LN) depends on the diagnosis of chronic compression before irreversible paralysis and digital loss occurs. In order to determine the effectiveness of a different approach for early identification of LN, neurosensory testing with the Pressure-Specified Sensory Device™ (PSSD), a validated and sensitive test, was performed in an endemic zone for leprosy. A cross-sectional study was conducted to analyze a patient sample meeting the World Health Organization (WHO) criteria for Hansen’s disease. The prevalence of LN was based on the presence of ≥1 abnormal PSSD pressure threshold for a two-point static touch. A total of 312 upper and lower extremity nerves were evaluated in 39 patients. The PSSD found a 97.4% prevalence of LN. Tinel’s sign was identified in 60% of these patients. An algorithm for early identification of patients with LN was proposed using PSSD testing based on the unilateral screening of the ulnar and deep peroneal nerves.
2From the Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation Laboratory, and the Departments of Medicine and Neurology, Johns Hopkins University School of Medicine; and the Curtis National Hand Center.
Background: Therapies to improve outcomes following peripheral nerve injury are lacking. Prolonged denervation of muscle and Schwann cells contributes to poor outcomes. In this study, the authors assess the effects of growth hormone therapy on axonal regeneration, Schwann cell and muscle maintenance, and end-organ reinnervation in rats.
Methods: Male Sprague-Dawley rats underwent sciatic nerve transection and repair and femoral nerve transection without repair and received either daily subcutaneous growth hormone (0.4 mg/day) or no treatment (n = 8 per group). At 5 weeks, the authors assessed axonal regeneration within the sciatic nerve, muscle atrophy within the gastrocnemius muscle, motor endplate reinnervation within the soleus muscle, and Schwann cell proliferation within the denervated distal femoral nerve.
Results: Growth hormone-treated animals demonstrated greater percentage increase in body mass (12.2 ± 1.8 versus 8.5 ± 1.5; p = 0.0044), greater number of regenerating myelinated axons (13,876 ± 2036 versus 8645 ± 3279; p = 0.0018) and g-ratio (0.64 ± 0.11 versus 0.51 ± 0.06; p = 0.01), greater percentage reinnervation of motor endplates (75.8 ± 8.7 versus 38.2 ± 22.6; p = 0.0008), and greater muscle myofibril cross-sectional area (731.8 ± 157 μm versus 545.2 ± 144.3 μm; p = 0.027).
Conclusions: In male rats, growth hormone therapy accelerates axonal regeneration, reduces muscle atrophy, and promotes muscle reinnervation. Growth hormone therapy may also maintain proliferating Schwann cells in the setting of prolonged denervation. These findings suggest potential for improved outcomes with growth hormone therapy after peripheral nerve injuries.
Improved nerve regeneration and functional outcomes would greatly enhance the utility of vascularized composite allotransplantation (VCA) such as hand and upper extremity transplantation. However, research aimed at achieving this goal has been limited by the lack of a functional VCA animal model. We have developed a novel rat midhumeral forelimb transplant model that allows for the characterization of upper extremity functional recovery following transplantation. At the final end point of 12 weeks, we found that animals with forelimb transplantation including median, ulnar and radial nerve coaptation demonstrated significantly improved grip strength and forelimb function as compared to forelimb transplantation without nerve approximation (grip strength: 1.71N ± 0.57 vs. no appreciable recovery; IBB scale: 2.6 ± 0.7? vs. 0.8 ± 0.40; p = 0.0005), and similar recovery to nerve transection-and-repair only (grip strength: 1.71N ± 0.57 vs. 2.03 ± 0.42.6; IBB scale: 2.6 ± 0.7 vs. 2.8 ± 0.8; p = ns). Moreover, all forelimb transplant animals with nerve coaptation displayed robust axonal regeneration with myelination and reduced flexor muscle atrophy when compared to forelimb transplant animals without nerve coaptation. In conclusion, this is the first VCA small-animal model that allows for reliable and reproducible measurement of behavioral functional recovery in addition to histologic evaluation of nerve regeneration and graft reinnervation.