Peripheral nervous system

Abstract

Background: HIV-associated distal sensory peripheral neuropathy is a growing problem because of longer survival times and intense antiretroviral usage. Feline immunode ciency virus (FIV) is a lentivirus that causes neurological disease and immunosuppression in domestic cats. Objective: To determine the extent of peripheral nervous system disease in animals infected with the infectious FIV molecular clone, FIV-Ch, which contains the full FIV-V1CSF env-encoding region in a laboratory-adapted FIV background vector. Methods: Neonatal cats were infected with live FIV-Ch (nD 9) or heat-inactivated (nD 8) virus, followed by weekly measurements of weight and neurobehavioral performance. At weeks 8 and 12 post-infection (PI), animals underwent necropsy and we harvested blood, sural and sciatic nerves, lumbar-sacral spinal cord and hind limb footpads for morphological, FACS and PCR analysis. Results: FIV-Ch infected animals showed reducedCD4 and CD8 T-lymphocyte levels in blood at 12 weeks PI, together with diminished neurobehavioral performance (p<0.01). Morphological studies of sural nerve revealed reduced ber areas in 12-week FIV-infected animals (33.0C 1.6 mm2) compared to age-matched control animals (42.6C2.1 mm2) (p< 0.05), which was accompanied by reduced myelin sheath thickness (p<0.05). Immunocytochemical studies of foot pads displayed reduced intraepidermal ber density of FIV-infected animals at 12 weeks PI (5.7C1.6 mm2) compared to control animals (15.7C5.4 mm2) (p<0.01). PCR studies of sciatic nerves and lumbar-sacral spinal cord indicated that provirus was detectable in both tissues among all infected animals at 12 weeks but not in controls. Viral RNA was found in both nerve and spinal cord of FIV-infected animals with concomitant detection of TNF-a mRNA. Conclusions: FIV infection results in the rapid onset of peripheral neuropathy that is de ned by axonal loss and reduced intraepidermal innervation with detection of viral genome in peripheral nerves, resembling HIV-associated neuropathy. These results suggest that peripheral neuropathy may be common among lentiviral infections and is associated with immune suppression. 66 Macrocytosis in HIV associated vacuolar myelopathy L. Monsha,1 L. Banks,2 J. Gobold,1 A. DiRocco2 1. Mount Sinai Medical Center (New York, USA) 2. Beth Israel Medical Center (New York, USA)