CYTOPATHOLOGIC AND NEUROCHEMICAL CORRELATES OF PROGRESSION TO MOTOR COGNITIVE IMPAIRMENT IN SIV-INFECTED RHESUS-MONKEYS/

Neurochemical, pathologic, virologic, and histochemical correlates of simian immunodeficiency virus (SIV)associated central nervous system ( CNS) dysfunction were assessed serially or at necropsy in rhesus monke ys that exhibited motor and cognitive deficits after SIV infection. So me infected monkeys presented with signs of acquired immunodeficiency disease (AIDS) at the time of sacrifice. Seven of eight animals exhibi ted motor skill impairment which was associated with elevated quinolin ic acid in cerebrospinal fluid (CSF). Examination of the brains reveal ed diffuse increases in glial fibrillary acidic protein immunoreactivi ty in cerebral cortex in all animals, regardless of evidence of immuno deficiency disease. Reactive astrogliosis preceded or was coincident w ith the onset of neuropsychological impairments. Virus rescue from CSF of six of eight infected animals showed that one of three animals wit h AIDS and none of three animals without AIDS at necropsy had virus re scue-positive CSF. Multinucleated giant cells were seen in the brain o f only one animal with end-stage AIDS and high systemic virus burden a t death. Neither systemic nor CNS virus burden was associated with the onset of CNS dysfunction. SIV-associated motor/cognitive impairment i s associated with subtle, widespread changes in CNS cytology and neuro chemistry, rather than with large increases in brain virus burden or w idespread virus-associated brain lesions.