Motor evoked potentials in a rhesus macaque model of neuro-AIDS.

ABSTRACT

Previous work using bone marrow passaged SIVmac239 (simian immunodeficiency virus) has shown that macrophage tropic strains of this virus enter the rhesus macaque brain early following inoculation (Sharma et al, 1992; Desrosiers et al, 1991; Zhu et al, 1995; and Narayan et al, 1997). As part of an effort to more fully characterize the extent of neurologic impairment associated with SIV infection of the brain, we used transcranial electrical stimulation of motor cortex and the spinal cord to evoke EMG potentials in two forelimb (EDC and APB) and two hindlimb (LG and AH) muscles. The latencies, magnitudes and thresholds of motor evoked potentials (MEPs) recorded from nine monkeys infected with neurovirulent SIVmac R71/17E were compared to pre-inoculation records from the same monkeys. Seven of nine monkeys developed simian AIDS within 4 months of inoculation and were euthanized. Two monkeys remained free of AIDS-related clinical illness for over 18 months following inoculation. Six of the seven monkeys with rapidly progressing disease showed post-inoculation latency increases ( > or = 2 s.d. of control) in at least one cortical MEP. Increases in cortical MEP latency ranged from 21-97% in different monkeys. All seven rapidly progressing animals showed post-inoculation increases in at least one spinal cord MEP latency. Maximum spinal cord MEP latency increases ranged from 22-147%. Increases in central conduction time (CCT) ranged up to 204% and exceeded two standard deviations of control in four monkeys. Neither of the two monkeys with slowly progressing disease showed significant increases in either cortical or spinal cord MEP latency or CCT. Only the monkeys with rapidly progressing disease exhibited classic AIDS-related neuropathology, although there was no consistent relationship between the severity of neuropathology and the extent of MEP abnormalities. In conclusion, our results demonstrate clear deficits in the functional integrity of both central and peripheral motor system structures associated with SIV infection and further support the use of SIV-infected rhesus macaques as a model of neuro-AIDS.