Neuropsychiatric impairment in AIDS or the AIDS-related complex is most commonly manifested as a progressive dementia which eventuates in a generalized encephalopathy. The dementia is rapidly progressive over several weeks to months and is associated with a degenerative CNS syndrome. The prevalence of dementia in AIDS is uncertain but is estimated to occur in 50% of patients affected with AIDS or the AIDS-related complex. The human immunodeficiency virus (HIV) is now known to penetrate the CNS. The virus has been isolated from filtered CSF, brain tissue and peripheral nerve. Despite the ability to detect HIV in CNS, HIV is recovered or detected in less than a third of patients with the AIDS-dementia complex. Thus, how the virus induces the dementia or encephalopathy remains an uncertainty. The number of infected cells, and, the level of viral antigen in brain is low; these factors coupled with the sparing of gray matter do not correlate with the clinical severity of the AIDS-dementia syndrome. Thus, alternative mechanisms to lytic viral encephalitis may account for the dementia. The investigator has preliminary evidence that there exists an immune network for neuropeptides and their receptors. Thus, the immune system would have the ability to modulate central nervous system function through a receptor-specific network. This interaction of the immune system with the central nervous system might occur in areas of the brain that normally lack blood- brain barrier (pineal gland and median eminence) or in areas of encephalomalacia where the blood-brain barrier has been compromised. Consequently, neuropsychiatric impairment in the AIDS-dementia complex might potentially result from an autoimmune mechanism in which perturbation of the dynamic steady state of the immune network for specific brain peptides induces selective modulation of denervation of peptidergic neurons and their projections. Such antibodies might contribute to the noncytopathic functional changes and potentially correlate with the clinical deficit. Furthermore, there is the possibility that antibodies to HIV determinants recognize cross-reactive epitopes on neuropeptides or their receptors.
| Roy, B F; Benkelfat, C; Hill, J L et al. (1994) Serum antibody for somatostatin-14 and prodynorphin 209-240 in patients with obsessive-compulsive disorder, schizophrenia, Alzheimer's disease, multiple sclerosis, and advanced HIV infection. Biol Psychiatry 35:335-44 |
