Acquired Immunodeficiency Syndrome (AIDS) is mainly characterized as an Immunodeficiency disease, although secondary infections can occur in the central nervous system (CNS) which can complicate the disease. The involvement of the CNS with human immunodeficiency virus (HIV) infected patients usually occurs in the late stages of the disease, but in 10% of cases it may be the initial manifestations of HIV infection. The neuropathologically documented CNS lesions in AIDS patients include opportunistic infections and lymphomas. Many of these secondary Infections are related to T-cell mediated immunodeficiency induced by HIV, as well as changes related directly to the HIV infection.

The most common Initial symptom seen in neurological disorders related to aids is subcortical dementia, known now as acquired immunodeficiency syndrome dementia complex. This CNS dysfunction is characterized by decreased concentration, impaired memory, abnormal motor performance, and behavioral changes. The latter changes seen in AIDS patients might project them as more subdued and less verbal than before. Also, they typically exhibit loss of emotional responsiveness and loss of interest in social or processional activities. Such profound neurologic dysfunction is almost invariably associated with advanced immunosuppresslon. The neuropsychological findings ore consistent with the subcortical dementia’s seen In Huntington's Disease and Parkinson's Disease.

The evidence accumulated to date indicates that HIV is the primary cause of the acquired immunodeficiency syndrome dementia complex (ADC) rather than a secondary opportunistic infection. The etiology behind ADC Is unclear, but seems to involve viral proteins as well as the metabolic products of HIV infected monocytes. It has been observed that approximately 95% of AIDS patients brains show signs of damage and 60% of patients develop dementia of one degree or another.

HIV encephalitis usually occurs at the terminal stage of the disease with few early symptomatic infections of the CNS reported. Although the cerebral spinal fluid indicates HIV sero-positive, most HIV carriers remain neurologically unimpaired during the Incubation period.

Complete postmortem examination shows that HIV sero-positive patients having cerebral vasculitis is significantly more frequent and often associated with lymphocytic meningitis. Also, granular ependymitis, myelin pallor with reactive astrocytosis and microglial proliferation were also more frequent and more severe In HIV sero-positive cases.

A note of caution here to recognize terminal changes found common to both HIU sero-positive and sero-negative cases. The HIV sero-negative cases with parallel life styles of the typical HIU sero-positive cases, i.e. intravenous drug abusers, exhibit cell ischemia, edema and diffuse vascular congestion. Thus, these common neuropathology’s are not exclusive to AIDS patients.

Another view into the disease is a relationship between the rote of CD4 lymphocyte decline and neuropsychological performance in HIV infected. A battery of neuropsychologic tasks and rate of CD4 lymphocyte decline in gay or bisexual men infected with the human immunodeficiency virus was studied. The subjects were volunteers for a longitudinal study of the human immunodeficiency virus infection and were not selected because of neuropsychiatric symptoms. Most were asymptomatic. Faster rates of decline in percent CD4 lymphocyte were related to poorer performance on measures of memory and reaction time. This relationship was independent of stage of illness and CD4 level of the time of neuropsychologic examination, and was not due to medication effects, i.e. AZT. The interesting message here is the rate of CD4 lymphocyte cell loss is associated with and may represent a risk factor for the development of the human immunodeficiency virus related neurobehavioral deficit.

The data gathered provided clear and consistent evidence that rate of decline in percent CD4 lymphocyte counts is related to poor performance on neuropsychologic tasks. Several studies that examined these HIV patients found relationships between CD4 cell counts and neuropsychologic measures. For example, patients with CD4 levels less than 200 had lower scores on measures of motor speed, verbal memory acquisition, visual motor speed, end mental tracking in comparison with patients with CD4 counts above 200.

A key to understanding the neuropsychological deficits observed is to know of some clinical measurement background chosen. The neuropsychologic test battery included standardized neuropsychologic measures and a series of simple and choice reaction time measures. These measures were selected in view of the subcortical dementia suspected by the HIV encephalopathy and on the basis of preliminary studies that indicated that the measures selected for this study were the most sensitive in discriminating HIV infected patients from control subjects. The neuropsychologic test battery included the Selective Reminding Test, Trail Making Test, and Grooved Pegboard Test, as well as a battery of simple and choice reaction time measures. The Selective Reminding Test is a measure of verbal memory that consists of a list of 12 unrelated words presented to subjects. Following initial presentation of the list, subjects are asked to recall the words. Subsequent trials involve presentation only of words not recalled on the preceding trial. Additional trials are presented until there are three consecutive trials of recall of the entire list, or a maximum of 12 trials. Simple reaction time was measured by requiring the patients to place their hands on a table in front of an instrument panel, and requiring them to depress a key as soon as a light was illuminated. This was performed with both the preferred and non-preferred hands. The some instrument was used for choice reaction time tasks in which the patients were asked to respond to only one of two possible colors that were illuminated. The Wechsler Adult Intelligence Scale-Revised was administered at the same time as the neuropsychologic measures.

The last HIV related neuropathology point of interest, and maybe the most important, is the virulence factor involved of the virus itself. There is no question that social changes have hastened the spread of HIV. Starting in the 1960's, war, tourism and commercial trucking forced the outside world on Africa's once isolated villages, where many scientists suspect the virus harbored less virulently to survive. At the same time, drought and industrialization prompted mass migrations from the countryside into cities. Urbanization shattered social structures that had long constrained sexual behavior. Prostitution exploded, and venereal disease flourished. Hypodermic needles came into wide use during the same period, creating another mode of infection.

Paul Ewald, an evolutionary biologist at Amherst College, makes a logical conclusion that these trends mentioned actually turned a chronic but relatively benign infection into a killer. The evidence is circumstantial but hard to discount. Ewald suspects that HIV has recently undergone a similar transformation. Unlike influenza viruses, which infect cells in the respiratory tract and spread through respiratory droplets, the HIV’s insinuate themselves into white blood cells. Infected cells, or new viruses, can pass between people, but only during sex or other exchanges of body fluid. Confined to an isolated population where no carrier had numerous sex partners, a virus like HIV would gain nothing from replicating aggressively within the body. It would do best to lie low leaving the host alive and mildly infectious for many years. But if people's sexual networks suddenly expanded, fresh hosts would become more plentiful, and infected hosts more dispensable. An HIV strain that replicated wildly, a more virulent strain, might kill people in three years instead of 30, but by making them more infectious while they lasted, it would still come out ahead.

Ewald is right in that the most virulent strains do show up in the populations where HIV is spreading the fastest. For example, 90% of AIDS today is caused by HIV-1 rather then the far less Virulent HIV-2 causing less then 10%. Thus, this virulence factor is suspected to be a primary player In HIV related neuropathology.

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F. Gray, M.C. Lescs, C. Deohane, F. Paraire, Bernard Marc, M. Durigon, R. Gherardi,. Early brain changes in HIV infection: Neuropathological Study of 11 HIV Seropositiue, Non-AIDS cases, 3/92

Mitchell, J.E., Marshall, D.W., Goethe, E, Leger, D., Boswell, R.N. Human Immunodeficiency virus: Immune system compromise and neuropsychological functioning . 1989

Ho, D.D., Rota, R.T., Schooley A.T. Isolation of HTLV-III from cerebrospinal fluid and neural tissue of patients with neurological syndromes related to the acquired immunodeficiency syndrome. 1985