Different neurologic manifestations occur at different stages of HIV infection. Shortly after contraction of the virus, some individuals develop acute aseptic meningitis with headache, fever and stiff neck, pleocytosis and antibody to HIV in the CSF[5]. In the asymptomatic stages of HIV infection there is a possibility of developing acute or chronic inflammatory demyelinating polyneuropathy, myopathy, or herpes zoster radiculitis. These symptoms, however, do not usually become apparent until representative symptoms develop, such as weight loss, fever, night sweats, diarrhea or opportunistic infections. During the Aids Related Complex (ARC) the same complication occur as in the asymptomatic stage, but in addition infected individuals may develop mild cognitive impairment, mononeuritis multiplex, or distal symmetric polyneuropathy. Once AIDS has developed, a wide variety of complications become apparent. These include dementia, HIV encephalopathy, vacuolar myelopathy, and CNS opportunistic infections and neoplasm’s.

There has been issues raised about cognitive impairment and early AIDS infection. Questions have been raised about Public safety being at risk if infected individuals were in safety-sensitive jobs. The American Academy of Neurology supports the conclusion that "there is no justification for HIV-1 serological screening as a strategy for detecting functional impairment in asymptomatic persons, because at present, there is no evidence for an increase of clinically significant neuropsychiatric abnormalities"[2]. This conclusion was also supported by the fact that impaired job performance can be caused by a number of more common problems ,such as alcoholism.

Infection with HIV-1 is frequently complicated in its late stages by the AIDS dementia complex, a neurological syndrome characterized by abnormalities in cognition, motor performance, and behavior. This dementia is due to a direct effect of the virus on the brain rather than an opportunistic infection. This brain infection is confined to a great extent to macrophages, microglia, and multinucleated cells that are formed by virus induced cell fusion[1]. Patient’s with the AIDS dementia complex present with characteristic and yet sometimes variable patterns of abnormalities. These include abnormalities in cognitive, motor, and behavioral function. This disorder initially presents with slowing and loss of precision in both mentation and motor control. Initially, patients frequently report that they must keep written notes in order to carry out normal daily functions. Also complex but formerly routine mental functioning takes longer and needs to be mentally broken down into specific steps [4]. Frequent loss of interest in work, social, and recreational activities are commonly reported by infected individuals. This list of symptoms could be easily mistaken for depression, but in depression dysphoria is present, while in AIDS dementia complex it is absent. Motor dysfunction usually lags behind the mentation abnormalities. The initial motor abnormalities include a mild gait unsteadiness and exaggerated tremor. Upon examination, a slowing of release reflexes and rapid alternating extremity movements is observed.

With the progression of the dementia. intellectual impairment becomes more perverse, affecting almost all aspects of mental functioning with further slowing of motor functions. Slowing of speech and mental drain ultimately progress until near or complete mutism and severe dementia result. Gait unsteadiness increases and gives way to hypokinesia and incontinence. Variations of the syndrome have been reported where patients present with an agitated mental state with mania or other forms of organic psychosis. The extrapyramida1 dysfunction mar resemble Parkinson’s disease with slow motor functioning and postural instability, but not resting tremor, as is present in the AIDS dementia complex. Neuropsychological studies reveal abnormalities that include difficulty with complex sequencing, impaired fine and rapid motor movement. and reduced verbal fluency, while other verbal abilities. including vocabulary and object naming, tend to be intact even in the more progressed stages [1].

A study conducted using positron emission tomography made it possible to distinguish patients with AIDS dementia complex from normal patients on the basis of patterns of brain glucose metabolism. The pathology of this disorder was characterized by variation between two patterns; one associated with impairment of fine motor control and the other correlated with verbal fluency and problem solving. Subcortical glucose metabolism pattern was associated with motor control abnormalities while cortical- patterns were associated with verbal and problem solving. Taking into account the progression of the complex basal ganglion and thalamic glucose hypermetabolism was initially seen, which was then followed later by the cortical and subcortical patterns[4].

The pathology of the AIDS dementia complex is complicated and variable. Histopathological studies revealed abnormalities in the central white matter, basal ganglia and the thalamus, the brain stem, and the spinal cord. Little abnormalities have been seen in the cortex. There have been three relative groupings that these abnormalities have been found to fall within. These groupings include diffuse pallor of the white matter, multinucleated cell encephalitis, and vacuolar myelopathy. The most common of these is diffuse pallor of the white matter which involves central and periventricular white matter. Multinucleated cells are found in a group of patients with a more severe clinical presentation[2]. Infiltrates are most commonly found in the basal ganglia, thalamus, and pons. Astrocytosis is commonly seen in association with these infiltrates while neurons are not seen to be affected. Vacuolar myelopathy is found to be localized to the spinal cord. This pathology tends to result from the edema within the layers of the myelin sheaths. The presentation resembles subacute combined degeneration, which results from a deficiency of vitamin B12. The difference in this case, is that serum levels of vitamin B12 in vacuolar myelopathy are normal.

Research today, points to an association between the AIDS Dementia complex and direct brain infection with HIV-1, when multinucleated cells are present. DNA southern blot analysis have shown that there is the presence of pro-viral DNA in the integrated and non-integrated forms present in patients with this pathology [4]. HIV-l has also been cultured directly from the brains and CSF of patients with the AIDS dementia complex. Immunohistochemical studies have also shown the presence of viral nucleic acids in these patients brains. Electron microscopy studies have detected virions in addition to all the other experiments.

The association between HIV-1/CNS infection and the clinical presentation at the different stages has yet to be discovered. Asymptomatic CNS infection that have been a low neuro-virulence as long as the immune defenses are at full strength. As the degree of immunosuppresslon increases in the later stages of HIV infection, the spread. of HIV-1 tends to escape the immune control which probably explains why the AIDS dementia complex begins to appear at this point. The continual decrease in the functioning of the immune system does not account for some of the neurological manifestations although. Thus some patients develop multiple opportunistic infections and have a minimal immune functioning and yet remain neurologically intact, while others show varying degrees of neurological deterioration but develop few opportunistic infections. It is possible the difference in viral strains can account for the differences in the pathologies.

Why is the brain infected? This question is of interest because HIV-1 appears to be localized to cells outside of the brain The brain however has been shown to contain messenger RNA for the CD4 molecule which is the lymphocyte receptor of HIV-1. It is as yet unknown which cells in the brain produce this messenger RNA [4].

How does HIV-1 damage the brain? The normal routes of cell destruction have been ruled out by the observation of the absence of productive infection or ]lysis of neurons or other glial cells. Infection of microglia, however, has been associated with local edema which appears to cause a demyelination. These observations point to an indirect mechanism of tissue damage and possible release of toxic substances by the infected cells.

Many aspects of infection with HIV-1 and CNS involvement have as yet to be discovered. New directions are constantly being brought out by researchers leading to new questions and hopefully the ultimate key to this puzzle.

REFERENCES:

1. Lechtenberg, R., Sher, J. H. AIDS in the Nervous system, Churchill Livingstone Publishers, New York, 1988.

2. Levy R. M., Bredesen, D. E. , Rosenblum M. L. Neurological manifestations of the acquired immunodeficiency syndrome (AIDS): Experience at UCSF and review of the literature. J. Neurosurg. : 62, 475-495 , (1985).

3. McDonald, I. . Weber J. HIV and the nervous system. AIDS: 3, 465-467, (1988).

4. Price, R. W. , Bruce, B., Sidtis, J., Rosenblum, M., Scheck, A. C. and Cleary, P. The brain in AIDS: Central Nervous System HIV-1 Infection and AIDS Dementia Complex. Science: 239, 586-591, (1988).