Since its discovery in 1981, AIDS has mainly been characterized as a disease effecting the bodying immune system. It has been recognized, however, that there are distinct neurological pathologies associated with the disease. AIDS neuropathology can be characterized by the existence of subcortical dementia, motor difficulties, and affective disorders. Most AIDS patients experience dementia of one form or another. It has been observed that approximately 95% of AIDS patients brain’s show signs of damage, and 60% of patients develop dementia of one degree or another.

The AIDS virus is an RNA retrovirus which attaches to and infects T helper cells and other cells of the immune system. The virus normally goes through a typical lytic life cycle which is seen in the pathology of most viruses. Originally the HIV virus was associated wilt the CD4 receptor found on the immune cells, but it has been discovered that the OKT4 receptor is also a site of entry for the virus. This receptor is not only present in macrophages, but it is also found in glial cells of the CNS.

There are basically three sites of entry where the HIV virus and infected macrophages can invade the CNS. The first is the blood brain barrier. If there is damage to the integrity of this barrier, the virus can easily pass into the brain tissue and proliferate. The second barrier is the blood CSF barrier. The choroid plexus males up this particular barrier, and the barrier is maintained by the existence of tight junctions. If there is a breakdown of these tight junctions, infected macrophages can pass from the blood into the CSF where they can pass to nearly any area of the CNS. The final site of entry, and perhaps the most likely' are the cicumventricular organs. This is the only site in the CNS where there is an absence of a barrier, and the macrophages carrying the virus are free to pass through these. From here the virus can spread almost anywhere in the CNS, but they intend to infect areas near their site of entry.

The most common initial symptom seen in neurological disorders related to AIDS is subcortical dementia. The cardinal feature of subcortical dementia include slowing of mental processes, progressive impairment of memory, and deficits in manipulating or using spontaneously acquired information (i.e., poor problem solving). However, unlike the cortical dementias, higher-order associative function is preserved' and intellectual impairment is milder in the subcortical dementias. In one study over one half of the patients developed severe global mental impairment within two months of onset of symptoms.

Motor changes are also present early during the course of the disease. These changes are manifested in a loss of balance and leg weakness. There have also been complaints of loss of motor coordination, a deterioration in handwriting, or tremor.

Behavioral, or affective changes are seen in about one third of patients. Apathy and social withdrawal are most frequently observed while irritability or emotional lability are less common. The typical clinical picture was that of a previously gregarious individual who gradually became more subdued and less verbal, with loss of emotional responsiveness and interest in social or professional activities. In the later stages of the disease, patients seem quietly confused and indifferent to their illness or their surroundings.

AIDS infection of the central nervous system has a very distinguishable pathology. Typically, the brain of an AIDS patient is shrunken, a change that can be detected in living patients by computerized tomography scans. The ventricles are larger than normal due to this atrophy. Accompanying the atrophy are lesions that are confined primarily to the white matter of the brain. Inflammation is usually present and includes perivascular and parenchymal infiltrates of lymphocytes and macrophages. These white matter abnormalities generally consist of three types: ill defined large areas of pallor, focal rarefaction containing infiltrates, and vacuolation. Since the white matter is what is primarily being affected, one can realize that this is due to the disruption and death of glial cells. These glial cells provide the myelin sheaths seen in the CNS, and their degeneration can bring about the motor symptoms seen in both upper and lower muscles of the body.

AIDS can also effect specific neurons, but this is usually seen in the very late stages of the disease. Subcortical gray matter involvement is characterized by macrophages, multinucleated cells, and lymphocytes with astrocytosis and generally involves the putamen, caudate, claustrum, and less frequently the globus pallidus. Similar lesions can be found in the brainstem, particularly in the pons. In one study, subcortical gray matter changes were discovered in the basal ganglia and brainstem of more than 80% of patients with dementia, whereas the same abnormalities were present in fewer than a third of those without dementia.

One should also note the specific changes which occur in the basal ganglia of children infected with the AIDS virus. Calcification of the basal ganglia of these children is a prominent feature. Apparently these patients are more susceptible to vascular injury, with calcium deposition an end-stage phenomenon. The etiology of the calcific vasculopathy is unknown at the current time.

Patients with AIDS often have another white matter abnormality that effects the spinal cord, called vacuolar myelopathy. The vacuolation is a "bubbly change" in the myelin tracts of the spinal cord. It is believed that it involves a separation between the layers of the myelin sheath. This abnormality most likely contributes to the leg weakness and other motor disturbances AIDS patients frequently experience.

Of course, AIDS is mainly characterized as an immunodeficiency disease, and secondary infections can occur in the CNS which can complicate the problems already discussed concerning the virus. Toxoplasmosis, previously a parasitic disease of neonates or severely immunosuppressed patients, appear as multiple abscess-like lesions on the brain. Cryptococcal meningitis is frequent, sometimes present as "tumor-like cryptococcomas". Uncommon CNS parasites such as Candida albicans and Aspergillus fumigatus have also been found in brain abscesses of AIDS patients.

Since AIDS is now seen to infect the CNS, one can easily see how the treatment of the disease poses a serious problem. A cure must be developed which can attack the virus in the peripheral organs as well as be able to cross the blood brain barrier. If the drug cannot do this, the CNS will continue to harbor the virus and degenerate as the disease progresses. This problem is one of the larger ones facing AIDS researchers at this time.

The following is a summary of the pathological progression of AIDS as seen in the CNS which physicians should recognize. The earliest features include diffuse pallor and mild vacuolation of the white matter accompanied by mild perivascular lymphocytic reaction. These changes, frequently seen in the non-demented group, are consistent with their sub-clinical state and suggest that these conditions occur in the great majority of AIDS patients. As the disease progresses past the asymptomatic stage, demyelination and cell reactions become more prominent. patients with the most severe symptoms, the presence of macrophages and multinucleated cells and widespread loss of white matter substance, are conspicuous and are clinically associated with profound cognitive impairment.

BIBLIOGRAPHY

Bridge, T. P. AIDS and HIV CNS Disease: A Neuropsychiatric Disorder. Alcohol, Drug Abuse, and Mental Health Administration, Intramural Research Program, National Institute of Mental Health, National Institute of Health, Bethesda, Maryland. 1988.

Belman, A. L., Lantos, G., Horoupian, D., Novick, B. E., Ultmann, M. H., Dickson, D. W., Rubinstein, A. AIDS: Calcification of the basal ganglia in infants and children. Neurology, Vol. 36, No. 9, pp. 1192-1199, September 1986.

Barnes, D. M. AIDS~Related Brain Damage Unexplained. Science, Vol. 232, pp 1091-93, May 1986.

Navia, B. A., Cho, L.-S., Petito, C. K., Price, R. W. The AIDS Dementia Complex: II. Neuropathology. Annals of Neurology, Vol. 19, No. 6, June 1986.

Taylor, Jill. Neuropathology of AIDS Instructional video for Indiana State University.