G. HIV-ASSOCIATED CNS DISORDERS -- CNS involvement may occur due to primary effects of HIV infection or to secondary effects of immune suppression

1. General Issues
Between 10 and 20% of HIV-infected patients present with neurologic signs as their first clinical manifestation of infection. In some, no other signs of AIDS develop. Between 50 and 70% of all AIDS patients eventually develop some features of what is called AIDS dementia or the AIDS related cognitive-motor complex. This term is used to describe the characteristic pattern of cognitive, motor, and behavioral dysfunction, including mood disturbances, seen in AIDS patients. At autopsy, between 60 and 90% of AIDS patients' brains show some form of pathology.
2. Pathologic Changes due directly to HIV infection (subacute encephalitis)
a. The pathology associated with the AIDS-related cognitive-motor complex, sometimes called subacute encephalitis, is located mainly in subcortical areas, with relative sparing of cerebral cortex. Microscopic changes include:

1) diffuse white matter pallor

2) perivascular infiltrates of lymphocytes and macrophages

3) foci of necrosis, gliosis, and/or demyelination

4) microglial nodules, macrophages and multinucleated cells
The virus enters the brain, probably primarily by way of macrophages, as HIV has been localized in CNS, mainly in macrophages, microglia and multinucleated giant cells. The virus is able to reproduce in the brain.

b. Vacuolar myelopathy is sometimes seen in the spinal cord. This change consists of white matter vacuolation in posterior and lateral columns, and is mainly due to swelling within mhyelin sheaths.
3. Secondary Effects of Immune Suppression
a. Opportunistic infections. In addition to HIV infection, opportunistic viral infection of the brain is a relatively frequent complication of HIV-related immunosuppression. A variety of viruses and fungi, have been identified, primarily:

-Cytomegalovirus
-Cryptococcus
-Toxoplasma

These infecting agents can be isolated from the brains of about 25% of AIDS patients.

b. Other secondary effects include increased incidence of primary CNS lymphoma and progressive multifocal leukoencephalopathy (PML) -- see below.

4. Peripheral Nervous System Pathology
a. PNS damage is seen in some HIV-infected patients. Inflammatory demyelinating neuropathy is the primary PNS pathology.


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