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Pathological Changes in the Nervous system in patients afflicted with AIDS
The human immuno-deficiency virus (HIV-1) infection affects most parts of the nervous system in the majority of AIDS patients. The brain and spinal cord, the peripheral nerves and muscles may all be affected.
Diseases affecting the nervous system in AIDS fall into two separate groups. The first group contains opportunistic infections, neoplasms and vascular complications, which are secondary diseases developing as a consequence of immunosuppression caused by HIV-1. The spectrum of these diseases is not greatly different from the range of similar diseases associated with other immunodeficient states. The second groups of diseases is related primarily with the virus itself. This is demonstrated in two entities, HIV-encephalitis and HIV leucoencephalopathy, although the causal role of the virus in other AIDS diseases remains to be established.
In Advanced AIDS multiple pathologies dominate the picture and the nervous system may be afflicted by more than one disease, for example the brain may show HIV-encephalitis in combination with opportunistic infections and lymphomas . The pathological spectrum is not the same in different risk groups, so the neuropathology varies in homosexual men, hemophiliacs, drug abusers and in children.
Viral, protozoal, bacterial and fungal infections may all develop. The most frequent are cytomegalovirus and toxoplasma infections which affects 15.8% and 13.6% respectively. Cryptococcus (7.6%), progressive multifocal leucoencephalopathy (a demyelinating disease caused by papovaviruses )(4.0%) and herpes simplex (1.6%) comes next.
Primary and secondary lymphomas may affect the central nervous system in 5.5% and 2.1 % cases, respectively. These are highly malignant B cell lymphomas, often undifferentiated with the usual angiocentric pattern and diffuse, extensive invasion of the brain. Kaposi’s sarcomas whether primary or secondary are extremely rare.
These are infarcts and hemorrhages, resulting from complex focal and generalised factors .
HIV-encephalitis may or may not be associated with cerebral atrophy. This type of encephalitis is characterised by multiple foci of cellular infiltrates composed of multinucleate giant cells (hallmark lesion of the infection), microglial cells, macrophages and a varying number of lymphocytes. Astrocytosis is often seen. The pattern of inflammation varies from case to case, but the white matter, deep grey matter and cortex are involved in this order of frequency. Macrophages, microglial cells and multinucleate giant cells may all be infected by HIV, and viral antigens and nucleic acids can be demonstrated by immunocytochemistry and in situ hybridisation.
In HIV leucoencephalopathy, the white matter is the area most affected with myelin loss, astrocytosis and the presence of macrophages and multinucleated giant cells which characterise this diffuse damage. The white matter of the cerebral hemispheres is usually extensively and symmetrically affected, but the cerebellar white matter may also be involved.
In vacuolar myelopathy, which has similarities with subacute combined degeneration of the spinal cord, the lateral and posterior luniculi are chiefly affected, particularly at the level of the thoracic cord. Histologically there is vacuolar swelling of the myelin lamellae, macrophage response and astrocytosis. In more severe cases, the axons may also be damaged. Similar lesions may also develop in the brain: this is vacuolar leucoencephalopathy. The aetiology is disputed: in addition to HIV infection of the spinal cord, metabolic cause, particularly B12 deficiency and an opportunistic infection may also contribute to the pathology.
There should be significant lymphocytic infiltration of the leptomeninges and perivascular spaces in the absence of any demonstrable pathogens.
This is a diffuse damage to the cerebral cortex, basal ganglia and brainstem nuclei, characterised by diffuse astrocytosis and ‘microglial activation.
In true cerebral vasculitis, the vascular wall is infiltrated by lymphocytes, as opposed to perivascular cuffing by mononuclear cells, often seen in the brain in HIV infection.
Neuronal loss has been documented, both in various areas of the cerebral cortex and in the subcortical grey matter.