The Neuropathology Of AIDS

The nervous system is a principal target of human innnuno-deficiency virus-i (HIV-1) infection: clinical and neuropathological examinations show that the nervous system is affected in the overwhelming majority of the patients. No parts of the nervous system's spared: the brain and spinal cord, the peripheral nerves and muscles may all be affected.

The neuropathological investigations have yielded three important observations:

1. Diseases affecting the nervous system fall into two separate groups.

The first group contains opportunistic infections, neoplasms and vascular complications, secondary diseases which develop as a consequence of immunosuppression caused by HIV-1. The spectrum of these diseases is not greatly different from the range of pathologies associated with other immunocompromissed states.

The second groups of diseases is associated primarily with HIV-1 1, although the causal role of the virus, with the exception of the first two entities, HIV-encephalitis and HIV leucoencephalopathy, remains to be established.

2. Multiple pathologies are the rule rather than the exception in advanced AIDS. The nervous system may be afflicted by more than one disease: the brain may not uncommonly show HIV-encephalitis in combination with opportunistic infections and lymphomas .

3. The pathological spectrum is not the same in different risk groups: the neuropathology varies in homosexual men, hemophiliacs, drug abusers and in children.

DISEASES OF THE CENTRAL NERVOUS SYSTEM IN AIDS

1. Secondary diseases

1.1. Opportunistic infections

Viral, protozoal, bacterial and fungal infections may all develop, and although there are geographical differences in incidence, cytomegalovirus and toxoplasma occur most frequently with an average of 15.8% and 13.6% respectively, followed by cryptococcus (7.6%), progressive multifocal leucoencephalopathy (a demyelinating disease caused by papovaviruses (4.0%) and herpes simplex (1.6%).

1.2. Neoplasms

Primary and secondary lymphomas may affect the central nervous system in 5.5% and 2.1 % cases, respectively. These are B cell lymphomas, highly malignant, often undifferentiated with the usual angiocentric pattern and diffuse, extensive invasion of the brain. Kaposi's sarcomas whether primary or secondary are extremely rare.

1.3. Vascular complications

These are infarcts and hemorrhages, resulting from complex focal and generalised factors .

2. HIV-associated diseases

2.1. HIV-encephalitis

Macroscopically HIV-encephalitis may or may not be associated with cerebral atrophy. Histologically the 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.

2.2. HIV leucoencephalopathy

In HIV leucoencephalopathy the white matter bears the brunt of the disease: myelin loss, astrocytosis and the presence of macrophages and multinucleated giant cells 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.

2.3. Vacuolar myelopathy and vacuolar leucoencephalopathy

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.

2.4. Lymphocytic meningitis

There should be significant lymphocytic infiltration of the leptomeninges and perivascular spaces in the absence of any demonstrable pathogens.

2.5. Diffuse poliodystrophy

This term was originally conceived to describe diffuse damage to the cerebral cortex, basal ganglia and brainstem nuclei, characterised by diffuse astrocytosis and 'microglial activation.

2.6. Cerebral vasculitis

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.

2.7. Neuronal loss

Neuronal loss has been recently documented, both in various areas of the cerebral cortex and in the subcortical grey matter. This phenomenon has particular importance in the clinical symptomatology of dementia.