HIVRelated Nervous System Diseases

The viruses may infect the brain, spinal cord, and peripheral nerves.

Cerebral Diseases

Involvement of the brain may present in three forms, often in combination: HIV encephalitis, HIV leukoen-cephalopathy, and diffuse poliodystrophy. The clinical manifestations are collectively referred to as AIDSdementia complex, HIV-associated dementia, or HIV-associated cognitive motor complex. These disorders develop in about 15% to 20 % of HIV patients and are major causes of disabilities and death.

Clinical features. The disease begins with a slowing of mental activities, difficulty with concentration, apathy, social withdrawal, and personality changes, followed by progressive memory impairment and loss of verbal skills, leading to a profound dementia and, ultimately, to a vegetative state. During the course of the disease, seizures, gait difficulty, weakness, ataxia, and tremor develop, and frontal release signs appear. Strokes—hemorrhagic or ischemic—due to hematologic and cardiovascular changes, may complicate the clinical course.

Diagnostic evaluation. Proton magnetic resonance spectroscopy (MRS) is valuable in detecting metabolic abnormalities during early stages of the disease and in monitoring therapeutic efficacy. A decrease in N-acetyl-transferase (NAA), a neuronal marker, suggests neuronal and axonal damage, whereas an elevation in choline, a cellular membrane marker, suggests myelin breakdown. In more advanced stages of infection, neu-roimaging demonstrates atrophy of the gray and white matter. The leukoencephalopathy appears on CT scan as hypodense, and on MRI T2-weighted images it appears as hyperintense, ill-defined white matter lesions. They produce no mass effect and do not enhance with contrast material. Examination of the CSF is useful in eliminating opportunistic infections.

Clinical course. After the onset of dementia, the course averages from a few to several months. Treatment with highly active antiretroviral therapy (HAART) apparently slows the progression of dementia, prolongs survival time, and decreases the incidence of some opportunistic infections. However, drug-resistant viral strains have caused a rise in the incidence of HIV encephalitis and the appearance of a malignant HIV leukoencephalopathy.

Encephalitis. Grossly, the brain volume is diminished, the convolutions are moderately atrophic, and the ventricles are dilated (Fig. 6.12).

The histology is characterized by a microglial nodular encephalitis (Fig. 6.13). Multiple discrete nodules composed of microglial cells and macrophages and multinucleated giant cells are dispersed throughout the cerebral cortex, white matter, deep gray structures, brainstem, and cerebellum. The multinucleated giant cells, derived from a fusion of macrophages, are the diagnostic hallmark of HIV infection. The microglia and macrophages and the multinucleated cells immuno-react for HIV p24 antigen. Perivascular lymphocytic cuffings are variable.

Leukoencephalopathy. Focal and diffuse myelin changes range from pallor and rarefaction to breakdown and phagocytosis of myelin debris. Axonal degeneration and axonal spheroids are detected in severely affected areas. Astrocytic proliferation accompanies the myelin changes (Fig. 6.14).

A severe leukoencephalopathy has been recognized in patients treated with HAART. It is characterized by extensive demyelination, axonal injury, and intense peri-vascular lymphocyte and macrophage infiltrations.

FIGURE 6.12

HIV encephalitis in a 44-year-old demented man. The brain shows a moderate convolutional atrophy.

FIGURE 6.12

HIV encephalitis in a 44-year-old demented man. The brain shows a moderate convolutional atrophy.

Diffuse Poliodystrophy. The term refers to loss of dendritic processes and loss of neurons in the cerebral cortex and deep gray structures.

HIV Vacuolar Myelopathy

This distinct spinal cord complication of HIV infection is characterized by spongy degeneration of myelin in \the lateral and posterior columns. Clinically, it presents with slowly progressive spastic paraparesis, loss of position and vibratory senses, and incontinence (Fig. 6.15).

HIV Neuropathy

Involvement of the peripheral nerves manifests as bilateral distal symmetric neuropathies and, less often, as sensory or autonomic neuropathies, polyradiculopa-thies, and mononeuropathy multiplex. Segmental demy-elination, axonal degeneration, perivascular lymphocytic infiltrations, and vasculitis are common (Fig. 6.16). Several etiologies include direct infection by HIV or cytomegalovirus, an immunologic mechanism, and nutritional, metabolic, and toxic factors.

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