Page 171 - AIDSBK23C

Page 171

CENTRAL NERVOUS SYSTEM PATHOLOGY IN AIDS

Clinical features of central nervous system (CNS) lesions with AIDS can be similar and
often require radiologic or laboratory differentiation. Neurologic examination helps establish the
presence of CNS lesions and to document their progression or response to therapy. Besides
organic disease, there are serious functional disorders resulting from the multitude of emotional
and psychosocial problems created by the devastating effect of HIV infection on the lives of its
victims. CNS lesions are typically identified in over 80% of autopsied AIDS patients. Of AIDS-
diagnostic diseases, cryptococcosis, cytomegalovirus, malignant lymphomas, and toxoplasmosis
are the most frequent (Table 5). About one-fifth of AIDS patients die from CNS diseases.[417]
The use of antiretroviral therapy (ART) alters the CNS complications with prolonged survival so
that progressive multifocal leukoencephalopathy (PML), toxoplasmosis, and cytomegalovirus are
less frequent complications, while stroke and CNS lymphoma increase.[737]
Diagnostic imaging including computerized tomography (CT) and magnetic resonance
imaging (MRI) are insensitive for early lesions and cannot detect small microglial nodules,
perivascular lesions, or granulomas. A clinical diagnosis of encephalopathy is often made before
a radiologic diagnosis, in which the only early change seen with MR imaging is atrophy.[738]
Stereotaxic biopsy following radiologic imaging can be useful for diagnosis, with a diagnostic
yield around 90%.[739] Cytologic examination of stereotaxic specimens can increase diagnostic
sensitivity, particularly for infectious conditions.[740]

HIV ENTRY INTO THE CNS.-- HIV can be carried to the CNS early following initial
infection. Entry probably occurs through breaches in the blood-brain barrier. The HIV Tat
protein can induce oxidative stress, compromise cellular viability, induce apoptosis, and disrupt
tight junctions in endothelial cells to produce HIV entry as well as ongoing cellular damage. The
HIV envelope protein gp160, cleaved into gp120 and gp41, has been shown to be neurotoxic.
Both the GSK3β and CDK5 signaling cascades mediate some of the neurotoxic effects of HIV
proteins. HIV resides within microglial cells, astrocytes, or perivascular macrophages, and these
infected cells can constitute the reservoir of infection from which the effects of ongoing HIV
replication lead to disease in the brain. The ongoing cellular damage appears clinically as an
encephalopathy or encephalitis.[741,742,743]

PRIMARY HIV INFECTION AND THE CNS.-- Few persons will have neurologic
findings associated with initial HIV infection. Those findings may include aseptic meningitis,
Bell's palsy, and inflammatory neuropathy. The aseptic meningitis is similar to that caused by
other viruses and presents with fever, headache, stiff neck, and photophobia. Examination of
cerebrospinal fluid may reveal a lymphocytic pleocytosis, normal to slightly elevated protein,
and normal glucose. Most persons recover, but a few have recurrent meningitis.[744]

HIV-ASSOCIATED NEUROCOGNITIVE DISORDER.-- A clinical syndrome
described loosely as "HIV encephalopathy" is often associated with a progressive debilitating
dementia, or "AIDS dementia complex" (ADC), or HIV-associated neurocognitive disorder
(HAND). This often begins with impaired memory and concentration along with psychomotor
slowing. It is progressive and continues to include motor deficits such as ataxia and tremor.
Behavioral disturbances range from apathy or withdrawal to frank psychosis. One sixth of