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March 2001
Discussion
The cause of dementia in HIV-infected children often is difficult to determine in the absence of biopsy tissue. The differential diagnosis includes primary HIV encephalopathy, progressive multifocal leukoencephalopathy (PML), CNS lymphoma, cytomegalovirus infection, and cerebral toxoplasmosis. Imaging studies and correlation with the clinical course can yield useful diagnostic information.
In this case, review of the enhanced CT scan reveals asymmetric enhancement of non-adjacent regions of white matter, with a relative sparing of the grey matter. Involved regions include the left cerebellum and left parietal cortex. These findings and the clinical course are consistent with the diagnosis of PML. Generally, patients with PML are afebrile. Headache is an uncommon symptom. Blindness, sensory abnormalities, and paresis are common findings. Cerebrospinal fluid analysis usually is normal, but mild pleocytosis may be present. Definitive diagnosis is by PCR-amplification of JC virus DNA from the spinal fluid.
JC virus, the causative agent of PML, is a ubiquitous DNA virus of the polyomavirus family that is benign in the immune-competent host. It is believed to remain “latent” in the kidney, brain, and lymphocytes. In the presence of abnormal cell-mediated (T-cell) immunity (e.g., AIDS, cancer chemotherapy, post-transplant or primary immune deficiency syndromes), JC virus reactivation occurs, the primary manifestation of which is a lytic infection of oligodendroglia. The disease is uncommon among children. The incidence of PML is higher among AIDS patients than among patients with other immunodeficiencies. This may be related to the ability of the HIV-tat protein to transactivate the JC virus late promoter. Treatment of PML requires immune reconstitution, as no specific antiviral agents are currently available. Despite antiretroviral therapy, many patients succumb to PML. Death within 3 to 6 months of clinical onset is the most frequent outcome.
Primary HIV encephalopathy is a diagnosis of exclusion that is poorly understood. Children with HIV can have variable patterns of neurologic decline, including static, plateau, and sub-acute progressive courses. The pathophysiology of these distinct entities may be related to immunogenetic factors and viral co-infections, particularly with cytomegalovirus, JC virus, and human herpesvirus-6.
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