Definitive diagnosis of PML requires neuropathologic demonstration of the typical histopathologic triad (demyelination, bizarre astrocytes, and enlarged oligodendroglial nuclei) coupled with the techniques to show the presence of JC virus. The presence of clinical and imaging manifestations consistent with the diagnosis and not better explained by other disorders coupled with the demonstration of JC virus by PCR in CSF is also considered diagnostic. Algorithms for establishing the diagnosis have been recommended.

Studies of the pathogenesis and molecular biology of JC virus infection over the last two decades have significantly changed our understanding of progressive multifocal leukoencephalopathy, which can be described as a subacute viral infection of neuroglial cells that probably follows reactivation of latent infection rather than being the consequence of prolonged JC virus replication in the brain. There is now sufficient evidence to suggest that JC virus latency occurs in kidney and B cells. However, JC virus isolates from brain or kidney differ in the regulatory regions of their viral genomes which are controlled by host cell factors for viral gene expression and replication. DNA sequences of noncoding regions of the viral genome display a certain heterogeneity among isolates from brain and kidney. These data suggest that an archetypal strain of JC virus exists whose sequence is altered during replication in different cell types. The JC virus regulatory region likely plays a significant role in establishing viral latency and must be acted upon for reactivation of the virus. A developing hypothesis is that reactivation takes place from latently infected B lymphocytes that are activated as a result of immune suppression. JC virus enters the brain in the activated B cell. Evidence for this mechanism is the detection of JC virus DNA in peripheral blood lymphocytes and infected B cells in the brains of patients with progressive multifocal leukoencephalopathy. Once virus enters the brain, astrocytes as well as oligodendrocytes support JC virus multiplication. Therefore, JC virus infection of neuroglial cells may impair other neuroglial functions besides the production and maintenance of myelin. Consequently our increased understanding of the pathogenesis of progressive multifocal leukoencephalopathy suggests new ways to intervene in JC virus infection with immunomodulation therapies. Perhaps along with trials of nucleoside analogs or interferon administration, this fatal disease, for which no consensus of antiviral therapy exists, may yield to innovative treatment protocols.

Progressive multifocal leukoencephalopathy (PML), a formerly rare disease, is estimated to occur in up to 5% of all patients with AIDS. The high prevalence of PML in AIDS patients currently enables a comprehensive evaluation of this disorder. We evaluated the clinical and radiographic features of PML in a large cohort of AIDS patients identified by retrospective chart review from 1981 to 1994. Two hundred and five patients were diagnosed with PML of which 154 met the inclusion criteria. Seventy-two (47%) were pathologically confirmed and the remaining 82 (53%) met clinical and radiographic criteria. There was a 12-fold increase in the frequency of PML between 1981-1984 and 1991-1994. PML affected 136 men and 18 women with AIDS. Eighty-four percent of cases were 20-50 years old (range 5 to 68 years). The most common AIDS risk factors were homosexuality (57%) among men and heterosexual transmission (28%) and intravenous drug abuse (28%) among women. In 27% of patients, PML heralded AIDS. Common manifestations included weakness, gait abnormalities, speech disturbance, cognitive disorders, headache, and visual impairment. The CD4 lymphocyte counts exceeded 200 cells in 11% at the time of presentation. Involvement of posterior fossa structures was evident in 48% of cranial magnetic resonance imaging (MRI) studies, but in only 11% of computed tomographies (CT) of the brain. Contrast enhancement, typically faint and peripheral, was seen in 10% of CT scans and 15% of MRIs. The median survival was 6 months and survival exceeded 1 year in 9%. PML is no longer a rare disease. It often heralds AIDS and may occur in the absence of significant decline in CD4 lymphocytes. Survival is generally poor, although prolonged survival beyond 1 year is not unusual.

The MR scans in SS show a rather distinctive pattern of supratentorial white matter lesions that always involve the corpus callosum. There is often deep gray matter, posterior fossa involvement, and frequent parenchymal with occasional leptomeningeal enhancement. The central callosal lesions differ from those in demyelinating disease, and should support the diagnosis of SS in patients with at least two of the three features of the clinical triad.

Human immunodeficiency virus (HIV) infection is associated with an increased risk for human herpesviruses (HHVs) and their related diseases. Methods for limiting the transmission of HHVs require a better understanding of the prevalence and infectiousness of oral HHVs in HIV-infected patients. We performed quantitative PCR to investigate the prevalence, quantity, risk, and correlates of salivary HHVs from 58 HIVseropositive individuals in a case control study. HHVs were significantly more prevalent in the salivas of HIV-seropositive persons than in those of the controls (odds ratios [ORs], 4.2 to 26.2; P < 0.008). In HIV-infected patients, Epstein-Barr virus (EBV), human herpesvirus 8 (HHV-8), cytomegalovirus (CMV), and herpes simplex virus type 1 (HSV-1) were detected in 90%, 57%, 31% and 16% of samples, respectively, compared with 48%, 24%, 2%, and 2%, respectively, of samples from controls. Multiple HHVs were observed in 71% of HIV-seropositive persons and only 16% of controls (OR, 13.0; 95% confidence interval, 5.29 to 32.56). HIV-positive patients had significantly higher EBV loads than HIV-negative persons (P < 0.0001). HIVinfected patients with CD4 counts above 200 cells/l had increased probability for having HHV-8 in saliva (P ‫؍‬ 0.009) compared with patients whose counts were less than 200. In contrast, HSV-1, EBV, and CMV were detected more often when CD4 counts were low. High salivary HHV loads were detected for those (n ‫؍‬ 7) with oral lesions. These findings suggest that saliva is a potential risk factor for the acquisition of multiple HHVs, and several host factors may function to accelerate HHV reactivation or replication in patients with HIV infection.