This disorder, due to JC virus, first observed clinically by Adams in 1952, was described morphologically in 1958 by Åstrom and coworkers, and then with a larger body of material by Richardson in 1961. It is characterized by widespread demyelinating lesions, mainly of the cerebral hemispheres but sometimes of the brainstem and cerebellum, and, rarely, of the spinal cord. The lesions vary greatly in size and severity—from microscopic foci of demyelination to massive multifocal zones of destruction of both myelin and axons involving large parts of a cerebral or cerebellar hemisphere. The abnormalities of the glia cells are distinctive. Many of the reactive astrocytes in the lesions are gigantic and contain deformed and bizarre-shaped nuclei and mitotic figures, changes that are seen otherwise only in malignant glial tumors. Also, at the periphery of the lesions, the nuclei of oligodendrocytes are greatly enlarged and contain abnormal inclusions. Many of these cells are destroyed, accounting for the demyelination. Vascular changes are lacking, and inflammatory changes are present but usually insignificant, except in a small number of interesting cases in which immune reconstitution by retroviral drugs for AIDS allows the emergence of intense inflammation.
PML usually develops in a patient with a neoplasm, mainly lymphoma and CML, or immunodeficiency state. Most cases are observed in patients with HIV in whom the incidence of PML approaches 5 percent but the disorder is increasingly occurring in patients who are being immunosuppressed for a variety of reasons including some of the potent drugs for treatment of multiple sclerosis. Other important associations are with nonneoplastic granulomatosis, such as tuberculosis or sarcoidosis. A series of the interesting occurrence of PML in the last of these, sarcoid, is given by Jamilloux and colleagues.
Personality changes and intellectual impairment may introduce the neurologic syndrome, which then evolves over a period of several days to weeks. Any one or some combination of hemiparesis progressing to quadriparesis, visual field defects, cortical blindness, aphasia, ataxia, dysarthria, dementia, confusional states, and coma are manifestations. Some of the cases under our observation had a predominantly an asymmetric cerebellar syndrome. Seizures are infrequent, occurring in only about 10 percent of cases. If untreated, usually meaning that immunosuppression is not ameliorated, death occurs in 3 to 6 months from the onset of neurologic symptoms and even more rapidly in patients with HIV unless antiretroviral treatment is undertaken. In the current era, the duration of disease is generally much longer.
Laboratory testing The CSF is usually normal. CT and MRI localize the usually nonenhancing, demyelinating lesions without mass effect (Fig. 32-4) but the variability in size, location, and multiplicity make the diagnosis more dependent on viral DNA isolation from CSF by PCR and on the context of immunosuppression. Up to 15 percent have faint peripheral contrast enhancement of lesions. Our colleagues have indicated to us that PCR from the CSF is generally 74 to 92 percent sensitive and 92 to 96 percent specific but less sensitive, approximately 60 percent in HIV patients receiving highly active anti-retroviral therapy.
An associated syndrome, in which a fulminant inflammatory response surrounding PML lesions in relation to rapid treatment of the underlying immunosuppressive state (immune reconstitution inflammatory syndrome, IRIS) is discussed in the following text.