HIV - Progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is a demyelinising disease caused by infection with a papova virus, the JC virus. The family of the Papovaviridae is divided into two genera: Papilloma virus (e.g. wart virus) and Polyoma virus (including JC virus, BK virus and the SV40 virus). The name papova is derived from papilloma, polyoma and vacuolating agent. They are small double-stranded DNA viruses that are potentially oncogenic. The infection preferentially destroys the oligodendrocytes, leading to demyelinisation since the myelin sheath around axons in the central nervous system is formed by concentric folds of the cytoplasma membrane of the oligodendrocytes (analogous to the Schwann cells in the peripheral nervous system). The disease was first described in 1958 by Aström. By injection into experimental animals the virus can induce a number of brain tumours (gliomas, meningomas, neuroblastomas, medulloblastomas). JC virus undergoes intranuclear replication in the astrocytes and oligodendrocytes, as well as in other cells (the virus can be found in epithelial cells in urine, liver, spleen, lymph nodes and lungs). Infections with this virus are frequent but nearly always remain without further consequences. However, in severe immunosuppresion (CLL, Hodgkin’s disease, sarcoidosis, SLE, AIDS) a neurological syndrome can occur. Selective destruction of myelin takes place, but the axons are spared. There is little inflammation (in contrast to multiple sclerosis, where there is an inflammatory lymphocytic infiltrate). Multiple distinct foci of myelin destruction are observed in brain tissue obtained via stereotactic biopsy. The foci become confluent after a while. The lesions are asymmetrical without any preferred localisation, although lesions rarely occur in the spinal cord. The oligodendrocytes exhibit intranuclear viral inclusions. Giant astrocytes with pleomorphic, hyperchromatic nuclei strongly reminiscent of glioblastomas also occur. The clinical evolution is rapid, with an average course of disease of 2 to 4 months. Remission seldom occurs. Mono- or hemiparesis, speech disorders, mental deterioration with progression to dementia and death are the rule. Transverse myelopathy is rare. There is no fever. Headache and fits or convulsions are exceptional. The differential diagnosis includes other opportunistic infections (mycobacteria, fungi, Toxoplasma, cytomegalovirus), syphilis, cerebral lymphoma, endocarditis with embolism, HIV encephalopathy and multiple sclerosis. The EEG is usually diffusely disturbed and aspecifically slow. The cerebrospinal fluid is normal, though the virus can be detected in the fluid by PCR. CT brain scans and, even better, MRI scans show the subcortical lesions in the white matter. There is no mass effect and no staining of the lesions with contrast medium. As regards treatment, the results with various medications have hitherto been disappointing. Regression of the lesions has sometimes been seen under treatment with “HAART”.