Introduction
Progressive multifocal leukoencephalopathy, which is abbreviated as PML was a fairly rare demyelinating disease of the white matter of the brain (thanks to www.nlm.nih.gov for this link) until the AIDS epidemic started.
As PML requires a weakened immune system to develop, it is no wonder that AIDS has significantly increased the frequency of this neurological disease.
It is caused by the human papovavirus, an RNA virus called JC virus (=JCV). We know from serological studies on children where by age 10 about 50% of them have antibody titers to JCV that this virus is widely distributed. However, normally JCV infection stays suppressed by the immune system’s cell mediated immune response. In the case of immune weakening diseases such as leukemias, lymphomas, AIDS and in transplant patients JCV can then be reactivated and cause PML (Ref. 12, p. 2138). Today about 5% of AIDS patients are suffering from PML.
Signs and symptoms
The typical symptom is a focal neulogical defect that can be associated with a white matter lesion of the brain using CT or MRI scan imaging. There might be an isolated muscle weakness, a gait disturbance, a speech defect or a blind spot from a visual field loss. Often these type of symptoms might be due to a demyelinating defect in the middle part or back part (“parieto-occipital region”) of the brain. If the cerebellum (behind and below the brain) is affected, an awkward broad legged gait and balance problems result (“ataxic gait”). In a few cases there might be sudden seizures and in another view there could be a total blindness due to demyelinating lesions in the visual cortex of both brain hemispheres. In patients with AIDS headaches are more common than in other patients with PML, the same is true for seizures (Ref. 6, p.1299 and Ref. 12, p. 2138).
Diagnostic tests
As already mentioned, the CT or MRI scan imaging will confirm the neurological finding of the neurologist. The specialist will likely want to do a lumbar puncture to obtain a cerebrospinal fluid sample for JCV polymerase chain reaction testing. This is a very sensitive and specific test although still indirect. The most specific and direct test, although invasive, is a brain biopsy with the help of a neurosurgeon for a histological investigation of the sample. There are characteristic changes in the connective tissue of the brain (oligodendral glia cell changes). Using the electron microscope the JCV particles can be detected in the that are 100% proof regarding the PML diagnosis.
Treatment
Unfortunately the prognosis is rather guarded for PML. No reliably effective antiviral therapy is available. Most cases die within 6 to 12 months from the point of diagnosis. However, recently in AIDS patients there has been a breakthrough using potent antiviral combination therapy including protease inhibitors and at least one author (Ref. 13) has reported encouraging results with some cures of PML when the underlying AIDS was controlled. It remains to be seen, whether the JC virus was eradicated in this situation or not and whether this therapy would benefit other PML patients who do not have AIDS.
References:
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12. Goldman: Cecil Textbook of Medicine, 21st ed., Copyright © 2000 W. B. Saunders Company
13. PE Sax: Infect DisClinics of N America Vol.15, No 2 (June 2001): 433-455.
14. David Heymann, MD, Editor: Control of Communicable Diseases Manual, 18th Edition, 2004, American Public Health Association.
