BEING ALIVE; April 1995
Sarah Huffbauer, MD

There are three main categories of central neurologic (occurring in the brain) syndromes in HIV: a) AIDS Dementia Complex, though to be caused by HIV itself, b) neoplasms (cancers), and c) opportunistic infections. In approximate order of frequency, neurologic opportunistic infections are caused by toxoplasmosis, cryptococcus and other fungi, viruses such as CMV and herpes, mycobacteria, and the virus which causes PML called papovavirus or Jacob-Crutchfeld virus.

Since up to 70-90% of healthy older adults have antibodies to the papovavirus, PML is most likely a reactivation of the virus in an immunocompromised person as opposed to a primary infection. Papovavirus was identified as a slowvirus (one which causes latent and usually benign infection) and as the cause of PML in 1958. PML was even rarer then, occurring mostly in people with leukemia or lymphoma. As the HIV epidemic has increased the incidence of PML, so has more interest in research into early diagnosis and treatment increased in the last decade.

As mentioned earlier, PML is similar to multiple sclerosis (which is much more common). Like MS, it is a demyelinating disease of the brain. Demyelination refers to destruction of the insulation-like cells called oligodendrocytes around nerve fibers. Like people with MS, people with PML often first experience subtle weakness or the lack of coordination of an arm or leg. Unique to PML, there is often some difficulty with thinking and/or speaking. Visual disturbances, seizures, memory problems and headache can sometimes follow. With rare exception, PML has been true to its name in that it is devastatingly progressive with a mean survival of 2-4 months after onset of symptoms and a survival range of 2 weeks to 18 months.

Also in line with its name, the usual findings on CT scan or MRI are multi-focal lesions within the brain. These lesions are best seen with MRI and are usually of high-signal intensity without enhancement. PML lesions must be distinguished from lymphoma which is also non-enhancing but usually only one lesion (unifocal instead of multifocal), and from toxoplasmosis which is usually quite enhancing on the scans. Unique to PML, there is rarely any edema (brain swelling) or mass effect (shifting of the brain to one side). The location of the lesions is usually subcortical at the junction between the gray and white matter, unlike MS which is cortical (higher white matter).

Other potential diagnostic tools, once imaging of the brain has been performed, are lumbar puncture and brain biopsy. Usually the cerebral spinal fluid from lumbar puncture is normal with occasional increases in lymphocytes (a type of white blood cells). A new test for papovavirus is the spinal fluid by PCR (polymerase chain reaction) is being developed and may have sensitivity of up to 80%. The clinical use of this test would allow diagnosis based on lumbar puncture and imaging alone, avoiding the more invasive brain biopsy. As it stands now, brain biopsy still provides the only definitive diagnosis. Biopsies are fairly low risk (only 3% serious complication rate) and can be done under local anesthetic with CT guidance.

While there is currently no effective treatment for PML, many antivirals have been tried. There are case reports of AZT alone being helpful, but there is also a 10% spontaneous remission rate, so it has been hard to draw useful conclusions. Dr. Christina Marra is conducting a randomized three arm trial for people with biopsy proven PML (ACTG243). The trial compares the best antiviral the person can tolerate alone, with best antiviral plus intrathecal (into the spinal fluid) Ara-C. Ara-C (cytosine arabinoside) is an antiviral and also used in chemotherapy. It has multiple potential toxicities, and so people receiving it must be carefully monitored. While PML is a grim diagnosis to receive or to make, the more we know about it, the more we can differentiate it from other more readily treatable central nervous system problems. Accurate diagnosis for neurologic problems in HIV can help to provide realistic prognoses and expectations. Ongoing research will, one hopes, identify effective treatment for PML in the near future.

(Sarah Huffbauer, MD, is a family physician practicing in the Seattle area. This article is reprinted from the Fall 1994 STEP Perspective, a publication of the Seattle Treatment Exchange Project. For subscription information, Call 1.800.869.STEP.)

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