Progressive Multifocal Leukoencephalopathy (PML)

Disease Associated with High Risk of Death, Brain Damage

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HIV can damage your immune system; that much is clear. As HIV becomes more active and makes more copies of itself, the damage can become increasingly severe, resulting in the increased risk for the development of opportunistic infections.

One of the most serious is a disease called progressive multifocal leukoencephalopathy (PML). The condition is described by its very name: "leuko" meaning white, "encephalo" meaning brain, and "pathy" meaning to disease. As such PML is the progressive damage of the white matter of the brain in multiple locations (multifocal). 

The condition is caused by the gradual stripping of the myelin sheath that covers nerve endings, particularly the white matter of the brain. As a demyelinating disease, PML manifests much in the same way as multiple sclerosis (MS), albeit faster.

The virus responsible for PML is one that most everyone has been exposed to called the JC virus (or John Cunningham virus). While it is estimated that 70-90% of the world's population has been exposed to the virus, it can only cause disease if a person has severe immune suppression as happens with AIDS.

PML has a high rate of mortality once diagnosed, with 30-50% of people dying within the first months of diagnosis. Those who survive typically have varying degrees of brain damage—some moderate, others severe.

PML is most likely to occur when the HIV-positive individual has a CD4 count of under 100 cells/mL. By definition, an AIDS diagnosis is made when the CD4 drops below 200 cells/mL

Signs and Symptoms of PML

The signs and symptoms of PML can resemble many other conditions, particularly in its early stages. Typically, the only sign of trouble may include:

  • A subtle weakness in the hands or legs
  • Difficulty thinking or concentrating
  • A lack of more coordination
  • Headaches

Often times, people mistake these symptom for fatigue, drug side effects, or even a mild stroke or transient ischemic attack. As the PML progresses, more serious symptoms may developing, including speech and vision impairment, as well as seizures and personality changes.

In some cases, patients may experience what is called an alien hand syndrome in which the hand moves on its own without the person even knowing it or being able to control it.

Diagnosis of PML

PML can typically be diagnosed in one of two ways:

  • By examining the spinal fluid for genetic evidence of JC virus supported by an MRI (magnetic resonance Imaging) scan to confirm lesions in the white matter of the brain.
  • Alternately, a brain biopsy can be used, coupled with techniques to confirm the presence of JC virus.

Is There Treatment for PML?

Prior to the advent of antiretroviral therapy (ART), PML was always fatal within a few weeks or months of diagnosis. While there is currently no drugs that can effectively inhibit or cure PML, the initiation of ART can lessen many of the symptoms by restoring some of the person's immune function.

It has been shown the ART can prolong the life of a person with PML for several years. On the flip side, the risk of PML can be greatly prevented by ensuring the early implementation of ART, ideally at the time of diagnosis and before the depletion of immune function.

A number of experimental treatments have also been explored, although results are mixed or anecdotal at best. They include the use of the anti-malarial drug mefloquine and treatment with interleukin-2 (a protein that regulates white blood cells). 

To date, there has been only a small handful of person who appear to have been cured of PML using mefloquine, while two patients appeared to recover using the immune protein, interleukin-2. Unfortunately, in both case, the high level toxicity associated with drug use complicates treatment in those with PML.  

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Article Sources
  • Sources:
  • National Institutes of Health (NIH). "Progressive Multifocal Leukoencephalopathy Information Page" Washington, D.C.; updated February 14, 2014; accessed February 24, 2016.
  • Shackelton, L.; Rambaut, A.; Pybus, G.; et al. "JC Virus evolution and its association with human populations". Journal of Virology. 2006; 80(20):9928–9933.
  • Gofton, T.; Al-Khotani, A.; O'Farrell, B.; et al. "Mefloquine in the treatment of progressive multifocal leukoencephalopathy". Journal of Neurology, Neurosurgery and Psychiatry. June 2010; 82(4):452-455.
  • Buckanovich R. Liu, G.; Stricker, C; et al.  "Nonmyeloablative allogeneic stem cell transplantation for refractory Hodgkin's lymphoma complicated by interleukin-2 responsive progressive multifocal leukoencephalopathy." Annual of Hematology. July 2002: 81(7): 410-413.