Multifocal Leukoencephalopathy (PML)
multifocal leukocencephalopathy (PML) is a life-threatening
infection of the brain that can occur in people living
with HIV. It is caused by a virus - the JC virus. The
"JC" are the initials of the first patient
to be diagnosed with PML. The virus is a polyomavirus,
a family of viruses that also includes human papillomavirus
"progressive" in PML means that it continues
to get worse and often leads to serious brain damage.
The "multifocal" means that the JC virus causes
disease in several different parts of the brain. The
"leukoencephalopathy" means that the disease
affects the white matter of the brain. More specifically,
the JC virus infects cells in the brain called oligodentrocytes.
These cells are responsible for producing myelin, a
fatty substance that helps protect nerves in the brain.
If too much myelin is lost and not replaced by oligodentrocytes,
the nerves become damaged and eventually stop working
than 70% of all adults in the United States are infected
with the JC virus, usually during early childhood. However,
the virus only becomes active in people who have compromised
immune systems. The includes people undergoing immune-suppressive
chemotherapy for cancer and people with damaged immune
systems due to HIV. Prior to the use of combination
anti-HIV drug therapy. It was estimated that between
3% and 10% of all people with AIDS developed PML. It
usually occurs in people with vary low T-cell counts,
but has been seen in some HIV-positive people with as
many as 500 T-cells.
is almost always progressive and fatal. Death usually
occurs between one and four months after the first symptoms
appear. However, there have been a number of reported
cases with survival ranging from several months to years.
What's more, up to 10% of people with PML spontaneously
recover, either with or without treatment.
are the symptoms of PML?
of PML include mental deterioration, vision loss, speech
disturbances, ataxia, paralysis, and coma. In rare cases,
seizures may occur.
is PML diagnosed?
of the symptoms of PML are similar to those seen with
other HIV-related diseases. Thus, it is important to
determine the exact cause of these symptoms so that
the correct treatment can be started.
most accurate way to diagnose PML is by conducting a
brain biopsy. To do this, a surgeon will need to remove
a small piece of brain tissue and send it to a lab for
analysis. However, a brain biopsy can be risky, especially
for those with compromised immune systems. It is also
possible to diagnose PML by analyzing magnetic resonance
imaging scans of the brain and/or by looking for the
JC virus in the fluid surrounding the spinal column.
This requires a spinal tap - a needle inserted into
the lower back to drain spinal fluid so that it can
is PML treated?
there are no treatments that have been proven to be
effective for PML. A handful of drug treatments have
been studied in clinical trials, including:
also known as cytosine arabinoside for Ara-C, is approved
for the treatment of certain cancers. Early studies
of this drug suggested that it was a possible treatment
for PML. However, a larger study conducted by the
U.S. government did not find cytarabine to be particularly
effective, whether the drug was injected into a vein
or directly into the brain.
though clinical trial results do not support its use,
cytarabine is still prescribed for some patients with
PML. To receive cytarabine, a patient will need to
have a shunt surgically implanted into his or her
skull. This allows doctors to inject cytarabine, through
the tube, directly into the brain. When treatment
is started, cytarabine is administered every day for
three days. After that, it is given twice a week for
two weeks, followed by once-weekly intrathecal injections
is also used to treat certain cancers. Like cytarabine,
early studies suggested that it was effective as a
treatment for PML, but a larger study reported in
early 2001 did not find it to be effective.
is approved for the treatment of cytomegalovirus.
Early test tube studies found that it was effective
against viruses similar to the JC virus. Two small
studies involving humans suggested that it might be
useful in treating PML. Larger studies are still needed
to determine how effective cidofovir really is. Cidofovir
can damage the kidneys, thus it should be combined
with probenecid to help protect kidney function.
- dose , delivered through an intravenous line, was
one of the first treatments studied for PML. While
it did help slow progression in some patients, few
patients experienced a reversal of symptoms or were
able to prevent death.
treatment of PML is not without hope, however. Combination
anti-HIV drug therapy has been shown to be extremely
beneficial for HIV-positive patients with PML. Because
PML is most likely to occur in patients with suppressed
immune systems - and anti-HIV therapy has been shown
to significantly increased T-cell counts and the general
health of the immune system - HIV-positive patients
with PML are more likely to live longer and to see their
symptoms improve, sometimes dramatically.
researchers agree that HIV-positive patients with PML
should use anti-HIV drugs that are known to cross the
"blood-brain barrier" - a protective coat
that lines blood vessels in the brain to prevent toxins
from passing through. Many of the nucleoside analogues,
especially, and the non-nucleoside analogues, particularly,
easily pass through the blood-brain barrier, and are
often used to treat patients with other HIV-related
brain diseases . If AZT is used to help treat PML, researches
suggest that a daily dose of 1,000 to 1,200 mg be used.
PML be prevented?
not at the present time. But because immune suppression
plays a major role in the development of PML, the best
possible way to prevent this diseases is to keep the
immune system healthy. This includes starting anti-HIV
therapy before the immune system becomes impaired.