A rare and usually fatal viral chronic condition that is characterised by progressive
damage or inflammation of the white matter of the brain at multiple locations. Progressive
multifocal leukoencephalopathy occurs almost exclusively in those with severe immune
deficiency.
Also known as progressive multifocal leukoencephalitis
It is caused by the JC virus. Normally present and kept under control by the immune
system. However, the use of immunosuppressive drugs prevent the immune system from
controlling the virus.
The JC virus is now firmly associated with the condition. However it has not been
established whether the condition is the result of a primary infection with JCV in
a person with impaired immunity or whether it follows reactivation of latent virus.
The pathogenesis of PML is not fully understood but it is postulated that in persons
with disorders of immunoregulation, polyomaviruses are no longer contained in a latent
state and replicate within the oligodendrocytes, causing the destruction of the cell
and the breakdown of the myelin sheath.
Progressive multifocal leukoencephalopathy is a unique demyelinating chronic condition
which usually occurs in a person with abnormal immune responses resulting from serious
chronic condition, treatment with cytotoxic drugs or irradiation, or long term immunosuppression.
The pathology of the condition is distinctive and consists of multiple foci of demyelination
of varying size from pinpoint lesions to areas of several centimetres. The lesions
may occur anywhere but are usually in the cerebral hemispheres, less often in the
cerebellum and brain stem and rarely in the spinal cord.
Typically, the condition evolves gradually, with impairment of mental function and
disturbance of speech and vision. Movement may also be affected. The chronic condition
then progresses rapidly and the person is severely disabled, eventually becoming
demented, blind and paralysed and finally coma and death.
Progressive multifocal leukoencephalopathy has a mortality rate of 30-50% in the
first few months following diagnosis but depends on the severity of the underlying
chronic condition and treatment received. Those who survive PML can be left with
severe neurological disabilities.
Only rarely has progressive multifocal leukoencephalopathy been reported occurring
spontaneously in an apparently healthy person.
Occasionally, progressive multifocal leukoencephalopathy may spontaneously arrest.
Diagnosis can be difficult and usually relies on a neurologist and radiologist assessing
the white matter of the brain on a computed tomography scan or a magnetic resonance
imaging (MRI). Tests of the cerebrospinal fluid can help distinguish between progressive
multifocal leukoencephalopathy and other Conditions. The rapid clinical progression
in immunocompromised persons is another distinguishing factor.
Typical symptoms:
Headaches.
Clumsiness and loss of coordination.
Asphasia (loss of language ability).
Memory loss.
Problems with seeing.
Progressive weakness of the arms and legs.
These symptoms depend upon which area of the brain is affected. They progress over
a period of days to weeks, and sometimes months, and in many eventually lead to death
unless the immune system can be reconstituted in time.
PML is a demyelinating chronic condition, in which the myelin sheath covering the
axons of nerve cells is gradually destroyed, impairing the transmission of nerve
impulses.
It affects the white matter, which is mostly composed of axons from the outermost
parts of the brain (cortex).
PML destroys oligodendrocytes and produces intranuclear inclusions.
PML is similar to multiple sclerosis, but progresses much more quickly.
