PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML)
- Cause: A progressive disease caused by JC virus
- Affected cells: Oligodendrocytes
Since oligodendrocytes are concerned with myelination; PML is associated with multifocal areas of demyelination distributed throughout the brain but sparing spinal cord and optic nerve.
- Oligodendrocytes: Densely staining enlarged nuclei containing viral inclusions
- Astrocytes: Hyperchromatic, deformed, bizarre nuclei containing mitotic figures.
PML is predominantly seen in patients with immunosuppressive disorders: AIDS (80%), hematological malignancies, transplant recipients.
- Focal neurological signs: Aphasia, dysarthria, hemiparesis/ monoparesis, ataxia
- Visual impairment (45%): Homonymous hemianopia
- Mental impairment (38%): Behavioral change, confusion, dementia
- Seizures (20%).
- MRI is the investigation of choice for PML as it is superior than CT and shows classical asymmetric nonenhancing coalescing lesions in white matter located periventricularly.
- PCR amplification of JCV-DNA in association with typical MRI lesion is diagnostic of PML.
- Brain biopsy demonstrates multiple demyelinating lesion in white matter of cerebrum, cerebellum and brainstem.
In most cases, death occurs within 3-6 months from the onset of neurological symptoms and even more rapidly in patients with AIDS.
- Currently, the best available therapy is reversal of the immune-deficient state, since there are no effective drugs that block virus infection without toxicity.
- In the case of HIV-associated PML, immediately beginning ART will benefit most individuals.
- Drugs that are being studies as potential treatment options (still not recommended): Cidofovir and Mefloquine.