progressive multifocal leukoencephalopathy (PML)

introduction

a rare, but often fatal demyelinating disease of the central nervous system caused by reactivation of human polyomavirus (the JC virus - named after the patient it was initially cultivated from - John Cunningham)
death can occur weeks to months after onset
~50% of the world's population are infected by the virus by age 20yrs, although most remain asymptomatic
PML results from reactivation of this virus due to immunosupression such as in:
- HIV / AIDS
- lymphoproliferative disorders
- neoplasia / cancer / tumours
- immunosupression following solid organ transplants
- immunosupressant medications such as:
  - cyclophosphamide
  - corticosteroids
  - mycophenolate mofetil
  - monoclonal antibodies (eg. rituximab, natalizumab)

progressive neurologic features over the course of a few weeks
early signs may be cognitive dysfunction such as mental slowness, disorientation, and behavioural changes
motor, gait, visual and sensory disturbances may occur
less common features include seizures and headache

consider PML in any person with progressive neurologic sugns or symptoms who is immunosupressed and has MRI evidence of multiple characteristic lesions
JC virus DNA on quantitative PCR of cerebrospinal fluid (CSF) - but may be false negative early

generally supportive
restore immune capacity if possible eg. cease immunosuppressants
no antiviral agents currently available (2013)
recovery of the immune system can trigger immune reconstitution inflammatory syndrome (IRIS) which may require RX with corticosteroids