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A

Progressive multifocal leukoencephalopathy


Learning objectives

  • Relevant as a stroke mimic
  • Understand what is PML
  • Recognition of PML
  • Treatment of PML

Introduction

  • JC Virus Encephalopathy seen in immunocompromised
  • AIDS-related condition of the brain
  • Oligodendrocytes are the preferred CNS cells infected by JCV
  • JC is a ubiquitous human papovavirus

Aetiology

  • The cause is felt to be JC virus which is a common infection
  • 40-90% of the general population have been exposed to JC virus
  • Usually asymptomatic and trivial unless immunocompromised
  • Infection of oligodendrocytes and demyelination
  • Advanced cancer or bone marrow transplants
  • HIV with very low CD4+ cell counts

Drug Causes

  • Tysabri (natalizumab) Anti- a4 integrin
  • Gilenya (fingolimod)
  • Tecfidera (dimethyl fumarate)
  • Rituximab Anti-CD20 Efalizumab Anti-CD11a
  • Adalimumab Anti-TNF-α
  • Infliximab Anti-TNF-α
  • Etarnecept Anti-TNF-α
  • Ruxolitinib Inhibitor of Janus kinases (JAKs) 1 and 2

Clinical

  • Focal neurology depending on site and size of white matter lesions
  • Weakness, sensory loss, ataxia, brainstem signs
  • Altered cognition, visual loss

Differentials

  • Multiple sclerosis
  • Susac syndrome
  • Progressive multifocal leukoencephalopathy

Differentials in the AIDS patient

  • Toxoplasmosis
  • CNS lymphoma
  • AIDS dementia complex
  • Cryptococcal meningitis
  • HIV encephalopathy
  • Cytomegalovirus (CMV) infection
  • Herpes infections

Investigations

  • FBC, U&E, CRP may be elevated
  • HIV test, syphilis
  • MRI brain shows single or multiple T2 weight lesions in the white matter. Can involve the corpus callosum similar to Glioma or lymphoma
  • LP with PCR for Herpes viruses, JC virus etc. Cell count.
  • Brain biopsy

Management

  • Diagnosis depends on clinical symptoms with MRI and CSF changes and Serology.
  • If HIV and low CD4 start HAART but 10-20% experience immune reconstitution inflammatory syndrome (IRIS) which can cause brain swelling and herniation
  • Cytosine arabinoside (ara-C, cytarabine, Cytosar-Ur), is given through a shunt directly into the brain
  • Studies of the anti-CMV drug, cidofovir, first looked encouraging for treating PML.
  • Some with CD4 > 200 recover without treatment other than anti-HIV therapy
  • May be a role for steroids

Reference


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