Progressive multifocal leukoencephalopathy

From Ganfyd

Progressive multifocal leukoencephalopathy (PML) is caused by activation of a usually quiescent papovavirus, often JC polyomavirus (JCV) but sometimes BK polyomavirus^[1] in the central nervous system. This is usually associated with overt immunosuppression. Thus associated with:

• AIDS - up to 4% of patients.
• Transplantation immunosuppression typically about 2 years after transplant^[2]
• Immunosuppressive drugs
  • Natalizumab
  • Rituximab - case of onset 4 months after therapy !
  • Fludarabine
  • Tacrolimus
  • Sirolimus^[3]

Clinical Presentation

Often subacute

• Hemiparesis
• Apathy
• Confusion

Death is often within 3 months of neurological presentation. However remission is well described.^[4] and may be associated with antiviral therapy^[5]

Treatment

Non proven but isolated case reports of cytarabine and cidofovir^[6].

Differential diagnosis

• Multiple sclerosis (increasingly important to distinguish given immunosuppressive therapies for this condition)

Aetiology

JC papovaviruses found in up to 70% of humans bind to B lymphocytes and are thus transported through the blood brain barrier where they bind to primary glial and stromal cells. There is some evidence that PML may occur in the recovery phase after immunosuppression when B lymphocytes infected by the virus are actually increasing in number. The virus is active in oligodendrocytes in the condition.

Pathology

• Lesions tend to be localized to cerebral gray-white matter junction
• Scallopping demyelination
  • lacks inflammatory reaction or necrosis
  • oligodendroglial nuclear inclusions at the periphery of demyelination

Diagnosis

• Suspicion by clinical history
• Detection of papovavirus virus
  • Immunohistochemical
  • Ultrastructural demonstration of virions
  • In-situ hybridization of the genome of polyomavirus - can test CSF although some early assays lacked sensitivity.

References