PML when treated with rituximab. Chakraborty S, Open. CC BY NC ND 3.0

Definition

JC (John Cunningham) virus (JC virus, JCV) is a polyoma virus (related to BK virus). It causes Progressive multifocal leukoencephalopathyi (PML) (see below) which is one demyelinating disease (may resemble MS) in people with a weak immune system, for example during anti-rheumatic treatment with rituximab (MabThera, Rixarthon). Primary infection is likely to occur via respiratory tract and mouth. The virus is latent (not active) to 30-70% of healthy individuals.

• In rheumatic disease and impaired immune system, the virus in the body can become active, for example, by Systemic Lupus Erythematosus (SLE) og GPA / Wegener, especially after treatment with rituximab or other treatment that weakens the immune system equivalent
• Particularly vulnerable are people with the neurological disease Multiple Sclerosis (MS) who gets treatment with natalizumab (Tysabri). The risk is estimated at approximately 4 / 1000 treated cases
• HIV infection is the largest risk factor and constitutes 80% of cases
• Malignant cancer in blood is a third risk factor and constitutes approx. 10%
• Other viruses that can be activated similarly are Cytomegalovirus (CMV), herpes simplex, varicella / herpes zoster

Occurrence

• PML incidence (prevalence) is 1: 200.000 but almost only in immunosuppressed individuals
  • Low number lymphocytes (especially T cells) (a subset of white blood cells) over time is risk factor

Disease Cause

• Reactivation of JC polyoma virus, most often when the immune system is impaired
• Viruses migrate to the brain where the disease develops

Symptoms

• Cognitive problems (concentration, memory, learning ability, communication)
• Coordination difficulties (balance, perform coordinated movements)
• Paresis (paralysis), field of vision loss
• It is not common with fever or other typical signs of infection

Diagnosis

• New neurological symptoms should suspect PML
• MRI of the brain
  • Many scattered small or large changes in white matter that usually do not take up contrast agent (unlike inflammatory areas)
  • The lesions can sit anywhere (large brain, small brain, brain stem, but most often subcortical. The changes may resemble those seen MS
• PCR examination from CSF can detect JC virus. The amount of viruses can be low. It is recommended to examine at least 1ml fluid
• Brain biopsy ensures the diagnosis
  • Histopathology (tissue sample, biopsy): Enlarged oligo-dendroglial cell nuclei at the boundary of demyelination and JC virus can be detected
• Blood tests
  • Virus testing is possible by JVC-ELISA technique, but the tests are (per 2017) not fully developed for routine use (StratifyJCV, Biogen)
  • Examination of immune status with counting of CD4 and CD8 positive T lymphocytes is recommended.

Differential diagnoses (similar conditions)

• Epstein-Barr virus infection
• HIV infection with brain manifestation
• Lymphoma with brain manifestation
• Multiple Sclerosis (MS)
• PACNS (primary CNS vasculitis)
• Reversible posterior leukoencephalopathy
• Varicella zoster infection with brain inflammation

Treatment

• Stop immunosuppressive treatment
• Medications are considered to be removed from circulation by plasmapheresis
• Immune Reconstitution Inflammatory Syndrome (IRIS) As a complication treated with corticosteroids
• Of antiviral agents (interferon, ciclofovir, cytarabine), it is only cytarabine that works, but comes poorly to the CNS (brain and spinal cord).
• Mefloquine is an antimalaria drug that may have effect

Medical prognosis

Severe disease, 20XNXX% dies during the first few months. Many of those who survive get permanent damage (reference: Adang L, 2015)

Literature

• Alstadhaug KB, 2017 (Tidsskr Nor Legeforen)
• Molloy ES, 2017
• Meuse RPPVM, 2016

Opportunistic infections, BINDEVEVSSYKDOMMER.no

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