
PML when treated with rituximab. Chakraborty S, Open. CC BY NC ND 3.0
Contents
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 travel 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
- Test (antibody) on virus is possible by JVC-ELISA technique, but the tests are (as of 2017) not fully developed for routine use (Stratify JCV, 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
Opportunistic infections, BINDEVEVSSYKDOMMER.no