Diagnosis of Tysabri-Related PML in Multiple Sclerosis

Symptoms, MRI, and Lumbar Puncture to Diagnosis PML

Doctor preparing patient for MRI
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Progressive multifocal leukoencephalopathy (PML) is a dangerous brain disease caused by the JC virus. This virus normally causes no symptoms when it infects a person, eventually lying dormant within their body. But when a person's immune system weakens (as in AIDS, lupus, or certain cancers), the virus can become reactivated, infecting the cells that make myelin (nerve coverings) -- this is the biology behind PML.

 

The importance of PML in MS is that it's a rare side effect of some disease-modifying therapies -- most notably, Tysabri (natalizumab). There are also a couple reported cases of PML in people with MS who have taken Gilenya (fingolimod) or Tecfidera (dimethyl fumarate).

Diagnosis of this potentially fatal disease requires a thorough and rapid evaluation by a doctor including a detailed history and physical examination, an MRI of the brain, and a lumbar puncture.

Testing for the JC Virus in the Cerebrospinal Fluid

In order to diagnose PML, a doctor will perform a lumbar puncture to analyze the cerebrospinal fluid (CSF) for the presence of the JC virus. This is done by performing a polymerase chain reaction (PCR) test on the CSF to see if the DNA of the JC virus is present.

The results of the PCR test to look for JC virus in the cerebrospinal fluid will be combined with clinical findings (symptoms of PML) and MRI results to arrive at a diagnosis.

MRI to Diagnose PML

A magnetic resonance imaging (MRI) scan of the brain will be ordered. On an MRI, PML usually shows up as many small, separate T2-weighted lesions. They may eventually join to form one large lesion.

Your Symptoms to Diagnose PML

Your doctor will want to know exactly how you have been feeling and when your new symptoms started.

It's important to be precise and detailed in your description. PML symptoms are variable but may include a change in thinking and personality, loss of coordination, vision problems, worsening weakness of the arms or legs, headaches, or seizures. 

Sometimes it can be challenging to distinguish symptoms of an MS relapse from PML. One clue, according to a 2009 study in the Archives of Neurology, is that a person having an MS relapse tends to have one primary symptom, whereas people with PML tend to have multiple symptoms. 

Brain Biopsy to Diagnose PML

If a person is on Tysabri, tests positive for the JC virus with a PCR CSF test, shows symptoms of PML, and has an MRI scan with findings consistent with PML, it's likely that the doctor will treat for PML. Rarely though, a brain biopsy is performed.

A brain biopsy is the removal of tiny pieces of brain tissue to use in the diagnosis of PML. The pieces of tissue are examined for the JC virus.

A brain biopsy is the "gold standard" of diagnostic tests for PML.

However, it does carry risks, including death.  In addition, the PML lesions may be impossible to reach to get a biopsy sample. Needless to say, this is not a popular procedure with patients or doctors, nor one that is used except in the most extreme of circumstances, in order to rule out other diseases. In the case of a person with MS who is on Tysabri, this is less of an issue than in a person with HIV/AIDS -- as the number of diseases that could mimic PML (toxoplasmosis, cryptococcal meningitis, or AIDS dementia complex) are more likely.

Bottom Line

If you begin to have any unusual or worsening symptoms while on Tysabri, contact your doctor immediately. Don't assume that it is "just an MS relapse" or paroxysmal symptoms. Get checked out as soon as possible. The sooner the treatment for PML is begun, the better your chances for survival.

Sources:

Boster A et al. Progressive multifocal leukoencephalopathy and relapsing-remitting multiple sclerosis: a comparative study. Arch Neurol. 2009 May;66(5):593-9.

Clifford DB et al. Natalizumab-associated progressive multifocal leukoencephalopathy in patients with multiple sclerosis: lessons from 28 cases. Lancet Neurol. 2010 Apr;9(4):438-46.

National MS Society (August 5th 2015). Case of PML Reported in Person Receiving Gilenya: UPDATED. Accessed February 1st 2016.

National MS Society (July 24th 2015). Case of PML Reported in Person Taking Tecfidera. Accessed February 1st 2016. 

PML Consortium. Healthcare Professionals: What is PML? Accessed February 1st 2016. 

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