Symptoms of PML and Multiple Sclerosis

Recognizing PML Symptoms vs. Those of an MS Relapse

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Progressive multifocal leukoencephalopathy (PML), is a rare but often fatal brain disease caused by the JC virus. This virus is normally held in check by your immune system so that it cannot cause damage.

However, if your immune system is weakened by a disease, such as HIV/AIDS, leukemia, lymphoma, or another cancer, or suppressed by a medication, the virus might reactivate and damage your brain. The brain damage caused by PML can lead to a variety of symptoms.

While PML is very rare overall, it's more of a concern if you have multiple sclerosis (MS) because some immunosuppressant medicines used to treat the disease increase your risk of developing PML.

 Tysabri (natalizumab) appears to be associated with the greatest risk for PML. However, other immunosuppressive MS medications might also pose a risk, including Gilenya (fingolimod), Tecfidera (dimethyl fumarate), Ocrevus (ocrelizumab), and possibly others.

PML Symptoms

MS itself does not increase your risk for PML. But if you or a loved one is taking a disease-modifying medication that suppresses the immune system, familiarizing yourself with the symptoms of PML allows you to be proactive and informed in monitoring for this serious potential complication.

Like MS symptoms, those associated with PML vary, depending on the area(s) of the brain affected.

Symptoms may include: 

  • Weakness, often on one side of the body
  • Impaired thinking ability, which often manifests as confusion and/or memory loss
  • Difficulty speaking
  • Poor coordination, typically experienced as clumsiness or walking difficulties 
  • Visual problems, such as blurred vision or not seeing clearly in a specific area of your visual field
  • Personality changes
  • Abnormal sensations or loss of sensation in an area of your body
  • Seizures, although this is relatively uncommon

PML vs. MS Relapse

The symptoms of PML are often indistinguishable from those of an MS relapse. This is not surprising because both diseases cause demyelination, meaning destruction of the protective substance that surrounds nerves. Loss of this protective substance, called myelin, disrupts the transmission of electrical signals between your brain and body.

Because the symptoms of PML and an MS relapse can be virtually identical, it's challenging to identify PML in the early stages of the disease. That said, the speed of development of new symptoms is a clue that helps differentiate whether they are due to PML or an MS relapse. PML symptoms typically do not occur suddenly but rather develop and progress over days to weeks.

Doctors can more definitively differentiate PML from MS by carefully evaluating a person's symptoms. Because PML is a widespread infection of the brain, it often causes more than one new or worsening symptom, whereas a single such symptom is more likely with an MS relapse. However, this is simply a clue, not a hard-and-fast rule.

Another key way to distinguish PML from an MS relapse is to examine the MRI scan of the affected person's brain.

Like MS, PML causes brain lesions visible on MRI, but they tend to differ from typical MS lesions in size, shape, location, and other characteristics.

A spinal tap to test the cerebrospinal fluid for the JC virus is also used to confirm a diagnosis of PML. Lastly, a brain biopsy is also sometimes performed. 

A Word From Verywell

We at Verywell understand that even the remote possibility of developing PML is a very serious concern when you're taking certain MS disease-modifying medications. If you are on Tysabri, Gilenya, Tecfidera, Ocrevus, or another immunosuppressant medication for MS and notice any new or worsening symptoms, contact your doctor right away.

While these symptoms do not always indicate the development of PML, immediate medical evaluation is necessary because this rare brain infection is life-threatening. Early diagnosis offers you the best chance for a good outcome should you develop PML.

Sources:

Bloomgren G, Richman S, Hotermans C, et al. Risk of Natalizumab-Associated Progressive Multifocal Leukoencephalopathy.N Engl J Med. 2012 May 17;366(20):1870-80.

Greenlee JE. Progressive Multifocal Leukoencephalopathy (PML). In: Porter RS, Kaplan JL, Lynn RB, et al. Merck Manual Professional Version.

Maas RPPWM, Muller-Hansma AHG, Esselink RAJ, et al. Drug-Associated Progressive Multifocal Leukoencephalopathy: A Clinical, Radiological, and Cerebrospinal Fluid Analysis of 326 Cases. J Neurol. 2016; 263(10): 2004–2021.

 National Organization for Rare Disorders. (2015). Progressive Multifocal Leukoencephalopathy.

Wollebo HS, White MK, Gordon J, Berger JR, Khalili K. Persistence and Pathogenesis of the Neurotropic Polyomavirus JC.  Ann Neurol. 2015 Apr; 77(4): 560–570.

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