What are the Symptoms of PML?

PML symptoms are variable like MS and can mimic those of an MS relapse.

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Tysabri (natalizumab), a disease-modifying therapy for relapsing multiple sclerosis, is for many people an effective medication, especially when other MS therapies have failed to reduce their disease progression or were not tolerated due to side effects.

That being said, the biggest risk of taking Tysabri— the thing that makes many people pause or even reconsider using this treatment—is the rare potential for developing progressive multifocal leukoencephalopathy (PML).

What is PML?

PML is a potentially fatal brain disease caused by reactivation of the JC virus. It's primarily associated with severely suppressed immune systems, such as in people with HIV/AIDS or certain cancers or autoimmune diseases. In people with MS, PML is linked with Tysabri use.

It's also been very rarely reported (a couple cases) in people with MS who have taken Gilenya (fingolimod) or Tecfidera (dimethyl fumarate). According to the National MS Society, there are too few cases in Gilenya and Tecfidera to determine the risk of PML in people taking these medications.

What are the Symptoms of PML

If you or a loved one is taking Tysabri, understanding the potential symptoms will allow you to be proactive and informed in monitoring for this devastating infection. While the symptoms of PML are variable (just like those in MS) here are some characteristic ones: 

  • Visual disturbances 
  • Personality changes, like emotional liability, and cognitive problems, like difficulties with memory, thinking and dementia may occur and are common
  • Deficits in motor function, especially weakness, and clumsiness, may occur in PML. Paralysis or an inability to use limbs on one side of the body (hemiparesis) may also occur. 

Other symptoms include a loss of balance that may lead to falls, seizures, and problems with speech. While fatigue is a common symptom of PML, it's a particularly challenging one to differentiate from the usual MS-related fatigue.

In addition, fatigue is a common side effect of Tysabri, especially in the first few days after an infusion. That being said, if something feels "different" about your fatigue, do not hesitate to contact your doctor.

How PML Symptoms May Mimic Your MS Symptoms

PML can be a difficult problem to detect right away, as doctors and even patients may mistakenly confuse the symptoms of PML with an MS relapse. Some experts think that cases of PML may go undiagnosed for some time because of this confusion.

Much like MS symptoms, the number of PML symptoms varies widely because they depend on the severity of the damage and the area of the brain is affected. That being said, one clue about PML symptoms is that they typically do not occur suddenly but develop over days or weeks.

Doctors can more definitely differentiate PML from MS by studying a person's symptoms and ordering an MRI scan of the brain. Like MS, PML also causes lesions, but they tend to differ from typical MS lesions in size, shape, and location. In addition, a lumbar puncture to test the cerebrospinal fluid for the JC virus can be used to confirm a diagnosis of PML and to distinguish from an MS relapse or other infection or inflammatory process.

In terms of symptom analysis, one study in the Archives of Neurology suggests that those with PML are more likely to have multiple symptoms whereas a person with an MS relapse is more likely to have a single neurological symptom—of course, this is simply a clue, not a hard and fast rule. 

A Word From Verywell

If you are taking Tysabri and notice any of the above symptoms (or other symptoms that are new or more severe), see your doctor right away. PML is a life-threatening brain infection and warrants immediate treatment.


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

Clifford, D.B., De Luca, A., Simpson, D.M., Arendt, G., Giovannoni, G., & Nath, A. (2010). Natalizumab-associated progressive multifocal leukoencephalopathy in patients with multiple sclerosis: lessons from 28 cases. Lancet Neurology, Apr; 9(4):438-46.

National Institute of Neurological Disorders and Stroke (NINDS). (September 2015). NINDS Progressive Multifocal Leukoencephalopathy Information Page.

National MS Society (August 2015). Case of PML Reported in Person Receiving Gilenya: UPDATED.

National MS Society (July 2015). Case of PML Reported in Person Taking Tecfidera.

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