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Symptoms of PML (Progressive Multifocal Leukoencephalopathy)

Many Symptoms of PML are Similar to MS Symptoms


Updated July 14, 2014

Tysabri (natalizumab), one of the newer disease-modifying therapies for multiple sclerosis, is, for many people, a wonderful drug. Like all of the medications available, it has its downsides. Probably the "biggie" for Tysabri -– the thing that makes many people pause or even reconsider using this treatment –- is progressive multifocal leukoencephalopathy (PML).

PML is a brain disease caused by the JC virus. It is primarily associated with severely suppressed immune systems, such as in people with HIV/AIDS. In people with MS, PML is linked with Tysabri use, with the risk increasing after two years of treatment.

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 many cases of PML may go undiagnosed for some time because of this confusion.

In order to find out what would cause a doctor to suspect PML, I referred to the article "Progressive multifocal leukoencephalopathy: Epidemiology, clinical manifestations and diagnosis" on UpToDate, a trusted electronic reference used by many physicians and patients. Take a look at what UpToDate has to say, then keep reading. I'll break it down and add in some additional information.

Symptoms of PML: An Overview from UpToDate

"PML usually manifests with subacute neurologic deficits including altered mental status, motor deficits (hemiparesis or monoparesis), limb ataxia, gait ataxia, and visual symptoms such as hemianopia and diplopia. Initial symptoms may vary greatly from patient to patient, depending on the location of their lesions in the central nervous system (CNS) white matter.

Seizures are usually thought to be a manifestation of cortical injury rather than white matter disease. Nonetheless, seizures occur in up to 18 percent of patients with PML, mainly when PML lesions are located immediately adjacent to the cortex."

The Similarities/Differences in PML Symptoms and MS Symptoms

Much like MS symptoms, the number of PML symptoms are widely varied, because they depend on the severity of the damage and which area of the brain is affected. They typically do not occur suddenly, but develop over days or weeks.

The most common symptoms that took people to the doctor to get their PML diagnosis were cognitive and personality changes, as well as noticeable problems with motor function.

Motor deficits: This presents as paralysis or inability to use one body part (monoparesis) or the limbs on one side of the body (hemiparesis). This is often described as progressive weakness or clumsiness.

Visual disturbances: This can be hemianopia, which means that there is blindness in one half of the visual field of one or both eyes. This can be confused with optic neuritis, which is a very common symptom of MS, although MS-related optic neuritis tends to have pain, whereas the vision loss with PML is typically not painful. Diplopia (double vision) may occur with PML, and is also a symptom of MS.

Loss of balance: Many people with MS have balance problems due to impaired proprioception or spasticity. However, PML can cause much more severe balance issues that lead to falling.

Seizures: While seizures are more common in people with MS than in the general population (up to 3% of people with MS vs. less than 1% of the general population), 1 in 5, or 20%, of people with PML experience a seizure, making it a much more common symptom. In many cases, seizures were the first symptom of PML (or at least the symptom that prompted the person to seek medical attention).

Speech difficulties: Aphasia, meaning the inability to understand or use language, is a fairly common symptom of PML. By contrast, the speech difficulties of MS, including dysphasia, dysarthria and dysphonia, are much more mild. Also, unlike PML, comprehension is not usually affected in MS.

Fatigue: While fatigue is mentioned in many sources as a common symptom of PML, it is 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. However, those of us with MS are very familiar with our particular brand of fatigue. If something feels "different" about your fatigue, do not hesitate to contact your doctor.

Confusion or disorientation: While many people with MS are affected by cognitive dysfunction that leads to short-term memory loss or slowed information processing speed, this symptom of PML is much more debilitating and noticeable.

Bottom Line

None of this information is intended to dissuade anyone from taking or considering Tysabri. Indeed, I feel that being armed with information can give people confidence and the tools they need to act to make the right decision and protect themselves from harm, regardless of their treatment strategies.

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. He or she will probably order a lumbar puncture to look for the JC virus in your cerebrospinal fluid, as well as an MRI scan of the brain. Like MS, PML also causes lesions that can be seen on MRI images -– however, they often differ from typical MS lesions in shape, size and location.

It is important that you act quickly to rule out PML. PML damage increases over time, and cases caught quickly can often be treated with good results. (Read more: What is the treatment for Tysabri-related PML?)

Want to learn more? See UpToDate's topic, "Progressive multifocal leukoencephalopathy: Epidemiology, clinical manifestations and diagnosis," for additional in-depth medical information.


Koralnik IJ. Progressive multifocal leukoencephalopathy: Epidemiology, clinical manifestations and diagnosis. UpToDate. Accessed January 2011.

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

Clifford DB, De Luca A, Simpson DM, Arendt G, GIovannoni G, Nath A. Nataulizumab-associated progressive multifocal leukoencephalopathy in patients with multiple sclerosis: lessons from 28 cases. Lancet Neurology. 2010 Apr; 9(4):438-46.

Steiner I. PML: underdiagnosed in patients on natalizumab. The Lancet Neurology; June 2010; Volume 9, Issue 6, Page 564.

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