PML and Tysabri Part 2: Diagnosis of PML
In my previous posts I have discussed Tysabri and the risk of the brain infection, progressive multifocal leukoencephalopathy (PML.) One of the most common and understandable questions asked by patients who are starting Tysabri are about the symptoms of PML. Unfortunately, these are not easy questions to answer.
Since PML is an infection of the brain, it can present with any symptom of brain dysfunction. These include:
- sensory disturbances
- personality changes or cognitive deficits
- trouble speaking
- visual disturbances
- loss of balance or poor coordination
Some of the above symptoms, such as language disturbances or significant personality/cognitive changes, are uncommon in MS except in the most advanced, severe cases. However, for the most part, these symptoms almost perfectly mimic the range of symptoms that people with MS experience. MS, after all, is also a brain disorder.
Additionally, like MS, the symptoms experienced by patients suffering from PML are not likely to be of abrupt onset; in fact, symptoms from PML might actually progress more slowly than those in MS. For these reasons, it is important to investigate whether PML is a possibility in any patient on Tysabri who experiences a change in his or her neurological status. This is especially the case since relapses in MS are uncommon in patients on Tysabri.
The first test to investigate for PML is to order a repeat MRI. Unfortunately, just as the clinical symptoms of PML mimic those of MS, the radiographic appearance of PML might also mimic MS, at least early in the disease state. Both illnesses appear as bright signals in the white matter of the brain. While the changes of PML will eventually become larger and more confluent than the numerous separate lesions of MS, in the early stages of PML the lesions can look identical to MS lesions. If the MRI looks unchanged compared to the previous MRI, however, the odds of PML are very low.
At right is an example of a patient with MS who contracted PML. The large white area in the red circle is from PML, while the other white lesions are from MS.
Most neurologists will order periodic screening MRIs on patients on Tysabri in the hopes of detecting PML on the MRI before it presents clinically. I have personally seen one case of PML connected with Tysabri, and it was detected through a routine MRI before the patient developed overt symptoms. (How often is a routine screening? What are the costs? Does insurance usually cover it?)
Finally, in any suspected case of PML, a lumbar puncture is the next step. The purpose is to try to directly detect the JC virus in the spinal fluid. If the virus is detected, then PML is confirmed. However, if the virus in not detected, PML is not ruled out; it is still possible that the infection is present. Ultimately, a doctor will have to consider a combination of the clinical picture, MRI findings, and lumbar puncture results to decide if a patient has PML or not. If there is any suspicion that a patient has PML, they will need to be treated for it.
I am available via e-mail at email@example.com and will try to answer all questions.