Tysabri is a dream come true for many individuals with Multiple Sclerosis. Personally, I have opted to take Gilenya (for now), but Tysabri was very tempting when I considered my options after it became apparent that Rebif would not work out for me any longer. However, along with Tysabri’s side effects comes one very sinister danger: PML. One patient on Gilenya has been diagnosed with PML, and it can happen to anyone whether or not they have MS. Knowing that medication (especially newer medications) may bring a risk of PML has frightened us all.
What is it?
PML (Progressive Multifocal Leukoencephalopathy) is a viral disease of the brain. It can be difficult to detect because it mimics MS so closely. However, as the name suggests, damage causd by PML is often gradual rather than seeming like a sudden relapse.
Progressive gradual rather than sudden
Multifocal occurring at multiple locations in the brain
Leuko white matter
Encephalo of the brain
Pathy damage / inflammation
This infection is almost always seen in individuals with severe immune deficiency – AIDS patients, cancer patients, transplant patients, individuals on Raptiva, and individuals taking Tysabri.
PML is fatal to approximately 20% of its victims; however, virtually no data is available to describe the condition or quality of life of the 80% who survive. The damage caused by PML can be massive, leaving survivors extremely disabled. PML is considered, like MS, to be a demyelinating disease – myelin sheath is destroyed in the subcortical white patter, especially in the parietal and occipital lobes. Damage occurs much more rapidly than during the normal course of disease for Multiple Sclerosis. In very rare cases, the infection will be asymptomatic. Symptoms that do occur can be almost anything representative of brain dysfunction including:
- sensory disturbances
- personality changes or cognitive deficits
- trouble speaking
- visual disturbances
- loss of balance or poor coordination
- cognitive deterioration
- alien hand syndrome (not a joke)
Many of these symptoms are already present to some degree in most of us living with Multiple Sclerosis. For that reason and because the onset of symptoms from PML can be slow, there are a few measures neurologists should take to monitor for PML in anyone who may be at risk.
What causes PML?
PML is triggered by the JC virus (the John Cunningham virus) – named for a patient diagnosed with PML in 1971 from whose tissue the virus was first cultured. Cases of PML have been reported in individuals using efalizumab, belatacept, rituximab, natalizumab (aka Tysabri), infliximab, chemotherapy, corticosteroids, and organ transplant drugs. This indicates that drugs which alter the immune system make us more susceptible to developing PML from the JC virus.
The JC virus is very common. As many as 90% of all humans will be infected with this virus during childhood or adolescence. The virus may simply be spread through contaminated water. Samples of the virus are used to trace human migration in our past because genetic variations are geographically specific. Typically we will create an antibody after exposure to this virus, but the virus can be reactivated when the immune system breaks down or is altered.
We become at risk for PML when the JC virus is reactivated.
How can PML be treated?
There are now blood tests for the JC virus. My neurologist has started testing me for this out of an abundance of caution even though I use Gilenya instead of Tysabri. If your blood test indicates that you have the JC virus, you must be closely monitored.
Frequent MRI is standard in monitoring lesions caused by Multiple Sclerosis. PML is also visible on MRI but because it can mimic MS in its early stages, repeating MRI is necessary. Unlike lesions caused by MS, visible PML continues to become larger and more confluent. If MRI results are consistent, it is unlikely that a patient has PML.
A lumbar puncture is necessary if MRI suggests a patient may have PML to attempt to detect the JC virus in the spinal fluid. This confirms PML although a negative result does not mean a patient is safe. At this point, doctors will have to examine MRI, blood tests, disease progression, and any symptoms a patient is experiencing to provide a clinical diagnosis.
If an individual is diagnosed with or suspected of having PML, we can then pursue treatment:
- Some recent experiments have shown promising results with mefloquine. Typically mefloquine is used to treat malaria, but it can also fight the JC virus. While we should not expect a reversal of damage, it may be possible that flooding a patient with this drug may prevent further damage
- Approximately two years ago Cytheris announced that they had successfully treated a patient with PML using CYT107 combined with Cidofovir
- In non-AIDS patients, Cytarabine (a type of chemotherapy) has been shown to stabilize a small portion of PML patients
More research is needed before we consider any of these to be true treatments for PML. There is no cure. Sometimes a patient’s immune system will improve enough to fight off the infection. Sometimes a patient will live with the infection for a long time. Sadly, sometimes the outlook is more bleak than that. Because this is such a dangerous, incurable disease we must focus on prevention and minimizing risk.
Have you or has someone you know been diagnosed with PML or tested positive for the JC virus?