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Here is My Question:

I am concerned of the risk of the onset of progressive multifocal leukoencephalopathy (PML) over the long-term. I was prescribed Tysabri for 8 months, than stopped after a flare-up which lead me to be hospitalized & a round of steroids. 

I was than switched to Tecfidera & after a year, the standard blood work resulted in "concerns" by my specialist. 

Additional blood work after the JCV test, I was found positive. So no new generation DMDs will be prescribed by my specialist due to these concerns. My concern is even though I have stopped using such, given the fact I am positive for the JCVirus, is there a risk that has been put into action which could lead to PML down the road? 

I was told once by my specialist once that these new DMDrugs could put these "side effects" into play either on the 1st dose or the 20th - no one knows for sure, as they are new drugs & not in use long enough to know the long-term impacts.
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I know I may get back the same answer but maybe others may have researched this further. I know the prognosis is not good if you do get such, but how long must one consider this hurdle & continue to watch for signs. Should I continue to have my blood work monitored?

Thanks for any help!


Answer:
​​I would really encourage you to read some of information on our website concerning the risk of PML (just type in "PML" in the search box in the upper right corner on this page), because most of the statements and assumptions mentioned in your question are incorrect. Let me briefly summarize for you.

1. A positive JCV antibody test is a risk factor for the development of PML on Tysabri therapy ONLY. It is not a risk factor for PML on other disease modifying therapies, probably because the risk of PML on other disease modifying therapies is so low.

2. No one has developed PML more than 6 months after stopping Tysabri. It is assumed, for good reason, that most people diagnosed with PML after stopping Tysabri probably developed the PML during the Tysabri treatment period. The PML in these cases was only detected several months later when it became symptomatic.

3. The risk of PML on Tysabri therapy does not become significant until a person has been on Tysabri for more than 2 years. This risk is partly dependent on the titer or amount of JCV antibodies measured in your testing. Those with a JCV antibody index > 1.0 have a higher risk of PML after 2 years of therapy. Remember, the risk of PML in the highest risk patient after 2 years of therapy is still only 1 in 100 or 1 percent. This is a pretty low risk, and a risk that many highly active MS patients will take if other options have not been effective. It is increasingly recognized that diligent clinical and MRI monitoring in high risk patients can detect PML early (presymptomatic) with very good outcomes after stopping Tysabri.

4. The risk of PML on Tecfidera and other DMTs is exceedingly low. There are fewer than 10 reported cases of PML on tecfidera or related compounds over the past 20 years. The only known risk factor for PML on Tecfidera is a sustained lowering of the absolute lymphocyte count below 500 to 600. This is why we recommend discontinuing Tecfidera if blood testing over several months reveals a sustained lowering of the absolute lymphocyte count to these low levels. As with Tysabri, it takes a long time for PML to develop while receiving therapy with tecfidera unless your are immunocompromised when you start on treatment. Within several weeks or months of stopping tecfidera, your lymphocyte count should return to normal and your risk of PML should become negligible.

Ultimately, the best therapy for you will depend on the stage of your disease and your risk factors for disease progression. If you are considered a person at high risk for significant MS disease progression over the next 5 years, you require highly active therapy. These therapies have some risks but these risks often pale in comparison to the risks associated with progressing disease.

Your MS doctor may consider you a low risk for getting significantly worse in the next 5 years. If this is the case your may simply benefit from an injectable therapy or Aubagio . If he considers you high risk, then you should consider an intermediate (Tecfidera or Gilenya) or highly active (Tysabri, Lemtrada, Rituximab) therapy. If you have a difference of opinion on this subject, you may benefit from a second opinion to clarify your situation.

Good luck

Revere (Rip) Kinkel MD
Director of the Multiple Sclerosis Program
Professor of Clinical Neurosciences
University of California San Diego

Here is My Question:
I have neuropathy pain, but I can still walk. I can't take very long walks like hours but in general walking is not an issue. Steep hills or stairs become a bit harder but I can still do it. I do feel pain in my leg if I over did it with anything using my leg. As I was diagnosed with MS three yrs ago,I am now worrying if one day I will not be able to walk. I try to stay positive and active and think it will be okay,till my husband made a comment that my walking is not so great.To be honest my walking is not so bad, it's just the pain I get after or during sometimes. Will my walking continue to get worse? I am 44 yrs old and have also walked a lot....and still walk but depending on the day or heat.

​Answer:
This question is common among patients with MS and can be quite anxiety provoking.  As I read your question, you refer to neuropathy pain.  Paresthesias (or abnormal sensory symptoms) can be painful in MS and can certainly be brought out by exertion and heat (or made worse by this).  It is really impossible for me to determine if your symptoms are due to this or something else (for instance, a
musculoskeletal problem).

You are correct that pain can influence your walking mechanics (and that may be what your husband is seeing).  Once again, I cannot tell. That would need to be evaluated by your neurologist.

I would encourage you to look at the "more" tab on the Healthcare Journey website and then select "symptoms" which will bring up a list that may apply to your situation.  There is a lot of good information here that can help calm the anxiety around MS symptoms.

As always, follow-up with your neurologist who can monitor for signs of progression (to determine if the MS is still "inactive").

A. Scott Nielsen, MD MMSc
Multiple Sclerosis Specialist
Department of Neurology
Kaiser Permanente Southern California

Here is My Question:

I'm an elderly urban female with a childhood history of pertussis, histoplasmosis, and lots of pneumonia.

Neuro symptoms at eighteen began with permanent severe fatigue, mild muscle soreness, and permanent loss of driving reaction time.

Two years later--trigeminal neuralgia. Eight years later--two incidents of idiopathic (three week) hearing loss years later--two year disorientation. Permanent stiff neck. Hand tingling. Increasingly marked walking difficulty. 

Recent difficulty producing speech sounds and (oddly) hearing speeded up speech on electrical devices. (I'm using subtitles.) When I read and speak, the rhythm sounds like metrics now. One online site said it's MS or a brain tumor. I had a clear brain scan two years ago and have scheduled a Tesla 3 scan for Early November. 

My internist suspects MS (once diagnosed by a vascular specialist)" but with no examination the neurologist said one in a million chances lesions wouldn't have on the previous (two year old) scan. His 'exam' was having me shut my eyes without falling. He strongly suggested CFS, but the only symptom I have on the CFS llists is fatigue. No 'brain fog' problems. No lymph node swelling, etc.

Opinion?


Answer:
​​It would be most unusual to experience MS for many decades without developing abnormalities on MR imaging. That being said, I am often told that an imaging study is normal or only reveal non-specific white matter hyperintensities, only to find on personal review that the MRI is anything but normal.

There is also a strong possibility that this is not MS. The only symptom you experienced that is specific for MS is the Trigeminal Neuralgia. This is also frequently misdiagnosed and turns out to be migraine or trigeminal autonomic cephalgia or atypical facial pain.

I would suggest seeing an MS specialist if you are concerned. After so many years, if you have MS it is certainly a relatively mild form of the disease; but I can certainly understand your interest in trying to understand the symptoms you’ve experienced off and on for so many years.

Revere (Rip) Kinkel MD
Director of the Multiple Sclerosis Program
Professor of Clinical Neurosciences
University of California San Diego