Renaming MS – Newly Released Guide for Clinicians
How many times have you heard that no two cases of Multiple Sclerosis are the same? You don’t really have to answer that question because we all know the answer --- a lot!! It has always left me a bit puzzled how if we all are so unique in our disease, how can they take all of us and fit us into a few narrowly defined categories.
In 1996, a group of MS researchers and clinicians developed the listing of sub-types of MS to use to classify our types of MS1; these common names were based on the physical characteristics they could observe, known as phenotypes. The identified phenotypes were Relapsing Remitting MS (RRMS), , Secondary Progressive MS (SPMS), Primary Progressive MS (PPMS), and Progressive Relapsing MS (PRMS).
Stop for a moment and think about what type of MS your doctor may have said you have, and then reflect on how often you wonder if that is really your particular form of this disease. I often wonder about my RRMS because I have only had a few dramatic episodes of relapses over many years, leaving me to wonder if maybe it could be SPMS or PPMS. It turns out doctors and researchers have wondered the same thing about MS and how could they better describe or classify our disease states.
Recently, a group of over 30 MS specialists, including Fred Lubin, MD, the lead researcher for the 1996 study, took another look at the MS phenotypes in Defining the clinical course of multiple sclerosis: The 2013 revisions2 , and revised these descriptions for further clarity.
I encourage everyone to read this scientific paper to see how these changes might affect their own MS label. The following is a very brief summary of these changes and why they were necessary-
Why do this review to identify phenotypes of MS?
- To give clinicians clearer characteristics to use for identifying and treating different types of MS
- To review and clearly state what is now known about MS compared to that knowledge in 1996
- To establish clearer phenotypes to use in developing clinical trials and seeking approval for drug use according to those phenotypes
Key Points the reviewers agree on
- Eliminate the label for clinical course of Relapsing Progressive MS (RPMS) because it appears it is a disease that overlaps other phenotypes and not a distinct one of its own
- Clinically isolate syndrome (CIS) should be included in the MS clinical descriptions. CIS is when there are clinical signs that a person has an inflammatory disease process going on that could be MS but doesn’t fully meet the McDonald Criteria of dissemination in space and time.
- Radiologically isolated syndrome (RIS) occurs when there are signs of disease in the MRI imaging of the brain that are highly suggestive of MS, but there are no other clinical signs to go with this information. The consensus is there is not enough evidence in RIS to classify it as an MS phenotype.
- When RRMS become SPMS is still hard to know and this area deserves further research.
- Previously, it was thought that PPMS is a separate disease but this report clearly states that it is part of the progressive MS group and should be considered one of the MS phenotypes.
Modifying characteristics of different phenotypes
Both relapsing and progressive MS should be distinguished with the use of the modifiers disease activity and/or disease progression. Each of these come with a separate set of recommendations as to how the neurologists should test and follow disease activity and disease progression.
Disease activity can be seen through MRI imaging where new or enhancing lesions may be found or relapses that are found through clinical exam. At a minimum, for people with RRMS, they suggest a brain MRI should be done every year, to look for disease activity. They do not recommend annual imaging of the spine unless the person is showing symptoms that are associated with spinal lesions. The results of this imaging would help to determine if the disease were active. RRMS patients who don’t show signs of new lesions, change in existing lesions, or enhancing lesions, would be considered not active RRMS.
The review group did not agree on how often people with PPMS should have MRI’s performed to look for disease activity and instead relies more on the clinical exam. They note that imaging should be done if there was an indication of disease activity.
The second modifier is disease progression, which refers to the change of disability. Observation of disease progression is done clinically by the doctor, and they suggest at minimum an annual exam to check disease progression for anyone with SPMS or PPMS. There are two classifications for progression - active progressing and not progressing and they note progression can occur over a short or long period of time and may be harder to identify.
MS disease modifiers by phenotypes
This is a summary of the descriptions clinicians are now encouraged to use:
- CIS Active
- CIS Not Active
Relapsing Remitting MS (RRMS) could be
- RRMS Active
- RRMS Not Active
Secondary Progressive MS and Primary Progressive MS share the same modifiers. Those modifiers can be:
- Active and with progression
- Active but without progression
- Not active but with progression
- Not active and without progression (stable disease)
What’s in a word?
This review group also recommends changing the common use of a few words so there can be better understanding of their meaning and eliminate confusion. Sustained disability should be changed to confirmeddisability. They make the point that sustained would indicate a permanence and with MS, our level of disability can come and go. Nothing is permanent with MS. The other word they would like to be used more selective would be the term progression – they cite the example of disability progression often used when making notes about our performance on the Expanded Disability Status Scale (EDSS), and suggest in its place the word worseningbe used. Their recommendation is the word progression or any forms of the word should only be used when talking about progressive forms of MS.
Areas of interest recommended for further research
The group could not agree on how they might use Patient Reported Outcomes (PRO) to indicate changes in the disease. This is disappointing because we know our own bodies best, and I believe PROs belong somewhere in the research models. To their credit, though, the study does say this should be investigated further.
Clinical studies will sometimes use brain volume (brain atrophy) as an assessment tool for efficacy of a drug or other interventions, but to date there are no standard ways doctors can apply this knowledge to the patient in a clinical setting. There is a correlation to disability and atrophy and developing these tools will be useful.
Research is in the very early stages of learning how biomarkers derived from either blood serum or cerebral spinal fluid (CSF) translate into the different MS phenotypes and the need for further development is mentioned in their study.
Things in the study that make me shout ‘hurrah!’
Without any doubt, the study say that BENIGN MS is not a phenotype. They also say malignant MS is not a phenotype. Their recommendation is because of the misuse and misunderstanding of these terms, and neither of these words should be used without careful consideration. Have you read questions from people wondering what it means that they have ‘benign ms?’ I have seen this diagnosis many times, and along with that always comes the refusal to treat the person with any of the disease modifying therapies because their disease is benign. The study clearly states the only way to know if MS is benign is retrospectively – in other words, only once we are dead can they figure out if our MS truly did not harm. No one should be forced to take that gamble and be refused treatment because their MS is benign. This is such good news to see in writing that I have to repeat it – There is no such thing as Benign MS!!!
The other moment in reading this study that made me smile is the continued recommendation that “the diagnosis of MS should be made on clinical grounds with input from imaging and paraclinical studies, where needed.” In other words, as I have said more than once- a diagnosis of MS can be made by a neurologist depending on our symptoms and history and does not require MRI evidence. That’s how it used to be done before MRI machines were readily available. We know that often the disease is active at a level that can’t be seen by our current MRI technology and software, and doctors can’t just rely on MRI images – they have to use their skills to diagnose MS
In summation to this study, the author writes:
“As we proposed to do in 1996 with the original MS phenotype descriptions, we hope that these modifications will serve to better characterize patients with MS and provide a framework for both clinical research and ongoing clinical care. “
Hopefully you find the ideas in this new classification as promising for positive change as I do. Having a common understanding of the phenotypes of MS is essential to moving forward with research and our personal care.
Wishing you well,
Have you ever experienced any of the following financial struggles due to your MS?