MS Types: new definitions, new ways of thinking

Once upon a time, there was just a one-size-fits-all way to describe the disease known as multiple sclerosis (MS).  However, it was apparent that there was a wide range of individual courses. Some, but not all patients, suffered attacks.  Some remained relatively stable for many years, while others steadily worsened.  

A big advancement came in 1996 when an advisory committee of the National MS Society published a guideline for categorizing patients into one of four disease types: 

1. relapsing remitting MS (RRMS), 
2. secondary progressive MS (SPMS), 
3. primary progressive MS (PPMS) and 
4. progressive relapsing MS (PRMS).  

RRMS was characterized by intermittent and unpredictable neurological attacks (exacerbations) that frequently left permanent disability.  Functional abilities and disabilities remained stable between such events.  By contrast, SPMS, PPMS and PRMS all demonstrated an unstable, gradually worsening baseline. This could begin from disease onset without ever having attacks (PPMS), proceed from onset with rare attacks along the way (PRMS) or follow a course of RRMS when stability between attacks is lost (SPMS).  

These different types don’t necessarily mean different underlying pathology (the abnormal disease traits in the immune system and nervous system), but it is clear that RRMS has the most inflammatory activity and is the most amenable to our current immune-based therapeutic agents.  This system of categories has helped us to tailor treatments to meet specific populations of MS patients, but this has been to the benefit of RRMS patients, while people with any of the progressive forms of MS have not received an equal amount of research, nor enjoyed the fruits of drug development. 

Recently, this system of MS categories has come under the scrutiny of the medical community.  The U.S. Food and Drug Administration has moved to approve drugs under a more general category of “relapsing forms of MS” which may include any individual who has relapses, whether or not she/he has progression.  

On an international level, a distinguished committee of MS experts led by the very same two authors of the original 1996 definitions (Fred Lublin and Steve Reingold) has proposed a modified system of categorizing people with MS.  This article is open access (http://www.neurology.org/content/46/4/907) if it piques your curiosity.  The proposed scheme is beginning to take hold, reflecting changes in how we think about the disease and also influencing such changes.

The first thing to know about this system is that we have three basic categories.  These are clinically isolated syndrome (CIS), RRMS, and Progressive disease.  CIS describes people who have had a first demyelinating event (such as optic neuritis), but have yet to fulfill the diagnostic criteria for MS. They are “inbound travelers” but not all will ultimately reach the station. RRMS is still based on having a history of clinical attacks with an otherwise stable status. They may worsen episodically, but not gradually as in progressive disease.  RRMS is now further defined as “active” or “not active.”  In this, being “active” is not a good thing.   Active means that the patient is having attack episodes or changes on MRI that represent attacks- new lesions, picked up with one of the MRI methods (with or without gadolinium contrast uptake).  Not active means the patient has no attacks and his/her MRIs are also stable. 

Progressive disease includes PPMS (progressive disability from onset) and SPMS (progressive disability after initial relapsing course).  These differences are “relative rather than absolute,” meaning that they share a lot in common and by implication may be treated in the same way, that is, with similar drugs and other approaches.  Progressive disease may be further defined as “active” or “not active,” acknowledging that exacerbation and MRI events may occur in progressive disease. 

They may also be described as “with progression” or “without progression.”  This acknowledges that some people who have progressive disease can enter a period where their disability level does not change, apparently static neurological function and level of disability. Unfortunately, this gives rise to a sub-category of “progressive disease without progression” which is bound to confuse people. Maybe this system is still a work in progress.  

If you are feeling confused, don’t worry, we’re all finding it a bit confusing. The important things to remember are:

• We are still talking about “relapsing remitting MS,” but are further describing it as “active” or “not active.” These two labels will carry great importance in determining treatments.  
• We can still use “secondary progressive” and “primary progressive” to describe MS, but they are both lumped more closely than before as “progressive disease” and can be further described based on the degree to which they are “active” and “progressing.”  Watch for treatments for “progressive MS” in the near future.
• MRI findings now contribute to the scheme, (active or not active), but progression is based on watching and examining people over time.  There are no lab tests (blood or spinal tap) that contribute to the new scheme, but such tests are evolving and are likely to be included in the future. 
• The system calls for at least an annual assessment of activity and progression based on a clinic visit and believes that an annual brain MRI is useful in RRMS and CIS.  There was no consensus on how frequently to MRI scan people with progressive MS.

To close this discussion, let’s have a quote from Alice in Wonderland: “It would be so nice if something made sense for a change.” We are certainly on our way to making sense of MS.