Multiple sclerosis is a complex disease which is difficult to describe and no two cases are identical. We know that it is a neurological disease characterized by clinical symptoms caused by demyelination in the central nervous system. We also know that the majority of the people who develop MS experience relapses, or acute attacks of new or worsening symptoms. Some people, however, experience a more steady progression of disability. Still others experience a combination of attacks and progression.
Accurate descriptions of identifiable MS disease courses are important for communication, clinical trial design and recruitment, prognosis estimation, and treatment decision-making. Standardized descriptions based primarily on clinical aspects of MS were published in 1996 following a survey of international MS experts and consensus reached by the US National Multiple Sclerosis Society (NMSS) Advisory Committee on Clinical Trials in Multiple Sclerosis. These descriptions form the terminology currently used to describe four subtypes (phenotypes) of MS - relapsing-remitting, primary progressive, secondary progressive, and progressive relapsing.
During the past 18 years, much has been learned regarding the pathology of MS including early manifestations of the disease which precede confirmed diagnosis. This increased understanding of MS and limitations in the current terminology used to describe MS prompted a re-examination of the disease subtypes by the International Advisory Committee on Clinical Trials of MS which convened in October 2012. Consensus and recommendations offered by the advisory committee were published online in the journal Neurology on World MS Day, May 28, 2014.
The committee recommends that the core descriptions of relapsing and progressive disease should be maintained, with certain modifications and clarifications. Suggested modifications include assessment of disease activity, as defined by clinical relapses and/or MRI activity (contrast-enhancing lesions; new or unequivocally enlarging T2 lesions assessed at least annually), and clinical evidence of disease progression independent of relapses over a given period of time in patients who have a progressive disease course (PPMS or SPMS).
The following are examples of newly proposed descriptions that consider measures of disease activity. A patient with RRMS who has a new gadolinium-enhancing lesion would be considered to be "RR-active." Conversely, a patient with a relapsing course but no relapses, gadolinium-enhancing activity, or new or enlarging T2 lesions would be "RR-not active." A patient with PPMS with no acute attacks and no MRI activity would be "PP-not active." However, a patient with PPMS who has an acute attack would be "PP-active," replacing the current progressive-relapsing MS definition.
Disease progression could also be used to further classify patients. A patient with PPMS who has not progressed over the past year would be considered to be "PPMS-not progressing." A patient with SPMS who has gradually worsened and has gadolinium-enhancing lesions on MRI would be classified as "SPMS-active and progressing." The committee suggests that use of the term worsening is preferable than the term progressing to describe a patient in the relapsing phase of disease whose disease is advancing due to frequent relapses and/or incomplete recovery from relapses to avoid confusion. The term progression sould be reserved for patients experiencing the progressive phase of MS.
The committee recommends that clinically isolated syndrome (CIS) be officially included as a subtype of MS. CIS has been recognized for years as the first clinical presentation of a disease that shows characteristics of inflammatory demyelination that could be MS, but does not yet fulfill the "dissemination in time" diagnostic criteria for MS. A patient with CIS who experiences another clinical relapse and/or new lesions would be re-classified as RR-active.
However, the committee suggests that radiographically isolated syndrome (RIS) not be considered a separate subtype of MS. A patient who shows inflammatory demyelinating lesions on MRI (perhaps conducted for an entirely different diagnostic purpose), but who displays no clinical signs or symptoms of MS, might be diagnosed with RIS. Follow-up is recommended in patients with RIS.
The committee also suggests that the terms benign MS and malignant MS should be used with caution. These terms have been used to describe severity of disease over time, but are often misunderstood and misused. They are not considered to be distinct MS subtypes. In reading the study, I noted that the terms spinal MS, chronic progressive MS, or end-stage MS, which can cause confusion, are not discussed as being distinct or accurate descriptions of MS.
The committee finally suggests that further research is needed to better define the value of imaging and biological markers in assessing, confirming, or revising MS subtype descriptions. Currently, not enough is known about measures of tissue damage (brain atrophy, evolution of black holes, or retinal nerve fiber thinning) or biological markers (in blood or cerebrospinal fluid) to be used to further distinguish MS subtypes. In addition, the committee suggests that the role of patient-reported outcomes should be studied to evaluate their value in assessing the clinical course of MS.
While improved terminology and classifications are useful in communication among patients, clinicians, and researchers, I wonder how newly-defined courses of MS might be handled by insurance companies when treatment options are considered. Each of the ten FDA-approved disease-modifying therapies used in MS are approved for relapsing forms of MS (which includes SPMS with relapses and PRMS for some). Three therapies (Copaxone, Betaseron, Extavia) are also approved for CIS.
Could the classification of "non-active" disease (meaning no clinical relapses and/or MRI activity) be used to discriminate against patients with MS? Or could "active" disease allow more patients to access disease-modifying treatment?
How would your MS be classified? I believe that my MS which has remained stable over the past few years would be considered RR-non active. However, that classification says nothing about the degree to which I may or may not have recovered from previous relapses. I have a number of residual symptoms which emerge when I am ill, fatigued, or overheated.
Lublin FD, Reingold SC, Cohen JA, et al. Defining the clinical course of multiple sclerosis: The 2013 revisions. Neurology. 2014 May 28. pii: 10.1212/WNL.0000000000000560. [Epub ahead of print]
Emrich, Lisa. "Differences between relapsing-remitting MS (RRMS) and other forms of MS." HealthCentral.com, 1 December 2013. Retrieved from https://www.healthcentral.com/multiple-sclerosis/c/19065/164358/relapsing-forms/
Emrich, Lisa. "What is ‘stage-4’ MS?" HealthCentral.com, 2009. Retrieved from https://www.healthcentral.com/multiple-sclerosis/educationcenter/what-is-stage4-ms.html
Emrich, Lisa. "Beginner’s Guide to MS: Do I have MS? What does it take to get diagnosed with MS?" HealthCentral.com, 1 April 2009. Retrieved from https://www.healthcentral.com/multiple-sclerosis/c/19065/62496/guide/
Emrich, Lisa. "Beginner’s Guide to MS: Multiple Sclerosis Diagnostic Criteria, The History." HealthCentral.com, 23 December 2008. Retrieved from https://www.healthcentral.com/multiple-sclerosis/c/19065/53217/sclero/
Lisa Emrich is a patient advocate, accomplished speaker, author of the award-winning blog Brass and Ivory: Life with MS and RA, and founder of the Carnival of MS Bloggers. Lisa uses her experience to educate patients, raise disease awareness, encourage self-advocacy, and support patient-centered research. Lisa frequently works with non-profit organizations and has brought the patient voice to health care conferences and meetings worldwide. Follow Lisa on Facebook, Twitter, and Pinterest.