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Multiple Sclerosis Centers of Excellence

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Determination of MS Subtypes

Overview
MS subtypes arose from the need to have a common language to describe and label the clinical course of MS. Defining the terms used to describe subtypes were important not only to physicians trying to describe what was happening to their patients, but also to researchers. In clinical trials, the more homogeneous the study population, the fewer patients are needed to demonstrate the benefits of a medication.

1996 MS Subtypes Consensus
In 1996 a consensus of MS specialists identified and defined four MS subtypes: relapsing-remitting (RRMS), secondary-progressive (SPMS), primary-progressive (PPMS), and progressive-relapsing (PRMS). These four subtypes guided MS research and clinical practice for many years.

2014 Proposed MS Subtypes Consensus
Recently, a proposed change in MS subtypes provides “refined descriptors that include consideration of disease activity (based on clinical relapse rate and imaging findings) and disease progression.” (Lublin et al. 2014). The two main subtypes proposed (or disease course) are Relapsing-Remitting MS and Progressive MS. The proposed nomenclature includes further delineation of Relapsing MS as Active (clinical relapses and/or MRI activity), or Not Active (no relapses or MRI activity), and Progressive MS as either Active with progression, Active but without progression in the last year, Not Active (but with progression), and/or Stable disease (not active and without progression).

In addition, the subtype of Clinically Isolated Syndrome (CIS) has formally been added with subcategories of Not Active (only one MS-like issue) and Active (once there is more than one issue, CIS is categorized as RRMS).

More information about these newly defined subtypes will be added to this article in the near future. Currently this article will reference the most widely used MS subtype descriptors, which are FDA indicated for DMTs. Look for updated descriptors in the near future.

Relapsing-Remitting MS
About 85% of people who are diagnosed have a pattern of disease that is known as Relapsing-Remitting MS (RRMS). This means that symptoms develop over a few days, remain for several weeks or months, and then resolve either completely or partially.

Secondary-Progressive MS
Over the years, people with RRMS have fewer relapses and have changes in functions that progress between relapses. This type or course of MS is known as Secondary Progressive MS (SPMS), meaning secondary to having RRMS. A person may experience a progression of symptoms over time without relapse. Most people who start with RRMS will change to SPMS over 10 to 20 years.

Primary Progressive MS
A smaller percentage of patients, 15% or less, do not experience a relapse. Rather these people experience a level of disability progression from the onset without any distinct relapses or remissions. This type of disease is called Primary Progressive MS (PPMS).

Progressive Relapsing MS
Progressive Relapsing MS (PRMS) subtype is related to PPMS. There is a clear progression of disease dysfunction from the onset of PRMS, but there are distinct acute relapses that may or may not include recovery. (Note: in the proposed descriptors (Lublin et al.), this category is eliminated.)

MS Subtypes and Research
The use of MS subtypes to select a homogeneous population for research studies has led to most medications being tested using RRMS. This is a reflection of RRMS being the most common subtype, and perhaps the easiest to intervene with existing knowledge, and the easiest to study. Research using RRMS requires fewer patients, simpler outcome measures, less time and, therefore, less financial resources to achieve an answer.

Measuring clinical outcomes in studies of progressive forms of MS have been more difficult. Negative results from studies of progressive forms of MS must be interpreted carefully because they may reflect inadequacies in our ability to measure outcomes, technical difficulties in conducting the study, patients entering the study later in the course of the disease, or differences in the biology of MS subtypes.

Predicting Disease Prognosis with MS Subtypes
Though patients are often concerned about which type of MS they might have, the use of subtypes in predicting prognosis is limited. It should be emphasized that these terms are used primarily for descriptive purposes.


 

Descriptions and graphs of the four recognized subtypes are shown below.

/MS/images/rr.JPG Relapsing/remitting MS is characterized by the abrupt onset of neurological dysfunction occurring over several hours or days. This is followed by recovery, which may be complete (left panel), but more commonly is partial so that there is a residual disability (right panel). Relapses must last at least 24 hours, but commonly last days to weeks. Disability that worsens through a series of attacks is still classified as relapsing/remitting MS.


/MS/images/ArticleImages/sp.JPG Over the years, people with RRMS have fewer relapses and have changes in functions that progress between relapses. This type or course of MS is known as Secondary Progressive MS (SPMS), meaning secondary to having RRMS. A person may experience a progression of symptoms over time without relapse. Most people who start with RRMS will change to SPMS over 10 to 20 years.


/MS/images/ArticleImages/sp.JPG Primary progressive MS slowly worsens from the onset. By definition, patients do not have attacks. Progression may be steady (left panel), or may have periods of faster or slower progression (right panel). There may even be periods of slight improvement. It is the complete absence of attacks that identifies this subtype.

/MS/images/ArticleImages/sp.JPG Progressive/relapsing MS begins like primary progressive, but relapses then develop later in the disease course. Following these relapses, there may be recovery (left panel) or no recovery (right panel). 



For More Information

Defining the Clinical Course of MS-Lublin et al (July 2014)

 

 

Updated: July 2015