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What are the differences between CIS, RRMS, SPMS, and PPMS?

What Are the Differences Between CIS, RRMS, SPMS, and PPMS?

Types of MS

In 2013, the International Advisory Committee on Clinical Trials of MS defined four types of multiple sclerosis (MS):

The classification and accurate descriptions are important for treatment decisions, as well as communicating, designing, and recruiting for clinical trials.1

Clinically isolated syndrome (CIS)

CIS is an episode of neurologic symptoms that are caused by inflammation and demyelination in the central nervous system. (Demyelination is the disease process that destroys the covering, the myelin, on the nerve cells. Myelin is important to the communication between nerve cells.) In CIS, the episode last at least 24 hours and may be the first clinical sign of MS, however, not everyone who experiences CIS goes on to develop MS. Researchers have found that when a person with CIS also has lesions on a brain MRI (magnetic resonance imaging) similar to those seen in people with MS, that person has a high risk of developing relapsing remitting MS.1,2

Relapsing remitting MS (RRMS)

RRMS is the most common type of MS, and approximately 85% of people with MS are diagnosed, at least initially, with RRMS. RRMS is characterized by periods of new or increased symptoms followed by periods of remission where there may be partial or complete recovery. Symptoms may completely disappear during times of remission, or a person may have some symptoms that remain. One unique characteristic of RRMS is that there is no evident disease progression during remission periods. During the course of RRMS, the disease can be further classified at different phases as:

  • Active – relapse of symptoms and/or evidence of new lesions on MRI
  • Not active – no change seen on MRI
  • Worsening – an increase in disability after a relapse
  • Not worsening – no change in disability1,2

Primary progressive MS (PPMS)

In PPMS, there is a worsening of neurologic function and an increase in disability from the beginning of symptoms. People with PPMS do not experience the remissions and relapses as people with RRMS do. PPMS can also be classified during the course of the disease as:

  • Active – relapse of symptoms and/or evidence of new lesions on MRI
  • Not active – period of stability without changes seen on MRI
  • With progression – evidence of disease worsening, with or without relapse or changes seen on MRI
  • Without progression – the level of disability stabilizes for a time1,2

Secondary progressive MS (SPMS)

SPMS is usually diagnosed retrospectively. That is, looking back over a person’s history with MS and seeing a gradual worsening after an initial relapsing disease process. SPMS may occur with or without exacerbations during the course of the disease. Most people with RRMS eventually transition to SPMS, but research has not yet identified a specific point at which the disease shifts from RRMS to SPMS. The transition is usually gradual.1,2

Additional research into the types of MS

Researchers hoped to find biomarkers, biological signs of the disease that may be found in blood or spinal fluid, to distinguish between the different types of MS, but to date, there have been no reliable differences that can be found. This continues to be an area of interest. In addition, more research is needed to clearly define and detect MS activity and progression.1

  1. Lublin FD, Reingold SC, Cohen JA, et al. Defining the clinical course of multiple sclerosis: The 2013 revisions. Neurology. 2014;83(3):278-286. doi:10.1212/WNL.0000000000000560.
  2. National MS Society. Accessed online on 3/14/17 at


  • MissNelda
    2 years ago

    As one that has SPMS I can say no, they do not treat the disease, they treat only the symptoms after testing everything to make sure they are making the right choices. I do not believe there is a difference in any of them and they all result in SPMS and PPMS, it is an end stage from what I have read. Yes you get attacks, yes most of the time. You have to watch your stress level and the heat you are around and you can only do about an hour or less of any work around the house, and you are in excruciating pain most of the time and suffer migraines over and over for days most months you will have 1 or 2 good days, then it all starts again, or it leaves for about a month or two. I believe they have to look at it as a genetic disease and study it in that manner, not other manners. These are my opinions if you don’t agree, that is ok, it is what I think.

  • TGN
    3 years ago

    If there are no biological differences or biomarkers that distinguish the different forms of MS, shouldn’t that be telling us something? For example, that there is probably no difference between the forms, especially PPMS & SPMS. Will Ocrevus not be prescribed to SPMS patients based on incorrect understanding? It is likely that progression is present in MS patients from the start.

    Also, can you explain this sentence: “SPMS may occur with or without exacerbations during the course of the disease”? How is that different from RRMS or PPMS? I think that the International Advisory Committee on Clinical Trials of MS has some thinking and explaining to do.

  • Julie
    3 years ago

    About 10 years ago my neuro told me I was PRMS (Progressive Remitting MS). I had never heard of it before. She told me I was progressive but I was still remitting. I was curious about this as I haven’t talked to anyone yet that has been given this label yet.

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