Differences Between Relapsing Multiple Sclerosis and Other Forms of MS

Patient Expert

Multiple sclerosis (MS) is a disease of the central nervous system, comprised of the brain, spinal cord, and optic nerves. MS is called a demyelinating disease because immune cells in the body attack the myelin sheath (the fatty substance which surrounds and protects nerve fibers) that then become damaged. It is damage to nerves and brain matter that causes the symptoms of MS.

MS is not a disease that follows a standard disease course, identical from person to person. However, the disease does present with certain patterns and characteristics which help neurologists classify the type of MS a person may have.  In general, MS can be divided into relapsing forms of the disease and progressive forms of the disease. Note that some forms of MS can have both relapsing and progressive features.

The four commonly accepted phenotypes (forms) of MS are:

  • Relapsing-remitting MS (RRMS)
  • Secondary-progressive MS (SPMS)
  • Primary-progressive MS (PPMS)
  • Progressive-relapsing MS (PRMS)

Relapsing-remitting MS (RRMS) is the most common type of MS affecting approximately 85% of MS patients at time of diagnosis. RRMS is characterized by unpredictable episodes, called relapses or exacerbations, of acute worsening of neurologic function which may involve new symptoms or a worsening of existing symptoms. With RRMS, relapses are typically followed by periods of partial or complete recovery, or remission, giving this form of the disease its name: relapsing-remitting MS. More women than men are diagnosed with RRMS, often between the ages of 20 and 40.

Persons with RRMS can experience residual symptoms between relapses, and may never return to their original baseline of neurologic function prior to diagnosis, but they do not typically experience chronic worsening (progression) of the disease between relapses. The majority of persons diagnosed with RRMS will experience a transition into the secondary-progressive form of the MS (SPMS), as fewer relapses and remissions occur while increased disability accumulates.

Benign MS is a subset of RRMS which is characterized by very mild and infrequent relapses. Recovery from attacks is complete without accumulated worsening of neurologic function. Approximately 15-20% of people with MS have this form of the disease. Benign MS can only be identified when there is minimal disability 10-15 years after disease onset and tends to be associated with less severe symptoms at onset.

Secondary-progressive MS (SPMS) is the only type of MS which can be considered a “next stage” form of the disease in terms of disease progression.  SPMS is characterized by a chronic steady worsening of the disease, with or without occasional relapses, incomplete remissions, or plateaus in progression. Before the use of disease-modifying therapies (DMTs), approximately 50% of people with RRMS developed SPMS within 10 years and 95% within 25 years. Long-term data is not yet available to determine the extent to which early treatment with disease-modifying therapies (DMTs) may significantly delay or limit this transition.

Primary-progressive MS (PPMS) is relatively rare, affecting approximately 10% of MS patients at time of diagnosis. PPMS is characterized by slowly worsening neurologic function from disease onset with occasional plateaus or minor improvements. The rate of disease progression may vary over time. Patients with PPMS do not experience distinct relapses or remissions. Primary-progressive MS generally appears in people older than 40 and affects men and women equally.

Progressive-relapsing MS (PRMS) is also relatively rare, affecting approximately 5% of MS patients. Like PPMS, primary-relapsing MS is characterized by a steady worsening of disease from onset while patients may experience the occasional relapse. Persons with PRMS may or may not experience some recovery, but not complete remissions. The main difference between RRMS and PRMS is the chronic worsening or disease progression between relapses.

How is relapsing-remitting MS different than other forms of MS?

  • RRMS is the most common form of MS and is characterized by acute relapses, followed by periods of partial or complete remission and stable disease activity.
  • While the majority of MS patients are initially diagnosed with RRMS, it may take time and observation to determine precisely which form of MS a person has if it is other than relapsing-remitting MS.
  • Most of the current disease-modifying drugs are indicated (i.e., FDA approved) for relapsing forms of MS. Researchers are working to develop effective treatment therapies for progressive forms of MS.
  • On magnetic resonance imaging (MRI) scans, RRMS is associated primarily with inflammation and active, or gadolinium-enhanced, lesions which indicate a temporary break in the blood-brain-barrier. Progressive MS is associated more with brain atrophy and “black holes,” or lesions which show permanent nerve damage.

Read the ‘Disease Courses in MS’ edition of MS in Focus magazine published by the Multiple Sclerosis International Federation (MSIF) for more information.

New Ways to Define and Categorize MS Published in 2014

Description of these four forms 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. 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 recommended 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).

Examples of new descriptions of MS based on disease activity:

  • RR-active: patient with RRMS who shows evidence of disease activity, such as a new gadolinium-enhancing lesion
  • RR-non active: patient with RRMS without recent relapses, gadolinium-enhancing activity, or new or enlarging T2 lesions
  • PP-active: patient with PPMS who has an acute attack (replacing the current progressive-relapsing MS definition)
  • PP-non active: patient with PPMS with no acute attacks and no MRI activity* ** SP-active:** patient with SPMS who has an acute attack (currently described as SPMS with relapses)

Examples of new descriptions of MS based on disease progression:

  • PP-not progressing: patient with PPMS who has not progressed over the past year* ** SP-active and progressing:** patient with SPMS who has gradually worsened and showed gadolinium-enhancing lesions on MRI
  • RR-active and worsening: a patient in the relapsing phase of disease whose disease is advancing due to frequent relapses and/or incomplete recovery from relapses

The committee recommended 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 suggested 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.