Multiple Sclerosis (MS)

Multiple sclerosis (MS) is an autoimmune disease affecting the brain and spinal cord, characterized by immune-mediated demyelination and axonal damage.1

Although there is uncertainty around disease prognosis and progression, the International Advisory Committee on Clinical Trials of MS defines 4 main disease courses in MS.2 These are: clinically isolated syndrome, relapsing-remitting multiple sclerosis, secondary progressive multiple sclerosis, and primary progressive multiple sclerosis. A fifth type, radiologically isolated syndrome, is defined by incidental MRI findings in the CNS that are highly suggestive of MS even though the patient is not experiencing symptoms of the disease. 

Clinically Isolated Syndrome

Clinically isolated syndrome is defined as the first episode of neurologic symptoms lasting at least 24 hours.3 It is caused by inflammation or demyelination in the brain and spinal cord, and is divided into 2 subtypes: monofocal and multifocal. Monofocal clinically isolated syndrome is characterized by a single neurological symptom caused by a single lesion. In multifocal clinically isolated syndrome, there are multiple symptoms caused by multiple lesions. Partial or complete recovery usually follows these episodes in both cases.

Clinically isolated syndrome may or may not progress to other courses of MS. Research suggests there is a 60% to 80% chance that a patient will develop MS in the future if lesions are detected in their brain by MRI. The chance of developing MS following clinically isolated syndrome is 20% if MRI does not detect MS-like lesions in the brain.4

Early treatment can delay the transition from clinically isolated syndrome to MS for people at high risk.5

Learn more about Clinically Isolated Syndrome.

Relapsing-Remitting MS

Relapsing-remitting multiple sclerosis is the most common disease course, with 85% of patients having this form at the time of diagnosis.6 The disease type is characterized by exacerbations caused by inflammatory attacks on the myelin sheath followed by periods of partial or complete recovery or remission. Periods of relapse can range from a few days to a few months. Remission periods can last months or years.7

Relapsing-remitting MS can be active or not active and worsening or not worsening. Active relapsing-remitting MS is characterized by relapses and/or evidence of new MRI findings. Worsening relapsing-remitting MS is characterized by a confirmed increase in disability following a relapse.6

This course of the disease is 2 to 3 times more common in women than in men.8 

Learn more about Relapsing-Remitting MS.

Secondary Progressive MS

In some instances, the relapsing-remitting form of the disease progresses to secondary progressive MS, which is characterized by a progressive worsening of neurologic function over time.9 Like relapsing-remitting MS, secondary progressive MS can also be active or not active, and with progression or without progression.

In active secondary progressive MS, patients experience relapses and/or there is evidence of new MRI activity during a specified period. In secondary progressive MS with progression, there is evidence of disability accumulation over time, with or without relapses or new MRI activity. 

Research has shown that 50% of patients diagnosed with relapsing-remitting MS transition to secondary progressive MS within 10 years, and 90% transition within 25 years.10

Learn more about Secondary Progressive MS.

Primary Progressive MS

Primary progressive MS is characterized by worsening neurologic function without prior relapses or remissions.11 This form of disease course can also be active or not active and with or without progression. 

Patients with primary progressive MS can experience brief periods of stable disease with or without relapse or new MRI activity. They can also experience periods of increasing disability with or without new relapses or lesions.

Primary progressive MS affects men and women equally.12 

Learn more about Primary Progressive MS.


  1. Podbielska M, Banik NL, Kurowska E, Hogan EL, et al. Myelin recovery in multiple sclerosis: the challenge of remyelination. Brain Sci. 2013;3(3):1282–1324. doi:10.3390/brainsci3031282
  2. Lublin FD, Reingold SC, Cohen JA, et al. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology. 2014;15;83(3):278–286. doi:10.1212/WNL.0000000000000560
  3. Clinically isolated syndrome (CIS). National Multiple Sclerosis Society. Accessed May 25, 2021.
  4. Marcus JF, Waubant EL. Updates on clinically isolated syndrome and diagnostic criteria for multiple sclerosis. Neurohospitalist. 2013;3(2):65-80. doi:10.1177/1941874412457183
  5. Kappos L, Edan G, Freedman MS, et al. The 11-year long-term follow-up study from the randomized BENEFIT CIS trial. Neurology. 2016;87:1-10. doi:10.1212/WNL.0000000000003078
  6. Relapsing-remitting MS (RRMS). National Multiple Sclerosis Society. Accessed May 25, 2021.
  7. Types of MS. MS International Federation. Accessed May 25, 2021.
  8. Goldenberg MM. Multiple sclerosis review. P T. 2012;37(3):175–184.
  9. Secondary progressive MS (SPMS). National Multiple Sclerosis Society. Accessed May 25, 2021.
  10. Gross HJ, Watson C. Characteristics, burden of illness, and physical functioning of patients with relapsing-remitting and secondary progressive multiple sclerosis: a cross-sectional US survey. Neuropsychiatr Dis Treat. 2017;13:1349–1357. doi:10.2147/NDT.S132079
  11. Primary progressive MS (PPMS). National Multiple Sclerosis Society. Accessed May 25, 2021.
  12. Primary progressive multiple sclerosis. Johns Hopkins Medicine. Accessed May 25, 2021.

Reviewed by Michael Sapko, MD, on 7/1/2021

Reviewed by Michael Sapko, MD, on 7/1/2021.