Clinically isolated syndrome

Elizabeth A Hartman MD (

Dr. Hartman of the University of Nebraska has no relevant financial relationships to disclose; Dr. Hartman's spouse owns stock in Amgen.

Anthony T Reder MD, editor. (

Dr. Reder of the University of Chicago received honorariums from Bayer, Biogen Idec, Caremark Rx, Genentech, Genzyme, Novartis, Mallinckrodt, Mylan, Serono, and Teva-Marion for service on advisory boards and as a consultant as well as stock options from NKMax America for advisory work.

Originally released June 7, 2010; last updated September 30, 2020; expires September 30, 2023


A clinically isolated syndrome is a first symptomatic episode of central nervous system dysfunction due to inflammatory demyelination. Risk factors for conversion to clinically definite multiple sclerosis have been identified, and treatment of high-risk individuals may delay subsequent relapses. Individuals with a clinically isolated syndrome may demonstrate accelerated brain atrophy and mild cognitive impairments. Revisions to the diagnostic criteria for relapsing-remitting multiple sclerosis are associated with a reduction in time to diagnosis of clinically definite multiple sclerosis in some clinically isolated syndrome patients. In this article, the author summarizes the diagnosis, evaluation, and prognostic implications of clinically isolated syndromes.

Key points


• Clinically isolated syndromes such as optic neuritis, transverse myelitis, and other syndromes compatible with a first episode of CNS demyelination warrant prompt evaluation to determine underlying etiology.


• Clinically isolated syndrome evaluation may yield important prognostic information regarding risk of multiple sclerosis, or may reveal an alternative diagnosis.


• Early treatment of select clinically isolated syndrome patients may delay subsequent relapses and eventual conversion to clinically definite multiple sclerosis.


• The “radiologically isolated syndrome” may have similar significance to clinically isolated syndromes.

Historical note and terminology

The first journal article including the term “clinically isolated syndrome” appeared in 1993 (Morrissey et al 1993). Increasing availability of MRI technology in the 1980s improved diagnosis of CNS demyelinating disorders, and the arrival of FDA-approved disease-modifying medications for multiple sclerosis starting in 1993 increased the importance of correct diagnosis and treatment. Long-term follow-up studies of patients presenting with an isolated clinical syndrome characteristic of multiple sclerosis led to the identification of baseline risk factors for conversion to clinically definite multiple sclerosis. Subsequent studies of clinically isolated syndrome patients revealed that early treatment with disease-modifying drugs may be beneficial in delaying a second demyelinating attack (Kinkel 2006; Comi 2009; Kappos 2009; Miller et al 2014).

Other descriptions of clinically isolated syndromes include: clinical onset of multiple sclerosis, isolated demyelination syndrome, first demyelinating episode, first presentation of multiple sclerosis, first attack of multiple sclerosis, and focal isolated idiopathic inflammatory demyelinating disorders.

The term “radiologically isolated syndrome” has evolved to describe individuals with brain MRI lesions suggestive of demyelination but without any associated clinical symptoms (Okuda et al 2009). Follow-up of patients with radiologically isolated syndrome has revealed a significant 30% to 45% risk of subsequent development of a clinically isolated syndrome, additional MRI demyelinating lesions, or multiple sclerosis over 2 to 5 years (Lebrun 2015). This risk appears especially elevated for patients with an asymptomatic spinal cord lesion, in whom 84% develop symptoms within four years (Okuda et al 2011). The literature on transverse myelitis suggests that the risk of a single symptomatic cord lesion developing into multiple sclerosis is approximately 40%.

The content you are trying to view is available only to logged in, current MedLink Neurology subscribers.

If you are a subscriber, please log in.

If you are a former subscriber or have registered before, please log in first and then click select a Service Plan or contact Subscriber Services. Site license users, click the Site License Acces link on the Homepage at an authorized computer.

If you have never registered before, click Learn More about MedLink Neurology  or view available Service Plans.

Find out how you can join MedLink Neurology