Clinically isolated syndrome

Elizabeth A Hartman MD (Dr. Hartman of CNOS received honorariums from Amgen, Bayer, Biogen, EMD Serono, Novartis, and Teva for speaking engagements and consulting fees from Biogen. Dr. Hartman's spouse owns stock in Amgen.)
Anthony T Reder MD, editor. (Dr. Reder of the University of Chicago served on advisory boards and as a consultant for Bayer, Biogen Idec, Caremark Rx, Genentech, Genzyme, Novartis, Questcor/Malinkrodt, Serono, and Teva-Marion.)
Originally released June 7, 2010; last updated July 4, 2016; expires July 4, 2019

This article includes discussion of clinically isolated syndrome, radiologically isolated syndrome, RIS, demyelinating syndrome, optic neuritis, transverse myelitis, and multiple sclerosis. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

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. 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 newly described “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).

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.

More recently, 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 10% to 34% risk of subsequent development of a clinically isolated syndrome, additional MRI demyelinating lesions, or multiple sclerosis (Lebrun et al 2009; Siva et al 2009). This risk appears especially elevated for patients with an asymptomatic spinal cord lesion, in whom 84% develop symptoms within 4 years (Okuda et al 2011). The literature on transverse myelitis suggests that the risk of a single symptomatic cord lesion changing to multiple sclerosis is approximately 40%.

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