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Immunotherapy for clinically isolated syndrome? Not necessarily...

Nature Clinical Practice Neurology volume 4, pages 236–237 (2008)Cite this article

A clinically isolated syndrome (CIS) is defined as a first neurological event caused by an inflammatory demyelinating lesion in the CNS, and is accompanied in most patients by several silent or asymptomatic MRI lesions that are suggestive of multiple sclerosis (MS). The common neurological events that occur are an episode of optic neuritis, or symptoms and signs consistent with involvement of the brainstem, spinal cord, or cerebral hemispheres. Individuals with CIS are considered to be at high risk of developing clinically definite MS (CDMS) and, therefore, are viewed by many clinicians as having 'early-stage MS'. This way of thinking has led many MS experts to support the initiation of long-term treatment with disease-modifying agents (DMAs) as soon as a patient presents with such an episode.1,2 However, CIS is not always MS, MS itself is an unpredictable disease that is clinically variable from patient to patient, and it is currently unclear who exactly will benefit from early treatment initiation. The practicing neurologist who sees patients with CIS, therefore, faces a theraupetic dilemma. Withholding medication from an individual in whom treatment might improve the disease course is equivalent to causing harm. On the other hand, giving long-term treatment to individuals who do not require it because they have a benign disease form, or in whom such a therapy might worsen the disease course, is also causing harm. So what are clinicians to do?

Most of the time, 'early MS' is not 'early' by the time it is diagnosed as CIS, as most patients who are admitted with 'first' clinical symptoms suggestive of MS already show a number of nonactive and old lesions of an undetermined age on their MRI scans. The true onset of MS is unknown and evidence suggests that MS is present subclinically long before the manifestations of clinical symptoms. The occurrence of asymptomatic or subclinical MS—clinically silent disease that is discovered by chance via imaging or at autopsy—indicates that MS can remain clinically silent for a considerable period of time or an entire lifetime.3 Moreover, MS-typical focal brain abnormalities on MRI or oligoclonal bands in the cerebrospinal fluid can also be detected in asymptomatic first-degree relatives of patients with MS. Advanced imaging and cerebrospinal fluid studies in these populations indicate that such abnormalities are not associated with the widespread tissue damage that is commonly found in patients with MS,4,5 a finding that supports the concept that disease expression can be highly variable between individuals. Having a diagnosis of CIS does not, therefore, necessarily imply the need for early treatment, because what is diagnosed as a first clinical event might simply be the temporary emergence of an ongoing mild disease.

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  1. Department of Neurology, Istanbul University Cerrahpaşa School of Medicine Cerrahpaşa, 34098 Istanbul, Turkey asiva@turk.net

Authors and Affiliations

  1. A Siva is Professor of Neurology and Head of the Clinical Neuroimmunology Unit in the Neurology Department, Cerrahpaşa School of Medicine, Istanbul University, Istanbul, Turkey.,

    Aksel Siva

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Siva, A. Immunotherapy for clinically isolated syndrome? Not necessarily.... Nat Rev Neurol 4, 236–237 (2008). https://doi.org/10.1038/ncpneuro0774

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