Elsevier

The Lancet Neurology

Volume 4, Issue 5, May 2005, Pages 281-288
The Lancet Neurology

Review
Clinically isolated syndromes suggestive of multiple sclerosis, part I: natural history, pathogenesis, diagnosis, and prognosis

https://doi.org/10.1016/S1474-4422(05)70071-5Get rights and content

Summary

In 85% of young adults with multiple sclerosis (MS), onset is a subacute clinically isolated syndrome (CIS) of the optic nerves, brainstem, or spinal cord. Methods of assessing the prognosis for patients who present with a CIS have been sought, because only 30–70% of patients with a CIS develop MS. When clinically silent brain lesions are seen on MRI, the likelihood of developing MS is high. MS can be diagnosed within 3 months of CIS presentation with certain MRI and CSF criteria. Disability from MS is less likely in patients with a CIS of optic neuritis or sensory symptoms only, few or no MRI lesions, a long period to the first relapse, and no disability after the first 5 years. Development of more reliable prognostic markers will enable new treatments to be targeted for those who are most likely to benefit. We encourage continued clinical and laboratory assessment of patients with a CIS.

Section snippets

Clinical presentation

Review of a large database of patients with CISs found that 21% presented with optic neuritis, 46% with longtract symptoms and signs, 10% with a brainstem syndrome, and 23% with multifocal abnormalities.1 Therefore, the syndrome was isolated in space in only 77% of presentations, although all presentations were isolated in time. The presentation of MS affects disease course and prognosis (panel 1).2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15

Studies of the clinical features and natural history

Pathology

There are few, if any, studies on the pathological changes that occur in CISs, and most that there are focus on more aggressive forms of inflammatory demyelination such as Balo's concentric sclerosis, Marburg's disease, Schilder's disease, and acute disseminated encephalomyelitis. Initial presentation with a large mass lesion (so-called tumefactive MS) may also pose diagnostic difficulties. However, the finding of many infiltrating macrophages in the setting of myelin loss with relative

Diagnosis

Clinical suspicion of demyelination is high when a young person has an episode consistent with damage to white-matter tracts; however, many diseases cause similar episodes. A comprehensive review of the differential diagnosis of MS is beyond the scope of this review; however a few caveats should be mentioned. First, the diagnosis in patients with CIS—MS, another neurological disorder, or CIS only—is a clinical decision and should be made by a neurologist experienced in the relevant differential

MRI assessment of long-term prognosis

Although many studies assess the predictive value of MRI in the short term, few have addressed the mid-term to long-term, partly because this technique was introduced in the mid 1980s. Research into the predictive value of MRI in the mid-term to long-term is crucial. Too short a follow-up will lead to ascertainment bias and might lead to overestimation of the role of MRI by identifying only those patients in whom the period for conversion is short. There is also little change in disability in

Search strategy and selection criteria

References for this review were identified from searches of the extensive files of the authors; presentations at the MAGNIMS Workshop, held in London in January 2004 (see acknowledgments); access to PubMed citations between 1985 and December 2004; and references from relevant articles. A few abstracts and reports from the MAGNIMS meeting were also included. The final reference list was generated from papers that were original and relevant to the topics covered in the review.

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