• Systemic Atrophies
• Neuroimaging
• Demyelinating Diseases

Clinically isolated syndrome (CIS) refers to the first neurologic episode in which a person experiences multiple sclerosis (MS)-related symptoms. According to the McDonalds 2010 criteria, MS can be diagnosed in patients with only one clinical episode. The diagnosis of CIS is reserved for patients who do not meet the criterion of dissemination in space and/or dissemination in time clinically and in the first magnetic resonance image (MRI). In this session, presenters debated whether or not patients with CIS should be treated.

Hans-Peter Hartung, MD, Heinrich Heine University, Düsseldorf, Germany, presented the case that patients with CIS should be treated. In the MAGNIMS study [Filippi M et al. Arch Neurol 2009;], patients had a first MRI at 1.3 months and a second one at 5.0 months. With regard to conversion to clinically definite MS (CDMS), the two MRIs demonstrated 47% and 43% sensitivity, 88% and 87% specificity, and 76.5% and 75% accuracy, respectively. The investigators concluded that a single MRI may suffice to identify a subset of CIS patients with a high risk of developing CDMS, even when it is performed within the first three months after the onset of symptoms.

Studies have shown that a shorter first inter-attack interval and incomplete recovery from the first attack are predictors of long-term disability in patients with relapsing-remitting MS (RRMS). A 20-year study found that an early high rate of MRI disease activity is associated with long-term disease progression. Numerous studies show that axonal damage occurs early in MS and is irreversible. Several Phase 3 trials of early therapy for CIS have been completed. The CHAMPS, ETOMS, BENEFIT, and PRECISE trials demonstrated that significantly fewer treated CIS patients versus placebo patients had CDMS at 2 years (Figure 1) [Jacobs LD et al. N Engl J Med 2000; Comi G et al. Lancet 2001; Kappos et al. Neurology 2006; Comi G et al. Lancet 2009].

• Download figure
• Open in new tab
• Download powerpoint

Figure 1.

Studies in CIS Populations.

Reproduced with permission from HP Hartung, MD.

Prof. Hartung concluded that irreversible axonal damage occurs early and has an impact on the development of disability. Disease-modifying therapy seems to be more effective if used earlier.

Karl Vass, MD, University of Vienna, Vienna, Austria, argued that patients with CIS should not be treated early for the following reasons: the definition of CIS is vague; not every patient with CIS will develop MS; many patients will develop only mild disease; and many patients will not accept immediate treatment. In a long-term follow-up of patients with CIS, among those with an abnormal MRI at baseline, 83% had converted to CDMS at 10 years. Only 50% of patients had developed CDMS within 2 years. Further, it takes a long time for significant disability to occur, which usually is preceded by additional relapses or more MRI activity [Confavreux C. N Engl J Med 2000].

In the CIS studies, ETOMS, CHAMPS, REFLEX, BENEFIT, and PRECISE [Comi G et al. Lancet 2001; Jacobs LD et al. N Engl J Med 2000; Kappos L et al. Neurology 2006; Kappos L et al. Lancet 2007; Comi G et al. Lancet 2009], 30% to 60% of the patients already had MS according to the McDonald 2010 Criteria. These study results provide insufficient evidence for efficacy of disease-modifying therapy in “new” CIS patients. Finally, clinical experience shows that many patients are not ready to begin therapy after a diagnosis of CIS.

Prof. Vass concluded that not every patient with CIS should be treated; more than 50% do not need disease-modifying therapy, which is insufficiently effective and expensive.

• © 2012 MD Conference Express®