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Published on: December 9, 2015
Conversion of clinically isolated syndrome to multiple sclerosis: a prospective study
Jan Kolčava1, Jan Kočica1, Monika Hulová1
1Faculty of Medicine, Masaryk University, Brno, Czech Republic; Department of Neurology, University Hospital Brno, Czech Republic.
Background:
Multiple sclerosis (MS) begins with an acute clinical attack (clinically isolated syndrome) in approximately 85% of patients. The conversion rate from clinically isolated syndrome to multiple sclerosis has been documented at 30% to 82% in previous studies. When an individual presents for evaluation after a single episode of inflammation of the CNS, several decisions regarding follow-up in subsequent years need to be made, including that of whether or not to start a therapy. There is, therefore, an emerging need to identify the predictive factors that anticipate conversion from CIS to MS.
Methods:
This paper presents a single-center prospective longitudinal study aimed at identification of the most powerful independent predictors for conversion from CIS to MS, utilizing the 2010 McDonald MS criteria and focusing on selected demographic, clinical, radiographical (magnetic resonance imaging - MRI), cerebrospinal fluid (predominantly oligoclonal bands - OCB) and electrophysiological parameters (multimodal sensory and motor-evoked potentials - EP). Two independent outcomes meeting MS criteria are evaluated: development of second clinical relapse (clinically definite multiple sclerosis) and progression in magnetic resonance imaging (based on new MRI T2 brain and/or spinal cord lesions). CIS patients were followed clinically and MRI was repeated at one and two years within the course of a follow-up period of at least 24 months (median 27, range 24-36 months).
Results:
Of the 64 CIS patients enrolled who completed at least a 2-year follow-up period (42 women and 22 men, median age 36.5, range 22-66 years), 45 (70.3%) (29 women and 16 men, median age 38; range 22-66 years) fulfilled the 2010 McDonald criteria for MS by dissemination in space (DIS) and time (DIT) over the follow-up period. Twenty-nine CIS patients converted to MS through a clinically symptomatic attack, and 16 CIS patients developed new T2 lesions on MRI, while 19 patients without progression remained stable as CIS. Confirmed among potential predictors for the conversion of CIS patients to MS were increased (>10) baseline MRI T2-hyperintense lesions (odds ratio (OR) 3.107, p = 0.046), OCB positivity (OR 5.958, p = 0.003) and subclinical EP abnormality (OR 14.400, p = 0.003). Multivariate statistical models (logistic regression and Cox proportional hazards regression models) confirmed these parameters as independent predictors of high sensitivity (84%) and acceptable specificity (63%).
Conclusion:
In addition to accepted predictors for the conversion of CIS to MS (i.e. baseline MRI T2 lesion load and OCB positivity), already implemented in current diagnostic criteria for MS, this study demonstrates, in addition, the high predictive value of subclinical multimodal evoked potential abnormalities.
Insights
Subclinical evoked potential abnormalities, along with MRI T2 lesions and OCB positivity, are strong predictors for clinically isolated syndrome (CIS) conversion to multiple sclerosis (MS). Early identification aids in timely treatment decisions for MS.
Area of Science:
- Neurology
- Neuroimmunology
- Clinical Neuroscience
Background:
- Multiple sclerosis (MS) often initiates with a clinically isolated syndrome (CIS), a single neurological attack.
- Predicting conversion from CIS to MS is crucial for timely therapeutic intervention.
- Existing studies show variable conversion rates, highlighting the need for precise predictive factors.
Purpose of the Study:
- To identify independent predictors for the conversion of CIS to MS.
- To evaluate demographic, clinical, MRI, CSF, and electrophysiological parameters.
- To utilize the 2010 McDonald MS diagnostic criteria for assessing conversion.
Main Methods:
- Prospective longitudinal study of 64 CIS patients over at least 24 months.
- Assessment of conversion to MS based on clinical relapse or new MRI lesions.
- Analysis of baseline MRI T2 lesions, oligoclonal bands (OCB), and multimodal evoked potentials (EP).
Main Results:
- 70.3% of CIS patients converted to MS within the follow-up period.
- Predictors for conversion included: >10 baseline MRI T2 lesions (OR 3.107), OCB positivity (OR 5.958), and subclinical EP abnormality (OR 14.400).
- Multivariate models confirmed these as independent predictors with 84% sensitivity and 63% specificity.
Conclusions:
- Baseline MRI T2 lesion load and OCB positivity are established predictors for CIS to MS conversion.
- Subclinical abnormalities in multimodal evoked potentials (EP) demonstrate significant predictive value.
- These findings enhance the ability to identify patients at high risk of MS progression.
