The natural course of pediatric clinically isolated syndrome

Abstract

Objective: Clinically isolated syndrome (CIS) is the first clinical central nervous system demyelinating event, compatible with the possible future development of multiple sclerosis (MS). Diagnostic criteria for pediatric CIS were first proposed by the International Pediatric Multiple Sclerosis Study Group (IPMSSG) in 2007 and then revised in 2012. CIS is characterized by monofocal or polyfocal events without encephalopathy, unless explained by fever. The most common clinical presentations of CIS in children are optic neuritis (ON), a brainstem and/or cerebellar syndrome, a spinal cord syndrome or syndrome attributed to cerebral hemispheres. The aim of this study was to identify the natural course of pediatric patients with CIS in Slovenia and to assess potential patient characteristics that predict progression to MS. Methods: We retrospectively reviewed the medical records of all pediatric patients (<18 years old) treated at the University Children’s Hospital Ljubljana who presented with CIS between 2006 and 2016. Results: We identified 39 patients with CIS in the 11 year period. The median age at the onset of symptoms was 15,4 years. The most common clinical presentation of CIS were symptoms attributed to cerebral hemispheric dysfunction and ON. Twenty (51%) patients experienced a second demyelinating episode. The mean interval between the first event and the recurrent episode was 11 ± 14 months. The mean follow-up was 3,2 ± 2 years. Twenty-nine (74%) patients developed childhood onset MS. Female sex was significantly associated with the development of MS (p=0,038). There was a significant difference in progression to MS comparing different clinical types of CIS (p=0,039). Subtypes involving cerebral hemispheres with or without brainstem are most often associated with later MS. Conclusion: Significant differences exist between different clinical subtypes of CIS regarding progression to MS. Larger clinical studies could reveal characteristics of CIS that would better predict progression of CIS to MS.