Anomalies Characteristic of Central Nervous System Demyelination: Radiologically Isolated Syndrome

Objective: To compare sensitivity and specificity of 2005 and newly proposed MAGNIMS 2016 MRI dissemination in space (DIS) criteria for multiple sclerosis (MS) to predict a first clinical neurological event in asymptomatic children with incidental MRI findings consistent with central nervous system demyelination, termed the radiologically isolated syndrome (RIS). Background: The diagnosis of RIS in adults requires that 2005 MRI criteria for DIS be met. We recently identified a cohort of children with RIS using newer validated 2010 DIS criteria (RIS-2010). Robust criteria for RIS in children are needed to better classify risk of developing clinical symptoms and to avoid unnecessary testing or therapies. Design/Methods: We analyzed a historical cohort of children ( Results: We identified 52 children with RIS-2010 detected at a median age of 15.0 (range 8.1–17.9) years. Mean follow-up time was 4.2 ± 4.9 years. A first clinical neurological event occurred in 18/52 children (34.6%) after a median of 1.7 (range 0.1–17.1) years. Diagnostic indices (95% C.I.) for 2016 vs. 2005 DIS criteria were: sensitivity: 100% (82–100%) vs. 67% (41–87%); specificity: 25% (11–41%) vs. 53% (35–70%); positive predictive value (PPV): 41% (26–57%) vs. 43% (24–63%). PPV for the 2010 DIS criteria was 35% (22–49%). The presence of spinal cord lesions on MRI was the only component independently associated with a first clinical neurological event (HR 3.4, 95% C.I.1.0–11.7; p=0.05). Conclusions: Proposed MAGNIMS 2016 DIS criteria have greater sensitivity, but much lower specificity than 2005 DIS criteria for predicting a first clinical neurologic event in children with RIS-2010. Greater false positive diagnoses using 2016 criteria may generate clinical counseling concerns. Asymptomatic spinal cord lesions on MRI strongly predict a first clinical neurologic event. Study Supported by: This study was made possible, in part by CTSA Grant Number UL1 TR000142 from the National Center for Advancing Translational Science (NCATS) at the National Institutes of Health and NIH roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NIH. Disclosure: Dr. Makhani has nothing to disclose. Dr. Lebrun Frenay has received personal compensation for activities with Genzyme, Novartis, Biogen, Merck, Teva, and Revue Neurologique as a member of the advisory board. Dr Siva has received personal compensation for activities with Biogen, Gen Pharma of Turkey, Novartis and Teva Turkey. Dr. Narula has nothing to disclose. Dr. Wassmer has nothing to disclose. Dr. Brenton has nothing to disclose. Dr. Carra Dalliere has nothing to disclose. Dr. De Seze has received personal compensation for activities with Merck, Biogen, Novartis, Roche, Teva, LFB, Alexion, and Sanofi Genzyme. Dr. De Seze has received research support from LFB and Novartis. Dr. Durand Dubief has nothing to disclose. Dr. Langille has nothing to disclose. Dr. Neuteboom has nothing to disclose. Dr. Pelletier has nothing to disclose. Dr. Pohl has nothing to disclose. Dr. Rojas has nothing to disclose. Dr. Shapiro has nothing to disclose. Dr. Stone has nothing to disclose. Dr. Tenembaum has received personal compensation for activities with Genzyme Corporation, Biogen, Bayer Schering Pharma, Teva Pharmaceutical, and Merck Serono as a consultant and speaker. Dr. Tintore has nothing to disclose. Dr. Uygunoglu has received personal compensation for activities with EMD Serono and Biogen. Dr. Vargas has nothing to disclose. Dr. Kantarci has nothing to disclose. Dr. Okuda has received personal compensation for activities with Acorda Therapeutics, Genentech, Inc, Genzyme Corporation, TEVA Neuroscience, EMD Serono, and Novartis. Dr. Okuda has received research support from Biogen. Dr. Pelletier has received personal compensation for activities with CNS Imaging Consultant, LLC as a consultant. Dr. Makhani has nothing to disclose. Dr. Makhani has nothing to disclose. Dr. Makhani has nothing to disclose.

Clarissa Carra Dalliere

Papers

Comparison of MRI Dissemination in Space Criteria for Predicting a First Clinical Event in Children with the Radiologically Isolated Syndrome (S2.001)