Performance of the 2023 Adult Criteria for the Radiologically Isolated Syndrome in Children and Comparison to the 2009 Criteria
Naila Makhani1, Christine Lebrun Frenay2, Aksel Siva3, Veronika Shabanova1, Evangeline Wassmer4, Jonathan Santoro5, Sona Narula6, James Brenton7, Soe Mar8, Francoise Durand Dubief9, Helene Zephir10, Guillaume Mathey11, Juan Ignacio Rojas12, Jerome De Seze13, Silvia Tenembaum14, Robert Thompson-Stone15, Olivier Casez16, Clarisse Carra-Dalliere17, Rinze F Neuteboom18, Nusrat Ahsan5, Hugo Arroyo19, Philippe Cabre20, Grace Gombolay21, Matilde Inglese22, Celine Louapre23, Monica Margoni24, Filipe Palavra25, Daniela Pohl26, Daniel Reich27, Aurelie Ruet28, Eric Thouvenot29, Niklas Timby30, Mar Tintore31, Ugur Uygunoglu3, Wendy Vargas32, Helene Verhelst33, Ronny Wickstrom34, Christina Azevedo35, Orhun Kantarci36, Eugene Shapiro37, Darin Okuda38, Daniel Pelletier39
1Yale University School of Medicine, Department of Pediatrics, 2CRCSEP Neurologie, 3Istanbul University Cerrahpasa School of Medicine, 4Birmingham Children's Hospital, 5Department of Neurology, Children's Hospital Los Angeles, 6CHOP, 7University of Virginia, 8Washington University School of Medicine, 9Hopital Pierre Wertheimer, 10Hospital Roger Salengro, 11Nancy University Hospital, 12Hospital Italiano, 13CHU de Strasbourg, 14National Pediatric Hospital Dr. Juan P Garrahan, 15University of Rochester, 16CHU De Grenoble, 17Montpellier University Hospital, 18Erasmus MC Rotterdam, 19Hospital de Pediatría SAMIC. Prof. Dr. J.P. Garrahan, 20CHU Martinique, 21Emory University/Children'S Healthcare of Atlanta, 22University of Genoa, 23Hôpital Pitié Salpêtrière, APHP, 2427. Multiple Sclerosis Center of the Veneto Region, 25Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, 26CHEO, 27National Institutes of Health, Neuroimmunology Branch, NINDS, 28Hopital Pellegrin, 29CHU De Nimes - Hopital Caremeau, 30Umea University, 3134. MS Center of Catalunya Cemcat, 32none, 33University Hospital Ghent, 34Karolinska Institutet, 35University of Southern California, 36Mayo Clinic, 37Yale Univ School of Medicine, 38UT Southwestern Medical Center, 39Keck School of Medicine of USC
Objective:
To evaluate and compare the performance of the 2023 and the 2009 adult criteria for the radiologically isolated syndrome (RIS) as predictors of a first clinical neurological event in children with RIS.
Background:
Revised diagnostic criteria were published for RIS in adults in 2023—criteria that differ from those originally proposed in 2009 and that should allow for earlier recognition. We do not know how the 2023 criteria perform in children with RIS, as compared with the 2009 criteria.
Design/Methods:
We evaluated these criteria in 95 children (<18 years) with RIS enrolled in an international longitudinal study. All children met the 2010 and 2017 MRI criteria for dissemination in space for MS on their index scans (Ped-RIS). Eighteen children (19%) did not have results for spinal cord imaging and/or unique oligoclonal bands in spinal fluid. We therefore performed both a complete case analysis (n=77) and used 30 imputed datasets (n=95).
Results:
Overall, 67.5% of the 95 children with Ped-RIS met 2023 RIS criteria and 49.5% met 2009 criteria (79.2% and 61.0% amongst 77 children with complete data). The proportion of children who subsequently developed a first clinical neurological event were similar at 35.9% vs. 34.0% (36.1% vs. 34.0% amongst children with complete data) across the two groups during a median follow-up time of 3.1 years (range 0.1-18.5 years). In the imputed dataset, diagnostic indices (with 95% C.I.s) for the 2023 versus the 2009 criteria were: sensitivity 89.1% (75.7%-100.0%) vs. 61.5% (42.8%-80.2%), specificity 40.7% (29.0%-52.3%) vs. 55.1% (43.3%-66.8%), positive predictive value 36.1% (24.3%-48.0%) vs. 34.0% (20.5%-47.6%), and negative predictive value 90.9% (79.8%-100.0%) vs. 76.2% (67.7%-90.8%).
Conclusions:
The 2023 adult RIS criteria perform favorably overall in children with higher sensitivity and modestly reduced specificity.