@article{a28b174c8c4646a88a6651cd35fe6fdf,
title = "Radiologically isolated syndrome in children",
abstract = "Objective: To describe clinical and radiologic outcomes of children with incidental findings on neuroimaging suggestive of CNS demyelination (termed {"}radiologically isolated syndrome{"} or RIS). Methods: Clinical and radiologic data were obtained from a historical cohort of children with no symptoms of demyelinating disease who had MRI scans that met the 2010 MRI criteria for dissemination in space for MS. Results: We identified 38 children (27 girls and 11 boys) with RIS now being prospectively followed at 16 sites in 6 countries. The mean follow-up time was 4.8 ± 5.3 years. The most common reason for initial neuroimaging was headache (20/38, 53%). A first clinical event consistent with CNS demyelination occurred in 16/38 children (42%; 95% confidence interval [CI]: 27%-60%) in a median of 2.0 years (interquartile range [IQR] 1.0-4.3 years). Radiologic evolution developed in 23/38 children (61%; 95% CI: 44%-76%) in a median of 1.1 years (IQR 0.5-1.9 years). The presence of ≥2 unique oligoclonal bands in CSF (hazard ratio [HR] 10.9, 95% CI: 1.4-86.2, p = 0.02) and spinal cord lesions on MRI (HR 7.8, 95% CI: 1.4-43.6, p = 0.02) were associated with an increased risk of a first clinical event after adjustment for age and sex. Conclusions: We describe the clinical characteristics and outcomes of children with incidental MRI findings highly suggestive of CNS demyelination. Children with RIS had a substantial risk of subsequent clinical symptoms and/or radiologic evolution. The presence of oligoclonal bands in CSF and spinal cord lesions on MRI were associated with an increased risk of a first clinical event.",
author = "Naila Makhani and Christine Lebrun and Aksel Siva and David Brassat and {Carra Dalli{\`e}re}, Clarisse and {De Seze}, J{\'e}r{\^o}me and Wei Du and {Durand Dubief}, Fran{\c c}oise and Orhun Kantarci and Megan Langille and Sona Narula and Jean Pelletier and Rojas, {Juan Ignacio} and Shapiro, {Eugene D.} and Stone, {Robert T.} and Mar Tintor{\'e} and Ugur Uygunoglu and Patrick Vermersch and Evangeline Wassmer and Okuda, {Darin T.} and Daniel Pelletier",
note = "Funding Information: Author affiliations are provided at the end of the article. Coinvestigators are listed at Neurology.org/nn. Funding information and disclosures are provided at the end of the article. Go to Neurology.org/nn for full disclosure forms. The Article Processing Charge was funded by the authors. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Funding Information: This publication 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 the NIH. Funding Information: N. Makhani received research support from Race to Erase MS Foundation. C. Lebrun served on the scientific advisory board for Biogen, Novartis, Merck, Genzyme, Teva, and Roche; received travel funding and/or speaker honoraria from Biogen, Merck, Genzyme, and Roche; served as an editorial advisory board member for Revue Neurologique (Paris) Elsevier, and Neurology and Therapy; and received research support from the French MS Society (SFSEP) EDMUS (OFSEP Center) Foundation. A. Siva received travel funding from Merck Serono, Biogen Idec/Gen Pharma of Turkey, Novartis, Genzyme, Roche, and Teva; served on the editorial board for Journal of Neurological Sciences, Journal of Headache and Pain, and Turkish Neurological Journal; consulted for Biogen Idec, Novartis, Merck Serono, Bayer, Teva, Genzyme, and Roche; served on the speakers{\textquoteright} bureau for Excemed, Genzyme, Merck Serono, Biogen Idec/Gen Pharma of Turkey, and Teva; and received research support from The Scientific and Technological Research Council of Turkey. D. Brassat served on the scientific advisory board for Chugai Pharma; received travel funding and/or speaker honoraria from Biogen, Bayer, Novartis, Sanofi, Almirall, Merck, and Teva and received research support from FP7 and PHRC. C. Carra-Dalliere received travel funding from Genzyme, Biogen, and Novartis. J. de Seze served on the editorial board for Revue Neurologique. W. Du reports no disclosures. F. Durand-Dubief served on the scientific advisory board for Merck Serono and Roche and received travel funding and/or speaker honoraria from Biogen, Merck Serono, Sanofi-Aventis, Genzyme, Novartis Pharma, Roche, and Teva. O. Kantarci received speaker honoraria from Novartis Pharmaceuticals and Biogen; did a grant review for the National Multiple Sclerosis Society; received research support from European Regional Development Fund, National Multiple Sclerosis Society, Biogen, Multiple Sclerosis Society, Mayo Foundation, Hilton Foundation, and Mayo Clinic; received compensation for consulting activities from Teva; his spouse serves on the data safety monitoring board of Takeda Global Research and Development Center, Inc, and the data monitoring boards of Pfizer Inc and Janssen Alzheimer Immunotherapy; and is funded by the NIH and Minnesota Partnership for Biotechnology and Medical Genomics. M. Langille and S. Narula report no disclosures. J. Pelletier served on the scientific advisory board for Biogen, Novartis, and Genzyme and received research support from Arsep and Novartis. J.I. Rojas served on the speakers{\textquoteright} bureau for Novartis Argentina, Genzyme Argentina, and Merck Serono Argentina. E.D. Shapiro received speaker honoraria from the Eastern Maine Medical Center and received research support from the NIH/NIAID/NDDK. R.T. Stone received research support from Novartis Pharmaceuticals. M. Tintor{\'e} served on the scientific advisory board from Biogen, Novartis, Genzyme, and Roche; received travel funding and/or speaker honoraria from Bayer, Teva, Biogen Idec, Merck Serono, Novartis, Sanofi-Aventis, Genzyme, Roche, and Almirall; served on the editorial board for Multiple Sclerosis Journal, Neurologia, and Revista de Neurologia; is editor of MSJ-ETC; served on the speakers{\textquoteright} bureau from Almirall, Bayer, Teva, Biogen Idec, Merck Serono, Novartis, Sanofi-Aventis, Genzyme, and Roche; and received research support from Bayer, Teva, Biogen Idec, Merck Serono, Novartis, Sanofi-Aventis, Genzyme, Roche, Almirall, Spanish Agency for Sanitary Investigations, REEM, and Angencia de Gestio d{\textquoteright}ajuts Universitaris I de Recerca of the Generalitat de Catalunya in Spain. U. Uygunoglu received travel funding from Merck Serono, Biogen Idec, and Novartis; served as an associate editor for Turkish Neurology Journal; and received research support from the Turkish Neurological Society. P. Vermersch served on the scientific advisory board for Sanofi, Biogen, Merck, Teva, Novartis, Roche, and Servier; received travel funding and/or speaker honoraria from Biogen, Roche, Novartis, Teva, Sanofi-Aventis, Almirall, Merck Serono, and Neurosciences et sclerose en plaques; received research support from Biogen, Bayer, Novartis, Merck, Teva, Sanofi Genzyme, and Roche; received travel funding and/or speaker honoraria from Biogen Idec, Teva, Genzyme, Shire, UCB, and Merck Serono; and received research support from Biogen Idec, Sanofi, Novartis UK MS Society, Action Medical Research, and Birmingham Children{\textquoteright}s Hospital Research Foundation. D.T. Okuda received travel funding and/or speaker honoraria from Acorda Therapeutics, Genentech, Genzyme, and Teva; consulted for Bayer, EMD Serono, Genzyme, and Novartis; served on the speakers{\textquoteright} bureau for Acorda Therapeutics, Genzyme, and Teva Neuroscience; and received research support from Biogen. D. Pelletier consulted for Biogen, EMD Serono, Sanofi Genzyme, Novartis, Hoffmann-La Roche, and Vertex and received research support from Biogen and National Multiple Sclerosis Society. Go to Neurology.org/nn for full disclosure forms.",
year = "2017",
month = oct,
day = "23",
doi = "10.1212/NXI.0000000000000395",
language = "English (US)",
volume = "4",
journal = "Neurology: Neuroimmunology and NeuroInflammation",
issn = "2332-7812",
publisher = "Lippincott Williams and Wilkins",
number = "6",
}