Clinical, environmental, and genetic determinants of multiple sclerosis in children with acute demyelination: a prospective national cohort study.
Abstract | BACKGROUND: METHODS: In our prospective national cohort study, we assessed children who presented with incident CNS demyelination to any of the 16 paediatric health-care facilities or seven regional health-care facilities in Canada. We did univariate and multivariable analyses to assess contributions of HLA-DRB1*15, Epstein-Barr virus, vitamin D status, MRI evidence of brain lesions, and CSF oligoclonal bands as determinants of multiple sclerosis. We used classification and regression tree analyses to generate a risk stratification algorithm for clinical use. FINDINGS: Between Sept 1, 2004, and June 30, 2010, we screened 332 children of whom 302 (91%) were eligible and followed-up for a median of 3·14 years (IQR 1·61-4·51). 63 (21%) children were diagnosed with multiple sclerosis after a median of 127 days (99-222). Although the risk of multiple sclerosis was increased with presence of one or more HLA-DRB1*15 alleles (hazard ratio [HR] 2·32, 95% CI 1·25-4·30), reduced serum 25-hydroxyvitamin D concentration (HR per 10 nmol/L decrease 1·11, 1·00-1·25), and previous Epstein-Barr-virus infection (HR 2·04, 0·99-4·20), no interactions between these variables were detected on multivariate analysis. Multiple sclerosis was strongly associated with baseline MRI evidence of one or more brain lesion (HR 37·9, 5·26-273·85) or CSF oligoclonal bands (6·33, 3·35-11·96), suggesting established disease. One patient diagnosed with multiple sclerosis had a normal MRI scan, and therefore sensitivity of an abnormal MRI scan for multiple sclerosis diagnosis was 98·4%. INTERPRETATION: FUNDING:
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Authors | Brenda Banwell, Amit Bar-Or, Douglas L Arnold, Dessa Sadovnick, Sridar Narayanan, Melissa McGowan, Julia O'Mahony, Sandra Magalhaes, Heather Hanwell, Reinhold Vieth, Raymond Tellier, Thierry Vincent, Giulio Disanto, George Ebers, Katherine Wambera, Mary B Connolly, Jerome Yager, Jean K Mah, Fran Booth, Guillaume Sebire, David Callen, Brandon Meaney, Marie-Emmanuelle Dilenge, Anne Lortie, Daniela Pohl, Asif Doja, Sunita Venketaswaran, Simon Levin, E Athen Macdonald, David Meek, Ellen Wood, Noel Lowry, David Buckley, Conrad Yim, Mark Awuku, Pamela Cooper, François Grand'maison, J Burke Baird, Virender Bhan, Ruth Ann Marrie |
Journal | The Lancet. Neurology
(Lancet Neurol)
Vol. 10
Issue 5
Pg. 436-45
(May 2011)
ISSN: 1474-4465 [Electronic] England |
PMID | 21459044
(Publication Type: Comparative Study, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2011 Elsevier Ltd. All rights reserved. |
Chemical References |
- Genetic Markers
- HLA-DR Antigens
- HLA-DRB1 Chains
- HLA-DRB1*15 antigen
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Topics |
- Acute Disease
- Adolescent
- Age Factors
- Canada
(epidemiology)
- Child
- Child, Preschool
- Cohort Studies
- Demyelinating Diseases
(diagnosis, epidemiology, genetics)
- Environmental Exposure
(adverse effects)
- Epstein-Barr Virus Infections
(diagnosis, epidemiology, genetics)
- Female
- Follow-Up Studies
- Genetic Markers
(genetics)
- Genetic Predisposition to Disease
- HLA-DR Antigens
(genetics)
- HLA-DRB1 Chains
- Humans
- Male
- Multiple Sclerosis
(diagnosis, epidemiology, genetics)
- Prospective Studies
- Risk Factors
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