Clinical features and viral serologies in children with multiple sclerosis: a multinational observational study.
BACKGROUND
The full spectrum of clinical manifestations and outcome, and the potential importance of regional or demographic features or viral triggers in paediatric multiple sclerosis (MS), has yet to be fully characterised. Our aim was to determine some of these characteristics in children with MS.


METHODS
137 children with MS and 96 control participants matched by age and geographical region were recruited in a multinational study. They underwent structured clinical-demographic interviews, review of academic performance, physical examination, disability assessment (MS patients only), and standardised assays for IgG antibodies directed against Epstein-Barr virus, cytomegalovirus, parvovirus B19, varicella zoster virus, and herpes simplex virus.


RESULTS
MS was relapsing-remitting at diagnosis in 136 (99%) children. The first MS attack resembled acute disseminated encephalomyelitis (ADEM) in 22 (16%) of the children, most under 10 years old (mean age 7.4 [SD 4.2] years). Children with ADEM-like presentations were significantly younger than were children with polyfocal (11.2 [4.5] years; p<0.0001) or monofocal (12.0 [3.8] years; p=0.0005) presentations. Permanent physical disability (EDSS>or=4.0) developed within 5 years in 15 (13%) of the 120 children for whom EDSS score was available. 23 (17%) had impaired academic performance, which was associated with increasing disease duration (p=0.02). Over 108 (86%) of the children with MS, irrespective of geographical residence, were seropositive for remote EBV infection, compared with only 61 (64%) of matched controls (p=0.025, adjusted for multiple comparisons). Children with MS did not differ from controls in seroprevalence of the other childhood viruses studied, nor with respect to month of birth, sibling number, sibling rank, or exposure to young siblings.


CONCLUSIONS
Paediatric MS is a relapsing-remitting disease, with presenting features that vary by age at onset. MS in children might be associated with exposure to EBV, suggesting a possible role for EBV in MS pathobiology.
Banwell
Brenda
B
Division of Neurology, The Hospital for Sick Children, University of Toronto, ON, Canada. brenda.banwell@sickkids.ca
Krupp
Lauren
L
Kennedy
Julia
J
Tellier
Raymond
R
Tenembaum
Silvia
S
Ness
Jayne
J
Belman
Anita
A
Boiko
Alexei
A
Bykova
Olga
O
Waubant
Emmanuelle
E
Mah
Jean K
JK
Stoian
Cristina
C
Kremenchutzky
Marcelo
M
Bardini
Maria Rita
MR
Ruggieri
Martino
M
Rensel
Mary
M
Hahn
Jin
J
Weinstock-Guttman
Bianca
B
Yeh
E Ann
EA
Farrell
Kevin
K
Freedman
Mark
M
Iivanainen
Matti
M
Sevon
Meri
M
Bhan
Virender
V
Dilenge
Marie-Emmanuelle
ME
Stephens
Derek
D
Bar-Or
Amit
A
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D000914:Antibodies, Viral / Q000097:blood*; D000956:Antigens, Viral / Q000276:immunology; D016022:Case-Control Studies; D002648:Child; D003710:Demography; D004185:Disability Evaluation; D004467:Economics; D005260:Female; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007406:Interview, Psychological; D008297:Male; D009103:Multiple Sclerosis / Q000453:epidemiology / Q000503:physiopathology / Q000821:virology; D019370:Observation; D010372:Pediatrics; D016036:Seroepidemiologic Studies; D012720:Severity of Illness Index; D018139:Simplexvirus / Q000276:immunology
D000914:Antibodies, Viral; D000956:Antigens, Viral