Lancet Neurol. 2011 May;10(5):436-45. doi: 10.1016/S1474-4422(11)70045-X. Epub 2011 Mar 31.

Clinical, environmental, and genetic determinants of multiple sclerosis in children with acute demyelination: a prospective national cohort study.

Banwell B, Bar-Or A, Arnold DL, Sadovnick D, Narayanan S, McGowan M, O’Mahony J, Magalhaes S, Hanwell H, Vieth R, Tellier R, Vincent T, Disanto G, Ebers G, Wambera K, Connolly MB, Yager J, Mah JK, Booth F, Sebire G, Callen D, Meaney B, Dilenge ME, Lortie A, Pohl D, Doja A, Venketaswaran S, Levin S, Macdonald EA, Meek D, Wood E, Lowry N, Buckley D, Yim C, Awuku M, Cooper P, Grand’maison F, Baird JB, Bhan V, Marrie RA.

Source

Division of Neurology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. brenda.banwell@sickkids.ca

Abstract

BACKGROUND:

HLA-DRB1*15 genotype, previous infection with Epstein-Barr virus, and vitamin D insufficiency are susceptibility factors for multiple sclerosis, but whether they act synergistically to increase risk is unknown. We aimed to assess the contributions of these risk factors and the effect of established precursors of multiple sclerosis, such as brain lesions on MRI and oligoclonal bands in CSF at the time of incident demyelination, on development of multiple sclerosis in children.

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:

Risk of multiple sclerosis in children can be stratified by presence of HLA-DRB1*15 alleles, remote Epstein-Barr virus infection, and low serum 25-hydroxyvitamin D concentrations. Similar to previous studies in adults, brain lesions detected on MRI and CSF oligoclonal bands in children are probable precursors to the clinical onset of multiple sclerosis. Children with a normal MRI are very likely to have a monophasic illness.

FUNDING:

Canadian Multiple Sclerosis Scientific Research Foundation.

Copyright © 2011 Elsevier Ltd. All rights reserved.

Comment in

Risk of multiple sclerosis in children with acute demyelination. [Lancet Neurol. 2011]

via Clinical, environmental, and genetic determina… [Lancet Neurol. 2011] – PubMed – NCBI.

J Neurol Neurosurg Psychiatry. 2012 May;83(5):565-71. doi: 10.1136/jnnp-2011-301876. Epub 2012 Feb 22.

A randomised, double blind, placebo controlled trial with vitamin D3 as an add on treatment to interferon β-1b in patients with multiple sclerosis.

Soilu-Hänninen M, Aivo J, Lindström BM, Elovaara I, Sumelahti ML, Färkkilä M, Tienari P, Atula S, Sarasoja T, Herrala L, Keskinarkaus I, Kruger J, Kallio T, Rocca MA, Filippi M.

Source

Department of Neurology, University of Turku, Turku, Finland. mersoi@utu.fi

Abstract

OBJECTIVES:

To study the safety and efficacy of vitamin D3 as an add on therapy to interferon β-1b (IFNB) in patients with multiple sclerosis (MS).

METHODS:

1 year, double blind, placebo controlled, randomised study in 66 MS patients. The primary outcomes were T2 burden of disease (BOD) on MRI scans, proportion of patients with serum levels of 25-hydroxyvitamin D (25(OH)D) ≥85 nmol/l or intact parathyroid hormone (PTH) ≤20 ng/l, and number of adverse events. Secondary outcomes were number of MRI enhancing T1 lesions and new T2 lesions, annual relapse rate, changes in the Expanded Disability Status Scale score, timed 25 foot walk test and timed 10 foot tandem walk tests.

RESULTS:

Median change in BOD was 287 mm(3) in the placebo group and 83 mm(3) in the vitamin D group (p=0.105). Serum levels of 25(OH)D increased from a mean of 54 (range 19-82) nmol/l to 110 (range 67-163) nmol/l in the vitamin D group. 84% of patients reached a serum 25(OH)D level >85 nmol/l in the vitamin D group and 3% in the placebo group (p<0.0001). Patients in the vitamin D group showed fewer new T2 lesions (p=0.286) and a significantly lower number of T1 enhancing lesions (p=0.004), as well as a tendency to reduced disability accumulation (p=0.071) and to improved timed tandem walk (p=0.076). There were no significant differences in adverse events or in the annual relapse rate.

CONCLUSION:

Vitamin D3 add on treatment to IFNB reduces MRI disease activity in MS.

TRIAL REGISTRATION NUMBER:

EudraCT number 2007-001958-99 and ClinicalTrialsGov number NCT01339676.

Comment in

Treating multiple sclerosis with vitamin D. [J Neurol Neurosurg Psychiatry. 2012]

Multiple sclerosis: Multiple sclerosis therapy–vitamin D under spotlight. [Nat Rev Neurol. 2012]

via A randomised, double blind, pl… [J Neurol Neurosurg Psychiatry. 2012] – PubMed – NCBI.

Mult Scler Int. 2012;2012:802796. doi: 10.1155/2012/802796. Epub 2012 Aug 5.

A Randomised, Double-Blind, Placebo-Controlled Trial with Vitamin D3 in MS: Subgroup Analysis of Patients with Baseline Disease Activity Despite Interferon Treatment.

Aivo J, Lindsröm BM, Soilu-Hänninen M.

Source

Department of Neurology, Turku University Hospital and University of Turku, Kiinamyllynkatu 4-8, 20520 Turku, Finland.

Abstract

We present a subgroup analysis of the first double-blind, placebo-controlled, randomised trial with vitamin D3 in MS. In the overall study population, there were 34 patients in the vitamin D arm and 32 patients in the placebo arm. All the patients were using interferon-β-1b (IFNB) therapy. The subgroup consisted of 15 patients in the vitamin D arm and 15 patients in the placebo arm, who had either at least one relapse during the year preceding the study or enhancing T1 lesions at the baseline MRI scan. We measured the total number of MRI T1 enhancing lesions, the number of new/enlarging T2 lesions and T2 lesion volume (BOD) (mm(3)), EDSS (Expanded Disability Status Scale), annual relapse Rate (ARR), timed 25-foot walk (T25FW), and timed 10-foot tandem walk (TT10W) at baseline and at 12 months in the vitamin D-treated and in the placebo-treated patients. There was a statistically significant reduction in the number of T1 enhancing lesions, a smaller T2 lesion volume growth and less new/enlarging T2 brain MRI lesions in the vitamin D3-treated than in the placebo-treated subgroup patients. The MRI results were slightly more pronounced in the subgroup than in the overall study population.

PMID:

22919492

[PubMed]

PMCID:

PMC3420140

Free PMC Article

via A Randomised, Double-Blind, Placebo-Controlle… [Mult Scler Int. 2012] – PubMed – NCBI.