25-Hydroxyvitamin D levels in acute monosymptomatic optic neuritis: relation to clinical severity, paraclinical findings and risk of multiple sclerosis
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Optic neuritis (ON) is a common first symptom of MS and only few studies have thus far investigated vitamin D at this early stage of MS. The objectives of the study were to examine total 25-hydroxyvitamin D levels (25HVITDL) in patients in acute (A) ON and to determine whether 25HVITD levels in AON (1) predict risk of RRMS and (2) are associated with visual tests of ON severity. A cross-sectional study was conducted of mean 25HVITDL differences between ON (n = 164) and MS (n = 948) patients and of prevalence of 25HVITDL deficiency (<50 nmol/L) in ON and MS (two-sample t test, χ 2 test). Associations between 25HVITDL and (1) clinical ON severity, (2) paraclinical findings suggestive of MS [logistic regression (LRA), Spearman correlation] and (3) hazard of MS development [Cox (C) RA] in ON patients were assessed. 25HVITDL were deseasonalized before analysis. The mean levels were 47.6 (ON) and 63.9 (MS) nmol/L (p < 0.0001), and a significantly higher prevalence of 25HVITD deficiency in ON (56 %; 35 %) (p < 0.0001), most pronounced in females, was shown. Associations were found between 25HVITDL and both CSF leukocyte count (ρ = −0.177, p = 0.028) and IgG index elevation (OR 0.980, p = 0.031). Forty-one ON patients developed MS during the study. Multivariate CRA showed no effect on hazard of MS (HR: 0.991, p 0.284). No association was found between 25HVITDL and visual tests (acuity, contrast vision) or OCT RNFL or GCL thickness. The study indicates a high prevalence of 25HVITD deficiency in AON. 25HVITDL was significantly associated with CSF leukocyte count, but not ON severity. The study indicates a possible role of vitamin D in the early stages of MS, but does not support the use of 25HVITDL as a predictor of MS development in acute ON.
KeywordsMultiple sclerosis Optic neuritis Clinically isolated syndrome Vitamin D
Conflicts of interest
Dr. Pihl-Jensen reports no disclosures. Dr. Frederiksen has served on a scientific advisory board and received funding for travel related to these activities and honoraria from Biogen Idec, Merck Serono, Teva Pharmaceutical Industries Ltd., Sanofi-Aventis, Novartis, Genzyme and Almirall. Jette Frederiksen has received speaker honoraria from Biogen Idec, Merck Serono and Teva. She has served as advisor on preclinical development for Takeda.
The study was approved by the Danish Health and Medicines Authority and the Danish Data Protection Agency. Due to the retrospective study design, approval from research ethics committee was not required.
- 6.Optic Neuritis Study Group (2008) Multiple sclerosis risk after optic neuritis: final optic neuritis treatment trial follow-up. Arch Neurol 65:727–732Google Scholar
- 9.Mowry EM, Waubant E, McCulloch CE, Okuda DT, Evangelista AA, Lincoln RR, Gourraud PA, Brenneman D, Owen MC, Qualley P, Bucci M, Hauser SL, Pelletier D (2012) Vitamin D status predicts new brain magnetic resonance imaging activity in multiple sclerosis. Ann Neurol 72:234–240PubMedCentralCrossRefPubMedGoogle Scholar
- 17.Soilu-Hanninen M, Aivo J, Lindstrom BM, Elovaara I, Sumelahti ML, Farkkila M, Tienari P, Atula S, Sarasoja T, Herrala L, Keskinarkaus I, Kruger J, Kallio T, Rocca MA, Filippi M (2012) A randomised, double blind, placebo controlled trial with vitamin D3 as an add on treatment to interferon beta-1b in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 83:565–571CrossRefPubMedGoogle Scholar
- 19.Ascherio A, Munger KL, White R, Kochert K, Simon KC, Polman CH, Freedman MS, Hartung HP, Miller DH, Montalban X, Edan G, Barkhof F, Pleimes D, Radu EW, Sandbrink R, Kappos L, Pohl C (2014) Vitamin D as an early predictor of multiple sclerosis activity and progression. JAMA Neurol 71:306–314PubMedCentralCrossRefPubMedGoogle Scholar
- 23.Derakhshandi H, Etemadifar M, Feizi A, Abtahi SH, Minagar A, Abtahi MA, Abtahi ZA, Dehghani A, Sajjadi S, Tabrizi N (2013) Preventive effect of vitamin D3 supplementation on conversion of optic neuritis to clinically definite multiple sclerosis: a double blind, randomized, placebo-controlled pilot clinical trial. Acta Neurol Belg 113:257–263CrossRefPubMedGoogle Scholar
- 24.Hupperts R (2014) Supplementation of VigantOL® oil versus placebo as add-on in patients with relapsing remitting multiple sclerosis receiving Rebif® treatment (SOLAR). https://clinicaltrials.gov/ct2/show/NCT01285401. Accessed 01 Dec 2014
- 26.Hutchinson M (2012) Dose-related Effects of vitamin D3 on immune responses in patients with clinically isolated syndrome (CISAVID). https://clinicaltrials.gov/ct2/show/NCT01728922. Accessed 01 Dec 2014
- 27.Carroll W (2013) Preventing the risk of multiple sclerosis using vitamin D in patients with a first demyelinating event in Australia and New Zealand (PrevANZ). http://www.msra.org.au/prevanz. Accessed 01 Dec 2014
- 28.Thouvennot E (2013) Efficacy of cholecalciferol (vitamin D3) for delaying the diagnosis of MS after a clinically isolated syndrome (D-Lay-MS). https://clinicaltrials.gov/ct2/show/NCT01817166?term=vitamin+d+clinically+isolated+syndrome&rank=22014. Accessed 01 Dec 2014
- 33.Sachs MC, Shoben A, Levin GP, Robinson-Cohen C, Hoofnagle AN, Swords-Jenny N, Ix JH, Budoff M, Lutsey PL, Siscovick DS, Kestenbaum B, de Boer IH (2013) Estimating mean annual 25-hydroxyvitamin D concentrations from single measurements: the Multi-Ethnic Study of Atherosclerosis. Am J Clin Nutr 97:1243–1251PubMedCentralCrossRefPubMedGoogle Scholar
- 37.Durup D, Jorgensen HL, Christensen J, Tjonneland A, Olsen A, Halkjaer J, Lind B, Heegaard AM, Schwarz P (2015) A reverse J-shaped association between serum 25-hydroxyvitamin D and cardiovascular disease mortality—the CopD-study. J Clin Endocrinol Metab (jc20144551) [Epub ahead of print]Google Scholar