Correlation between vitamin D and alterations in MRI among patients with multiple sclerosis
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Department of Neurology, Medical University, Lublin, Poland
Patryk Piotr Jasielski   

Department of Neurology, Medical University of Lublin, Lublin, Poland
Multiple sclerosis (MS) is a disease of unknown etiology. Diagnosis of MS is primarily based on detection of myelin damage by magnetic resonance imaging (MRI) and classification of demyelination according to the McDonald Criteria. Cholecalciferol (vitamin D3) has been shown to affect the onset and progression of MS via its immunomodulating properties. The role of vitamin D in MS pathogenesis and treatment deserves further investigation, as there is sufficient evidence to suggest a correlation between vitamin D blood level and brain MRI lesion load.

State of knowledge:
Elevated blood vitamin D concentration is linked with demyelination, as determined by T2-weighted and gadolinium-enhanced MRI. Blood vitamin D blood levels are affected by sun exposure, among other factors; however, there is no evident connection between abnormalities in myelination and seasonality. Vitamin D supplementation among MS patients has been associated with a lower probability of new lesions and loss of existing lesion volume, as observed seen in T1-weighted MRI scans (p=0.03). An increase in TGF-beta levels was noted among patients using vitamin D supplementation, which may suggest a mechanism by which cholecalciferol may improve MS prognosis. Patients with clinically isolated syndrome (CIS) exhibited an inverse correlation between vitamin D concentration and risk of new lesions as seen in T2-weighted MRI scans. Moreover, vitamin D intake among these patients lowered the risk of progression to clinically definite multiple sclerosis (CDMS). Daily intake of vitamin D during fingolimod treatment correlated strongly with lower numbers of new lesions. High dose vitamin D supplementation during interferon beta-1a treatment was linked to lower mean percentage of lesions compared with volume pre-treatment seen by T2-weighted MRI.

Recent findings advocate for the monitoring of vitamin D blood levels in MS patients. Vitamin D supplementation should be considered in both MS patients and patients with CIS, where other signs of disease may be delayed. Moreover, vitamin D supplementation appears to lower the likelihood of new demyelination changes apparent in MRI examinations.

Wallin MT, Culpepper WJ, Nichols E, et al. Global, regional, and national burden of multiple sclerosis 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019; 18: 269–285.
Ramagopalan SV, Dobson R, Meier UC, et al. Multiple sclerosis: risk factors, prodromes, and potential causal pathways. Lancet Neurol. 2010; 9: 727–739.
Handel AE, Giovannoni G, Ebers GC, et al. Environmental factors and their timing in adult-onset multiple sclerosis. Nat Rev Neurol. 2010; 6: 156–66.
McDonald WI, Compston A, Eden G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001; 50(1): 121–127.
Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018; 17(2): 162–173.
Filippi M, Rocca MA, Ciccarelli O, et al. MRI criteria for the diagnosis of multiple sclerosis: MAGNIMS consensus guidelines. Lancet Neurol. 2016; 15(3): 292–303.
Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983; 33(11): 1444–1452.
Marzęda A, Szkatuła J, Petit V, et al. Witamina D w zdrowiu oraz w chorobie – przegląd literatury. In: Środowisko a zdrowie. Andrzej Borzęcki (ed), Lublin 2017, Norbertinum Wydawnictwo – Drukarnia – Księgarnia spółka z o.o: 304–312.
Correale J, Ysrraelit MC, Gaitán MI. Immunomodulatory effects of Vitamin D in multiple sclerosis. Brain 2009; 132: 1146–60.
Di Rosa M, Malaguarnera M, Nicoletti F, et al. Vitamin D3: a helpful immuno-modulator. Immunology 2011; 134: 123–139.
McFarland HF, Martin R. Multiple sclerosis: a complicated picture of autoimmunity. Nat Immunol. 2007; 8: 913–919.
Chen S, Sims GP, Chen XX, et al. Modulatory effects of 1,25-dihydroxy -vitamin D3 on human B cell differentiation. J Immunol. 2007; 179: 1634–1647.
Nuyts AH, Lee WP, Bashir-Dar R, et al. Dendritic cells in multiple sclerosis: key players in the immunopathogenesis, key players for new cellular immunotherapies? Mult Scler. 2013; 19: 995–1002.
O’Connell K, Sulaimani J, Basdeo SA. Effects of vitamin D3 in clinically isolated syndrome and healthy control participants: A double-blind randomised controlled trial. Mult Scler J Exp Transl Clin. 2017; 3(3). doi: 10.1177/2055217317727296
Mowry EM, Waubant E, McCulloch CE, et al. Vitamin D status predicts new brain magnetic resonance imaging activity in multiple sclerosis. Ann Neurol. 2012; 72(2): 234–240.
Fahmi RM, Lotfy SM, Mohamed WS, et al. Vitamin D levels in patients with multiple sclerosis. Egypt J Neurol Psychiatr Neurosurg. 2014; 51(2): 145–152.
Mowry EM, Azevedo CJ, McCulloch CE, et al. Body mass index, but not vitamin D status, is associated with brain volume change in MS. Neurology. 2018; 91(24): e2256–e2264.
Darwish H, Farran N, Hannoun S, et al. Serum vitamin D level is associated with speed of processing in multiple sclerosis patients. J Steroid Biochem Mol Biol. 2020; 200: 105628.
Bäcker-Koduah P, Bellmann-Strobl J, Scheel M, et al. Vitamin D and Disease Severity in Multiple Sclerosis-Baseline Data From the Randomized Controlled Trial (EVIDIMS). Front Neurol. 2020; 11: 129.
Loken-Amsrud KI, Holmoy T, Bakke SJ, et al. Vitamin D and disease activity in multiple sclerosis before and during interferon-ß treatment. Neurology. 2012; 79(3): 267–273.
Wawrzyniak S, Mikołajewska E, Kuczko-Piekarska E, et al. Association of vitamin D status and clinical and radiological outcomes in a treated MS population in Poland. Brain Behav. 2016; 7(2): e00609.
Abbatemarco JR, Fox RJ, Li H, et al. Vitamin D and MRI measures in progressive multiple sclerosis. Mult Scler Relat Disord. 2019; 35: 276–282.
Aivo J, Hänninen A, Ilonen J, et al. Vitamin D3 administration to MS patients leads to increased serum levels of latency activated peptide (LAP) of TGF-beta. J Neuroimmunol. 2015; 280: 12–15.
Sistani SS, Moghtaderi A, Dashipoor AR, et al. Seasonal variations of 25-OH vitamin D serum levels in Multiple Sclerosis patients with relapse using MRI. Eur J Transl Myol. 2019; 29(3): 8361.
Zivadinov R, Treu CN, Weinstock-Guttman B. Interdependence and contributions of sun exposure and vitamin D to MRI measures in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2013; 84(10): 1066.
Camu W, Lehert P, Pierrot-Deseilligny C, et al. Cholecalciferol in relapsing-remitting MS: A randomized clinical trial (CHOLINE). Neurol Neuroimmunol Neuroinflamm. 2019; 7(1): e648.
Derakhshandeh, Etemadifar M, Feizi A, et al. 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. 2013; 113(3): 257–263.
Stein MS, Liu Y, Gray OM, et al. A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis. Neurology.2011; 77(17): 1611–1618.
Smolders J, Mimpen M, Oechtering J, et al. Vitamin D3 supplementation and neurofilament light chain in multiple sclerosis. Acta Neurol Scand. 2020; 141(1): 77–80.
Rosjo E, Lindstrom JC, Holmoy T, et al. Natural Variation of Vitamin D and Neurofilament Light Chain in Relapsing-Remitting Multiple Sclerosis. Front Neurol. 2020; 11: 329.
Sandberg L, Biström M, Salzer J, et al. Vitamin D and axonal injury in multiple sclerosis. Mult Scler. 2016; 22(8): 1027–1031.
Zhang Y, Liu G, Han X, et al. The association of serum 25-hydroxyvitamin D levels with multiple sclerosis severity and progression in a case-control study from China. J Neuroimmunol. 2016; 297: 127–131.
Dörr J, Bäcker-Koduah P, Wernecke KD, et al. High-dose vitamin D supplementation in multiple sclerosis – results from the randomized EVIDIMS (efficacy of vitamin D supplementation in multiple sclerosis) trial. Mult Scler J Exp Transl Clin. 2020; 6(1): 2055217320903474.
Efendi H. Clinically Isolated Syndromes: Clinical Characteristics, Differential Diagnosis, and Management. Noro Psikiyatr Ars. 2015; 52(Suppl 1): 1–11.
Shaheen HA, Sayed SS, Daker Li, et al. Does vitamin D deficiency predict early conversion of clinically isolated syndrome? A preliminary Egyptian study. Int J Neurosci. 2018; 128(10): 946–951.
Martinelli V, Dalla Costa G, Colombo B, et al. Vitamin D levels and risk of multiple sclerosis in patients with clinically isolated syndromes. Mult Scler. 2014; 20(2): 147–155.
Mowry EM, Pelletier D, Gao Z. Vitamin D in clinically isolated syndrome: evidence for possible neuroprotection. Eur J Neurol. 2016; 23(2): 327–332.
Naeini AR, Darvishi M, Aminianfar M, et al. Evaluation of the frequency and the relationship between EBV VCA IgM positive and EBV VCA IgG positive and serum level of 25 (OH) D3 in patients with CIS. Int J Pharm Sci Res. 2019; 11: 358–362.
Ascherio A, Munger KL, White R, et al. Vitamin D as an early predictor of multiple sclerosis activity and progression. JAMA Neurol. 2014; 71(3): 306–14.
Linden J, Granasen G, Salzer J, et al. Inflammatory activity and vitamin D levels in an MS population treated with rituximab. Mult Scler J Exp Transl Clin. 2019 11; 5(1): 2055217319826598.
Hupperts R, Smolders J, Vieth R, et al. Randomized trial of daily high-dose vitamin D3 in patients with RRMS receiving subcutaneous interferon ß-1a. Neurology. 2019; 93(20): e1906–e1916.
Hongell K, Silva DG, Ritter S, et al. Efficacy and safety outcomes in vitamin D supplement users in the fingolimod phase 3 trials. J Neurol. 2018; 265(2): 348–355.
Ferre’ L, Clarelli F, Sferruzza G, et al. Basal vitamin D levels and disease activity in multiple sclerosis patients treated with fingolimod. Neurol Sci. 2018; 39(8): 1467–1470.
Fitzgerald KC, Munger KL, Köchert K, et al. Association of Vitamin D Levels With Multiple Sclerosis Activity and Progression in Patients Receiving Interferon Beta-1b. JAMA Neurol. 2015; 72(12): 1458–1465.
Feng X, Wang Z, Howlett-Prieto Q, et al. Vitamin D enhances responses to interferon-ß in MS. Neurol Neuroimmunol Neuroinflamm. 2019; 6(6): e622.
Munger KL, Köchert K, Simon KC, et al. Molecular mechanism underlying the impact of vitamin D on disease activity of MS. Ann Clin Transl Neurol. 2014; 1(8): 605–617.
Rotstein DL, Healy BC, Malik MT, et al. Effect of vitamin D on MS activity by disease-modifying therapy class. Neurol Neuroimmunol Neuroinflamm. 2015; 2(6): e167.