Evaluation of the relationship between serum cholesterol levels and multiple sclerosis disease activity

Objectives: Multiple sclerosis (MS) is an immune-mediated, inflammatory, demyelinating, neurodegenerative disease of the central nervous system affecting young adults. Cholesterol and lipids are essential components of nerve cells and are abundant in the myelin sheath. In this study, we aimed to investigate the relationship between plasma cholesterol levels and severity of the disease and lesion burden in cranial magnetic resonance imaging. Methods: A total of 70 patients (22 males and 48 females) with the diagnosis of MS were included in the study. Age, gender, duration of disease, Expanded Disability Status Scale (EDSS) scores, total number of relapses since diagnosis, current treatment and lipid levels of all participants were recorded. The patients were grouped according to EDSS scores, total number of relapses and number of lesions observed in cranial MRI and the data were compared among the groups. Results: The mean age was 38.62 ± 9.94 years and the duration of the disease was 7.50 ± 5.88 years. The mean EDSS score was 2.80 ± 1.69. Total cholesterol, triglyceride and LDL levels were found to be significantly higher in the group with more than 3 relapses. Patients with > 9 lesions were older and EDSS scores were higher. In correlation analysis; there was a significant positive correlation between total cholesterol and LDL levels and EDSS scores and disease duration. Conclusions: We found that the number of relapses, disease duration, and EDSS scores were significantly correlated with cholesterol levels. The changes in plasma cholesterol levels which are easily accessible laboratory tests may provide insight into MS disease activity and progression.

Keywords:

multiple sclerosis, total cholesterol, low-density lipoprotein high-density lipoprotein, triglycerides,

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1. Comabella M, Montalban X. Body fluid biomarkers in multiple sclerosis. Lancet Neurol 2014;13:113-26.
2. Durfinova M, Prochazkova L, Petrlenicova D, Bystricka Z, Oresanska K, Kuracka L, et al. Cholesterol level correlate with disability score in patients with relapsing-remitting form of multiple sclerosis. Neurosci Lett. 2018;687:304-7.
3. Zhornitsky S, McKay KA, Metz LM, Teunissen CE, Rangachari M. Cholesterol and markers of cholesterol turnover in multiple sclerosis: relationship with disease outcomes. Mult Scler Relat Disord 2016;5:53-65.
4. Maggio B, Cumar FA. Experimental allergic encephalomyelitis: dissociation of neurological symptoms from lipid alterations in brain. Nature 1975;253:364-5.
5. Bjorkhem I, Lutjohann D, Diczfalusy U, Stahle L, Ahlborg G, Wahren J. Cholesterol homeostasis in human brain: turnover of 24S-hydroxycholesterol and evidence for a cerebral origin of most of this oxysterol in the circulation. J Lipid Res 1998;39:1594-600.
6. Leoni V, Masterman T, Diczfalusy U, De Luca G, Hillert J, Bjorkhem I. Changes in human plasma levels of the brain specific oxysterol 24S-hydroxycholesterol during progression of multiple sclerosis. Neurosci Lett 2002;331:163-6.
7. Teunissena CE, Dijkstra CD, Polman CH, Hoogervorst ELJH, von Bergman K, Lütjohann D. Decreased levels of the brain specific 24S-hydroxycholesterol and cholesterol precursors in serum of multiple sclerosis patients. Neurosci Lett 2003;347:159-62.
8. Vega GL, Weiner MF, Lipton AM, von Bergmann K, Lütjohann D, Moore C, et al. Reduction in levels of 24S-hydroxycholesterol by statin treatment in patients with Alzheimer disease. Arch Neurol 2003;60:510-5.
9. Tall AR, Yvan-Charvet L. Cholesterol, inflammation and innate immunity. Nat Rev Immunol 2015;15:104-16.
10. Sitia S, Tomasoni L, Atzeni F, Ambrosio G, Cordiano C, Catapano A, et al. From endothelial dysfunction to atherosclerosis. Autoimmun Rev 2010;9:830-4.
11. Frohman EM, Racke MK, Raine CS. Multiple sclerosis--the plaque and its pathogenesis. N Engl J Med 2006;354:942-55.
12. Schmitz G, Grandl M. Role of redox regulation and lipid rafts in macrophages during Ox-LDL-mediated foam cell formation. Antioxid Redox Signal 2007;9:1499-518.
13. Newcombe J, Li H, Cuzner ML. Low density lipoprotein uptake by macrophages in multiple sclerosis plaques: implications for pathogenesis. Neuropathol Appl Neurobiol 1994;20:152-62.
14. Palavra F, Marado D, Mascarenhas-Melo F, Sereno J, Teixeira-Lemos E, Nunes CC, et al. New markers of early cardiovascular risk in multiple sclerosis patients: oxidized-LDL correlates with clinical staging. Dis Markers 2013;34:341-8.
15. Besler HT, Comoglu S. Lipoprotein oxidation, plasma total antioxidant capacity and homocysteine level in patients with multiple sclerosis. Nutr Neurosci 2003;6:189-96.
16. Fellows K, Uher T, Browne RW, Weinstock-Guttman B, Horakova D, Posova H, et al. Protective associations of HDL with blood-brain barrier injury in multiple sclerosis patients. J Lipid Res 2015;56:2010-8.
17. Jorissen W, Wouters E, Bogie JF, Vanmierlo T, Noben JP, Sviridov D, et al. Relapsing-remitting multiple sclerosis patients display an altered lipoprotein profile with dysfunctional HDL. Sci Rep 2017;7:43410.
18. Giubilei F, Antonini G, Di Legge S, Sormani MP, Pantano P, Antonini R, et al. Blood cholesterol and MRI activity in first clinical episode suggestive of multiple sclerosis. Acta Neurol Scand 2002;106:109-12.
19. Weinstock-Guttman B, Zivadinov R, Horakova D, Havrdova E, Qu J, Shyh G, et al. Lipid profiles are associated with lesion formation over 24 months in interferon-beta treated patients following the first demyelinating event. J Neurol Neurosurg Psychiatry 2013;84:1186-91.