Homocysteine and Multiple Sclerosis


Authors: M. Cingelová;  L. Procházková;  J. Martinková;  P. Kukumberg
Authors‘ workplace: II. Neurologická klinika LF UK a UN Bratislava
Published in: Cesk Slov Neurol N 2013; 76/109(5): 565-569
Category: Review Article

Overview

Multiple sclerosis (MS) is a chronic inflammatory autoimunne disorder that affects central nervous system. The etiology of MS remains unknown. Genetic predisposition combined with environmental factors seem to be involved. Recently, homocysteine has been proposed as a potentially important player in MS pathogenesis, not only during disease development but during disease progression as well. Among the MS-linked psychiatric problems, the association between hyperhomocysteinemia (hyperHCy) and depression and cognitive dysfunction is the most researched. HyperHCy might be inherited or acquired. The most common cause of acquired HCy includes vitamin B12 and folate deficiency, chronic renal failure, hypothyreoidism and chronic drug exposure. Therefore, it is important to identify these comorbidities or risk factors early, as they may impact on the pathogenesis and course of MS.

Key words:
multiple sclerosis – homocysteine – depression – cognitive impairment

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manu­script met the ICMJE “uniform requirements” for biomedical papers.


Sources

1. Čaprnda M, Rašlová K. Súčasný pohľad na homocysteín vo svete poznatkov klinických štúdií. Interná Med 2006; 6(6): 344– 347.

2. Weiss N, Keller C, Hoffmann U, Loscalzo J. Endothelial dysfunction and atherothrombosis in mild hyperhomocysteinemia. Vasc Med 2002; 7(3): 227– 239.

3. Austin RC, Lentz SR, Werstuck GH. Role of hyperhomocysteinemia in endothelial dysfunction and atherothrombotic disease. Cell Death Differ 2004; 11 (Suppl 1): S56– S64.

4. Mattson MP, Shea TB. Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders. Trends Neurosci 2003; 26(3): 137– 146.

5. Parnetti L, Bottiglieri T, Lowenthal D. Role of homocysteine in age‑related vascular and non‑vascular diseases. Aging 1997; 9(4): 241– 257.

6. Durand P, Prost M, Loreau N, Lussier‑ Cacan S, Blache D. Impaired homocysteine metabolism and atherothrombotic disease. Lab Invest 2001; 81(5): 645– 672.

7. Finkelstein JD. The metabolism of homocysteine: pathways and regulation. Eur J Pediatr 1998; 157 (Suppl 2): S40– S44.

8. Valkovič P, Blažíček P, Benetin J, Kukumberg P. Homocysteín, levodopa a Parkinsonova choroba. Cesk Slov Neurol N 2006; 69/ 102(3): 183– 188.

9. Selhub J. Homocysteine metabolism. Annu Rev Nutr 1999; 19: 217– 246.

10. Welch GN, Loscalzo J. Homocysteine and atherothrombosis. N Engl J Med 1998; 338(15): 1042– 1050.

11. Morris SM, Jacques PF, Rosenberg IH, Selhub J, Bowman BA, Gunter EW et al. Serum total homocysteine concentration is related to self‑ reported heart attack or stroke historyamong men and women in the NHANES III. J Nutr 2000; 130(12): 3073– 3076.

12. Perry IJ, Refsum H, Morris RW, Ebrahim SB, Ueland PM, Shaper AG. Prospective study of serum total homocysteine concentration and risk of stroke in middle‑ aged British men. Lancet 1995; 346(8987): 1395– 1398.

13. Haynes WG. Hyperhomocysteinemia, vascular function and atherosclerosis: effects of vitamins. Cardiovasc Drugs Ther 2002; 16(5): 391– 399.

14. Stanger O, Herrmann W, Pietrzik K, Fowler B, Geisel J, Dierkes J et al. DACH‑ LIGA homocystein (german, austrian and swiss homocysteine society): consensus paper on the rational clinical use of homocysteine, folic acid and B‑ vitamins in cardiovascular and thrombotic diseases: guidelines and recommendations. Clin Chem Lab Med 2003; 41(11): 1392– 1403.

15. Sachdev P. Homocysteine and neuropsychiatric disorders. Rev Bras Psiquiatra 2004; 26(1): 49– 55.

16. Havrdová E. Roztroušená skleróza. Neurol Prax 2008; 4: 193.

17. Obeid R, Kostopoulos P, Knapp JP, Kasoha M, Becker G, Fassbender K et al. Biomarkers of folate and vitamin B12 are related in blood and cerebrospinal fluid. Clin Chem 2007; 53: 326– 333.

18. Baig SM, Ali Qureshi G. Homocysteine and vitamin B12 in multiple sclerosis. Biogenic Amines 1995; 11(6): 479– 485.

19. Besler HT, Comoglu S. Lipoprotein oxidation, plasma total anti oxidant capacity and homocystein level in patients with multiple sclerosis. Nutr Neurosci 2003; 6(3): 189– 196.

20. Salemi G, Gueli MC, Vitale F, Battaglieri F, Guglielmini E, Ragonese P et al. Blood lipids, homocysteine, stress factors, and vitamins in clinically stable multiple sclerosis patients. Lipids Health Dis 2010; 9: 19.

21. Masoud SA, Fakharian EN. Relationship between homocysteine blood level and multiple sclerosis. Inter J Med Med Sciences 2009; 1(5): 230– 232.

22. Ramsaransing GS, Fokkema MR, Teelken A, Arutjunyan AV, Koch MK, DeKeyser J. Plasma homocysteine levels in multiple sclerosis. J Neurol Neurosurg Psychiatry 2006; 77(2): 189– 192.

23. Reynolds E. Vitamin B12, folic acid and the nervous system. Lancet Neurol 2006; 5(11): 949– 960.

24. Russo C, Morabito F, Piromalli LF. Hyperhomocysteinemia in multiple sclerosis. Eur J Neurol 2003; 10 (Suppl): 104.

25. Tajouri L, Martin V, Gasparini C, Ovcaric M, Cur­tain R, Lea RA et al. Genetic investigation of methylene tetra hydro folate Reductase (MTHFR) and Catecol‑ 0- methyl transferase (COMT) in multiple sclerosis. Brain Res Ball 2006; 69(3): 327– 331.

26. Ashtari F, Abari Sh, Salehi Nejad V. Serum homocysteine level in patients with multiple sclerosis. J Res Med Sci 2005; 10(5): 302– 304.

27. Goodkin DE, Jacobsen DW, Galvez N, Daughtry M,Secic M, Green R. Serum cobalamin deficiency is uncommon in multiple sclerosis. Arch Neurol 1994; 51: 1110– 1114.

28. Rio J, Montalban J, Tintore M, Codina A, Malinau MR. Serum homocystein levels in multiple sclerosis. Arch Neurol 1994; 51: 1181.

29. Dalal S, Parkin SM, Homer‑ Vanniasinkam S, Nicolaou A. Effect of homocysteine on cytokine production by human endothelial cells and monocytes. Ann Clin Biochem 2003; 40: 534– 541.

30. Liao D, Tan H, Hui R, Li Z, Jiang X, Gaubatz Jet al. Hyperhomocysteinemia decreases circulating high‑density lipoprotein by inhibiting apolipoprotein A‑ I protein synthesis and enhancing HDL cholesterol clearance. Circ Res 2006; 99: 598– 606.

31. Kim JK, Mastronardi FG, Wood DD, Lubman DM, Zand R, Moscarello MA. Multiple sclerosis: an important role for post‑translational modifications of myelin basic protein in pathogenesis. Mol Cell Proteomics 2003; 2(7): 453– 462.

32. Lipton SA, Kim KW, Choi YB, Kumar S, D’Emilia DM, Rayudu PV et al. Neurotoxicity associated with dual actions of homocysteine at the N‑ methyl‑ D‑ aspartate receptor. Proc Natl Acad Sci USA 1997; 94: 5923– 5928.

33. Diaz‑ Arrastia R. Homocysteine and Neurologic disease. Arch Neurol 2000; 57(10): 1422– 1428.

34. Krumdieck CL, Prince CW. Mechanisms of homocysteine toxicity on connective tissues: implications for the morbidity of aginig. J Nutr 2000; 130: 365– 368.

35. Jakubowski H. Homocysteine thiolactone: metabolic origin and protein homocysteinylation in humans. J Nutr 2000; 130: 377– 381.

36. Au‑ Yeung KK, Woo CW, Sung FL, Yip JC, Siow YL. Hyperhomocysteinemia activates nuclear factor‑ kappa B in endothelial cells via oxidative stress. Circ Res 2004; 94(1): 28– 36.

37. Petzold A, Brassat D, Mas P, Rejdak K, Keir G, Giovannoni G et al. Treatment response in relation to inflammatory and axonal surrogate marker in multiple sclerosis. Mult Scler 2004; 10: 281– 283.

38. Benz B, Grima G, Do KQ. Glutamate‑induced homocysteic acid release from astrocytes: possible implication in glia‑ neuron signaling. Neuroscience 2004; 124(2): 377– 386.

39. Bottiglieri T, Laundry M, Crellin R, Toone BK, Carney MW, Reynolds EH. Homocysteine, folate methylation, and monoamine metabolism in depression. J Neurol Neurosurg Psychiatry 2000; 69: 228– 232.

40. Tolmunen T, Hintikka J, Voutilainen S, Ruusunen A,Alfthan G, Nyyssonen K et al. Association between depressive symptoms and serum concentration of homocysteine in men: a population study. Am J Clin Nutr 2004; 80: 1574– 1578.

41. Bjelland I, Tell GS, Vollest SE, Refsum H, Ueland PM. Folate, vitamin B12, homocysteine, and the MTHFR 677 → T polymorphism in anxiety and depression: the Hordaland Homocysteine Study. Arch Gen Psychiatry 2003; 60(6): 618– 626.

42. Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta‑analysis. BMJ 2002; 325: 1202– 1209.

43. Thomas AJ, O’Brien JT, Davis S, Ballard C, Barber R, Kalaria RN et al. Ischemic basis for deep white matter hyperintensities in major depression. A neuropathological study. Arch Gen Psychiatry 2002; 59: 785– 792.

44. Almeida OP, Lautenschlager N, Flicker L, Leedman P,Vasikaran S, Gelavis A et al. Association between homocysteine, depression, and cognitive function in community‑ dwelling older women from Australia. J Am Geriatr Soc 2004; 52(2): 327– 328.

45. Bottiglieri T. Homocysteine and folate metabolism in depression. Prog Neuro Psychopharmacol Biol Psychiatry 2005; 29: 1103– 1112.

46. Havrdová E, Čechová Z. Roztroušená skleróza a depresia. Psychiatr Prax 2005; 6(5): 224– 226.

47. Triantafyllou N, Evangelopoulos ME, Kimiskidis VK, Kararizou E, Boufidou F, Fountoulakis KN et al. Increased plasma homocysteine levels in patients with multiple sclerosis and depression. Ann Gen Psychiat 2008; 7: 17.

48. Faiss JH. Cognitive dysfunction in different stages in multiple sclerosis‑ presentation of 3 cases. J Neurol 2007; 254 (Suppl): II77– II79.

49. Brassington JC, Marsh NV. Neuropsychological aspects of multiple sclerosis. Neuropsychol Rev 1998; 8(2): 43– 77.

50. Russo C, Morabito F, Louise F, Piromalli A, Battaglia L, Vinci A et al. Hyperhomocysteinemia is associated with cognitive impairment in multiple sclerosis. J Neurol 2008; 255: 64– 69.

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Paediatric neurology Neurosurgery Neurology

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