Effect of Methylprednisolone and Interferon Treatment on Blood Vitamin B12, Folic Acid and Homocysteine Levels in Patients with Multiple Sclerosis

Year 2019, , 325 - 338, 30.09.2019

Mesrure Köseoğlu , İpek Midi Tülay Çevlik Serkan Özben , Goncagül Haklar Dilek Günal

https://doi.org/10.26453/otjhs.472020

Abstract

Changes in blood homocysteine, vitamin B12 and
folic acid levels have been reported during multiple sclerosis (MS) and
treatment period; however, the exact mechanism has not been enlightened. We investigated the changes of serum
B12, folic acid, and plasma homocysteine levels before and after high-dose IV
methylprednisolone treatment and after interferon-β treatment in patients
admitted with an acute attack of MS.31 patients followed for clinically
definite MS (8 male, 23 female) and 10 control individuals were included in the
study. 20 patients were admitted with an acute attack and were administered 1000 mg/day methylprednisolone for 7 days. 27
patients started interferon-β treatment. Serum B12, folic acid, and plasma
Homocysteine levels measured before and after the 1 month after high dose
steroid treatment and after 3-month interferon-β treatment were compared with
pre-treatment levels and healthy controls. Baseline B12 levels were lower in patients with MS than in healthy
controls, which is consistent with previous findings. Both methylprednisolone and interferon-β treatments increased
serum B12 and folic acid levels compared with baseline; however, only the
increase following methylprednisolone treatment was statistically significant.In
our study, elevated B12 and folic acid levels and decreasing of homocysteine
levels without reaching statistical significance following methylprednisolone
have caused different debates.

Keywords

multiple sclerosis, methylprednisolone, interferon-beta, vitamin B12, folic acid, homocysteine

Multipl Skleroz Hastalarında Metilprednizolon ve İnterferon Tedavisinin Kan Vitamin B12, Folik Asid ve Homosistein Düzeyleri Üzerine Etkisi

Abstract

Multipl Skleroz (MS) hastalığının
seyrinde ve tedavi sürecinde homosistein, vitamin B12 ve folik asit
düzeylerindeki değişiklikler bildirilmiş ancak tam mekanizması
aydınlatılamamıştır. Çalışmamızda, akut atak ile başvuran
hastalarda yüksek doz metilprednizolon tedavisi öncesinde, sonrasında ve interferon-β tedavisi sonrasında
serum B12, folik asit ve homosisitein düzeylerindeki değişiklikler
incelenmiştir. Çalışmaya 1 yıl içinde akut atak ile başvuran,
klinik kesin MS tanısı konarak takip edilen 31 hasta (8 erkek, 23 kadın) ve 10 kontrol olgusu dahil edildi. 20 hasta
akut atak ile başvurdu 7 gün süreyle 1000 mg/gün metilprednizolon uygulandı. 27
hastaya interferon-β tedavisi
başlandı. Yüksek doz steroid tedavi sonrası 1. ay düzeyleri ve interferon-β tedavisi alan hastaların 3. ay sonundaki serum vitamin B12, folik asit ve plazma homosistein düzeyleri ölçülerek kontrol grubu ve tedavisi
öncesi düzeyleri ile karşılaştırıldı. Kontrol grubuna göre MS hastalarının
bazal B12 değerleri daha önceki bulgularla tutarlı olarak daha düşüktü. Hem
metilprednizolon, hem de interferon-β tedavisi sonrası B12 ve folik asid değerlerinde
yükselme saptandı ancak sadece metilprednizolon tedavisi sonrasındaki artış istatiksel
olarak anlamlıydı. Çalışmamızda saptanan metilprednizolon sonrası yükselen B12 ve folik asid düzeyleri
ve istatistiksel anlamlılığa ulaşmayan homosistein düzeylerindeki düşme eğilimi farklı
tartışmalar yaratmaktadır.

Keywords

multipl skleroz, metilprednizolon, interferon-β, vitamin B12, folik asit, homosistein

References

• Chitnis T, Khoury SJ. Neuroimmunology. In Neurology in Clinical Practice. Ed: Bradly WG, Daroff RB, Fenichel GM, Jankovic J. Volume 1, Fifth edition. Butterworth-Heinemann, Elsevier Inc; 2008. p. 807–829.
• Grann V, Glass GB. Blood serum levels and intestinal absorption of vitamin B12 in multiple sclerosis. J Lab Clin Med. 1961;57:562–567.
• Simpson CA. Vitamin B12 levels in the serum and cerebrospinal fluid in multiple sclerosis. J Neurol Neurosurg Psychiatry. 1964;27:174–77.
• Bieniowa A, Czarnecki J, Retinger M. Vitamin B12 level in the blood serum in multiple sclerosis. Neurol Neurochir Psychiatr Pol. 1964;14:797–800.
• Basil W, Brown JK, Matthews DM. Observations on vitamin B12 in serum and cerebrospinal fluid in multiple sclerosis. J Clin Path. 1965;18:317–321.
• Nijst TQ, Wevers RA, Schoonderwaldt HC, et al. Vitamin B12 and folate concentrations in serum and cerebrospinal fluid of neurological patients with special reference to multiple sclerosis and dementia. J Neurol Neurosurg Psychiatry. 1990;53:951–954.
• Reynolds EH, Linnell JC, Faludy JE. Multiple sclerosis associated with vitamin B12 deficiency. Arch Neurol. 1991;48:808–811.
• Reynolds EH, Bottiglieri T, Laundy M, et al. Vitamin B12 metabolism in multiple sclerosis. Arch Neurol. 1992;49:649–652.
• Besler HT, Comoğlu S. Lipoprotein oxidation, plasma total antioxidant capacity and homocysteine level in patients with multiple sclerosis. Nutr Neurosci. 2003;6:189–196.
• Vrethem M, Mattsson E, Hebelka H, et al. Increased plasma homocysteine levels without signs of vitamin B12 deficiency in patients with multiple sclerosis assessed by blood and cerebrospinal fluid homocysteine and methylmalonic acid. Mult Scler. 2003;9:239–245.
• Frequin ST, Wevers RA, Braam M, Barkhof F, Hommes OR. Decreased vitamin B12 and folate levels in cerebrospinal fluid and serum of multiple sclerosis patients after intravenous methylprednisolone. J Neurol. 1993;240:305–308.
• McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the international panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50:121–127.
• Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33:1444–1452.14. Bolander-Gouaille C, Bottiglieri T. Homocysteine: Related Vitamins and Neuropsychiartics Disorders. Paris: Springer; 2003.15. Qureshi GA, Halawa A, Baig S, et al. Multiple sclerosis and neurotransmission. Biogenic Amines. 1996;12:353–376.
• Baig SM, Qureshi GA, Minami M. The interrelation between the deficiency of vitamin B12 and neurotoxicity of homocysteine with nitrite in some of neurologic disorders. Biogenic Amines. 1998;14:1–14.
• Ramsaransing GS, Fokkema MR, Teelken A, et al. Plasma homocysteine levels in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2006;77:189–192.
• Smith DR, Balashov KE, Hafler DA, et al. Immune deviation following pulse cyclophosphamide/methylprednisolone treatment of multiple sclerosis: increased interleukin-4 production and associated eosinophilia. Ann Neurol. 1997;42:313– 318.
• Miller A, Shapiro S, Gershtein R, et al. Treatment of multiple sclerosis with copolymer-1 (copaxone): implicating mechanisms of Th1 to Th2/Th3 immunedeviation. J Neuroimmunol. 1998;92:113–121.
• Kozovska ME, Hong J, Zang YC, et al. Interferon beta induces T-helper 2 immune deviation in MS. Neurology. 1999;53:1692–1697.
• Borgia G, Reynaud L, Gentile I, et al. Pernicious anemia during IFN-alpha treatment for chronic hepatitis C. J Interferon Cytokine Res. 2003;23:11–12.
• Nousari HC, Kimyai-Asadi A, Tausk FA. Subacute cutaneous lupus erythematosus associated with interferon beta 1a. Lancet. 1998;352:1825–1826.
• Durelli L, Ferrero B, Oggero A, et al. Autoimmune events during interferon beta 1b therapy for multiple sclerosis. J Neurol Sci. 1999;162:74– 83.
• Kreiss Y, Cohen O, Pras E, et al. Subacute thyroiditis in a patient with multiple sclerosis treated with interferon beta 1a. Neurology 1999;53:1606.
• Schwid SR, Goodman AD, Mattson DH. Autoimmune hyperthyroidism in patients with multiple sclerosis treated with interferon beta 1b. Arch Neurol. 1997;54:1169–1170.
• Rotondi M, Mazziotti G, Biondi B, et. Long-term treatment with interferon beta therapy for multiple sclerosis and occurrence of Graves’ disease. J Endocrinol Invest. 2000; 23:321– 324.
• Miller A, Korem M, Almog R, et al. Vitamin B12, demyelination, remyelination and repair in multiple sclerosis. J Neurol Sci. 2005;233:93–97.
• Mastronardi FG, Min W, Wang H, et al. Attenuation of experimental autoimmune encephalomyelitis and non-immune demyelination by IFN-beta plus vitamin B12: treatment to modify notch-1/sonic hedgehog balance. J Immunol. 2004;172:6418–6426.