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Jeneralize Tonik Klonik Tip Epilepsi Tanısı Konulan, Monoterapi ve Politerapi Olarak Antiepileptik Tedavi Alan Hastalarda Akut Faz Reaktanları ve Oksidan-Antioksidan Parametrelerin Araştırılması

Year 2021, Volume: 12 Issue: 44, 158 - 164, 24.12.2021
https://doi.org/10.17944/mkutfd.910039

Abstract

Amaç: Bu çalışmada akut faz reaktanları ile oksidatif stres ve epilepsi arasındaki ilişkinin araştırılması amaçlanmıştır.
Gereç ve Yöntem: Hasta grubu, Çocuk Nörolojisi polikliniğine başvuran ve ILAE sınıflamasına göre jeneralize tip epilepsi tanısı alan, 33’ü monoterapi, 34’ü ise politerapi şeklinde antiepileptik ilaç tedavisi almakta olan 67 hastadan oluşmaktaydı. Kontrol grubu, epilepsi veya bilinen herhangi bir kronik hastalığı olmayan, aynı yaş aralığında benzer sosyodemografik özelliklere sahip özelliklere sahip 30 sağlıklı gönüllü katılımcıyı içeriyordu. Toplam anti-oksidan durumu (TAS) ve toplam oksidan durumu (TOS) Erel tarafından geliştirilen yönteme göre ölçülmüş ve oksidatif stres indeksi (OSI) hesaplanmıştır. Hassas C-reaktif protein (Hs-CRP) seviyeleri ölçüldü.
Bulgular: Antiepileptik monoterapi ve politerapi alan hastaların hem TOS hem OSI düzeyleri kontrol grubuna göre istatistiksel olarak anlamlı derecede yüksek bulundu(p=0.004), antiepileptik monoterapi ve politerapi alan hastaların TOS düzeyleri sırasıyla 19.29±1.27, 19.22±1.26, kontrol grubu 14.49±1.75, antiepileptik monoterapi ve politerapi alan hastaların OSI düzeyleri sırasıyla 1.66±0.12, 1.72±0.11, kontrol grubu 1.27±0.11). Monoterapi ve politerapi alan hastaların Hs-CRP düzeyi (sırasıyla 0.59±0.06 mg/L, 1.09±0.06 mg/L), kontrol grubuna göre (0.42±0.02 mg/L) istatistiksel olarak anlamlı derecede yüksek bulundu.
Sonuç: Bu çalışmada, epileptik nöbetin oksidatif stres parametrelerini arttırdığı ve antioksidan mekanizmaların oksidatif hasarı azaltmada yetersiz kaldığı sonucuna varılmıştır. Ayrıca yüksek serum Hs-CRP seviyeleri göz önüne alındığında, dirençli epilepsinin tedavisinde inflamatuar süreci kontrol edebilen tedavi stratejilerinin geliştirilmesi son derece önemlidir.

Thanks

Sayın Editör Ekteki “Jeneralize tonik klonik tip epilepsi tanısı konulan ,monoterapi ve politerapi olarak antiepileptik tedavi alan hastalarda akut faz reaktanları ve oksidan - antioksidan parametrelerin araştırılması” başlıklı makale, yayın fırsatı için seçkin derginize gönderilmiş orijinal, yayınlanmamış orijinal bir makaledir. Saygılarımla. Uz.Dr.Sedat Yaşin

References

  • Menkes JH, Sarnat HB. Paroxysmal disorders. In: Menkes JH, Sarnat HB. Child Neurology (6th Ed). Philadelphia. Lippincott Williams&Wilkins. 2000; 919-1026.
  • Dasheiff RM. Sudden unexpected death in epilepsy: a series from an epilepsy surgery program and speculation on the relationship to sudden cardiac death . J Clin Neurophysiol. 1991; 8: 216-22. https://doi.org/10.1097/00004691-199104000-00010
  • Conway JM, Kriel RL, Birnbaum AK. Antiepileptic Drug Therapy in Children: An Overview. In: Swaiman KF, Ashwal S, Pediatric Neurology Principles &Practise (3th ed). Philadelphia. Mosby Elsevier. 2006; 1105-30.
  • Gershov D, Kim S, Brot N, et al. C-reactive protein binds to apoptotic cells, protects the cells from assembly of the terminal complement components, and sustains an antiinflammatory innate immune response: Implications for systemic autoimmunity. J Exp Med 2000; 192:1353-64. https://doi.org/10.1084/jem.192.9.1353
  • Doumatey AP, Zhou J, Adeyemo A, Rotimi C. High sensitivity C-reactive protein (Hs-CRP) remains highly stable in long-term archived human serum. Clin Biochem.2014 Mar;47(4-5):315-8. https://doi.org/10.1016/j.clinbiochem.2013.12.014
  • Rafieian-Kopaei M, Setorki M, Doudi M, Baradaran A, Nasri H. Atherosclerosis: process, indicators, risk factors and new hopes. Int J Prev Med. 2014 Aug;5(8):927-46.
  • Erel 0. A new automated colorimetric method for measuring total oxidant status. Clin Biochem. 2005; 38 (12): 1103-11. https://doi.org/10.1016/j.clinbiochem.2005.08.008
  • Bostjan Martinc, Iztok Grabnar, and Tomaz Vovk. The Role of Reactive Speciesin Epileptogenesis and Influence of Antiepileptic Drug Therapy on Oxidative Stress. Curr Neuropharmacol. 2012; 10(4): 328-43. https://doi.org/10.2174/157015912804499447
  • Gomez-Marcos MA, Recio-Rodriguez JI, Patino-Alonso MC, Agudo-Conde C, Gomez-Sanchez L, Rodriguez-Sanchez E, et al. Relationships between high sensitive C-reactive protein and markers of arterial stiffness in hypertensive patients. Differences by sex. BMC Cardiovasc Disord 2012; 12: 37-8. https://doi.org/10.1186/1471-2261-12-37
  • Assadpour Piranfar M. The correlation between high-sensitivity C-reactive protein (HSCRP) serum levels and severity of coronary atherosclerosis. Int Cardiovasc Res J 2014; 8: 6-8.
  • Wasilewska A, Tenderenda E, Taranta-Janusz K, Zoch-Zwierz W. High-sensitivity C-reactive protein and mean platelet volume in paediatric hypertension. Pediatr Nephrol 2010; 25:1519-27. https://doi.org/10.1007/s00467-010-1513-2
  • VanGilder RL, Davidov DM, Stinehart KR, Huber JD, Turner RC, Wilson KS, et al. C- reactive protein and long-term ischemic stroke prognosis. J Clin Neurosci 2014; 21: 547-53. https://doi.org/10.1016/j.jocn.2013.06.015
  • Almroth G, Lonn J, Uhlin F, Nayeri F, Brudin L, Andersson B, et al. Fibroblast growth factor 23, hepatocyte growth factor, interleukin-6, high-sensitivity Creactive protein and soluble urokinase plasminogen activator receptor. Inflammation markers in chronic haemodialysis patients? Scand J Immunol 2013; 78:285-90 . https://doi.org/10.1111/sji.12082
  • Engelhart MJ, Geerlings Ml, Meijer J, Kiliaan A, Ruitenberg A, van Swieten JC, et al. Inflammatory proteins in plasma and the risk of dementia: the Rotterdam study. Arch Neurol 2004; 61: 668-72 https://doi.org/10.1001/archneur.61.5.668
  • Calik M, Oğuz E, Sarikaya S, Kocaturk O, Koca B, Gungor HE, Aksoy N, Yoldaş TK, Iscan A. An evaluation of serum paraoxonase together with arylesterase activities and oxidative stress in children with intractable epilepsy: across-sectional study. Epilepsy Res. 2014 Nov; 108(9): 1591 -6. https://doi.org/10.1016/j.eplepsyres.2014.08.007
  • Ethemoglu O, Ay H, Koyuncu I, Gönel A. Comparison of cytokines and prooxidants/antioxidants markers among adults with refractory versus well- controlled epilepsy: A cross-sectional study. Seizure. 2018 Aug;60:105-109. https://doi.org/10.1016/j.seizure.2018.06.009
  • Hassanzadeh P, Arbabi E, Rostami F. The ameliorative effects of sesamol against seizures, cognitive impairment and oxidative stressin the experimental model of epilepsy. Iran J Basic Med Sci. 2014 Feb; 17(2): 100-7.
  • Ben-Menachem E., Kyllerman M., Marklund S. Superoxide dismutase and glutathione peroxidase function in progressive myoclonus epilepsies Epilepsy Res. 2000; 40: 33-9. https://doi.org/10.1016/S0920-1211(00)00096-6
  • Shin EJ, Jeong JH, Chung YH, Kim WK, Ko KH, Bach JH, Hong JS, Yoneda Y,Kim HC. Role of oxidative stres in epileptic seizures. Neurochem Int. 2011; 59(2): 122-37. https://doi.org/10.1016/j.neuint.2011.03.025
  • Yürekli VA, Nazıroğlu M. Selenium and topiramate attenuates blood oxidative toxicity in patients with epilepsy. Biol Trace Elem Res. 2013 May; 152(2): 180-6. : https://doi.org/10.1007/s12011-013-9616-9
  • Ashrafi MR, Azizi Malamiri R, Shams S, Rashidi Ranjbar N, Ebrahimi Nasrabadi S, Haghi Ashtiani M, Saladjegheh N, Vakili Zarch V. Serum Total Antioxidant Capacity of Epileptic Children before and after Monotherapy with Sodium Valproate, Carbamazepine, and Phenobarbital. Iran J Child Neurol. 2018 Summer;12(3):24-31.Aycicek A, Iscan A. The effects of carbamazepine, valproic acid and phenobarbital on the oxidative and antioxidative balance in epileptic children. Eur Neurol. 2007;57(2):65-9. Epub 2006 Dec 15. https://doi.org/10.1159/000098053
  • Menon B, Ramalingam K, Kumar RV. Oxidative stress in patients with epilepsy is independent of antiepileptic drugs. Seizure 2012; 21 (10): 780-4. https://doi.org/10.1016/j.seizure.2012.09.003
  • Varoglu, A.O., Yildirim, A., Aygul, R., Gundogdu, O.L., Sahin, Y.N., Effects of valproate, carbamazepine, and levetiracetamon the antioxidant and oxidant systems in epileptic patients andtheir clinical importance. Clin Neuropharmacol 2010; 33:155-7. https://doi.org/10.1097/WNF.0b013e3181d1e133
  • Shahar E, Attias U, Savulescu D, Genizin J, Gavish M, Nagler R. Oxidative stress, metalloproteinase and LDH in children with intractable and non-intractable epilepsy as reflected in salivary analysis. Epilepsy Res. 2014 Jan; 108(1): 117-24. https://doi.org/10.1016/j.eplepsyres.2013.10.003
  • Rubio C, Rubio-Osornio M, Retana-Marquez S, Veronica Custodio ML, Paz C. In vivo experimental models of epilepsy. Cent Nerv Syst Agents Med Chem. 2010 Dec 1;10(4):298-309. https://doi.org/10.2174/187152410793429746
  • Ishikawa N, Kobayashi Y, Fujii Y, Kobayashi M. Increased interleukin-6 and high- sensitivity C-reactive protein levels in pediatric epilepsy patients with frequent, refractory generalized motor seizures. Seizure. 2015 Feb; 25:136-40. https://doi.org/10.1016/j.seizure.2014.10.007
  • Librizzi L, Noe F, Vezzani A, de Curtis M, Ravizza T. Seizure-induced brain-borne inflammation sustains seizure recurrence and blood-brain barrier damage. Ann Neurol 2012; 72: 82-90. https://doi.org/10.1002/ana.23567
  • Rojas A, Jiang J, Ganesh T, Yang MS, Lelutiu N, Gueorguieva P, et al. Cyclooxygenase-2 in epilepsy. Epilepsia 2014; 55:17-25. https://doi.org/10.1111/epi.12461
  • Kwon YS, Pineda E, Auvin S, Shin D, Mazarati A, Sankar R. Neuroprotective and antiepileptogenic effects of combination of anti-inflammatory drugs in the immature brain. J Neuroinflamm 2013; 10: 30-1. https://doi.org/10.1186/1742-2094-10-30
  • Yuen AW, Bell GS, Peacock JL, Koepp MM, Patsalos PN, Sander JW. Effects of AEDs on biomarkers in people with epilepsy: CRP, HbA1c and eGFR. Epilepsy Res 2010; 91:187-92. https://doi.org/10.1016/j.eplepsyres.2010.07.011
  • Tan TY, Lu CH, Chuang HY, Lin TK, Liou CW, Chang WN, et al. Long-term antiepileptic drug therapy contributes to the acceleration of atherosclerosis. Epilepsia 2009; 50:1579-86. https://doi.org/10.1111/j.1528-1167.2009.02024.x

Investigation on Acute Phase Reactants and Oxidant - Antioxidant Parameters in Patients Diagnosed as Having Generalized Tonic Clonic Type Epilepsy on Antiepileptic Monotherapy and Polytherapy

Year 2021, Volume: 12 Issue: 44, 158 - 164, 24.12.2021
https://doi.org/10.17944/mkutfd.910039

Abstract

Objective: This study aimed to investigate the relationship between acute-phase reactants and oxidative stress and epilepsy.
Methods: The patient group consisted of 67 patients who applied to the Pediatric Neurology outpatient clinic and were diagnosed with generalized type epilepsy according to ILAE classification, 33 were receiving monotherapy and 34 were receiving antiepileptic medication in the form of polytherapy. The control group included 30 healthy volunteer participants with similar sociodemographic characteristics in the same age range, without epilepsy or any known chronic disease. Total anti-Oxidant Status (TAS) and total Oxidant Status (TOS) were measured according to the method developed by Erel, and the oxidative stress index (OSI) was calculated. Sensitive C-reactive protein (Hs-CRP) levels were measured.
Results: Both TOS and OSI levels of the patients who received antiepileptic monotherapy and polytherapy were statistically significantly higher than the control group (p = 0.004, the TOS levels of the patients who received antiepileptic monotherapy and polytherapy were 19.29 ± 1.27, 19.22 ± 1.26, respectively, control group 14.49 ± 1.75, OSI levels of patients receiving antiepileptic monotherapy and polytherapy 1.66 ± 0.12, 1.72 ± 0.11, control group 1.27 ± 0.11), respectively. The Hs-CRP level (0.59 ± 0.06 mg / L, 1.09 ± 0.06 mg / L, respectively) of the patients who received monotherapy and polytherapy was statistically significant compared to the control group (0.42 ± 0.02 mg / L) significantly higher.
Conclusion: In this study, the findings suggest that epileptic seizures increase oxidative stress parameters and antioxidant mechanisms are insufficient to reduce oxidative damage. In addition, considering the high serum Hs-CRP levels, it is extremely important to develop treatment strategies that can control the inflammatory process in treating resistant epilepsy.

References

  • Menkes JH, Sarnat HB. Paroxysmal disorders. In: Menkes JH, Sarnat HB. Child Neurology (6th Ed). Philadelphia. Lippincott Williams&Wilkins. 2000; 919-1026.
  • Dasheiff RM. Sudden unexpected death in epilepsy: a series from an epilepsy surgery program and speculation on the relationship to sudden cardiac death . J Clin Neurophysiol. 1991; 8: 216-22. https://doi.org/10.1097/00004691-199104000-00010
  • Conway JM, Kriel RL, Birnbaum AK. Antiepileptic Drug Therapy in Children: An Overview. In: Swaiman KF, Ashwal S, Pediatric Neurology Principles &Practise (3th ed). Philadelphia. Mosby Elsevier. 2006; 1105-30.
  • Gershov D, Kim S, Brot N, et al. C-reactive protein binds to apoptotic cells, protects the cells from assembly of the terminal complement components, and sustains an antiinflammatory innate immune response: Implications for systemic autoimmunity. J Exp Med 2000; 192:1353-64. https://doi.org/10.1084/jem.192.9.1353
  • Doumatey AP, Zhou J, Adeyemo A, Rotimi C. High sensitivity C-reactive protein (Hs-CRP) remains highly stable in long-term archived human serum. Clin Biochem.2014 Mar;47(4-5):315-8. https://doi.org/10.1016/j.clinbiochem.2013.12.014
  • Rafieian-Kopaei M, Setorki M, Doudi M, Baradaran A, Nasri H. Atherosclerosis: process, indicators, risk factors and new hopes. Int J Prev Med. 2014 Aug;5(8):927-46.
  • Erel 0. A new automated colorimetric method for measuring total oxidant status. Clin Biochem. 2005; 38 (12): 1103-11. https://doi.org/10.1016/j.clinbiochem.2005.08.008
  • Bostjan Martinc, Iztok Grabnar, and Tomaz Vovk. The Role of Reactive Speciesin Epileptogenesis and Influence of Antiepileptic Drug Therapy on Oxidative Stress. Curr Neuropharmacol. 2012; 10(4): 328-43. https://doi.org/10.2174/157015912804499447
  • Gomez-Marcos MA, Recio-Rodriguez JI, Patino-Alonso MC, Agudo-Conde C, Gomez-Sanchez L, Rodriguez-Sanchez E, et al. Relationships between high sensitive C-reactive protein and markers of arterial stiffness in hypertensive patients. Differences by sex. BMC Cardiovasc Disord 2012; 12: 37-8. https://doi.org/10.1186/1471-2261-12-37
  • Assadpour Piranfar M. The correlation between high-sensitivity C-reactive protein (HSCRP) serum levels and severity of coronary atherosclerosis. Int Cardiovasc Res J 2014; 8: 6-8.
  • Wasilewska A, Tenderenda E, Taranta-Janusz K, Zoch-Zwierz W. High-sensitivity C-reactive protein and mean platelet volume in paediatric hypertension. Pediatr Nephrol 2010; 25:1519-27. https://doi.org/10.1007/s00467-010-1513-2
  • VanGilder RL, Davidov DM, Stinehart KR, Huber JD, Turner RC, Wilson KS, et al. C- reactive protein and long-term ischemic stroke prognosis. J Clin Neurosci 2014; 21: 547-53. https://doi.org/10.1016/j.jocn.2013.06.015
  • Almroth G, Lonn J, Uhlin F, Nayeri F, Brudin L, Andersson B, et al. Fibroblast growth factor 23, hepatocyte growth factor, interleukin-6, high-sensitivity Creactive protein and soluble urokinase plasminogen activator receptor. Inflammation markers in chronic haemodialysis patients? Scand J Immunol 2013; 78:285-90 . https://doi.org/10.1111/sji.12082
  • Engelhart MJ, Geerlings Ml, Meijer J, Kiliaan A, Ruitenberg A, van Swieten JC, et al. Inflammatory proteins in plasma and the risk of dementia: the Rotterdam study. Arch Neurol 2004; 61: 668-72 https://doi.org/10.1001/archneur.61.5.668
  • Calik M, Oğuz E, Sarikaya S, Kocaturk O, Koca B, Gungor HE, Aksoy N, Yoldaş TK, Iscan A. An evaluation of serum paraoxonase together with arylesterase activities and oxidative stress in children with intractable epilepsy: across-sectional study. Epilepsy Res. 2014 Nov; 108(9): 1591 -6. https://doi.org/10.1016/j.eplepsyres.2014.08.007
  • Ethemoglu O, Ay H, Koyuncu I, Gönel A. Comparison of cytokines and prooxidants/antioxidants markers among adults with refractory versus well- controlled epilepsy: A cross-sectional study. Seizure. 2018 Aug;60:105-109. https://doi.org/10.1016/j.seizure.2018.06.009
  • Hassanzadeh P, Arbabi E, Rostami F. The ameliorative effects of sesamol against seizures, cognitive impairment and oxidative stressin the experimental model of epilepsy. Iran J Basic Med Sci. 2014 Feb; 17(2): 100-7.
  • Ben-Menachem E., Kyllerman M., Marklund S. Superoxide dismutase and glutathione peroxidase function in progressive myoclonus epilepsies Epilepsy Res. 2000; 40: 33-9. https://doi.org/10.1016/S0920-1211(00)00096-6
  • Shin EJ, Jeong JH, Chung YH, Kim WK, Ko KH, Bach JH, Hong JS, Yoneda Y,Kim HC. Role of oxidative stres in epileptic seizures. Neurochem Int. 2011; 59(2): 122-37. https://doi.org/10.1016/j.neuint.2011.03.025
  • Yürekli VA, Nazıroğlu M. Selenium and topiramate attenuates blood oxidative toxicity in patients with epilepsy. Biol Trace Elem Res. 2013 May; 152(2): 180-6. : https://doi.org/10.1007/s12011-013-9616-9
  • Ashrafi MR, Azizi Malamiri R, Shams S, Rashidi Ranjbar N, Ebrahimi Nasrabadi S, Haghi Ashtiani M, Saladjegheh N, Vakili Zarch V. Serum Total Antioxidant Capacity of Epileptic Children before and after Monotherapy with Sodium Valproate, Carbamazepine, and Phenobarbital. Iran J Child Neurol. 2018 Summer;12(3):24-31.Aycicek A, Iscan A. The effects of carbamazepine, valproic acid and phenobarbital on the oxidative and antioxidative balance in epileptic children. Eur Neurol. 2007;57(2):65-9. Epub 2006 Dec 15. https://doi.org/10.1159/000098053
  • Menon B, Ramalingam K, Kumar RV. Oxidative stress in patients with epilepsy is independent of antiepileptic drugs. Seizure 2012; 21 (10): 780-4. https://doi.org/10.1016/j.seizure.2012.09.003
  • Varoglu, A.O., Yildirim, A., Aygul, R., Gundogdu, O.L., Sahin, Y.N., Effects of valproate, carbamazepine, and levetiracetamon the antioxidant and oxidant systems in epileptic patients andtheir clinical importance. Clin Neuropharmacol 2010; 33:155-7. https://doi.org/10.1097/WNF.0b013e3181d1e133
  • Shahar E, Attias U, Savulescu D, Genizin J, Gavish M, Nagler R. Oxidative stress, metalloproteinase and LDH in children with intractable and non-intractable epilepsy as reflected in salivary analysis. Epilepsy Res. 2014 Jan; 108(1): 117-24. https://doi.org/10.1016/j.eplepsyres.2013.10.003
  • Rubio C, Rubio-Osornio M, Retana-Marquez S, Veronica Custodio ML, Paz C. In vivo experimental models of epilepsy. Cent Nerv Syst Agents Med Chem. 2010 Dec 1;10(4):298-309. https://doi.org/10.2174/187152410793429746
  • Ishikawa N, Kobayashi Y, Fujii Y, Kobayashi M. Increased interleukin-6 and high- sensitivity C-reactive protein levels in pediatric epilepsy patients with frequent, refractory generalized motor seizures. Seizure. 2015 Feb; 25:136-40. https://doi.org/10.1016/j.seizure.2014.10.007
  • Librizzi L, Noe F, Vezzani A, de Curtis M, Ravizza T. Seizure-induced brain-borne inflammation sustains seizure recurrence and blood-brain barrier damage. Ann Neurol 2012; 72: 82-90. https://doi.org/10.1002/ana.23567
  • Rojas A, Jiang J, Ganesh T, Yang MS, Lelutiu N, Gueorguieva P, et al. Cyclooxygenase-2 in epilepsy. Epilepsia 2014; 55:17-25. https://doi.org/10.1111/epi.12461
  • Kwon YS, Pineda E, Auvin S, Shin D, Mazarati A, Sankar R. Neuroprotective and antiepileptogenic effects of combination of anti-inflammatory drugs in the immature brain. J Neuroinflamm 2013; 10: 30-1. https://doi.org/10.1186/1742-2094-10-30
  • Yuen AW, Bell GS, Peacock JL, Koepp MM, Patsalos PN, Sander JW. Effects of AEDs on biomarkers in people with epilepsy: CRP, HbA1c and eGFR. Epilepsy Res 2010; 91:187-92. https://doi.org/10.1016/j.eplepsyres.2010.07.011
  • Tan TY, Lu CH, Chuang HY, Lin TK, Liou CW, Chang WN, et al. Long-term antiepileptic drug therapy contributes to the acceleration of atherosclerosis. Epilepsia 2009; 50:1579-86. https://doi.org/10.1111/j.1528-1167.2009.02024.x
There are 31 citations in total.

Details

Primary Language English
Subjects Clinical Sciences, Health Care Administration
Journal Section Original Articles
Authors

Suna Sarıkaya 0000-0002-1176-0326

Sedat Yaşin 0000-0001-8067-8388

Mustafa Çalık 0000-0002-6383-3355

Tahir Yoldaş 0000-0003-4950-9142

Publication Date December 24, 2021
Submission Date April 7, 2021
Acceptance Date May 17, 2021
Published in Issue Year 2021 Volume: 12 Issue: 44

Cite

Vancouver Sarıkaya S, Yaşin S, Çalık M, Yoldaş T. Investigation on Acute Phase Reactants and Oxidant - Antioxidant Parameters in Patients Diagnosed as Having Generalized Tonic Clonic Type Epilepsy on Antiepileptic Monotherapy and Polytherapy. mkutfd. 2021;12(44):158-64.