THE EFFECTS OF SYSTEMIC INFLAMMATORY INDICES, LACTATE, AND BLOOD GAS PARAMETERS ON DRUG-RESISTANT AND DRUG-NONRESISTANT EPILEPSY

Abstract

Epilepsy is one of the neurological diseases that affects a significant number of individuals in the world. In addition to having important effects on the social lives of the patients, this disease is a significant cause of disability. Neurological mechanisms underlying the disease are still being investigated. The patients’ gender, age, hemogram parameters (white blood cells, hemoglobin, erythrocyte, neutrophil, lymphocyte, monocyte, eosinophil, platelet), arterial bold gas values, drugs used, presence of drug-resistant epilepsy, and the duration of the disease were analyzed. The patients were divided into two groups of similar ages and genders as drug-resistant epilepsy and drug-nonresistant epilepsy patients. This grouping was made according to ILAE classification by considering the patients’ anamnesis, clinical history, seizure frequency, and antiepileptic drugs currently used. 77 drug-resistant and 129 drug-nonresistant epilepsy patients, 206 in total, were included in the study. 64.9% of the drug-resistant epilepsy group were male, and the remaining 35.1% were female, while 65.9% of the drug-nonresistant epilepsy group were male and 34.1% were female. No significant difference was found between the groups in terms of systemic inflammatory indices. Disease duration of the patients in the drug-resistant epilepsy group was significantly higher than the disease duration of the patients in the drug-nonresistant epilepsy group. A negative and significant correlation was found between pH and pO2, pCO2, and lactate. In addition, a positive and significant correlation was determined between pO2 and lactate, and a negative and significant correlation was found between pO2 and pCO2. It was determined that there was no significant difference between drug-resistant epilepsy patients and drug-nonresistant epilepsy patients in terms of parameters used as a systemic inflammatory biomarker in epilepsy patients. New biomarkers that would create a significant difference in these patients should be investigated.

Keywords

• epilepsy
• drug-resistant epilepsy
• NLR
• PLR
• MLR
• lactate
• blood gas

References

1. 1. Kwan P, Schachter SC, Brodie MJ. Drug-resistant epilepsy. N Engl J Med. 2011; 365(10): 919-926.
2. 2. Löscher W, Potschka H, Sisodiya SM, Vezzani A. Drug Resistance in Epilepsy: Clinical Impact, Potential Mechanisms, and New Innovative Treatment Options. Pharmacol Rev. 2020; 72(3): 606-638.
3. 3. Ioannou P, Foster DL, Sander JW, Dupont S, Gil-Nagel A, Drogon O’Flaherty E, et al. The burden of epilepsy and unmet need in people with focal seizures. Brain Behav. 2022; 12(9): e2589.
4. 4. Ngugi AK, Bottomley C, Kleinschmidt I, Sander JW, Newton CR. Estimation of the burden of active and life-time epilepsy: a meta-analytic approach. Epilepsia. 2010; 51(5): 883-890.
5. 5. Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000; 342(5): 314-319.
6. 6. Campos-Bedolla P, Feria-Romero I, Orozco-Suárez S. Factors not considered in the study of drug-resistant epilepsy: Drug-resistant epilepsy: Assessment of neuroinflammation. Epilepsia Open. 2022; 7(Suppl 1): 68-80.
7. 7. Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Mathern G, Moshé SL, et al. Definition of drug resistant epilepsy: Consensus proposal by the ad hoc Task Force of the ILAE commission on Therapeutic Stretegies. Epilepsia. 2010; 51(6): 1069-1077.
8. 8. Mula M, Cock HR. More than seizures: improving the lives of people with refractory epilepsy. Eur J Neurol. 2015; 22(1): 24-30.

9. 9. Tomson T, Walczak T, Sillanpaa M, Sander JW. Sudden unexpected death in epilepsy: a review of incidence and risk factors. Epilepsia. 2005; 46: 54-61.
10. 10. Sharma D, Gandhi N. Role of Platelet to Lymphocyte Ratio (PLR) and its Correlation with NIHSS (National Institute of Health Stroke Scale) for Prediction of Severity in Patients of Acute Ischemic Stroke. Journal of the Association of Physicians of India. 2021; 69(1): 56–60.
11. 11. Wang J, Zhang X, Tian J, Liu H, Tang H, Yang C. Predictive values of systemic inflammatıry responses index in early neurological deterioration in patients with acute ischemic stroke. J. Integr. Neurosci. 2022; 21(3): 94.
12. 12. Gong P, Liu Y, Gong Y, Chen G, Zhang X, Wang S, et al. The association of neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, and lymphocyte to monocyte ratio with post-thrombolysis early neurological outcomes in patients with acute ischemic stroke. Journal of Neuroinflammation. 2021; 18(1): 51.
13. 13. Osalusi BS, Ogunjimi L, Akinyinka AA, Aderinola A, Olusola-Bello M, Oboh D. A case-Control study of neutrophil-Lymphocyte ratio as a biomarker of inflammation in adults with epilepsy. Annals of Health Research. 2023; 9(2): 120-128.
14. 14. Olivo S, Stella AB, Pavan S, Cegalin M, Furlanis G, Cheli M, et al. Admission neutrophil-to-lymphocyte ratio predicts length of hospitalization and need for ICU admission in adults with Status Epilepticus. Seizure. 2023; 106: 80-84.
15. 15. Stredny C, Rotenberg A, Leviton A, Loddenkemper T. Systemic inflammation as a biomarker of seizure propensity and a target for treatment to reduce seizure propensity. Epilepsia Open.2023; 8(1): 221-234.
16. 16. Güneş M, Büyükgöl H. Relationship between generalized epileptic seizure and neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and neutrophil mediated inflammation. Int J Neurosci. 2020; 130 (11): 1095-1100.
17. 17. Magnusson C, Herlits J, Höglind R, Wennberg P, Tranberg AE, Axelsson C, et al. Prehospital lactate levels in blood as a seizure biomarker: A multi-center observational study. Epilepsia. 2021; 62(2): 408-415.
18. 18. Dogan EA, Unal A, Unal A, Erdogan C. Clinical utility of serum lactate levels for differential diagnosis of generalized tonic–clonic seizures from psychogenic nonepileptic seizure and syncope. Epilepsy&Behavior. 2017; 75: 13-17.
19. 19. Murray CJ, Vos T, Lozano R, Naghavi M, Flaxman AD, Michaud C, et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012; 380(9859): 2197–2223.
20. 20. Rana A, Musto AE. The role of inflammation in the development of epilepsy. Journal of Neuroinflammation. 2018; 15: 144.
21. 21. Rakhade SN, Jensen FE. Epileptogenesis in the immature brain: emerging mechanisms. Nat Rev Neurol. 2009; 5(7): 380-391.
22. 22. Laxer KD, Trinka E, Hirsch LJ, Cendes F, Langfitt J, Delanty N, et al. The consequences of refractory epilepsy and its treatment. Epilepsy Behav. 2014; 37: 59-70.
23. 23. Terrone G, Salamone A, Vezzani A. Inflammation and Epilepsy: Preclinical findings and potential clinical translation. Current Pharmaceutical Design. 2017; 23(37): 5569-5576.
24. 24. Benini R, Roth R, Khoja Z, Avoli M, Wintermark P. Does angiogenesis play a role in the establishment of mesial temporal lobe epilepsy. International Journal of Developmental Neuroscience. 2016; 49: 31-36.
25. 25. Kämppi L, Puolakka T, Ritvanen J, Tuppurainen K, Päkkilä J, Kuisma M, et al. Burden of suspected epileptic seizures on emergency services: A population- based study. Eur J Neurol. 2023; 30(8): 2197-2205.
26. 26. Akıl E, Bulut A, Kaplan İ, Özdemir H.H, Arslan D, Aluçlu M.U. The increase of carcinoembryonic antigen (CEA), high-sensitivity C-reactive protein, and neutrophil/ lymphocyte ratio in Parkinson’s disease. Neurol Sci. 2015; 36(3): 423-428.
27. 27. Zahorec R. Neutrophil-to-lymphocyte ratio, past, present and future perspectives. Bratisl Lek Listy. 2021; 122(7): 474-488.
28. 28. Tang H, Lu W, Li B, Li C, Xu Y, Dong J. Prognostic significance of Neutrophil-to-lymphocyte Ratio in biliary tract cancers: a systematic review and meta-analysis. Oncotarget. 2017; 8(22): 36857-36868.
29. 29. Afari ME, Bhat T. Neutrophil to Lymphocyte Ratio (NLR) and cardiovascular diseases: an update. Expert Rev Cardiovasc Ther. 2016; 14(5): 573-577.
30. 30. He J, Bian X, Song C, Zhang R, Yuan S, Yin D, et al. High neutrophil to lymphocyte ratio with type 2 diabetes mellitus predicts poor prognosis in patients undergoing percutaneous coronary intervention: a large –scale cohort study. Cardiovascular Diabetology. 2022; 21: 156.
31. 31. Hosseini S, Mofrad AME, Mokarian P, Nourigheimasi S, Azarhomayoun A, Khanzadeh S, et al. Neutrophil to Lymphocyte Ratio in Epilepsy: A systematic review. Mediators of Inflammation. 2022; 2022: 497399