{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T16:27:57Z","timestamp":1777307277275,"version":"3.51.4"},"reference-count":52,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T00:00:00Z","timestamp":1748390400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Epilepsy is a chronic neurological disorder frequently influenced by systemic inflammation, nutritional status, and comorbid conditions, which may worsen seizure outcomes. Given the increasing recognition of these factors in disease progression, this study aimed to investigate the relationship between the Modified Charlson Comorbidity Index (mCCI), inflammatory hematological parameters, and the prognostic nutritional index (PNI) with seizure frequency and clinical prognosis in patients with epilepsy. Methods: A total of 159 participants were enrolled between January 2021 and January 2023, including 53 healthy controls (mean age: 44 \u00b1 14.2 years; female: 21, male: 32), 53 epilepsy patients without comorbidity (mean age: 33 \u00b1 12.5 years; female: 28, male: 25), and 53 epilepsy patients with comorbidities (mean age: 56.2 \u00b1 13.8 years; female: 22, male: 31). The participants were divided into three groups: 53 patients with isolated epilepsy, 53 patients with epilepsy and comorbid conditions, and 53 healthy individuals with no known diseases, matched for age and sex with the patient groups, who presented for routine check-ups. The mCCI was calculated for patients with comorbid epilepsy. Inflammatory hematological parameters and the PNI were assessed in all participants using previously obtained complete blood count data. Results: Inflammatory markers such as white blood cell count, neutrophil count, C-reactive protein (CRP), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and mean platelet distribution width (PDW) were significantly higher in epilepsy patients with comorbidities compared to other groups. Epilepsy patients with comorbidities had a higher seizure frequency compared to those without comorbidities (75.5% vs. 54.7%, p &lt; 0.001). The PNI was lowest in epilepsy patients with comorbidities, showing a significant difference between all groups (p &lt; 0.001). High comorbidity burden increased seizure risk by 4.56 times (95% CI: 1.30\u201316.01), each unit increase in the SII raised the risk by 1.13 times (95% CI: 1.08\u20131.19), and each unit decrease in the PNI increased the risk by 1.14 times (OR = 0.88, p &lt; 0.001). Cerebrovascular disease and hemiplegia were also significant risk factors, increasing seizure risk by 4.15 and 4.48 times, respectively. Conclusions: Our study demonstrates that inflammatory hematological parameters, particularly SII and MCCI scores, are elevated in epilepsy patients and further increase with comorbidities. These markers are strongly associated with seizure occurrence, highlighting the prognostic significance of systemic inflammation and comorbidity burden in epilepsy. Given the frequent observation of low PNI values in patients with comorbid conditions, which may reflect compromised nutritional status, and given associations suggest a role in poor clinical outcomes, comprehensive management is essential. Monitoring the PNI and SII may help stratify high-risk patients for targeted nutritional and anti-inflammatory interventions.<\/jats:p>","DOI":"10.3390\/nu17111847","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T12:28:42Z","timestamp":1748435322000},"page":"1847","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Association of Comorbidity and Inflammatory and Nutritional Markers with Epilepsy and Seizure Frequency"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1828-1811","authenticated-orcid":false,"given":"Demet","family":"Aygun","sequence":"first","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, Istanbul Atlas University, 34408 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1347-8498","authenticated-orcid":false,"given":"Hafize","family":"Uzun","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine, Istanbul Atlas University, 34408 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1159\/000503831","article-title":"The epidemiology of epilepsy","volume":"54","author":"Beghi","year":"2020","journal-title":"Neuroepidemiology"},{"key":"ref_2","unstructured":"WHO (2025, January 04). Epilepsy. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/epilepsy."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Zaitsev, A.V., and Khazipov, R. (2023). Molecular and Cellular Mechanisms of Epilepsy. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241512415"},{"key":"ref_4","unstructured":"GBD Epilepsy Collaborators (2025). Global, regional, and national burden of epilepsy, 1990-2021: A systematic analysis for the Global Burden of Disease Study 2021. Lancet Public Health, 10, e203\u2013e227."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/ane.12014","article-title":"The impact of epilepsy on patients\u2019 lives","volume":"126","author":"Kerr","year":"2012","journal-title":"Acta Neurol. Scand."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1146\/annurev.physiol.63.1.815","article-title":"On the cellular and network bases of epileptic seizures","volume":"63","author":"McCormick","year":"2001","journal-title":"Annu. Rev. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.jocn.2008.08.026","article-title":"Cortical hyperexcitability and epileptogenesis: Understanding the mechanisms of epilepsy\u2013part 1","volume":"16","author":"Badawy","year":"2009","journal-title":"J. Clin. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1111\/j.0013-9580.2003.12005.x","article-title":"Epilepsies as dynamical diseases of brain systems: Basic models of the transition between normal and epileptic activity","volume":"44","author":"Blanes","year":"2003","journal-title":"Epilepsia"},{"key":"ref_9","first-page":"201","article-title":"Pathophysiology of epilepsy","volume":"100","author":"Engelborghs","year":"2000","journal-title":"Acta Neurol. Belg."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Stafstrom, C.E. (2010). Pathophysiological mechanisms of seizures and epilepsy: A primer. Epilepsy, CRC Press.","DOI":"10.1201\/EBK1420085594-c1"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s42494-024-00153-8","article-title":"Clinical characteristics and impact of comorbidities on the prognosis of senile epilepsy in Southwest China: A retrospective cohort study","volume":"6","author":"Cao","year":"2024","journal-title":"Acta Epileptol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"663","DOI":"10.2217\/fnl.09.32","article-title":"Association of epilepsy and comorbid conditions","volume":"4","author":"Seidenberg","year":"2009","journal-title":"Future Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Lee, J., Choi, A., and Kim, S. (2024). Effects of Psychiatric Comorbidities on the Prognosis of New-Onset Pediatric Epilepsy: A Retrospective Nationwide Cohort Study. J. Clin. Med., 13.","DOI":"10.3390\/jcm13154500"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1111\/j.0013-9580.2004.17504.x","article-title":"The epidemiology of the comorbidity of epilepsy in the general population","volume":"45","author":"Gaitatzis","year":"2004","journal-title":"Epilepsia"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.yebeh.2007.01.005","article-title":"Mortality in epilepsy","volume":"10","author":"Hitiris","year":"2007","journal-title":"Epilepsy Behav."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.clineuro.2016.12.017","article-title":"Role of comorbidities and in-hospital complications in short-term status epilepticus outcome","volume":"154","author":"Belluzzo","year":"2017","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1111\/epi.17022","article-title":"Comorbidities in patients with epilepsy: Frequency, mechanisms and effects on long-term outcome","volume":"62","author":"Giussani","year":"2021","journal-title":"Epilepsia"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kabboord, A.D., Godfrey, D., Gordon, A.L., Gladman, J.R.F., Van Eijk, M., van Balen, R., and Achterberg, W.P. (2020). The modified functional comorbidity index performed better than the Charlson index and original functional comorbidity index in predicting functional outcome in geriatric rehabilitation: A prospective observational study. BMC Geriatr., 20.","DOI":"10.1186\/s12877-020-1498-z"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.jstrokecerebrovasdis.2014.08.034","article-title":"Validity of the modified Charlson comorbidity index as predictor of short-term outcome in older stroke patients","volume":"24","author":"Denti","year":"2015","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Maldonado-Cabrera, A., Angulo-Molina, A., Haque, U., Velazquez, C., \u00c1lvarez-Villase\u00f1or, A.S., Santacruz-G\u00f3mez, K.J., and Gallego-Hern\u00e1ndez, A.L. (2021). Acute inflammatory mediators in young adult patients with COVID-19 in Mexico. Pathogens, 10.","DOI":"10.3390\/pathogens10081056"},{"key":"ref_21","first-page":"37","article-title":"Evaluation of inflammation parameters in complete blood count in patients diagnosed with vestibular migraine","volume":"20","author":"Ertugay","year":"2021","journal-title":"KBB-Forum"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"372","DOI":"10.3109\/14397595.2015.1091136","article-title":"Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) were useful markers in assessment of inflammatory response and disease activity in SLE patients","volume":"26","author":"Qin","year":"2016","journal-title":"Mod. Rheumatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.1182\/bloodadvances.2018018051","article-title":"Development of a prognostically relevant cachexia index in primary myelofibrosis using serum albumin and cholesterol levels","volume":"2","author":"Tefferi","year":"2018","journal-title":"Blood Adv."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1007\/s00508-018-1318-z","article-title":"Assessing serum albumin concentration, lymphocyte count and prognostic nutritional index might improve prognostication in patients with myelofibrosis","volume":"130","author":"Lucijanic","year":"2018","journal-title":"Wien. Klin. Wochenschr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1111\/j.1528-1167.2009.02397.x","article-title":"Definition of drug resistant epilepsy: Consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies","volume":"51","author":"Kwan","year":"2010","journal-title":"Epilepsia"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/0021-9681(87)90171-8","article-title":"A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation","volume":"40","author":"Charlson","year":"1987","journal-title":"J. Chronic Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1016\/0895-4356(94)90129-5","article-title":"Validation of a combined comorbidity index","volume":"47","author":"Charlson","year":"1994","journal-title":"J. Clin. Epidemiol."},{"key":"ref_28","first-page":"1001","article-title":"Prognostic nutritional index in gastrointestinal surgery of malnourished cancer patients","volume":"85","author":"Onodera","year":"1984","journal-title":"Nihon Geka Gakkai Zasshi"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e68","DOI":"10.1111\/epi.12982","article-title":"The performance of three mortality risk-adjustment comorbidity indices in a community epilepsy cohort","volume":"56","author":"Keezer","year":"2015","journal-title":"Epilepsia"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4973996","DOI":"10.1155\/2022\/4973996","article-title":"Neutrophil to lymphocyte ratio in epilepsy: A systematic review","volume":"2022","author":"Hosseini","year":"2022","journal-title":"Mediat. Inflamm."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.neuchi.2019.09.025","article-title":"Serum endocan and preoperative systemic inflammatory markers in patients with epilepsy","volume":"66","author":"Ozdemir","year":"2020","journal-title":"Neurochirurgie"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1080\/00207454.2020.1722662","article-title":"Relationship between generalized epileptic seizure and neutrophil\/lymphocyte ratio, platelet\/lymphocyte ratio, and neutrophil mediated inflammation","volume":"130","year":"2020","journal-title":"Int. J. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Shi, X., Zhang, X., Song, S., Pan, H., Huang, C., Sun, T., Wang, S., and Xu, J. (2024). Correlation between inflammatory markers over time and disease severity in status epilepticus: A preliminary study. Front. Neurol., 15.","DOI":"10.3389\/fneur.2024.1334415"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.seizure.2023.02.001","article-title":"Admission neutrophil-to-lymphocyte ratio predicts length of hospitalization and need for ICU admission in adults with Status Epilepticus","volume":"106","author":"Olivo","year":"2023","journal-title":"Seizure"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.seizure.2024.10.006","article-title":"Association of blood count-derived immunoinflammatory makers and risk of epilepsy: A prospective cohort of 497,291 participants","volume":"123","author":"Huang","year":"2024","journal-title":"Seizure"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/hr.2016.16","article-title":"Elevated circulating sST2 associated with subclinical atherosclerosis in newly diagnosed primary hypertension","volume":"39","author":"Ates","year":"2016","journal-title":"Hypertens. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"24","DOI":"10.2174\/157339551101150417101550","article-title":"Inflammation and inflammatory cell recruitment in acute cerebrovascular diseases","volume":"11","author":"Tuttolomondo","year":"2015","journal-title":"Curr. Immunol. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Sarejloo, S., Dehesh, M., Fathi, M., Khanzadeh, M., Lucke-Wold, B., Ghaedi, A., and Khanzadeh, S. (2023). Meta-analysis of differences in neutrophil to lymphocyte ratio between hypertensive and non-hypertensive individuals. BMC Cardiovasc. Disord., 23.","DOI":"10.1186\/s12872-023-03304-w"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Larmann, J., Handke, J., Scholz, A.S., Dehne, S., Arens, C., Gillmann, H.-J., Uhle, F., Motsch, J., Weigand, M.A., and Janssen, H. (2020). Preoperative neutrophil to lymphocyte ratio and platelet to lymphocyte ratio are associated with major adverse cardiovascular and cerebrovascular events in coronary heart disease patients undergoing non-cardiac surgery. BMC Cardiovasc. Disord., 20.","DOI":"10.1186\/s12872-020-01500-6"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/nrneurol.2010.178","article-title":"The role of inflammation in epilepsy","volume":"7","author":"Vezzani","year":"2011","journal-title":"Nat. Rev. Neurol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1186\/s12974-018-1192-7","article-title":"The role of inflammation in the development of epilepsy","volume":"15","author":"Rana","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/S0006-8993(99)02439-7","article-title":"Sodium valproate inhibits production of TNF-alpha and IL-6 and activation of NF-kappaB","volume":"857","author":"Ichiyama","year":"2000","journal-title":"Brain Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"108358","DOI":"10.1016\/j.yebeh.2021.108358","article-title":"Effect of valproate and add-on levetiracetam on inflammatory biomarkers in children with epilepsy","volume":"125","author":"Labh","year":"2021","journal-title":"Epilepsy Behav."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/j.seizure.2014.04.011","article-title":"Chronic valproate or levetiracetam treatment does not influence cytokine levels in humans","volume":"23","author":"Guenther","year":"2014","journal-title":"Seizure"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Tsukagoshi, M., Araki, K., Igarashi, T., Ishii, N., Kawai, S., Hagiwara, K., Hoshino, K., Seki, T., Okuyama, T., and Fukushima, R. (2024). Lower Geriatric Nutritional Risk Index and Prognostic Nutritional Index Predict Postoperative Prognosis in Patients with Hepatocellular Carcinoma. Nutrients, 16.","DOI":"10.3390\/nu16070940"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Misirlioglu, N.F., Uzun, N., Ozen, G.D., \u00c7alik, M., Altinbilek, E., Sutasir, N., Baykara Sayili, S., and Uzun, H. (2024). The Relationship between Neutrophil-Lymphocyte Ratios with Nutritional Status, Risk of Nutritional Indices, Prognostic Nutritional Indices and Morbidity in Patients with Ischemic Stroke. Nutrients, 16.","DOI":"10.20944\/preprints202403.0871.v1"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Jhang, S.-W., Liu, Y.-T., Kor, C.-T., Wu, Y.-P., and Lai, C.-H. (2024). Low Prognostic Nutritional Index Predicts In-Hospital Complications and Case Fatality in Patients with Spontaneous Intracerebral Hemorrhage: A Retrospective Study. Nutrients, 16.","DOI":"10.20944\/preprints202405.0727.v1"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1080\/1028415X.2021.1905371","article-title":"Nutritional intake and its impact on patients with epilepsy: An analytical cross-sectional study","volume":"25","author":"Ismail","year":"2022","journal-title":"Nutr. Neurosci."},{"key":"ref_49","first-page":"s00441779269","article-title":"Ketogenic diet in pharmacoresistant epilepsies: A clinical nutritional assessment. Dieta cetog\u00eanica na epilepsia f\u00e1rmaco-resistente: Avalia\u00e7\u00e3o cl\u00ednica-nutricional","volume":"82","author":"Viana","year":"2024","journal-title":"Arq. Neuropsiquiatr."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/1475-2891-5-14","article-title":"Evaluation of nutritional status in children with refractory epilepsy","volume":"5","author":"Bertoli","year":"2006","journal-title":"Nutr. J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e20240166","DOI":"10.1590\/1806-9282.20240166","article-title":"A preliminary study on the association between prognostic nutritional index and neutrophil-to-lymphocyte ratio with nutritional status and inflammation in febrile children\u2019s susceptibility to seizures","volume":"70","year":"2024","journal-title":"Rev. Assoc. M\u00e9dica Bras."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.4103\/1673-5374.335823","article-title":"Basic mechanisms of peripheral nerve injury and treatment via electrical stimulation","volume":"17","author":"He","year":"2022","journal-title":"Neural Regen. Res."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/11\/1847\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:42:38Z","timestamp":1760031758000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/11\/1847"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,28]]},"references-count":52,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["nu17111847"],"URL":"https:\/\/doi.org\/10.3390\/nu17111847","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,28]]}}}