Association of Comorbidity and Inflammatory and Nutritional Markers with Epilepsy and Seizure Frequency

Abstract

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 +/- 14.2 years; female: 21, male: 32), 53 epilepsy patients without comorbidity (mean age: 33 +/- 12.5 years; female: 28, male: 25), and 53 epilepsy patients with comorbidities (mean age: 56.2 +/- 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 < 0.001). The PNI was lowest in epilepsy patients with comorbidities, showing a significant difference between all groups (p < 0.001). High comorbidity burden increased seizure risk by 4.56 times (95% CI: 1.30-16.01), each unit increase in the SII raised the risk by 1.13 times (95% CI: 1.08-1.19), and each unit decrease in the PNI increased the risk by 1.14 times (OR = 0.88, p < 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.