[1] 14w Peripheral inflammatory markers and metabolic profiles in temporal lobe epilepsy and functional dissociative seizures

[1] 283w Background: Temporal lobe epilepsy (TLE) and functional dissociative seizures (FDS) are distinct conditions that share overlapping clinical, neuropsychiatric, and biological features, including depressive symptoms, obesity-related metabolic dysregulation, and alterations in systemic inflammatory markers. Understanding the interplay among these factors may provide insight into their shared biological burden.Objective: This study aimed to investigate the relationships among systemic inflammatory markers, adipokines, obesity, seizure frequency, and depressive symptom burden in patients with drug-resistant TLE, drug-responsive TLE, and FDS.Methods: Seventy-four patients were enrolled and divided into three groups: drugresistant TLE (n = 24), drug-responsive TLE (n = 25), and FDS (n = 25). Demographic and clinical data, physical activity levels, and depression scores were collected.Serum levels of IL-1β, IL-6, TNF-α, BDNF, leptin, and adiponectin were measured using ELISA. Group comparisons were initially performed using One-Way ANOVA or Kruskal-Wallis tests. Multiple linear regression models were subsequently constructed to adjust for potential confounders, including age, sex, and body mass index (BMI). Adjusted p values < 0.05 were considered statistically significant. Results:In crude analyses, IL-1β, leptin, and adiponectin levels differed significantly across groups. However, after adjustment for age, sex, and BMI, only leptin (adjusted p = 0.014) and adiponectin (adjusted p = 0.005) remained significantly associated with the diagnostic group. The difference in IL-1β levels did not retain statistical significance after adjustment (adjusted p = 0.067). IL-6, TNF-α, and BDNF levels did not differ significantly between groups in either crude or adjusted analyses. Beck Depression Inventory scores were numerically higher in the FDS and drug-resistant TLE groups, but the difference did not reach statistical significance. No significant differences were observed in BMI or physical activity levels, and the majority of participants were classified as overweight or having stage 1 obesity.

[1] 127w Temporal lobe epilepsy (TLE) is the most common type of focal epilepsy. In patients with TLE, seizures are often characterized by impaired awareness accompanied by automatisms, language and speech alterations, and unilateral dystonic posturing. 1 Functional dissociative seizures (FDS), on the other hand, are psychogenic disorders that resemble epileptic seizures in terms of symptoms but do not involve abnormal epileptiform activity in the brain. They are frequently misdiagnosed as epilepsy, which may lead to unnecessary treatments. This nonepileptic condition may even be misinterpreted by healthcare providers as being feigned. FDS should not be considered malingering, as it is neither conscious nor intentional. 2 While TLE and FDS have distinct etiopathologies, they may exhibit overlapping clinical and biological associations, including depression, obesity, and alterations in peripheral inflammatory markers.

[2] 139w In addition to neurological manifestations, psychiatric comorbidities are also frequently observed in patients with TLE. Previous studies have reported that the prevalence of psychiatric disorders in individuals with TLE is higher than in those with generalized epilepsy. It has been suggested that hippocampal sclerosis may be associated with an increased risk of frontotemporal network dysfunction leading to psychiatric comorbidity. 3 For FDS, psychiatric disorders are considered not only comorbidities but also potential etiological factors. 4 In a prior study, it was reported that 33.3% of patients followed with a diagnosis of FDS were diagnosed with depressive disorder, while 16.7% were diagnosed with an anxiety disorder. 5 The presence of depression may negatively affect disease course, treatment response, and quality of life in both TLE and FDS, representing a shared clinical burden rather than a distinguishing feature between these conditions.

[3] 113w Obesity and obesity-related metabolic alterations are frequently reported in both TLE and FDS. Previous studies have provided evidence suggesting a bidirectional relationship between epilepsy and obesity. While patients with epilepsy exhibit a greater susceptibility to being overweight or obese compared with the general population, individuals with higher body mass index (BMI) may have an increased risk of developing epilepsy. 6 In FDS, the development of obesity is likely multifactorial, involving a complex interplay between chronic psychological stress, potential side effects of psychotropic or anti-seizure medications, and a sedentary lifestyle often associated with the burden of the disorders. 7 These findings indicate that metabolic factors may contribute to the pathophysiological processes in both conditions.

[4] 160w Alterations in systemic inflammatory profiles have been suggested as a potentially relevant factor in both TLE and FDS. Characterized by the activation of immune cells in the brain, neuroinflammation can disrupt intercellular communication and the integrity of neuronal networks by increasing the release of proinflammatory cytokines and chemokines. Various studies have demonstrated that neuroinflammation plays a role in the pathogenesis and progression of TLE. 8 Similarly, the elevated levels of proinflammatory cytokines observed in patients with FDS suggest that these systemic inflammatory markers may be associated with the clinical profile of the disorder, potentially reflecting a physiological response to chronic stress. 9 Whereas metabolic perturbations in TLE are predominantly secondary to Conclusion: After controlling for age, sex, and BMI, metabolic markers-particularly leptin and adiponectin-remained independently associated with diagnostic group, whereas inflammatory cytokines did not demonstrate robust independent differences. These findings suggest that metabolic dysregulation may represent a more prominent differentiating factor than systemic inflammation among patients with TLE and FDS.

[5] 51w • Metabolic markers (leptin, adiponectin) significantly differ between TLE and FDS patients. • Initial differences in IL-1β levels lost significance after multivariable adjustment. • Systemic IL-6, TNF-α, and BDNF levels do not reliably differentiate FDS from TLE cohorts. • Depressive burden is high but comparable across both epileptic and functional groups.

[6] 130w localized neurogenic inflammation and the pharmacological effects of anti-seizure medications, the etiopathogenesis of FDS is linked to chronic psychological trauma and severe emotional distress. This prolonged neuroendocrine stress burden frequently precipitates sustained dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. 10 The resultant chronic HPA axis hyperactivity and subsequent hypercortisolemia exert direct modulatory effects on peripheral adipose tissue metabolism, driving adipokine dysregulation independent of primary epileptogenic brain lesions. 11 Therefore, alterations in peripheral adipokine profiles provide a quantifiable reflection of the stress-induced metabolic dysregulation intrinsic to FDS. Ultimately, these divergent pathophysiological pathways provide a biological rationale for expecting distinct systemic metabolic profiles in FDS compared to TLE, despite their semiological overlap. Despite these overlapping features, TLE and FDS differ substantially in their underlying mechanisms, making accurate differential diagnosis essential for appropriate management.

[7] 72w In conclusion, a comprehensive examination of depression, obesity, and systemic inflammatory profile in TLE and FDS may contribute to a better understanding of the shared and distinct biological and psychosocial burden associated with these disorders. Rather than serving as diagnostic tools, the observed inflammatory and metabolic alterations highlight the complex interplay between systemic inflammation, metabolic status, and chronic seizure-related stress, underscoring the importance of a multidisciplinary and holistic approach to patient management.

[1] 124w When the demographic data presented in Table 1 were evaluated, no statistically significant differences were observed between the FDS, drug-resistant TLE, and drugresponsive TLE groups in terms of age, height, weight, and body mass index (BMI) (p = 0.396, p = 0.448, p = 0.522, and p = 0.348, respectively). In contrast, when examining the variable of disease onset age, the FDS group showed 5-47) 33.5 (27.25-41.75) 29 (21.5-44.5) 0.396 Height (cm) 162 (160-167) 165 (160-172.75) 165 (156.5-171) 0.448 Weight (kg) 70 (62-80) 72 (62.5-81.75) 83 (59.5-91) 0.522 BMI (kg/m 2 ) 26.6 (24.4-30.75) 25.6 (23.63-28.63) 29.4 (22.65-31.95) 0.348 Age at Onset (years) 28 (17-40.5) 14.00 (7.5-24.75) 16 (6-31) 0.010* Note: Data are presented as median (interquartile range). *Statistically significant differences (p < 0.05).

[2] 70w a significantly higher onset age compared to the other groups (p = 0.010). There were 21 women (84%) in the FDS group, 10 women (41.7%) in the drug-resistant TLE group, and 16 women (64%) in the drug-responsive TLE group. A significant difference in gender distribution was identified among the groups. The proportion of female participants was statistically higher in the FDS group compared with the TLE group (p = 0.006).

[3] 161w When the biochemical parameters presented in Table 2 were evaluated, no significant differences were observed between the FDS, drug-resistant TLE, and drug-responsive TLE groups in terms of IL-6, TNF-α, and BDNF levels in both crude and adjusted analyses. In the initial analysis, significant differences were found between the groups for IL-1β, leptin, and adiponectin levels (Crude p = 0.033, p = 0.027, and p = 0.016, respectively). However, to adjust for sex, age, and BMI, multiple linear regression models were performed. Following this adjustment, IL-1β lost its statistical significance (Adjusted p = 0.067). In contrast, leptin and adiponectin levels remained statistically significant even after the adjustment for these potential confounders (Adjusted p = 0.014 and p = 0.005, respectively). Post-hoc analyses revealed that the drug-responsive TLE group had significantly lower leptin levels and significantly higher adiponectin levels compared to the other groups. No statistically significant differences were observed between the drug-resistant and drug-responsive TLE groups for these parameters (p > 0.05).

[4] 80w According to the data presented in Table 3, a statistically significant difference was observed between the study groups in terms of seizure frequency over the past three months (p < 0.001). In the FDS group, 48% of patients experienced more than one seizure per month, whereas the drug-resistant TLE group had the highest proportion in this category (83.3%). In contrast, the highest proportion of patients experiencing fewer than one seizure per month was observed in the drug-responsive TLE group (72%).

[5] 37w According to the results presented in Tables 4 and 5, no statistically significant differences were observed between the study groups in terms of physical activity levels and depression scores (p = 0.292 and p = 0.123, respectively).

[6] 51w In the assessment of physical activity, 36% of patients in the FDS group were classified as "very active," 60% as "minimally active," and 4% as "inactive." In the drugresistant TLE group, these proportions were 20.8%, 62.5%, and 16%, respectively, while in the drug-responsive TLE group, they were 16%, 76%, and 8%.

[7] 17w Regarding depression scores, the mean Beck Depression Inventory scores were 22.84 ± 9.11, 21.75 ± 13.58, and

[8] 189w T A B L E 2 Evaluation of biochemical analysis results. Variables FDS (n = 25) Drug-resistant TLE (n = 24) Drug-responsive TLE (n = 25) Crude p Adjusted p IL-6 (pg/mL) 24.90 (21.33-28.06) 26.22 (23.57-28.55) 26.00 (23.80-29.28) 0.723 0.888 TNF-α (pg/mL) 19.39 (18.50-20.29) 18.90 (18.30-20.94) 19.07 (18.09-23.08) 0.692 0.552 IL-1β (pg/mL) 36.98 (32.91-39.96) 35.47 (30. 11-37.82) 32.72 (28. 3-32.72)* 0.033* 0.067 BDNF (ng/mL) 160.59 (138. 14-179.80) 156.24 (114.21-179.17) 150.39 (134.13-163.69) 0.559 0.595 Leptin (ng/mL) 14.44 (12.62-15.23) 14.83 (9.36-17.01) 11.56 (10.52-14.25)* 0.027* 0.014* Adiponectin (ng/mL) 2733.11 (2464.80-2733.11) 3234.14 (2603.56-3995.30) 3399.95 (2768.74-4029.95)* 0.016* 0.005* Note: Data are expressed as median (interquartile range). Crude p-values were obtained from the Kruskal-Wallis test. Adjusted p-values were derived from multivariable linear regression models adjusted for sex, age, and body mass index (BMI). *Statistically significant differences (p < 0.05). Variables PNES (n = 25) Drug-resistant TLE (n = 24) Drug-responsive TLE (n = 25) p Seizure frequency in the last 3 months < 0.001 Once a month 4 (%16) 3 (%12,5) 3 (%12) Less than once a month 9 (%36) 1 (%4,2) 18 (%72) More than once a month 12 (%48) 20 (%83,3) 4 (%16)

[9] 7w Note: Data are presented as n (%).

[1] 123w In this study, the relationships among systemic inflammatory markers, depression, obesity, and seizure frequency were examined in patients with TLE and FDS, and intergroup differences were evaluated. Our findings highlight the importance of a comprehensive assessment of the biological and psychosocial factors that influence the clinical course of epilepsy and FDS. Analysis of the demographic data revealed a significant difference in gender distribution among the groups. The higher number of women with FDS is consistent with the literature, which reports a greater prevalence of psychogenic seizures in females. 12 No statistically significant differences were observed between the groups in terms of age or marital status, suggesting that these demographic variables are not directly associated with seizure types within the context of our study.

[2] 246w In our initial analysis, we observed elevated IL-1β levels in the FDS group compared to the drug-responsive TLE group; however, this difference lost statistical significance following multivariable adjustment for sex, age, and BMI. A previous study investigating IL-1β levels in drug-resistant epilepsy and FDS similarly reported no significant difference between these two groups. 13 In line with that study, our adjusted results demonstrated no significant variance in IL-1β levels between FDS and drug-resistant TLE patients. The absence of a significant difference between these groups after adjustment does not necessarily imply an absence of systemic inflammation. It is highly plausible that IL-1β levels are upregulated in both functional seizures and epilepsy through distinct underlying drivers-such as chronic psychological stress and HPA axis dysregulation in FDS and neurogenic inflammation in TLE. An enhanced inflammatory response involving IL-1β in patients with drug-resistant epilepsy has been welldescribed in previous experimental models, such as those by Fu et al. 14 Although FDS is primarily considered a psychologically based condition, the potential involvement of systemic inflammatory responses linked to chronic stress should be considered when evaluating its multifaceted nature. However, a major limitation of our study is the absence of a healthy control group, which restricts our ability to definitively state whether these markers are absolutely elevated compared to a normative population. Consequently, while our findings suggest that FDS and TLE may share a comparable baseline of inflammatory burden, future studies incorporating healthy controls are required to clarify their exact pathogenic roles.

[3] 72w In our study, leptin and adiponectin levels differed significantly across the groups, and importantly, these differences remained statistically robust even after multivariable adjustment for sex, age, and BMI. Our findings align with previous literature reporting a disruption in adipokine balance in temporal lobe epilepsy. Specifically, Toscano et al. 15 reported elevated leptin and reduced adiponectin levels in patients with TLE, emphasizing this adipokine profile as a potential indicator of chronic low-grade inflammation.

[4] 207w Our study expands upon these findings by comparatively evaluating FDS, drug-resistant TLE, and drugresponsive TLE cohorts. While the FDS group exhibited the most prominent alterations-characterized by significantly higher leptin and lower adiponectin levels compared to the drug-responsive TLE group-we found no statistically significant difference between the two TLE subgroups. Although there was a numerical trend toward higher leptin and lower adiponectin in the drug-resistant TLE patients, the lack of statistical significance suggests that systemic adipokine levels may not directly reflect the degree of drug resistance or seizure frequency in our specific cohort. The markedly elevated leptin levels observed primarily in the FDS group suggest a potential association between metabolic-inflammatory imbalance and increased neuropsychiatric vulnerability. While leptin is recognized for its proinflammatory properties, its elevation in our study might reflect a broader systemic metabolic response rather than a primary driver of epileptic activity. As noted by Toscano et al., the persistence of chronic inflammation in TLE is associated with glial activation, cytokine release, and interactions between the peripheral immune system and the brain. 15 However, in our cohort, the lack of a statistically significant difference in leptin levels between drug-resistant and drugresponsive TLE patients indicates that systemic leptin does not directly dictate drug resistance or hinder seizure control.

[5] 116w Similarly, while adiponectin is an anti-inflammatory adipokine shown in animal models to reduce hippocampal excitotoxicity, its levels did not significantly differ between our TLE subgroups. Although Toscano et al. reported reduced adiponectin levels in TLE patients, and our drugresponsive TLE group exhibited the highest adiponectin levels numerically, the absence of statistical significance between the TLE cohorts suggests that systemic adipokine levels alone cannot reliably stratify disease severity or treatment response in epilepsy. Furthermore, as no direct correlation analyses were performed between individual seizure frequencies and inflammatory markers, these interpretations remain strictly hypothesis-generating. Further research is required to determine whether these peripheral metabolic changes truly correlate with mechanisms that influence seizure threshold or limbic excitability in humans.

[6] 152w Another important contribution of our study is the finding of elevated leptin levels in the FDS group. Although the biological mechanisms underlying FDS are often approached within a psychosocial framework, an increasing number of studies indicate that stress, inflammation, and metabolic responses may play a role in FDS. Our findings provide biochemical support for the potential mediatory role of leptin within the stress-inflammation axis in FDS. These findings should not be interpreted as evidence of a primary biological etiology for FDS, but rather as indicators of systemic stress-related physiological responses that may accompany FDS. Specifically, the chronic hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and subsequent hypercortisolemia inherent to chronic psychological trauma may directly drive peripheral adipokine dysregulation and leptin resistance. 10,11 This neuroendocrine cascade provides a mechanistic explanation for the significant variance of these metabolic markers in the FDS cohort, acting independently of the traditional neurogenic inflammation typically associated with epileptic seizures.

[7] 121w Beyond their potential diagnostic implications, the robust alterations observed in adipokine levels-namely leptin and adiponectin-provide important insights into the systemic metabolic and low-grade inflammatory burden, particularly within the FDS cohort. While our adjusted analyses indicated that variations in IL-1β were largely confounded by demographic factors, the persistence of profound adipokine dysregulation highlights that functional dissociative seizures are associated with significant, biologically measurable metabolic alterations. Understanding that FDS presents with this distinct systemic profile, likely intertwined with chronic psychological stress and HPA axis dysregulation, is clinically important. Rather than serving merely as standalone diagnostic tools, these biomarkers underscore the necessity for holistic management strategies that address not only the neuropsychiatric symptoms but also the underlying systemic metabolic health in these patient populations.

[8] 221w Similar to the adjusted results for IL-1β, no significant differences were observed between the study groups in other peripheral inflammatory markers, namely IL-6 and TNF-α levels, neither in crude nor adjusted analyses. Although the literature has widely reported that TLE is associated with chronic neuroinflammation, 16 our results indicate that systemic levels of IL-6 and TNF-α do not significantly differ between FDS, drug-resistant TLE, and drug-responsive TLE patients. The lack of a statistically significant variance suggests that these specific peripheral cytokines may not directly mirror localized neuroinflammatory processes, or their systemic fluctuations are too subtle to serve as reliable discriminators among these conditions in our cohort. Similarly, the absence of a significant difference in BDNF levels across the groups indicates that peripheral BDNF alone is not a sensitive biomarker for differentiating functional dissociative seizures from epilepsy. However, as a major limitation, the absence of a healthy control group prevents us from determining whether the baseline levels of these markers are uniformly elevated across all patient groups compared to a normative population, or if they remain within healthy physiological limits. These findings further highlight that while central neuroinflammation is a key component of TLE pathogenesis, its reflection in peripheral blood via basic cytokines and neurotrophic factors appears to be limited, emphasizing the need for more specific systemic biomarkers and controlled comparative studies.

[9] 259w According to the depression assessment results, Beck Depression Inventory scores were numerically higher in the FDS and drug-resistant TLE groups compared to the drug-responsive TLE group; however, these differences did not reach statistical significance. This finding indicates that depressive symptom burden is prevalent across patients with chronic seizure disorders but does not appear to differ according to seizure type or treatment response in this cohort. Consistent with previous literature reporting high rates of depression and anxiety in individuals with FDS, our results support the notion that depressive symptoms represent a shared psychological burden rather than a distinguishing feature between epileptic and functional dissociative seizures. 17 No statistically significant differences were observed between groups in terms of physical activity level and body mass index (BMI). However, along with the use of anti-seizure medications, a sedentary lifestyle, and the physiological impact of chronic stress on the HPA axis, these factors suggest that these individuals represent a population at increased metabolic risk. This multifaceted etiology underscores that weight gain in these patients is not merely a consequence of a single factor but a result of combined behavioral, pharmacological, and biological influences. It is important to note that even a BMI above 25 kg/m 2 , representing an overweight status, contributes to this cumulative metabolic burden. Importantly, the absence of significant differences in BMI between groups does not preclude meaningful differences in metabolic or inflammatory profiles. Adipokine alterations, such as elevated leptin or reduced adiponectin levels, may occur independently of overt obesity and may therefore better reflect underlying metabolic stress than BMI alone.

[10] 287w There are several limitations to this study that should be acknowledged. First, the sample size in each group was relatively small, which may limit the statistical power to detect subtle differences, particularly between the two TLE subgroups. Second, the absence of a healthy control group means we cannot definitively conclude whether the observed biomarker levels-even those that remained significant after adjustment, such as leptin and adiponectin-are pathologically elevated or diminished compared to a normative physiological baseline; they can only be interpreted relative to the other patient groups. Furthermore, while all blood samples were collected at least 24 h after the last seizure or functional event to ensure a baseline state, the relatively high frequency of events in nearly half of the FDS group within the preceding month might still exert a residual influence on systemic metabolic and inflammatory markers. However, the study's primary focus was the comparative evaluation of these clinically overlapping patient populations. Future studies employing larger, demographically matched cohorts that include healthy controls are warranted to further clarify the exact pathophysiological role of these systemic biomarkers. Another limitation of the present study is that, although our multivariable analyses systematically adjusted for demographic variables and BMI, we did not account for the specific classes, dosages, or polytherapy regimens of anti-seizure medications (ASMs) and psychotropic agents utilized by the cohort. It is well-established that specific ASMs (e.g., valproic acid, carbamazepine) and various psychotropic medications frequently prescribed for FDS exert pleiotropic effects on metabolic homeostasis. Consequently, while the study groups exhibited comparable mean BMI distributions, the potential for pharmacological confounding on adipokine secretion patterns cannot be definitively excluded. Future large-scale, prospective studies are warranted to stratify metabolic and inflammatory biomarker data according to specific psychopharmacological and ASM regimens.

[11] 147w In conclusion, our study demonstrates that while systemic inflammatory cytokines may not reliably differentiate between TLE and FDS after adjusting for demographic factors, significant alterations in metabolic adipokine profiles-specifically leptin and adiponectinare evident, particularly in patients with FDS. These findings suggest that rather than a standalone inflammatory response, there is a distinct systemic metabolic dysregulation associated with these chronic disorders. Although the non-specific nature of these systemic biomarkers limits their utility as direct differential diagnostic tools, their significant variance highlights the complex biological and metabolic underpinnings of both epileptic and functional seizures. Furthermore, depressive symptoms contribute significantly to the overall clinical burden in both TLE and FDS; however, they do not differentiate between epileptic and functional events in this cohort. Ultimately, these findings advocate for a multidisciplinary clinical approach that integrates metabolic and psychological evaluations alongside standard neurological care to provide comprehensive management for these patient populations.

[1] 41w The primary materials used in the study included standard laboratory equipment such as a refrigerator, incubator, magnetic stirrer, centrifuge devices, automatic pipettes, a pH meter, and micro-ELISA kits. In addition, Cloude-Clone ELISA kits and biochemistry tubes were utilized for biochemical analyses.

[2] 29w A total of 74 patients who presented to the Neurology Outpatient Clinic of Erciyes University Faculty of Medicine were included in this study. Participants were divided into three groups:

[3] 80w 1. Patients with drug-resistant Temporal Lobe Epilepsy (n = 24) 2. Patients with drug-responsive Temporal Lobe Epilepsy (n = 25) 3. Patients with functional dissociative seizures (FDS) (n = 25) 2.3 | Inclusion criteria • Having experienced seizure (epileptic or psychogenic nonepileptic) confirmed by video-EEG monitoring as the gold standard for diagnosis. Specifically, the diagnosis of FDS was established based on the recording of typical habitual events during video-EEG without concomitant epileptiform discharges. • Absence of a degenerative brain disease.

[4] 33w • History of neurological or psychiatric disorders (e.g., schizophrenia, dementia)/ • Patients with comorbid epilepsy and FDS were excluded to ensure clear differentiation between the study groups. • Visual impairment or intellectual disability.

[5] 54w Information was obtained from the participants regarding age, sex, educational status, neurological and psychiatric disorders, and medications used. Physical activity levels were assessed using the IPAQ. The questionnaire includes vigorous and moderate activities, walking, and sitting times performed in the past week. The collected data were used to calculate the MET (metabolic equivalent) score.

[6] 155w Five milliliters of blood samples were collected from the participants. To maintain the stability of IL-1β and other cytokines, blood samples were allowed to clot at room temperature for 30 min and were then centrifuged at 3000 rpm for 10 min. The serum samples were immediately separated and stored at -80°C until the day of analysis. Although video-EEG monitoring was performed for diagnostic confirmation, blood samples for this study were collected during routine outpatient follow-up visits, not during video-EEG monitoring. This approach was chosen to avoid the confounding effects of acute seizure stress, hospitalization, and post-ictal acute inflammation. Consequently, blood samples were obtained during the interictal period (at least 24 h after the last seizure) to ensure that cytokine levels reflected chronic systemic inflammatory profiles rather than acute post-ictal changes. Additionally, samples were collected between 08:00 and 10:00 AM following an overnight fast to control for the circadian and metabolic variations of leptin and adiponectin.

[7] 32w Levels of TNF-α, IL-6, IL-1β, BDNF, leptin, and adiponectin were measured using the ELISA method. The ELISA kits operate based on a non-competitive method relying on the formation of an antigen-antibody complex.

[8] 161w The normality of the data was assessed using histograms, Q-Q plots, and the Shapiro-Wilk test. For normally distributed data, the arithmetic mean ± standard deviation (X ± SD) was used, whereas for non-normally distributed data, the median and interquartile range were reported. Comparisons between groups were performed using One-Way ANOVA or the Kruskal-Wallis test. Specifically, for significant biomarkers (IL-1β, leptin, and adiponectin), inter-group differences were analyzed using the Kruskal-Wallis H test followed by Dunn's post-hoc pairwise comparisons. To prevent Type I error inflation, p-values were adjusted via Bonferroni correction. Furthermore, multivariable linear regression analyses using log-transformed biomarker levels were performed to adjust for potential confounders, including sex, age, and body mass index (BMI). For demographic variables showing significant inter-group differences (specifically, age at onset), pairwise comparisons were conducted using the Mann-Whitney U test. Categorical data were compared using Pearson's χ 2 test. All analyses were performed using IBM SPSS 23 software, and a p-value of < 0.05 was considered statistically significant.

[1] 11w adiponectin, functional dissociative seizures, leptin, systemic inflammatory markers, temporal lobe epilepsy

[2] 51w The BDI is a 21-item test that measures the severity of depression. Participants rated each item on a four-point scale, and those with a total score of 17 or higher were considered to be depressed. BDI scores were analyzed to assess depressive symptom severity rather than to establish categorical psychiatric diagnoses.

[3] 21w Patients' existing medical conditions were evaluated using the CCI scoring system, and patients were classified according to their level of comorbidity.

[4] 27w 2.5.5 | Body mass index (BMI) BMI was calculated by dividing body weight by the square of height, and obesity status was categorized based on this value.

[5] 54w Comparison of seizure frequency among groups in the last 3 months. 16.84 ± 9.45 in the FDS, drug-resistant TLE, and drugresponsive TLE groups, respectively. Although mean BDI scores were numerically higher in the FDS and drugresistant TLE groups, these differences did not reach statistical significance, indicating that depressive symptom burden was comparable across groups.