Serum HMGB1 in febrile seizures.

The role of high-mobility group box 1 (HMGB1) in the pathogenesis of febrile seizures (FSs) is unclear. In our controlled follow-up study, we compared serum levels of HMGB1 (s-HMGB1) in the same individuals after the first FS, during febrile episodes without a FS, after recurrent FS, during healthy periods after FS, and between patients and controls. In all, 122 patients with FSs were included in the final analysis, including 18 with recurrent FSs with a complete follow-up protocol. We recruited 30 febrile children and 18 matched febrile children without seizures as controls. S-HMGB1 was lower in patients with recurrent FSs after the first FS than that in matched febrile control children (median 1.12 µg/L (0.14-2.95) vs 1.79 µg/L (0.33-47.90), P<0.04). We did not find any other differences in s-HMGB1 between the groups. S-HMGB1 did not differ in different types of FSs. We updated a meta-analysis of s-HMGB1 in patients with FSs and found that the differences were significant only in the studies conducted in East Asian populations. We conclude that S-HMGB1 does not seem to be a key factor in the pathogenesis of FSs but differences in HMGB1 concentrations could explain some of the ethnicity related susceptibility to FSs.

Growth and differentiation factor-15 as a potential prognostic biomarker for status-epilepticus-associated-with-fever: A pilot study.

OBJECTIVE: Biomarkers predicting poor outcomes of status-epilepticus-associated-with-fever (SEF) at an early stage may contribute to treatment guidance. However, none have been reported thus far. We investigated the dynamics of serum growth and differentiation factor (GDF)-15 after seizure onset in patients with SEF and determined whether GDF-15 can predict poor outcomes, particularly in the first 6 h after seizure onset. METHODS: We enrolled 37 pediatric patients with SEF and eight patients with simple febrile seizures (SFS) and collected their blood samples within 24 h of seizure onset and eight febrile control patients between March 1, 2017 and September 30, 2020. All patients were aged ≤15 years. RESULTS: In the SEF group, the median post-seizure serum GDF-15 values were 1,065 (<6h), 2,720 (6-12 h), and 2,411 (12-24 h) pg/mL. The median serum GDF-15 in the first 6 h was measured in patients with SEF without a significant past medical history (n = 21) and was found to be statistically significantly higher (1,587 pg/mL) than in the febrile control (551 pg/mL) and SFS (411 pg/mL) groups. The median serum GDF-15 was statistically significantly higher in patients with SEF with sequelae (n = 5) and patients with acute encephalopathy with biphasic seizures/reduced diffusion/hemorrhagic shock and encephalopathy syndrome (n = 6) than in patients with SEF without sequelae (n = 16) (15,898 vs 756 pg/mL) and patients with prolonged FS (n = 15) (9,448 vs 796 pg/mL). CONCLUSIONS: This study demonstrates the dynamics of serum GDF-15 in patients with SEF and indicates the potential of GDF-15 as an early predictor of poor outcomes.

Evaluation of risk factors associated with first episode febrile seizure.

OBJECTIVE: Febrile convulsion (FC) is one of the most common neurological findings in children. This study was aimed to investigate the difference in laboratory parameters between Febrile Seizure and control groups. PATIENTS AND METHODS: In this study, 169 children admitted to the pediatric emergency department with their first episode of FS and 189 control groups were retrospectively analyzed. The demographic characteristics and laboratory parameters of children were obtained from their files. RESULTS: Upper respiratory tract infection (URTI) was determined the most common disease (81.6%) in the FC group followed by acute gastroenteritis (AGE) (15.4%) and urinary tract infection (UTI) (3%), respectively. Similarly, URTI was detected as the most common disease (81.8%) in control groups. It was determined that there was no statistically significant difference between the two groups in terms of diseases. The leukocyte and neutrophil counts of the children with FC were significantly higher but the mean corpuscular volume of lenfosit and lenfosit/neutrophil ratio was significantly lower than the control groups (p= 0.009, <0.001, 0.001, <0.001, <0.001, respectively). Children with FC had significantly higher blood glucose, urea, creatinine, creatine kinase, alkaline phosphatase and albumin levels compared with the control groups (p<0.001, in all parameters). On the other hand, the potassium, sodium and chlorine levels of the Children with FCs were significantly lower than control groups (p=0.017, <0.001, p <0.001, respectively). CONCLUSIONS: To conclude, febrile patients with high leukocyte counts, high neutrophil counts, and several biochemical parameters should be carefully monitored for FCs due to the increasing seizure risk.

The evaluation of vitamin K status in children with febrile seizure.

BACKGROUND: Febrile seizure is the most common neurological disorder in childhood. The exact pathophysiology of febrile seizures is unknown. Recent studies showed the role of vitamin K in nonhematological and inflammatory disorders. This study aimed to investigate the serum vitamin K levels in children with febrile seizures. AIMS: To evaluate vitamin K levels in children with febrile seizures. STUDY DESIGN: Prospective case-control study. METHODS: This multicenter study examined representative populations in 8 different cities in Turkey between April 1, 2018 and April 1, 2019. Blood samples were taken from all children at presentation. Vitamin K1, vitamin K2, tumor necrosis factor-alpha, interleukin 1 beta, and interleukin 6 levels were determined by enzyme-linked immunosorbent assay. RESULTS: A total of 155 children were included in the study-84 children with febrile seizures and 71 children in febrile control group. Serum vitamin K1 and vitamin K2 levels were also higher in children with febrile seizures than in the controls. The results of statistical analysis showed that vitamin K1 and vitamin K2 levels were correlated with tumor necrosis factor-alpha, interleukin 1 beta, and interleukin 6 levels. The median vitamin K1 and vitamin K2 levels of children experiencing their first febrile seizure were higher than those in children with recurrent febrile seizures. Type of febrile seizure has no effect on serum vitamin K1 and vitamin K2 levels. CONCLUSION: In children with febrile seizures, vitamin K levels are higher than those in the control group. These new findings may contribute to elucidating the etiopathogenesis of febrile seizures.

The role of inflammatory markers and calculated osmotic pressure in the classification of febrile seizures.

OBJECTIVE: Systemic inflammatory response may contribute to the onset of febrile seizures (FSs). The neutrophil-to-lymphocyte ratio (NLR) has been reported to be useful for differentiating simple and complex FSs in children with a first FS. This study aimed to determine whether easily measurable inflammatory markers were useful for distinguishing between the types of FSs in children with FSs not limited to the first FS. PATIENTS AND METHODS: We conducted a retrospective study of children aged 6-60 months who were presented to the Atsugi City Hospital in Japan for the treatment of FSs between December 2018 and February 2020. A complex FS was defined as a seizure with multiple seizures during the same febrile illness, prolonged seizures and/or focal seizures. A simple FS was defined as a seizure without the characteristics of complex FS. We assessed complete blood count, C-reactive protein, and calculated osmotic pressure. RESULTS: A total of 205 children with FSs (simple, 139; complex, 66) fulfilled the inclusion criteria. None of the inflammatory markers, including NLR, could predict the FS type. The median osmotic pressure was 279.0, 278.8, 283.3, and 278.3 mOsm/kg H2O for children with simple, multiple, prolonged, and focal seizures, respectively. Children with prolonged seizures had a significantly higher calculated osmotic pressure than those with simple FSs (p<0.001) and multiple seizures during the same febrile illness (p=0.004). CONCLUSIONS: Easily measurable inflammatory markers, including NLR, were not useful for distinguishing between types of FSs in children. Large multicenter studies are needed to evaluate the association between osmotic pressure and FS.

Acute Phase Serum Leptin, Adiponectin, Interleukin-6, and Visfatin Are Altered in Chinese Children With Febrile Seizures: A Cross-Sectional Study.

Adipokines, including leptin, visfatin, adiponectin, and interleukin-6 (IL)-6, play multiple roles in the pathophysiology of epilepsy and febrile seizures (FS). We aimed to investigate the associations among plasma adipokines, mainly leptin, visfatin, adiponectin, or IL-6, and the prognosis of FS. This prospective cross-sectional study was conducted from January 2017 to December 2018 at the Wuxi Second People' Hospital China. The levels of serum leptin, visfatin, adiponectin, and IL-6 in 55 children with FS (FS group) were compared with 42 febrile children without seizure (FC group) and 48 healthy children (HC group) in an acute phase. The correlation with clinical indicators was determined by logistic regression analysis. Serum adiponectin and IL-6 levels were significantly higher in the FS group than in the FC and HC groups (p < 0.05), but there was no statistical difference between the FC and HC groups. In addition, logistic regression analysis showed that high concentrations of adiponectin and IL-6 were significantly associated with the occurrence of FS. For leptin and visfatin, they were significantly lower in the FS and FC groups than in the normal control group, but there was no statistical difference between the FS and FC groups. Our results suggest that higher plasma levels of IL-6 and adiponectin may serve as an additional biomarker in the early treatment or follow-up of the FS children.

Quantitative Serum Proteomic Study Reveals that Fibrinogen-Related Proteins May Participate in the Pathophysiological Process of Simple Febrile Convulsion.

Simple febrile convulsion (SFC) is a common disease that is mainly caused by fever from extracranial infections. In this study, we used proteomic approaches involving discovery and validation cohorts to examine the proteomes of serum from children who were diagnosed with SFC, children with fever but without convulsion, and healthy children (normal controls). We identified 86 proteins involved in different biological pathways that were significantly different between the SFC and normal control groups. Of these 86 proteins, 35 had higher expression in the SFC group compared with the normal control group, whereas 51 had lower expression. Notably, fibrinogen-related proteins involved in the coagulation system pathway were markedly decreased in the SFC group. Targeted and absolute quantification of fibrinogen-related proteins was performed and validated the potential of these proteins as biomarkers. Thus, fibrinogen-related proteins may participate in the pathophysiological process of SFC and may be potential biomarkers for the diagnosis of SFC.

Increased levels of NLRP3 in children with febrile seizures.

OBJECTIVE: Febrile seizures (FS) are the most common convulsions in childhood. Interleukin-1beta (IL-1ß) is proposed to play an important role in the development of FS, from in vitro data and data from peripheral blood samples. IL-1ß secretion is needed for activation of the NLR family, pyrin-domain containing 3(NLRP3) inflammasome. However, whether NLRP3 play a role in the development of FS remains unknown. This study aimed to investigate the role of NLRP3 in FS. METHODS: Thirty-two FS cases and twenty-two matched controls were included in this study. Control samples were collected from children with febrile illness without seizures. We detected their levels of IL-1ß and NLRP3 by Enzyme linked immunosorbent assay and Western blot, respectively. RESULTS: Serum IL-1ß levels weresignificantlyhigher in FS patients (Median = 301.64 pg/ml) than in fever only controls (Median = 159.48 pg/ml) (P < 0.05). Additionally, NLRP3 protein levels of peripheral blood mononuclear cells (PBMC) were significantly higher in typical FS than in fever only controls (P < 0.05). Moreover, serum levels of IL-1ß were significantly correlated with levels of NLRP3 protein (r = 0.787, P < 0.001). CONCLUSIONS: In this study, our results firstly indicated that NLRP3 protein was significantly up-regulated in the typical FS children compared in fever only controls. Increased NLRP3 can mediate IL-1ß secretion that is responsible for the occurrence of FS.

Investigating the Relationship between Serum Levels of Interleukin-22 and Interleukin-1 Beta with Febrile Seizure.

A febrile seizure is the most common type of seizure in young kids, which is not fully known. Inflammatory mediators can affect the pathogenesis of the disease. Considering the controversy about the impacts of interleukin 1 beta (IL-1ß) and the lack of a study on interleukin 22 (IL-22), the purpose of the present study was to investigate the relationship between IL-22 and IL-1ß serum levels with febrile seizure in young kids. Our case-control study has been conducted on 120 young kids aged 6-60 months with the sign of the fever. Rectal temperature was measured for allcases. Patients with febrile seizure (n=60) and patients with fever and without a seizure (n=60) were investigated as case and control groups, respectively. Serum levels of IL-22 and IL-1ß were measured in all participants through the ELISA method. The serum level of IL-1ß was significantly higher in the case group compared to the control group (p˂0.001), while there were no significant differences between the two groups in terms of IL-22 (p=0.92). Unlike IL-1ß (p≤0.021), IL-22 showed no difference between two groups according to some demographic and clinical features like gender, age group, family history of febrile seizure, family history of epilepsy, and evolutionary status (p>0.22). Logistic multiple regression analysis showed that, unlike IL-1ß (p˂0.001), IL-22 does not change the chance of febrile seizure in the study groups (p=0.737). The findings of this study indicated that, unlike IL-1ß, IL-22 has not any changes/effects in the febrile seizure.

Prospective case control study of iron deficiency and the risk of febrile seizures in children in South Korea.

BACKGROUND: Febrile seizures are the most common type of seizure in the first 5 years of life, and many factors that increase seizure risk have been identified. This study was performed to examine the association between iron status and febrile seizures in children in South Korea. METHODS: A prospective unmatched case control study was performed in 63 cases of febrile seizures and 65 controls with febrile illness but no seizures. RESULTS: Serum iron, plasma ferritin, and transferrin saturation were significantly lower in children with febrile seizures compared to the controls. Iron deficiency, defined as ferritin < 30 ng/mL, was more prevalent in the febrile seizure group (49.2%) than in the control group (16.9%). Serum iron < 22 ng/dL (odds ratio 3.42, 95% confidence interval [CI] 1.31-8.9, P = 0.012) and ferritin < 30 ng/mL (odds ratio 6.18, 95% CI 2.32-16.42, P < 0.001) were associated with increased risk of developing febrile seizures in multivariate logistic regression analysis. CONCLUSION: These observations suggest that iron deficiency prior to development of anemia may increase risk of febrile seizures.

Ratio of Alpha 2-Macroglobulin Levels in Cerebrospinal Fluid and Serum: An Expression of Neuroinflammation in Acute Disseminated Encephalomyelitis.

BACKGROUND: Acute encephalitis and encephalopathy are life-threatening diseases in children. However, no laboratory examinations are performed for their early diagnosis and treatment. Alpha 2-macroglobulin (α2M) is a blood glycoprotein that increases during the early stages of inflammation. In the present study, we investigated the role of α2M levels in acute encephalitis and encephalopathy. METHODS: We analyzed the cerebrospinal fluid and serum samples from patients with acute disseminated encephalomyelitis, infection-related acute encephalopathy, febrile status epilepticus, and febrile seizure simplex type. Samples were collected from the pediatric department of hospitals throughout the Fukushima Prefecture between January 1, 1999, and May 31, 2012. RESULTS: α2M levels in the cerebrospinal fluid were 4.7 (3.8-8.4) µg/mL for acute disseminated encephalomyelitis, 2.1 (1.1-2.3) µg/mL for infection-related acute encephalopathy, 1.1 (0.9-6.4) µg/mL for febrile status epilepticus, and 1.0 (0.8-1.1) µg/mL for febrile seizure simplex type. α2M levels in patients with acute disseminated encephalomyelitis were significantly higher than those in patients with infection-related acute encephalopathy and febrile seizure simplex type (P = 0.019 and P = 0.002, respectively). The ratio of α2M level in the cerebrospinal fluid to that in the serum in patients with acute disseminated encephalomyelitis was significantly higher than the ratio in patients with febrile status epilepticus (P = 0.04). In patients with acute disseminated encephalomyelitis, α2M levels in the cerebrospinal fluid decreased with treatment. CONCLUSIONS: Our results suggest that α2M levels in the cerebrospinal fluid reflect the neuroinflammatory status of patients with acute disseminated encephalomyelitis.

Increased von Willebrand factor parameters in children with febrile seizures.

INTRODUCTION: Primary blood coagulation and wound sealing are orchestrated by von Willebrand factor (VWF), a large multimeric glycoprotein. Upon release of arginine vasopressin (AVP), VWF containing high molecular weight multimers is secreted. By measuring copeptin, the C-terminal part of the AVP prohormone, we recently found strongly increased AVP levels in children with febrile seizures (FS) as compared to children with fever but without seizures. It is unknown if increased AVP levels in FS are of any biological function. Therefore, our a priori hypothesis was that children with FS have increased VWF parameters in parallel with higher AVP levels. METHODS: We conducted a prospective, cross-sectional study of children aged between 6 months and 5 years. Children that presented at our emergency department with fever or a recent FS (within four hours) were evaluated to be included to the study. We measured serum copeptin and VWF parameters, including analyses of VWF:Antigen (WVF:Ag), VWF:collagen binding activity (VWF:CB) and VWF multimers in children with FS, febrile infections without seizures and additionally, in a non-febrile control group. RESULTS: We included 54 children in our study, 30 with FS, 10 in the febrile control group, and 14 in the non-febrile control group. Serum copeptin levels were significantly higher in children with FS (median [IQR] 24.73 pmol/l [13.65-68.65]) compared to the febrile control group (5.66 pmol/l [4.15-8.07], p = 0.002) and the non-febrile control group (4.78 pmol/l [3.33-5.3], p<0.001). VWF:CB levels were also significantly higher in children with FS (VWF:CB 2.29 U/ml [1.88-2.97]) as compared to the febrile (VWF:CB 1.41 U/ml [1.27-1.93], p = 0.048) and the non-febrile control group (VWF:CB 1.15 U/ml [0.98-1.21], p<0.001). VWF:Ag tended to be higher in children with FS compared to both control groups. Multivariate regression analysis revealed FS and copeptin as major determinants of VWF:CB. CONCLUSIONS: Our results suggest that increased secretion of AVP in children with FS is associated with higher plasma levels of VWF parameters. Especially VWF:CB may serve as additional biomarker in the diagnosis of FS.

The role of Mean Platelet Volume/platelet count Ratio and Neutrophil to Lymphocyte Ratio on the risk of Febrile Seizure.

Systemic inflammatory response has been implicated as a contributor to the onset of febrile seizures (FS). The four novel indices of the inflammatory response such as, neutrophil-to-lymphocyte ratio (NLR), mean platelet volume (MPV), platelet count (PLT) ratio and red blood cell distribution width (RDW) have been investigated in FS susceptibility and FS types (simple febrile seizure and complex febrile seizure). However, the potential role of these inflammatory markers and MPV/PLT ratio (MPR) in Chinese children with FS has yet to be fully determined. This study investigated the relevance of NLR, MPV, PLT, MPR and RDW in febrile children with and without seizures. 249 children with FS and 249 age matched controls were included in this study. NLR and MPR were calculated from complete blood cell counts prior to therapy. Differences in age, gender and these inflammatory markers between the FS group and the control group were evaluated using the chi-square test, t-test or logistic regression analysis. Receiver Operating Characteristic (ROC) curve was used to determine the optimal cut-off value of NLR and MPR for FS risk. Interactions between NLR and MPR on the additive scale were calculated by using the relative excess risk due to interaction (RERI), the proportion attributable to interaction (AP), and the synergy index (S). It has been shown that the elevated NLR and MPR levels were associated with increased risk of FS. The optimal cut-off values of NLR and MPR for FS risk were 1.13 and 0.0335 with an area under the curve (AUC) of 0.768 and 0.689, respectively. Additionally, a significant synergistic interaction between NLR and MPR was found on an additive scale. The mean levels of MPV were lower and NLR levels were higher in complex febrile seizure (CFS) than simple febrile seizure (SFS), and the differences were statistically significant. ROC analysis showed that the optimal cut-off value for NLR was 2.549 with 65.9% sensitivity and 57.5% specificity. However, no statistically significant differences were found regarding average values of MPR and RDW between CFS and SFS. In conclusion, elevated NLR and MPR add evidence to the implication of white cells subsets in FS risk, and our results confirmed that NLR is an independent, albeit limited, predictor in differentiating between CFS and SFS. Moreover, NLR and MPR may have a synergistic effect that can influence the occurrence of FS.

Metabolic profile of oxidative stress and trace elements in febrile seizures among children.

Febrile seizures (FS) are frequent convulsive disorders, occurring in infants and young children. The present study aims to assess and compare the serum levels of oxidative stress markers and some essential trace minerals in FS with normal or abnormal EEG and evaluate the effect of antioxidant therapy on the clinical outcome. This study has been carried out on 80 children with FS (40 with simple FS and 40 with complex FS) and 40 febrile children without seizures. Clinical and EEG findings were recorded for the included patients. Biochemical assays of serum nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD), copper (Cu), zinc (Zn) and selenium (Se), using colorimetric methods, were measured in the studied groups. The overall results showed an increased values of NO, MDA and Cu with decreased values of SOD, Zn and Se in patients with FS (simple and complex) in comparison with febrile children without seizures (p < 0.05 for all). Additionally, NO and MDA was increased in complex FS patients with EEG abnormalities in comparison with complex FS with normal EEG findings (p < 0.05); NO and MDA were also significantly decreased after valproate therapy in complex FS patients (p < 0.05 for all). In conclusions, oxidative stress, decreased Zn and Se with increased Cu may play a role in FS. Valproate improves the oxidative stress status in complex FS.

Interleukin-4 and tumor necrosis factor-alpha levels in children with febrile seizures.

PURPOSE: The pathophysiology of febrile seizures remains unclear. Cytokines have been suggested to play a role in the pathogenesis of febrile seizures. We compared TNF-α and IL-4 levels in patients with febrile seizure (FS) with those in controls and identified the relationship between cytokines and various other factors. METHOD: Fifty FS patients who visited Konkuk University Hospital from December 2015 to December 2016 were included. Thirty-nine patients who had fever without seizures were enrolled as the control group. Serum samples from febrile patients with a history of febrile seizures without present seizures (FPH) (N = 12) and from the afebrile seizure (AF) group (N = 13) were also analyzed. In the FS group, we compared cytokine levels among patients stratified by sex, family history, seizure recurrence, duration of seizure and serum lactate levels. RESULTS: The median serum TNF-α level in the FS group (19.54 pg/mL) was significantly higher than that in the control group (15.86 pg/mL). Higher median serum IL-4 levels were detected in the FS group (3.38 pg/mL) than in the control group (3.30 pg/mL). In the FS group, the serum IL-4 and TNF-α levels correlated with seizure recurrence and serum lactate levels, but they did not correlate with family history, duration of seizures or sex. CONCLUSIONS: Our study supports the hypothesis that TNF-α production is involved in the pathogenesis of febrile seizures. IL-4 is believed to be involved in the pathogenesis of febrile seizures. The number of seizures and lactate levels were correlated with IL-4 and TNF-α levels.

Dynamic thiol/disulphide homeostasis in children with febrile seizure.

PURPOSE: Febrile seizure (FS) is the most common type of seizure in children and its etiopathogenesis is still not fully understood. We aimed to investigate the thiol/disulphide balance in children who had experienced FS in our study. METHODS: We included 40 FS and 40 control group subjects in the study. The total thiol, native thiol, and disulphide levels were measured and the disulphide/native thiol, disulphide/total thiol and native thiol/total thiol ratios were calculated in both groups. RESULTS: The mean age and gender distribution of the patients and control group subjects were similar. The total thiol level was lower in the FS group than the control group with no statistical significance (p = 0.123). Native thiol was significantly lower in the FS group than the control group (p = 0.031). The disulphide level and the disulphide/native thiol and disulphide/total thiol ratios were statistically significantly higher in the FS group than the control group while the native thiol/total thiol ratio was lower. CONCLUSION: The fact that the disulphide level was higher and the native thiol level lower in the FS group than the control group suggests that the thiol/disulphide balance may have shifted in favor of oxidants and that oxidants may have a role in FS pathogenesis.

Serum Interleukin-6 Levels in Children with Febrile Seizures.

OBJECTIVE: To compare levels of Interleukin-6 (IL-6) in children with febrile seizures and febrile controls. METHODS: Study conducted in a tertiary-care hospital in Northern India from November 2013 to April 2015, enrolling 160 children (80 each with febrile seizures and febrile controls), aged 6 - 60 months. Serum IL-6 estimated by ELISA method. Iron study done as per standard technique. All the cases of febrile seizure were followed up at 1 week, 3 months and 6 months for recurrence of seizures. RESULTS: The mean serum IL-6 levels in children with febrile seizures was 62.0 (63.9) pg/mL and febrile controls was 86.9 (70.6) pg/mL (P=0.025). CONCLUSION: Serum IL-6 levels were significantly lower in children with febrile seizures as compared to febrile controls.

Effect of melatonin on cytokine levels in a hyperthermia-induced febrile seizure model.

Higher serum cytokine levels have been reported in children admitted with febrile seizures and in some experimental models. However, other studies have shown that cytokine levels are influenced by melatonin. In this study, we investigated serum cytokine levels in a hyperthermia-induced febrile rat seizure model and the effect of melatonin. A total of 28 male Sprague-Dawley rats were divided into four groups: the control (C) group, healthy melatonin (MT) group, and hyperthermia-induced febrile seizure groups with (HIFS-MT) and without (HIFS) administration of melatonin. Melatonin (80 mg/kg) was given intraperitoneally 15 min before the seizure. HIFS was induced by placing the rats in 45°C water. The rats were sacrificed under anesthesia after the seizure. Blood samples were drawn by transcardiac puncture to measure serum cytokine and melatonin levels. Serum interleukin (IL)-1ß, IL-6, IL-10, and tumor necrosis factor (TNF)-α levels were lower in the HIFS group than those in the C group (p = 0.005, p = 0.200, p = 0.011, and p = 0.016, respectively). All serum cytokine levels of rats in the MT and HIFS-MT groups were similar to those in the C group. This experimental rat model demonstrated that serum cytokine levels decrease with HIFS and that administering melatonin maintains serum cytokine levels. These results suggest that cytokines may play role in the anticonvulsive activity of melatonin in rats with febrile seizures.

Analysis of plasma multiplex cytokines and increased level of IL-10 and IL-1Ra cytokines in febrile seizures.

BACKGROUND: Febrile seizures are the most common form of childhood seizures. Fever generation involves many cytokines, including both pro- and anti-inflammatory cytokines. Some of these cytokines also induce febrile seizures. We compared cytokine production in children with a fever alone (healthy control group) and febrile seizure children group. Also, we evaluated the cytokine level of children with a fever alone and febrile seizure history. METHODS: Fifty febrile seizure patients and 39 normal control patients who visited the emergency department of Konkuk University Hospital from December 2015 to December 2016 were included in this study. Blood was taken from the peripheral vessels of children in all groups within 1 h of the seizure, and serum was obtained immediately. Serum samples from patients with only a fever and a febrile seizure history (N = 13) and afebrile seizure controls (N = 12) were also analyzed. RESULTS: The serum IL-10 and IL-1Ra levels were significantly higher in the febrile seizure patients than in the fever-only control, fever only with a febrile seizure history, and afebrile seizure groups (p < 0.05). The serum IFN-γ and IL-6 levels were significantly higher in the febrile seizure patients than in the afebrile seizure group (p < 0.05). The serum IL-8 levels were higher in the febrile seizure patients than in the fever only controls (p < 0.05). CONCLUSIONS: The serum levels of the IFN-γ, IL-6, and IL-8 pro-inflammatory cytokines and the serum levels of the IL-10 and IL-1Ra anti-inflammatory cytokines were significantly higher in the febrile seizure children. Furthermore, the serum level of IL-1Ra was more increased in the febrile seizure group than in the same patients with only a fever. Our data suggest that increased serum IL-10 and IL-1Ra may play potential roles as anti-inflammatory cytokines in a compensation mechanism that shortens the seizure duration or prevents a febrile seizure attack. Therefore, anti-inflammatory cytokines, including IL-10 and IL-1Ra, have potential as therapeutic targets for the prevention of seizures and nervous system development of children.

Thiol/disulfide homeostasis as a novel indicator of oxidative stress in children with simple febrile seizures.

Simple febrile seizures are generally benign, but during the seizure, elevated levels of glutamate and high levels of oxygen use due to the high metabolic brain activity result in oxidative stress. However, the relationship between febrile seizures and oxidative stress remains unclear. In this study, we investigated thiol/disulfide homeostasis as a new oxidative stress parameter in patients with simple febrile seizures. This study was performed between February 2016 and May 2016 at the Pediatric Emergency Unit. The study population consisted of 40 patients with a diagnosis of simple febrile seizure and 30 control participants aged 8-59 months. Total thiol, native thiol and disulfide levels, disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol ratios were used as thiol/disulfide homeostasis parameters and were quantified in patient and control groups. Furthermore, correlations with seizure duration were investigated. In the patient group, native and total thiol levels and native thiol/total thiol ratios were low, and disulfide levels, disulfide/native thiol, and disulfide/total thiol ratios were significantly higher than in the control group. Negative correlations were observed between seizure duration, total and native thiol levels, and native thiol/total thiol ratio, whereas positive correlations were observed between seizure duration and disulfide/native thiol and disulfide/total thiol ratio. The sensitivities of both disulfide/native thiol and disulfide/total thiol ratios were high for simple febrile seizures. Simple febrile seizures may cause impairment in favor of disulfide bonds in thiol/disulfide homeostasis. Overall, these changes may contribute to neuronal cell damage after simple febrile seizures.