Time courses of HMGB1 and other inflammatory markers after generalized convulsive seizures.

PURPOSE: Neuroinflammation and disruption of blood brain barrier (BBB) are important players in epileptogenesis, ictogenesis and pharmacoresistance. In this context, we investigated blood levels of HMGB1 and other inflammatory and BBB markers after generalized and focal to bilateral tonic-clonic seizures in serum, summarized under the term generalized convulsive seizures (GCS). METHODS: We included consenting adults who were admitted to the epilepsy monitoring unit. Blood samples were drawn at baseline and immediately after a GCS as well as after 2, 6 and 24 h. We measured leukocytes, c-reactive protein (CRP), the danger-associated molecular patterns (DAMPs) high mobility group box 1 (HMGB1) and S100, receptor of advanced glycation end products (RAGE) alongside the BBB markers intercellular adhesion molecule-1 (ICAM1) and matrix metalloproteinase 9 (MMP9). Noradrenaline and lactate measurements were available from a previous study. P-levels <0.05 were regarded as significant. RESULTS: Twenty-eight patients with 28 GCS were included. Leukocytosis occurred immediately after GCS and normalized within two hours (p < 0.001). S100 and HMGB1 both increased by ∼80 % (p < 0.001). MMP9 peaked after six hours with levels at 48.6 % above baseline. RAGE decreased by 17.6 % with a nadir at 24 h. CRP increased by 118 % with a peak at 24 h. ICAM1 remained stable (p = 0.068). Postictal HMGB1 correlated with postictal leukocytosis (r = 0.42; p = 0.025) and with MMP9 levels six hours later (r = 0.374; p = 0.05). Postictal lactate levels correlated with MMP9 at 6 h (r = 0.48; p = 0.01) and CRP at 24 h (r = 0.39; p = 0.04). Postictal noradrenaline correlated with lactate (r = 0.57; p = 0.02) and leukocytes (r = 0.39; p = 0.047). DISCUSSION: The serum level of the DAMPs HMGB1 and S100 increase immediately after GCS. The hypothetical mechanism includes central nervous processes, such as glutamate toxicity and ROS release from seizing neurons but also muscular tissues. BBB breakdown is marked by the release of MMP9. Further research is needed to understand the complex interactions between electrical and metabolic stress, neuroinflammation and BBB mechanics in seizures and epilepsy. CONCLUSION: Our study reveals signs of inflammation, neuronal damage and transitory disruption of BBB following single GCS, underscoring the widespread and possibily detrimental effects of recurrent seizures on brain properties. The long term impact on the disease course, however, is unclear.

Relationship between generalized epileptic seizure and neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and neutrophil mediated inflammation.

Aim: There is a close relationship between systemic inflammation and epileptic seizure. Recently, neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) have been defined as significant inflammation biomarkers. In the present study, it was aimed to determine levels of NLR, PLR, and mean platelet volume (MPV) during generalized tonic clonic epileptic seizures, and to investigate their relationships with epileptic seizures.Methods: The present study was conducted on 72 patients with epilepsy who applied with primary and secondary generalized tonic clonic epileptic seizures according to classification of the International League Against Epilepsy (ILAE), and 72 healthy individuals as the control group. Neutrophil and lymphocyte counts, NLR, PLR, and MPV values of patients were evaluated both in acute (in the first hour of epileptic seizure) and subacute (in hour 72 of epileptic seizure) phases by biochemical analysis.Results: Statistically significant differences were determined in laboratory values of white blood cell (WBC) (p < 0.001), neutrophil (p < 0.001), lymphocyte (p < 0.001), NLR (p < 0.001), MPV (p < 0.05), platelet (p < 0.001), C-reactive protein (CRP) (p < 0.05) in acute phase; and in lymphocyte (p < 0.05), NLR (p < 0.05), platelet (p < 0.001), and CRP (p < 0.001) in subacute phase between patients and healthy controls. Statistically significant differences were determined in laboratory values of WBC (p < 0.001), neutrophil (p < 0.001), lymphocyte (p < 0.05), NLR (p < 0.001), CRP (p < 0.001), and PLR (p < 0.05) in patient group between acute and subacute phases. In patient group, mean lymphocyte count was determined lower in acute phase than subacute phase (p < 0.05).Conclusion: The most striking finding of the present study is determination of 1 unit increase in NLR results in 1.95 folds increase in epileptic seizure risk in binary logistic regression analysis. Additionally, it indicates that epileptic seizure is correlated with NLR, PLR, and neutrophil mediated inflammation. To the best of authors knowledge, this is the first report indicating that there is a relationship between epileptic seizure and PLR, neutrophil mediated inflammation, and that 1 unit increase in NLR increases epileptic seizure risk by 1.95 folds.

Vitamin D status of untreated children and adolescent Egyptian patients with genetic generalized epilepsy: A case-control study.

PURPOSE: Antiepileptic drugs (AEDs) are commonly incriminated for vitamin D deficiency in children with epilepsy. The aim of this study was to examine 25(OH) vitamin D status among children and adolescents with genetic generalized epilepsy (GGE) who had never received AEDs and its relation to seizure frequency and epilepsy duration. METHODS: This case-control study was conducted on 42 recently diagnosed patients with GGE, aged ≤18 years and 40 age- and gender-matched controls. Serum 25(OH) vitamin D level was performed for all participants. RESULTS: Serum 25(OH) vitamin D level was significantly lower in patients (median = 22 ng/ml, interquartile range (IQR) = 16.6-28.6) compared with controls (median = 58.4 ng/ml, IQR = 53-68), (P-value < 0.001). Patients with ≥4 seizures per month had a significantly lower level of serum 25(OH) vitamin D (median = 17.7 ng/ml, IQR = 16-24) than patients with lower seizure frequency (median = 28.3 ng/ml, IQR = 24.2-40.2), (P-value = 0.004). Also, there was a statistically significant negative correlation between the duration of epilepsy and serum 25(OH) vitamin D level (r = -0.309, P-value = 0.046). The receiver operating characteristic curve analysis showed that serum 25(OH) vitamin D level with a cutoff value of 23.9 distinguished patients with low seizure frequency (five or less per year) from patients with higher seizure frequency with a sensitivity and specificity of 80% and 74%, respectively (area under the curve (AUC) = 0.798). CONCLUSION: Vitamin D deficiency is found in treatment-naive children with epilepsy and adolescents with GGE, and it is associated with higher seizure frequency, longer disease duration, and younger age at onset.

Circulating microRNAs as potential biomarkers for genetic generalized epilepsies: a three microRNA panel.

BACKGROUND AND PURPOSE: Genetic generalized epilepsies (GGEs) encompass a group of syndromes of mainly genetic causes, characterized by the involvement of both hemispheres. MicroRNAs (miRNAs) are small non-coding RNAs with a critical role in the regulation of neuronal biological processes through gene expression modulation. Dysregulated miRNA expression has been shown in epilepsy. Due to their stability in biological fluids like serum, miRNAs have assumed a prominent role in biomarker research. Our aim was to evaluate circulating levels of three miRNAs in GGE patients and assess their putative diagnostic value. METHODS: MiR-146a, miR-155 and miR-132 were quantified by real-time polymerase chain reaction in the serum of 79 GGE patients (47 women, 32 men, 35.1 ± 12.4 years) and 67 healthy individuals (41 women, 26 men, 42.4 ± 10.1 years). Relative expression values were calculated using the 2-ΔΔCt method. Receiver operating characteristic curve analysis was performed to assess diagnostic value. MiRNA expression was correlated with clinicopathological features. RESULTS: Serum levels of miR-146a and miR-155 were significantly upregulated in GGE patients relative to controls (3.13 and 6.05, respectively). Combined miR-146a, miR-155 and miR-132 serum levels performed well as a diagnostic biomarker, discriminating GGE patients from controls with an area under the curve of 0.85, 80% specificity and 73% sensitivity. CONCLUSIONS: Our results indicate that miR-146a, miR-155 and miR-132 may partake in GGE epileptogenesis. A panel of three circulating miRNAs with potential value as a GGE biomarker is reported for the first time. Novel biomarkers may help to identify new treatment targets and contribute to improved patients' quality of life through earlier diagnosis and a more precise prognosis.

Cardiac stress after electroconvulsive therapy and spontaneous generalized convulsive seizures: A prospective echocardiographic and blood biomarker study.

AIM: Knowledge about cardiac stress related to seizures in electroconvulsive therapy (ECT) and spontaneously occurring generalized convulsive seizures (GCS) is limited. The aim of the present study was to analyze cardiac function and circulating markers of cardiac stress in the early postictal period after ECT and GCS. METHODS: Patients undergoing ECT in the Department of Psychiatry, Psychotherapy and Psychosomatics and patients undergoing diagnostic video-EEG monitoring (VEM) in the Department of Neurology were prospectively enrolled between November 2017 and November 2018. Cardiac function was examined twice using transthoracic echocardiography within 60 min and >4 h after ECT or GCS. Established blood markers (troponin T high-sensitive, N-terminal pro brain natriuretic peptide) of cardiac stress or injury were collected within 30 min, 4 to 6 h, and 24 h after ECT or GCS. In the ECT group, the troponin T values were also correlated with periprocedural heart rate and blood pressure values. Because of organizational or technical reasons, the measurement was not performed in all patients. RESULTS: Twenty patients undergoing ECT and 6 patients with epilepsy with a GCS during VEM were included. Postictal echocardiography showed no wall motion disorders and no change in left ventricular and right ventricular functions. Four of 17 patients displayed a transient increase in high-sensitive cardiac troponin T 4-6 h after the seizure (3 patients with ECT-induced seizure). None of these 4 patients had signs of an acute cardiac event, and periprocedural blood pressure or heart rate peaks during ECT did not significantly differ in patients with and without troponin T elevation. CONCLUSIONS: Signs of mild cardiac stress can occur in some patients following ECT or GCS without clinical complications, probably related to excessive catecholamine release during the seizure.

Blood markers of cardiac stress after generalized convulsive seizures.

OBJECTIVE: Generalized convulsive seizures (GCS) are associated with high demands on the cardiovascular system, thereby facilitating cardiac complications. To investigate occurrence, influencing factors, and extent of cardiac stress or injury, the alterations and time course of the latest generation of cardiac blood markers were investigated after documented GCS. METHODS: Adult patients with refractory epilepsy who underwent video-electroencephalography (EEG) monitoring along with simultaneous one-lead electrocardiography (ECG) recordings were included. Cardiac biomarkers (cardiac troponin I [cTNI]; high-sensitive troponin T [hsTNT]; N-terminal prohormone of brain natriuretic peptide [NT-proBNP]; copeptin; suppression of tumorigenicity-2 [SST-2]; growth differentiation factor 15, [GDF-15]; soluble urokinase plasminogen activator receptor [suPAR]; and heart-type fatty acid binding protein [HFABP]) and catecholamines were measured at inclusion and at different time points after GCS. Periictal cardiac properties were assessed by analyzing heart rate (HR), HR variability (HRV), and corrected QT intervals(QTc). RESULTS: Thirty-six GCS (6 generalized-onset tonic-clonic seizures and 30 focal to bilateral tonic-clonic seizures) were recorded in 30 patients without a history of cardiac or renal disease. Postictal catecholamine levels were elevated more than twofold. A concomitant increase in HR and QTc, as well as a decrease in HRV, was observed. Elevations of cTNI and hsTNT were found in 3 of 30 patients (10%) and 6 of 23 patients (26%), respectively, which were associated with higher dopamine levels. Copeptin was increased considerably after most GCS, whereas SST-2, HFABP, and GDF-15 displayed only subtle variations, and suPAR was unaltered in the postictal period. Cardiac symptoms did not occur in any patient. SIGNIFICANCE: The use of more sensitive biomarkers such as hsTNT suggests that signs of cardiac stress occur in about 25% of the patients with GCS without apparent clinical symptoms. SuPAR may indicate clinically relevant troponin elevations. Copeptin could help to diagnose GCS, but specificity needs to be tested.

Clinical utility of serum lactate levels for differential diagnosis of generalized tonic-clonic seizures from psychogenic nonepileptic seizures and syncope.

BACKGROUND: The differential diagnosis of generalized tonic-clonic seizures (GTCS), psychogenic nonepileptic seizures (PNES), and syncope constitutes a major challenge. Misdiagnosis rates up to 20 to 30% are reported in the literature. PURPOSE: To assess the clinical utility of serum lactate levels for differentiation of GTCS, PNES, and syncope based on gender differences. METHODS: Data from 270 patients were evaluated retrospectively. Only patients ≥18 years old with the final diagnosis of GTCS, PNES, or syncope in their chart were recruited. Serum lactate levels were measured in the first 2h of the index event. RESULTS: Serum lactate levels in patients with GTCS (n=157) were significantly higher than in the patients with PNES (n=25) (p<0.001) and syncope (n=88) (p<0.001). When compared with the females, serum lactate levels in patients with GTCS were significantly higher in the male subgroup (p=0.004). In male patients the ROC analysis yielded a serum lactate value of 2.43mmol/l with a sensitivity of 0.85 and a specificity of 0.88 as the optimal cut-off value to distinguish GTCS from other events. The ROC analysis for the AUC yielded a high estimate of 0.94 (95% confidence interval: 0.91-0.98). When a cut-off value of 2.43mmol/l was chosen for the females, which was an optimal value for male patients, the specificity was 0.85, however, the sensitivity was 0.64. CONCLUSION: We propose that serum lactate level when measured in the first 2h after the index event has a high clinical utility in the differential diagnosis of GTCS, PNES, and syncope. With concomitant clinical signs and physical examination findings besides neuroimaging and EEG, elevated levels of lactate should be taken into account when evaluating a patient with impaired consciousness. On the other hand, the suggested cut-off value 2.43mmol/l might not have a discriminative effect between GTCS, PNES, and syncope in female patients. This finding should be verified in a prospectively designed study with a larger patient population.

Changes in serum miRNAs following generalized convulsive seizures in human mesial temporal lobe epilepsy.

MicroRNAs (miRNAs) are key regulators of gene expression and are involved in the pathomechanisms of epilepsy. MiRNAs may also serve as peripheral biomarkers of epilepsy. We investigated the miRNA profile in the blood serum of patients suffering from mesial temporal lobe epilepsy (mTLE) following a single focal seizure evolving to a bilateral convulsive seizure (BCS) during video-EEG monitoring. Data of 15 patients were included in the final analysis. MiRNA expression was determined using Real Time-PCR followed by thorough bioinformatical analysis of expression levels. We found that more than 200 miRNAs were differentially expressed in the serum of patients within 30 min after a single seizure. Validation of the 20 top miRNA candidates confirmed that 4 miRNAs (miR-143, miR-145, miR-532, miR-365a) were significantly deregulated. Interestingly, in a sub-group of patients with seizures occurring during sleep, we found 10 miRNAs to be deregulated up to 20-28 h after the seizure. In this group of patients, miR-663b was significantly deregulated. We conclude that single seizures are associated with detectable transient miRNA alterations in blood serum in the early postictal phase. The significant upregulation of miR-663b following BCS arising during sleep indicates potential suitability of this miRNA as a potential biomarker for seizure diagnostics.

Elevated serum miR-106b and miR-146a in patients with focal and generalized epilepsy.

BACKGROUND: Epilepsy is a chronic neurological disorder characterized by recurring seizures. Although scalp electroencephalograms (EEG) and neuroimaging have been used in clinical diagnosis of epilepsy, the more economical, rapid and non-invasive biomarker is still desirable, contributing to the accurate clinical diagnosis and facilitating the appropriate treatment. METHODS: The expression of four epilepsy-associated miRNAs (miR-106b, miR-146a, miR-194-5p and miR-301a) was measured by quantitative RT-PCR in the serum of 90 epilepsy patients and control populations. RESULTS: It was found that the serum miR-106b, miR-146a and miR-301a were significantly increased but serum miR-194-5p was significantly decreased in epilepsy patients compared with healthy control populations. In addition, serum miR-106b (r=0.6412) and miR-146a (r=0.5896) were correlated with NHS3 score in epilepsy patients. Furthermore, the ROC result of serum miR-106b for prediction of epilepsy was 0.786, higher than those of serum miR-146a (AUC=0.774), miR-194 (AUC=0.686) or miR-310a (AUC=0.696). The combination of serum miR-106b and miR-146a gained a better sensitivity/specificity for prediction of epilepsy (AUC=0.887). CONCLUSION: Our preliminary findings indicate that upregulated serum miR-106b and miR-146a might be a potential biomarker for epilepsy evaluation.

GC-MS-Based metabolomics discovers a shared serum metabolic characteristic among three types of epileptic seizures.

OBJECTIVE: Understanding the overall and common metabolic changes of seizures can provide novel clues for their control and prevention. Here, we aim to investigate the global metabolic feature of serum for three types of seizures. METHODS: We recruited 27 patients who had experienced a seizure within 48h (including 11 who had a generalized seizure, nine who had a generalized seizure secondary to partial seizure and seven who had a partial seizure) and 23 healthy controls. We analyzed the global metabolic changes of serum after seizures using gas chromatography-mass spectrometry-based metabolomics. Based on differential metabolites, the metabolic pathways and their potential to diagnose seizures were analyzed, and metabolic differences among three types of seizures were compared. RESULTS: The metabolic profiles of serum were distinctive between the seizure group and the controls but were not different among the three types of seizures. Compared to the controls, patients with seizures had higher levels of lactate, butanoic acid, proline and glutamate and lower levels of palmitic acid, linoleic acid, elaidic acid, trans-13-octadecenoic acid, stearic acid, citrate, cysteine, glutamine, asparagine, and glyceraldehyde in the serum. Furthermore, these differential metabolites had common change trends among the three types of seizures. Related pathophysiological processes reflected by these metabolites are energy deficit, inflammation, nervous excitation and neurotoxicity. Importantly, transamination inhibition is suspected to occur in seizures. Lactate, glyceraldehyde and trans-13-octadecenoic acid in serum jointly enabled a precision of 92.9% for diagnosing seizures. CONCLUSIONS: There is a common metabolic feature in three types of seizures. Lactate, glyceraldehyde and trans-13-octadecenoic acid levels jointly enable high-precision seizure diagnosis.

Concentration of Il-1ß, Il-2, Il-6, TNFα in the blood serum in children with generalized epilepsy treated by valproate.

BACKGROUND: The aim of the study was the comparison of concentrations of IL-1ß, IL-2, IL-6 and TNFα before and after valproate (VPA) treatment in blood serum in patients with generalized seizures diagnosed and treated in the Department of Developmental Neurology, Poznan University of Medical Sciences from January 2006 to May 2007. METHODS: The analysis was conducted in a group of 21 patients with well controlled, generalized seizures (mean age 7.7±4.7 years) before and after 4-6 months of VPA therapy. Quantitative determination IL-1ß, IL-2, IL-6 and TNFα were performed with method of enzyme-linked immunosorbent assay (ELISA). The serum drug concentration was determined with the use of fluorescence-polarization-immunoassay system (FPIA). RESULTS: The concentration of IL-6 in blood serum of patients decreased significantly (p<0.001) after 4-6 months of VPA therapy, but concentration of IL-1ß (p=0.732), IL-2 (p=0.865), TNFα (p=0.079) did not change significantly. The serum concentration of VPA in all of patients was in therapeutic range (mean 77.53±19.71µg/ml). CONCLUSIONS: The serum level of pro-inflammatory IL-6 in patients with generalized epilepsy decreased in statistically significant way during VPA therapy, so the anti-inflammatory properties of VPA are also important for the effective control of seizure. Due to the incompatibility of reports on the influence of VPA on cytokine system in patients with generalized epilepsy, this problem needs more investigations, especially in the group of children.

Nonconvulsive seizures in subarachnoid hemorrhage link inflammation and outcome.

OBJECTIVE: Nonconvulsive seizures (NCSz) are frequent following acute brain injury and have been implicated as a cause of secondary brain injury, but mechanisms that cause NCSz are controversial. Proinflammatory states are common after many brain injuries, and inflammation-mediated changes in blood-brain barrier permeability have been experimentally linked to seizures. METHODS: In this prospective observational study of aneurysmal subarachnoid hemorrhage (SAH) patients, we explored the link between the inflammatory response following SAH and in-hospital NCSz studying clinical (systemic inflammatory response syndrome [SIRS]) and laboratory (tumor necrosis factor receptor 1 [TNF-R1], high-sensitivity C-reactive protein [hsCRP]) markers of inflammation. Logistic regression, Cox proportional hazards regression, and mediation analyses were performed to investigate temporal and causal relationships. RESULTS: Among 479 SAH patients, 53 (11%) had in-hospital NCSz. Patients with in-hospital NCSz had a more pronounced SIRS response (odds ratio [OR]=1.9 per point increase in SIRS, 95% confidence interval [CI]=1.3-2.9), inflammatory surges were more likely immediately preceding NCSz onset, and the negative impact of SIRS on functional outcome at 3 months was mediated in part through in-hospital NCSz. In a subset with inflammatory serum biomarkers, we confirmed these findings linking higher serum TNF-R1 and hsCRP to in-hospital NCSz (OR=1.2 per 20-point hsCRP increase, 95% CI=1.1-1.4; OR=2.5 per 100-point TNF-R1 increase, 95% CI=2.1-2.9). The association of inflammatory biomarkers with poor outcome was mediated in part through NCSz. INTERPRETATION: In-hospital NCSz were independently associated with a proinflammatory state following SAH as reflected in clinical symptoms and serum biomarkers of inflammation. Our findings suggest that inflammation following SAH is associated with poor outcome and that this effect is at least in part mediated through in-hospital NCSz.

Low glycaemic index diet reduces seizure susceptibility in a syndrome-specific mouse model of generalized epilepsy.

PURPOSE: Clinical evidence suggests that low glycaemic index diets are effective at reducing seizure frequency potentially through the stabilization of blood glucose levels. Here we investigate if diets containing carbohydrates with varying glycaemic index (GI) can modulate seizure susceptibility in a mouse model of generalized epilepsy. METHODS: Electrocortical recordings were made from mice harboring the GABAAγ2 (R43Q) epilepsy mutation after three weeks on a low-or high-GI diet. Standard rodent diet was used as a control. Occurrence and durations of spike-wave-discharges (SWDs) were measured. An insulin injection was used to reduce blood glucose to levels known to precipitate SWDs in the GABAAγ2 (R43Q) mouse on the low and high-GI diets. KEY FINDINGS: SWD occurrence was reduced by approximately 35% in mice on the low-GI compared to high-GI diet. SWD occurrence was not different between high-GI diet and a standard diet suggesting that low-GI diet is protective. Weight gain of mice for all diet groups was identical suggesting that they were equally well tolerated. Under low blood glucose conditions SWD occurrence increased in the low and high-GI diets. Importantly, under low glucose conditions the low-GI diet no longer conferred protection against SWDs. SIGNIFICANCE: SWDs were reduced in mice on a low GI-diet suggesting it may be an effective and well tolerated therapy for generalized epilepsy. The lack of effect of low-GI diet when glucose levels are reduced suggests that seizure protection in the GABAAγ2 (R43Q) mouse model may be due to the diets ability to stabilize blood glucose levels.

Low-dose sodium valproate in the treatment of idiopathic generalized epilepsies.

OBJECTIVE: Most patients with idiopathic generalized epilepsies (IGEs) have good seizure control when on antiepileptic drugs. To analyze prospectively the response to low-dose sodium valproate (VPA) treatment (<1000 mg/day) together with plasma VPA levels in a cohort of patients with IGE. METHODS: Patients with IGE were selected and followed for almost 2 years. In patients on VPA with no seizures in the last year, VPA dose was lowered to <1000 mg/day. Newly diagnosed patients with IGE started treatment on VPA directly on this low dose. RESULTS: Fifty-four patients were included, with juvenile myoclonic epilepsy (JME) in 23 (42.6%), juvenile absence epilepsy (JAE) in 17 (31.5%), and generalized tonic-clonic seizures only (GTCS only) in 14 (25.9%). VPA at low dose was administered to 38 (70%) patients. Mean plasma VPA level was 44.21 mg/l (18-78; SD 15.18). Seizure relapse during the 2-year follow-up was observed in 8 (21%). A reduction in adverse events was observed (P < 0.048). The only factor related to efficacy of VPA at low dose was syndromic diagnosis. Low-dose VPA controlled 92.9% (13) of patients with GTCS only, 78.3% (18) of those with JME, and 29.5% (5) of those with JAE. CONCLUSIONS: Low-dose VPA was a highly effective treatment for the majority of those with JME and GTCS only. The seizures in JAE tended to be more resistant to treatment, usually requiring higher doses of VPA or polytherapy.

Blood levels of cytokines in children with idiopathic partial and generalized epilepsy.

PURPOSE: Antiepileptic drugs have been reported to reduce the levels of serum immunoglobulins and affect the production and levels of certain cytokines. We investigated the effects of valproic acid (VPA) and topiramate (TPM) on the blood levels of interleukin (IL)-1α, IL-1ß, IL-6, IL-10, and TNF-α in children with idiopathic generalized and partial epilepsy. METHODS: Forty prepubertal children aged 6-12 (mean 8.3±1.7) years, 19/40 (47.5%) female and 21/40 (52.5%) male, with idiopathic generalized or partial epilepsy diagnosed in the child neurology outpatient clinic were included. The patients were divided into two treatment groups: 20 were treated with VPA and 20 with TPM. The plasma levels of IL-1α, IL-1ß, IL-6, IL-10, TNF-α were measured using ELISA method before the initiation of treatment and at the 6th and 12th months of the treatment. The Chi-square test was used to compare qualitative data. To compare the periods, recurrence measurements were done using variance analysis and Freidman 2-sided variance analysis. p<0.05 was considered as statistically significant. RESULTS: In the VPA group, the levels of IL-1α significantly increased at 12 months while the levels of IL-10 decreased at 6 months of treatment compared to values before treatment (p<0.05). There was no significant difference in levels of IL-1ß, IL-6, TNF-α (p>0.05). In the TPM group, lower levels of IL-10 were observed at 6th and 12th months compared to the onset of treatment (p<0.05). CONCLUSION: The results of this study demonstrated that VPA and TPM might lead to changes in the levels of cytokines in epileptic patients. The next step would be to investigate the relation of these findings to the outcome of epilepsy and response to treatment.

Patients with generalised epilepsy have a higher white blood cell count than patients with focal epilepsy.

BACKGROUND: Immunological alterations have been noted following seizures in the acute period, however little is known about the effect of type and severity of epilepsy on leukocyte count in the absence of seizures. METHODS: We performed a retrospective chart review of adult epilepsy patients presenting for evaluation over a four-month period. Demographics, epilepsy type and characteristics, number and type of antiepileptic drugs, as well as medical co-morbidities were noted. RESULTS: A total of 241 patients fulfilled study criteria. Variables correlating with leukocyte count were identified using univariate analysis. Based on multivariate analysis, only the correlation with type of epilepsy and use of more than two antiepileptic drugs remained statistically significant. Patients with generalised epilepsy had a higher leukocyte count (7.21 k/µL) compared to those with focal epilepsy (6.53 k/µL); the main difference was due to the number of monocytes. CONCLUSION: These findings raise the possibility that there are different neuro-immune profiles between patients with generalised and focal epilepsy.

[Association of type 1 diabetes mellitus and epilepsy in children. A cohort of 10 cases]. / Association diabète de type 1et épilepsie chez l'enfant. À propos d'une série de 10 cas.

UNLABELLED: The association of type 1 diabetes mellitus (DM) and epilepsy has been previously reported. However, the physiopathology of this association remains misunderstood. OBJECTIVE: To describe epilepsy combined with type 1 DM in children. METHODS: Retrospective monocentric study of all the epileptic and type 1 diabetic children consulting at the Timone University Hospital, Marseille, France. For each patient, the type of epilepsy and its electroclinical and radiographic characteristics were studied as well as the type of diabetes (biological characteristics, glycemic control), and the onset of these 2 diseases. RESULTS: Ten patients are reported. Five suffered from generalized epilepsy (4 idiopathic, 1 nonidiopathic) and 5 from focal epilepsy (4 non-idiopathic, 1 idiopathic). For most of these cases, presence of GAD (glutamic acid decarboxylase) autoantibodies were confirmed and epilepsy followed diabetes. CONCLUSIONS: The 2 most common types of epilepsy in this association are idiopathic generalized epilepsy and non-idiopathic temporal epilepsy. Several mechanisms could be involved (immune, glycemia, and genetic disorders).

Thyroid hormone levels in children receiving carbamazepine or valproate.

Antiepileptic therapy is associated with alteration of thyroid hormone levels. We evaluated the effect of valproate and carbamazepine therapy on the thyroid hormone profile of epileptic children. Subjects included children aged 2-12 years receiving therapy for at least 6 months. Free triiodothyronine, free thyroxine, and thyroid-stimulating hormone were measured by electrochemiluminescent assay in 30 children receiving carbamazepine, 34 children receiving valproate, and 30 age- and sex-matched control subjects. Groups were similar for age, body mass index, and duration of therapy. Thyroid-stimulating hormone (mean ± S.D.) was 2.67 ± 1.66, 4.53 ± 1.9, and 3.61 ± 1.75 µ IU/mL in the control, valproate, and carbamazepine group, respectively (P < 0.001). Free thyroxine was 1.39 ± 0.19, 1.40 ± 0.63, 1.11 ± 0.19 ng/dL (P = 0.009). Free triiodothyronine was 4.03 ± 0.74, 4.14 ± 0.94, 3.92 ± 0.68 pg/mL (P = 0.54). When groups were compared 2 at a time, there was no difference in free triiodothyronine (P > 0.05). Free thyroxine levels in the carbamazepine group were significantly different from valproate (P = 0.015) and control (P = 0.027). Thyroid-stimulating hormone increased with both valproate and carbamazepine compared to control but was significant with valproate (P < 0.001). We conclude that carbamazepine and valproate therapy alters thyroid functions by decreasing free thyroxine levels. Compensation by increase in thyroid-stimulating hormone is better with valproate. The need for monitoring and supplementation should be assessed further.

No effects of the gonadal hormones on photoparoxysmal EEG responses in idiopathic generalised epilepsy.

PURPOSE: It is accepted that the estradiol hormone is proconvulsant and progesterone is anti-convulsant. In this study the effects of gonadal hormones on photoparoxysmal responses on EEG in idiopathic generalised epilepsy were researched. METHOD: Twenty-two women with photosensitive idiopathic generalised epilepsy having regular menstrual cycles were recruited into the study. Patients presenting photoparoxysmal responses were selected from routine EEG recordings. Blood samples were taken on day 14 (E) and 25 (P) of the menstrual cycle to confirm E and P peaks. An EEG recording was performed for each patient on E and P days. RESULT: No statistically significant differences were monitored with respect to frequency, duration of the photoparoxysmal responses on E and P peaks days (p>0.05). COMMENT: In this study no correlation could be demonstrated among menstrual cycle and photoparoxysmal responses.