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.

The discriminative value of blood gas analysis parameters in the differential diagnosis of transient disorders of consciousness.

AIM: The differentiation between epileptic and non-epileptic episodes can be challenging. Our aim was to compare lactate, anion gap (AG), bicarbonate and the Denver Seizure Score (DSS) as point-of-care test (POCT) markers for episodes of transient alterations of consciousness. METHODS: The blood serum parameters were drawn at arrival in the emergency department (ED) within 2 h of the episode. After calculating AG and DSS values, the four parameters were compared retrospectively between patients with generalized tonic-clonic seizures (GTCS) (n = 165) and patients with other disorders of consciousness [syncopes (n = 43), and psychogenic non-epileptic seizures (n = 15)]. Additionally, we compared all values among men and women. RESULTS: In GTCS patients, all four parameters differed significantly compared to non-epileptic episode patients (p < 0.001). Serum lactate showed significant additional benefit over the remaining values, with an AUC of 0.947 (95% CI 0.92-0.975) and a high sensitivity and specificity for an optimal cut-off value of 2.45 mmol/l. For DSS, the AUC was 0.857 (95% CI 0.808-0.906; cut-off: 0.35), and for AG 0.836 (95% CI 0.783-0.889; cut-off: 12.45 mmol/l). In the case of serum bicarbonate, the AUC was 0.831 (95% CI 0.775-0.886; cut-off: 22.75 mmol/l). In the sex-dependent comparison, the results were similar. Men showed more significant differences in the compared values than women. CONCLUSIONS: Serum lactate is best suited as POCT marker in the differential diagnosis of epileptic and non-epileptic episodes and is superior to AG, DSS and bicarbonate. The differences among sexes may pose a challenge in their implementation and interpretation.

Epilepsy under my skin?

A 44-year-old male patient was admitted to the hospital for observation after an unwitnessed syncope. Physical examination revealed skin purpura and bilateral tongue haematoma. Laboratory studies were unremarkable. Radiological imaging showed no abnormalities of the vasculature, signs of thrombosis or brain anomalies. Biopsy of a purpuric lesion revealed extravasation of erythrocytes. After excluding several causes of both syncope and purpura, the typical location of these thoracocervicofacial purpura, the tongue haematoma and an elevated prolactin level (which came back later) led to the diagnosis of an epileptic seizure. The patient was referred to the neurology department for follow-up. Within 3 weeks, the purpura were completely resolved, and the patient remained free of seizures during follow-up. In case of an unwitnessed syncope, an epileptic seizure should be carefully considered and thoracocervicofacial purpura can be the pivotal manifestation leading to this diagnosis.

Can ischemia-modified albumin be used to differentiate between generalized seizures and pseudoseizures?

BACKGROUND/AIM: In recent years ischemia-modified albumin (IMA) has been suggested as a marker that can be used in differentiating nonconvulsive conditions from epilepsy. The purpose of this study was to investigate changes in IMA levels caused by generalized clonic tonic (GTC) seizures. MATERIALS AND METHODS: A total of 114 children presenting to the Karadeniz Technical Pediatric Emergency Polyclinic with GTC seizures were included in the study. Sixteen cases meeting the inclusion criteria were included in the study and sixteen healthy children were enrolled as the control group. The patients' IMA, albumin, and IMA/albumin values at hours 0 and 1 following the episode were compared with control group values. RESULTS: IMA levels in the patient group were significantly higher at hour 1 compared to hour 0, and were also significantly higher than those of the control group levels at hour 1. In addition, the patient group IMA/albumin index value at hour 1 was significantly higher than the baseline value. IMA levels increased significantly with length of seizure. CONCLUSION: Although there were no markers of hypoxia in patients undergoing GTC seizures in this study, hypoxia was observed to develop, and this caused serum IMA levels to rise in line with seizure duration.

Serum metalloproteinase 9 levels increase after generalized tonic-clonic seizures.

Metalloproteinase 9 (MMP9) is a member of a family of enzymes that mediate the degradation of extracellular matrix proteins, and is especially involved in blood-brain barrier maintenance. Increased levels of MMP9 have been observed in many neurological disorders, including epilepsy, suggesting it may be involved in the pathogenesis of seizures. We investigated changes in MMP9 serum levels after acute seizures in epilepsy patients. Concentrations of MMP9 in serum were measured by ELISA in 43 patients 1-3, 24, and 72h after generalized tonic-clonic seizure and once in participants of the control group. MMP9 levels were significantly increased 1-3 and 24h after seizure and decreased to control levels 72h after seizure. Our results suggest that MMP9 is released after or just before seizure; however, further studies are needed to resolve the consequences of the observed MMP9 increase.

CSF and plasma adipokines after tonic-clonic seizures.

PURPOSE: Adipokines, especially leptin and adiponectin, have gained increasing importance in pathophysiology of various neurological diseases including epilepsy. There are experimental data suggesting a role for leptin in the genesis of seizures and neuroprotection related to seizures. However there are no clinical studies on the effects of epileptic seizures on adipokines. METHODS: We measured cerebrospinal fluid (CSF) and plasma levels of leptin, adiponectin and adipsin after provoked or unprovoked primary or secondarily generalized tonic-clonic seizures in 13 female patients and seven controls. The samples were taken within 24h after the seizure onset. RESULTS: Leptin plasma levels correlated negatively with the time to sample withdrawal, i.e. the longer the time interval between the seizure and the sample the lower the leptin levels in the patients. Interestingly, plasma adiponectin levels were significantly increased after the seizure episode. CONCLUSION: This study provides further evidence that there are seizure-induced acute changes in adipokine metabolism. Leptin concentrations seem to decrease during the first 24h after the seizure whereas adiponectin levels increase. The meaning of this response is far from clear, but it might be an endogenous attempt to prevent harmful effects of epileptic seizures in the central nervous system.

Assessment of the levels of serum Hsp 70 and ghrelin in children with simple febrile convulsions.

BACKGROUND: In this study we aimed to evaluate the serum levels of Heat-shock protein (Hsp) 70 and acylated and desacylated ghrelin in patients suffering from a simple febrile convulsion. METHODS: This cross-sectional study included patients who were diagnosed with a simple febrile convulsion, afebrile tonic-clonic epileptic seizure and upper respiratory tract infection when admitted to our hospital. All patients were aged between six months and 60 months. Patients enrolled in this study were divided into five groups. Group I: patients with a simple febrile convulsion and body temperature of 38º C to 39° C; group II: patients with a simple febrile convulsion and body temperature of 39.1° C to 41° C; group III: patients with primary generalised tonic-clonic seizure and normal body temperature; group IV: patients with upper respiratory infection without convulsion and a body temperature of 38° C to 39° C; and group V: patients with upper respiratory infection without convulsion and a body temperature of 39.1° C to 41° C. The control group included healthy children who were followed up in the healthy children polyclinic. Serum levels of Hsp70 and acylated and des-acylated ghrelin were studied from the blood samples collected from the patients and control group. RESULTS: Serum levels of Hsp70 were higher in the febrile convulsion (groups I, II) and epileptic convulsion and infection (groups IV, V) groups than in the controls (P<0.0001). Moreover, serum levels of acylated and desacylated ghrelin were higher in the simple febrile convulsion (groups I and II) and epileptic convulsion and infection (groups IV and V) groups than in the control (P<0.05). CONCLUSIONS: We demonstrated that serum levels of Hsp70 and acylated and desacylated ghrelin increased in patients with a simple febrile convulsion.

"Herbal seizures"--atypical symptoms after ibogaine intoxication: a case report.

INTRODUCTION: Misuse of various new psychotropic substances such as ibogaine is increasing rapidly. Knowledge of their negative side effects is sparse. CASE PRESENTATION: We present a case of intoxication with the herbal substance ibogaine in a 22-year-old white man. After taking a cumulative dose of 38 g (taken in two doses), he developed visual memories, nausea and vomiting. He developed a generalized tonic-clonic seizure with additional grand mal seizures. He was treated with midazolam and levetiracetam. Extended drug screenings and computed tomography and magnetic resonance imaging findings were all negative. CONCLUSIONS: Knowledge of the side effects of ibogaine has mainly come from reports of cardiovascular complications; seizures are rarely mentioned and experimental findings are inconsistent. It seems that ibogaine acts like a proconvulsive drug at high doses.

N-Acetylcysteine (NAC)-Induced Hyponatremia Caused by an Electronic Medical Record (EMR) Order Error.

INTRODUCTION: Intravenous N-acetylcysteine (NAC) causes few adverse drug events, with mild anaphylactoid reactions being the most common. Hyponatremia as a complication of hypoosmolar NAC solution has been reported. We describe how a locally constructed electronic medical record (EMR) order set for IV NAC resulted in a seizure from hyponatremia due to excess free water administration. CASE REPORT: A 13-month-old female with no past medical history presented to a hospital after ingesting an unknown number of acetaminophen 500 mg tablets. The 4-h acetaminophen concentration was 343 mcg/mL, and she was started on IV NAC. 8.2 h into her 21-h IV NAC protocol, she developed a tonic-clonic seizure. Repeat serum sodium was 124 mEq/L, a decrease from 142 mEq/L at the time of admission. She was treated with hypertonic saline, lorazepam, and levetiracetam and had no further seizures. A brain MRI and EEG were both normal. After the seizure was stabilized, the providers noticed that the patient had receive a total of 900 mL of D5W (112.5 mL/kg) in the first 9 h of hospitalization. This was caused by a poorly constructed, restrictive, EMR order set that did not allow customization of the IV NAC preparation. DISCUSSION: Because the 21-h IV NAC administration involves preparation of 3 different doses infused over 3 different time intervals, an order set was developed to reduce ordering errors. However, error in its construction caused the pharmacist to prepare a solution containing too much free water, decreasing patient's intravascular sodium and resulting in a seizure. CONCLUSION: The purposes of our case report were to highlight the dangers of overreliance on EMR order sets and to recognize hyponatremic seizures as an adverse reaction of an inappropriately prepared IV NAC.

Increased cerebral oxygenation precedes generalized tonic clonic seizures.

Based on previous fMRI and SPECT studies, it has been suggested seizures may be preceded by increased cerebral blood flow. Recently, we demonstrated transcutaneous regional cerebral oxygen saturation (rSO2) sensors are feasible for use in patients undergoing video EEG monitoring. We reanalyzed our data to determine if seizures were consistently marked by increased cerebral oxygenation. Patients with histories of generalized tonic clonic seizures (GTCS) were recruited into our study. All subjects were evaluated with continuous 30-channel scalp EEG and 2 rSO2 sensors placed on each side of the forehead. We calculated the mean rSO2 value for the 1h epochs in the non-ictal (2h prior to seizure onset) and pre-ictal (1h prior to onset) periods. Seven primary/secondarily GTCS from 5 patients were captured. The mean rSO2 value in the non-ictal period was 75.6 ± 5.7%. This increased to 76.0 ± 6% in the pre-ictal period (p=0.032). Four of the 7GTCS (57.1%) were marked by ≥ 3 sequential rSO2 values in the pre-ictal period that were ≥ 3 SDs greater than the mean non-ictal rSO2 value. Three GTCS (42.9%) were marked by sustained cerebral hyperemia for ≥ 15 consecutive readings. Our results suggest increased cerebral blood flow could be non-invasively used to predict seizure occurrence.

Serum phenytoin concentrations in paediatric patients following intravenous loading.

Phenytoin is used to treat acute tonic-clonic seizures in children who have not responded to a benzodiazepine. In the UK, the loading dose of phenytoin is 18 mg/kg. There is limited evidence on whether this loading dose will achieve the desired levels in paediatric patients. Intravenous loading doses of phenytoin were retrospectively and prospectively audited over 19 months. Doses were normalised for weight and compared with the serum phenytoin concentrations. Errors in dose calculations and adverse events were recorded. Serum phenytoin concentrations were measured on 31 occasions in 27 children (24 retrospective and 10 prospective) between 60 and 180 (median, 153) min after completion of the loading dose. Serum phenytoin concentrations were within the therapeutic range (10-20 µg/ml) on 24 occasions. No errors in dose calculations or adverse effects were identified. A phenytoin loading dose of 18 mg/kg gave serum concentrations within the recommended therapeutic range in most children.

[Serotoninergic mediator system in the pathogenesis and treatment of idiopathic generalized epilepsy].

Psychoemotional status and blood serotonin level were investigated in 69 patients with different forms of idiopathic epilepsy during the seizures and interictal period. Twenty-two patients with juvenile myoclonic epilepsy, 22 patients with absence forms and 22 patients with generalized convulsive seizures, aged 10-47 years, were included in the study. We found the significant decrease in blood serotonin levels during the interictal period, with the lower levels seen after generalized convulsive and myoclonic seizures. After the treatment with antidepressant fluvoxamine as add-on treatment, 16 patients revealed improved psychoemotional well-being and quality of life as well as a decreased number of generalized convulsive seizures along with the increasing of blood serotonin level.

Mean daily plasma concentrations of beta-endorphin, leu-enkephalin, ACTH, cortisol, and DHEAS in epileptic patients with complex partial seizures evolving to generalized tonic-clonic seizures.

INTRODUCTION: A multitude of mechanisms have been implicated in the pathophysiology of epilepsy. OBJECTIVE: To assess mean daily plasma concentrations of ACTH, cortisol, DHEAS, leu-enkephalin, and beta-endorphin in epileptic patients with complex partial seizures evolving to tonic-clonic in relation to frequency of seizure occurrence (groups with seizure occurrences - several per week and several per year) and duration of the disease (groups less than and more than 10 years). We decided to analyse mean daily values of beta-endorphin and leu-enkephalin because of significant differences in concentrations of these substances in blood during the day. MATERIAL AND METHODS: The study was performed on 17 patients (14 males + 3 females; mean age 31.8 yrs) treated with carbamazepine (300-1800 mg/day). The control group consisted of six age-matched healthy volunteers. Blood was collected at 8 a.m., 2 p.m., 8 p.m., and 2 a.m. Intergroup analysis was performed with the use of ANOVA Kruskal-Wallis test. RESULTS: Mean daily concentrations of ACTH and cortisol in the blood of the patients with epilepsy were higher in comparison with those of the healthy volunteers, independently of the frequency of seizures and duration of the disease. Mean daily concentrations of beta-endorphin in the blood of the patients with epilepsy were higher in the groups of patients with more severe clinical course of disease (with more frequently occurring epilepsy seizures and longer duration of the disease) in comparison with healthy subjects. Mean daily concentrations of leu-enkephalin in the blood of the patients with epilepsy were higher in the group of patients with short duration of the disease in comparison with the group with long duration of the disease. CONCLUSIONS: 1. Pituitary-adrenal axis hyperactivity is observed in patients with clinically active epilepsy, independently of the frequency of seizures and duration of the disease. 2. Changes in endogenous opioid system activity are related to the clinical activity of epilepsy - beta-endorphin concentrations are connected with frequency of seizures and duration of the disease and leu-enkephalin concentrations with duration of the disease. 3. Endogenous opioid peptides might take part in the neurochemical mechanism of human epilepsy. (Pol J Endocrinol 2010; 61 (1): 103-110).

Serum concentration/dose ratio of topiramate during pregnancy.

PURPOSE: To study the impact of pregnancy on the serum concentration/dose ratio (C/D-ratio) of topiramate (TPM). METHODS: Twelve women with epilepsy using TPM during pregnancy, and 15 pregnancies were studied. The main target variable was the C/D-ratio at baseline and during pregnancy. Additional variables were changes in TPM dose, concomitant use of other antiepileptic drugs, seizure frequency, and pregnancy outcome. Clinical and pharmacological data were obtained from the women's medical records. RESULTS: The average C/D-ratios in the second and third trimester were 30% (p = 0.002, n = 11) and 34% (p = 0.001, n = 8) lower than the baseline values, respectively. The interindividual variability was pronounced. Increased seizure frequency was common in pregnant women using TPM, but a correlation to the decline in TPM C/D-ratio could not be established from our data. DISCUSSION: Dose-corrected serum concentrations of TPM appear to decline gradually throughout pregnancy. The underlying mechanisms are not known. Increased glomerular filtration may play a major role. During pregnancy, therapeutic drug monitoring of TPM may be useful.