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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.

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.

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., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

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.

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., (Copyright © 2016. Published by Elsevier B.V.)

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., (Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

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.

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.

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.

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., (Copyright © 2014 Elsevier B.V. All rights reserved.)

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.

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.

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).

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.

Introduction: The mechanism by which blood transfusion increases blood pressure in a substantial proportion of patients with congenital hemolytic anemia is unknown. Vascular endothelium dysfunction and increased endogenous vasoactive substances have been postulated in the pathogenesis of hypertension following multiple blood transfusions. The present study was undertaken to test the hypothesis whether increased circulating vasoconstrictors following blood transfusions, if documented, is a potent modulator of hypertension in patients with congenital anemia., Materials and Methods: Four children with congenital hemolytic anemia developed severe hypertension and convulsions 2 to 4 days after they received multiple blood transfusions. None had a history of prior hypertension, kidney disease or seizures before the blood transfusion. Baseline blood and urine samples were obtained for routine renal function studies. Blood samples were also drawn during and 2 weeks after the clinical events for determination of epinephrine, norepinephrine, dopamine, and plasma renin activity., Results: Kidney function was normal in all the 4 patients. All had elevated plasma renin activity and increased blood epinephrine, norepinephrine, and dopamine concentrations during hypertensive crises. Hypertension responded to antihypertensive drugs with the patients remaining normotensive 3 to 6 days after commencing therapy. All recovered without further seizures. The elevated plasma renin activity, epinephrine, norepinephrine, and dopamine levels returned to reference levels 2 weeks after completion of the last blood transfusion., Conclusions: These data suggest that increased activity of vasoconstrictors in the recipient plasma may be responsible for the development of hypertension after multiple blood transfusions.

We report the case of a 54-year-old woman who was admitted for benzodiazepine withdrawal. After 6 weeks of carbamazepine treatment (600, then 200 mg) the patient suddenly suffered from a grand mal seizure. Laboratory findings revealed a clinical significant hyponatremia of Na 125 mmol/l (baseline: 143 mmol/l). CCT and ECG were normal. To our knowledge, this is the first description of a seizure related to hyponatremia in an adult carbamazepine-treated patient.

Low doses of ethanol may antagonize the pharmacological effects of nicotine. Recently, it has been shown that the effects of ethanol on nicotine discrimination are not correlated with blood ethanol levels. The aim of the present study was to evaluate whether ethanol (0.5-2g/kg, i.p.) could block nicotine-induced seizures in C57BL/6J mice and to correlate ethanol's actions with blood ethanol concentrations. For comparison, the effects of a gamma-aminobutyric acid A (GABAA)/benzodiazepine receptor positive modulator, midazolam (0.25-40 mg/kg, i.p.), and a gamma-aminobutyric acid B receptor agonist, baclofen (2.5-20 mg/kg, i.p.), were assessed in the same procedure. Nicotine (3-9 mg/kg, s.c.) induced clonic-tonic seizures in a dose-dependent manner. Ethanol, administered 5 or 50 min before nicotine, dose dependently antagonized seizures elicited by 6 mg/kg nicotine. The anticonvulsant effects of ethanol correlated with blood ethanol levels and were comparable to those exerted by midazolam. Baclofen antagonized only the tonic component of nicotine-induced convulsions. The anticonvulsant doses of ethanol (0.5-2 g/kg), midazolam (0.5-1 mg/kg), and baclofen (5-10 mg/kg) did not affect spontaneous locomotor activity in a control experiment. The present results indicate that (i) ethanol may block nicotine-induced seizures in mice at doses that do not alter locomotor activity and (ii) the anti-seizure effects of ethanol depend on blood ethanol levels and are comparable to those exerted by the GABAA positive modulator midazolam.

Background: In view of considerable differences of opinion regarding the reproductive steroid hormonal pathogenesis in catamenial epilepsy, hormonal analysis of estrogen and progesterone in catamenial epileptics for a precise correlation is of significant importance., Methods: Clinical, neurological and physiological assessments, and radioimmunoassay of plasma estradiol-17beta and progesterone a day prior to the onset of menstruation were carried out in noncatamenial and mild catamenial epileptics having multiple frequency tonic-clonic (primary and secondary generalized) seizures., Results: Highly significant rise (p > 0.0001) of estradiol-17beta was obtained for catamenial epileptics compared to normal subjects as well as noncatamenial epileptics (p > 0.02). However, nonsignificant fluctuations of progesterone were found for both catamenial and noncatamenial epileptics against normal subjects as well as catamenial versus noncatamenial epileptics., Conclusions: The present report suggests that estradiol have a precise role in the mild premenstrual exacerbation of seizures. However, no significant change in progesterone levels might have been due to mild exacerbation of seizures in these patients. Furthermore, we suggest the importance of how we collect and categorize the data and which pathophysiologic process/ clinicobiological mechanism is involved in patients with catamenial epilepsy. Contradictory results in literature may be related to differential levels of excitation/inhibition equilibrium during various cycle phases. More precise studies including the determination of the blood levels of antiepileptic drugs, however, are required.

Objective: To report a case of carbamazepine-induced acute hyponatremia resulting in seizures., Case Summary: A 44-year-old white woman developed acute hyponatremia and 2 subsequent tonic-clonic seizures after ingesting twice her evening dose of carbamazepine (usual evening dose 600 mg). On admission, her serum sodium level was 122 mEq/L. An infusion of NaCl 0.9% was begun and, within 24 hours, the serum sodium level had returned to her previous level of 136 mEq/L. The woman's preadmission carbamazepine concentration was 8.6 microg/mL, and it was 11.3 micorg/mL on admission. Carbamazepine was withheld and, the following day, the concentration was 5.6 microg/mL. The woman had experienced a similar event 6 months earlier when she also took a large dose of carbamazepine., Discussion: We attributed the acute hyponatremia and seizures to the large increase in dose of carbamazepine in the presence of other risk factors for hyponatremia. Hyponatremia associated with carbamazepine has been well described. The incidence ranges from 1.8% to 40% depending on the patient population studied. Severe hyponatremia in patients treated with monotherapy is uncommon. Several risk factors have been reported to increase the risk of hyponatremia including age >40 years, concomitant use of medications associated with hyponatremia, menstruation, psychiatric condition, surgery, psychogenic polydipsia, and female gender. Treatment is focused on removal of the precipitating factors or discontinuation of carbamazepine therapy. Use of the Naranjo probability scale indicated a highly probable relationship between acute hyponatremia and carbamazepine in our patient., Conclusions: Hyponatremia with carbamazepine is well known. The factors associated with increased risk are less understood. An increased awareness of these risks, careful monitoring, and patient education are important in the prevention of neurologic complications.

The World Health Organization recognizes biochemical markers of myocardial injury as one of the three criteria for the diagnosis of acute myocardial infarction. We report the first case of elevated troponin I in a patient after a grand mal seizure in the hospital, with no evidence of myocardial infarction and no rhabdomyolysis. Cardiac catheterization and two-dimensional echocardiographic findings were normal. Four months later, the patient was readmitted, again having experienced a grand mal seizure. She was asymptomatic for cardiac disease in both instances. There was a temporal correlation between troponin I levels and seizures. Studies have shown that a troponin level above 3.5 ng/mL implies significant myocardial injury. Our patient had troponin I values as high as 5.5 ng/mL and 6.3 ng/mL. This case implies that troponin I can be significantly increased after a grand mal seizure, and with low clinical suspicion for myocardial injury this abnormality should be disregarded.

We describe the case of an 84-year-old woman who developed a confusional state and suffered from a generalized tonic-clonic seizure while she was treated with imipenem, a beta-lactam antibiotic. Focal and generalized epileptiform discharges and a photoparoxysmal response were prominent with transient changes on the EEG.

Objectives: To perform MRI cerebellum volumetry in patients exposed to phenytoin and to identify factors associated with cerebellar atrophy (CA)., Methods: From 100 consecutive epilepsy patients we selected those with phenytoin use for more than 2 months and with MRI scan available for volumetric studies. We obtained cerebellar volumes corrected for total intracranial volume. Volumes below 2 standard deviations from the mean of control group were considered abnormal., Results: We studied 56 patients (33 women). Mean age was 33.6 years and mean duration of epilepsy was 17.6 years. Mean daily dose of phenytoin was 301 mg. CA was detected in 20 (35.7%) patients. CA was not associated with frequent generalised seizures. CA correlated with duration of epilepsy (r=-0.34; P=0.01) and years of treatment with phenytoin (r=-0.48; P=0.001), but not with age and mean daily dosage of phenytoin (P>0.05). However, a multiple correlation analysis as well as a backward stepwise multiple regression analysis including all variables showed that only duration of treatment was significantly associated with CA (P=0.001)., Conclusions: CA is frequently associated with long-term use of phenytoin. Although duration of epilepsy may have an influence in the CA, this is clearly less important than the time of exposure to phenytoin.

The purpose of this study was to investigate the clinical safety of sodium valproate and total and unbound valproic acid plasma concentrations after rapid infusion in hospitalized, acutely ill children. Four children (5-15 years) completed the study. Sodium valproate doses (8.3-15.4 mg/kg) were administered in

Purpose: S-100 protein is a sensitive marker of various brain diseases; however, its role in epilepsy is controversially discussed in the literature. We therefore studied the temporal profile of serial concentrations of S-100 protein in serum after secondarily generalized tonic-clonic seizures during video-EEG monitoring., Methods: Ten patients with mesial temporal lobe epilepsy were prospectively studied. Serum S-100 protein was measured after a seizure-free period of > or =24 h (baseline) and 30 min, 3, 6, 12, and 24 h after a secondarily generalized tonic-clonic seizure of temporal lobe origin in nine and a convulsive status epilepticus in one patient., Results: All S-100 levels were within the normal range, except for those of one patient at baseline. Mean values were 0.045 microg/L (range, 0.003-0.13 microg/L) at baseline, 0.038 microg/L (range, 0.003-0.09 microg/L) at 30 min, 0.036 microg/L (range, 0.003-0.08 microg/L) at 3 h, 0.034 microg/L (range, 0.003-0.07 microg/L) at 6 h, 0.034 microg/L (range, 0.003-0.08 microg/L) at 12 h, and 0.035 microg/L (range, 0.003-0.09 microg/L) at 24 h after seizure offset. There were no significant differences between mean concentrations at any interval postictally., Conclusions: We could not detect any significant alterations in serum S-100 protein concentration either after a single secondarily generalized tonic-clonic seizure or after convulsive status epilepticus in patients with temporal lobe epilepsy. Our data do not confirm previous work, which suggested serum S-100 protein to be a suitable marker for epileptic seizures.

Zheng Tai Instant Powder [symbol: see text] is a complex prescription of traditional Chinese medicine indicated for grand mal epilepsy. Its effect on central nervous system, energy metabolism, neurotransmitters and hemorheology were studied in animal models. The results demonstrated that the effect of Zheng Tai Instant Powder is mild, long-lasting and effective in treatment and prevention of epilepsy without any side effects.

Normeperidine, a major metabolite of meperidine, is half as potent as meperidine as an analgesic but two to three times more potent as a convulsant. Renal failure significantly increases the plasma half-life of normeperidine. The intensity of the central nervous system excitation is highly correlated with the plasma concentration of normeperidine. Moreover, normeperidine toxicity is not reversed by naloxone, which may exacerbate it. We report a patient with end-stage renal disease undergoing maintenance continuous cycler peritoneal dialysis who had been receiving meperidine for pain control. The patient subsequently developed myoclonic contractions and a grand mal seizure. The patient was successfully treated with hemodialysis (using an F8 dialyzer) for presumed normeperidine-induced seizure. During hemodialysis, normeperidine average blood clearance was 73 mL/min, average plasma clearance was 50 mL/min, and average percentage of plasma extraction was 24%. There also was a 26% reduction in plasma concentration of normeperidine over 3 hours of hemodialysis. In conclusion, our findings suggest that hemodialysis may be used effectively for treating patients with suspected normeperidine-induced neurotoxicity.

Orphenadrine is an anticholinergic drug used mainly in the treatment of Parkinson's disease. It has a peripheral and central effect and a known cardiotoxic effect when taken in large doses. We report the successful outcome of the treatment of a 2 1/2-year-old girl who accidentally ingested 400 mg of orphenadrine hydrochloride (Disipal). One hour after ingestion she presented neurological symptoms: confusion, ataxic walking, and periods of severe agitation. Generalized tonic-clonic seizures appeared resistant to the administration of multiple antiepileptics. They ceased after a supplementary dose of intravenous diazepam, endotracheal intubation, and mechanical ventilation. An episode of ventricular tachycardia responded well to i. v. lidocaine. Physostigmine was administered in three successive doses. The initial orphenadrine plasma level (3,55 microg/ml) was in the toxic range, associated with high mortality. The calculated elimination half-life was 10.2 h and the molecule and/or its metabolites were found up to 90 h after ingestion.

Serum neuron-specific enolase (s-NSE) and s-100 protein (s-100) are sensitive markers of various brain diseases. We investigated both of these markers in nine patients within 5 min, 6 h, 12 h, and 48 h after a single tonic-clonic seizure. The mean peak s-NSE level was significantly higher after 5 min (11.97 +/- 8.56 microg/l) and 48 h (10.31 +/- 8.92 microg/l, P < 0.05) than the levels of seizure-free, age-matched controls. Five patients had increased s-NSE levels regarding the upper limit of normal as mean + 3 SD. s-100 was not detected either in controls or epileptic patients. These data indicate that s-NSE in contrast to s-100 may be an in vivo marker after generalized seizures in some patients.

The Authors discuss the role of plasma prolactin concentration as a marker to discriminate epileptic and non epileptic seizures. In 40 children was determined prolactin during the first seizure (30 feverish and 10 non feverish seizures). The analysis of the results shows that during non feverish seizures prolactin concentration in higher, but we don't know if the same seizures are the beginning of epilepsy. So plasma prolactin concentration is a parameter of moderate interest in diagnosis and prognosis in childhood paroxismal disorders.

A 11-year-old girl suffering from grand mal epilepsy underwent antiepileptic therapy with carbamazepine (600 mg/daily). Two weeks after increasing the dose (900 mg/day) she suddenly developed relatively sharply limited, sunburn-like brown reddish macular lesions with central scaling and partly hyperkeratotic areas on the hands, feet, face, knees, gluteal and axillar regions. Otherwise no health disorders were found; in particular no neurological or gastrointestinal symptoms occurred. After reduction of the doses (450 mg/day) these skin lesions faded away. With exception of elevated serum levels of carbamazepine, nicotinamide and vitamin B6, all blood tests were in normal range. Interactions of carbamazepine with the vitamin B6- nicotinamide metabolism are the reason for these previously undescribed cutaneous side effects in connection with carbamazepine therapy. The present case demonstrates a toxic, non-allergic reaction during carbamazepine treatment with pellagroid skin symptoms.

A longitudinal study to estimate the serum calcium, phosphate and alkaline phosphatase levels of 89 ambulatory epileptic children, aged between 3 years and 12 years, and having generalised tonic-clonic seizures, was carried out. None was on any form of medication for the treatment of seizures prior to presentation. Each patient received only phenobarbitone during the period of study. Serum levels of the biochemical parameters were determined at presentation, 6 months and 12 months, while serum phenobarbitone levels were estimated at 6 months and 12 months. Mean serum calcium, phosphate and alkaline phosphatase of the patients remained within the normal range. Using the paired 't' test, the differences in the levels of the parameters at the three measurements were not statistically significant (P > 0.05). Serum phenobarbitone levels remained within the therapeutic range during the period of study. Our results show that over a 12-month period, serum levels of calcium, phosphate, and alkaline phosphatase, remain normal in ambulant epileptic children treated with phenobarbitone.

Meperidine is a widely prescribed opioid analgesic used in a variety of clinical situations. The parent compound has central nervous system depressant effects. However, the sole active metabolite, normeperidine, is a central nervous system excitatory agent and has the ability to cause seizures, especially in patients with renal failure. Patients with normal renal function rarely manifest seizure activity when given meperidine, but if the drug is used in large doses at frequent dosing intervals, seizures may occur. Reported here is the case of a man with normal renal function who had a tonic-clonic seizure due to meperidine that was administered for the pain of underlying chronic pancreatitis.

A 15-year-old boy presented to the emergency department with status epilepticus and a blood ethanol concentration of 757 mg/dL. Mechanical ventilation and substantial amounts of benzodiazepines were required. His hospital course was complicated by aspiration pneumonia, but he had no episodes of hypoglycemia. He received 2.8 hours of hemodialysis, which increased the rate of ethanol elimination, but there is no evidence that hemodialysis improved his clinical outcome. To our knowledge, this is the highest blood ethanol level reported in a child or adolescent who survived.

To assess the effects of neonatal seizures on the hypothalamus and to test clinical use of prolactin as a neonatal seizure marker, we studied postictal and recovery baseline serum prolactin levels in 19 neonates whose seizures were classified according to their clinical and EEG features. Postictal prolactin levels were obtained 30 min after the seizure, and recovery levels were ascertained 2-4 days later. The ratio of postictal prolactin level to recovery baseline level (prolactin ratio) was used as an indicator of postictal prolactin increase. The specificity and sensitivity of a prolactin ratio of > 2 was compared with the current standard of diagnosis (seizure discharges recorded by ictal EEG). Infants with electroclinical seizures had significantly higher prolactin ratios than control infants or infants with seizures without EEG correlation. Marked prolactin increases were noted only in infants with focal tonic seizures and temporal electrode involvement. A prolactin ratio of > 2 had a specificity of 100% and a sensitivity of 40%. We conclude that neonatal seizures have variable effects on the hypothalamus and that the low sensitivity and the need to await recovery levels limit the clinical value of prolactin ratio as a neonatal seizure marker.

In a prospective study, 139 patients who presented newly diagnosed primarily generalized tonic-clonic seizures (GTCS) were treated with monotherapy controlled-release carbamazepine (CR-CBZ) (TegretolCR) during one year. Ninety-three patients completed the trial. Patients were assessed for seizure control and tolerance. Mean number of seizures in the year before entry into the trial was 2.42 +/- 1.69, during one year follow-up this number was 0.77 +/- 2.44 (n = 93). Total number of patients remaining seizure-free during 12 months was 72 out of 93 patients completing the trial. Overall efficacy and tolerance was rated by the investigators as excellent in the majority of patients (respectively 86% and 77%). The results suggest that TegretolCR might be a drug of choice for first line treatment of tonic-clonic seizures given the excellent efficacy and relative lack of toxicity.

CBZ-10,11-epoxide is a major metabolite of CBZ. It has anticonvulsive properties and may be responsible for side-effects of CBZ treatment. Fifty-two children between the age of 2 weeks and 15 years were treated with CBZ (mean dosage 17 mg/kg body weight) either as mono- (n = 36) or in polytherapy (n = 16). The drug was delivered as an oral solution, as a nonretarded tablet or, most frequently, as a retarded tablet. The duration of treatment ranged from 1 to 94 months with 23 patients being on treatment for less than 3 months. Blood samples were taken with random timing after the last ingestion of the drug. The relative concentration of CBZ epoxide (expressed in % of CBZ) was higher in infants (median 48.9%) than in older children (median 14.9% in the 12-15-year-old group). A significant linear correlation with age was found (p < 0.001). In addition to young age, polytherapy (p < 0.01) and administration as a nonretarded formulation rather than as a retarded tablet (p < 0.05) induced a higher relative concentration of the epoxide. The relative concentration of the epoxide did not correlate with the serum CBZ concentration and the duration of treatment. Although in our study high epoxide levels were not related to clinical side effects, we recommend that in very young children polytherapy treatment with carbamazepine should be performed with caution and in difficult cases a determination of the epoxide level should be considered.

In 11 patients with epilepsy serum myoglobin level determinations were performed by the RIA method 10 minutes, 1 hour, 4, 12, and 24 hours after tonic-clonic seizure and were compared with myoglobin concentrations in a group of 30 healthy persons. A statistically significant increase of myoglobin concentration was shown already in the first hour after the seizure with maximal level, almost five times exceeding the baseline level in the fourth hour, and slightly lower--four times exceeding the baseline--12 hours after the seizure. The correlative studies, comparing the profile of myoglobinaemia with the clinical picture (duration of the disease, age and sex, presence or lack of EEG changes, type of therapy used) showed no statistical significance.

Traditional medicine is practised to some degree in all cultures. Many different types of herbal preparations and "oils" are widely used in Malaysia, too. We report a case of acute salicylism due to accidental ingestion of one brand of such oils. Compulsory labelling of traditional drugs with their chemical ingredients is suggested for proper and timely management of such cases.

The alcohol-withdrawal syndrome was examined in 76 persons suffering from chronic alcohol dependency. Twenty persons showed only slight withdrawal symptoms. Thirty-two showed pronounced predelirium. Twenty-four patients developed delirium tremens. Commencing on the day on which alcohol was last consumed, potassium and magnesium levels in the blood serum were measured for 8 days until the 7th day after withdrawal from alcohol. The more pronounced the alcohol withdrawal syndrome, the sharper the decline in the level of potassium and magnesium in the blood serum. In each case, the decline in the magnesium serum level preceded that of the potassium serum level by one day. On the basis of the clinically and experimentally observed repercussions of the magnesium level (delirium symptoms, including grand mal), the magnesium blood level decline is attributed greater significance than that of the potassium blood level decline. The repercussions on magnesium and potassium blood levels resulting from the accompanying catecholamine release and of hyperventilation during delirium are discussed.