Antiepileptic Drug Usage Research Articles

Antiepileptic drugs and suicide-related behavior: Is it the drug or comorbidity?

We sought to compare trends of suicide-related behavior (SRB) before and after initiation of antiepileptic drug (AED) therapy among AED users (with and without epilepsy) to that of individuals without AED use controlling for sociodemographic characteristics and mental health comorbidity. We used national Veterans Health Administration (VHA) data for post-9/11 veterans who received VHA care (2013-2014) without prior AED use. We conducted generalized estimation equation (GEE) analyses, stratified by epilepsy status and type of AED received, to assess the trend of SRB prevalence the year prior to and after the index date (date of first AED prescription/date of first health care encounter for non-AED users) controlling for sociodemographic factors and mental health comorbidity. The GEE analysis showed significant curvilinear trends of SRB prevalence over the 24-month study period among the AED users, indicating that the probability of SRB diagnoses increased over time with a peak before the index month and decreased thereafter. Similar patterns were observed among non-AED users, but significantly lower odds for SRB. Among AED users, there were no significant differences by epilepsy status; however, higher SRB prevalence and differential SRB trajectory measures were observed among those who received AEDs with mood-stabilizing action. The peak of SRB prior to and rapid reduction in SRB after initiation of AED, and the finding that individuals eventually prescribed a mood-stabilizing AED (vs other AED or levetiracetam) had higher odds of SRB, suggests a strong possibility that the relationship of AED and SRB is one of residual confounding.

The risk of Stevens‐Johnson syndrome and toxic epidermal necrolysis in new users of antiepileptic drugs: Comment on data sparsity

The risk of Stevens‐Johnson syndrome and toxic epidermal necrolysis in new users of antiepileptic drugs: Comment on data sparsity

Seizure outcomes of supratentorial brain tumor resection in pediatric patients.

This study aims to identify the prevalence of and risk factors for seizure development after supratentorial brain tumor resection in pediatric patients. This could be used to guide the postoperative management and usage of anti-epileptic drugs (AEDs). Retrospective study was conducted for patients between 0 and 21 years with supratentorial tumor resection between 2005 and 2015 at a single institution. Two hundred patients (114 males/86 females) were identified. Median age at resection (±SD) was 9.025 ± 5.720 years and mean follow-up was 4 ± 2 years. Resection was gross total in 82 patients (41%) and partial in 118 patients (59%); 66 patients (33%) experienced preoperative seizures, and 67 patients (34%) experienced postoperative seizures; 18 patients (27%) had early seizures, and 49 patients (73%) had late seizures. Univariate analysis identified risk factors for postoperative seizures as: preoperative seizures (P < 0.001), age less than 2 years (P = 0.003), temporal location (P < 0.001), thalamic location (P = 0.017), preoperative hyponatremia (P = 0.017), World Health Organization grade (P = 0.008), and pathology (P = 0.005). Multivariate regression identified 5 robust risk factors: temporal location (odds ratio [OR] 4.7, 95% CI: 1.7-13.3, P = 0.003), age <2 years (OR 3.9, 95% CI: 1.0-15.4; P = 0.049), preoperative hydrocephalus (OR 3.8, 95% CI: 1.5-9.4; P = 0.005), preoperative seizure (OR 2.8, 95% CI: 1.2-6.5; P = 0.016) and parietal location (OR 0.25, 95% CI: 0.06-0.99; P = 0.049). Extent of resection did not correlate with seizure development (P > 0.05). This study reveals 5 risk factors for postoperative seizures after resection of supratentorial tumors. These factors should be considered in postoperative management of these patients.

Pattern of Usage of Anti Epileptic Drugs In A Tertiary Neuro Care Unit In India

Pattern of Usage of Anti Epileptic Drugs In A Tertiary Neuro Care Unit In India

Women with epilepsy in childbearing age: Pregnancy-related knowledge, information sources, and antiepileptic drugs

Pregnancy-related issues in epilepsy (PRIE) are essential for management of epilepsy in women. We conducted a study among women with epilepsy (WWE) aged 15–45years about their knowledge, sources, and needs for information regarding PRIE, which included their current antiepileptic drugs (AEDs) usage. Women with epilepsy, visitors of Croatian Association for Epilepsy webpage, were offered an online questionnaire, and 200 responses were analyzed. The mean number of correct answers about PRIE was 3.5 out of 5. Main predictors of knowledge on PRIE were a prior consultation with a neurologist and higher usage of books/brochures. A prior neurologist consultation on PRIE was stated by 45% of subjects. As the preferred future mode of being informed on PRIE, majority of women (61%) chooses their neurologist, 22% written materials distributed by a neurologist, and only 13% Internet. Levetiracetam was the most commonly used AED (34.5%). Valproate was used by 26%, and of those 59% stated no previous consultation on PRIE with their neurologist. In summary, we believe our study shows that knowledge of PRIE among WWE in their childbearing age is unsatisfactory, as are the neurologist consultation rates about PRIE. Our results demonstrate that, despite modern technologies, educational activities should be based on neurologist consultations and providing the patients with appropriate written materials. This is especially true for the relatively large proportion of women still taking valproate.

Anticonvulsant effect of Bacopa monnieri extracts on Catecholamine metabolism during PTZ-induced Epilepsy in different brain regions of Albino Rat

In the modern era, Epilepsy is one of the most prevalent serious neurological disorders, affecting 0.5 to 1.0% of the world’s population. Epileptic seizures are paroxysmal clinical events arising from neuronal hyper-excitability and hypersynchrony of the cerebral cortex, either locally (partial seizures) or diffusely in both hemispheres (generalized seizures). The agitated neuronal activity that occurs during a seizure is caused by a sudden imbalance between the inhibitory and excitatory signals in the brain with glutamate, ?-aminobutyric acid (GABA), noradrenaline, serotonin, and dopamine. Since long term usage of antiepileptic drugs cause high incidence of pharmacoresistence and untoward side effects, attention has been paid in recent years to screen bioactive compounds from natural medicinal plants for treatment of several neurological disorders including Epilepsy. Keeping in view of relative importance of natural medicinal plants, the present study is mainly focused to characterize the anti-convulsant effect of Bacopa monnieri (BM), an Indian herb which is being extensively used in Ayurvedic treatments related to neurological complications. The present study was designed to assess the neurotoxicity of PTZ on the metabolism of Biogenic amines (Nor-epinephrine, Epinephrine, Dopamine, Serotonin) in different brain regions (Cerebral cortex, Cerebellum, Pons medulla and Hippocampus) of rat and explore the possible antiepileptic effect of different extracts (Ethanol, n-Hexane, Chloroform, Ethyl acetate, n-Butanol and Aqueous extracts) of BM in comparison with Diazepam (DZ) (Reference control). PTZ-Induced epilepsy caused significant decrease in all the catecholamine levels in all brain regions. On par with Diazepam pretreatment, different extracts of BM except aqueous extract (AE) significantly increased the monoamine contents in all the regions of brain. Mono amine oxidase (MAO) activity levels showed elevation in different brain regions of rat during PTZ-induced epilepsy which was reversed in epileptic animals pretreated with different extracts except AE and DZ. These findings suggest that BM causes perceptible changes in the biogenic amine metabolism as one of the major facets of its anticonvulsant activity. Hence, BM extract can be effectively used in the treatment of Epilepsy and other related neurological disorders.

Alterations in the Glutamate metabolism and Aminotransferases (AAT, ALAT) during PTZ – induced Epilepsy: Protective role of Bacopa monnieri

Epilepsy, a common chronic neurological disorder characterized by repeated, spontaneous seizures, also known as seizure disorder. Seizure related neuronal injury has been assumed to be mediated by glutamate, the excitatory amino acid, in the central nervous system that causes a sudden imbalance between the inhibitory and excitatory signals in the brain with glutamate, γ-aminobutyric acid (GABA), noradrenaline, serotonin, and dopamine. Since long term usage of antiepileptic drugs cause high incidence of pharmacoresistence and untoward side effects, attention has been paid in recent years to screen bioactive compounds from natural medicinal plants for treatment of several neurological disorders including Epilepsy. Keeping in view of relative importance of natural medicinal plants, the present study is mainly focused to characterize the anti-convulsant effect of Bacopa monnieri (BM), an Indian herb which is being extensively used in Ayurvedic treatments related to neurological complications. The present study is designed to assess the neurotoxicity of Pentylene tetrazole (PTZ), an epileptic compounds, on the Glutamate metabolism and Amino transferases in different brain regions (Cerebral cortex, Cerebellum, Pons medulla and Hippocampus) of rat and to explore the possible antiepileptic effect of different extracts (Ethanol, n-Hexane, Chloroform, Ethyl acetate, n-Butanol and Aqueous extracts) of BM in comparison with Diazepam (DZ) (Reference control). The activities of glutamate dehydrogenase (GDH), glutamine synthetase (GS) and glutamine content were decreased in different regions of brain during PTZ induced epilepsy which were increased in epileptic rats pretreated with different extracts of Bacopa monnieri except EAE and AE. Glutaminase activity was increased in PTZ induced epilepsy and decreased on pretreatment with all the extracts of BM except AE. In addition aspartate (AAT) and alanine aminotransferase (ALAT) activity levels were increased during PTZ induced epilepsy when compared with normal control and levels were reversed on pretreatment with different extracts of BM. Recoveries of these parameters during antiepileptic treatment suggest that the bioactive factors present in the extracts offer neuroprotection by interrupting the pathological cascade of glutamatergic hyperexcitation that occurs during epileptogenesis.

Preliminary Asian experience of using perampanel in clinical practice

BackgroundTo analyze the efficacy and safety of perampanel over a 3-month period in a sample of Asian people with epilepsy. MethodsThe efficacy and safety of perampanel as an adjunctive therapy for patients with epilepsy were retrospectively reviewed and analyzed. Patients were categorized according to seizure type, concomitant antiepileptic drug usage, and perampanel dosage. ResultsA total of 210 patients were included in the study and 131 patients completed 3 months of perampanel treatment. The average dosage of perampanel was 5.31 mg/day, and the 50% responder rate (≥50% seizure frequency reduction) in all patients was 45.8%, with a 27.5% seizure-free rate. For focal seizures, focal to bilateral tonic-clonic seizures, and primary generalized seizures, the 50% responder rates were respectively 29.4%, 49.5%, and 36.4%. In total, 39.5% of patients experienced adverse events within 3 months of observation period, and the rate of drug withdrawal due to adverse events was 8.6%. Dizziness, ataxia, irritability/aggression were the most common adverse events. ConclusionsThe efficacy and safety of perampanel in a real-world setting with Asian patients is comparable to that in clinical trials that have included fewer Asian patients.

The risk of Stevens-Johnson syndrome and toxic epidermal necrolysis in new users of antiepileptic drugs.

Older antiepileptic drugs (AEDs) are known to cause Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN). However, evidence for newer AED is sparse. We quantified risks of SJS/TEN in association with use of all AEDs in the United Kingdom. In a matched case-control study of 480 previously validated SJS/TEN cases (1995-2013) we used conditional logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs), and calculated absolute risks of SJS/TEN within separate cohorts of new users of 28 AEDs. We assessed causality between drugs and SJS/TEN in each exposed case, using an adapted version of the algorithm of drug causality for epidermal necrolysis (ALDEN) score. We observed a strong association between SJS/TEN and new use of carbamazepine (OR 92.57, 95% CI 19.89-∞), phenytoin (OR 49.96, 95% CI 10.13-∞), and lamotrigine (OR 26.90, 95% CI 4.88-∞), where causality, according to the ALDEN score, was very probable or probable for most exposed cases. Absolute risks for SJS/TEN were highest for phenytoin (45.86 cases/100,000 exposed), lamotrigine (44.17 cases/100,000 exposed), and carbamazepine (20.38 cases/100,000 exposed). Despite increased ORs for valproate (40,941 exposed), gabapentin (116,037 exposed), pregabalin (59,967 exposed), and clobazam (4,300 exposed), ALDEN suggested no causal association. There were no observed cases of SJS/TEN among new users of levetiracetam (n=96,77), clonazepam (n=18,075), or topiramate (n=11,307). The results of our study are consistent with those of previous studies of SJS/TEN, which found increased risks of SJS/TEN in new use of carbamazepine, phenytoin, and lamotrigine. Despite frequent use, no ALDEN-score confirmed cases were observed in new users of valproate, gabapentin, pregabalin, levetiracetam, topiramate, or clonazepam.

Fetal growth and premature delivery in pregnant women on antiepileptic drugs.

To evaluate the effects of epilepsy and antiepileptic drugs (AEDs) used during pregnancy on fetal growth and preterm delivery. This study included singleton liveborn infants born to women enrolled in the North American Antiepileptic Drug Pregnancy Registry between 1997 and 2016. Data were collected prospectively through telephone interviews. The prevalence of preterm birth (<37 weeks) and small for gestational age status (SGA) among infants exposed prenatally to AEDs when used by women with epilepsy (WWE) or women without epilepsy (WWOE) was compared with that among infants unexposed to AEDs and born to WWOE. Multivariate log-binomial regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). The study population included infants born to 6,777 AED-WWE, 696 AED-WWOE, and 486 no-AED-WWOE. The risk of prematurity was 6.2% for no-AED-WWOE, 9.3% for AED-WWE (RR = 1.5, 95% CI = 1.0-2.1), and 10.5% for AED-WWOE (RR = 1.5, 95% CI = 1.0-2.4). Prenatal exposure to AEDs in WWE and WWOE was associated with a mean lower birth weight of 110 and 136g, respectively, as compared to no-AED-WWOE. The prevalence of SGA was 5.0% for no-AED-WWOE, 10.9% for AED-WWE (RR = 2.0, 95% CI = 1.3-3.0), and 11.0% for AED-WWOE (RR = 1.9, 95% CI = 1.2-2.9). Within users of AEDs in monotherapy, the prevalence of SGA ranged from 7.3% for lamotrigine to 18.5% for topiramate. Women on AEDs during pregnancy, whether for epilepsy or for other neuropsychiatric indications, are at a higher risk of delivering prematurely and giving birth to SGA newborns. The risk may vary by drug. Ann Neurol 2017;82:457-465.

Seizures and Choice of Antiepileptic Drugs Following Subarachnoid Hemorrhage: A Review.

Seizures are important complications following a subarachnoid hemorrhage (SAH). The evidence for the use of antiepileptic drugs (AEDs) in treatment and prevention of those seizures is conflicting. The purpose of this review is to provide an up-to-date evidence summary of the incidence and outcomes of seizures following an SAH as well as the use of different AEDs post-SAH in order to evaluate the need for seizure prophylaxis, the choice of AEDs, and their dosing considerations in SAH patients. A literature search of PubMed, Medline, Embase, and the Cochrane Library was performed. A total of 37 studies were reviewed, mostly observational. Definitions of seizures in temporal relation to initial hemorrhage were variable. Similarly, the rates of seizures varied in the literature, ranging from 0 to 31%. Given the reported adverse outcomes associated with AED usage, seizure prophylaxis is not warranted. Levetiracetam appears to be better tolerated than phenytoin in SAH patients, though further research is needed. Higher initial dosing of levetiracetam might be required due to its enhanced clearance in SAH patients. In conclusion, there is a lack of quality evidence to definitively recommend the use of one AED over another. Further prospective research comparing the use of different AEDs in patients with an SAH is needed.

Toxicological Profile of Carbamazepine and Levetiracetam on Some Biochemical and Haematological Parameters in Rats

The prolonged usage of antiepileptic drugs has necessitated the need to study their toxicological profiles using in experimental animals. The toxicological effects of carbamazepine (CBZ) and levetiracetam (LEV) on some biochemical and haematological parameters were evaluated in rats. Haematological parameters evaluated include packed cell volume (PCV), Haemoglobin (Hb) and white blood cell (WBC), while some biochemical parameters studied were liver enzyme tests such as alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lipid profiles tests such as total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL) and low density lipoprotein (LDL). In addition, the body weight and morphological assessment of the vital body organs were determined. Results showed that CBZ and LEV did not significantly affect the haematological parameters. Animals treated with CBZ showed a significant increase in TC and HDL levels at 400 and 1000 mg/kg doses. There was no significant increase in the TC, HDL, LDL and TG in rats treated with LEV. CBZ and LEV treated animals at the doses of 400 and 1000 mg/kg showed a significant increase in body weights from the 6th day after commencement of treatment. There was also a significant increase in the weights of the liver, kidney and heart of the animals treated with CBZ and LEV. The colour and texture of the organs did not change. However, no appreciable weight increase was observed with the lung.

Antiepileptic drug discontinuation by people with epilepsy in the general population

Rate, reasons, and predictors of antiepileptic drug (AED) discontinuation were investigated in a well-defined cohort of people with epilepsy to verify efficacy and tolerability of treatment up to 20 years from treatment initiation. The history of AED usage in children and adults with epilepsy registered with 123 family physicians in an area of Northern Italy between 2000 and 2008 was recorded. Cumulative probabilities of AED withdrawal for specific reasons were estimated using cumulative incidence functions. The probabilities of withdrawing for terminal remission, and of achieving sustained remission while still on treatment, were also evaluated. The roles of sex, age at diagnosis, seizure types, duration at diagnosis, and syndrome were assessed with hazard ratios and 95% confidence intervals. Seven hundred thirty-one of 747 individuals were treated with one or more AEDs during the disease course. The three commonest drugs were valproate, carbamazepine, and phenobarbital. Reported reasons for AED withdrawal were, in decreasing order, terminal remission, ineffectiveness, and adverse events. The probability of withdrawing the first AED for terminal remission was 1.0% at 1 year and increased to 20.0% at 20 years. Corresponding rates were 2.9% and 12.6% for ineffectiveness and 0.5% and 3.3% for adverse events. Reasons for withdrawal varied with individuals' age, sex, disease characteristics, and drugs. The initial AED given was retained in the majority of cases. Terminal remission, lack of efficacy, and adverse effects were, in decreasing order, the commonest reasons for AED discontinuation. Withdrawal could be predicted by age at diagnosis, sex, and clinical characteristics and varies among drugs.

Bone loss with antiepileptic drug therapy: a twin and sibling study.

To investigate the longitudinal associations of bone mineral measures with antiepileptic drug (AED) use, including enzyme-inducing (EIAED) and non-enzyme-inducing (NEIAED) types, and other predictors of bone loss in a study of 48 same-sex twin/age-matched sibling pairs (40 female, 8 male) discordant for AED use. Using dual-energy X-ray absorptiometry (DXA), areal bone mineral density (aBMD) and content (BMC) at the hip regions, forearm, lumbar spine, and whole body were measured twice, at least 2years apart. The mean within-pair difference (MWPD), MWPD%, and mean annual rate of aBMD change were adjusted for age, weight, and height. Predictors of bone loss were evaluated. AED users, compared to non-users, at baseline and follow-up, respectively, had reduced aBMD at the total hip (MWPD% 3.8, 4.4%), femoral neck (4.7, 4.5%), and trochanter regions (4.1, 4.6%) (p<0.05). For the whole cohort, the annual rate of change in all aBMD/BMC (p>0.05) regions did not differ within pairs. Nevertheless, EIAED users had greater aBMD loss than non-users (n=20 pairs) at the total hip (1.7 vs. 0.3%, p=0.013) and whole body regions (0.7% loss vs. 0.1% BMD gain, p=0.019), which was not found in NEIAED-discordant pairs (n=16). AED use >20years predicted higher aBMD loss at the forearm (p=0.028), whole body (p=0.010), and whole body BMC (p=0.031). AED users had reduced aBMD at the hip regions. Prolonged users and EIAED users had greater aBMD loss, predicting a higher risk of bone fragility. Further prospective studies of AED effects on bone microarchitecture are needed.

Antiepileptic drug therapy in patients with autoimmune epilepsy.

Objective:We aimed to report the pattern of usage and efficacy of antiepileptic drugs (AEDs) in patients with autoimmune epilepsy (AE).Methods:We retrospectively studied the Mayo Clinic's electronic medical record of patients with AE in which seizures were the main presenting feature. Clinical data, including demographics, seizure characteristics, type of AED and immunotherapy used, presence of neural antibody, and treatment outcomes, were reviewed.Results:The medical records of 252 adult patients diagnosed with autoimmune encephalitis and paraneoplastic disorders were reviewed. Seizure was the initial presentation in 50 patients (20%). Serum and/or CSF autoantibodies were detected in 41 (82%) patients, and 38 (76%) patients had neural autoantibodies. The majority (n = 43, 86%) received at least 1 form of immunotherapy in combination with AEDs, while the remainder received AEDs alone. Twenty-seven patients (54%) became seizure free: 18 (36%) with immunotherapy, 5 (10%) with AEDs alone, and 4 (8%) with AEDs after immunotherapy failure. Levetiracetam was the most commonly used (42/50); however, it was associated with 0% seizure-free response. AED seizure-free responses occurred with carbamazepine (n = 3) [3/16, 18.8%], lacosamide (n = 3) [3/18, 16.6%] with phenytoin (n = 1) [1/8, 12.5%], or oxcarbazepine (n = 2) [2/11, 18.1%]. Regardless of the type of therapy, voltage-gated potassium channel-complex antibody–positive patients were more likely to become seizure free compared with glutamic acid decarboxylase 65 antibody–positive cases (12/17 vs 2/10, p = 0.0183).Conclusions:In select patients, AEDs alone were effective in controlling seizures. AEDs with sodium channel blocking properties resulted in seizure freedom in a few cases. Prospective studies are needed to clarify AED selection and to elucidate their immunomodulatory properties in AE.

Teratogenicity of Antiepileptic Drugs.

ObjectiveAntiepileptic drugs (AED) have chronic teratogenic effects, the most common of which are congenital heart disease, cleft lip/palate, urogenital and neural tube defects. The aim of our study is to examine teratogenic effects of AED and the correlation between these malformations and AED in single or multiple pregnancies.MethodsThis is a retrospective study of malformations in children born to mothers currently followed up by our outpatient clinics who used or discontinued AED during their pregnancy. Their children were then investigated using echocardiography, urinary ultrasound, cranial magnetic resonance image, and examined by geneticists and pediatric dentists.ResultsOne hundred and seventeen children were included in the study. Ninety one of these children were exposed to AED during pregnancy. The most commonly used AED were valproic acid and carbamazepine in monotherapy. The percentage of major anomaly was 6.8% in all children. Dysmorphic features and dental anomalies were observed more in children exposed especially to valproic acid. There were 26 mothers with two and four mothers with three pregnancies from the same fathers. No correlation was found between the distribution of malformations in recurring pregnancies and AED usage.ConclusionOur study has the highest number of dysmorphism examined in literature, found in all the children exposed to valproic acid, which may account for the higher rate of facial dysmorphism and dental anomalies. On lower doses of valproic acid, major malformations are not seen, although the risk increases with polytherapy. Our data also indicate possible effects of genetic and environmental factors on malformations.

Effects of Antiepileptic Drugs on the Carotid Artery Intima-Media Thickness in Epileptic Patients.

Background and PurposeIt has been reported that taking antiepileptic drugs (AEDs) may increase the risk of atherosclerosis. We performed a meta-analysis to evaluate the carotid artery intima-media thickness (CA-IMT) as a surrogate factor for atherosclerosis in epileptic patients.MethodsWe searched NCBI (PubMed), ISI Web of Knowledge, EMBASE, and the Cochrane Library databases for studies of the association between AEDs and CA-IMT in epileptic patients. A random-effects meta-analysis was used to pool results across studies.ResultsFifteen studies involving 1,775 epileptic patients were included in the analysis. The overall CA-IMT was significantly larger among users of AEDs [mean difference (MD)=0.09 mm, 95% confidence interval (CI)=0.06–0.12 mm). When stratified by age, the MD was similar in adult patients (MD=0.09 mm, 95% CI=0.06–0.13 mm), but no significant difference was observed in children (MD=0.03 mm, 95% CI=0.00–0.07 mm). Regarding specific AEDs, monotherapy with carbamazepine (CBZ) or valproic acid (VPA) was associated with a larger CA-IMT, while phenytoin monotherapy was not and the result for lamotrigine was inconclusive.ConclusionsThis study suggests that using AEDs is associated with the CA-IMT in patients with epilepsy, particularly for adult patients. In particular, CBZ and VPA may be related to a significant increase in CA-IMT.

Insulinoma with a History of Epilepsy: Still a Possible Misleading Factor in the Early Diagnosis of Insulinoma

A delayed diagnosis of insulinoma remains a clinical issue. Hypoglycemic symptoms can mimic neuropsychiatric disorders such as epilepsy. A 27-year-old woman with a history of epilepsy and anti-epileptic drugs (AEDs) developed repeated seizures and neuropsychiatric symptoms after a 9-year asymptomatic interval. She had received transient treatment with AEDs before the possibility of hypoglycemia was considered. Following a clinical diagnosis of insulinoma, distal pancreatectomy was performed; her seizures didn't occur again. The early diagnosis of insulinoma requires vigilance not only for hypoglycemia in patients with neuropsychiatric symptoms but also for the possible masking effects of a history of epilepsy and preceding AED usage.

Changing antiepileptic drug use for seizures in US neonatal intensive care units from 2005 to 2014.

Neonatal seizures are a common problem in the neonatal intensive care unit and are frequently treated with antiepileptic drugs. Limited data exist on current or changing antiepileptic drug use for seizures in the neonatal intensive care unit.We sought to describe trends of antiepileptic drug exposure in a large volume of US neonatal intensive care unit from 2005 to 2014 and we hypothesized increasing levetiracetam exposure over the 10-year study period. Retrospective cohort study of infants from the Pediatrix Medical Group Clinical Data Warehouse, a large, multicenter, deidentified data set. Data were analyzed for trends in 2-year time periods. Our cohort included infants with a diagnosis of seizures who received an antiepileptic drug that were discharged from the neonatal intensive care unit from 1 January 2005 to 31 December 2014. Among 778 395 infants from 341 facilities, we identified 9134 infants with a seizure diagnosis who received an antiepileptic drug. Phenobarbital was used in 98% of the cohort. From 2005-2006 to 2013-2014 phenobarbital exposure declined from 99 to 96% (P<0.001), phenytoin exposure decreased from 15 to 11% (P<0.001) and levetiracetam exposure increased 10-fold from 1.4 to 14% (P<0.001). Overall, <1% of infants were exposed to carbamazepine, lidocaine or topiramate. Infants with seizures were overwhelmingly exposed to phenobarbital, despite a significant increase in levetiracetam exposure. The use of phenytoin declined and has been surpassed by levetiracetam as the second most widely used antiepileptic in the neonatal intensive care unit. These changes in antiepileptic drug usage patterns have occurred in the absence of novel efficacy data in neonates.

Rufinamide in patients with Lennox-Gastaut syndrome

Rufinamide in patients with Lennox-Gastaut syndrome Peggy O Clark,1 Patricia A Gibson2 1Cincinnati Children&rsquo;s Hospital Medical Center, The University of Cincinnati College of Medicine, Cincinnati, OH, 2Epilepsy Information Service, Wake Forest University School of Medicine, Winston-Salem, NC, USA Objectives: Lennox&ndash;Gastaut syndrome (LGS) is an epileptic encephalopathy with an onset at the age of ~4 years. LGS is notoriously difficult to manage, as most patients experience multiple seizures per day, despite their concomitant use of several antiepileptic drugs (AEDs). Rufinamide (BANZEL&reg;) is an AED approved by the US Food and Drug Administration for the adjunctive treatment of seizures associated with LGS in pediatric patients aged &ge;1 year and in adults. The&nbsp;expert care of nurses knowledgeable in the treatment options for LGS is valuable to patients and caregivers. This review summarizes the existing knowledge on LGS and data from clinical and real-world studies on the use of rufinamide in patients with LGS.Methods: Recent review articles and information from the Epilepsy Foundation Website were reviewed for data on LGS treatment. Primary articles on rufinamide were also selected for review.Results and conclusion: The efficacy and safety of rufinamide have been evaluated in children and adults by using double-blind, open-label, and observational studies. In general, these studies indicate that rufinamide effectively reduces the frequency and severity of multiple seizure types associated with LGS and has tolerable side effects, the most common being vomiting and somnolence. Dosing modifications based on age, weight, and concomitant AED usage are recommended for patients using rufinamide. Keywords: Lennox&ndash;Gastaut syndrome, anticonvulsants, rufinamide