Trends in enzyme-inducing antiseizure medication use: A retrospective analysis among adults with epilepsy.

BACKGROUND: Enzyme-inducing antiseizure medications (EIASMs) were associated with drug interactions and long-term adverse effects. Therefore, it was suggested that epilepsy treatment should be started with non-EIASMs, and in patients treated with EIASMs, replacement with non-EIASMs should be evaluated OBJECTIVE: To assess potent EIASM use among patients with epilepsy at their first visit in our epilepsy outpatient clinic. METHODS: We retrospectively reviewed the computerized database and the medical records of all the patients who had their first visit in our outpatient epilepsy clinic during a 10-year period (2012-2021). Of 730 patients with ASM treated epilepsy, 243 (33%) were receiving potent EIASMs. RESULTS: The annual potent EIASM use decreased from 35.1 % in 2012 to 11.8 % in 2021. Most of the patients who received potent EIASM had their first visit during 2012-2015 compared to the following years (56.8 % vs 43.2 %) (p = 0.0001). Patients with epilepsy receiving potent EIASMs were older (44.3 vs 34.7) (p = 0.0001), more likely men (60.9 % vs 47.2 %) (p = 0.001), with longer disease duration (13 vs 9.3 y) (p = 0.0001), higher rate of neuropsychiatric comorbidity (37 % vs 27.9 %) (p = 0.014), and were treated with more ASMs (1.6 vs 1.3) (p = 0.0001) compared to patients receiving non-EIASMs. CONCLUSIONS: Potent EIASM use has been declining over the past decade. Additional efforts to further decrease EIASM use should be exerted among all patients with ASM-treated epilepsy, with emphasis on men with focal epilepsy and epilepsy duration > 10 years.

Guidelines and epilepsy practice: Antiseizure medication initiation following an unprovoked first seizure in adults.

OBJECTIVES: Adherence rate to evidence-based clinical practice guidelines is relatively low and the impact of guidelines on clinical practice in epilepsy is variable. The 2015 practice guideline on the management of an unprovoked first seizure in adults specifies clinical variables associated with increased risk of seizure recurrence and the impact of immediate antiseizure medication (ASM) treatment on seizure outcome. We aimed to evaluate the impact of the evidence-based guideline for the management of an unprovoked first seizure in adults on clinical practice in our adult neurology department. METHODS: We retrospectively reviewed the computerized database of 169 adult patients admitted to the adult neurology department at Shamir-Assaf Harofeh Medical Center following a first unprovoked seizure between October 2011 and October 2018. RESULTS: ASMs were initiated in 86% of patients with a first unprovoked seizure pre- and in all patients admitted post- guideline publication. Monotherapy and use of old generation ASMs were more common in both groups and a combination of old- and new generation ASMs - among the pre-guideline group. The pre-guideline decision to initiate ASM treatment was significantly influenced only by epileptiform discharges in the electroencephalogram (EEG). DISCUSSION: This is the first study to evaluate the impact of the 2015 practice guideline on the initiation of ASM treatment after a first unprovoked seizure in adults. Further studies are needed to assess the global contribution of the guideline to clinical practice and its impact on patient outcomes.

Folic acid supplementation in women of childbearing age with epilepsy: No association with type or number of antiepileptic drugs.

BACKGROUND: For over two decades, a daily folic acid (FA) supplementation has been recommended for women of childbearing age with epilepsy. This recommendation is based on evidence that FA administration before conception and during pregnancy can decrease the risk of fetal malformations in the general population, improve cognitive development, and reduce the risk of autistic traits in children exposed in utero to antiepileptic drugs (AEDs). OBJECTIVE: The aim of this study was to evaluate FA supplementation rate in nonpregnant women of childbearing age with epilepsy and its relation to AED type and number. METHODS: We retrospectively reviewed the computerized database and the medical records of all the women who had a first visit to our outpatient epilepsy clinic (Shamir-Assaf Harofeh Medical Center, Zerifin, Israel) during a 10-year period (2012-2021). RESULTS: Only 61 (22%) of 282 nonpregnant women of childbearing age with epilepsy treated with AEDs received FA supplementation. Ninety-two (33%) of the women were treated with AED polytherapy, and 41 (15%) received valproic acid in monotherapy or polytherapy. FA supplementation rate was higher in women aged ≤40 versus >40 (25% vs. 8.5%) (p = .004). No correlation was found between FA supplementation and AED type or number. CONCLUSIONS: FA supplementation rate was low and was unaffected by AED treatment. Patient and physician-targeted interventions should be implemented to increase FA prescription and patient adherence.

Potential feasibility of a remote first visit in the epilepsy clinic.

BACKGROUND: Since the beginning of coronavirus disease (COVID-19) epidemic in Israel in early 2020, follow-up visits through phone consultations were available only for patients treated in our outpatient epilepsy clinic. OBJECTIVE: To assess the potential feasibility of phone consultation instead of in-person first visit in the outpatient epilepsy clinic. METHODS: The computerized database and medical records of all the patients who had an in-person first visit in our outpatient epilepsy clinic during a 4-year period (2018-2021) were retrospectively reviewed. Potential feasibility of a remote visit was assessed for all visits and was deemed possible when physical examination or vagal nerve stimulator (VNS) examination or parameter adjustment was not reported in the visit summary. RESULTS: The study group included 462 patients who had an in-person first visit in the outpatient epilepsy clinic during the study period. A remote first visit was deemed potentially feasible in 404 (87%) patients. Those in whom a remote first visit was deemed potentially infeasible were older (p = 0.0001), with longer disease duration (p = 0.001) and higher rates of antiseizure medication polytherapy (p = 0.0001), VNS and additional symptoms (p = 0.0001). CONCLUSIONS: A remote visit may be potentially feasible for most patients who are scheduled for a first visit in the epilepsy clinic. An in-person visit may remain the preferred option for patients with additional neurological symptoms or a VNS, and may also be considered in older patients and those with longer disease duration or antiseizure medication polytherapy.

Reasons for delayed treatment initiation in Guillain-Barre syndrome.

OBJECTIVE: The goal of this study was to analyze the reasons for delayed diagnosis of Guillain-Barre syndrome (GBS). METHODS: We retrospectively reviewed the records of all adult patients with GBS treated at Shamir Medical Center (SMC) from 2006 to 2018. We divided the patients into two groups: those with early initiation of treatment (within 24 h of arrival to ED), and those with later initiation of treatment (>24 h after arrival). We extracted epidemiological and clinical data regarding those groups, and compared them. RESULTS: 100 patients with GBS were treated between 2006 and 2018 at SMC. 50 patients were treated within 24 h of arrival, and in 50 - treatment was initiated later. Of those with delayed treatment, 9 had mild disease, but did receive a working diagnosis of GBS. 41 patients were not diagnosed initially as a clear-cut GBS, and alternative diagnoses were considered, the most common were orthopedic (11/41), vascular (7/41) or nutritional deficiency (6\41). Findings that increased the likelihood for alternative diagnoses to be considered first were severe limb or back pain (26/41); intact or brisk reflexes (17/41); and an atypical pattern of weakness (7\41). CONCLUSIONS: GBS is a challenging diagnosis. Acknowledging the heterogeneity of its presentation and knowing its pitfalls is crucial for the prompt and accurate diagnosis of the disease.

Therapeutic levetiracetam monitoring during pregnancy: "mind the gap".

BACKGROUND: Epilepsy is one of the most common chronic neurological conditions and its treatment during pregnancy is challenging. Levetiracetam (LEV) is an antiepileptic medication frequently used during pregnancy. Only a few small studies have been published on LEV monitoring during pregnancy, demonstrating decreased serum LEV levels during the first and second trimester; however, the most significant decrease was observed during the third trimester of pregnancy. In this study we aimed to evaluate LEV pharmacokinetics during different stages of pregnancy. METHODS: We followed up and monitored serum levels of pregnant women treated with LEV for epilepsy. RESULTS: Fifty-nine women with 66 pregnancies during the study period were included. The lowest raw LEV serum concentrations were observed during the first trimester. Compared with the pre-pregnancy period, raw serum concentration was lower by 5.76 mg/L [95% confidence interval (CI) (2.78, 8.75), p = 0.039] during the first trimester. Comparing the decrease in the first trimester with either the second or the third, no significant changes were observed (p = 0.945, p = 0.866). Compared with pre-pregnancy measurements, apparent clearance was increased by 71.08 L/day [95%CI (16.34, 125.83), p = 0.011] during the first trimester. About 30% of LEV serum levels during pregnancy were below the laboratory quoted reference range. CONCLUSIONS: Raw LEV serum levels tend to decrease during pregnancy, mainly during the first trimester contrary to previous reports. Monitoring of LEV serum levels is essential upon planning pregnancy and thereafter if pre-pregnancy LEV levels are to be maintained. However, more studies are needed to assess the correlation with clinical outcome.

Antiepileptic Drug Treatment in Community-Dwelling Older Patients with Epilepsy: A Retrospective Observational Study of Old- Versus New-Generation Antiepileptic Drugs.

INTRODUCTION: The use of antiepileptic drugs (AEDs) in older patients with epilepsy is challenged by polypharmacy and decreased drug elimination. Newer AEDs have a lower potential for drug interactions and are reported to be better tolerated by the elderly than old-generation AEDs. OBJECTIVE: The objective of this study was to evaluate AED use and the related adverse event rate in an outpatient cohort of older patients with epilepsy. METHODS: We retrospectively reviewed the computerized database and medical records of all the patients aged ≥60 years who visited our epilepsy outpatient clinic (Assaf Harofeh Medical Center, Zerifin, Israel) during a 4-year period from February 2012 to February 2016. In this study, phenytoin, valproic acid, carbamazepine, phenobarbital, clobazam, and clonazepam were defined as old-generation AEDs. Gabapentin, levetiracetam, lamotrigine, topiramate, oxcarbazepine, lacosamide, and perampanel were defined as new-generation AEDs. RESULTS: The study group included 115 patients aged 60-90 years (mean 70.5 ± 7.8 years), 70 (61%) of whom were men. Co-morbidities were present in 98.3% of the patients, including neuropsychiatric illnesses in 21.2%. Present medical treatment included new-generation AEDs in 49 (44.5%) and both old- and new-generation AEDs in 20 (18.2%) patients. The most commonly used current AEDs were phenytoin, gabapentin, levetiracetam, and lamotrigine. Adverse reactions mainly included fatigue and CNS-related symptoms, and were more frequent among patients treated with new-generation AEDs than in those treated with old-generation AEDs or a combination of old- and new-generation AEDs; however, these reactions were mostly related to levetiracetam treatment. The likelihood of levetiracetam-related adverse events was increased by slow levetiracetam titration [defined as a weekly dose increase of ≤250 mg/day in this study; odds ratio (OR) 16.35, 95% confidence interval (CI) 2.94-90.98], and by low- (OR 5.68, 95% CI 1.40-22.95) and high (OR 4.24, 95% CI 1.28-14.02) levetiracetam dosages compared with patients treated with lamotrigine or gabapentin. CONCLUSIONS: New-generation AEDs were administered to most of the patients in this outpatient clinic-based cohort of older patients with epilepsy. In order to decrease levetiracetam-related adverse events in this age group, we suggest that a slower titration rate (e.g., an increase of ≤125 mg/day each week) and lower maximal dosage (e.g., 1500 mg/day) of the drug should be considered.

The yield of non-elective inpatient video-EEG monitoring in adults.

BACKGROUND: Inpatient video-EEG monitoring (VEM) can contribute to the diagnosis and treatment in many of the monitored patients. Most admissions to VEM are elective and are scheduled ahead before the monitoring session. PURPOSE: To retrospectively evaluate the yield of non-elective VEM sessions. METHODS: We retrospectively reviewed the VEM recordings and medical records of all the patients admitted to our one-bed VEM unit from June 2007 to June 2015. A VEM session was diagnostic when a seizure, an event or previously unreported interictal epileptiform discharges were recorded. RESULTS: The study group included 304 adults aged 18-92 years (mean 40.4 ± 17.4 years), 181 (59%) women. The diagnostic yield of non-elective and elective VEM session was similar (66 and 69%, respectively). In non-elective VEM, fewer patients had known epilepsy (p = 0.0001), session duration was shorter (p = 0.0001), and seizures and interictal epileptiform discharges were recorded less frequently compared to elective VEM (p = 0.005 and p = 0.0001, respectively). CONCLUSION: Non-elective VEM can provide useful information in patients admitted to the neurology department with recent neurological or behavioral events. A timely and correct diagnosis in these patients can potentially reduce unnecessary use of antiepileptic drugs in patients with psychogenic nonepileptic seizures and the morbidity and mortality associated with undiagnosed seizures.

Quantitative EEG After Brain Stimulation and Cognitive Training in Alzheimer Disease.

PURPOSE: Medications are the currently accepted symptomatic treatment of Alzheimer disease (AD), but their impact on delaying the progression of cognitive deficits and functional impairment is limited. The authors aimed to explore long-term electrophysiological effects of repetitive transcranial magnetic stimulation interlaced with cognitive training on quantitative electroencephalography (EEG) in patients with AD. METHODS: Quantitative EEG was assessed on non-repetitive transcranial magnetic stimulation interlaced with cognitive training treatment days before treatment and after each treatment phase in seven patients with mild AD. RESULTS: After 4.5 months (54 sessions) of treatment, a significant increase of delta activity over the temporal region was found compared with pretreatment values. Nonsignificant increases of the log EEG power were found for alpha band over the frontal and temporal regions, beta band over the frontal region, theta band over the frontal, temporal, and parieto-occipital regions, and delta band over the frontal and parieto-occipital regions. Nonsignificant decreases were found for alpha over the parieto-occipital region, and for beta over the temporal and parieto-occipital regions. A positive correlation was found between log alpha power over the frontal and temporal regions at 6 weeks and Mini-Mental State Examination (MMSE) scores at 6 weeks and 4.5 months, and between log alpha power over the parieto-occipital regions and MMSE scores at 6 weeks. A negative correlation was found between log alpha power over the frontal and temporal regions at 6 weeks and baseline Alzheimer's Disease Assessment Scale-cognitive subscale scores. CONCLUSIONS: Repetitive transcranial magnetic stimulation interlaced with cognitive training has long-term effects on quantitative EEG in patients with mild AD. Further research on the quantitative EEG long-term effects of transcranial magnetic stimulation interlaced with cognitive training is required to confirm the authors' data.

Tolerability and efficacy of perampanel in children with refractory epilepsy.

AIM: There are few reports on the tolerability and efficacy of perampanel, a new antiepileptic drug with a novel mechanism of action, in children and adolescents. We aimed to describe our experience with perampanel add-on and mono-therapy in children with refractory epilepsy. METHOD: Computerized medical records of children treated with perampanel in the paediatric neurology clinic from December 2012 to October 2015 were reviewed. RESULTS: Twenty-four children treated with perampanel (15 females, 9 males) aged 1 year 6 months to 17 years (mean 10y, standard deviation [SD] 4y 5mo) were identified. Adverse events were more common in children aged 12 years or older (89%) compared to younger children (53%), and were mainly behavioural. Ten (42%) children had 50 per cent or higher seizure reduction, two (8%) children had 33 per cent seizure reduction, and seizures were less severe in one (4%) child. Perampanel was discontinued in 13 (54%) children mostly due to adverse events. The mean duration of follow-up in the remaining 11 children was 8.1 months (SD 5.2) (range 1.3-17mo). INTERPRETATION: Perampanel is associated with a relatively high rate of behavioural adverse events mostly in adolescents with refractory epilepsy.

How valuable is inpatient electroencephalogram for medical decision-making?

BACKGROUND: The electroencephalogram (EEG) can support the diagnosis of epilepsy, diagnose nonconvulsive status epilepticus and aid in the classification of epileptic seizures. Its contribution to the diagnosis of other medical conditions or to decision-making in other clinical situations was not established. Practically, EEG laboratories frequently encounter EEG referrals that are not based on current recommendations. OBJECTIVES: To assess the value of inpatient EEG in medical decision-making. METHODS: We retrospectively reviewed the inpatient computerized medical information management system and the EEG laboratory computerized database for all adult inpatient standard, sleep-deprived and bedside EEGs performed during a one-year period. Change in diagnosis and/or treatment and the clinical justification for ordering an EEG recording were determined. RESULTS: The study group included 584 patients, 313 (54%) men, aged 55·5 ± 20·8 years (range 18-95 years). The EEG was clinically justified in 372 (63·7%) and led to change in diagnosis and/or treatment in 47 (8%) patients. These patients were significantly more likely to be admitted to the neurology department (P = 0·033), have an admission and discharge diagnosis of seizure or epilepsy (P = 0·0001), have a clinically justified EEG (P = 0·0001) and have an EEG recording with electrographic seizures (P = 0·0001), interictal epileptiform discharges (P = 0·0001) and background abnormalities (P = 0·003). CONCLUSIONS: Inpatient EEG can mostly contribute to diagnosis and treatment in patients with a seizure or epilepsy. An informed use of the EEG can increase its yield and reduce the number of unnecessary referrals, thus shortening waiting time and enabling earlier diagnosis and treatment in yet undiagnosed patients.

Postural stability in patients with different types of head and neck trauma in comparison to healthy subjects.

OBJECTIVE: Dizziness is a common complaint in patients following mild head or neck trauma, but neurological signs are usually rare or absent. The aim of the study was to compare postural control in patients with different types of head and neck trauma to healthy subjects. METHODS: Balance function was evaluated by computerized dynamic platform posturography (CDPP) in 57 dizzy patients with whiplash injury (n = 11), mild head trauma without loss of consciousness (HTNLC) (n = 23), whiplash injury and mild head trauma without loss of consciousness (WHTNLC) (n = 12) and mild head trauma with loss of consciousness (n = 11) and in 14 healthy subjects. RESULTS: Compared to healthy subjects and after adjustment for inter-group age differences, sway index (SI) was significantly higher in patients with WHTNLC in three of the tests. There were no significant differences within the patient group according to type of injury. When time following the injury was considered, the SI was non-significantly higher within the first week after trauma compared to other time intervals. CONCLUSION: The severity of the postural abnormality in patients with head and/or neck trauma is not uniform and is influenced by the type of trauma.

Genetic risk factors for antiepileptic drug-induced hypersensitivity reactions in Israeli populations.

The human leukocyte antigen (HLA) alleles B*15:02 and A*31:01 have been identified as predictive markers of adverse cutaneous effects of carbamazepine and phenytoin in Asian and North European populations, respectively. Our aim was to estimate the distribution of these alleles in Jewish and Arab populations in Israel. The HLA-B*15:02 and HLA-A*31:01 carrier rate was estimated based on data from the Hadassah Bone Marrow Registry. Data on Stevens-Johnson syndrome (SJS)- and toxic epidermal necrolysis (TEN)-related hospitalizations were obtained from the Israeli Ministry of Health (MOH) registries and from four Israeli medical centers. Of 83,705 Jewish and Arab-Muslim donors, 81 individuals of known origin carried the HLA-B*15:02. Among them, 66 were Jews of India-Cochin descent. Of the Cochin Jewish donors, 12.7% were B*15:02 carriers. HLA-A*31:01 carrier incidence among Arab and Jewish Israeli populations (3.5% and 2.2%, respectively) was within the range reported in other countries. We did not identify SJS- or TEN-related hospitalizations of Jews of Indian descent. Yet, this population should be considered at greater risk for antiepileptic drug-induced SJS and TEN. Until further data on actual risk are available, such patients should be typed for HLA-B before treatment with carbamazepine or phenytoin.

Posturography in MS patients treated with high dose methylprednisolone.

OBJECTIVES: To evaluate the sensitivity of the balance sway index (SI) to drug-induced functional changes during acute relapse in patients with MS. METHODS: Dynamic posturography was used to derive the SI in 11 healthy subjects and 13 MS patients before and after intravenous high dose methylprednisolone (HDMP). RESULTS: In both groups, SI was lower in the least demanding task and increased with test complexity. Compared to the healthy group, patients were distinguished by a higher SI both prior to and following administration of HDMP (p < 0.008). However, the effect of the drug on patients' SI was unremarkable. Total Expanded Disability Status Scale score was lower after treatment compared to pre-treatment values (p < 0.001), with significantly lower mean score recorded in patients with pyramidal and cerebellar abnormalities (p = 0.017 and p = 0.011, respectively). DISCUSSION: The SI measure of dynamic posturography is not sensitive to short-term HDMP-induced functional changes during acute relapse in patients with MS. Further studies are needed to evaluate modified balance protocols and the possible long-term treatment effects of HDMP on SI.

Feasibility of sleep-deprived EEG in children.

BACKGROUND: Non-sedated EEG recording in children can be technically challenging, particularly when behavioral disorders are present. We aimed to assess the feasibility and the efficacy of non-sedated sleep-deprived EEG in children with behavioral disorders and in young children. METHODS: We retrospectively reviewed the EEG recordings and computerized medical records of all pediatric inpatients at least 2-month-old that had a sleep-deprived EEG during a 5-year period between 2009 and 2014. RESULTS: We present the data of 261 children, 142 (54%) boys, mean age 7.9 ± 4.9 years, 67 (26%) aged 0.5-4 years. Behavioral disorders were reported in 38 (15%) of the patients. Mean recording duration was 50.8 ± 12.5 min, and mean sleep duration- 31.8 ± 15.2 min. Thirty-seven (14%) patients slept less than 15 min during the EEG, including 19 (7%) patients with no sleep during the recording. Sleep duration and the presence of interictal epileptiform discharges did not significantly differ between children with/without behavioral disorders and in those younger/older than 4 years. Patients that did not fall asleep during the EEG did not differ from the others regarding presence of behavioral disorders or age. CONCLUSIONS: These results suggest that non-sedated sleep-deprived EEG is feasible in young children and in those with behavioral disorders. Further studies are needed in order to better characterize the etiologies of sleepless pediatric sleep-deprived EEG recordings.

Correlation between efficacy of levetiracetam and serum levels among children with refractory epilepsy.

BACKGROUND: Levetiracetam is used as adjunctive therapy in various types of seizures. Studies evaluating the effect of levetiracetam on children with refractory epilepsy are scarce. The aim of this study was to evaluate the correlation between serum concentration of levetiracetam and either efficacy or tolerability in children with refractory epilepsy, and to determine the value of levetiracetam blood level monitoring. METHODS: Medical records of 50 children with refractory epilepsy treated with levetiracetam and regularly followed at Assaf Harofeh Medical Center were retrospectively reviewed. Trough serum levetiracetam concentration was determined using high-performance liquid chromatography and correlated with the administered dose and clinical report. RESULTS: No correlation between levetiracetam serum levels and clinical efficacy, tolerability or administered dosage was found. The average dose of levetiracetam was 43.7 ± 20.0 (range 14-100) mg/kg/day and the average serum concentration was 16.0 ± 9.5 (range 2.5-38.5) µg/mL. Forty-five patients (95%) had more than a 50% reduction of seizure frequency, with 22 (44%) patients becoming seizure-free for at least 6 months. Adverse events related to levetiracetam were reported in 15 (30%) patients. No correlation between serum concentrations and adverse events was found. These results were not affected by gender, age, type of seizure, and other drugs. CONCLUSIONS: Determination of serum concentration is not needed in all children treated with levetiracetam. Serum concentrations may be valuable either in patients with refractory epilepsy for compliance evaluation or in patients with satisfactory control of seizures for determination of their therapeutic baseline.

Seizure occurrence during pediatric short-term EEG.

AIM: To identify the patients who are more likely to experience a seizure during short-term EEG recording. METHODS: We retrospectively reviewed the EEG recordings and medical records of 294 patients, who were admitted to the Pediatric Departments in Assaf Harofeh Medical Center, and referred for a short-term EEG during a 5-years period following a seizure. RESULTS: Fifteen (5.1%) patients had seizures during short-term EEG. The likelihood of seizure occurrence was increased by history of seizures (odds ratio 11.86, 95% confidence interval 2.54-55.37), abnormal neurological examination (odds ratio 3.33, 95% confidence interval 1.05-10.55), and the presence of interictal epileptiform discharges (odds ratio 10.07, 95% confidence interval 1.26-80.42). Treatment with antiepileptic drugs and mental retardation were significantly more common among patients with seizures. CONCLUSIONS: Children with a higher likelihood of a seizure during short-term EEG can be identified using data mainly obtained by history and neurological examination.

Efficacy and safety of felbamate in children with refractory epilepsy.

BACKGROUND: Despite the introduction of multiple new antiepileptic drugs in the past two decades, many patients with epilepsy continue to experience uncontrolled seizures or significant side effects. AIM: To present our experience with felbamate therapy in children with drug-resistant epilepsy. METHODS: We retrospectively reviewed the medical charts and video-EEG recordings of all patients receiving felbamate until May 2012. Efficacy was determined according to seizure frequency during the week prior to treatment initiation and the week after the maximal dosage of felbamate was reached. RESULTS: Fifty patients (34 boys) aged 4 months to 17 years (mean--5.5 years) were identified. Nearly third of the patients had Lennox-Gastaut syndrome. Mean epilepsy duration was 3.4 years (range--1 month to 13 years). The mean number of previous antiepileptic drugs was 7.5. The mean duration of follow-up was 1.1 years. Seizure frequency decreased by at least 50% in 29 (58%) patients. Side effects were reported in 22 (44%) patients, none of them included aplastic anemia or liver failure. In the responder group, the maximal dose of felbamate was lower and the patients were older compared to non-responders. CONCLUSIONS: Despite current recommendations, felbamate is initiated following multiple AEDs. Based on its efficacy and safety data, earlier initiation of felbamate is recommended in children with refractory epilepsy.

[Epilepsy in pregnancy].

Most women with epilepsy will need to continue antiepileptic drugs prior to and during pregnancy. Pre-conception counseling should be available to all wormen with epilepsy who are considering pregnancy, and should address obstetrical complications, change in seizure frequency, and adverse pregnancy outcome. Supplementation with folic acid. 0.4-5 mg/day, is recommended for all women with epilepsy of childbearing potential, especially 3 months prior to conception and throughout the first trimester. It is advisable to obtain serum drug concentrations before pregnancy, when seizure control is optimal, in order to establish a baseline. Serum concentration should be performed each trimester among patients with good seizure control, and monthly in patients with complicated epilepsy, breakthrough seizures, significant side effects, and those treated with lamotrigine or oxcarbazepine. The incidence of major congenital malformations in offspring of women treated with antiepileptic drugs has ranged from 4 to 10%, corresponding to a two-fold increase from the expected incidence in the general population. Malformation rates are higher with valproate, lower with carbamazepine and lamotrigine, and dose-effect relationship has been shown for teratogenicity especially with valproate. An expert morphological assessment, targeted at the neural axis, heart and face, should be performed at 11-13 weeks and 18-22 weeks. There is generally no contraindication to breast feeding among mothers with epilepsy, but further studies are needed to establish the safety of newer antiepileptic drugs.