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Objective: To update the 2004 American Academy of Neurology (AAN) guideline for treating new-onset focal or generalized epilepsy (GE) with second- and third-generation antiepileptic drugs (AEDs). Methods: The 2004 AAN criteria was used to systematically review literature (January 2003 to November 2015), classify pertinent studies according to the therapeutic rating scheme, and link recommendations to evidence strength. Results: Several second-generation AEDs are effective for new-onset focal epilepsy. Data are lacking on efficacy in new-onset generalized tonic–clonic seizures, juvenile myoclonic epilepsy, or juvenile absence epilepsy, and on efficacy of third-generation AEDs in new-onset epilepsy. Recommendations: Lamotrigine (LTG) should (Level B) and levetiracetam (LEV) and zonisamide (ZNS) may (Level C) be considered in decreasing seizure frequency in adults with new-onset focal epilepsy. LTG should (Level B) and gabapentin (GBP) may (Level C) be considered in decreasing seizure frequency in patients ≥60 years with new-onset focal epilepsy. Unless there are compelling adverse-effect–related concerns, ethosuximide (ETS) or valproic acid (VPA) should be considered before LTG to decrease seizure frequency in treating absence seizures in childhood absence epilepsy (Level B). No high-quality studies suggest clobazam, eslicarbazepine, ezogabine, felbamate, GBP, lacosamide, LEV, LTG, oxcarbazepine, perampanel, pregabalin, rufinamide, tiagabine, topiramate, vigabatrin, or ZNS is effective in treating new-onset epilepsy because no high-quality studies exist in adults of various ages. A recent FDA strategy allows extrapolation of efficacy across populations; therefore, for focal epilepsy, eslicarbazepine and lacosamide (oral only for pediatric use) as add-on or monotherapy in persons ≥4 years old and perampanel as monotherapy received FDA approval.

Objective: To update the 2004 American Academy of Neurology (AAN) guideline for managing treatment-resistant (TR) epilepsy with second- and third-generation antiepileptic drugs (AEDs). Methods: 2004 criteria were used to systematically review literature (January 2003 to November 2015), classify pertinent studies according to the therapeutic rating scheme, and link recommendations to evidence strength. Results: Forty-two articles were included. Recommendations: The following are established as effective to reduce seizure frequency (Level A): immediate-release pregabalin and perampanel for TR adult focal epilepsy (TRAFE); vigabatrin for TRAFE (not first-line treatment; rufinamide for Lennox–Gastuat syndrome (LGS) (add-on therapy). The following should be considered to decrease seizure frequency (Level B): lacosamide, eslicarbazepine, and extended-release topiramate for TRAFE (ezogabine production discontinued); immediate- and extended-release lamotrigine for generalized epilepsy with TR generalized tonic–clonic (GTC) seizures in adults; levetiracetam (add-on therapy) for TR childhood focal epilepsy (TRCFE) (1 month to 16 years), TR GTC seizures, and TR juvenile myoclonic epilepsy; clobazam for LGS (add-on therapy); zonisamide for TRCFE (6–17 years); oxcarbazepine for TRCFE (1 month to 4 years). The text presents Level C recommendations. AED selection depends on seizure/syndrome type, patient age, concomitant medications, and AED tolerability, safety, and efficacy. This evidence-based assessment informs AED prescription guidelines for TR epilepsy and indicates seizure types and syndromes needing more evidence. A recent FDA strategy allows extrapolation of efficacy across populations; therefore, for focal epilepsy, eslicarbazepine and lacosamide (oral only for pediatric use) as add-on or monotherapy in persons ≥4 years of age and perampanel as monotherapy received FDA approval.

ObjectiveTo update the 2004 American Academy of Neurology (AAN) guideline for treating new-onset focal or generalized epilepsy with second- and third-generation antiepileptic drugs (AEDs).MethodsThe 2004 AAN criteria were used to systematically review literature (January 2003–November 2015), classify pertinent studies according to the therapeutic rating scheme, and link recommendations to evidence strength.ResultsSeveral second-generation AEDs are effective for new-onset focal epilepsy. Data are lacking on efficacy in new-onset generalized tonic-clonic seizures, juvenile myoclonic epilepsy, or juvenile absence epilepsy, and on efficacy of third-generation AEDs in new-onset epilepsy.RecommendationsLamotrigine (LTG) should (Level B) and levetiracetam (LEV) and zonisamide (ZNS) may (Level C) be considered in decreasing seizure frequency in adults with new-onset focal epilepsy. LTG should (Level B) and gabapentin (GBP) may (Level C) be considered in decreasing seizure frequency in patients ≥60 years of age with new-onset focal epilepsy. Unless there are compelling adverse effect–related concerns, ethosuximide or valproic acid should be considered before LTG to decrease seizure frequency in treating absence seizures in childhood absence epilepsy (level B). No high-quality studies suggest clobazam, eslicarbazepine, ezogabine, felbamate, GBP, lacosamide, LEV, LTG, oxcarbazepine, perampanel, pregabalin, rufinamide, tiagabine, topiramate, vigabatrin, or ZNS is effective in treating new-onset epilepsy because no high-quality studies exist in adults of various ages. A recent Food and Drug Administration (FDA) strategy allows extrapolation of efficacy across populations; therefore, for focal epilepsy, eslicarbazepine and lacosamide (oral only for pediatric use) as add-on or monotherapy in persons ≥4 years old and perampanel as monotherapy received FDA approval.

Background Clobazam has been used in clinical practice as an adjunctive treatment for diverse seizure types and epilepsy syndromes. We evaluated the efficacy and safety of clobazam in a large sample of patients with refractory epilepsy at a tertiary pediatric center. Methods We retrospectively reviewed patients treated with clobazam between January 2001 and July 2013 who had a follow-up visit at least one month after starting clobazam. Response was defined as ≥50% reduction in seizure frequency compared with baseline seizure frequency during the 3 months before the introduction of clobazam. We examined the relationship between dose range and response rate. Results Four-hundred twenty-five patients were prescribed clobazam, of whom 300 (median age 9.1 years, interquartile range 4.7-13.3 years) had follow-up data greater than 1 month. Median follow-up was 5 months (interquartile range 3-11 months). Response to treatment with clobazam was observed in 203 of 300 (67.7%) patients, of whom 84 (28%) became seizure-free. The median starting dose was 0.2 (interquartile range 0.13-0.33) mg/kg/day with a target dose of 0.48 (0.26-0.80) mg/kg/day. Twenty-seven (9%) patients discontinued clobazam, 16 (59.3%) because adverse effects, 10 (37%) because of a lack of efficacy, and one (3.7%) because of a combination of adverse effects and lack of efficacy. The most common adverse effects were tiredness in 44 of 300 (14.6%) and mood or behavioral changes in 23 (7.7%). Conclusions Clobazam is a well-tolerated antiepileptic drug with good response rates in pediatric patients with refractory epilepsy.

BACKGROUND AND PURPOSE: Determination of hemispheric language dominance is critical for planning epilepsy surgery. We assess the usefulness of spatiotemporal source analysis of magnetoencephalography for determining language laterality. MATERIALS AND METHODS: Thirty-five patients with epilepsy were studied. The patients performed a semantic word-processing task during MEG recording. Epochs containing language-related neuromagnetic activity were averaged after preprocessing. The averaged data between 250 and 550 ms after stimulus were analyzed by using dynamic statistical parametric mapping. ROIs were obtained in the opercular and triangular parts of the inferior frontal gyrus, superior temporal gyrus, and supramarginal gyrus in both hemispheres. We calculated laterality indices according to 1) dSPM-amplitude method, based on the amplitude of activation in the ROIs, and 2) dSPM-counting method, based on the number of unit dipoles with activation over a threshold in the ROIs. The threshold was determined as half of the maximum value in all ROIs for each patient. A LI ≥0.10 or ≤−0.10 was considered left- or right-hemisphere dominance, respectively; a LI between −0.10 and 0.10 was considered bilateral. All patients underwent an intracarotid amobarbital procedure as part of presurgical evaluation. RESULTS: The dSPM-counting method demonstrated laterality consistent with the IAP in 32 of 35 patients (91.4%), the remaining 3 (8.6%) demonstrated bilateral language representation, whereas the dSPM-amplitude method showed 18 (51.4%) concordant and 17 (48.6%) bilateral. No laterality opposite to the IAP was found. CONCLUSIONS: Spatiotemporal mapping of language lateralization with the dSPM-counting method may reduce the necessity for an IAP in as many as 90% of patients.

We report our pediatric experience with lacosamide, a new antiepileptic drug, approved by the US Food and Drug Administration as adjunctive therapy in focal epilepsy in patients more than 17 years old. We retrospectively reviewed charts for lacosamide use and seizure frequency outcome in patients with focal epilepsy (Wilcoxon signed rank test). Sixteen patients (7 boys) were identified (median dose 275 mg daily, 4.7 mg/kg daily; mean age 14.9 years, range 8-21 years). Patients were receiving a median of 2 antiepileptic drugs (interquartile range [IQR] 1.7-3) in addition to having undergone previous epilepsy surgery (n=3), vagus nerve stimulation (n=9), and ketogenic diet (n=3). Causes included structural (encephalomalacia and diffuse encephalitis, 1 each; stroke in 2) and genetic abnormalities (Aarskog and Rett syndromes, 1 each) or cause not known (n=10). Median seizure frequency at baseline was 57 per month (IQR 7-75), and after a median follow-up of 4 months (range 1-13 months) of receiving lacosamide, it was 12.5 per month (IQR 3-75), (P

We describe our experience with intraoperative electroencephalography in moyamoya surgery, a method to monitor for ischemic changes during the procedure and to minimize the risk of intraoperative and perioperative stroke. Case records and intraoperative electroencephalography recordings of all patients (n = 220) treated with surgical revascularization for moyamoya (pial synangiosis) performed for 14 years (1994-2008) were reviewed. Electroencephalographic slowing occurred in 100 cases (45.5%), and was persistent in nine cases (9%). Slowing coincided with specific operative manipulations, most commonly while suturing the donor vessel to the pia, and during closure of the craniotomy. Slowing generally occurred bilaterally, independently of the side of intervention. The presence, length, and severity of slowing were not predictive of perioperative ischemic events. We present additional data on intraoperative electroencephalography with a modified montage to accommodate the craniotomy. Although not predictive of perioperative ischemic events in this series, electroencephalographic changes were correlated with specific operative interventions, and revealed global responses to unilateral manipulation. These findings suggest that prospective analyses of this technique may elucidate additional methods of predicting (and possibly preventing) perioperative ischemic events.

Rufinamide is a new antiepileptic drug recently approved as adjunctive treatment for generalized seizures in Lennox-Gastaut syndrome. We undertook a retrospective analysis of 77 patients with refractory epilepsy and receiving rufinamide to evaluate the drug's efficacy, tolerability, safety, and dosing schedules. It appeared efficacious in diverse epilepsy syndromes, with the highest responder rate in focal cryptogenic epilepsies (81.1% of patients with >50% response rate), and in diverse seizure types, with the highest responder rate in tonic/atonic and partial seizures (48.6% and 46.7% of patients with >50% response rate, respectively). Rufinamide was well tolerated: only 13% of patients developed side effects necessitating drug withdrawal. These findings suggest that rufinamide may possess good efficacy and tolerability, and that its efficacy may extend to epilepsy syndromes beyond Lennox-Gastaut, including both partial and generalized epilepsy syndromes.

The newer antiepileptic drugs (AEDs) provide more therapeutic options and overall improved safety and tolerability for patients. To provide the best care, physicians must be familiar with the latest tolerability and safety data. This is particularly true in children, given there are relatively fewer studies examining the effects of AEDs in children compared with adults. Since we now have significant paediatric literature on each of these agents, we provide a comprehensive and current literature review of the newer AEDs, focusing on safety and tolerability data in children and adolescents. Because the safety profiles in children differ from those in adults, familiarity with this literature is important for child neurologists and other paediatric caregivers. We have organized the data by organ system for each AED for easier reference.

PRO: In the past decade, genotyping has started to help the neurologic practitioner treat patients with three types of epilepsy causing mutations, namely (1) SCN1A, a sodium channel gene mutated in Dravet's sporadic severe myoclonic epilepsy of infancy (SMEI and SMEB); (2) laforin (dual specificity protein phosphatase) and malin (ubiquitin E3 ligase) in Lafora progressive myoclonic epilepsy (PME); and (3) cystatin B in Unverricht-Lundborg type of PME. Laforin, malin, and cystatin B are non-ion channel gene mutations that cause PME. Genotyping ensures accurate diagnosis, helps treatment and genetic counseling, psychological and social help for patients and families, and directs families to organizations devoted to finding cures for specific epilepsy diseases. In SCN1A and cystatin B mutations, treatment with sodium channel blockers (phenytoin, carbamazepine, oxcarbazepine, lamotrigine) should be avoided. Because of early and correct diagnosis by genotyping of SCN1A mutations, the avoidance of sodium channel blockers, and aggressive treatment of prolonged convulsive status, there is hope that Dravet's syndrome may not be as severe as observed in all past reports. Genotyping also identifies nonsense mutations in Lafora PME. Nonsense mutations can be corrected by premature stop codon readthrough drugs such as gentamicin. The community practitioner together with epilepsy specialists in PME can work together and acquire gentamicin (Barton-Davis et al., 1999) for "compassionate use" in Lafora PME, a generalized lysosome multiorgan storage disorder that is invariably fatal. In Unverricht-Lundborg PME, new cohorts with genotyped cystatin B mutations have led to the chronic use of antioxidant N-acetylcysteine and combination valproate clobazam or clonazepam plus antimyoclonic drugs topiramate, zonisamide, piracetam, levetiracetam, or brivaracetam. These cohorts have minimal ataxia and no dementia, questioning whether the syndrome is truly progressive. In conclusion, not only is genotyping a prerequisite in the diagnosis of Dravet's syndrome and the progressive myoclonus epilepsies, but it also helps us choose the correct antiepileptic drugs to treat seizures in Dravet's syndrome and Unverricht-Lundborg PME. Genotyping also portends a brighter future, helping us to reassess the true course, severity, and progressive nature of Dravet's syndrome and Unverricht-Lundborg PME and helping us craft a future curative treatment for Dravet's syndrome and Lafora disease. Without the genotyping diagnosis of epilepsy causing mutations we are stuck with imprecise diagnosis and symptomatic treatment of seizures. CON: Genotyping of epilepsy may help to better understand the genetics of epilepsy, to establish an etiology in a patient with epilepsy, to provide genetic counseling, and to confirm a clinical diagnosis. However, critical analysis reveals that genotyping does not contribute to an improved treatment for the patients. In order to improve treatment, genotyping would have to (1) improve our ability to select the drug of choice for a given epilepsy or epileptic syndrome; (2) improve our ability to predict the individual risk of adverse reactions to certain drugs; (3) improve our ability to avoid unnecessary treatments or treatments that could aggravate seizures. Many example illustrate the lack of impact of genetic information on the treatment outcome: we do not treat Dravet syndrome more successfully since SCN1A testing became available; we do not treat Lafora disease more successfully since testing for laforin and malin became available; we do not need to know the genetic nature of Unverricht-Lundborg disease or test for the cystatin B mutation in order to select or avoid certain drugs; we do not treat Rett syndrome more successfully since MECP2 testing became available; we do not treat JME more successfully since we know its genetic origin; we do not treat autosomal dominant nocturnal frontal lobe epilepsy more successfully since we know its genetic origin and can test for its mutation. The clinical characteristics as well as the response to treatment of these epilepsy syndromes have been well established before genotyping became available. It can not be argued that genotyping is necessary for establishing a diagnosis or ensure accurate diagnosis. Since not all individuals with given syndromes have been shown to have the corresponding mutation, the clinical diagnosis must have been based on well-established clinical criteria. In addition, the presence or absence of the mutation in a given patient has never been shown to specifically predict the response to any form of treatment, positive or negative. Finally, the appropriate psychological and social help in a given patient will not depend on the identification of a mutation. This does not leave any role for genotyping in epilepsy for the sole reason of improving treatment of the patient. Claiming that the result of genotyping predicts optimal treatment in certain epilepsies is equivalent to stating that genotyping for diabetes has become available and that, based on this breakthrough, insulin can now be selected as the treatment of choice in those who test positive.

Although no randomized studies have demonstrated a positive impact of therapeutic drug monitoring (TDM) on clinical outcome in epilepsy, evidence from nonrandomized studies and everyday clinical experience does indicate that measuring serum concentrations of old and new generation antiepileptic drugs (AEDs) can have a valuable role in guiding patient management provided that concentrations are measured with a clear indication and are interpreted critically, taking into account the whole clinical context. Situations in which AED measurements are most likely to be of benefit include (1) when a person has attained the desired clinical outcome, to establish an individual therapeutic concentration which can be used at subsequent times to assess potential causes for a change in drug response; (2) as an aid in the diagnosis of clinical toxicity; (3) to assess compliance, particularly in patients with uncontrolled seizures or breakthrough seizures; (4) to guide dosage adjustment in situations associated with increased pharmacokinetic variability (e.g., children, the elderly, patients with associated diseases, drug formulation changes); (5) when a potentially important pharmacokinetic change is anticipated (e.g., in pregnancy, or when an interacting drug is added or removed); (6) to guide dose adjustments for AEDs with dose-dependent pharmacokinetics, particularly phenytoin.

Epilepsy is one of the most common neurological disorders of childhood, and antiepileptic drugs represent the main component of its treatment. The current emphasis in epilepsy treatment is to improve quality of life, not only by suppressing seizure, but also by minimizing the side effects of medications. The last 15 years have been characterized by significant advances in the development of new agents that have helped us to get closer to this goal. Knowledge of the essential properties, key indications and interactions of each antiepileptic drug will help to optimize efficacy and reduce adverse reactions. Age is also a determining factor of the epilepsy phenotype and its treatment. This review addresses the principles of pediatric epilepsy treatment, summarizes the profile of each of the commonly used antiepileptic drugs, and provides a treatment paradigm for particular seizures and epilepsy syndromes of childhood.

Interictal fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) is a component of the presurgical evaluation of patients with medically intractable epilepsy, including patients with malformations of cortical development. The authors describe 3 cases of focal cortical malformations that displayed asymmetrically higher uptake on FDG-PET performed in the interictal state in patients undergoing evaluation for possible focal resection for refractory localization-related epilepsy. The evaluation included routine and prolonged video electroencephalography (EEG), magnetic resonance imaging (MRI), interictal FDG-PET with concurrent EEG, and single-photon emission computed tomography (SPECT). All 3 patients had focal cortical malformations on MRI corresponding to regions of asymmetrically higher uptake on FDG-PET. EEG confirmed that the FDG-PET studies were performed in the interictal state. The lesions included a large region of subcortical heterotopia in the right frontal lobe, a left temporal lobe dysplasia, and a region of subcortical heterotopia in the right occipital lobe. In both patients with subcortical heterotopia, there were other focal regions of cortical malformation that were not associated with abnormal or asymmetric uptake on FDG-PET. Previous reports describe decreased uptake on interictal PET in most cases of focal cortical malformations. Normal to increased uptake has been reported with band heterotopia. The authors demonstrate that other types of focal malformations of cortical development, including focal subcortical heterotopia and lobar dysplasia, can be associated with asymmetrically higher uptake on interictal FDG-PET.

To evaluate the sensitivity of a simultaneous whole-head 306-channel magnetoencephalography (MEG)/70-electrode EEG recording to detect interictal epileptiform activity (IED) in a prospective, consecutive cohort of patients with medically refractory epilepsy that were considered candidates for epilepsy surgery.Seventy patients were prospectively evaluated by simultaneously recorded MEG/EEG. All patients were surgical candidates or were considered for invasive EEG monitoring and had undergone an extensive presurgical evaluation at a tertiary epilepsy center. MEG and EEG raw traces were analysed individually by two independent reviewers.MEG data could not be evaluated due to excessive magnetic artefacts in three patients (4%). In the remaining 67 patients, the overall sensitivity to detect IED was 72% (48/67 patients) for MEG and 61% for EEG (41/67 patients) analysing the raw data. In 13% (9/67 patients), MEG-only IED were recorded, whereas in 3% (2/67 patients) EEG-only IED were recorded. The combined sensitivity was 75% (50/67 patients).Three hundred and six-channel MEG has a similarly high sensitivity to record IED as EEG and appears to be complementary. In one-third of the EEG-negative patients, MEG can be expected to record IED, especially in the case of lateral neocortical epilepsy and/or cortical dysplasia.

OBJECTIVES. The objectives of this study were to delineate the etiologic profile and neurodevelopmental outcome of neonatal seizures in the current era of neonatal intensive care and to identify predictors of neurodevelopmental outcome in survivors.METHODS. Eighty-nine term infants with clinical neonatal seizures underwent neurologic examination, electroencephalography (EEG), neuroimaging, and extensive diagnostic tests in the newborn period. After discharge, all infants underwent regular neurologic evaluations and, at 12 to 18 months, formal neurodevelopmental testing. We tested the prognostic value of seizure etiology, neurologic examination, EEG, and neuroimaging.RESULTS. Etiology was found in 77 infants. Global cerebral hypoxia-ischemia, focal cerebral hypoxia-ischemia, and intracranial hemorrhage were most common. Neonatal mortality was 7%; 28% of the survivors had poor long-term outcome. Association between seizure etiology and outcome was strong, with cerebral dysgenesis and global hypoxia-ischemia associated with poor outcome. Normal neonatal period/early infancy neurologic examination was associated with uniformly favorable outcome at 12 to 18 months; abnormal examination lacked specificity. Normal/mildly abnormal neonatal EEG had favorable outcome, particularly if neonatal neuroimaging was normal. Moderate/severely abnormal EEG, and multifocal/diffuse cortical or primarily deep gray matter lesions, had a worse outcome.CONCLUSIONS. Mortality associated with neonatal seizures has declined although long-term neurodevelopmental morbidity remains unchanged. Seizure etiology and background EEG patterns remain powerful prognostic factors. Diagnostic advances have changed the etiologic distribution for neonatal seizures and improved accuracy of outcome prediction. Global cerebral hypoxia-ischemia, the most common etiology, is responsible for the large majority of infants with poor long-term outcome.

Antiepileptic drugs may paradoxically worsen seizure frequency or induce new seizure types in some patients with epilepsy. The mechanisms of seizure aggravation by antiepileptic drugs are mostly unknown and may be related to specific pharmacodynamic properties of these drugs. This article provides a review of the various clinical circumstances of seizure exacerbation and aggravation of epilepsy by antiepileptic drugs as well as a discussion of possible mechanisms underlying the occasional paradoxical effect of these drugs. Antiepileptic drug-induced seizure aggravation can occur virtually with all antiepileptic medications. Drugs that aggravate seizures are more likely to have only one or two mechanisms of action, either enhanced gamma-aminobutyric acid-mediated transmission or blockade of voltage-gated sodium channels. Antiepileptic drug-induced seizure exacerbation should be considered and the accuracy of diagnosis of the seizure type should be questioned whenever there is seizure worsening or the appearance of new seizure types after the introduction of any antiepileptic medication.

Antiepileptic drugs are often used for the treatment of both epilepsy and a wide range of behavioral and psychiatric disorders. The treatment of patients with epilepsy has been the proving ground for antiepileptic drugs, not only with respect to their efficacy in the treatment of seizures but also for clarifying their dose-related and idiosyncratic adverse events. This information has been useful in treating patients with behavioral and psychiatric disorders. Indeed, the number of prescriptions written for many antiepileptic drugs for nonepileptic uses far exceeds those written for the same drugs for epilepsy. Because patients with chronic epilepsy have a higher incidence of axis I psychiatric disorders, physicians can choose an antiepileptic drug to treat both the epilepsy and psychiatric comorbidity in selected patients. Guided by the principles of evidence-based medicine as outlined by the American Academy of Neurology and the American Academy of Pediatrics, this article reviews the application of antiepileptic drugs for epilepsy and behavioral and psychiatric disorders in children. (J Child Neurol 2004;19(Suppl 1):S39-S48).

Objective: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) (gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, and zonisamide—reviewed in the order in which these agents received approval by the US Food and Drug Administration) in the treatment of children and adults with newly diagnosed partial and generalized epilepsies.Methods: A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane library for relevant articles from 1987 until September 2002, with selected manual searches up until 2003.Results: There is evidence either from comparative or dose-controlled trials that gabapentin, lamotrigine, topiramate, and oxcarbazepine have efficacy as monotherapy in newly diagnosed adolescents and adults with either partial or mixed seizure disorders. There is also evidence that lamotrigine is effective for newly diagnosed absence seizures in children. Evidence for effectiveness of the new AEDs in newly diagnosed patients with other generalized epilepsy syndromes is lacking.Conclusions: The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with newly diagnosed epilepsy and identify those seizure types and syndromes where more evidence is necessary.

Summary: Purpose: Topiramate (TPM) has been widely used as an adjunctive therapy for treating epilepsy. TPM is reported to have multiple mechanisms of action, including inhibition of carbonic anhydrase, which may result in metabolic acidosis from decreased serum bicarbonate (HCO3-). Methods: Clinical data from 30 children who received TPM as adjunctive therapy for medically refractory epilepsy were reviewed at Children's Hospital, Boston. Serum HCO3-levels were assessed before, during, and after discontinuing TPM (n = 9). When multiple data were available, mean values were used for analysis. Results: Of the 30 patients, 21 had a >10% decrease in HCO3- levels. The mean decrease in HCO3- among the 21 patients was 4.7 mEq/L, and maximum was 10 mEq/L. No clinical symptoms occurred, and HCO3- supplement was not needed, except for one patient who developed tachypnea from worsened acidosis after prolonged status epilepticus during a suspected viral illness. Among the 21 patients, TPM was discontinued in seven children because of a lack of efficacy, and in two because of anorexia. After discontinuing TPM, the serum HCO3- returned to the previous level before starting TPM in all nine. Conclusions: Decreased HCO3- levels occurred in the majority of patients reviewed, usually only to a small to moderate extent, but by 8 and 10 mEq/L in two cases. In patients at risk for acidosis, the decrease in HCO3- may cause significant consequences, such as severe acidosis or renal calculi. Monitoring HCO3- levels before and during TPM therapy may be indicated, especially with conditions that predispose to acidosis.

Purpose This study aimed to evaluate lexical retrieval, presurgery and postsurgery, among children and adolescents who had undergone temporal lobe resection for intractable epilepsy and to compare outcomes in patients whose surgery involved the left temporal lobe or the right temporal lobe. Materials and methods A retrospective chart review identified 36 patients from a major pediatric epilepsy treatment center who had undergone temporal lobe resection (21 underwent left temporal lobe resection; 15 underwent right temporal lobe resection) for intractable epilepsy and who had completed neuropsychological testing that included a measure of confrontation naming (Boston Naming Test, BNT) and verbal fluency (Delis–Kaplan Executive Function System (D-KEFS) Fluency) prior to and after surgery. Linear mixed effects regression models were used to evaluate presurgery and postsurgery changes and to compare the left temporal lobe resection group with the right temporal lobe resection group. Principal results Confrontation naming performance declined after left, but not right, temporal lobe resection (p Major conclusions Left temporal lobe resection for intractable epilepsy is associated with a decline in lexical retrieval. The risk of decline in specific language functions following surgery involving the left temporal lobe should be incorporated in the counseling of patients and families in decision-making with regard to surgery.

Summary Objective Reports of studies evaluating rufinamide as an add-on therapy in children and adolescents with refractory epilepsy are restricted to a few publications. Prospective multicenter studies including children and adults have yielded important information about several types of epilepsies and syndromes. We evaluated the use of rufinamide in a single pediatric center with a large cohort and long-term follow-up period. Methods We retrospectively included patients taking rufinamide from November 2008 to March 2013. Response was defined by a seizure reduction of ≥50% compared to baseline. Results Three hundred patients with a median age of 9.1 years (range 0.4–29.6 years) were reviewed. Median follow-up was 9 months (range 1–37 months). Epilepsy etiology was classified as genetic (23.7%), structural/metabolic (41%), and unknown cause (35.3%). Overall, rufinamide treatment led to a median seizure frequency reduction of 59.2% from responders to baseline. Seizure reduction was greater in patients with genetic etiology compared to structural/metabolic (66.2% vs. 45.5% responders, p = 0.005). Rufinamide was discontinued in 110 (36.7%) of 300 patients: 63 (21%) due to unsatisfactory response, 47 (15.7%) due to side effects, and in 18 (6%) of those due to both. Most common adverse effects were sleepiness, vomiting, mood changes, nausea, and loss of appetite. Median time to loss of efficacy was 11.6 months (range 3–28 months). Significance Rufinamide provides satisfactory seizure reduction as an adjunctive treatment in refractory epilepsy. Results need to be interpreted in the setting of data acquisition, including inherent biases of retrospective studies. Patients with a known genetic etiology may have better responses than patients with structural/metabolic etiology. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

This chapter will review methodology of single photon emission computed tomography (SPECT) and positron emission tomography (PET), radiopharmaceuticals, imaging instrumentation, image fusion, and clinical applications in children. Both SPECT and PET can depict regional cerebral perfusion, glucose metabolism, and other functions and provide images of the location, quantification, and biokinetics of radiopharmaceutical agents. In addition, these techniques can detect rapid changes due to normal brain activity in different functional conditions or those caused by pharmacologic or cognitive stimulation. Improvements in the production and distribution of 18F-FDG and better PET systems have facilitated the widespread use of PET. Advances in imaging systems and data processing in SPECT have resulted in systems that are simpler to operate and that yield 3D images of high functional and anatomic resolution.

Prader-Willi syndrome is a chromosomal disorder caused by absence of expression of the paternal active genes in the 15q11∼q13 chromosome region; it is associated with an increased incidence of epilepsy and narcolepsy. Presented here is the case of a 2.5-year-old boy with Prader-Willi syndrome and a history of neonatal superior sagittal sinus thrombosis with new onset of atonic seizures with electrographic onset from the parasagittal region. It is postulated that microscarring from neonatal venous sinus thrombosis, history of febrile seizures, and Prader-Willi syndrome are factors predisposing him to epilepsy. The importance of video electroencephalography with electromyography electrodes is emphasized for Prader-Willi syndrome patients with drop episodes, to differentiate cataplexy from seizures. This being a novel report of a Prader-Willi syndrome patient with atonic seizures, the literature on seizure semiology among patients with Prader-Willi syndrome is reviewed.

In the treatment of children with epilepsy, the role of topiramate has been expanding gradually. The main factor that has contributed to this trend is the relatively large body of information that has accumulated on the clinical pharmacology of topiramate in children, including its broad-spectrum efficacy, pediatric pharmacokinetics, side-effect profile, and safety. It has also become increasingly apparent with time that topiramate, in contrast to other broad-spectrum antiepileptic drugs used in children, does not seem to be associated with a significant risk of any serious or life-threatening adverse effects. The present review summarizes the available evidence related to the clinical pharmacology of topiramate in children and provides an update on its known mechanisms of action. Finally, available experimental data on the neuroprotective effect of topiramate are reviewed because of their considerable clinical potential in the treatment of children and newborns. (J Child Neurol 2000;15:S27-S30).

A 13-year-old boy with Lennox-Gastaut syndrome characterized by absence, myoclonic, complex-partial, and secondarily generalized tonic-clonic seizures, presents with progressive obtundation and loss of motor and verbal skills over a 2-day period. Initial evaluation revealed therapeutic phenytoin serum concentrations. This article discusses the differential diagnosis and management approach used in this setting, as well as the appropriate interpretation of antiepileptic drug serum concentrations.

Until 1993, six antiepileptic drugs (phenytoin, phenobarbital, primidone, ethosuximide, carbamazepine, and valproate) accounted for the overwhelming majority of prescriptions written for the treatment of epilepsy. Among those, only valproate was truly a broad-spectrum drug, with some or good efficacy against all seizure types. Since 1993, felbamate, gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, zonisamide, and pregabalin were approved in the United States for the treatment of epilepsy. All were initially tested and approved as add-on treatment of partial-onset seizures, with or without secondary generalization. The era that began in 1993 was characterized not only by a new generation of antiepileptic drugs, but also by controlled trials in specific epileptic syndromes and in seizure types other than partial onset. From these trials, a gradually expanding pattern of a broader antiepileptic efficacy spectrum has emerged for several of the newer drugs, although some of them still retain a narrow spectrum, such as gabapentin, tiagabine, oxcarbazepine, and pregabalin (table). View this table: Table Current FDA-approved indications of newer antiepileptic drugs The Lennox-Gastaut syndrome is a generalized epilepsy that is notoriously refractory to treatment. In a trial reported in 1993, felbamate was the first drug ever to be submitted to a controlled trial in this syndrome, and it was found to be superior to placebo, in particular against the most debilitating drop attacks.1 Following this lead, subsequent similar placebo-controlled trials in this syndrome demonstrated the efficacy of lamotrigine2 and then topiramate.3 Another generalized seizure type, absence seizures, was shown in a controlled trial to respond to lamotrigine.4 Generalized tonic-clonic seizures (GTCS) are …

SUMMARY: Distinguishing propagated epileptic activity from primary epileptic foci is of critical importance in presurgical evaluation of patients with medically intractable focal epilepsy. We studied an 11-year-old patient with complex partial epilepsy by using simultaneous magnetoencephalography (MEG) and electroencephalography (EEG). In EEG, bilateral interictal discharges appeared synchronous, whereas MEG source analysis suggested propagation of spikes from the right to the left frontal lobe.

We studied nine cases of focal cortical dysplasia (FCD) by MRI, with surface-rendered 3D reconstructions. One case was also examined using single-voxel proton MR spectroscopy (MRS). The histological features were reviewed and correlated with the MRI findings. The gyri affected by FCD were enlarged and the signal of the cortex was slightly increased on T1-weighted images. The gray-white junction was indistinct. Signal from the subcortical white matter was decreased on T1- and increased on T2-weighted images in most cases. Contrast enhancement was seen in two cases. Proton MRS showed a spectrum identical to that of normal brain.

Summary: Purpose: The standard practice of switching patients to carbamazepine (CBZ) involves initiating a low dose and raising it by small increments until the desired dose is reached, to avoid intolerable adverse effects (AE). In a pilot study, a protocol using single-dose kinetic studies was developed to switch patients to CBZ through rapid-dose increments and to manage concurrent rapid taper of the previous antiepileptic drugs (AEDs) without causing AE. The purpose of this prospective study was (a) to reassess whether a rapid switchover to CBZ could be done with minimal or no AE and without causing an increase in seizures; (b) to determine whether the maintenance dose of CBZ predicted at the time of the singledose kinetic study can yield the desired concentration at steady state (Css); and (c) to determine the degree to which the calculated maintenance dose of CBZ will need to be adjusted after the previous AED has been discontinued for a four-week period. Methods: Twenty-five patients taking phenytoin (PHT) and/ or phenobarbital (PB) andor primidone (PRM) underwent a rapid switchover to CBZ following a 10 mg/kg single-dose kinetic study (day 1) which allowed calculation of a maintenance dose necessary to yield a mean Css of 10.2 (±2.2) mgA. On day 2, patients received a CBZ dose equivalent to 10 mgkg + 200 mg; thereafter, they underwent daily dose increments of 200 mg until the calculated maintenance dose was reached. Dose increments were modified in the case of AE. Concurrent tapering of the previous AED was started as of day 1: PHT by 100 mg/day, while PB and PRM were stopped on day 1: PB was restarted before patients were to be discharged from the hospital if a PB serum concentration above 10 mgA was identified at that time. Pharmacokinetic data and occurrence of AE were compared between the two groups at the time of the single-dose kinetic study, at the completion of the switchover to CBZ, and 4 weeks after discontinuation of the previous AED. Results: All patients completed the switchover to CBZ within a mean time period of 6 days (±2), reaching a mean maintenance dose of 1, 639 mg/day (±370) which yielded a mean CSS of 11.3 (±3.2) mg/l. The maintenance dose had to be lowered by 20.4% (±8.3) in 59% of patients within the four-week period following discontinuation of at least one of the previous AEDs. None of the patients experienced an increase in seizure frequency relative to baseline. Fifteen (60%) patients had no AE; five (20%) experienced AE of mild severity. AE rated as moderately severe (n = 4) or severe (n = 1) occurred in patients with a static encephalopathy (p = 0.02, Fisher's exact test) and among patients 2–55 years (p = 0.017, Fisher's exact test). Conclusions: A rapid switch-over to CBZ from PHT, PB, or PRM can be carried out safely with no, or minimal, AE in young adults, unless they suffer from static encephalopathy.

Lennox-Gastaut syndrome (LGS) is a severe epileptic encephalopathy that shares many features and characteristics of other treatment-resistant childhood epilepsies. Accurate and early diagnosis is essential to both prognosis and overall patient management. However, accurate diagnosis of LGS can be clinically challenging. This article summarizes key characteristics of LGS and areas of overlap with other childhood epilepsies. Drawing upon input from a committee of established LGS experts convened in June 2012 in Chicago, Illinois, the authors highlight key diagnostic tests for making the differential diagnosis and propose a diagnostic scheme for people with suspected LGS.

This chapter covers the main steps involved in the initiation of antiepileptic drug therapy. Aspects covered specifically include the decision whether or not to initiate treatment, the selection process of a drug of first choice for a given patient with a particular seizure type or epilepsy syndrome, and the process of initiating therapy with the selected drug of first choice. Suggested choices of antiepileptic drugs by seizure type or epilepsy syndrome are summarized in a table. In an appendix, these drugs are reviewed individually with regard to their clinical use. The emphasis is on initial dose, dosage escalation, common and serious adverse effects, baseline evaluation, monitoring of therapy, and relevant drug interactions.

✓ Amygdalohippocampectomy (AH) is an accepted surgical option for treatment of medically refractory mesial temporal lobe epilepsy. Operative approaches to the amygdala and hippocampus that previously have been reported include: the sylvian fissure, the superior temporal sulcus, the middle temporal gyrus, and the fusiform gyrus. Regardless of the approach, AH permits not only extirpation of an epileptogenic focus in the amygdala and anterior hippocampus, but interruption of pathways of seizure spread via the entorhinal cortex and the parahippocampal gyrus. The authors report a modification of a surgical technique for AH via the parahippocampal gyrus, in which excision is limited to the anterior hippocampus, amygdala and parahippocampal gyrus while preserving the fusiform gyrus and the rest of the temporal lobe. Because transparahippocampal AH avoids injury to the fusiform gyrus and the lateral temporal lobe, it can be performed without intracarotid sodium amobarbital testing of language dominance and language mapping. Thus the operation would be particularly suitable for pediatric patients in whom intraoperative language mapping before resection is difficult.

For many years, the medical treatment of epilepsy was based on the use of the same few drugs, which were chosen according to the seizure type in a fairly standardized manner. In the recent past, there have been several changes, and more are expected in the near future. Since 1993, three new antiepileptic drugs have been released in the United States, and two more are expected to be released before the end of 1997. Because the full spectrum of efficacy and side effects of these drugs has not yet been established, the present management of epilepsy requires a larger degree of flexibility, and it is necessary to become acquainted with the new drugs and to follow closely new reports on the experience with new drugs. This is particularly true for the management of epilepsy in children, because controlled studies in children tend to be completed later than those in adults and antiepileptic drug use in children is often "off label." The present review of newer antiepileptic drug consists of a brief summary of background information on each drug, followed by a closer analysis of recently published papers. Information on pediatric use is reviewed, when available. The new antiepileptic drugs selected for discussion are gabapentin, lamotrigine, felbamate, vigabatrin, and topiramate.

There is an intricate reciprocal relationship between epilepsy and sleep. The seizure threshold is often affected by changes in the level of arousal; certain seizure types occur predominantly or almost exclusively during sleep or upon awakening; many epileptiform electroencephalogram abnormalities are activated by sleep or sleep depriviation. Inversely, certain epilepsies are often associated with sleep disturbances, and epilepsy can affect sleep patterns and sleep architecture. Also, it may be difficult to differentiate certain nocturnal nonepileptic events from epileptic seizures occurring during sleep. Finally, antiepileptic drugs used in the treatment of sleep-related epilepsies can have an effect on sleep. The following is an analysis and review of these complex interactions between epilepsy and sleep.

The purpose of this report was to update the 2006 International League Against Epilepsy (ILAE) report and identify the level of evidence for long-term efficacy or effectiveness for antiepileptic drugs (AEDs) as initial monotherapy for patients with newly diagnosed or untreated epilepsy. All applicable articles from July 2005 until March 2012 were identified, evaluated, and combined with the previous analysis (Glauser et al., 2006) to provide a comprehensive update. The prior analysis methodology was utilized with three modifications: (1) the detectable noninferiority boundary approach was dropped and both failed superiority studies and prespecified noninferiority studies were analyzed using a noninferiority approach, (2) the definition of an adequate comparator was clarified and now includes an absolute minimum point estimate for efficacy/effectiveness, and (3) the relationship table between clinical trial ratings, level of evidence, and conclusions no longer includes a recommendation column to reinforce that this review of efficacy/evidence for specific seizure types does not imply treatment recommendations. This evidence review contains one clarification: The commission has determined that class I superiority studies can be designed to detect up to a 20% absolute (rather than relative) difference in the point estimate of efficacy/effectiveness between study treatment and comparator using an intent-to-treat analysis. Since July, 2005, three class I randomized controlled trials (RCT) and 11 class III RCTs have been published. The combined analysis (1940-2012) now includes a total of 64 RCTs (7 with class I evidence, 2 with class II evidence) and 11 meta-analyses. New efficacy/effectiveness findings include the following: levetiracetam and zonisamide have level A evidence in adults with partial onset seizures and both ethosuximide and valproic acid have level A evidence in children with childhood absence epilepsy. There are no major changes in the level of evidence for any other subgroup. Levetiracetam and zonisamide join carbamazepine and phenytoin with level A efficacy/effectiveness evidence as initial monotherapy for adults with partial onset seizures. Although ethosuximide and valproic acid now have level A efficacy/effectiveness evidence as initial monotherapy for children with absence seizures, there continues to be an alarming lack of well designed, properly conducted epilepsy RCTs for patients with generalized seizures/epilepsies and in children in general. These findings reinforce the need for multicenter, multinational efforts to design, conduct, and analyze future clinically relevant adequately designed RCTs. When selecting a patient's AED, all relevant variables and not just efficacy and effectiveness should be considered.

The choice of an antiepileptic drug (AED) is guided primarily by efficacy and safety criteria. However, the pharmacokinetic properties of an AED determine its ease of use, i.e., its ability to predictably produce and maintain optimal plasma concentrations. Desirable and clinically important pharmacokinetic properties of an AED include complete or constant bioavailability, slow enteral absorption or availability of a sustained-release formulation, availability of a parenteral formulation for acute treatment, rapid penetration into the brain, a single-compartment volume of distribution, low and nonsaturable protein binding, and linear elimination kinetics, with an elimination half-life of about 24 h. The absence of autoinduction of enzymatic biotransformation, active metabolites, and pharmacokinetic drug interactions is also important. In clinical practice, the most undesirable pharmacokinetic properties are lack of a parenteral formulation, short elimination half-life, nonlinear elimination kinetics, autoinduction of enzymatic biotransformation, and interaction with other drugs. No AED is presently marketed or under development that meets all of the desirable criteria. Some of the newer AEDs, although not "ideal" agents, have pharmacokinetic profiles that are not shared by their predecessors, including elimination exclusively by the kidney, absence of drug interactions, and dose-related bioavailability.

During the past 25 years, our armamentarium of antiepileptic drugs has grown, and there continue to be new drugs in the pipeline. As premarketing studies are often limited to adult cohorts, the great majority of these new drugs were initially marketed with an indication for the treatment of partial

In the past year, several new antiepileptic drugs have emerged that have potential benefits for children with epilepsy. The spectrum of adverse effects is the principal feature that differentiates among the older drugs used to treat partial and related seizures, including simple partial, complex partial, and partial secondarily generalized seizures. Based on studies in adults with refractory seizures, the new or investigational compounds felbamate, gabapentin, lamotrigine, and vigabatrin should be active against these types of seizures in children, but none of them have been subjected to pediatric randomized controlled trials, and no studies have been done that compare new and old drugs in this category. Thus, the new drugs hold promise in children with these types of seizures, but their role relative to old drugs has not been elucidated. Several of the new drugs are active against myoclonic and generalized tonic-clonic seizures, but thus far, none have been proven to possess antiabsence activity in children. Open-label investigations suggest that lamotrigine may be helpful in Lennox-Gastaut syndrome, and vigabatrin in infantile spasms. Only felbamate has been evaluated in a randomized controlled study in children, in which it has proven beneficial against astatic and generalized tonic-clonic seizures in children with Lennox-Gastaut syndrome. Whereas investigations of these and other novel drugs are ongoing, this is an active and exciting period in pediatric antiepileptic drug development. (J Child Neurol 1994;9(Suppl):2S1-2S7).

Summary: : Four antiepileptic drugs (AEDs) represent > 90% of all AEDs prescribed in the United States. The efficacies of the available AEDs are surprisingly similar and far from complete, and none is entirely safe. Thus, the incidence of side effects is often the determining factor in the choice of AED. Clinical decisions about which AED to select should be made on the basis of the combination of efficacy and toxicity, expressed as a protective or therapeutic index (TI). Efficacy seldom comes without some degree of toxicity, whereas toxicity can occur in the absence of any efficacy. As the dose of the AED increases, efficacy can reach a plateau but toxicity does not. Complete seizure control should not be the final goal of epilepsy treatment; optimal AED therapy is equal to the highest possible TI, not necessarily to maximal seizure control. Each AED has a different TI, and each has a different TI in every patient. This is confounded further when combinations of AED are prescribed.

Although the current trend is to use monotherapy in the treatment of epilepsy, combination therapy is still employed in patients who have failed to respond to monotherapy. There is little clinical or experimental documentation of evidence against or in favor of anticonvulsant combination therapy. In this context, anticonvulsant and neurotoxic pharmacodynamic interactions between phenytoin (PHT) and valproate (VPA) were assessed in an experimental model in mice. All results were expressed in terms of brain drug concentrations for eliminating any pharmacokinetic interaction from the analysis. Both the median neurotoxic and the median anticonvulsant brain concentrations were determined for each drug used alone and for the combination. The interaction for the combination of PHT and VPA was shown to be supraadditive for the anticonvulsant activity, indicating an antiepileptic potentiation, whereas neurotoxicity was simply additive. These results suggest a potential benefit in terms of overall efficacy versus toxicity for the combination of PHT and VPA, as compared with PHT or VPA used alone.

Patients in whom carbamazepine (CBZ) monotherapy is discontinued for preoperative EEG/video monitoring often display toxicity if their previous maintenance dosage is resumed, even after a few days without CBZ. To determine whether this is due to rapid reversibility of autoinduction of CBZ metabolism, single-dose studies of CBZ pharmacokinetics were performed before and after discontinuation for monitoring in 6 adults receiving CBZ monotherapy. The CBZ-free period was 5.7 +/- 1.1 days (mean +/- SD). The pharmacokinetic parameters of CBZ before and after discontinuation were volume of distribution (Vd) 1.28 +/- 0.29 versus 1.22 +/- 0.331/kg (NS), elimination half-life (t1/2) 13.7 +/- 1.67 versus 22.2 +/- 2.36 h (p < 0.001), and clearance (Cl) 1.54 +/- 0.39 versus 0.92 +/- 0.32 L/kg/day (p = 0.012). Assuming that deinduction is a first-order process, a deinduction t1/2 of 3.84 days was obtained by log linear regression analysis. We showed that after CBZ discontinuation half of the enzymatic autoinduction is already lost after 3.84 days, indicating very rapid deinduction. Our results also provide the necessary information to predict clearance and appropriate dosage reduction for CBZ at time of reintroduction.

A 16-year-old girl was referred from the epilepsy clinic for urgent admission to the long-term EEG monitoring unit. She had a prior history of both epileptic and nonepileptic seizures of multiple types, but presented to the clinic for evaluation of a new type of movement, present for 1 month. Over that time period her home antiseizure regimen (levetiracetam and topiramate) had been serially increased with no relief. She described (and demonstrated) a tonic spasm of the right lower face which had a sudden onset and lasted 30–90 seconds. In retrospect, her parents reported small facial twitches which preceded the full-blown spasms by 2 months. These spells appeared to worsen with stress and attention. Short episodes were not painful, but as the episodes became more frequent she developed progressively worsening masseter pain. On the day of admission, she experienced these spasms every 5–10 minutes, more frequently during the examination. Between episodes, her neurologic examination had normal results, with no sensory or motor changes to the face. The video on the Neurology ® Web site at www.neurology.org provides an example. ### Questions for consideration: 1. What is your differential for this facial spasm? 2. How would you evaluate this movement? GO TO SECTION 2 At the top of our differential were true seizures and nonepileptic events, including pseudoseizures. Review of the first day's awake EEG supported our initial clinical suspicion; her facial spasms had no electrographic correlate. On the first morning following admission, we began a discussion with her mother regarding nonepileptic seizures. On that day, the patient had 2 nontraumatic falls which her parents agreed were identical to her previously characterized nonepileptic events. Upon review of her overnight EEG (figure 1), however, we were forced to rethink her presentation and expand our differential. Figure 1 A typical EEG during the facial spasm Overnight EEG illustrating a typical facial spasm. Sleep spindles …

Objective The purpose of this study was to determine the safety and efficacy of rufinamide for treatment of epileptic spasms. Methods We retrospectively reviewed patients treated with rufinamide for epileptic spasms from January 2009 to March 2010. Age, presence of hypsarrhythmia, change in seizure frequency following rufinamide initiation, and side effects were assessed. Patients who had a ≥ 50% reduction in spasm frequency were considered responders. Results Of all 107 children treated with rufinamide during the study period, 38 (36%) had epileptic spasms. Median patient age was 7 years (range: 17 months to 23). One patient had hypsarrhythmia at the time of treatment with rufinamide, and 9 other patients had a history of hypsarrhythmia. Median starting dose of rufinamide was 9 mg/kg/day (range: 2–18) and median final treatment dose was 39 mg/kg/day (range: 8–92). All patients were receiving concurrent antiepileptic drug therapy, with the median number of antiepileptic drugs being 3 (range: 2–6). Median duration of follow-up since starting rufinamide was 171 days (range: 10–408). Responder rate was 53%. Median reduction in spasm frequency was 50% (interquartile range = –56 to 85%, P 99% reduction in spasms. Rufinamide was discontinued in 7 of 38 patients (18%) because of lack of efficacy, worsening seizures, or other side effects. Minor side effects were reported in 14 of 38 patients (37%). Conclusions Rufinamide appears to be a well-tolerated and efficacious adjunctive therapeutic option for children with epileptic spasms. A prospective study is warranted to validate our observations.

We describe 17 children with nocturnal or early-morning seizures who were switched to a proportionally higher evening dose of antiepileptic drugs and were retrospectively reviewed for seizure outcome and side effects. Of 10 children with unknown etiology, clinical presentation was consistent with nocturnal frontal lobe epilepsy (NFLE) in 5 and benign epilepsy with centrotemporal spikes (BECTS) in 3. After a mean follow-up of 5.3 months, 15 patients were classified as responders; 11 of these became seizure free (5 NFLE, 1 BECTS, 5 with structural lesions) and 4 (2 BECTS, 2 with structural lesions) experienced 75-90% reductions in seizures. Among two nonresponders, seizures in one had failed to resolve with epilepsy surgery. Nine subjects (53%) received monotherapy after dose modification, and none presented with worsening of seizures. Two complained of transient side effects (fatigue/somnolence). Differential dosing led to seizure freedom in 64.7% (11/17) of patients, and 88.2% (15/17) experienced ≥ 50% reductions in seizures.