Lexical retrieval pre- and posttemporal lobe epilepsy surgery in a pediatric sample.

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<0.05). This effect was not documented for verbal fluency. 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.

Lennox-Gastaut syndrome: a consensus approach to differential diagnosis.

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.

Safety and retention rate of rufinamide in 300 patients: a single pediatric epilepsy center experience.

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.

Comparing stimulant effects in youth with ADHD symptoms and epilepsy.

To retrospectively examine response to stimulant treatment in patients with epilepsy and ADHD symptoms as predicted by seizure freedom for six months, use of methylphenidate (MPH) versus amphetamine (AMP) preparations, cognitive level, and medical records were searched for patients under the age of 18 with epilepsy and ADHD symptoms treated with MPH or AMP (n=36, age=10.4 ± 3.5; male=67%). "Responders" had a CGI-improvement score of ≤ 2 and did not stop medication because of adverse effects. "Worsened" patients discontinued medication because of agitation/emotional lability. Seizure freedom did not predict treatment response. Lower cognitive level was associated with increased rate of worsening (p=0.048). No patients who were seizure-free at the start of the medication trial experienced an increase in seizures. Of the patients having seizures at the start of trial, one patient on MPH and two patients on AMP had increased seizures during the trial. Seizures returned to baseline frequency or less after stimulant discontinuation or anticonvulsant adjustment. Methylphenidate was associated with a higher response rate, with 12 of 19 given MPH (0.62 ± 0.28 mg/kg/day) compared with 4 of 17 given AMP (0.37 ± 0.26 mg/kg/day) responding (p=0.03). Methylphenidate treatment and higher cognitive level were associated with improved treatment outcome, while seizure freedom had no clear effect. Confidence in these findings is limited by the study's small, open-label, and uncontrolled design.

Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes.

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.

Gelastic epilepsy and hypothalamic hamartomas: neuroanatomical analysis of brain lesions in 100 patients.

Hypothalamic hamartomas present with isolated fits of ictal laughter (gelastic epilepsy) or a combination of gelastic and other types of seizures. Many of these patients also suffer from cognitive decline, neuropsychiatric comorbidities and precocious puberty. Although there is a large body of anecdotal evidence about hypothalamic hamartomas and gelastic seizures, many questions still remain to be answered. For instance, which specific hypothalamic regions are most affected by the location of hamartomas causing laughing versus other types of seizures? Does the neuroanatomical localization of the lesions differ in cases with only gelastic seizures or a combination of gelastic and other types of seizures? Does the location of the lesions correlate with the presence of precocious puberty, and does the type of lesion influence the severity or the type of seizures? In a retrospective review of clinical and structural neuroimaging data from 100 cases of gelastic epilepsy and hypothalamic hamartoma, we aimed to address these questions by analysing the clinical presentation and the neuroanatomical features of the hypothalamic lesions in these patients. Our findings suggest that in all 100 cases, lesions were centred at the level of the mammillary bodies in the posterior hypothalamus. Compared with the patients with pure gelastic seizures (n = 32), those with gelastic and other types of seizures (n = 68) had significantly longer duration of epilepsy (P < 0.001), whereas age of seizure onset, the volume of lesions and the proximity to the mammillary bodies were not different between the two groups. In contrast, patients with cognitive or developmental impairment and those with precocious puberty had significantly larger lesions involving the anterior and posterior hypothalamus.

Propagation of epileptic spikes reconstructed from spatiotemporal magnetoencephalographic and electroencephalographic source analysis.

The purpose of this study is to assess the accuracy of spatiotemporal source analysis of magnetoencephalography (MEG) and scalp electroencephalography (EEG) for representing the propagation of frontotemporal spikes in patients with partial epilepsy. This study focuses on frontotemporal spikes, which are typically characterized by a preceding anterior temporal peak followed by an ipsilateral inferior frontal peak. Ten patients with frontotemporal spikes on MEG/EEG were studied. We analyzed the propagation of temporal to frontal epileptic spikes on both MEG and EEG independently by using a cortically constrained minimum norm estimate (MNE). Spatiotemporal source distribution of each spike was obtained on the cortical surface derived from the patient's MRI. All patients underwent an extraoperative intracranial EEG (IEEG) recording covering temporal and frontal lobes after presurgical evaluation. We extracted source waveforms of MEG and EEG from the source distribution of interictal spikes at the sites corresponding to the location of intracranial electrodes. The time differences of the ipsilateral temporal and frontal peaks as obtained by MEG, EEG and IEEG were statistically compared in each patient. In all patients, MEG and IEEG showed similar time differences between temporal and frontal peaks. The time differences of EEG spikes were significantly smaller than those of IEEG in nine of ten patients. Spatiotemporal analysis of MEG spikes models the time course of frontotemporal spikes as observed on IEEG more adequately than EEG in our patients. Spatiotemporal source analysis may be useful for planning epilepsy surgery, by predicting the pattern of IEEG spikes.

Current dipole orientation and distribution of epileptiform activity correlates with cortical thinning in left mesiotemporal epilepsy.

To evaluate cortical architecture in mesial temporal lobe epilepsy (MTLE) with respect to electrophysiology, we analyze both magnetic resonance imaging (MRI) and magnetoencephalography (MEG) in 19 patients with left MTLE. We divide the patients into two groups: 9 patients (Group A) have vertically oriented antero-medial equivalent current dipoles (ECDs). 10 patients (Group B) have ECDs that are diversely oriented and widely distributed. Group analysis of MRI data shows widespread cortical thinning in Group B compared with Group A, in the left hemisphere involving the cingulate, supramarginal, occipitotemporal and parahippocampal gyri, precuneus and parietal lobule, and in the right hemisphere involving the fronto-medial, -central and -basal gyri and the precuneus. These results suggest that regardless of the presence of hippocampal sclerosis, in a subgroup of patients with MTLE a large cortical network is affected. This finding may, in part, explain the unfavorable outcome in some MTLE patients after epilepsy surgery.

Adaptive phase I study of OROS methylphenidate treatment of attention deficit hyperactivity disorder with epilepsy.

OBJECTIVE: The goal of this study was to pilot a randomized controlled trial of OROS methylphenidate (OROS-MPH) to treat attention deficit hyperactivity disorder (ADHD) plus epilepsy. METHODS: Thirty-three patients, 6-18years of age, taking antiepileptic drugs and with a last seizure 1-60months prior were assigned to a maximum daily dose of 18, 36, or 54mg of OROS-MPH in a double-blind placebo-controlled crossover trial. RESULTS: There were no serious adverse events and no carryover effects in the crossover trial. OROS-MPH reduced ADHD symptoms more than did placebo treatment. There were too few seizures during the active (5) and placebo arms (3) to confidently assess seizure risk; however, considering exposure time, we observed an increased daily risk of seizures with increasing dose of OROS-MPH, suggesting that potential safety concerns require further study. CONCLUSION: A larger study to assess the effect of OROS-MPH on seizure risk is needed. A crossover design including subjects with frequent seizures could maximize power and address high patient heterogeneity and recruitment difficulties.

In-session seizures during low-frequency repetitive transcranial magnetic stimulation in patients with epilepsy.

Low-frequency repetitive transcranial magnetic stimulation (rTMS) is emerging as a therapeutic tool for patients with intractable epilepsy. Although seizures during treatment have been reported as adverse events in some patients, the nature and severity of seizures that may be provoked by low-frequency rTMS in patients with epilepsy have not been extensively studied. Accordingly, this article documents seizures in patients (n=5) with intractable epilepsy and average seizure frequency greater than one per day who underwent 1-Hz rTMS for seizure suppression. We report three observations in the present case series: (1) in each instance the in-session seizure was typical in semiology to the patient's habitual seizures, (2) the duration of each documented seizure was either the same as or shorter than the patients' baseline seizures, and (3) the overall neurological outcome on follow-up was not affected by the in-session seizures. More data will be required for valid conclusions with respect to safety and tolerability of low-frequency rTMS in patients with epilepsy, but it is noteworthy from our perspective that seizures during rTMS in this series were similar to the patients' habitual seizures, occurred in patients with epilepsy with baseline seizure frequency exceeding one per day, and did not correlate with a poor neurological outcome or with absence of clinical response to rTMS.

Debate: Does genetic information in humans help us treat patients? PRO--genetic information in humans helps us treat patients. CON--genetic information does not help at all.

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.

Antiepileptic drugs--best practice guidelines for therapeutic drug monitoring: a position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies.

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.

Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs I: Treatment of new-onset epilepsy: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society.

OBJECTIVE: To 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). METHODS: The 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. 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 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.

Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs II: Treatment-resistant epilepsy: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society.

OBJECTIVE: To update the 2004 American Academy of Neurology guideline for managing treatment-resistant (TR) epilepsy with second- and third-generation antiepileptic drugs (AEDs). METHODS: 2004 criteria were used to systemically 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-Gastaut 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-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-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 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 of age and perampanel as monotherapy received FDA approval.

Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs I: Treatment of new-onset epilepsy: Report of the American Epilepsy Society and the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.

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.

Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs II: Treatment-resistant epilepsy: Report of the American Epilepsy Society and the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.

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.

Focal cortical malformations can show asymmetrically higher uptake on interictal fluorine-18 fluorodeoxyglucose positron emission tomography (PET).

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.

Topiramate in patients with juvenile myoclonic epilepsy.

BACKGROUND: Topiramate is a broad-spectrum agent effective against primarily generalized tonic-clonic seizures (PGTCS) as well as partial-onset seizures. Juvenile myoclonic epilepsy is one of the most common idiopathic generalized epilepsies, with most patients experiencing PGTCS. OBJECTIVE: To evaluate topiramate as add-on therapy in patients with juvenile myoclonic epilepsy. DESIGN: Post-hoc analysis of a patient subset from 2 multicenter, double-blind, randomized, placebo-controlled, parallel-group trials. SETTING: Eighteen centers in the United States; 10 centers in Europe; 1 center in Costa Rica (primary trials). PATIENTS: A total of 22 patients with juvenile myoclonic epilepsy participating in placebo-controlled trials assessing topiramate (target dose, 400 mg/d in adults) in inadequately controlled PGTCS. MAIN OUTCOME MEASURE: Reduction of PGTCS. RESULTS: A 50% or more reduction of PGTCS in 8 of 11 topiramate-treated patients (73%) and 2 of 11 placebo-treated patients (18%) (P = .03). Reductions in myoclonic, absence, and total generalized seizures were also observed, although topiramate vs placebo differences did not achieve statistical significance. CONCLUSION: As a broad-spectrum agent, topiramate is an effective option for patients with juvenile myoclonic epilepsy.

Aggravation of epilepsy by antiepileptic drugs.

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.

Electroencephalography in neonatal seizures: comparison of a reduced and a full 10/20 montage.

This study compares a reduced electrode montage (9 electrodes) with the full 10/20 electrode montage for the ability to detect and characterize neonatal seizures and background electroencephalographic (EEG) characteristics, utilizing new digital technology allowing "remontage" of previously acquired records. A total of 151 neonatal EEG records were retrospectively and blindly analyzed by two readers. Records were first analyzed for seizure number, topography, duration, and characteristics of EEG background using the reduced montage, before reanalysis with the full montage. One hundred eighty-seven seizures were identified in 31 ictal recordings using the full montage. Using the reduced montage, 166 seizures were identified in 30 records. The sensitivity and specificity of the reduced montage for detecting electrographic seizures was 96.8% and 100% respectively. In only one patient's record, the single seizure was missed altogether. For grading background abnormalities, the sensitivity and specificity of reduced montage was 87% and 80%. Although there are inherent weaknesses in reduced montages with respect to both underestimation and overestimation of seizure number, a nine-electrode reduced montage can be a sensitive tool for identification of neonatal seizures and assessment of background characteristics of neonatal electroencephalography.