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Hyperosmolar hyperglycemic state (HHS), a life-threatening complication of diabetes mellitus, may initially manifest with a broad spectrum of neurological symptoms. These include encephalopathy, coma, chorea-hemiballismus and epileptic activity. Focal motor seizures are among the most common manifestations whilst aphasia has rarely been described so far. Based on a recent experience from our hospital, we herein report a rare case of a patient with nonketotic hyperglycemia-induced global aphasia, followed by focal motor seizures and attempt a comprehensive review of the literature with regards to the various neurological syndromes through which, undiagnosed diabetes and HHS may present. Neurological aspects of HHS are not so well-documented and are certainly under-represented in the literature.

Our objective was to provide expert consensus recommendations to improve treatment tolerability through dose adjustments of concomitant antiseizure medications (ASMs) during addition of cenobamate to existing ASM therapy in adult patients with uncontrolled focal seizures.A panel of seven epileptologists experienced in the use of ASMs, including cenobamate, used a modified Delphi process to reach consensus. The panelists discussed tolerability issues with concomitant ASMs during cenobamate titration and practical strategies for dose adjustments that may prevent or mitigate adverse effects. The resulting recommendations consider concomitant ASM dose level and specify proactive (prior to report of an adverse effect) and reactive (in response to report of an adverse effect) dose adjustment suggestions based on concomitant ASM pharmacokinetic and pharmacodynamic interactions with cenobamate. Specific dose adjustment recommendations are provided.We recommend proactively lowering the dose of clobazam, phenytoin, and phenobarbital due to their known drug-drug interactions with cenobamate, and lacosamide due to a pharmacodynamic interaction with cenobamate, to prevent adverse effects during cenobamate titration. Reactive lowering of a concomitant ASM dose is sufficient for other ASMs at standard dosing owing to quick resolution of adverse effects. For carbamazepine and lamotrigine doses exceeding the upper end of standard dosing (e.g., carbamazepine, greater than 1200 mg/day; lamotrigine, greater than 500 mg/day), we encourage consideration of proactive dose reduction at cenobamate 200 mg/day to prevent potential adverse effects. All dose reductions for adverse effects can be repeated every 2 weeks as dictated by the adverse effects. At cenobamate 200 mg/day, we recommend that patients be evaluated for marked improvement of seizures and further dose reductions be considered to reduce potentially unnecessary polypharmacy.The primary goal of the recommended dose reductions of concomitant ASMs is to prevent or resolve adverse effects, thereby allowing cenobamate to reach the optimal dose to achieve the maximal potential of improving seizure control.Some people with epilepsy need to take more than one seizure medicine as part of their treatment. Taking more than one seizure medicine, however, can increase the risk of unwanted side effects. One approach to preventing side effects when adding a new seizure medicine is to lower the amount (dose) of existing seizure medicines. Cenobamate is a newer seizure medicine available in the USA for adults with focal seizures (also referred to as partial-onset seizures). Cenobamate, like many seizure medicines, must be titrated over time to a target dose. A group of epilepsy specialists met and developed recommendations for when and how to change the doses of existing seizure medicines when adding cenobamate. The goal of these recommendations is to prevent or reduce side effects like sleepiness or dizziness. The authors recommend that the dose of specific seizure medicines, including clobazam, lacosamide, phenytoin, and phenobarbital, be lowered as cenobamate is started or as cenobamate’s dose is being increased (but before side effects occur). Regular doses of other seizure medicines can be lowered if a side effect occurs because reducing the dose of the other seizure medications can often stop the side effect. These recommendations may help patients successfully reach their optimal dose of cenobamate with fewer side effects, potentially improving their seizure control.

On March 18, 2021, an online council of experts in the field of epilepsy treatment was held, dedicated to the use of perampanel in the additional therapy of focal seizures (FS) and primary generalized tonic-clonic seizures (PGTCS) in children 4–12 years old. During the event, the features of the use of perampanel in this group of patients were discussed, considering the specifics of everyday clinical practice, current possibilities of PGTCS and FS therapy in children, its goals, as well as unsolved problems in the treatment of pediatric patients with PGTCS and FS. Particular attention was paid to the role of perampanel in the treatment of PGTCS and FS in children and its effectiveness in specific types of focal seizures.

Introduction: Brivaracetam (BRV) is an antiseizure medication (ASM), which has been approved as an adjunctive treatment in adults and pediatric patients aged four years and older with focal onset seizures. It is a second-generation levetiracetam (LEV) derivative, sharing the same mechanism of action, binding synaptic vesicles 2A (SV2A). BRV shows higher binding affinity and selectivity and higher brain permeability than LEV.Areas covered: This article reviews randomized controlled trials, retrospective and prospective studies published up to December 2020, searched in electronic databases MEDLINE, EMBASE and the Clinical Trial Database and provide an overview of efficacy, safety and tolerability of BRV in pediatric patients with partial epilepsy. Furthermore, the authors provide their expert opinion on the drug and give their future perspectives.Expert opinion: The analysis of the literature data has demonstrated the safety and efficacy of BRV in pediatric patients, with more evidence in children aged 4 to 16 years with an onset of focal seizures. However, a positive response was also achieved in patients affected by some encephalopathic epilepsies. Comparative efficacy studies between BRV and other ASMs, in addition to well-designed RCTs that include larger pediatric populations are needed to better define the role and potentiality of this ASM.

Introduction The aim of this study was to compare healthcare resource utilization (HCRU) before and after initiation of eslicarbazepine acetate (ESL) in the long-term care (LTC) setting (rehabilitation center, mental health center, LTC non-skilled nursing facility/assisted-living facility, home health, assisted living, nursing home, other/unknown). Methods This retrospective analysis used IQVIA’s New Data Warehouse, which includes deterministically linked LTC, prescription, and professional fee claims data and IQVIA Hospital Charge Data Master database. The study period was 1 April 2013 to 31 December 2019. The index date was the date of ESL initiation in the LTC setting. Inclusion criteria were: (1) ≥ 1 new ESL prescription between 1 April 2014 and 31 December 2018; (2) diagnosis of focal seizure (FS) during the 12 months pre-index date; and (3) no ESL prescription during the 12-month period pre-index. A 12-month pre-post analysis compared epilepsy-specific and all-cause HCRU before and after ESL initiation. Categorical variables were compared with McNemar’s tests. Results A total of 307 patients (mean age 52.2 years, 57.7% male) with FS were included, of whom 24.8% were in nursing homes. Patients used a mean of 3.1 antiseizure drugs prior to initiation of ESL, and 87.9% of patients initiated ESL as adjunctive treatment. There were significant reductions in proportion of patients with epilepsy specific physician office visits, emergency department (ED) visits, hospitalizations, and all-cause physician office visits and hospitalizations in the post-index period compared to the pre-index period (P

Resumen Las convulsiones epilépticas focales se originan en una localización focal del cerebro con descargas eléctricas anormales que pueden suceder por distintas causas, y pueden ocurrir en un bajo porcentaje de animales; son signos diferentes a la típica mioclonía tónico-clónica. El objetivo del presente trabajo es exponer casos clínicos de perros que presentaron vómitos, sialorrea y regurgitación como signos clínicos de convulsiones epilépticas focales. Estos perros, además de presentar tales signos digestivos mencionados, no mostraron alteraciones reveladoras en los datos de laboratorio ni en los métodos complementarios de imágenes solicitados. Debido a la escasa respuesta terapéutica y al empeoramiento de la condición de los pacientes (pérdida de peso severa), luego de descartar causas periféricas de vómitos y/o regurgitación, se consideró la posibilidad de que el estímulo del vómito fuera central. Por lo tanto, se realizó un electroencefalograma (EEG). En todos los casos el trazado del EEG evidenció anomalías. Dada las condiciones clínicas descritas, se implementó el tratamiento con fenobarbital y la evolución de los tres casos clínicos fue favorable. Los perros con presencia de convulsiones epilépticas focales autonómicas pueden presentar una variada sintomatología clínica que depende de las regiones cerebrales dañadas que las producen. Por eso es importante tener en cuenta dentro de los diferenciales de signos clínicos que pueden tener origen central como el vómito, principalmente cuando la causa permanece sin ser diagnosticadas, la epilepsia focal autonómica. Abstract Focal seizures originate in a focal location of the brain with abnormal electric discharges due to different causes and may occur in a low percentage of animals and their signs are different from the typical tonic-clonic myoclony. This work aims to disclose some clinical cases of dogs with vomit, sialorrhea and regurgitation as clinical signs of focal seizures. In addition to these digestive signs, the dogs did not show any noteworthy alteration in the laboratory test results, neither in the complementary imaging methods included in the study. Due to the scant therapeutic response and as the dogs got worse (a serious loss of weight), having ruling out any peripheral cause of vomit and/or regurgitation, the possibility of a central cause was considered. The dogs underwent an electroencephalogram (EEG) and in all cases the EEG results showed anomalies. Due to the described clinical conditions, a phenobarbital treatment was administered and the three cases clinical cases evolved positively. Dogs with focal autonomic seizures may show various clinical symptoms depending on the damaged brain regions they come from. Therefore, it is important to consider a central cause -focal autonomic epilepsy- for the differential clinical signs such as the vomit, mostly when there is not a clearly diagnosed cause.

Aims This post hoc analysis assessed the efficacy and safety/tolerability of adjunctive perampanel in patients from China (aged ≥12 years) with focal seizures (FS), with/without focal to bilateral tonic‐clonic seizures (FBTCS), or generalized tonic‐clonic seizures (GTCS). Methods Study centers in China were identified using data from five double‐blind, randomized, phase III studies of adjunctive perampanel (2‐12 mg/day) and their open‐label extensions (OLEx). Efficacy assessments included median percent reduction in seizure frequency per 28 days, and 50% and 75% responder and seizure‐freedom rates. Safety/tolerability assessments included monitoring of treatment‐emergent adverse events (TEAEs). Results Overall, 277 patients (placebo, n = 79; perampanel, n = 198) were included in the double‐blind safety analysis set. The full analysis set comprised 274 patients (FS, n = 238 [placebo, n = 60; perampanel, n = 178]; FBTCS, n = 120 [placebo, n = 31; perampanel, n = 89]; GTCS, n = 36 [placebo, n = 18; perampanel, n = 18]). Median percent reductions in seizure frequency for placebo vs perampanel were as follows: 16.6% vs 32.4% (FS; P, Adjunctive perampanel was associated with greater median percent reductions in seizure frequency per 28 days vs placebo in Chinese patients with focal or generalized seizure types during double‐blind, randomized, phase III studies.During OLEx studies, adjunctive perampanel showed efficacy for up to 4 years for FS and FBTCS, and up to 2 years for GTCS.Perampanel was generally well tolerated during short‐ and long‐term treatment.

Objectives: To evaluate cutaneous allergic reactions in clinical trials of adjunctive eslicarbazepine acetate (ESL) for focal seizures. Materials and methods: Data were analyzed from three phase III randomized, double-blind, placebo-controlled studies of adjunctive ESL in adults (placebo, n = 426; ESL, n = 1021) and two randomized, double-blind, placebo-controlled studies (and open-label extensions [OLEs]) of adjunctive ESL in children aged 4-17 years (placebo, n = 160; ESL, n = 202; OLE, n = 337). Results: Adult studies: Rash (ESL 1.9%, placebo 0.9%) and pruritus (ESL 1.2%, placebo 0.9%) were the most frequent rash-related treatment-emergent adverse events (TEAEs). Most rash-related TEAEs were mild or moderate in severity. Incidence of rash increased with increasing ESL dose, but was not higher for patients who initiated treatment with higher ESL doses. Pediatric studies: Allergic dermatitis (ESL 3.0%, placebo 0) and rash (controlled studies: ESL 1.0%, placebo 1.3%; OLE periods: ESL ≤1.2%) were the most frequent rash-related TEAEs. There was one case of DRESS in the ESL group. Most rash-related TEAEs were mild or moderate in severity and judged as not related to treatment with ESL. Conclusions: Serious skin rashes were rare during adult and pediatric clinical trials of ESL. Although the incidence of rash with ESL was low, it is important for patients/caregivers to be made aware of the potential signs and symptoms associated with serious skin rashes. Fil: Rogin, Joanne. Minneapolis Clinic of Neurology. Midwest Center for Seizure Disorders; Estados Unidos Fil: Resnick, Trevor. Florida International University; Estados Unidos Fil: Strom, Laura. University of Colorado Denver Health Sciences. Department of Neurology; Estados Unidos Fil: Ben Menachem, Elinor. Sahlgrenska Academy Institute of Neuroscience and Physiology; Suecia Fil: Kochen, Sara Silvia. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; Argentina Fil: Blum, David. Sunovion Pharmaceuticals Inc; Estados Unidos Fil: Gama, Helena. São Mamede de Coronado. BIAL - Portela & Ca, S.A.; Portugal Fil: Soares da Silva, Patrício. São Mamede de Coronado. BIAL - Portela & Ca, S.A.; Portugal. Universidad de Porto; Portugal Fil: Li, Yan. Sunovion Pharmaceuticals Inc; Estados Unidos Fil: Grinnell, Todd. Sunovion Pharmaceuticals Inc; Estados Unidos

BACKGROUND: The management of epilepsy in older adults has become part of daily practice because of an aging population. Older patients with epilepsy represent a distinct and more vulnerable clinical group as compared with younger patients, and they are generally under-represented in randomized placebo-controlled trials. Real-world studies can therefore be a useful complement to characterize the drug's profile. Brivaracetam is a rationally developed compound characterized by high-affinity binding to synaptic vesicle protein 2A and approved as adjunctive therapy for focal seizures in adults with epilepsy. OBJECTIVE: The aim of this study was to assess the 12-month effectiveness and tolerability of adjunctive brivaracetam in older patients (≥65 years of age) with epilepsy treated in a real-world setting. METHODS: The BRIVAFIRST (BRIVAracetam add-on First Italian netwoRk STudy) was a 12-month retrospective multicenter study including adult patients prescribed adjunctive brivaracetam. Effectiveness outcomes included the rates of seizure response (≥50% reduction in baseline seizure frequency), seizure freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events and the incidence of adverse events. Data were compared for patients aged ≥65 years of age ('older') vs those aged

Objective: Post-stroke epilepsy (PSE) is one of the most common causes of acquired epilepsy and accounts for about 10-15% of all newly diagnosed epilepsy cases. However, evidence about the clinical profile of antiseizure medications in the PSE setting is currently limited. Brivaracetam (BRV) is a rationally developed compound characterized by high-affinity binding to synaptic vesicle protein 2A. The aim of this study was to assess the 12-month effectiveness and tolerability of adjunctive BRV in patients with PSE treated in a real-world setting. Methods: This was a subgroup analysis of patients with PSE included in the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST). The BRIVAFIRST was a 12-month retrospective, multicentre study including adult patients prescribed adjunctive BRV. Effectiveness outcomes included the rates of seizure response (≥50% reduction in baseline seizure frequency), seizure‐freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events (AEs) and the incidence of AEs. Results: Patients with PSE included in the BRIVAFIRST were 75 and had a median age of 57 (interquartile range, 42-66) years. The median daily doses of BRV at 3, 6, and 12 months from starting treatment were 100 (100-150) mg, 125 (100-200) mg and 100 (100-200) mg, respectively. At 12 months, 32 (42.7%) patients had a reduction in their baseline seizure frequency by at least 50%, and the seizure freedom rates was 26/75 (34.7%). During the 1-year study period, 10 (13.3%) patients discontinued BRV. The reasons of treatment withdrawal were insufficient efficacy in 6 (8.0%) patients and poor tolerability in 4 (5.3%) patients. Adverse events were reported by 13 (20.3%) patients and were rated as mild in 84.6% and moderate in 15.4% of cases. Significance: Adjunctive BRV was efficacious and generally well-tolerated when used in patients with PSE in clinical practice. Adjunctive BRV can be a suitable therapeutic option for patients with PSE.

Cenobamate (CNB) is the latest antiseizure medication (ASM) authorized for the treatment of focal-onset seizures in adults. Although the precise mechanism of action of CNB is not yet fully understood, this drug inhibits the persistent, rather than transient, voltage-gated sodium channel currents and is a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors, differently from benzodiazepines. CNB has a non-linear pharmacokinetic with a terminal half-life range of about 50/60 hours within the therapeutic dose range, which allows once daily administration. Cenobamate inhibits cytochrome P450 (CYP) 2C19 and induces CYP3A4 and 2B6, and hence can potentially interact with ASMs (eg, phenytoin, carbamazepine and clobazam) and no-ASMs drugs. In two randomized, double-blind, placebo-controlled trials in patients with focal epilepsies, CNB has shown a particularly good efficacy with a rate of seizure freedom of about 20% during the maintenance period in participants treated with the dose of 400 mg/day. The most common treatment-emergent adverse effects include central nervous system-related symptoms, like dizziness, diplopia, somnolence, and gait disturbances. Safety issues of particular interest are severe skin reactions (drug reaction with eosinophilia and systemic symptoms) and QT shortening, which contraindicates its use in subjects with familial short QT syndrome or in combination with other QT-shortening drugs. The recommended starting dose is 12.5 mg/day, which can be gradually titrated to the target dose (200 mg/day) and further increased up to 400 mg/day. There are several aspects of CNB that need to be still addressed, including the long-term efficacy and the efficacy in patients with generalized seizures. Ongoing studies will clarify these issues. The clinical relevance of the peculiar pharmacokinetics and the pattern of drug–drug interactions also require further investigation.

A 16-year-old male was referred by the primary care physician (PCP) for a second opinion. An initial evaluation in another sleep center suggested a working diagnosis of night terrors for the last two years. The child would wake up frequently screaming for few minutes before going back to sleep with no recollection of these events later. A video during the polysomnography (PSG) showed the patient having one of his typical events. He was eventually diagnosed with Sleep-related Hypermotor Epilepsy (SHE) seizures. This case highlights the importance of differentiating parasomnia and seizures, particularly for the sleep medicine providers that incorporate providers from different academic backgrounds. We will discuss the clinical challenges to make the distinction for the referring providers and demonstrate the importance of video-PSG to establish the diagnosis.

Purpose: To evaluate the efficacy and tolerability of adjunctive perampanel (PER) in Chinese patients with focal-onset seizures, with or without secondarily generalized tonic-clonic seizures.Methods: Fifty-six patients aged 14–72 years were recruited consecutively in this single-center prospective observational study. All patients received PER as add-on treatment on the basis of clinical judgment. Seizure frequency, adverse events (AEs), and retention rates were obtained at 3 and 6 months after PER introduction.Results: The overall response rates were 60 and 71.1% after 3 and 6 months, respectively, and the freedom of seizures at the same points were reached in 8 and 15.8%. The retention rates were 89.3% at the 3-month follow-up and 67.9% at the 6-month follow-up. The overall incidence of adverse events was 55.4%. The leading reported AEs were dizziness (39.3%) and somnolence (25%).Conclusions: Our study confirmed the efficacy and tolerability of adjunctive PER in Chinese patients in real-life conditions. Based on our treatment experience, a lower maintenance dose of PER would be needed in Chinese patients.

Rasmussen encephalitis (RE) is a rare disease of unknown etiology that causes severe chronic unihemispheric inflammatory disease of the central nervous system mainly in children. It leads to intractable seizures, cognitive decline and progressive neurological deficits in the affected hemisphere. We report two cases of RE, as defined by fulfillment of the 2005 Bien criteria. The diagnostic challenge of characterizing this rare disease will be highlighted by the extensive serum, CSF, MR imaging and EEG data in the two patients. In addition, we will review the various forms of therapy attempted in these two patients, namely anti-epileptic drug therapy and immunomodulatory therapy. Hemispherectomy was done for the second patient with favorable outcomes of controlling seizures, but unfortunately, he died because of meningitis. Until the causes of Rasmussen's encephalitis are known, it is difficult to anticipate how treatments will improve. Such a situation creates a therapeutic dilemma; hemispherectomy is not favored because of the inevitable postoperative functional deficits, but a real risk exists that treatments used to delay progression of the disease will defer definitive surgical treatment beyond the time when an optimum post-hemispherectomy outcome could be expected., Highlights • Rasmussen encephalitis (RE) causes severe chronic unihemispheric inflammatory disease. • RE should be suspected in any patient with refractory seizures. • Its recognition is important because early intervention with surgery can improve outcomes.

Summary Objective This study was undertaken to examine long‐term (up to 7.8 years) retention rate, safety, and tolerability of the antiseizure medication (ASM) cenobamate as adjunctive treatment in the open‐label extension (OLE) of study YKP3089C013 (C013; ClinicalTrials.gov: NCT01397968). Methods Patients who completed the 12‐week, multicenter, multinational, double‐blind, randomized, placebo‐controlled C013 study, which examined adjunctive cenobamate treatment of adults with uncontrolled focal seizures, were eligible to enroll in the OLE. During the OLE, dose adjustments of cenobamate and concomitant ASMs were allowed. Safety assessments included frequency of treatment‐emergent adverse events (TEAEs) and serious TEAEs, TEAE severity, and TEAEs leading to discontinuation. Probability of patient continuation in the OLE was examined using a Kaplan–Meier analysis. Results One hundred forty‐nine patients entered the OLE (median duration of cenobamate treatment = 6.25 years). As of the data cutoff, 57% of patients (85/149) remained in the OLE (median treatment duration = 6.8 years, range = 6.4–7.8 years). The median modal daily cenobamate dose was 200 mg (range = 50–400 mg). The probability of treatment continuation at 1–6 years of cenobamate treatment was 73%, 67%, 63%, 61%, 60%, and 59%, respectively. Among patients who continued at 1 year (n = 107), the probability of continuing at Years 2–5 was 92%, 87%, 83%, and 82%. The most common discontinuation reasons were patient withdrawal (19.5%, 29/149), adverse event (10.1%, 15/149), and lack of efficacy (5.4%, 8/149). TEAEs leading to discontinuation in 1% or more of patients were fatigue (1.3%, 2/149), ataxia (1.3%, 2/149), and memory impairment or amnesia (1.3%, 2/149). Dizziness (32.9%, 49/149), headache (26.8%, 40/149), and somnolence (21.5%, 32/149) were the most frequently reported TEAEs and were primarily mild or moderate in severity. Significance Long‐term retention in the C013 OLE study demonstrated sustained safety and tolerability of adjunctive cenobamate treatment up to 7.8 years in adults with treatment‐resistant focal seizures taking one to three ASMs.

OBJECTIVE: To assess the feasibility and accuracy of seizure detection based on heart rate variability (HRV) using a wearable electrocardiography (ECG) device. Noninvasive devices for detection of convulsive seizures (generalized tonic-clonic and focal to bilateral tonic-clonic seizures) have been validated in phase 2 and 3 studies. However, detection of nonconvulsive seizures still needs further research, since currently available methods have either low sensitivity or an extremely high false alarm rate (FAR). METHODS: In this phase 2 study, we prospectively recruited patients admitted to long-term video-EEG monitoring (LTM). ECG was recorded using a dedicated wearable device. Seizures were automatically detected using HRV parameters computed off-line, blinded to all other data. We compared the performance of 26 automated algorithms with the seizure time-points marked by experts who reviewed the LTM recording. Patients were classified as responders if >66% of their seizures were detected. RESULTS: We recruited 100 consecutive patients and analyzed 126 seizures (108 nonconvulsive and 18 convulsive) from 43 patients who had seizures during monitoring. The best-performing HRV algorithm combined a measure of sympathetic activity with a measure of how quickly HR changes occurred. The algorithm identified 53.5% of the patients with seizures as responders. Among responders, detection sensitivity was 93.1% (95% CI: 86.6%-99.6%) for all seizures and 90.5% (95% CI: 77.4%-97.3%) for nonconvulsive seizures. FAR was 1.0/24 h (0.11/night). Median seizure detection latency was 30 s. Typically, patients with prominent autonomic nervous system changes were responders: An ictal change of >50 heartbeats per minute predicted who would be responder with a positive predictive value of 87% and a negative predictive value of 90%. SIGNIFICANCE: The automated HRV algorithm, using ECG recorded with a wearable device, has high sensitivity for detecting seizures, including the nonconvulsive ones. FAR was low during the night. This approach is feasible in patients with prominent ictal autonomic changes.

Objective To examine the frequency of hyponatremia and potentially related symptoms in clinical trials of eslicarbazepine acetate (ESL) in adults with focal‐ (partial‐) onset seizures. Methods This post hoc, exploratory analysis included data from three controlled phase 3 trials of adjunctive ESL (400‐1200 mg once daily), two phase 3 trials of ESL monotherapy (1200‐1600 mg once daily), and their open‐label extension studies. Exploratory endpoints included clinical laboratory measurements of serum sodium concentrations ([Na+]), incidences of hyponatremia‐related treatment‐emergent adverse events (TEAEs), and incidences of TEAEs that are potential symptoms of hyponatremia. Results The controlled trials of adjunctive ESL and ESL monotherapy included 1447 (placebo, n = 426; ESL, n = 1021) and 365 (ESL, n = 365) patients, respectively; 639 and 274 patients continued onto uncontrolled, open‐label extensions. In the controlled and uncontrolled trials ≤3.3% of patients taking ESL had a minimum postdose [Na+] measurement ≤125 mEq/L, 10 mEq/L decrease in [Na+] from baseline

The cellular activity underlying human focal seizures, and its relationship to key signatures in the EEG recordings used for therapeutic purposes, has not been well characterized despite many years of investigation both in laboratory and clinical settings. The increasing use of microelectrodes in epilepsy surgery patients has made it possible to apply principles derived from laboratory research to the problem of mapping the spatiotemporal structure of human focal seizures, and characterizing the corresponding EEG signatures. In this review, we describe results from human microelectrode studies, discuss some data interpretation pitfalls, and explain the current understanding of the key mechanisms of ictogenesis and seizure spread.

Objectives To compare frequency analysis to human raters and determine the interrater agreement of postictal EEG changes after focal seizures. Methods 24 focal seizures with and without impaired awareness recorded with scalp-EEG in the epilepsy monitoring unit were selected. Five board-certified neurophysiologists annotated seizure termination and end of postictal changes for all seizures. We assessed agreement using intraclass correlation, described the band-power changes by time-frequency analysis, and correlated these measures with the rater annotations. Results Interrater agreement on the duration of the postictal changes was moderate (0.64, 95% confidence interval: 0.36–0.82). The interrater agreement for seizure termination was excellent (1.00). Median duration of the postictal interval of seizures with impaired awareness was significantly shorter than for seizures with retained awareness (p = 0.0004). Mean postictal duration was 16.4 min. Seizure duration did not predict duration of the postictal changes. We found a strong correlation of 0.8 between the median human rater and the duration of the decrease in spectral edge frequency. Conclusions The agreement of neurophysiologists is moderate for duration of postictal changes and high for seizure termination. Rater determination of postictal duration is correlated with measures of EEG slowing. Significance Disagreement between neurophysiologists on postictal duration need to be considered.

Detection of epileptogenic focus based on electroencephalogram (EEG) signal screening is an important pre-surgical step to remove affected regions inside the human brain. Considering the fact above, in this work, a novel technique for detection of focal EEG signals is proposed using a combination of empirical mode decomposition (EMD) and Teager–Kaiser energy operator (TKEO). EEG signals belonging to focal (Fo) and non-focal (NFo) groups were at first decomposed into a set of intrinsic mode functions (IMFs) using EMD. Next, TKEO was applied on each IMF and two higher-order statistical moments namely skewness and kurtosis were extracted as features from TKEO of each IMF. The statistical significance of the selected features was evaluated using student's t-test and based on the statistical test, features from first three IMFs which show very high discriminative capability were selected as inputs to a support vector machine classifier for discrimination of Fo and NFo signals. It was observed that the classification accuracy of 92.65% is obtained in classifying EEG signals using a radial basis kernel function, which demonstrates the efficacy of proposed EMD-TKEO based feature extraction method for computer-based treatment of patients suffering from focal seizures.

This study was funded by Laboratorios Bial, S.A. (Madrid, Spain)., The authors thank Alejandro Pedromingo (Bio-estadistica. com, Madrid, Spain) for the statistical analysis, and Isabel San Andrés (Incimed, Madrid, Spain) for performing the literature search. Their participation has been funded by Laboratorios Bial, S.A. (Madrid, Spain)., Aim of the study To assess the effectiveness, overall tolerability of eslicarbazepine acetate (ESL) as an initial or early monotherapy treatment of adult patients with focal epilepsy under real-world practice conditions. Materials and methods We focused on real-world longitudinal studies that included or separately reported the results of at least one of the efficacy outcomes of interest. A DerSimonian-Laird random effects model was used with the presentation of the 95% confidence intervals of the estimate Results 5 studies met our selection criteria and were included in the quantitative synthesis. All studies were observational and uncontrolled studies, and all but one were retrospective studies. The pooled proportion of patients who were seizure-free for the entire study period was 64.6% (95% CI, 45.7 to 79.8) at month 6 and 56.6% (95% CI, 50.2 to 62.8) at month 12. Pooled retention rates were 95.0% (95% CI, 90.3 to 97.5) at 6 months and 83.6% (95% CI, 73.9 to 90.1) at 12 months. The pooled proportion of patients who reported at least one adverse event was 27.2% (95% CI, 21.7 to 33.6), and the pooled proportion of patients who discontinued ESL due to adverse events was 8.9% (95% CI 6.2 to 12.6). Conclusions Our results suggest that initial or early monotherapy with ESL is effective and well-tolerated for the management of adult patients with focal epilepsy in clinical practice, with results that are at least similar to those reported in the pivotal randomized clinical trial of ESL monotherapy. No new safety signals with ESL have been identified in this systematic review., Bial Group

Hemimegalencephaly (HME) and its more localized form - posterior quadrantic dysplasia (PQD) - are rare malformations of cortical development (MCD) that normally manifest as refractory focal epilepsy and cognitive impairment in children. We report a case study of a 19-year-old woman who presented with seizure-like symptoms to the emergency department after discontinuing her seizure treatment having fled her country. MRI revealed typical signs of PQD. This case study demonstrates how an unusual mild clinical presentation led to the late diagnosis of this rare MCD.

Background. Adequate selection of the 1st antiepileptic drug (AED) is an obligatory condition for the successful treatment of epilepsy. It is well known that the first drug in the treatment of infantile spasms (IS) in tuberous sclerosis complex (TSC) is vigabatrin (VGB). With regard to focal seizures (FS) in TSC, there are certain differences: some authors insist on VGB (P. Curatolo, 2012), others as the first choice drugs are mentioning carbamazepine and valproate (A. Saxena, 2015). Data in general on the possible effectiveness of medical treatment of epilepsy in TSC, and the effectiveness of different AEDs are also contradictory.Objective: to make a comparative evaluation of the efficacy of various AEDs in the treatment of epilepsy in patients with TC.Materials and methods. Retrospective analysis of medical records of patients hospitalized with epilepsy and TSC in the Department of Epileptology and Psychoneurology, Research and Clinical Institute for Pediatrics named after Yu.E Vel’tishev of N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia, for the last 2 years was completed. Efficacy analysis was conducted in 134 patients (91 (67.9 %) with FS and 43 (32.1 %) with IS). Efficacy was estimated as the remission of epileptic seizures during 6 months. The percentage of patients with remission was also evaluated (seizures were stopped for 1 year or more) and percentage of patients with a decrease in the number of seizures. The results of the first monotherapy and the subsequent administration of two and three AEDs were analyzed.Results. Low efficiency of AEDs in starting monotherapy was noted – the remission of seizures within 6 months on any AED was only 27.5 % (25 from 91) with FS, with IS – 13.9 % (6 from 43). Remission on any 1st AED was observed only in 13.2 % (12 from 91) and 6.9 % (3 from 43), respectively. The effectiveness of individual AED is low, especially in achieving stable remission. So, valproate caused remission of FS in 14 (22.2 %) from 63, but in the future remission was stable only in 11 (17.5 %) from 63. VGB as the first monotherapy proved to be effective in 5 from 6 patients with FS and in 4 from 6 patients with IS. The introduction of the 2nd drug added another 13.3 % and 38.6 % of patients with remission of seizures, the 3rd AED – 7.3 % and 7.7 % in FS and IS, respectively. Most often, an effective drug in additional therapy was VGB. The efficiency of VGB was reduced if it was used not as the first, but as the second and third AED. The percentage of unsuccessful treatment (including combined therapy) is estimated as 51.5 % and 47.8 % of patients with FS and IS, respectively.Conclusion. Epilepsy associated with TSC is less sensitive to AEDs and gives a smaller percentage of remissions. Perhaps in our country this is due to the difficulties of prescription of VGB as a starting therapy for epilepsy in the patients with tuberous sclerosis complex.

Objective To evaluate and compare the effects of concomitant lamotrigine (LTG) or carbamazepine (CBZ) on the incidence of treatment-emergent adverse events (TEAEs) in patients taking adjunctive eslicarbazepine acetate (ESL) for focal (partial-onset) seizures (FS). Methods These post-hoc analyses of data pooled from three randomized, double-blind, placebo-controlled studies of adjunctive ESL (BIA-2093-301, −302 and −304) included adults (≥16 years) with FS refractory to 1–3 antiepileptic drugs (AEDs). Patients were randomized equally to placebo, ESL 400 mg (Studies 301 and 302 only), 800 mg, or 1200 mg once daily (8-week baseline, 2-week titration, and 12-week maintenance periods). TEAEs, TEAEs leading to discontinuation, and serious AEs (SAEs) were evaluated in patients taking, or not taking, LTG (excluding those taking CBZ or phenytoin [PHT]; i.e., the +LTG and −LTG/–CBZ subgroups), or CBZ (excluding those taking LTG or PHT; i.e., the +CBZ and −LTG/–CBZ subgroups) at baseline. Results LTG was used concomitantly by 248 patients (+LTG; placebo, n = 81; ESL, n = 167) and CBZ by 613 patients (+CBZ; placebo, n = 172; ESL, n = 441); 361 patients were taking neither LTG nor CBZ (−LTG/–CBZ; placebo, n = 109; ESL, n = 252). The overall incidence of TEAEs with ESL (any dose) was numerically higher for +CBZ (77%) than for +LTG (73%) or –LTG/–CBZ (68%; statistical significance not tested). Among patients taking ESL, dizziness, diplopia, and vomiting were reported more frequently in the +CBZ subgroup (30%, 14%, and 10%, respectively) than in the +LTG (16%, 8%, 5%) or –LTG/–CBZ (11%, 3%, 5%) subgroups. The overall incidence of TEAEs leading to discontinuation with ESL was higher for +CBZ (21%) than for +LTG (13%) or –LTG/–CBZ (15%). Dizziness leading to discontinuation with ESL was reported more frequently in the +CBZ subgroup than in the +LTG or –LTG/–CBZ subgroups (9%, 3%, and 3%, respectively). The overall incidence of SAEs in patients taking ESL was comparable across subgroups (+LTG, 5%; +CBZ, 6%; –LTG/–CBZ, 5%). The results were similar when evaluating placebo-adjusted incidences. Conclusion There was a potential pharmacodynamic interaction between AEDs with a putatively similar mechanism of action, with a seemingly lesser interaction between ESL and LTG versus ESL and CBZ. If combining ESL with LTG or CBZ, clinicians should be aware of the potential risk for an increased incidence of TEAEs typically associated with voltage-gated sodium channel inhibitors (e.g., dizziness, blurred vision, vertigo, diplopia, headache, or vomiting).

Objective To evaluate the success of initiation of adjunctive brivaracetam in patients who required a change in antiepileptic drug (AED) regimen and substituted at least one AED with brivaracetam. Methods In this retrospective noninterventional study conducted in specialized epilepsy centers across Germany, patients initiated adjunctive brivaracetam between February 15, 2016, and August 31, 2016, as part of an intended change in AED regimen. The primary effectiveness variable was the proportion of patients who continued on brivaracetam after 3 months, and withdrew at least one AED either before or within 6 months after brivaracetam initiation. Results Five hundred and six patients had at least one brivaracetam dose and were included in the safety set (SS). Four hundred and seventy patients started to reduce the dose of one AED before/after brivaracetam initiation, had at least one concomitant AED at brivaracetam initiation, and were included in the full analysis set (FAS) for effectiveness analyses. At baseline, patients had a median of seven lifetime AEDs and a median of 3.8 seizures/28 days. In the SS, 85.2% of patients withdrew one AED before/after initiation of brivaracetam, most commonly levetiracetam (49.4%). 46.2% of patients substituted another AED with brivaracetam within 24 hours (fast withdrawal). The proportions of patients (FAS) who continued on brivaracetam after 3 and 6 months and withdrew one AED were 75.5% and 46.6%, respectively. After 6 months, 32.1% of patients were 50% responders; 13.0% were seizure‐free. In the SS, 34.6% of patients reported treatment‐emergent adverse events (TEAEs); 21.9% had TEAEs that were assessed by the treating physician as drug‐related. Incidences of behavioral AEs before (3‐month baseline) and after brivaracetam initiation in patients who withdrew levetiracetam were 19.2% and 8.0%, respectively (5.0% and 7.7% in patients who withdrew other AEDs). Significance Brivaracetam was effective and well‐tolerated in patients who required a change in AED drug regimen and initiated adjunctive brivaracetam in German clinical practice.

Autoimmune encephalitis with anti-N-methyl-d-aspartate receptor autoantibodies (NMDA-R-Abs) is a recently described disease affecting adult and pediatric patients. Symptoms of the disease are now perfectly described in the adult population but the clinical presentation is less known in young children. The aim of the present study was to describe the clinical presentation and the specificities of symptoms presented by young children with NMDA-R-Abs encephalitis to improve diagnosis of this disease, and to compare these to a series of previously published female adult patients. Fifty cases of children younger than twelve years of age diagnosed with NMDA-R-Abs encephalitis between January 1, 2007 and December 31, 2016 (27 females and 23 males) were retrospectively studied. The first neurological symptoms observed in young children with NMDA-R-Abs encephalitis were characterized by seizure (72%), especially focal seizure (42%), within a median of 15 days before other encephalitis symptoms; other patients mostly had behavioral disorders (26%). The seizures were frequently difficult to diagnose because of the transient unilateral dystonic or tonic posturing presentation or sudden unilateral pain in the absence of clonic movements. A post-ictal motor deficit was also frequently observed. This clinical presentation is different from that observed in adult females with NMDA-R-Abs encephalitis who initially present mainly psychiatric disorders (67%) or cognitive impairment (19%), and less frequently seizures (14%). The diagnosis of NMDA-R-Abs encephalitis should be systematically considered in young children of both sexes who present neurological symptoms suggesting recent seizures (focal or generalized) without obvious other etiology.

Objective: To assess effectiveness and tolerability of first-line and conversion to lacosamide monotherapy for focal seizures. Materials and Methods: Retrospective, non-interventional chart review of lacosamide monotherapy patients aged ≥16 years in Europe. Outcomes included retention rate at observational point (OP) 3 (12 ± 3 months), seizure freedom rates at OP2 (6 ± 3 months) and OP3 and adverse drug reactions (ADRs). Results: A total of 439 patients were included (98 first-line and 341 conversion to monotherapy; 128 aged ≥65 years [25 first-line and 103 conversion to monotherapy]). First-line and conversion to monotherapy retention rates were 60.2% (59/98; 95% confidence interval [CI] 49.8%-70.0%) and 62.5% (213/341; 57.1%-67.6%), respectively. Kaplan-Meier estimates of 12-month retention rates were 81.2% and 91.4% for first-line and conversion to monotherapy, respectively. First-line and conversion to monotherapy retention rates in patients aged ≥65 years were 60.0% (38.7%-78.9%) and 68.9% (59.1%-77.7%), respectively. At OP2, 66.3% of first-line and 63.0% of conversion to monotherapy patients were seizure free. At OP3, 60.2% of first-line and 52.5% of conversion to monotherapy patients were seizure free. In the ≥65 years subgroup, seizure freedom rates at OP2 were 72.0% and 68.0% for first-line and converted to monotherapy, respectively, and at OP3, 68.0% and 56.3%, respectively. Overall, 52 of 439 (11.8%) patients reported ADRs (16.4% in ≥65 years subgroup), most commonly dizziness (5.0%), headache (2.1%) and somnolence (1.6%). Conclusions: Lacosamide was effective and well tolerated as first-line or conversion to monotherapy in a clinical setting in adult and elderly patients with focal seizures, This study was supported by UCB Pharma

Brivaracetam (BRV; Briviact) is a new antiepileptic drug (AED) approved for adjunctive treatment of focal (partial-onset) seizures in adults. BRV is a selective, high-affinity ligand for synaptic vesicle 2A (SV2A) with 15- to 30-fold higher affinity than levetiracetam, the first AED acting on SV2A. It has high lipid solubility and rapid brain penetration, with engagement of the target molecule, SV2A, within minutes of administration. BRV has potent broad-spectrum antiepileptic activity in animal models. Phase I studies indicated BRV was well tolerated and showed a favorable pharmacokinetic profile over a wide dose range following single (10–1,000 mg) and multiple (200–800 mg/day) oral dosing. Three pivotal Phase III studies have demonstrated promising efficacy and a good safety and tolerability profile across doses of 50–200 mg/day in the adjunctive treatment of refractory focal seizures. Long-term data indicate that the response to BRV is sustained, with good tolerability and retention rate. BRV is highly effective in patients experiencing secondarily generalized tonic–clonic seizures. Safety data to date suggest a favorable psychiatric adverse effect profile in controlled studies, although limited postmarketing data are available. BRV is easy to use, with no titration and little drug–drug interaction. It can be initiated at target dose with no titration. Efficacy is seen on day 1 of oral use in a significant percentage of patients. Intravenous administration in a 2-minute bolus and 15-minute infusion is well tolerated. Here, we review the pharmacology, pharmacokinetics, and clinical data of BRV.

Purpose Perampanel is a first-in-class antiepileptic medication approved for the treatment of partial (focal) seizures, and as adjunctive treatment for primarily generalized tonic-clonic seizures. The pharmacology, efficacy data, adverse-effect profile, pharmacokinetics and place in therapy are reviewed. Summary Perampanel is indicated for use in patients with epilepsy who are 12 years of age or older. It is the first medication designed specifically to be a non-competitive antagonist at post-synaptic α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors. Efficacy in refractory seizures has been established, and ongoing efficacy demonstrated by post-marketing data. The drug is completely absorbed, and exhibits a half-life that allows for once-daily administration in doses up to 12 mg/day. Drug interactions are minimal, but increased doses may be necessary when given with strong inducers of cytochrome P450 enzymes, including when perampanel is co-administered with other antiepileptics that exhibit this property. The most common adverse effects noted in both clinical trials and post-marketing are dizziness and somnolence. Psychiatric and behavioral adverse events have been documented in both adult and pediatric patients, including those with no corresponding diagnostic history. Conclusion Perampanel is a novel adjunctive antiepileptic medication that is an effective option for adolescents and adults with partial seizures, and primarily generalized tonic-clonic seizures uncontrolled with other medications.

The International League Against Epilepsy (ILAE) has developed and approved the Operational classification of seizure types 2017 and the Classification of the Epilepsies 2017 . According to the ILAE 2017 Operational classification of seizure types, seizures can be initially divided into focal or generalized; and the seizure onset is of crucial importance in this case. Focal seizures are optionally subdivided into focal aware seizures and focal impaired awareness seizures. Several new types of generalized-onset seizures were implemented. Specific motor and non-motor classifiers may be added. Unknown onset seizures are placed separately. Three levels of diagnostics are specified in the 2017 ILAE Classification of the Epilepsies: seizure type (defined in accordance with the 2017 ILAE Operational classification of seizure types), epilepsy type (focal, generalized, combined generalized and focal, unknown), and epilepsy syndrome. An etiologic diagnosis should be considered at each step along the diagnostic pathway. A patient ’s epilepsy may be classified into more than one etiological category. The term “benign” is replaced by the terms “self-limited” and “pharmacoresponsive” to be used where appropriate. The term “developmental and epileptic encephalopathy” can be applied in whole or in part where appropriate. The 2017 Operational classification of seizure types and the 2017 ILAE Classification of the Epilepsies can be helpful both in routine clinical practice and scientific research that will assist in improving epilepsy care and quality of life of patients with epilepsies.

Objectives This study aimed to determine the efficacy and safety of perampanel added to monotherapy in patients with focal-onset seizures, with or without secondarily generalized tonic-clonic seizures. Materials & methods In this multicentre, open-label trial, enrolled patients were treated with perampanel monotherapy. During a 12-week titration period, perampanel was incrementally increased by 2 mg/d over ≥2-week intervals. Patients then entered a 24-week maintenance period. The primary objective was to investigate the 50% responder rate in total seizure frequency, with 75% and 100% responder rates as secondary objectives. Treatment-emergent adverse events (TEAEs) and adverse drug reactions were recorded. A post hoc analysis was performed to investigate the effect of titration speed and different concomitant AEDs on the efficacy and safety of perampanel. Results Of the 85 patients analysed, seizure reductions of 50%, 75% and 100% were observed in 80.0% (95% confidence interval [CI]: 69.9-87.9), 71.8% (95% CI: 61.0-81.0) and 47.1% (95% CI: 36.1-58.2) during the maintenance period, respectively. The 50%, 75% and 100% response rates in patients with secondarily generalized tonic-clonic seizures were 87.5% (95% CI: 61.7-98.5), 87.5% (95% CI: 61.7-98.5) and 75.0% (95% CI: 47.6-92.7), respectively. The most common TEAEs were dizziness (50.0%), somnolence (9.8%) and headache (8.8%). The efficacy outcomes and safety profile of perampanel were more favourable with slow titration and relatively consistent when stratified by concomitant AEDs. Conclusions Perampanel was effective and well tolerated as a first add-on to monotherapy in patients with focal-onset seizures, with or without secondarily generalized seizures.

Introduction Clinical practice studies help guide antiepileptic drug (AED) therapy in patient groups routinely excluded from clinical trials, such as the elderly. The Euro-Esli study investigated the effectiveness and safety/tolerability of eslicarbazepine acetate (ESL) when used in everyday clinical practice in Europe. A subanalysis of data from elderly patients (≥ 60 years) included in the Euro-Esli study was conducted to assess these aspects of ESL use in this population. Methods Euro-Esli was a pooled analysis of 14 European clinical practice studies. Effectiveness parameters included responder (≥ 50% seizure frequency reduction) and seizure freedom rates after 3, 6 and 12 months of treatment and at last visit. Safety and tolerability were assessed throughout the follow-up by evaluating adverse events (AEs) and ESL discontinuation due to AEs, respectively. Data were compared for patients aged ≥ 60 versus those aged

Neurocysticercosis is a frequent cause of seizures in endemic countries. It is caused by the larvae of the tapeworm Taenia solium. The larvae once hosted in the cerebral parenchyma evolve into viable cysts, called the vesicular stage (with little or no inflammatory reaction), and may remain at this stage for years, or may enter in an inflammatory‐degenerative process (colloidal phase) that ends with calcified nodules. Edema and MRI contrast enhancement associated with these calcifications have been described, suggesting that it may be associated with seizures. However, most of these reports were either cross‐sectional case‐control series or case reports with a single time point MRI. Therefore, the clinical significance of recurring perilesional edema and contrast enhancement around calcified lesions is still uncertain. Here, we describe repeated MRIs of a patient with calcified neurocysticercosis over 4 years. The seizures were associated with edema and contrast enhancement that disappeared in the seizure‐free periods, occurring only around one calcified nodule that coincided with the EEG findings and seizure semiology, although he had three additional calcifications. These findings support the association between pericalcification contrast enhancement and edema with recent seizures. This MRI finding may be a marker to define the epileptogenic focus in epilepsies with calcified neurocysticercosis.

Although epileptologists have a lot of antiepileptic drugs (AEDs) at their disposal now and there are more than 10 novel AEDs; until the present time, two groups of drugs (valproic acid and carbamazepine, which were designed in the 1970s) have remained the gold standard for the treatment of epilepsy. These 2 AEDs are called traditional or standard and the European literature on epileptology describes them as first-choice anticonvulsants. Carbamazepine has a narrower spectrum of therapeutic action and may aggravate a few types of seizures. On the contrary, valproates are effective in all forms of epilepsy, both focal and generalized ones. The anticonvulsant properties of valproic acid were discovered in 1962. Now valproates are successfully used in various age groups of patients with different forms of epilepsy and types of seizures during both mono- and polytherapy in more than 100 countries of Europe and the world, by firmly holding the leading position. A lot of cheaper valproic acid generic drugs have emerged in clinical practice in the past decades. By and large, almost 20 valproates that have one common active ingredient (valproic acid) and are commonly used to treat epilepsy are now available on the global pharmaceutical market. The authors give the results of trials and describe their own experience with Valparin XR, an extended-release valproic acid drug. The results of the trials and clinical experience show the efficacy and good tolerability of Valparin XR in the treatment of epilepsy.

Purpose: Evaluate real-life experience with eslicarbazepine acetate (ESL) after first monotherapy failure in a large series of patients with focal epilepsy. Method: Multicentre, retrospective, 1-year, observational study in patients older than 18 years, with focal epilepsy, who had failed first antiepileptic drug monotherapy and who received ESL. Data from clinical records were analysed at baseline, 3, 6 and 12 months to assess effectiveness and tolerability. Results: Eslicarbazepine acetate was initiated in 253 patients. The 1-year retention rate was 92.9%, and the final median dose of ESL was 800 mg. At 12 months, 62.3% of patients had been seizure free for 6 months; 37.3% had been seizure free for 1 year. During follow-up, 31.6% of the patients reported ESL-related adverse events (AEs), most commonly somnolence (8.7%) and dizziness (5.1%), and 3.6% discontinued due to AEs. Hyponatraemia was observed in seven patients (2.8%). After starting ESL, 137 patients (54.2%) withdrew the prior monotherapy and converted to ESL monotherapy; 75.9% were seizure free, 87.6% were responders, 4.4% worsened, and 23.4% reported ESL-related AEs. Conclusion: Use of ESL after first monotherapy failure was associated with an optimal seizure control and tolerability profile. Over half of patients were converted to ESL monotherapy during follow-up.

Purpose The literature on the efficacy and safety of rufinamide in childhood-onset epilepsy syndromes currently includes approximately 600 paediatric patients. This paper summarizes the views of a panel of experienced European epileptologists with regard to the current role of rufinamide in the treatment of childhood epilepsies. Results Rufinamide is effective in decreasing the seizure frequency in the Lennox-Gastaut syndrome (LGS), especially tonic and atonic seizures. It might consequently be preferred to other drugs as a second-line treatment for LGS when drop-attacks are frequent. The mean responder rate in the published studies is 38% with seizure freedom achieved in 2.4% of patients. Rufinamide has shown some efficacy in epileptic encephalopathies other than LGS. It can be also effective as adjunctive therapy in children and adolescents with drug-resistant partial seizures. The available data suggest that rufinamide has an acceptable risk/benefit ratio with quite a low risk of aggravating seizures. Common adverse effects (somnolence, nausea and vomiting) are usually mild and self-limiting; they are more frequently observed during titration than in the maintenance phase, suggesting that low escalation rates might be associated with fewer adverse effects. Rufinamide appears to have a favourable cognitive profile compared with other antiepileptic drugs. Conclusion Rufinamide is only approved for adjunctive treatment of seizures associated with LGS in children 4 years of age and older. There are very few data on rufinamide treatment at the onset of LGS or early in the course of the disorder; whether early treatment will improve outcome has yet to be determined.

Purpose We present six patients with epilepsy of infancy with migrating focal seizures (EIMFS) and provide a comprehensive evaluation of potassium bromide therapy. Method Between February 1, 2007 and July 31, 2012, six patients who met the diagnostic criteria of EIMFS were treated with potassium bromide. Potassium bromide was added to other antiepileptic drugs (AEDs) in doses ranging from 30 to 80mg/kg/day. Plasma bromide concentration was monitored. A therapeutic bromide concentration between 75 and 125mg/dL was considered to be ideal. Results Four of six children responded well to bromide. One of these patients became seizure free, but remained severely mentally impaired. Two boys, currently 4 and 6 years of age, respectively, have monthly seizures as well as axial hypotonia and severe language impairment. The fourth child responded well to bromide, having only weekly seizures and moderate psychomotor retardation. The patient who became seizure free improved visual contact and head control. In the other three patients with good control, the seizures became focal without secondary generalization and status epilepticus and hospital admission was not required. The remaining two patients did not respond well to bromide. Adverse effects were seen in three cases: vomiting in one, drowsiness in another, and acneiform eruption in the face in the remaining patient. Adverse effects resolved with dose reduction. Conclusion Early treatment with bromides should be considered in EIMFS to control the seizures and status epilepticus and to avoid progressive cognitive impairment. Potassium bromide is an old AED. Plasma concentration monitoring should be considered.

Summary Backgrand. Lateralized periodic discharges (LPDs) are infrequent electroencephalograph (EEG) findings, and may present in ictal or interictal form. They are regarded as potential electrophysiologic signs of convulsive or nonconvulsive status epilepticus (NCSE). We report four patients who presented with NCSE and one who presented with convulsive status epilepticus in the postictal period, characterized by LPDs in EEG recordings in the first year after stroke. Material and methods. We prospectively evaluated patients who clinically presented with status epilepticus associated LPDs between March 2014 and March 2015. We investigated patients that presented with a new stroke occurrence. We excluded the other LPD etiologies. EEG studies of five patients (two men) who were admitted to our emergency unit with confusion, three of whom had visual symptoms; four were treated for NCSE as diagnosed with LPDs. The fifth patient had convulsive status epilepticus with LPD in the postictal period. Results and Discussion. None of the five patients, who were aged between 68 and 92 years, showed any etiologic factor other than a history of cerebrovascular disease (CVD). Magnetic resonance imaging studies of the patients revealed old infarcts and transitional diffusion restrictions. The clinical and EEG findings decreased substantially upon antiepileptic drug treatment. Herein, we illustrate the first patient who had confusion, visual hallucinations, and ictal and interictal LPD in her consecutive EEGs. Conclusions. CVDs may pave the way for LPDs in patients with a history of stroke because CVDs cause structural brain damage. Patients who present with a similar clinical profile and imaging signs of stroke should be checked for NCSE, particularly in the presence of LPDs in EEGs.

RATIONALE: Benign focal seizures of adolescence (BFSA) described by Loiseau et al in 1972, is considered a rare entity, but maybe underdiagnosed. Although mild neuropsychological deficits have been reported in patients with benign epilepsies of childhood, these evaluations have not so far been described in BFSA. The aim of this study is to evaluate neuropsychological functions in BFSA with new onset seizures (

We describe the electroclinical features, therapy, and long-term evolution of 17 patients with migrating focal seizures in infancy, and analyzed the charts of these patients seen between February 1985 and July 2005. Three different electroclinical patterns were recognized: (1) 8 cases with alternating simple focal motor seizures at onset. The ictal electroencephalography (EEG) pattern was characterized by recurrence of rhythmic focal spikes or rhythmic sharp activity in the Rolandic region; (2) 5 cases with complex focal seizures and progressive appearance of polymorphic δ-θ activity in 1 temporo-occipital region recurring independently; (3) 4 cases with focal complex seizures with motor manifestations. Ictal EEG showed flattening or fast activity in 1 frontotemporal region followed by unilateral fast poly-spikes in alternating clusters in both hemispheres. The focal seizures were refractory to antiepileptic drugs, and all patients except 3 had severe developmental delay. Migrating focal seizures in infancy is a newly defined and rare, but underrecognized, epileptic encephalopathy.

Epilepsia partialis continua (EPC) refers to focal and recurrent seizures that happenevery few seconds to minutes for extended periods of time. The most common causesof these seizures are stroke, Rasmussen’s encephalitis (in children), and viral encephalitis.Metabolic disorders, like hyperglycemic hyperosmolar state (HHS), infrequentlycause EPC. Correction of the HHS stops the EPC and eliminates the need for antiepilepticdrugs. Synaptic transmission in the central nervous system requires normal glucoseconcentrations. Hyperglycemia can lower the seizure threshold, and this possiblyexplains the development of seizures in patients with HHS.

There is an ample evidence that hypopigmentation of the skin along the Blaschko’s lines is frequently associated with neurological disorders. Nowadays, the term “Hypomelanosis of Ito” (HI) is applied when, together with the cutaneous lesions, various and multisystem organs are involved. Among these, the most frequent are cerebral manifestations, such as cognitive delay and epileptic seizures. For this reason, hypomelanosis of Ito has been included in the group of neurocutaneous syndromes, neurologic manifestations being one of the most frequent. Epileptic seizures have been reported in patients with this disorder, but in a very few particular attention has been focused on the type and frequency of epilepsy and on the response to the treatment. Herein, we report on five patients with HI who showed episodes of epileptic seizures with onset in childhood, in absence of malformative anomalies except for the skin lesions. A survey on the frequency and types of epileptic seizures in HI children and in the literature is reported.

Background: Eslicarbazepine acetate (ESL) is a new antiepileptic drug (AED) licensed as adjunctive therapy in adults with partial-onset or focal seizures. Objective: To evaluate in a clinical practice setting the long-term efficacy and safety of ESL in patients with focal seizures. Methods: ESLIBASE was a retrospective study that included all patients with focal seizures who started ESL between January 2010 and July 2012 at 12 hospitals. ESL was prescribed individually according to real-life practice. Efficacy and safety were evaluated over 1 year. Switching from carbamazepine (CBZ) and oxcarbazepine (OXC) was assessed. Results: Three hundred and twenty-seven patients were included; 78% of patients were taking >= 2 other AEDs at baseline. Most (87%) began ESL because of poor seizure control and13% because of adverse events (AEs) with CBZ or OXC. After 1 year, 237 patients (72.4%) remained on ESL. At 3, 6 and 12 months, the responder rate was 46.3%, 57.9%, and 52.5%, and 21.0%, 28.0%, and 25.3% of patients were seizure free. The responder rate significantly increased when ESL was combined with a non-sodium channel-targeting drug (non-SC drug) (66.7%) versus an SC drug (47.7%; p < 0.001). At 12 months, 40.7% of patients had >= 1 AE; AEs led to treatment discontinuation in 16.2%. Dizziness, nausea, and somnolence were the most common AEs. The tolerability profile improved in >50% of the patients who switched from CBZ or OXC to ESL because of AEs. Conclusions: ESL was well tolerated and effective in a real-world setting over 1 year. Side-effect profile improved when OXC and CBZ recipients were switched to ESL. (C) 2014 Elsevier B.V. All rights reserved.

Summary Objective In one third of patients with a diagnosis of pharmacoresistant focal epilepsy who are candidates for therapeutic surgery, cerebral areas responsible for seizure generation can be defined exclusively with invasive intracranial recordings. A correct presurgical identification of the epileptogenic zone (EZ) with intracranial electrodes has a direct impact on postsurgical outcome. We aimed at identifying biomarkers of the EZ based on computer-assisted inspection of intracranial electroencephalography (EEG). Methods Computer-driven intracranial EEG analysis in the domains of time, frequency, and space was retrospectively applied to a population of 10 patients with focal epilepsy to detect EZ electrophysiologic markers. Next, a prospective study was performed on 14 surgery candidate patients. The stereo-EEG computer-assisted analysis of EZ boundaries performed blind from patients data was compared to that defined with the traditional visual inspection completed by neurophysiologists. Results In the retrospective study, the EZ was characterized by the combined detection of three biomarkers observed at seizure onset: (1) fast activity at 80–120 Hz associated with (2) very slow transient polarizing shift and (3) voltage depression (flattening). Correlations between these indexes were calculated for each seizure. In the prospective study, the quantified analysis based on the three biomarkers confirmed a complete overlap between leads within the EZ identified by expert clinicians. In 2 of 14 patients the proposed biomarkers partially identified the EZ. Significance Our findings demonstrate and validate with a prospective unbiased study the use of three neurophysiologic intracranial EEG parameters as excellent biomarkers of ictogenesis and as reliable indicators of EZ boundaries.

Aim The goal of antiepileptic treatment is to achieve seizure freedom or seizure control. The aim of this paper is to review the evidence for the use of lacosamide for adjunctive treatment of refractory focal seizures with or without secondary generalization, within the scope of the 2012 update of the Clinical Guideline published by the National Institute for Health and Clinical Excellence (NICE). Methods Clinical evidence for the use of lacosamide and other antiepileptic drugs (AEDs) was systematically reviewed, evaluated, and presented to the Guideline Development Group. Only randomized clinical trials were included. Outcomes of clinical efficacy (seizure freedom, 50% reduction in seizure frequency, time to first seizure, time to 12-month remission, treatment withdrawal, and time to treatment withdrawal), experience of adverse events, and cognitive and quality of life outcomes were reviewed. A decision model was built to weigh the clinical benefits of each adjunctive AED, measured by seizure control and seizure reduction, compared with the harm from adverse events, as measured by withdrawals from treatment due to adverse events. Results Lacosamide was included as part of the recommended AEDS to be used in tertiary epilepsy centers. The evidence review showed that more participants who received lacosamide as an adjunctive treatment had at least a 50% reduction in seizure frequency compared with those taking placebo. However, more participants on lacosamide were found to experience adverse events and withdrawal from treatment compared with those on placebo. The cost-effectiveness analysis showed that compared with placebo, the benefits gained from adjunctive lacosamide were modest and uncertain, whereas the costs were significantly high. Compared with other AEDs licensed for adjunctive therapy in focal seizures, lacosamide was associated with fewer quality-adjusted life years and higher costs. Therefore, the Guideline Development Group noted that the balance of benefit and harm needs to be carefully monitored in all patients.

Circadian rhythm of seizure is underestimated in the study of focal epilepsies. A review of the current literature revealed a clear correlation between cortical epileptogenic focus and the circadian phase of seizure peak occurrence in adult patients. A single diurnal peak at 19:00 was found in seizures originating from the occipital lobe, between 5:00 and 7:00 in frontal lobe seizures, and between 16:00 and 17:00h in temporal lobe seizures. Two diurnal peaks, between 5:00 and 7:00, and at 23:00 are reported in seizures from the parietal lobe, and between 7:00 to 8:00 and 16:00 to 17:00 in mesial temporal onset seizures. This circadian character of seizure occurrence in focal epilepsies may not be unique to partial seizures since recent clinical and experimental data indicate that generalized seizures also demonstrate circadian effects. The clinical evidence on generalized seizures and epilepsies is not recent, but a formal integration of circadian rhythmicity in our understanding and clinical management of epilepsies may be warranted.

Despite the significant progress made in epileptology, resistant epilepsies constitute approximately 30 % of all forms of epilepsy. An overview of recent literature is provided on the efficacy and safety of a new antiepileptic drug zonisamide (Zonegran) in the treatment of epilepsy with emphasis on monotherapy. The mode of action, pharmacokinetic characteristics, the effectiveness and tolerance of zonisamide in resistant focal epilepsy, as well as other types of seizures and forms of epilepsy are described. Indications for use of the drug are discussed. Also a wider potential for application of zonisamide are described: in the treatment of generalized seizures, in monotherapy as well as in children and adolescents. At present, Zonegran is registered for application in children from 6 years and older, with focal seizures, in additional therapy. The authors present their own observation of high efficacy of zonisamide in adjunctive therapy in a child of 9 years with cryptogenic focal epilepsy. Onset of epileptic seizures at the age of 5 months. Since the onset of the disease the child has received a lot of antiepileptic drugs in various combinations, with no significant effect. Zonisamide (Zonegran) was introduced in therapy 4 months ago in combination with the valproate acid drug (which the child received over the years), and since the release to the full dose epileptic seizures are absent up to present. It should be noted that there was not a single remission of four-month duration since the onset of the disease. Moreover, normalization of sleep has been noted. Tolerability of the therapy is good. No side effects were noted.

Researchers at the All India Institute of Medical Sciences, New Delhi, India, and VU University Medical Center, Amsterdam report a 6-year-old Indian boy with infantile-onset Alexander disease having an unusually mild clinical course and a de novo mutation in the glial fibrillary acidic protein (GFAP) gene.

The efficacy of the ketogenic diet in the treatment of intractable focal seizures was studied retrospectively in 34 patients (mean age, 7.5 yrs; range, 4 months to 29 yrs) and compared to 100 patients with generalized seizures at the Cleveland Clinic, OH.