La señal de la cruz: un automatismo muy poco frecuente en la epilepsia del lóbulo temporal. Descripción de dos casos / The sign of the cross: a very rare automatism in temporal lobe epilepsy. Two case reports

Introducción: En la evaluación de la epilepsia farmacorresistente, el análisis detallado de la semiología es fundamental para establecer una hipótesis diagnóstica de la localización de la zona epileptógena. La señal de la cruz es un automatismo manual complejo muy infrecuente descrito por primera vez en 2008 y poco referido en la bibliografía. Caso clínico: Presentamos dos casos con presencia de la señal de la cruz de nuestra serie de pacientes monitorizados mediante videoelectroencefalograma, uno de ellos estudiado también con electrodos profundos, en los que describimos la localización de la descarga en el momento de realizar la señal de la cruz. Se realiza también una revisión bibliográfica para intentar establecer un valor localizador y/o lateralizador de este signo.(AU)

Introduction: In the evaluation of drug-resistant epilepsy, a detailed analysis of the semiology is essential to establish a diagnostic hypothesis of the location of the epileptogenic zone. Cross-sign (CS) is a very infrequent complex manual automatism described for the first time in 2008 and rarely reported in the literature. Case report: We present two cases from our series of patients monitored by video-EEG, one of whom also studied with deep electrodes, in which we describe the location of the discharge while performing the CS. A bibliographic review is also carried out to try to establish a localizing and/or lateralizing value of this sign. Conclusion: The sign of the cross is a rare ictal automatism that occurs in patients with temporal lobe epilepsy. The hand used to make the sign of the cross is the dominant one, regardless of the origin of the crises.(AU)

[The sign of the cross: a very rare automatism in temporal lobe epilepsy. Two case reports]. / La señal de la cruz: un automatismo muy poco frecuente en la epilepsia del lóbulo temporal. Descripción de dos casos.

INTRODUCTION: In the evaluation of drug-resistant epilepsy (DRF), a detailed analysis of the semiology is essential to establish a diagnostic hypothesis of the location of the epileptogenic zone. Cross-sign (CS) is a very infrequent complex manual automatism described for the first time in 2008 and rarely reported in the literature. CASE REPORT: We present two cases from our series of patients monitored by videoEEG, one of whom also studied with deep electrodes, in which we describe the location of the discharge while performing the CS. A bibliographic review is also carried out to try to establish a localizing and/or lateralizing value of this sign. CONCLUSION: The sign of the cross is a rare ictal automatism that occurs in patients with temporal lobe epilepsy. The hand used to make the sign of the cross is the dominant one, regardless of the origin of the crises.

TITLE: La señal de la cruz: un automatismo muy poco frecuente en la epilepsia del lóbulo temporal. Descripción de dos casos.Introducción. En la evaluación de la epilepsia farmacorresistente, el análisis detallado de la semiología es fundamental para establecer una hipótesis diagnóstica de la localización de la zona epileptógena. La señal de la cruz es un automatismo manual complejo muy infrecuente descrito por primera vez en 2008 y poco referido en la bibliografía. Caso clínico. Presentamos dos casos con presencia de la señal de la cruz de nuestra serie de pacientes monitorizados mediante videoelectroencefalograma, uno de ellos estudiado también con electrodos profundos, en los que describimos la localización de la descarga en el momento de realizar la señal de la cruz. Se realiza también una revisión bibliográfica para intentar establecer un valor localizador y/o lateralizador de este signo. Conclusión. La señal de la cruz es un raro automatismo ictal que ocurre en pacientes con epilepsia del lóbulo temporal. La mano empleada para la señal de la cruz es la dominante, independientemente del origen de las crisis.

New therapeutic approach in Dravet syndrome and Lennox-Gastaut syndrome with cannabidiol. / Cannabidiol en los síndromes de Dravet y Lennox-Gastaut: un nuevo abordaje terapéutico.

INTRODUCTION: Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) are two serious epileptic syndromes with paediatric onset which are refractory to therapy and are associated with an important increase in mortality rates and comorbidities compared to the general population. These pathologies have a strong impact on the lives of patients and their families, because they undergo multiple pharmacological therapies (many of them without specific indication), with frequent changes due to poor efficacy and associated adverse effects. The specialists who care for these patients highlight unmet needs and the lack of specific, safe and effective treatments for better management of the syndrome. DEVELOPMENT: A group of four neurologists specializing in epilepsy has met to review the scientific literature and evaluate the efficacy and safety of oral solution cannabidiol in the treatment of these syndromes, both in randomized clinical trials (CT) and in some observational studies. CONCLUSIONS: Cannabidiol is positioned as an innovative therapy that allows better control of epileptic seizures and comorbidities of DS and LGS, furthermore its efficacy and safety have been evaluated in more than 700 patients. In CTs, cannabidiol significantly reduced the percentage of convulsive seizures and drop seizures compared to placebo in patients with DS and LGS respectively, which could improve their quality of life and that of their family members. The most frequent adverse effects reported were somnolence and decreased appetite. Elevated liver aminotransferase levels were also reported, especially in patients given concomitant sodium valproate. This therapy may allow better control of the epileptic seizures associated with these syndromes.

TITLE: Cannabidiol en los síndromes de Dravet y Lennox-Gastaut: un nuevo abordaje terapéutico.Introducción. Los síndromes de Dravet (SD) y Lennox-Gastaut (SLG) son dos síndromes epilépticos graves y de inicio en la edad pediátrica, refractarios al tratamiento, asociados a un notable incremento en las tasas de mortalidad y comorbilidades respecto a la población general. Suponen un fuerte impacto en la vida de los pacientes y sus familiares, ya que los pacientes están sometidos a múltiples terapias farmacológicas (muchas sin indicación específica), con cambios frecuentes debido a la escasa eficacia y a los efectos adversos. Los especialistas que les atienden destacan las necesidades no cubiertas y la falta de tratamientos específicos, seguros y eficaces para un mejor manejo de la enfermedad. Desarrollo. Se ha reunido un grupo formado por cuatro neurólogos especialistas en epilepsia para hacer una revisión de la literatura científica y evaluar los resultados de eficacia y seguridad de la solución oral de cannabidiol en el tratamiento de estos síndromes, tanto en ensayos clínicos aleatorizados como en diversos estudios observacionales. Conclusiones. El cannabidiol se sitúa como una terapia innovadora que permite un mejor control de las crisis epilépticas y comorbilidades del SD y el SLG; además, su eficacia y seguridad han sido evaluadas en más de 700 pacientes. En los ensayos clínicos redujo significativamente el porcentaje de crisis convulsivas y de caída en comparación con placebo en los pacientes con SD y SLG, respectivamente, y puede mejorar su calidad de vida y la de sus familiares. Los efectos adversos más frecuentes fueron la somnolencia y la disminución del apetito. También se notificaron niveles elevados de aminotransferasas hepáticas, especialmente en pacientes tratados concomitantemente con ácido valproico. Esta terapia podría permitir un mejor control de las crisis epilépticas asociadas a estas patologías.

Cannabidiol en los síndromes de Dravet y Lennox-Gastaut: un nuevo abordaje terapéutico / New therapeutic approach in Dravet syndrome and Lennox-Gastaut syndrome with cannabidiol

Introducción: Los síndromes de Dravet (SD) y Lennox-Gastaut (SLG) son dos síndromes epilépticos graves y de inicio en la edad pediátrica, refractarios al tratamiento, asociados a un notable incremento en las tasas de mortalidad y comorbilidades respecto a la población general. Suponen un fuerte impacto en la vida de los pacientes y sus familiares, ya que los pacientes están sometidos a múltiples terapias farmacológicas (muchas sin indicación específica), con cambios frecuentes debido a la escasa eficacia y a los efectos adversos. Los especialistas que les atienden destacan las necesidades no cubiertas y la falta de tratamientos específicos, seguros y eficaces para un mejor manejo de la enfermedad. Desarrollo: Se ha reunido un grupo formado por cuatro neurólogos especialistas en epilepsia para hacer una revisión de la literatura científica y evaluar los resultados de eficacia y seguridad de la solución oral de cannabidiol en el tratamiento de estos síndromes, tanto en ensayos clínicos aleatorizados como en diversos estudios observacionales. Conclusiones: El cannabidiol se sitúa como una terapia innovadora que permite un mejor control de las crisis epilépticas y comorbilidades del SD y el SLG; además, su eficacia y seguridad han sido evaluadas en más de 700 pacientes. En los ensayos clínicos redujo significativamente el porcentaje de crisis convulsivas y de caída en comparación con placebo en los pacientes con SD y SLG, respectivamente, y puede mejorar su calidad de vida y la de sus familiares. Los efectos adversos más frecuentes fueron la somnolencia y la disminución del apetito. También se notificaron niveles elevados de aminotransferasas hepáticas, especialmente en pacientes tratados concomitantemente con ácido valproico. Esta terapia podría permitir un mejor control de las crisis epilépticas asociadas a estas patologías.(AU)

Introduction: Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) are two serious epileptic syndromes with paediatric onset which are refractory to therapy and are associated with an important increase in mortality rates and comorbidities compared to the general population. These pathologies have a strong impact on the lives of patients and their families, because they undergo multiple pharmacological therapies (many of them without specific indication), with frequent changes due to poor efficacy and associated adverse effects. The specialists who care for these patients highlight unmet needs and the lack of specific, safe and effective treatments for better management of the syndrome. Development: A group of four neurologists specializing in epilepsy has met to review the scientific literature and evaluate the efficacy and safety of oral solution cannabidiol in the treatment of these syndromes, both in randomized clinical trials (CT) and in some observational studies. Conclusions: Cannabidiol is positioned as an innovative therapy that allows better control of epileptic seizures and comorbidities of DS and LGS, furthermore its efficacy and safety have been evaluated in more than 700 patients. In CTs, cannabidiol significantly reduced the percentage of convulsive seizures and drop seizures compared to placebo in patients with DS and LGS respectively, which could improve their quality of life and that of their family members. The most frequent adverse effects reported were somnolence and decreased appetite. Elevated liver aminotransferase levels were also reported, especially in patients given concomitant sodium valproate. This therapy may allow better control of the epileptic seizures associated with these syndromes.(AU)

Perampanel effectiveness and safety as early add-on treatment for focal-onset seizures: PEREAGAL study.

BACKGROUND: Perampanel (PER) is an effective adjunctive therapy for controlling focal-onset seizures (FOS), but few studies have examined its effects as an early add-on for the treatment of FOS in daily clinical practice. METHODS: Our retrospective, multicenter, observational study evaluated the effectiveness and safety of PER as an early add-on in 77 patients with FOS, with and without focal to bilateral tonic-clonic seizures (FBTCS) after 3, 6 and 12 months in a real-world setting. RESULTS: After 12 months of treatment (median dose 6 [4,8] mg/day), the retention rate was 79.2 % and 60 % of patients (39/65) experienced a ≥50 % reduction in seizure frequency relative to baseline. The seizure-free rate was 38.5 % for all seizures (25/65) and 60 % for FBTCS (12/20). The responder rate at 12 months was significantly higher when PER was given with one concomitant AED (72.2 %) compared to when PER was given with two concomitant AEDs (44.8 %). Drug-related adverse events (AEs) were reported in 40.3 % of patients, most of them being mild (64.2 %). Twelve patients (15.6 %) discontinued treatment because of AEs. CONCLUSIONS: PER is an effective and safe early add-on for patients with refractory FOS, especially for those with FBTCS.

Observational multicentre study into the use of antiepileptic drugs in Spanish neurology consultations. / Estudio observacional multicéntrico español sobre el empleo de fármacos antiepilépticos en consultas de neurología.

INTRODUCTION: The study aims to quantify the types of antiepileptic drugs (AED) prescribed in neurology consultations. MATERIAL AND METHOD: This descriptive, observational study included a sample of 559 patients older than 14 years, diagnosed with epilepsy, and receiving pharmacological treatment. Data were collected at outpatient consultations by 47 Spanish neurologists in May 2016. Epilepsy was defined based on the International League Against Epilepsy classification. According to the year of marketing, AEDs were categorised as classic (before 1990) or new (after 1990). We performed a descriptive analysis of qualitative and quantitative variables. RESULTS: Female patients accounted for 54.6% of the sample. Mean age was 42.7 years; mean age of onset was 22.4. Regarding epilepsy type, 75.7% of patients experienced partial seizures, 51.5% were symptomatic,32.4% had refractory epilepsy, 35.6% had been seizure-free for the previous year, and 59.2% had associated comorbidities.A total of 1103 AED prescriptions were made; 64.6% of prescriptions were for new AEDs; 85.4% of patients received new AEDs. Patients received a mean of 2 AEDs (range, 1-5). A total of 59.6% of patients received polytherapy.The most frequently prescribed AEDs were levetiracetam (42.6%), valproic acid (25.4%), lamotrigine (19.5%), carbamazepine (17.9%), and lacosamide (17.5%). No AED was employed exclusively as monotherapy. The most frequently prescribed AEDs for generalised and partial seizures were valproic acid (48.2%) and levetiracetam (43.2%), respectively. Valproic acid was less frequently prescribed to female patients. Patients with refractory epilepsy or with associated comorbidities were more frequently prescribed a combination of new and classic AEDs (48.7% and 45.6%, respectively) than only one type of AED. CONCLUSIONS: The majority of patients received new AEDs. The combination of classic and new AEDs was more frequently prescribed to patients with refractory epilepsy or with associated comorbidities.

Retrospective study of perampanel efficacy and tolerability in myoclonic seizures.

OBJECTIVES: Perampanel is an antiepileptic drug (AED) approved for add-on treatment of focal seizures (with or without generalization) and primary generalized tonic-clonic (GTC) seizures. Our objective was to explore the effectiveness and tolerability of adjunctive perampanel in patients with drug-resistant myoclonic seizures, after failure of other AEDs. MATERIALS AND METHODS: Retrospective, multicenter, observational study. Data were collected from individual patient clinical files and analysed using appropriate descriptive statistics and inferential analyses. RESULTS: Data are reported for 31 patients with mean age 36.4 years, who had an average epilepsy duration of 18 years, previously taken an average of 5.03 AEDs, and were taking an average of 2.4 AEDs on perampanel initiation. Patients exhibited myoclonic, GTC, absence, tonic and focal seizures, and most had associated cognitive decline and/or ataxia. Median time on perampanel was 6 months, most common dose was 6 mg, and overall retention rate was 84%. The responder rate for myoclonic seizures was defined via reduction of days with myoclonic seizures per month. At 6 months, 15 (48.4%) of the 31 patients were classed as myoclonic seizure responders, 10 (32.3%) were myoclonic seizure free, and 39% saw improvements in functional ability. Of 17 patients with GTC seizures at baseline, 9 (53%) were responders at 6 months, and 8 (47.1%) were seizure free. The most frequent side effects were psychiatric disorders, instability, dizziness and irritability, and mostly resolved with dose reduction. Five patients discontinued perampanel due to side effects. CONCLUSIONS: Perampanel caused clinically meaningful improvements in patients with drug-resistant myoclonic seizures. It was generally well tolerated, but psychiatric and neurological side effects sometimes required follow-up and dose reduction.

[Functional hemispherectomy: long-term follow-up in a series of five patients]. / Hemisferectomia funcional: seguimiento a largo plazo en una serie de cinco casos.

INTRODUCTION: Functional hemispherectomy consists in palliative epilepsy surgical procedure usually performed in patients with pharmaco-resistant epilepsy and hemispheric syndromes. It is based on the neural disconnection of the affected hemisphere with preservation of the vascular supply. AIM: To analyze long-term prognosis and safety of the hemispherectomies performed in our institution. PATIENTS AND METHODS: Retrospective analysis collecting the following variables: age, gender, age of epilepsy onset, type of seizures, etiology, age of epilepsy surgery, prognosis and potential surgical complications. All patients had a minimum of five years of follow up. RESULTS: Five patients (60% females) underwent hemispherotomy between 1999 and 2010. Age of epilepsy onset was 36 months and time of evolution until surgery was 7 years. The most frequent type of seizures were simple motor seizures with secondary generalization (n = 5). Three patients remained seizure free persistently after surgery and another patient had a more than 90% improvement. Time of follow up was 13 years. One patient suffered a bacterial meningitis without sequelae. Six years after surgery a patient suffered hydrocephalous requiring ventriculoperitoneal shunt. CONCLUSIONS: Functional hemispherectomy constitutes an effective method to treat patients with pharmaco-resistant epilepsy, extensive unihemispheric pathology and seizures limited to that hemisphere. Late complications may occur thus long-term follow-up is needed.

TITLE: Hemisferectomia funcional: seguimiento a largo plazo en una serie de cinco casos.Introduccion. La hemisferectomia funcional es una de las tecnicas quirurgicas con intencion paliativa que se pueden realizar en pacientes con epilepsia farmacorresistente y sindromes hemisfericos. Se basa en la desconexion neuronal del hemisferio afectado preservando el arbol vascular. Objetivo. Analizar el pronostico y la seguridad a largo plazo de las hemisferectomias realizadas en nuestro centro. Pacientes y metodos. Revision retrospectiva de los casos intervenidos, recogiendo las siguientes variables clinicas: edad, sexo, edad de inicio de la epilepsia, tipo de crisis, etiologia de la epilepsia, edad de intervencion, pronostico posquirurgico y posibles complicaciones. El seguimiento minimo fue de cinco años. Resultados. Cinco pacientes (60% mujeres) fueron intervenidos entre 1999 y 2010. La edad de inicio de la epilepsia fue de 36 meses, y el tiempo de evolucion hasta la cirugia, de 7 años. El tipo de crisis mas habitual fueron las crisis parciales simples motoras con generalizacion secundaria (n = 5). Tres pacientes permanecieron libres de crisis tras la cirugia, y otro paciente mejoro mas de un 90%. El tiempo medio de seguimiento fue de 13 años. Como complicaciones, una paciente sufrio una meningitis bacteriana sin secuelas posteriores. A los seis años de la cirugia, un paciente presento una hidrocefalia que requirio la implantacion de una valvula de derivacion ventriculoperitoneal. Conclusiones. La hemisferectomia funcional constituye un procedimiento quirurgico eficaz para el tratamiento de pacientes con epilepsia farmacorresistente, patologia hemisferica extensa y crisis limitadas a ese hemisferio. Hay complicaciones que pueden aparecer tardiamente, por lo que se aconseja un seguimiento a largo plazo de estos pacientes.

VNS and pregnancy: A multicentric experience of four cases.

BACKGROUND: Vagus nerve stimulation system (VNS) has been employed worldwide as adjunctive therapy in drug-resistant epileptic patients. Only nine previous pregnancies with six-positive outcomes have been reported in women with epilepsy treated with VNS since 1998. AIMS OF THE STUDY: To communicate the experience of pregnancies in women treated with VNS in our country. METHODS: Clinical data of four female patients treated with VNS during pregnancy and delivery in five gestations is described. RESULTS: Four pregnancy outcomes were positive and one ended in spontaneous abortion, probably more related to the use antiepileptic drugs than VNS itself. Two births were vaginal and the other two with cesarean section. None of the complications during delivery were attributed to VNS. No teratogenicity was documented. CONCLUSIONS: Based on our experience VNS constitutes a safe therapy for the treatment of drug-resistant epilepsy in women of childbearing potential and during pregnancy and delivery. Larger series will be useful to confirm this finding.

Efficacy and safety of eslicarbazepine-acetate in elderly patients with focal epilepsy: Case series.

PURPOSE: Eslicarbazepine-acetate (ESL) is a third generation antiepileptic drug licensed as adjunctive therapy in adults with focal seizures. Efficacy and safety of ESL have been established in real-life setting. However, data about outcomes in elderly patients are scarce. Primary endpoint was to evaluate outcomes of ESL in elderly patients. METHOD: This was a retrospective survey that included patients >65years with focal seizures who started ESL between January 2010 and July 2012 at 12 Spanish Hospitals. ESL was prescribed individually according to real-life practice. Efficacy and safety were evaluated over 1year. These patients were included within the bigger study ESLIBASE. RESULTS: We included 29 patients, most of them males (18). Mean age was 71.2 year-old and epilepsy evolution was 20 years. Eighteen were pharmacorresistant at baseline. At 12 months, the mean dose was 850mg/day, the retention rate 69%, the responder rate 62% and 24.1% were seizure-free. At 12 months, 16 patients (55.2%) had ≥1 adverse effect (AE), that led to discontinuation in 7 patients. Dizziness, nausea and ataxia were the most common AEs. The tolerability profile improved in 4/5 patients who switched from carbamazepine (CBZ) or oxcarbazepine (OXC) to ESL due to AEs. CONCLUSIONS: ESL was well-tolerated and effective in elderly patients in a real-life setting over 1year, with a dose around 800mg/day. AE effects improved in most of who switched from CBZ or OXC to ESL.

EARLY-ESLI study: Long-term experience with eslicarbazepine acetate after first monotherapy failure.

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.

Safety, efficacy and outcome-related factors of perampanel over 12 months in a real-world setting: The FYDATA study.

BACKGROUND: Real-world data of current antiepileptic drugs (AEDs) used to treat focal seizures is of importance to understand the efficacy and safety outside of the clinical trial setting. Here we report real-world data from a large series of patients treated with perampanel for 1year. METHODS: FYDATA was a multicentre, retrospective, 1-year observational study assessing the efficacy and safety of adjuvant perampanel in patients ≥12 years of age with focal epilepsy in a real-world setting. At 12 months, the proportion of patients who were seizure free, median percentage seizure reduction, proportion of responders, retention rate and proportion of patients with adverse events (AEs) were assessed. Analyses were also performed to identify any patient-, medication- and disease-related factors associated with a large clinical response or carry a risk for AEs. RESULTS: A total of 464 patients were included in the study with a retention rate of 60.6% at 1year. The mean number of prior AEDs was 7.8. The median percentage reduction in overall seizures was 33.3% (75% for secondary generalised seizures) after 1year, with 7.2% of patients achieving seizure freedom. Furthermore, patients on non-enzyme-inducing AEDs were more likely to achieve seizure freedom, and logistic regression revealed that patients aged ≥65 years, those with epilepsy due to a vascular aetiology and those who had received fewer prior AEDs showed a better clinical response to perampanel. A total of 62.9% of the patients experienced AEs at 12 months; dizziness, somnolence and irritability were the most frequent AEs. Patients with prior psychiatric comorbidities (hyperactivity and personality disorder) were more likely to experience psychiatric AEs with perampanel, and slower titration schedules were associated with less AEs overall. CONCLUSION: Perampanel, for the treatment of focal epilepsy in a real-world setting in a refractory population, over 1year, demonstrates a similar efficacy and safety profile to that observed in clinical trials. Our results have implications for the optimisation of perampanel use in a clinical setting.

The Spanish Neurological Society official clinical practice guidelines in epilepsy.

Previous Official Clinical Practice Guidelines (CPGs) in Epilepsy were based on expert opinions and developed by the Epilepsy Study Group of the Spanish Neurological Society (GE-SEN). The current CPG in epilepsy is based on the scientific method, which extracts recommendations from published scientific evidence. A reduction in the variability in clinical practice through standardization of medical practice has become its main function. SCOPE AND OBJECTIVES: This CPG is focused on comprehensive care for individuals affected by epilepsy as a primary and predominant symptom, regardless of the age of onset and medical policy. METHODOLOGY: 1. Creation of GE-SEN neurologists working group, in collaboration with Neuropediatricians, Neurophysiologists and Neuroradiologists. 2. Identification of clinical areas to be covered: diagnosis, prognosis and treatment. 3. Search and selection of the relevant scientific evidence. 4. Formulation of recommendations based on the classification of the available scientific evidence. RESULTS: It contains 161 recommendations of which 57% are consensus between authors and publishers, due to an important lack of awareness in many fields of this pathology. CONCLUSIONS: This Epilepsy CPG formulates recommendations based on explicit scientific evidence as a result of a formal and rigorous methodology, according to the current knowledge in the pre-selected areas. This paper includes the CPG chapter dedicated to emergency situations in seizures and epilepsy, which may present as a first seizure, an unfavorable outcome in a patient with known epilepsy, or status epilepticus as the most severe manifestation.

Associated Inosine to interferon: results of a clinical trial in multiple sclerosis.

BACKGROUND: Uric acid (UA) could act as a natural peroxynitrite scavenger with antioxidant properties. It has been proposed that hyperuricemia might protect against multiple sclerosis (MS). METHODS: Patients with relapsing-remitting MS starting treatment with interferon beta-1a 44 µg sc 3/week were randomly assigned to receive either inosine 3 g/day or placebo in a double-blind manner. Follow-up was 12 months. Outcome measures were adverse events and UA laboratory results. Secondary end point was clinical and radiological activity of MS. Relapse rates, percentage of patients without relapses, and progression to secondary MS (SPMS) were assessed. RESULTS: Thirty six patients were included. Two patients in the inosine group showed UA serum level above 10 mg/ml, and symptoms derived from renal colic not leading to hospital admission. Ten additional patients had asymptomatic hyperuricemia (>7 mg). Efficacy parameters (clinical and radiological) were similar between groups. No patient progressed to SPMS CONCLUSIONS: Inosine administration was associated with hyperuricemia and renal colic with no additional effect on MS. We cannot conclude inosine is a safe and well-tolerated drug. Doses of around 2 g/day may be more appropriate for future trials.

Prognosis in epilepsy: initiating long-term drug therapy.

INTRODUCTION: Prognosis in epilepsy refers to the probability of either achieving seizure remission (SR), whether spontaneously or using antiepileptic drugs (AED), or failing to achieve control of epileptic seizures (ES) despite appropriate treatment. Use of AED is recommended after a second unprovoked ES. For a first episode, the decision of whether or not to start drug treatment depends on the risk of recurrence and the advantages or disadvantages of the antiepileptic drug. The main goal of treatment is achieving absence of ES without adverse effects (AE). AED is selected according to epilepsy type and the demographic and clinical characteristics of the patient. DEVELOPMENT: A PubMed search located articles and recommendations by the most relevant scientific societies and clinical practice guidelines concerning epilepsy prognosis and treatment. Evidence and recommendations are classified according to the prognostic criteria of the Oxford Centre for Evidence-Based Medicine (2001) and the European Federation of Neurological Societies (2004) for therapeutic actions. CONCLUSIONS: Most newly diagnosed epileptic patients achieve good control over their ES. The majority of the AEDs available at present provide effective control over all types of ES, and choice therefore depends on the patient's individual characteristics. Treatment should be initiated as monotherapy at the lowest effective dose, which in half of all patients provides ES control and is well tolerated. In cases in which the first AED is not effective, alternative therapy should be started, and monotherapy should be employed before combination therapy where possible. The probability of achieving good control over ES decreases with each successive treatment failure.

Drug-resistant epilepsy: definition and treatment alternatives.

INTRODUCTION: Drug-resistant epilepsy affects 25% of all epileptic patients, and quality of life decreases in these patients due to their seizures. Early detection is crucial in order to establish potential treatment alternatives and determine if the patient is a surgical candidate. DEVELOPMENT: PubMed search for articles, recommendations published by major medical societies, and clinical practice guidelines for drug-resistant epilepsy and its medical and surgical treatment options. Evidence and recommendations are classified according to the criteria of the Oxford Centre for Evidence-Based Medicine (2001) and the European Federation of Neurological Societies (2004) for therapeutic actions. CONCLUSIONS: Identifying patients with drug-resistant epilepsy is important for optimising drug therapy. Experts recommend rational polytherapy with antiepileptic drugs to find more effective combinations with fewer adverse effects. When adequate seizure control is not achieved, a presurgical evaluation in an epilepsy referral centre is recommended. These evaluations explore how to resect the epileptogenic zone without causing functional deficits in cases in which this is feasible. If resective surgery is not achievable, palliative surgery or neurostimulation systems (including vagus nerve, trigeminal nerve, or deep brain stimulation) may be an option. Other treatment alternatives such as ketogenic diet may also be considered in selected patients.

Long-term safety and efficacy of eslicarbazepine acetate in patients with focal seizures: results of the 1-year ESLIBASE retrospective study.

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 and 13% 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.