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.

Specificity of electroclinical features in the diagnosis of ring chromosome 20.

BACKGROUND: Ring chromosome 20 (R20) syndrome is a chromosomal disorder characterized mainly by drug-resistant frontal lobe seizures, recurrent nonconvulsive status epilepticus (NCSE), and typical EEG features. The aim of this study was to investigate if this triad is common and specific to all patients with R20. METHODS: In this cross-sectional study (from 2000 to 2011), we selected patients who fulfilled at least two out of three criteria: drug-resistant frontal lobe seizures, recurrent NCSE, and characteristic electroencephalography (EEG) features. In all patients, diagnosis was based on karyotype analysis of at least 100 metaphases. RESULTS: We identified 36 patients who met at least two of the selected criteria: six patients (16.7%) with R20 and 30 (83.3%) without R20 (non-R20). All patients with R20 met all three criteria. Eleven (36.7%) patients without R20, however, also displayed the full triad. In 19 patients without R20 (63.3%), one of the three clinical features was missing: frontal lobe seizures were not resistant to antiepileptic drugs (AED) in four (13.3%), recurrent NCSE was missing in six (20%), and nine (30%) patients did not have typical EEG features. Based on this data, specificity was 63.3%, positive predictive value was 35.3%, and sensitivity and negative predictive values were 100%. Additionally, a review of all publications describing the R20 phenotype revealed that 81.98% of patients with R20 display the full electroclinical triad. CONCLUSIONS: In our study, all patients with R20 displayed the three electroclinical characteristics. This is in line with previous reports (presenting high sensitivity and negative predictive value). However, these features can also be observed in other epilepsies and are not specific to R20. Our findings suggest that in the presence of the full triad of symptoms, karyotype analysis focused on chromosome 20 should be conducted.

Validity of the clinical and content scales of the Multiphasic Personality Inventory Minnesota 2 for the diagnosis of psychogenic non-epileptic seizures.

INTRODUCTION: The use of the Multiphasic Personality Inventory Minnesota 2 (MMPI-2) for the diagnosis of psychogenic non-epileptic seizures (PNES) is controversial. This study examines the validity of the clinical scales and, unlike previous works, the content scales. METHODS: Cross-sectional study of 209 patients treated in the epilepsy unit. We performed a logistic regression analysis, taking video-electroencephalography as the reference test, and as predictor variables age, sex, IQ and clinical (model A) or content scales (model B) of the MMPI-2. The models were selected according to the Aikake index and compared using the DeLong test. RESULTS: We analyzed 37 patients with PNES alone, or combined with seizures, and 172 patients with seizures only. The model consisting of sex, Hs (hypochondriasis) and Pa (paranoia) showed a sensitivity of 77.1%, a specificity of 76.8%, a percentage of correct classification of 76.8%, and an area under the curve (AUC) of 0.836 for diagnosing CNEP. Model B, consisting of sex, HEA (health concerns) and FRS (fears), showed a sensitivity of 65.7%, a specificity of 78.0%, a percentage of correct classification of 75.9% and an AUC of 0.840. DeLong's test did not detect significant differences. CONCLUSIONS: The MMPI-2 has a moderate validity for the diagnosis of PNES in patients referred to an epilepsy unit. Using content scales does not significantly improve results from the clinical scales.

Drug-resistant epilepsy: current recommendations for diagnosis and treatment in Spain.

INTRODUCTION: Drug-resistant epilepsy (DRE) is a top-priority social health problem which requires early individual treatment due to its dramatic repercussions for the patient and society. DEVELOPMENT: The International League Against Epilepsy (ILAE) has recently defined DRE as that in which the seizures are not controlled after having correctly taken two appropriate and well tolerated anti-epileptic drugs, with lack of control being understood as the appearance of seizures within one year or in a period less than three times the inter-seizure interval before starting treatment. This International Society recommends a rapid and detailed assessment of all patients in an Epilepsy Unit. A Clinical Epilepsy Unit (CEU) is understood as a group of professionals who, acting in collaboration, have the diagnosis and treatment of the patient with epilepsy as their primary objective. CEUs in Spain may be stratified into different levels depending on the activity carried out in each of them. The specific epilepsy clinic is considered the fundamental type of CEU and includes the necessary figure of an expert in epilepsy. Prolonged video-monitoring is performed in medical CEUs. In medical-surgical CEUs epilepsy surgery with varying degrees of difficulty is also performed. CONCLUSIONS: All CEUs must cooperate with consensus protocols, and there must be a two-way flow between them. Stratification of CEUs increases efficacy and efficiency, due to there being a sufficient number of them to ensure easy access by all patients with epilepsy.

Consensus-recommended diagnostic and therapeutic guidelines for drug-resistant epilepsy in Spain (Consenso RATE-España).

OBJECTIVE: To ascertain the opinions of an Epilepsy Expert Group and prepare a consensus document on the definition of drug-resistant epilepsy (DRE) according to the International League Against Epilepsy (ILAE) and the different healthcare levels for the patient with epilepsy in Spain. MATERIAL AND METHODS: The study was conducted using the Delphi method, by means of successive rounds of questionnaires. A scientific committee prepared a preliminary document and fourteen associated questions, which were sent by e-mail to the panel of experts. They included items related to the concept of DRE, health care levels and the route between these levels for patients with DRE. RESULTS: A total of 41 experts answered the questionnaire. They agreed regarding the necessity and applicability of the DRE definition according to the ILAE, the need for an expert panel on epilepsy, specialist epilepsy clinics, and clinical epilepsy units stratified depending on the level of activities they carried out. There was moderate consensus on the resources and activity of the clinical units of reference and there was no consensus on the referral of patients who have suffered an epileptic seizure to an epilepsy clinic. CONCLUSIONS: The expert panel agreed with the definition of DRE according to the ILAE and on referring patients with DRE for a detailed study in an epilepsy clinic or epilepsy clinical unit. They highlighted the need for video-EEG monitoring in the study of patients with DRE and the need to propose other forms of treatment in selected patients.

Stereoelectroencephalography in the preoperative assessment of patients with refractory focal epilepsy: experience at an epilepsy centre.

OBJECTIVE: Stereoelectroencephalography (SEEG) is a technique for preoperative evaluation of patients with difficult-to-localise refractory focal epilepsy (DLRFE), enabling the study of deep cortical structures. The procedure, which is increasingly used in international epilepsy centres, has not been fully developed in Spain. We describe our experience with SEEG in the preoperative evaluation of DLRFE. MATERIAL AND METHODS: In the last 8 years, 71 patients with DLRFE were evaluated with SEEG in our epilepsy centre. We prospectively analysed our results in terms of localisation of the epileptogenic zone (EZ), surgical outcomes, and complications associated with the procedure. RESULTS: The median age of the sample was 30 years (range, 4-59 years); 27 patients (38%) were women. Forty-five patients (63.4%) showed no abnormalities on brain MR images. A total of 627 electrodes were implanted (median, 9 electrodes per patient; range, 1-17), and 50% of implantations were multilobar. The EZ was identified in 64 patients (90.1%), and was extratemporal or temporal plus in 66% of the cases. Follow-up was over one year in 55 of the 61 patients undergoing surgery: in the last year of follow-up, 58.2% were seizure-free (Engel Epilepsy Surgery Outcome Scale class I) and 76.4% had good outcomes (Engel I-II). Three patients (4.2%) presented brain haemorrhages. CONCLUSION: SEEG enables localisation of the EZ in patients in whom this was previously impossible, offering better surgical outcomes than other invasive techniques while having a relatively low rate of complications.

Socio-occupational and employment profile of patients with epilepsy.

OBJECTIVE: Epilepsy has a significant impact on quality of life. Many studies have observed higher unemployment rates among patients with epilepsy. However, unemployment rates vary according to the clinical conditions, country, and group studied. METHODS: Between October 2007 and February 2008, we performed a cross-sectional multicenter epidemiological study to evaluate the socio-occupational and employment profiles of 872 adult patients with epilepsy followed in outpatient epilepsy clinics in Spain. RESULTS: Fifty-eight percent of the patients were employed at the time of the survey, 10.9% of the patients were unemployed, and 12.5% were occupationally incapacitated. CONCLUSION: Patients with epilepsy had employment rates similar to those of the general population, and slightly higher levels of unemployment. The main factors associated with unemployment and incapacity were the presence of refractory epilepsy, the occurrence of a seizure in the last 12 months, level of education, and polytherapy.

[Treatment of epilepsy with perampanel: conversion from add-on therapy to monotherapy]. / Tratamiento de la epilepsia con perampanel: desde la terapia añadida a la conversión a monoterapia.

INTRODUCTION: Perampanel (PER) is an antiepileptic drug approved in Europe as add-on therapy for patients with focal onset seizures (with or without secondary generalisation) from the age of 4 years, and for primary generalised tonic-clonic seizures from 7 years of age. OBJECTIVE: Review current evidence on treatment with PER monotherapy after conversion from adjunctive therapy. DEVELOPMENT: Two retrospective multicentre studies in which PER was used as monotherapy show that low doses (6-8 mg/day) of PER were effective and well tolerated in a subgroup of patients with less severe epilepsies than patients who participated in clinical trials (where PER was used as add-on therapy). In these studies, the retention rate exceeded 90% at 3 months, and 70% at 6, and 12 months. The responder rate was > 75% at 3 months, and the rate of seizure-free patients exceeded 50% at 3 and 6 months, and 37% at 12 months. Compared to other observational studies and clinical trials where PER was used as add-on therapy, no adverse effects other than those already known were observed. Four other studies examining the effects of conversion to PER monotherapy in a small number of patients support these results. CONCLUSIONS: In routine clinical practice, conversion to PER monotherapy, at relatively low doses, is an effective and well-tolerated treatment for patients with focal and generalised tonic-clonic seizures.

TITLE: Tratamiento de la epilepsia con perampanel: desde la terapia añadida a la conversión a monoterapia.Introducción.El perampanel (PER) es un fármaco anticrisis epilépticas aprobado en Europa como terapia añadida para pacientes con crisis de inicio focal (con o sin crisis focal a bilateral tonicoclónica) desde los 4 años, y para las crisis tonicoclónicas generalizadas desde los 7 años. Objetivo. Revisar la evidencia existente sobre el tratamiento con PER en conversión a monoterapia. Desarrollo. Dos estudios multicéntricos retrospectivos en los que el PER se convirtió a monoterapia muestran que este fármaco en dosis bajas (6-8 mg/día) fue especialmente eficaz y bien tolerado en un subgrupo de pacientes con epilepsias menos graves que los pacientes que participaron en los ensayos clínicos en donde el PER se empleó como terapia añadida. En estos estudios, la tasa de retención superó el 90% a los tres meses y el 70% a los seis y a los 12 meses. La tasa de respondedores fue > 75% a los tres meses, y la tasa de pacientes libres de crisis llegó a superar el 50% a los tres y a los seis meses, y el 37% a los 12 meses. En comparación con otros estudios donde el PER se empleó como terapia añadida, no se observaron efectos adversos diferentes a los ya conocidos. Otros cuatro estudios que examinaron los efectos del PER en conversión a monoterapia en un número pequeño de pacientes apoyan estos resultados. Conclusiones. En la práctica clínica habitual, el PER es un tratamiento eficaz y bien tolerado cuando se usa en conversión a monoterapia, en dosis relativamente bajas, en pacientes con crisis focales y tonicoclónicas generalizadas.

Treatment initiation in epilepsy: an expert consensus in Spain.

OBJECTIVE: The goals of this study were to explore the diverse criteria surrounding indications for antiepileptic therapy and to establish a consensus on drug selection for initial monotherapy in adult patients with epilepsy. METHODS: The study was performed using the modified Delphi method, which aims to achieve professional consensus by means of a series of questionnaires. Three different groups of items were evaluated: the beginning of antiepileptic treatment, the drug selected for initial monotherapy with respect to the type of epilepsy, and the drug selected for initial monotherapy with respect to comorbidity. RESULTS: Sixty experts completed two rounds of a questionnaire. In the first round, consensus was reached on 135 of the 194 questions analyzed. After the second round, consensus was reached on 148 items. The main findings of the survey revealed a consensus on beginning treatment after the first seizure when the EEG showed abnormalities such as generalized spike-wave discharges, when MRI demonstrated an epileptogenic brain lesion, and in elderly patients. Regarding to the antiepileptic drug selected for initial monotherapy with respect to type of epilepsy, levetiracetam and lamotrigine were recommended for generalized tonic-clonic seizures regardless of sex or age; levetiracetam was recommended for myoclonic epilepsy regardless of sex; valproic acid, ethosuximide, levetiracetam, and lamotrigine were chosen for absence epilepsy; and carbamazepine, levetiracetam, lamotrigine, and oxcarbazepine were recommended for partial epilepsy regardless of age or sex. Finally, in the evaluation of drug selection with respect to comorbidity, first-generation drugs were less recommended than second-generation drugs, which were clearly preferable. The drugs on which there was a greater consensus were levetiracetam, lamotrigine, valproic acid, and topiramate. CONCLUSIONS: There is a tendency to begin treatment after the first seizure, depending on the results of additional testing. In general, first-generation drugs are less recommended for different types of epilepsy, especially in the presence of a comorbid condition. However, the authors are conveying perceptions and opinions, the effect of which on treatment outcomes has not been evaluated.

Efficacy and safety of 800 and 1200 mg eslicarbazepine acetate as adjunctive treatment in adults with refractory partial-onset seizures.

OBJECTIVES: To evaluate the efficacy and safety of eslicarbazepine acetate (ESL) as adjunctive therapy in adults with partial-onset seizures. MATERIAL AND METHODS: Double-blind, placebo-controlled, parallel-group, multicenter study consisting of an 8-week baseline period, after which patients were randomized to placebo (n = 87) or once-daily ESL 800 mg (n = 85) or 1200 mg (n = 80). Patients received half dose during 2 weeks preceding a 12-week maintenance period. RESULTS: Seizure frequency over the maintenance period was significantly (P < 0.05) lower than placebo in both ESL groups. Responder rate was 23% (placebo), 35% (800 mg), and 38% (1200 mg). Median relative reduction in seizure frequency was 17% (placebo), 38% (800 mg), and 42% (1200 mg). The most common adverse events (AEs) (>10%) were dizziness, somnolence, headache, and nausea. The majority of AEs were of mild or moderate severity. CONCLUSIONS: Once-daily treatment with ESL 800 and 1200 mg was effective and generally well tolerated.

Biomagnetic profiles of verbal memory success in patients with mesial temporal lobe epilepsy.

The risk of cognitive decline after mesial temporal lobe (MTL) resection in the dominant hemisphere for treatment of epilepsy has been assessed with the intracarotid amytal procedure and functional neuroimaging. In this study we used magnetoencephalography (MEG) to analyze memory profiles in patients with left hippocampal sclerosis (HS). Biomagnetic brain activity related to successful memory was compared in nine patients with left HS and nine age-matched controls. Patients manifested a higher number of activity sources over the right inferior parietal lobe in the late portion of the time window, and higher activity in the right than in the left MTL between 400 and 800 ms. This was reinforced by a -0.46 MTL laterality index, which indicates right MTL dominance. Controls showed a higher number of dipoles in the left anterior ventral prefrontal region, between 400 and 600 ms, and in the left MTL across the whole time window. Three patients who underwent a left temporal lobectomy, were seizure free, and who did not exhibit memory impairment after left temporal lobectomy, showed no activity in the left MTL presurgically. These results could support the ability of MEG to describe the time-modulated brain activity related to memory success in patients with epilepsy with left HS.

Self-reported memory problems in everyday activities in patients with epilepsy treated with antiepileptic drugs.

OBJECTIVE: The goal of this study was to assess everyday memory complaints in a large cohort of patients with epilepsy treated with antiepileptic drugs and to determine demographic, clinical, and emotional state factors associated with patients' self-perception of memory disturbances. METHODS: This cross-sectional epidemiological study was carried out in routine clinical practice using the Questionnaire of Memory Efficiency (QME) and the Hospital Anxiety and Depression Scale (HADS). RESULTS: Six hundred sixty-one patients were recruited. The time since epilepsy diagnosis was 17.3 years (SD=12.5); the number of seizures in the past year 13.8 (SD=4.8); the proportion of patients free of seizures in the last year 42.5%; the proportion of patients with partial seizures 73.2%; and the proportion of patients on monotherapy 56.3%. Total QME score was 110.0 (SD=18.6). Depression and anxiety scores and polytherapy explained 38.7% of the QME variance. CONCLUSIONS: Subjective memory functioning in this cohort of patients with epilepsy was relatively good. Complaints expressed by these patients are explained mainly by the presence of depressive and anxiety symptoms.

Ascertaining the epidemiology, patient flow and disease management for Dravet syndrome in Spain. / Determinacion de la epidemiologia, el flujo de pacientes y el tratamiento del sindrome de Dravet en España.

INTRODUCTION: Dravet syndrome (DS) is a rare, drug resistant epilepsy that starts very early in life with febrile seizures followed by cognitive impairment and diverse seizure types. AIM: To generate evidence on the epidemiology of DS, its diagnosis, patient-flow, treatment and unmet needs from the perspective of Spanish experts. DEVELOPMENT: A two-round Delphi study involving 19 physicians was conducted. Questionnaires were based on literature review and validated by clinical experts. Consensus was reached when topics were subject to routine clinical practice and individual experience, or the coefficient of variation among answers was <= 0.3. The estimated number of new DS patients is 73 per year. Prevalence is estimated to be between 348-540 patients. DS is mostly diagnosed in children. Survival varies from 5 to 60 years. There is no standardised follow-up of patients beyond the age of 18 and mortality rates are uncertain. No standard guidelines exist for diagnosing or treating DS. It takes 9 to 15 months to confirm the diagnosis and genetic testing is unevenly available. Valproic acid, clobazam, stiripentol and topiramate are commonly used. Poor efficacy and safety are the main reasons for treatment switch. CONCLUSIONS: The epidemiology of DS in Spain is not well known and several areas of unmet needs still exist. Experts' views offer a starting point for further research into the reality of DS in Spain. Epidemiological studies, consensus criteria, easy access to genetic testing, treatment options, training and research into quality of life aspects are highly needed.

TITLE: Determinacion de la epidemiologia, el flujo de pacientes y el tratamiento del sindrome de Dravet en España.Introduccion. El sindrome de Dravet (SD) es una epilepsia rara y resistente a los farmacos que comienza en etapas muy precoces de la vida con convulsiones febriles, seguidas de deterioro cognitivo y diversos tipos de crisis epilepticas. Objetivo. Generar datos objetivos sobre la epidemiologia del SD, su diagnostico, el flujo de pacientes, el tratamiento y las necesidades no cubiertas desde el punto de vista de expertos españoles. Desarrollo. Se efectuo un estudio Delphi de dos rondas en el que participaron 19 medicos. Los cuestionarios se basaron en una revision de la bibliografia y fueron validados por expertos clinicos. Se alcanzo consenso si los temas se referian a la practica clinica habitual y la experiencia individual, o si el coeficiente de variacion entre las respuestas era <= 0,3. El numero estimado de pacientes nuevos con SD es de 73 al año. La prevalencia se calcula entre 348 y 540 pacientes. El SD se diagnostica principalmente en niños. La supervivencia varia entre los 5 y los 60 años. No existe ningun seguimiento normalizado para los pacientes de mas de 18 años de edad, y las tasas de mortalidad son inciertas. No existen guias normalizadas para diagnosticar o tratar el SD. Se tarda de 9 a 15 meses en confirmar el diagnostico, y la disponibilidad de los analisis geneticos es irregular. Normalmente se utilizan el acido valproico, el clobazam, el estiripentol y el topiramato. La escasa eficacia y la seguridad son los motivos principales de los cambios de tratamiento. Conclusiones. La epidemiologia del SD en España es poco conocida, y sigue habiendo necesidades no cubiertas en algunas areas. Las opiniones de expertos suponen un punto de partida para poder investigar la realidad del SD en España. Los estudios epidemiologicos, los criterios de consenso, el acceso facil a las pruebas geneticas, las opciones de tratamiento, la formacion y la investigacion de la calidad de vida relacionada con la salud constituyen todos ellos aspectos muy necesarios.

Stereoelectroencephalography in the preoperative assessment of patients with refractory focal epilepsy: Experience at an epilepsy centre. / Estereoelectroencefalografía en la evaluación prequirúrgica de epilepsias focales refractarias: experiencia de un centro de epilepsia.

OBJECTIVE: Stereoelectroencephalography (SEEG) is a technique for preoperative evaluation of patients with difficult-to-localise refractory focal epilepsy (DLRFE), enabling the study of deep cortical structures. The procedure, which is increasingly used in international epilepsy centres, has not been fully developed in Spain. We describe our experience with SEEG in the preoperative evaluation of DLRFE. MATERIAL AND METHODS: In the last 8 years, 71 patients with DLRFE were evaluated with SEEG in our epilepsy centre. We prospectively analysed our results in terms of localisation of the epileptogenic zone (EZ), surgical outcomes, and complications associated with the procedure. RESULTS: The median age of the sample was 30 years (range, 4-59 years); 27 patients (38%) were women. Forty-five patients (63.4%) showed no abnormalities on brain MR images. A total of 627 electrodes were implanted (median, 9 electrodes per patient; range, 1-17), and 50% of implantations were multilobar. The EZ was identified in 64 patients (90.1%), and was extratemporal or temporal plus in 66% of the cases. Follow-up was over one year in 55 of the 61 patients undergoing surgery: in the last year of follow-up, 58.2% were seizure-free (Engel Epilepsy Surgery Outcome Scale class I) and 76.4% had good outcomes (Engel I-II). Three patients (4.2%) presented brain haemorrhages. CONCLUSION: SEEG enables localisation of the EZ in patients in whom this was previously impossible, offering better surgical outcomes than other invasive techniques while having a relatively low rate of complications.

Strategies to detect adverse effects of antiepileptic drugs in clinical practice.

OBJECTIVE: The aim was to study the frequency and types of adverse effects (AEs) in patients treated with antiepileptic drugs (AEDs) according to the strategies used by the neurologist to detect them. METHOD: This cross-sectional epidemiological study was carried out in standard clinical practice. Two strategies were used to detect AEs: spontaneous reporting by the patient, and a checklist of possible treatment-related adverse reactions completed by the patient. RESULTS: A total of 579 patients were recruited for the study. Roughly a third (33.7%) reported AEs spontaneously, and 65.2% did so when administered the checklist. The main reason for changing medication was lack of efficacy, but significant side effects were also an important reason for modifying treatment in those patients who reported higher levels of discomfort. CONCLUSIONS: The use of an active approach is recommended for detection of AEs of AED treatment. AEs appear to have a key effect on the decision to change treatment.

[«Apuntes en Neurologia¼ (Notes in Neurology): a synthesis of the evidence on common paroxysmal neurological disorders and on neurodegenerative disorders]. / «Apuntes en Neurologia¼: una sintesis de la evidencia en trastornos neurologicos comunes paroxisticos y en trastornos neurodegenerativos.

«Apuntes en Neurologia¼ is an initiative in which prominent national and international leaders, with broad academic recognition, came together to synthesise the most outstanding clinical aspects within their area of interest and to discuss the latest developments in a more accessible language. Understanding the factors that affect the onset and progression of any neurological disease through a review is important to be able to develop strategies to reduce the burden of these diseases. Moreover, knowledge of the clinical aspects is essential to solve the problems of daily clinical practice. The data collected here reflect the weight of evidence and some of them anticipate a promising future in the treatment of these diseases. This first edition focuses on common paroxysmal neurological disorders such as migraine, epilepsy and sleep disorders, as well as neurodegenerative disorders such as Parkinson's disease and cognitive impairment. These are clearly different pathologies, although some of them such as migraine and epilepsy, may share clinical symptoms. Sleep disorders, however, are important manifestations of neurodegenerative diseases that are sometimes clinically apparent long before the onset of other neurological symptoms. After recalling pathophysiology and diagnosis, the current review focuses on bringing together the main advances in five of the major neurological diseases.

TITLE: «Apuntes en Neurologia¼: una sintesis de la evidencia en trastornos neurologicos comunes paroxisticos y en trastornos neurodegenerativos.«Apuntes en Neurologia¼ es una iniciativa en la cual lideres de primera linea nacional e internacional, con amplio reconocimiento academico, se reunieron para sintetizar los aspectos clinicos mas destacables dentro de su area de interes y acercar las novedades en una lengua mas proxima. Entender los factores que afectan al inicio y progresion de cualquier enfermedad neurologica a traves de una revision es importante para el desarrollo de estrategias en pro de reducir la carga de estas enfermedades, y conocer los aspectos clinicos es esencial para poder resolver los problemas de la practica clinica diaria. Los datos aqui recogidos reflejan el peso de la evidencia y algunos de ellos anticipan un futuro prometedor en el tratamiento de estas enfermedades. Esta primera edicion se centra en trastornos neurologicos comunes paroxisticos como la migraña, la epilepsia y las alteraciones del sueño, y en trastornos neurodegenerativos como la enfermedad de Parkinson y el deterioro cognitivo. Se trata de patologias claramente diferentes, si bien algunas de ellas, como la migraña y la epilepsia, pueden compartir sintomatologia clinica. Los trastornos del sueño, por su parte, son manifestaciones importantes de enfermedades neurodegenerativas que, en ocasiones, son clinicamente evidentes mucho antes del inicio de otros sintomas neurologicos. Tras recordar la fisiopatologia y el diagnostico, la revision actual se centra en acercar los principales avances en cinco de las principales enfermedades neurologicas.

Estereoelectroencefalografía en la evaluación prequirúrgica de epilepsias focales refractarias: experiencia de un centro de epilepsia / Stereoelectroencephalography in the preoperative assessment of patients with refractory focal epilepsy: Experience at an epilepsy centre

Objetivo: La estereoelectroencefalografía (E-EEG) es una técnica de evaluación prequirúrgica en pacientes con epilepsia focal refractaria de difícil localización (EFRDL) que permite explorar con electrodos profundos regiones cerebrales de difícil acceso y la profundidad de la corteza. Esta técnica, en auge en centros internacionales, apenas se ha desarrollado en España. Describimos nuestra experiencia con la E-EEG en la evaluación de pacientes con EFRDL. Material y métodos: En los últimos 8 años, 71 pacientes con EFRDL fueron evaluados con E-EEG en nuestro centro. Analizamos prospectivamente los resultados obtenidos en la localización, los resultados quirúrgicos y las complicaciones asociadas a la técnica. Resultados: La mediana de edad fue de 30 años (rango 4-59 años), 27 pacientes eran mujeres (38%). La RM cerebral fue negativa en 45 pacientes (63,4%). Se implantaron 627 electrodos (mediana de 9 electrodos por paciente, rango 1-17), con un 50% de implantaciones multilobares. En 64 (90,1%) pacientes se localizó la zona epileptógena (ZE), siendo extratemporal o temporal plus en el 66% de los casos. En 55 pacientes de los 61 intervenidos el seguimiento fue superior al año: en el último año de seguimiento 32/55 pacientes (58,2%) estaban libres de crisis (Engel I) siendo los resultados favorables (Engel I-II) en el 76,4% de las intervenciones. Tres pacientes (4,2%) presentaron una hemorragia cerebral. Conclusión: La E-EEG permite localizar la ZE en pacientes en quienes anteriormente no era posible, ofreciendo unos resultados quirúrgicos superiores a otras técnicas invasivas y una tasa de complicaciones relativamente baja. (AU)

Objective: Stereoelectroencephalography (SEEG) is a technique for preoperative evaluation of patients with difficult-to-localise refractory focal epilepsy (DLRFE), enabling the study of deep cortical structures. The procedure, which is increasingly used in international epilepsy centres, has not been fully developed in Spain. We describe our experience with SEEG in the preoperative evaluation of DLRFE. Material and methods: In the last 8 years, 71 patients with DLRFE were evaluated with SEEG in our epilepsy centre. We prospectively analysed our results in terms of localisation of the epileptogenic zone (EZ), surgical outcomes, and complications associated with the procedure. Results: The median age of the sample was 30 years (range, 4-59 years); 27 patients (38%) were women. Forty-five patients (63.4%) showed no abnormalities on brain MR images. A total of 627 electrodes were implanted (median, 9 electrodes per patient; range, 1-17), and 50% of implantations were multilobar. The EZ was identified in 64 patients (90.1%), and was extratemporal or temporal plus in 66% of the cases. Follow-up was over one year in 55 of the 61 patients undergoing surgery: in the last year of follow-up, 58.2% were seizure-free (Engel Epilepsy Surgery Outcome Scale class I) and 76.4% had good outcomes (Engel I-II). Three patients (4.2%) presented brain haemorrhages. Conclusion: SEEG enables localisation of the EZ in patients in whom this was previously impossible, offering better surgical outcomes than other invasive techniques while having a relatively low rate of complications. (AU)

Effect of lamotrigine on sexual function in patients with epilepsy.

OBJECTIVE: To assess the course of sexual function in epilepsy patients treated with lamotrigine. MATERIAL AND METHODS: This open study included 141 patients treated with lamotrigine for a period of 8 months: 79 patients initiated treatment with lamotrigine monotherapy, and 62 were switched to lamotrigine because of lack of efficacy or adverse events to a previous antiepileptic drug (AED). Patients were assessed at baseline and after 4 and 8 months of treatment. In the baseline and final visits the Changes in Sexual Functioning Questionnaire (CSFQ) was applied. Analysis was performed in an intent-to-treat population. RESULTS: In women who started treatment with lamotrigine, a significant improvement was observed, both in total CSFQ score (increase of 5.39 +/- 6.95 points; p < 0.05), and in the five dimensions of the scale (desire/frequency, desire/interest, pleasure, arousal/excitement and orgasm). In men, a significant improvement was only observed in the pleasure dimension. In the group of patients in whom a previous AED was substituted by lamotrigine, significant improvement was recorded in the dimensions of pleasure and orgasm in men and desire/frequency in women, whilst in women the desire/interest dimension showed a decrease. CONCLUSIONS: In this observational study, an improvement in sexual dysfunction was observed in association with lamotrigine. This could have been the result of improvement of the epilepsy, changes in quality of life, elimination of side effects from other AEDs, or a mood-stabilizing effect of lamotrigine.

Tratamiento de la epilepsia con perampanel: desde la terapia añadida a la conversión a monoterapia / Treatment of epilepsy with perampanel: conversion from add-on therapy to monotherapy

Introducción: El perampanel (PER) es un fármaco anticrisis epilépticas aprobado en Europa como terapia añadida para pacientes con crisis de inicio focal (con o sin crisis focal a bilateral tonicoclónica) desde los 4 años, y para las crisis tonicoclónicas generalizadas desde los 7 años. Objetivo: Revisar la evidencia existente sobre el tratamiento con PER en conversión a monoterapia. Desarrollo: Dos estudios multicéntricos retrospectivos en los que el PER se convirtió a monoterapia muestran que este fármaco en dosis bajas (6-8 mg/día) fue especialmente eficaz y bien tolerado en un subgrupo de pacientes con epilepsias menos graves que los pacientes que participaron en los ensayos clínicos en donde el PER se empleó como terapia añadida. En estos estudios, la tasa de retención superó el 90% a los tres meses y el 70% a los seis y a los 12 meses. La tasa de respondedores fue > 75% a los tres meses, y la tasa de pacientes libres de crisis llegó a superar el 50% a los tres y a los seis meses, y el 37% a los 12 meses. En comparación con otros estudios donde el PER se empleó como terapia añadida, no se observaron efectos adversos diferentes a los ya conocidos. Otros cuatro estudios que examinaron los efectos del PER en conversión a monoterapia en un número pequeño de pacientes apoyan estos resultados. Conclusiones: En la práctica clínica habitual, el PER es un tratamiento eficaz y bien tolerado cuando se usa en conversión a monoterapia, en dosis relativamente bajas, en pacientes con crisis focales y tonicoclónicas generalizadas.(AU)

Introduction: Perampanel (PER) is an antiepileptic drug approved in Europe as add-on therapy for patients with focal onset seizures (with or without secondary generalisation) from the age of 4 years, and for primary generalised tonic-clonic seizures from 7 years of age. Objective: Review current evidence on treatment with PER monotherapy after conversion from adjunctive therapy. Development: Two retrospective multicentre studies in which PER was used as monotherapy show that low doses (6-8 mg/day) of PER were effective and well tolerated in a subgroup of patients with less severe epilepsies than patients who participated in clinical trials (where PER was used as add-on therapy). In these studies, the retention rate exceeded 90% at 3 months, and 70% at 6, and 12 months. The responder rate was > 75% at 3 months, and the rate of seizure-free patients exceeded 50% at 3 and 6 months, and 37% at 12 months. Compared to other observational studies and clinical trials where PER was used as add-on therapy, no adverse effects other than those already known were observed. Four other studies examining the effects of conversion to PER monotherapy in a small number of patients support these results. Conclusions: In routine clinical practice, conversion to PER monotherapy, at relatively low doses, is an effective and well-tolerated treatment for patients with focal and generalised tonic-clonic seizures.(AU)