Estudio comparativo del uso de fármacos antiepilépticos durante el embarazo en un periodo de 12 años. Eficacia de los nuevos fármacos lamotrigina, levetiracetam y oxacarbamacepina / Comparative study of antiepileptic drug use during pregnancy over a period of 12 years in Spain. Efficacy of the newer antiepileptic drugs lamotrigine, levetiracetam, and oxcarbazepine

Introducción: El patrón de uso de fármacos antiepilépticos (FAE) durante el embarazo difiere entre países y está cambiando. Se desconoce en qué medida ello afecta a la población española. La eficacia de los nuevos fármacos en el control de las crisis es motivo de preocupación y puede haber cambiado a lo largo de los años debido a un mejor conocimiento de su uso durante el embarazo. Con el objetivo de analizar estos 2 aspectos reportamos los resultados del registro EURAP España durante un periodo de 12 años. Material y métodos: Tras el consentimiento informado, las pacientes son incluidas en el registro y evaluadas al inicio del embarazo, al final del segundo y tercer trimestres, después del parto y al año del nacimiento. Para los objetivos de este estudio hemos analizado: FAE, tipo de epilepsia, frecuencia de crisis por trimestres y a lo largo del embarazo, porcentaje de pacientes libres de crisis, y frecuencia de malformaciones congénitas mayores. Hemos comparado estas variables en 2 periodos (junio de 2001-octubre de 2007) y (enero de 2008-mayo de 2015). Resultados: Un total de 304 monoterapias del periodo antiguo se comparan con 127 del periodo nuevo. Observamos un ascenso del uso de levetiracetam (LEV) y un descenso del uso de carbamacepina (CBZ), fenitoína y fenobarbital; un leve descenso del uso de valproato (VPA), y un leve aumento de lamotrigina (LTG) y oxacarbamacepina (OXC). El tipo de epilepsia se mantiene estable para CBZ y VPA, pero cambia para LTG, con menos epilepsias generalizadas tratadas con este fármaco en el periodo nuevo. Ello no se asocia con un cambio significativo de la frecuencia de crisis, pero sí con un mejor control de las crisis de novo en el tercer trimestre. LEV se asocia a niveles de control de crisis similares a los de CBZ y VPA y mejor que con LTG. De las pacientes tratadas con LEV, un 64% tenían una epilepsia generalizada. Conclusiones: El patrón de uso de los diferentes FAE durante el embarazo está cambiando en España, con menos uso de CBZ, fenitoína y fenobarbital y un aumento del uso de LEV. El tipo de epilepsia también cambia, con un porcentaje inferior de pacientes tratadas con LTG para epilepsias generalizadas. LEV controla las crisis de manera similar a los fármacos clásicos y mejor que la LTG (AU)

Introduction: The prescription pattern of antiepileptic drugs (AEDs) during pregnancy is changing but to what extent this is occurring in Spain remains unknown. The efficacy of newer drugs for controlling seizures is a key issue and may have changed over the years as doctors gained familiarity with these drugs during pregnancy. To assess these 2 topics, we report the results from the Spanish EURAP register gathered over a 12-year period. Material and methods: After signing informed consent forms, patients were included in the register and evaluated at onset of pregnancy, at the end of the second and third trimesters, after delivery, and one year after delivery. For the purposes of this study, we analysed AEDs, type of epilepsy, seizure frequency per trimester and throughout pregnancy, percentage of seizure-free pregnancies, and frequency of congenital malformations. We then compared data from 2 periods (June 2001-October 2007) and (January 2008-May 2015). Results: We compared 304 monotherapies from the older period to 127 from the more recent one. There was a clear increase in the use of levetiracetam (LEV) with declining use of carbamazepine (CBZ), phenytoin, and phenobarbital; a slight decline in use of valproate (VPA), and a slight increase in the use of lamotrigine (LTG) and oxcarbazepine (OXC). Epilepsy types treated with CBZ and VPA remained unchanged, whereas fewer cases of generalised epilepsy were treated with LTG in the new period. This trend was not associated with significant changes in seizure frequency, but rather linked to better control over de novo seizures in the third trimester. LEV was similar to CBZ and VPA with regard to levels of seizure control, and more effective than LTG. Generalised epilepsy accounted for 64% of the cases treated with LEV. Conclusions: The prescription pattern of AEDs during pregnancy has changed in Spain, with diminishing use of CBZ, phenytoin, and phenobarbital. Changes also reflect the type of epilepsy, since there is less use of LTG for generalised epilepsy. LEV provides similar seizure control to that of the older AEDs, and it is more effective and better than LTG (AU)

Comparative study of antiepileptic drug use during pregnancy over a period of 12 years in Spain. Efficacy of the newer antiepileptic drugs lamotrigine, levetiracetam, and oxcarbazepine. / Estudio comparativo del uso de fármacos antiepilépticos durante el embarazo en un periodo de 12 años. Eficacia de los nuevos fármacos lamotrigina, levetiracetam y oxacarbamacepina.

INTRODUCTION: The prescription pattern of antiepileptic drugs (AEDs) during pregnancy is changing but to what extent this is occurring in Spain remains unknown. The efficacy of newer drugs for controlling seizures is a key issue and may have changed over the years as doctors gained familiarity with these drugs during pregnancy. To assess these 2 topics, we report the results from the Spanish EURAP register gathered over a 12-year period. MATERIAL AND METHODS: After signing informed consent forms, patients were included in the register and evaluated at onset of pregnancy, at the end of the second and third trimesters, after delivery, and one year after delivery. For the purposes of this study, we analysed AEDs, type of epilepsy, seizure frequency per trimester and throughout pregnancy, percentage of seizure-free pregnancies, and frequency of congenital malformations. We then compared data from 2 periods (June 2001-October 2007) and (January 2008-May 2015) RESULTS: We compared 304 monotherapies from the older period to 127 from the more recent one. There was a clear increase in the use of levetiracetam (LEV) with declining use of carbamazepine (CBZ), phenytoin, and phenobarbital; a slight decline in use of valproate (VPA), and a slight increase in the use of lamotrigine (LTG) and oxcarbazepine (OXC). Epilepsy types treated with CBZ and VPA remained unchanged, whereas fewer cases of generalised epilepsy were treated with LTG in the new period. This trend was not associated with significant changes in seizure frequency, but rather linked to better control over de novo seizures in the third trimester. LEV was similar to CBZ and VPA with regard to levels of seizure control, and more effective than LTG. Generalised epilepsy accounted for 64% of the cases treated with LEV. CONCLUSIONS: The prescription pattern of AEDs during pregnancy has changed in Spain, with diminishing use of CBZ, phenytoin, and phenobarbital. Changes also reflect the type of epilepsy, since there is less use of LTG for generalised epilepsy. LEV provides similar seizure control to that of the older AEDs, and it is more effective and better than LTG.

[Malformations and fetal death in the Spanish antiepileptic drug and pregnancy registry: results at 6 years]. / Malformaciones y muerte fetal en el registro español de fármacos antiepilépticos y embarazo: resultados a los 6 años.

INTRODUCTION: Pregnancy registries provide trustworthy information about the risks associated to antiepileptic drugs (AEDs). EURAP is a Prospective International Registry which include patients who takes AEDs at the time of conception. The data of the Spanish centers which are contributing to EURAP reflects the reality of our milieu. OBJECTIVES: To study the incidence of major congenital malformations (MCM) /and/or fetal-perinatal death (MFP) and determine his relationship to AEDs in the Spanish EURAP registry. METHODS: After informed consent, patients were included in the prospective Registry and evaluated: at the beginning, at the end of the second and third trimester, after delivery and one year after birth. A variety of variables were collected: demographic, type of epilepsy, frequency of seizures during pregnancy, AEDs and dose, potential toxics, folate use and dose, obstetric complications and information of the newborn. After 6 years of recruitment (June 2001-October 2007) we analyzed the results of this Registry in Spain with special attention on the incidence of major congenital malformations and foetal-perinatal death. RESULTS: Of a whole of 540 cases included in the Registry, 490 were prospective (included before the 16th week), of these we had complete information in 368 cases. Major congenital maLformations were present in 5% (n=13) of the child exposed to monotherapy and 12% (n=6) of those exposed to polytherapy (p=0.08). All polytherapy combinations with MCM, contained valproate. Of the variables analyzed only low weight at birth and the AEDs used showed statistically significant association with MCM and MFP. The percentage of MCM was superior for valproate, particularly at doses equal or superior of 1000 mg/day (16%), although differences were not statistically significant. The majority of ours patients were on monotherapy (83%) with AEDs at low doses and were taking 5 mg of folate. CONCLUSIONS: Patients on polytherapy, particularly those with valproate in combination present more risk of MCM. For monotherapy exposures only weight at birth and the AEDs used have association statistically significant with MC/MFP. Valproate in our series presents more risk than lamotrigine and does not show differences with regard to carbamazepine.

Malformaciones y muerte fetal en el registro español de fármacos antiepilépticos y embarazo: resultados a los 6 años / Malformations and fetal death in the Spanish antiepileptic drug and pregnancy registry: results at 6 years

Introducción. Los registros de embarazadas epilépticas proporcionan información fiable sobre los riesgos asociados al tratamiento antiepiléptico durante el embarazo. Con este fin se está realizado el registro EURAP, que es un estudio prospectivo observacional internacional que incluye mujeres tratadas con fármacos antiepilépticos (FAE) durante la concepción. Los datos de los centros españoles que participan en el registro reflejan cuál es la realidad en nuestro medio. Objetivos. Estudiar la incidencia de malformaciones congénitas (MCM) y/o muerte fetal perinatal (MFP), así como los posibles factores relacionados con las mismas en el registro EURAP España. Material y métodos. Tras el consentimiento informado las pacientes son incluidas en el registro prospectivo y son evaluadas en diferentes periodos: al inicio del embarazo, al final del segundo y tercer trimestre, después del parto y al año del nacimiento. Las variables que se analizan son: datos demográficos, tipo de epilepsia y frecuencia de crisis durante el embarazo, los FAE y dosis, otros tóxicos potenciales, uso de ácido fólico y dosis, complicaciones obstétricas y datos sobre el recién nacido. Tras 6 años de seguimiento (junio 2001- octubre 2007) se analizan los resultados de este registro en España, con especial énfasis en la incidencia de MCM y MFP. Resultados. De un total de 540 casos incluidos en el registro, son prospectivos (incluidos antes de la semana 16) 490 casos y disponemos de todos los datos para el análisis en 368. Presentaron MCM el 5% (n=13) de los neonatos expuestos a monoterapia y el 12% (n=6) de los expuestos a politerapia (p=0,08). Todas las politerapias asociadas a MCM incluían el ácido valproico. De las variables estudiadas sólo el bajo peso al nacer y el fármaco utilizado mostraron una asociación estadísticamente significativa con MCM y MFP. El porcentaje de MCM fue superior para el ácido valproico, particularmente a dosis igual o superior a 1.000 mg (16%), aunque las diferencias no fueron estadísticamente significativas. La mayoría de las pacientes estaban en monoterapia (83%) con dosis bajas de FAE y tomaban 5 mg de ácido fólico. Conclusiones. Los hijos de pacientes en politerapia, particularmente si incluyen el ácido valproico, son los que presentan más MCM. De los pacientes en monoterapia únicamente el peso al nacer y el FAE presentaban asociación significativa con MCM/MFP. En nuestra serie, el ácido valproico presenta más riesgo que la lamotrigina y no se observan diferencias respecto a carbamazepina (AU)

Introduction: Pregnancy registries provide trustworthy information about the risks associated to antiepileptic drugs (AEDs). EURAP is a Prospective International Registry which include patients who takes AEDs at the time of conception. The data of the Spanish centers which are contributing to EURAP reflects the reality of our milieu. Objectives: To study the incidence of major congenital malformations (MCM) /and/or fetal-perinatal death (MFP) and determine his relationship to AEDs in the Spanish EURAP registry. Methods: After informed consent, patients were included in the prospective Registry and evaluated: at the beginning, at the end of the second and third trimester, after delivery and one year after birth. A variety of variables were collected: demographic, type of epilepsy, frequency of seizures during pregnancy, AEDs and dose, potential toxics, folate use and dose, obstetric complications and information of the newborn. After 6 years of recruitment (June 2001-October 2007) we analyzed the results of this Registry in Spain with special attention on the incidence of major congenital malformations and foetal-perinatal death. Results: Of a whole of 540 cases included in the Registry, 490 were prospective (included before the 16th week), of these we had complete information in 368 cases. Major congenital maLformations were present in 5% (n=13) of the child exposed to monotherapy and 12% (n=6) of those exposed to polytherapy (p=0.08). All polytherapy combinations with MCM, contained valproate. Of the variables analyzed only low weight at birth and the AEDs used showed statistically significant association with MCM and MFP. The percentage of MCM was superior for valproate, particularly at doses equal or superior of 1000 mg/day (16%), although differences were not statistically significant. The majority of ours patients were on monotherapy (83%) with AEDs at low doses and were taking 5 mg of folate. Conclusions: Patients on polytherapy, particularly those with valproate in combination present more risk of MCM. For monotherapy exposures only weight at birth and the AEDs used have association statistically significant with MC/MFP. Valproate in our series presents more risk than lamotrigine and does not show differences with regard to carbamazepine (AU)

[Ambiguous epileptic syndrome: from the point of view of adults]. / Sindromes epilépticos ambiguos: perspectivas desde el adulto.

AIM: To review a series of neurological problems that we frequently encounter in our day-to-day clinical practice and which are difficult to diagnose correctly because of the type of presenting symptoms and clinical features they have. DEVELOPMENT: In spite of the fact that a good patient record and detailed neurological examination are still essential, use of long-term (LT) video-EEG monitoring is sometimes indispensable given the ambiguity of the clinical signs and symptoms. Selected subjects were young adult patients of both sexes who had been referred to the Epilepsy Unit at our hospital for study, due to the existence of doubts about their diagnosis. A detailed patient record was drawn up for each patient, and they were also submitted to a neurological examination and LT video-EEG monitoring, which lasted between two and six days. In some of these patients, the diagnosis was modified following their admission and important changes were introduced in their treatment. CONCLUSIONS: LT video-EEG is an important test when it comes to establishing a correct neurological diagnosis in patients with mixed or poorly defined clinical symptoms.

Fármacos antiepiléticos clásicos y de nueva generación: diferencias de sexo en la efectividad / Clasic antiepileptic and new generation antiepileptic drugs: gender differences

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[Cerebrovascular disease in a tertiary care hospital. The current situation and points to be improved]. / Patología cerebrovascular en un hospital terciario. Situación actual y puntos de mejora.

INTRODUCTION: Caring for patients suffering from a cerebrovascular diseases requires a large quantity of resources which must be optimised. The aim of this study is to analyse the management of stroke in a tertiary care hospital. PATIENTS AND METHODS: All admissions with a diagnosis of stroke were analysed retrospectively for the year 2003. Length of stay, computed tomography in the Emergency Room, origin, previous admissions during the last year, presence of vascular risk factors, stroke subtype, complications and mortality during admission and destination when discharged from hospital, were all recorded. RESULTS: 936 patients were admitted to hospital with a diagnosis of stroke. 80.22% corresponded to acute ischaemic strokes (27.14% lacunar, 18.57% transient ischaemic attacks, 10.25% cardioembolic, 15.44% aterothrombotic, 8.44% infarct of undetermined cause, 0.24% unusual aetiology) and 19.78% corresponded to haemorrhagic strokes (13.99% intraparenchymatous hemorrhage, 5.79% subarachnoid hemorrhage). Intra-hospital mortality was 5.3%. 11% suffered from complications while in hospital, and average length of stay was 10.4 days, being much longer for those patients discharged to a medium-long stay centre (17.5 days). Compared to other series, the incidence of cardioembolic and aterothrombotic subtypes of stroke is low. However, because of the inclusion of neurosurgical patients, an increase of cerebral haemorrhages is observed. CONCLUSIONS: Intra-hospital morbidity and mortality and average length of stay in our series are consistent with those from other centres of similar characteristics. A better coordination with medium-long stay centres along with the presence of neurologists on call, would certainly improve these variables.

[Problems of diagnosis and treatment in frontal epilepsies]. / Problemas diagnósticos y tratamiento de las epilepsias frontales.

OBJECTIVE: In this paper we review the anatomy, clinical features, problems of diagnosis and alternative treatment of the frontal epilepsies. DEVELOPMENT: A knowledge of the functional anatomy of the frontal lobe, the largest in the brain, is essential to understanding the varied features of the epileptic seizures arising in it. Unlike seizures arising in the temporal lobe in which the anatomicoclinical correlation is clearer since the rhinencephalum and especially the amygdala are almost always involved, in frontal seizures it is very difficult to systematize the relationship between the clinical signs and the organization of the discharge since there is wide cortico subcortical propagation, both homolateral and contralateral. There are therefore various types of frontal seizures which we define from a clinical point of view. They are the ones causing the greatest problems of differential diagnosis with epileptic pseudo seizures. A continuous video EEG recording is often necessary to differentiate them. Resonance imaging has meant a major advance in making an aetiological diagnosis of this type of seizure. It can show cortical dysplasia, heterotopia and small tumours or vascular malformations which are not visualized by other means. We give a brief description of the newly discovered genetic frontal epilepsies. Finally we review the different types of treatment indicated for them. CONCLUSIONS: Between 20% and 30% of all partial epilepsies start in the frontal lobe, and they form 30% of all surgical operations. The correct diagnosis of frontal seizures is still a challenge for the neurosurgeon. Advances in neurophysiology, neuro radiology and genetics have been, and still are, very important in better understanding of the disorder.

[Indications and results of nonpharmacological treatments of epilepsies: vagal stimulation, ketogenic diet and gamma rays]. / Indicaciones y resultados de los tratamientos no farmacológicos de las epilepsias: estimulación vagal, dieta cetógena y rayos gamma.

OBJECTIVES: In this paper we review alternative non pharmacological treatments for patients with epilepsy, both focal and generalized, which are resistant to the pharmacological treatment normally used. DEVELOPMENT: Vagal nerve stimulation (VNS) is a recently used palliative technique whose mechanism is not clearly understood. We analyze the clinical trials reported to date and the main indications and contra indications. Although the ketogenic diet (KD) has been used since the 1920s, recently there has been renewed interest in using it. Several papers have been published describing its use in children with epilepsy which was difficult to control. The complex metabolic and endocrine aspects of this type of diet make it difficult to select patients who may benefit from it. Gamma knife surgery is a new technique which has been discussed in this paper since it has been recently used in cases of refractory epilepsy, especially temporal medial epilepsy and hypothalamic hamartomas. CONCLUSIONS: VNS and KD are alternative treatments which may be used in patients whose condition cannot be satisfactorily controlled by pharmacological treatment and are not candidates for the surgery of epilepsy. Gamma knife surgery is a surgical technique which has recently been introduced for the treatment of these patients.

Indicaciones y resultados de los tratamientos no farmacológicosde las epilepsias: estimulación vagal, dieta cetógena y rayos gamma / Indications and results of non-pharmacological treatments of epilepsies: vagal stimulation, ketogenic diet and gamma rays

Objetivo. En el presente trabajo se revisan las alternativas de tratamiento, no farmacológico, en los casos de pacientes con epilepsias, tanto focales como generalizadas, que son refractarios al tratamiento farmacológico habitual. Desarrollo. La estimulación del nervio vago (VNS) es una técnica paliativa de reciente utilización, cuyo mecanismo de acción no se conoce bien. Se analizan los ensayos clínicos existentes hasta la actualidad y sus principales indicaciones y contraindicaciones. Aunque el uso de la dieta cetógena (DC) se remonta a los años 20, últimamente ha habido un resurgimiento en su utilización y se han publicado diversos trabajos realizados en niños con epilepsias de difícil control. Los complejos aspectos metabólicos y endocrinos de este tipo de dieta hacen difícil la selección de los pacientes posibles candidatos. La cirugía con gamma knife en realidad no es más que una técnica quirúrgica, que se ha revisado en este trabajo por su novedosa utilización en los casos de epilepsias refractarias, en especial epilepsias mesiales (mediales) temporales y hamartomas hipotalámicos. Conclusiones. La VNS y la DC son tratamientos alternativos para pacientes que no se controlan adecuadamente con tratamiento farmacológico y no son candidatos a cirugía de la epilepsia. La cirugía con gamma knife es una técnica quirúrgica de reciente utilización en estos pacientes. (AU)

Epilepsia y embarazo / Pregnancy and epilepsy

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