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)

[Frontal seizures recorded by magnetoencephalography. Case report]. / Crisis frontales registradas mediante magnetoencefalografía. Caso clínico.

INTRODUCTION: This paper reports the usefulness of magnetoencephalography (MEG) in the anatomical localization of the onset and spread of seizures. CASE REPORT: In a 34-year-old male patient who suffered from drug-resistant complex partial seizures (sometimes generalized) with loss of awareness, magnetic resonance imaging revealed a probable left frontobasal cortical dysplasia. Ictal scalp electroencephalogram showed left frontotemporal theta waves. Electrocorticography (ECoG) registered interictal polyspike discharges and located the seizure onset in the lateral orbital side of the left frontal lobe. Three seizures were registered by MEG, clinically similar to the ones usually experienced by the patient. MEG ictal spike dipole location showed seizure onset coming from the left inferior frontal gyrus (as the ECoG), spreading on to other frontal areas, insula and temporal lobe, all in the left hemisphere. CONCLUSION: MEG may be considered as a useful diagnosis modality in the study of partial seizure physiopathology as well as in its presurgical evaluation.

Crisis frontales registradas mediante magnetoencefalografía. Caso clínico / Frontal seizures recorded by magnetoencephalography. Case report

Introducción. Este artículo expone un ejemplo de la utilidadde la magnetoencefalografía (MEG) en la localización anatómicadel inicio y la propagación de las crisis epilépticas. Caso clínico.Se trata de un paciente de 34 años con crisis parciales complejas farmacorresistentes.La resonancia magnética presenta una probabledisplasia cortical frontobasal izquierda. El electroencefalograma ictalde superficie revela ondas theta frontotemporales izquierdas. Enel registro con electrodos subdurales se demuestra la existencia deanomalías epileptiformes interictales durante el sueño, entre las quepredominan las polipuntas, y crisis de inicio focal en la cara lateroorbitariadel lóbulo frontal izquierdo. La MEG registra tres crisis clínicamentesimilares a las experimentadas por el paciente y permitelocalizar el inicio de las crisis en la circunvolución frontal inferiorizquierda, con propagación a otras áreas frontales, la ínsula y ellóbulo temporal, todo ello en el hemisferio izquierdo. Conclusión. LaMEG puede considerarse como un elemento diagnóstico útil en el estudiode la fisiopatología de las crisis parciales, así como en la evaluaciónprequirúrgica

Introduction. This paper reports the usefulness of magnetoencephalography (MEG) in the anatomical localization ofthe onset and spread of seizures. Case report. In a 34-year-old male patient who suffered from drug-resistant complex partialseizures (sometimes generalized) with loss of awareness, magnetic resonance imaging revealed a probable left frontobasalcortical dysplasia. Ictal scalp electroencephalogram showed left frontotemporal theta waves. Electrocorticography (ECoG)registered interictal polyspike discharges and located the seizure onset in the lateral orbital side of the left frontal lobe. Threeseizures were registered by MEG, clinically similar to the ones usually experienced by the patient. MEG ictal spike dipolelocation showed seizure onset coming from the left inferior frontal gyrus (as the ECoG), spreading on to other frontal areas,insula and temporal lobe, all in the left hemisphere. Conclusion. MEG may be considered as a useful diagnosis modality in thestudy of partial seizure physiopathology as well as in its presurgical evaluation

Fármacos antiepilépticos clásicos y de nueva generación: diferencias de sexo en la efectividad y en las reacciones adversas / Classic antiepileptic and new generation antiepileptic drugs: gender differences in effectiveness and adverse drug reactions

Introducción. Las mujeres sufren más reacciones adversas a los fármacos que los hombres y además las reacciones son diferentes según el sexo. Los fármacos antiepilépticos (FAEs) de nueva generación tienen como principal objetivo reducir los efectos secundarios de los clásicos sin perder la efectividad de éstos. Objetivos. a) Identificar las variables sociodemográficas y clínicas asociadas a recibir tratamiento de monoterapia con FAEs de nueva generación, y b) comparar la efectividad, las reacciones adversas y la calidad de vida entre pacientes tratados en régimen de monoterapia con FAEs clásicos o con nuevos, examinando las posibles diferencias de sexo. Pacientes y métodos. A partir de una encuesta realizada en 32 centros sanitarios en la que participaron 990 pacientes de 16 a 64 años con epilepsia (tasa de respuesta: 96 %). Para los objetivos de este estudio se han seleccionado los pacientes que seguían tratamiento en régimen de monoterapia (496). Las variables dependientes fueron la efectividad para el control de las crisis, los efectos adversos y tres dimensiones de calidad de vida del cuestionario SF-36 (vitalidad, salud percibida y salud mental). Resultados. El 21 % de las mujeres y el 8% de los hombres eran tratados con FAEs de nueva generación. Las mujeres recibían con mayor frecuencia FAEs de nueva generación. Además, también la edad de inicio de la epilepsia se asoció positivamente con recibir tratamiento con FAEs nuevos y se observó un gradiente. Si en los hombres no se observaron diferencias en la efectividad, las reacciones adversas y en la calidad de vida entre los dos tipos de FAEs, las mujeres las tratadas con los de nueva generación tuvieron menos efectos adversos, pero el control de las crisis fue peor. Conclusiones. Los FAEs de nueva generación se prescriben con mayor frecuencia a las mujeres. En éstas, pero no en los hombres, los FAEs de nueva generación podrían tener menos efectos adversos, pero ser menos efectivos para el control de las crisis epilépticas

Introduction. Women are more likely to suffer adverse drug reactions. Moreover adverse drug reactions differ depending on gender. The main objective of new generation antiepileptic drugs (AED) is to reduce adverse drug reactions while maintaining the same effectiveness as the classic ones. Objectives. a) To identify sociodemographic and clinical variables associated with being treated with new generation AEDs, and b) to compare effectiveness, averse drug reactions and quality of life among patients treated with monotherapy, either with classic or with new generation AEDs, examining the potential gender differences. Patients and methods. A survey among 990 patients aged 16-64 with epilepsy was carried out in 32 Spanish hospitals (response rate: 96 %). For the purposes of this study patients treated with monotherapy (n = 496) were selected. The outcome variables were: effectiveness in seizure control, adverse drug reactions and three dimensions of the SF-36 questionnaire (vitality, mental health and self-perceived health status). Results. 21 % of women and 8% of men were treated with new AEDs. Women were more likely to be treated with new generation AEDs. Moreover, age of epilepsy onset was also positively related to new AEDs and a gradient was found. Whereas no differences in effectiveness, adverse drug reactions or quality of life were observed among men, among women, those treated with new generation AEDs had less adverse drug reactions but, on the other hand, effectiveness for controlling seizures was lower. Conclusions. Women are more likely to be treated with new AEDs. Althought these new treatments seem to have less adverse drug reactions among females, their effectiveness in controlling seizures are lower than that of classic AEDs

[Classic antiepileptic and new generation antiepileptic drugs: gender differences in effectiveness and adverse drug reactions]. / Fármacos antiepilépticos clásicos y de nueva generación: diferencias de sexo en la efectividad y en las reacciones adversas.

INTRODUCTION: Women are more likely to suffer adverse drug reactions. Moreover adverse drug reactions differ depending on gender. The main objective of new generation antiepileptic drugs (AED) is to reduce adverse drug reactions while maintaining the same effectiveness as the classic ones. OBJECTIVES: a) To identify sociodemographic and clinical variables associated with being treated with new generation AEDs, and b) to compare effectiveness, averse drug reactions and quality of life among patients treated with monotherapy, either with classic or with new generation AEDs, examining the potential gender differences. PATIENTS AND METHODS: A survey among 990 patients aged 16-64 with epilepsy was carried out in 32 Spanish hospitals (response rate: 96 %). For the purposes of this study patients treated with monotherapy (n = 496) were selected. The outcome variables were: effectiveness in seizure control, adverse drug reactions and three dimensions of the SF-36 questionnaire (vitality, mental health and self-perceived health status). RESULTS: 21 % of women and 8% of men were treated with new AEDs. Women were more likely to be treated with new generation AEDs. Moreover, age of epilepsy onset was also positively related to new AEDs and a gradient was found. Whereas no differences in effectiveness, adverse drug reactions or quality of life were observed among men, among women, those treated with new generation AEDs had less adverse drug reactions but, on the other hand, effectiveness for controlling seizures was lower. CONCLUSIONS: Women are more likely to be treated with new AEDs. Although these new treatments seem to have less adverse drug reactions among females, their effectiveness in controlling seizures are lower than that of classic AEDs.

High-dose intravenous-penicillin in neurosyphilis: effect on intrathecal synthesis of IgG, IgM, IgA and IgD.

We evaluated occurrence and levels of intrathecal synthesis of IgG, IgM, IgA and IgD by calculating corresponding index values in 8 patients with definite and 4 with suspected or possible neurosyphilis, prior to, during and after high-dose intravenous penicillin therapy. Four patients with active neurosyphilis displayed intrathecal synthesis of IgG, IgM and IgA. Only 2 of them showed elevated IgD index, and both had taboparesis, pleocytosis and positive VDRL in CSF, and simultaneous elevation of the IgG, IgA and especially of the IgM indices. This suggests that intrathecal synthesis of IgD may occur in patients with severe CNS inflammation in response to diffuse CNS treponemal damage. Penicillin therapy incited transitory elevation of one or more of the immunoglobulin index values in most patients, possibly in response to massive treponemal lysis inside the CNS. Thereafter, the values became mostly normalized but exceptions occurred, including one patient who had elevated IgG and IgM index which persisted 31 months after therapy. Our data indicate that determinations of immunoglobulin indices performed on consecutive specimens from individual patients with neurosyphilis may be helpful in the evaluation of treatment.

[Prolonged and severe photodermatitis, an early manifestation of ataxia telangiectasia]. / Fotodermatitis prolongada y severa, una manifestación precoz de la ataxia-telangiectasia.

We report two new cases of ataxia-telangiectasia (A-T) in two child brothers. The first symptom of the disease was a serious and prolonged pellagra-like photodermatitis. This rare manifestation of the has not be reported before and it could be explain by a defect in DNA repair.