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)

Estudio epidemiológico de neurinomas del acústico en Aragón y La Rioja / Epidemiological study of acoustic neurinomas in Aragon and La Rioja

No disponible

[Early presentation of crises and the development of epilepsy in cerebral intra-parenchymatous hemorrhage]. / Presentación precoz de crisis y evolución de la epilepsia en la hemorragia intraparenquimatosa cerebral.

PATIENTS AND METHODS: Of a total of 283 patients with spontaneous or hypertensive cerebral intraparenchymatous hemorrhage, 18 (6.3%), with no previous epilepsy, had crises whilst being followed-up for a period of between 2 and 7 years. In 14 cases the hematoma was lobar and 4 involved the basal ganglia or thalamus. In 8 cases (2.8% of all hemorrhage), these crises occurred during the first 24 hours, or as a first symptom of intraparenchymatous hemorrhage. One patient presented with status epilepticus with generalized crises and two had subentrant secondarily generalized partial crises at the time of the ictus. Treatment with anti-epileptic drugs was started in 13 patients. Twelve patients (4.2% of the hemorrhages) developed symptomatic epilepsy with partial crises with or without secondary generalization. RESULTS AND CONCLUSIONS: The maximum rate of recurrence was four crises per year. However, in one patient, reduction of the dose of medication led to the appearance of status epilepticus. Patients with crises of late onset developed epilepsy more often than those who had early crises. In those with crises there was a predominance of bilobular involvement with participation of the parietal lobe and extension of the hematoma or oedema to the cerebral cortex.

[Ischemic stroke and auricular septal aneurysm: six cases]. / Ictus isquémico y aneurisma del septo auricular: estudio de seis casos.

INTRODUCTION: Aneurysms of the atrial septum (AAS) are uncommon. They have been considered to be related to embolic phenomena. They are usually associated with other cardiac anomalies, especially persistence of the formen ovale. PATIENTS AND METHODS: We studied six patients diagnosed during a period of 24 months as having ischemic ictus and AAS. They were investigated for vascular risk factors and possible causes of cardiac embolism by means of ECG, transthoracic and transoesophagic echography (ETE). Cases with the clinical characteristics of embolism were anticoagulated. RESULTS: Five patients were men with an average age of 47.6 years. Three had the clinical features of established ictus, one of RIND and two of AIT. Three patients had vascular risk factors. The TSA study showed pathology of the carotid arteries to be present in three patients. In all six cases the AAS was identified on ETE. There were no thrombi in the atria in any case, and in two there was left-right communication. In four patients the condition was considered to have a cardio-embolic origin. No patient has had further episodes of cerebral ischaemia. DISCUSSION: It seems there is a certain risk of cerebral embolus associated with AAS. The simultaneous presence of alterations in cardiac rhythm together with other structural cardiac pathology seems to have a synergic effect on this. Paradoxical embolism, arrhythmias and intra-aneurysmal thrombi appear to be the mechanisms involved in the appearance of emboli. The best therapeutic approach is still unknown. New studies are therefore necessary to establish whether or not it is necessary to anticoagulate these patients.

[Ocular myasthenia: clinical course and strategies for treatment]. / Miastenia ocular: evolución clínica y estrategia terapéutica.

INTRODUCTION: Ocular myasthenia gravis is a localized form of myasthenia in which only the extra-ocular muscles are clinically affected, namely the levator palpebrae superioris and orbicularis oculi. Two years after onset of the ocular condition, it became generalized in 44-53% of the patients. OBJECTIVE: 1. To describe the clinical features, diagnostic characteristics and clinical course of seven patients who fulfilled the criteria for diagnosis of ocular myasthenia and in whom the condition did not become generalized: 2. Review recent papers on this. Material and methods. We studied seven patients (two men and two women) diagnosed as having ocular myasthenia gravis, and followed them up for at least three years. RESULTS: The average age was 56.5. The clinical findings were of ptosis of the eyelids and diplopia. All seven patients were treated with pyridostigmine. In six cases prednisone was also given and in one patient thymectomy was done. There was a satisfactory result in all cases. CONCLUSIONS: The basic treatment of ocular myasthenia is with anticholinesterases and corticosteroids. Occasionally other immunosuppressives may be required. Prednisone seems to reduce the number of patients who go on to develop the generalized form.

[Essential tremor: a review of pathogenic mechanisms]. / Temblor esencial: una revisión sobre sus mecanismos patogénicos.

INTRODUCTION: Essential tremor (ET) is the commonest involuntary movement observed and is seen when a given posture is maintained. Although it does not affect life expectancy, it may cause considerable functional disability and serious psychological effects in the affected person. DEVELOPMENT: ET is a heterogeneous clinical condition. Its physiopathology is still not known, is very complex and involves many mechanisms, both structural and biochemical, although as yet there is no theory to include them all. In view of what is known at present, it may be accepted that there is a central oscillator at olive-cerebellar-thalamic-cortical-spinal level, which is the primary generator of ET, modulated by a peripheral component. The tremor results from interaction between increased central excitability and peripheral regulation, which in turn reinforces the central overactivity. It may also be that the monoaminergic system (catecholaminergic and serotoninergic), adrenoreceptors (especially the B2 muscular adreno-receptors) and the bodily structure itself, amongst other factors, may influence the pathogenic mechanism of ET. It is likely that there is a multifactorial genetic disorder which predetermines this physiopathogenic process, although this has not yet been determined. CONCLUSIONS: In this paper we review the various hypotheses and existing knowledge related to the aetiopathogenesis of TE.

[Pineal gland cysts: clinical and radiological course]. / Quistes de glándula pineal: evolución clínica y radiológica.

We describe the clinical and radiologic evolution of pineal gland cysts found in computed tomography or magnetic resonance images in 12 patients. The patients had complained of headache and/or lateralized sensory symptoms. None had signs of intracranial hypertension or tectal dysfunction. Only one patient, who had partial epilepsy and a large cyst, was treated by ventriculo-cystic shunt; the rest were treated conservatively. The follow-up period in 11 patients was from 2 to 5 years. No changes were observed in cyst size or radiological characteristics; nor did signs of tectal dysfunction develop. In patients with no signs or symptoms directly attributable to these cysts, surgery can be avoided if no radiological changes are found upon follow-up.

[Subclinical hypothyroidism as a cause of reversible cognitive deterioration]. / Hipotiroidismo subclínico como causa de deterioro cognitivo reversible.

Hypothyroidism, which is treatable by hormone substitution, is one of the most frequent causes of symptomatic dementia. The effectiveness of hormone therapy for improving mental status is well established, but full reversibility of symptoms is unusual. We report the case of a woman whose disease began with progressive cognitive deterioration and tremor; laboratory tests revealed subclinical hypothyroidism, which was watched carefully over the next three years. When thyroid hormone therapy was begun, there was marked clinical improvement, which reversed only when the patient voluntarily withdrew treatment for a few weeks.

[Cerebral cavernous angiomas in pregnancy. Two cases and a review of literature]. / Angiomas cavernosos cerebrales en gestantes: estudio de dos casos y revisión de la literatura.

Whether pregnancy increases the risk of bleeding of cavernous angioma, as it does with other types of cerebral vascular malformation, is not known at present. We monitored the pregnancies of two patients with cerebral cavernous angiomas. One patient, whose long-standing epilepsy had until then been considered cryptogenic, with seizure occurring every 3 to 5 years, remained asymptomatic throughout her pregnancy which ended in spontaneous abortion. The parietal cavernous angioma was partially calcified and the tissue showed signs of earlier hemorrhage. The first symptom in the second patient was first-trimester hemorrhage from inside and around the angioma which was located in the optic chiasm. The lesion was fully excised in both patients. We review the literature and analyze the mechanisms that may be implicated in the clinical presentation during pregnancy of this type of cerebral vascular malformation.

[The development of epilepsy during fetal gestation: a prospective study of 45 women]. / Evolución de la epilepsia durante el período gestacional: estudio prospectivo en 45 gestantes.

We observed a clinical deterioration of epilepsy observed during pregnancy in 29% of 45 consecutive epileptic women. Increase in frequency of attacks is not related to type of attack, previous frequency, type of epilepsy, age at first appearance, family history or presence of anomalies by computed tomography imaging. No association has been found between recurrence of attacks and maintenance of sub-therapeutic plasma levels of anti-epileptic drugs (AED). In 60% of the patients who deteriorate, there is a temporal relation between increase in attacks and the suspension of or reduction of AED doses. Changes observed during one pregnancy cannot always predict what will happen during subsequent pregnancies.

[Failure of empirical treatment with ceftriaxone in motor neuron disease]. / Fracaso del tratamiento empírico con ceftriaxona en la enfermedad de la motoneurona.

We describe two patients with lateral amyotrophic sclerosis who, after informed consent, received empirical treatment with intravenous cephtriaxone at a dose of 2 g/24 hours for three weeks, with no positive results. The pharmacokinetics of this cephalosporin is analyzed, along with the relationship between motor neuron disease, neuroborreliosis and immunoreactivity to Borrelia burgdorferi.