[Frequency, semiology and prognosis of benign infantile epilepsy]. / Frecuencia, semiologia y pronostico de la epilepsia infantil benigna.

INTRODUCTION: Benign infantile epilepsy is an epileptic syndrome of infancy. Until now, only a small number of case-series have been published. AIM: To study the frequency, semiology and prognosis of benign infantile epilepsy. PATIENTS AND METHODS: The 827 patients with one or more epileptic seizures seen at our hospital between 1 June 1994 and 1 March 2011 were included and prospectively followed. A diagnosis of benign infantile epilepsy was made in patients that fulfilled the following criteria at six month of evolution: one or more focal and/or generalised seizures, onset before 24 months, no neurological deficit and normal neuroimaging and interictal EEG. RESULTS: 77 cases (9%) met the diagnostic criteria. Semiology of the seizures was similar to that of other focal seizures in children under 24 months. 25% of the patients remained as isolated seizures. Among those with two or more seizures, the probability of achieving a 3 year initial remission without antiepileptic treatment was 86%. In the subgroup of patients with focal seizures without family history the probability was 74% and in five cases a global developmental delay/intellectual disability was detected thereafter. CONCLUSIONS: Benign infantile epilepsy is a frequent epileptic syndrome. Semiology of seizures is not useful to characterize the syndrome. A diagnosis of benign infantile epilepsy at six month of evolution implies a reasonably good prognosis, but possibly not as good as for other self-limited epilepsies of infancy.

TITLE: Frecuencia, semiologia y pronostico de la epilepsia infantil benigna.Introduccion. La epilepsia infantil benigna es un sindrome epileptico sobre el que hasta ahora se ha publicado tan solo un pequeño numero de series de casos. Objetivo. Estudiar la frecuencia, semiologia y pronostico de la epilepsia infantil benigna. Pacientes y metodos. Los 827 pacientes con una o mas crisis epilepticas no provocadas que consultaron en nuestro hospital entre el 1 de junio de 1994 y el 1 de marzo de 2011 fueron incluidos y seguidos prospectivamente. Se diagnosticaron de epilepsia infantil benigna los pacientes que cumplieron los siguientes criterios a los seis meses de evolucion: una o mas crisis focales o generalizadas, inicio antes de los 24 meses, ausencia de deficits neurologicos y electroencefalograma y neuroimagen normales. Resultados. Cumplieron los criterios diagnosticos 77 casos (9%). La semiologia de las crisis fue similar a la de otras crisis focales en niños menores de 24 meses. Un 25% de los pacientes permanecio como con crisis aisladas. Entre los de dos o mas crisis epilepticas, la probabilidad de alcanzar una remision inicial de tres años sin tratamiento antiepileptico fue del 86%. En el subgrupo de pacientes con crisis focales sin antecedentes familiares, la probabilidad fue del 74%, y en cinco casos se detecto posteriormente un retraso psicomotor o discapacidad intelectual. Conclusiones. La epilepsia infantil benigna es un sindrome epileptico frecuente. La semiologia de las crisis no es util para caracterizar el sindrome. El diagnostico de epilepsia infantil benigna a los seis meses de evolucion implica un pronostico razonablemente bueno, pero posiblemente no tanto como el de otras epilepsias autolimitadas de la infancia.

Síndrome del túnel carpiano como primer síntoma en las formas leves de mucopolisacaridosis / Carpal tunnel syndrome as the first symptom in mild forms of mucopolysaccharidosis

Introducción: El síndrome del túnel carpiano (STC) es una neuropatía compresiva del nervio mediano en el túnel carpiano, entidad poco frecuente en la edad pediátrica y en adultos jóvenes. Está claramente documentada la relación existente entre la aparición del STC y las enfermedades de depósito, como las mucopolisacaridosis (MPS), una de las causas que cabe tener en cuenta en el diagnóstico de STC en una persona joven. Objetivos: Estudiar la existencia de enfermedad de depósito lisosomal en pacientes afectados de STC menores de 30 años, diagnosticados en el Servicio de Neurofisiología del Hospital Torrecárdenas de Almería en los últimos 5 años (fase retrospectiva). Resultados: Se diagnosticaron 91 pacientes con STC durante el periodo 2005-2010, de los que finalmente 30 cumplieron criterios de inclusión en el estudio, con un predominio de mujeres de 20-22 y 24-27 años de edad. Se encontraron 5 casos con sospecha de enfermedad de depósito (16%), 2 de los cuales (6%) eran falsos positivos y 3 (10%) fueron diagnosticados de MPS. Conclusión: La existencia de un STC en personas menores de 30 años debe considerarse como un posible signo de alerta de una enfermedad de depósito, como la MPS (AU)

Introduction: Carpal tunnel syndrome (CTS) is a compressive neuropathy of the median nerve in the carpal tunnel, and is a rare pathology in children and young adults. The relationship between the occurrence of CTS and storage diseases such as mucopolysaccharidosis (MPS) is clearly documented, and should be considered when faced with a young person presenting with an apparently idiopathic CTS. Objectives: To study the frequency of lysosomal storage disease in patients under the age of 30 diagnosed with carpal tunnel syndrome in the past five years (retrospective phase) by the Neurophysiology Service of Hospital de Torrecárdenas (Almería). Results: 91 patients with CTS were diagnosed in the period 2005-2010, of which 30, predominantly women aged between 20-22 and 24-27 years old, met the criteria for inclusion in the study. Five patients were found with suspected lysosomal storage disease (16%) of which two (6%) were false positives and three (10%) were diagnosed with MPS. Conclusion: The existence of CTS in patients aged under 30 years should alert the physician to suspect lysosomal storage diseases, such as MPS, in the differential diagnosis of the case (AU)

Hemiparesia como signo de comienzo de la enfermedad de la sustancia blanca evanescente. Identificación de una nueva mutación / Left hemiparesis as a sign of onset of vanishing white matter disease. Identification of a new mutation

La enfermedad de la sustancia blanca evanescente es una enfermedad genética de herencia autosómica recesiva que afecta a la sustancia blanca cerebral. Existen varios fenotipos que difieren en la gravedad y la edad de inicio. Clásicamente, se caracteriza por la aparición de ataxia, espasticidad y un deterioro motor progresivo con exacerbaciones desencadenadas por procesos febriles y traumatismos craneales leves. Niña de 2,5 años, que tras traumatismo craneal leve, presentó marcha atáxica, hemiparesia izquierda y reflejos osteotendinosos exaltados. En la resonancia magnética cerebral se observó afectación difusa y simétrica de la sustancia blanca cerebral, con hiposeñal en T1 e hiperseñal en T2, y FLAIR. Se sospechó enfermedad de la sustancia blanca evanescente que se confirmó en el estudio genético al encontrar 2 mutaciones consideradas patogénicas, en el gen EIF2B5, una de ellas no descrita previamente. La hemiparesia debe incluirse entre las manifestaciones clínicas de la enfermedad de la sustancia blanca evanescente. El diagnóstico precoz puede ayudar a evitar infecciones y traumatismos, así como a realizar un adecuado consejo genético a las familias. Nuestro caso aporta además la identificación de una nueva mutación en el gen EIF2B5 (p.Gly132Ala en la posición 395), no descrita previamente, cuyas características sugieren que es patogénica con elevada probabilidad, por lo que estimamos que debería ser considerada entre las mutaciones del complejo EIF2B responsables de la enfermedad (AU)

Vanishing white matter disease is a genetic disorder of autosomal recessive inheritance that affects the brain white matter There are various phenotypes that differ in severity and age at onset. Usually, it is characterized by ataxia, spasticity and a progressive motor decline with exacerbations triggered by fever and mild head traumas. The patient was a 2.5 year-old girl who developed unstable gait, left hemiparesis and increased tendon reflexes following a mild head trauma. Brain MRI showed diffuse and symmetric white matter abnormalities with decreased signal on T1 and increased signal on T2 and FLAIR sequences. Vanishing White Matter disease was suspected. The diagnosis was confirmed by genetic molecular testing that showed 2 mutations in EIF2B5 gene. Both mutations were considered pathogenic, although one had not been previously described. Hemiparesis must be included among clinical features of vanishing white matter disease. Early diagnosis can help to avoid infections and traumas and allows families to be genetically counselled. Our case contributes with the identification of a new mutation in EIF2B5 gene (p.Gly132Ala in position 395), not previously described. Its characteristics suggest a high probability of being pathogenic. We believe that it should be considered among the complex EIF2B mutations responsible for the disease (AU)

[Left hemiparesis as a sign of onset of vanishing white matter disease. Identification of a new mutation]. / Hemiparesia como signo de comienzo de la enfermedad de la sustancia blanca evanescente. Identificación de una nueva mutación.

Vanishing white matter disease is a genetic disorder of autosomal recessive inheritance that affects the brain white matter There are various phenotypes that differ in severity and age at onset. Usually, it is characterized by ataxia, spasticity and a progressive motor decline with exacerbations triggered by fever and mild head traumas. The patient was a 2.5 year-old girl who developed unstable gait, left hemiparesis and increased tendon reflexes following a mild head trauma. Brain MRI showed diffuse and symmetric white matter abnormalities with decreased signal on T1 and increased signal on T2 and FLAIR sequences. Vanishing White Matter disease was suspected. The diagnosis was confirmed by genetic molecular testing that showed 2 mutations in EIF2B5 gene. Both mutations were considered pathogenic, although one had not been previously described. Hemiparesis must be included among clinical features of vanishing white matter disease. Early diagnosis can help to avoid infections and traumas and allows families to be genetically counselled. Our case contributes with the identification of a new mutation in EIF2B5 gene (p.Gly132Ala in position 395), not previously described. Its characteristics suggest a high probability of being pathogenic. We believe that it should be considered among the complex EIF2B mutations responsible for the disease.

Recurrence risk after withdrawal of antiepileptic drugs in children with epilepsy: a prospective study.

AIM: To study recurrence risk after withdrawal of antiepileptic drugs in children with epilepsy. METHODS: All children younger than 14 with two or more unprovoked seizures 24h apart who were seen at our Hospital between 1994 and 2004 were included consecutively and prospectively followed. Patients previously examined in other centres were excluded. All patients who entered a remission were proposed to stop medication and were followed. RESULTS: Three hundred and fifty three children with two or more unprovoked seizures were attended. A total of 238 entered a remission period and were proposed to stop medication, 216 accept. Mean seizure-free time before medication withdrawal was 2.2 years. Kaplan-Meier estimate of recurrence risk was 23% at 2 years (95% CI: 17-29) and 28% at 5 years (95% CI: 22-34). A remote symptomatic etiology, various seizure types and a history of prior febrile seizures or prior neonatal seizures were associated with a significant increase in recurrence risk in univariable and multivariable analyses using Cox proportional hazards model. Recurrence risk at 2 years was 17% (95% CI: 11-23) for idiopathic/cryptogenic epilepsies and 41% (85% CI: 28-54) for remote symptomatic epilepsies. Recurrence risks at 2 years by epileptic syndrome were West syndrome (0%), benign rolandic epilepsy (10%), epilepsy without unequivocal partial or generalized seizures (11%), benign infantile seizures (13%), absence epilepsy (16%), cryptogenic partial epilepsies (20%), symptomatic partial epilepsies (45%), symptomatic generalized epilepsies (54%). CONCLUSIONS: Recurrence risk after withdrawal of antiepileptic treatment in children is low. Etiology and syndromic diagnosis are the main predictive factors.

Response to sequential treatment schedules in childhood epilepsy: risk for development of refractory epilepsy.

PURPOSE: To investigate response to sequential treatment schedules and risk of development of refractory epilepsy in childhood. METHODS: All children younger than 14 years with two or more unprovoked seizures seen at our hospital between 1994 and 2004 were included and prospectively followed. "Seizure control" was defined as a 2-year seizure-free interval without further recurrences except those related to attempts of medication withdrawal and "refractory epilepsy" as failure of >2 drugs plus >1 seizure/month for > or =18 months. RESULTS: 343 Patients were included, 191 males and 152 females. Mean age at diagnosis was 4y 10 mo (SD 3 year 10 month). Mean follow-up period was 76.2 mo (SD 35.2). The probability of achieving "seizure control" was 70% and 86% at 5 and 10 years. 59% of patients were "controlled" with the first drug used. Among patients failing the first, second and third therapeutic regimen due to lack of efficacy, 39%, 23% and 12% respectively were finally "controlled" with subsequent treatment schedules Risk of development of refractory epilepsy was 8% and 12% at 6 and 10 years. CONCLUSION: After failing a first drug, a significant proportion of children can still be controlled with subsequent therapeutic schedules. Only a small proportion develops refractory epilepsy.

Early prediction of refractory epilepsy in childhood.

PURPOSE: To investigate early predictors (6 months after diagnosis) of refractory epilepsy. STUDY DESIGN: prospective cohort study. INCLUSION CRITERIA: all consecutive children <14 years with two or more unprovoked seizures 24h apart, who were seen at our hospital between 1994 and 2004. EXCLUSION CRITERIA: patients previously examined in other centres. DEFINITIONS: refractory epilepsy: failure of >2 drugs plus >1 seizure/month for >or=18 months. ANALYSIS: risk of developing refractory epilepsy was calculated using Kaplan-Meier survival curves. Univariable and multivariable analyses of potential predictors of developing refractory epilepsy were carried out using Cox proportional hazards model. RESULTS: 343 patients were included. Mean age at diagnosis was 4.8 years (+/-3.8 SD). Mean follow-up period was 76.2 (+/-35.2 SD) months (range 24-139). Risk of developing refractory epilepsy was 8% at 6 years. Risk for idiopathic syndromes was 2%. For non-idiopathic syndromes the risk was 38% for patients with age at onset <1 year plus >1 seizure during the first 6 months after diagnosis, 9% for age at onset <1 year plus 0-1 seizures during the first 6 months, 22% for age at onset >or=1 year plus >1 seizures during the first 6 months and 3% for age at onset >or=1 year plus 0-1 seizures during the first 6 months. CONCLUSION: Risk of developing refractory epilepsy is very low in idiopathic syndromes. For the rest of patients, a simple model comprising three variables allows more accurate prediction of risk of refractoriness.

Recurrence risk after a first remote symptomatic unprovoked seizure in childhood: a prospective study.

The aim of this study was to assess recurrence risk after a first remote symptomatic unprovoked seizure in childhood. All consecutive patients younger than 14 years with a first remote symptomatic unprovoked seizure who were seen at our hospital between 1994 and 2006 were included in the study and prospectively followed. Only two patients received antiepileptic treatment. Sixty-three children were included, with 35 males and 28 females. Mean age at first seizure was 4 years (SD 3y 5mo). Kaplan-Meier estimate of recurrence risk was 59% (95% confidence interval [CI] 47-71), 76% (95% CI 65-87), 85% (95% CI 76-94), and 87% (95% CI 78-96) at 6, 12, 18, and 24 months respectively. A total of 55 children out of 63 were affected by a static encephalopathy of pre- or perinatal origin. In this subgroup, recurrence risk at 12 and 24 months was 79% (95% CI 68-90) and 89% (95% CI 80-98). Univariable analysis using the Cox proportional hazards model showed that presence of global developmental delay/intellectual disability and Todd's paresis were associated with a significant increase in recurrence risk. In multivariable analysis, only Todd's paresis was significantly associated. Recurrence risk after a first remote symptomatic unprovoked seizure in childhood is much higher than what some previous studies suggests.