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Resumen Introduccion Las terapias dieteticas cetogenicas (TDC) tienen efecto neuroprotector y anticonvulsivante, reducen las crisis epilepticas y mejoran el estado cognitivo en pacientes epilepticos. Nuestro proposito fue evaluar los efectos de las TDC en ninos con epilepsia refractaria (eficacia, efectos secundarios, impacto en el estado nutricional y crecimiento). Metodos Se realizo un estudio observacional descriptivo retrospectivo y prospectivo en un hospital terciario espanol (enero de 2000-diciembre de 2018). Ciento sesenta pacientes pediatricos con epilepsia fueron tratados con TDC (82 varones; edad media 5 anos 9 meses). Las convulsiones, los farmacos antiepilepticos, la antropometria, los efectos secundarios y los parametros analiticos se controlaron al inicio del tratamiento y a los 3, 6, 12 y 24 meses. Resultados En estos intervalos los pacientes libres de crisis fueron: 13,7%, 12,5%, 14,4% y 10,6%, respectivamente, lograndose una reduccion de las convulsiones ≥ 50% en el 41,9%, 37,5%, 28,7% y 16,2%. Los efectos secundarios fueron frecuentes, especialmente trastornos digestivos, hipercalciuria, hipoglucemia, disfuncion hepatica y dislipidemia. La prealbumina, la proteina de union al retinol, la vitamina A y el magnesio disminuyeron significativamente. La talla se vio afectada, especialmente en ninos menores de 2 anos. Conclusiones Las TDC son efectivas para la epilepsia refractaria infantil. Sin embargo, los efectos adversos son frecuentes y pueden afectar al estado nutricional y al crecimiento.

To evaluate the effectiveness and tolerability of cannabidiol (CBD) in patients with developmental and epileptic encephalopathies, including Dravet syndrome (DS), and Lennox-Gastaut syndrome (LGS), in a Spanish Expanded Access Program (EAP).This was a multicenter, retrospective, observational study of patients treated with purified CBD in 14 hospitals across Spain. Patients with (1) written informed consent and (2) at least 6 months follow-up before the closure of the database were included. Primary effectiveness endpoints included reductions (100 %, ≥75 %, ≥50 %, ≥25 %, or 0 %) or worsening in seizure frequency (all seizure types and most disabling seizures) at 1-, 3-, 6-, and 12-month visits and at the last visit, and median relative seizure reduction between baseline and last visit. Secondary effectiveness endpoints included retention rate, reduction in seizure severity, status epilepticus, healthcare utilization, and quality of life. Primary safety endpoints included rates of adverse events (AEs) and AEs leading to discontinuation.One hundred and two patients (DS 12 %; LGS 59 %; other epilepsy syndromes 29 %) with a mean age of 15.9 years were enrolled. Patients were highly refractory to antiseizure medications (ASMs); mean number of prior failed ASMs was 7.5 (SD 3.7). The mean CBD dose was 13.0 mg/kg/day at the last visit. The proportion of patients with ≥50 % reduction in the total number of seizures from baseline was 44.9 % at 6 months and 38.9 % at 12 months. The median number of total seizures per month reduced by 47.6 % from baseline to the last visit. At 12 months, seizure severity was lower in 33/54 patients (61.1 %) and unchanged in 17/54 patients (31.5 %). Quality of life, based on the CAVE scale, increased from a mean score of 17.9 ± 4.7 (n = 54) at baseline to 21.7 ± 5.5 (n = 51) at the last patient visit (21.2 % improvement). The mean treatment retention time was 10.3 months. There were no statistically significant changes in the number of status epilepticus episodes, but lower healthcare utilization was observed. Adverse events occurred in sixty-eight patients (66.7 %), and the most common were somnolence (34.3 %) and diarrhea (12.7 %). Cannabidiol was discontinued exclusively due to AEs in 7.8 % of patients, increasing to 25.5 % when both lack of efficacy and AEs were considered together.Cannabidiol demonstrated promising effectiveness and tolerability in patients with developmental and epileptic encephalopathies taking part in a Spanish EAP.

Epileptic encephalopathy related to CACNA1E has been described as a severe neurodevelopmental disorder presenting with early-onset refractory seizures, hypotonia, macrocephaly, hyperkinetic movements, and contractures and is associated with an autosomal dominant inheritance pattern. Most pathogenic variants described to date are missense variants with a gain of function effect, and the role of haploinsufficiency has yet to be clarified. We describe 2 cases of CACNA1E encephalopathy. Notable findings include congenital contractures and movement disorders predating onset of epilepsy, particularly dystonia. We further compared the key phenotypic features depending on variant location. In conclusion, the appearance of congenital contractures, areflexia, and movement disorders before the onset of epilepsy may provide key guidance in the diagnosis of epileptic CACNA1E encephalopathy. A genotype-phenotype correlation was found between the presence of movement disorders and severe intellectual disability and the location of the variant in the CACNA1E gene.

Hyperammonemic encephalopathy is a rare but potentially dangerous complication of the antiepileptic drug (AED) sodium valproate (VPA). We report a retrospective study of 25 pediatric patients, (15 females [60%]; age: 7.6 ± 4.9 years), with different underlying disorders, who suffered from hyperammonemia due to VPA and who were treated with carglumic acid (CA). The duration of treatment with VPA was 15 ± 1 month, with a dose of 40 ± 16.6 mg/kg/d. VPA blood levels were 75.5 ± 60 mg/L with seven patients being overdosed (>100 mg/L). Twenty‐three patients received concomitant treatment with other AEDs. The initial dose of CA was 100 mg/kg. Subsequently, CA doses of 25 mg/kg were given to 22 patients every 6 hours (average treatment length 2.17 ± 1.1 days) until ammonemia was normalized. In nine patients, CA was used in combination with other drugs to treat hyperammonemia. In all cases, blood ammonia levels were brought under control and symptoms of hyperammonemia resolved. Two hours after CA administration, the average reduction in ammonium levels was 53 ± 29 and 88.6 ± 47.5 μmol/L at 24 hours, resulting in a statistically significant decrease when compared to pretreatment levels. There were no statistically significant differences between sexes, in the presence or not of cognitive impairment or previous carnitine treatment. There were no statistically significant differences when comparing treatment with CA plus ammonia scavengers vs CA alone. In 17 patients (68%) VPA was discontinued and 62% of the patients who maintained treatment had recurrent episodes of hyperammonemia.

Introduction Sturge-Weber syndrome (SWS) is a neurocutaneous syndrome with typical clinical features including seizures, chronic hemiplegia, hemianopsia and intellectual impairment. Progressive clinical decline may be attributable, at least in part, to progressive venous ischemia. Transcranial Doppler (TCD) ultrasonography could be useful to monitor the degree of hemodynamic involvement and its progression. Purpose To determine whether there is an association between the degree of asymmetry in TCD and intensity of clinical and radiological involvement and whether there is a correlation between clinical changes and changes in serial TCD. Methods In fourteen SWS pediatric patients and two “possible cases” (infants younger than two years old without previously known brain involvement, but with other typical signs of SWS) mean flow velocity in the middle cerebral arteries (MCA) was measured by TCD in both hemispheres. The percent difference between hemispheres (asymmetry) was calculated. Clinical and radiological severity was scored using scales. The correlation between TCD asymmetry and SWS clinical and radiological scores was analyzed at baseline, as well as the correlation between the changes in the different variables (TCD asymmetry, clinical and radiological cores) during evolution and in relation to the changes due to therapy. Results The percentage of MCA velocity asymmetry was positively correlated with the clinical severity score (p = 0.04), and with seizure frequency (p = 0.014). Throughout evolution, therapeutic and clinical changes were associated with noticeable changes in transcranial doppler asymmetry in some cases. Conclusions TCD may provide a noninvasive method to assess the severity of blood flow abnormalities at baseline and a method to monitor children for progressive changes over time.

Rett syndrome (RTT) is an early-onset neurodevelopmental disorder that is caused by mutations in the MECP2 gene; however, defects in other genes (CDKL5 and FOXG1) can lead to presentations that resemble classic RTT, although they are not completely identical. Here, we attempted to identify other monogenic disorders that share features of RTT. A total of 437 patients with a clinical diagnosis of RTT-like were studied; in 242 patients, a custom panel with 17 genes related to an RTT-like phenotype was run via a HaloPlex-Target-Enrichment-System. In the remaining 195 patients, a commercial TruSight-One-Sequencing-Panel was analysed. A total of 40 patients with clinical features of RTT had variants which affect gene function in six genes associated with other monogenic disorders. Twelve patients had variants in STXBP1, nine in TCF4, six in SCN2A, five in KCNQ2, four in MEF2C and four in SYNGAP1. Genetic studies using next generation sequencing (NGS) allowed us to study a larger number of genes associated with RTT-like simultaneously, providing a genetic diagnosis for a wider group of patients. These new findings provide the clinician with more information and clues that could help in the prevention of future symptoms or in pharmacologic therapy.

Ketogenic dietary therapies (KDT) produce anticonvulsant and neuroprotective effects, reduce seizures and improve the cognitive state in patients with epilepsy. Our purpose was to evaluate the effects of KDT in children with refractory epilepsy (effectiveness, side effects, impact on nutritional status and growth).A retrospective and prospective observational descriptive study was conducted in a Spanish tertiary hospital (January 2000 to December 2018). One hundred sixty pediatric patients with epilepsy were treated with KDT (82 males; mean age 5 years 9 months). Seizures, anti-epileptic drugs, anthropometric measures, side effects, and laboratory assessment were monitored baseline and at 3, 6, 12 and 24 months after the onset of KDT.In these time intervals, the seizure-free patients were: 13.7, 12.5, 14.4 and 10.6%, respectively, and a reduction of seizures ≥ 50% was achieved in 41.9, 37.5, 28.7 and 16.2%. Side effects were frequent, especially digestive disorders, hypercalciuria, hypoglycemia, hepatic dysfunction and dyslipidemia. Prealbumin, retinol binding protein, vitamin A and magnesium decreased significantly. Height was affected, especially in children below 2 years.KDT are effective for refractory epilepsy in children. However, adverse effects are frequent, and it may affect nutritional status and growth.

Background and objectives To determine the efficacy, tolerance, and safety of BRV in children with epilepsy. Methods A retrospective study of patients with epilepsy who received treatment with BRV before age 16 years and underwent a minimum follow-up of 3 months. Method and results Sixty-six patients were included in the study. Patients received BRV at a mean age of 8.8 years (range 1−16 years). The majority (93.4 %) had refractory epilepsy, 27 with epileptic encephalopathy. The median maximum dose used was 4.3 mg/kg/day. In 30.3 % of the cases, seizure frequency was reduced by over 50 %, and 9 % remained seizure-free. Greater efficacy was observed in those patients who received higher doses and when a direct switch from levetiracetam (LEV) to BRV was performed. The ineffectiveness of LEV was not related to a failure to respond to BRV treatment. Side effects were identified in 24.2 % of the cases, the most frequent being irritability and drowsiness. Conclusions BRV appears to be an effective, safe, and well-tolerated AED in children with refractory epilepsy.

Teleneurology in Spain had not been implemented so far in clinical practice, except in urgent patients with stroke. Telemedicine was hardly used in epilepsy, and patients and neurologists usually preferred onsite visits. Our goal was to study impressions of adult and pediatric epileptologists about the use of telemedicine after emergent implementation during the new coronavirus 2019 (COVID-19) pandemic. Methods An online survey was sent to the members of the Spanish Epilepsy Society and the members of the Epilepsy Study Group of the Catalan Neurological Society, inquiring about different aspects of telemedicine in epilepsy during the pandemic lockdown. Results A total of 66 neurologists responded, mostly adult neurologists (80.3%), the majority with a monographic epilepsy clinic (4 out of 5). Of all respondents, 59.1% reported to attend more than 20 patients with epilepsy (PWE) a week. During the pandemic, respondents handled their epilepsy clinics mainly with telephone calls (88%); only 4.5% used videoconference. Changes in antiseizure medications were performed less frequently than during onsite visits by 66.6% of the epileptologists. Scales were not administered during these visits, and certain types of information such as sudden expected unrelated death in epilepsy (SUDEP) were felt to be more appropriate to discuss in person. More than 4 out of 5 of the neurologists (84.8%) stated that they would be open to perform some telematic visits in the future. Conclusions In Spain, emergent implantation of teleneurology has shown to be appropriate for the care of many PWE. Technical improvements, extended use of videoconference and patient selection may improve results and patient and physician satisfaction.

Background: The ketogenic diet (KD) is an effective treatment against drug-resistant epilepsy in children. The KD is a diet rich in fats that produces anticonvulsant and neuroprotective effects that reduces seizures and improves the cognitive state. Nevertheless, it can produce side effects that sometimes can be serious. Further, the effect on growth is quite controversial when used for an extended period of time. The aim of this paper was to assess the effectiveness, side effects, and repercussions in the development of children who have been treated with a KD for more than 2 years. Methods: Observational descriptive study of 26 pediatric patients on a KD, with data collection at baseline, at 3, 6, and 12 months, and then once a year. Number of seizures, type of seizures, anti-seizure drugs, anthropometry, side effects, and alterations in laboratory assessment were monitored. Results: In every assessment, about 60%&ndash, 75% of the patients experienced a reduction in number of seizures of over 90%, and at least 50% experienced side effects, of which digestive issues, alteration in the lipid metabolism, and hypercalciuria were the most common. The KD significantly affected height after 2 years of treatment. Conclusions: The KD is an effective treatment for drug-resistant epilepsy. Its side effects, although common, are very mild, therefore, this constitutes a very safe treatment for children of all ages. More studies are needed to identify and prevent potential causes of growth retardation in children on the KD.

Background: GRIN-related disorders (GRD), the so-called grinpathies, is a group of rare encephalopathies caused by mutations affecting GRIN genes (mostly GRIN1, GRIN2A and GRIN2B genes), which encode for the GluN subunit of the N-methyl D-aspartate (NMDA) type ionotropic glutamate receptors. A growing number of functional studies indicate that GRIN-encoded GluN1 subunit disturbances can be dichotomically classified into gain- and loss-of-function, although intermediate complex scenarios are often present. Methods: In this study, we aimed to delineate the structural and functional alterations of GRIN1 disease-associated variants, and their correlations with clinical symptoms in a Spanish cohort of 15 paediatric encephalopathy patients harbouring these variants. Results: Patients harbouring GRIN1 disease-associated variants have been clinically deeply-phenotyped. Further, using computational and in vitro approaches, we identified different critical checkpoints affecting GluN1 biogenesis (protein stability, subunit assembly and surface trafficking) and/or NMDAR biophysical properties, and their association with GRD clinical symptoms. Conclusions: Our findings show a strong correlation between GRIN1 variants-associated structural and functional outcomes. This structural-functional stratification provides relevant insights of genotype-phenotype association, contributing to future precision medicine of GRIN1-related encephalopathies.

Resumen: Se estima que unos 70 millones de personas padecen epilepsia a nivel mundial de los cuales más de la mitad son niños, en los que la prevalencia estimada se sitúa en torno al 0,5-0,8%. Aunque existen diversas terapias, el tratamiento de la epilepsia se basa mayoritariamente en fármacos, que en función de su año de comercialización se clasifican como de primera, segunda o tercera generación. En el presente artículo se revisan las principales características de los fármacos antiepilépticos de última generación (lacosamida, acetato de eslicarbazepina, brivaracetam, perampanel, retigabina, everolimus y cannabidiol) que, con excepción de la retigabina (ya no está comercializada), se consideran seguros y efectivos en población pediátrica. El everolimus y el cannabidiol tienen indicaciones muy concretas (esclerosis tuberosa, síndrome de Dravet y síndrome de Lennox Gastaut) mientras que el resto están indicados en el manejo de crisis de origen focal en niños a partir de 4 años. Estas nuevas moléculas han sido desarrolladas para aportar un perfil farmacocinético y de tolerancia superior a los fármacos previamente disponibles y es previsible que a medida que aumente su uso, se vaya perfilando y ampliando su verdadero potencial. Además, por primera vez en epileptología pediátrica, se ha utilizado la extrapolación de datos de efectividad en adultos (junto con estudios de seguridad y farmacocinética específicos en población pediátrica), para acelerar la aprobación de uso en población infantil. Abstract: It is estimated that about 70 million people all over the world suffer from epilepsy, half of which are children, in whom the prevalence is around 0.5 to 0.8%. Although there are several therapies, the treatment of epilepsy is based mainly on drugs, which, depending on the year of coming onto the market are classified as first, second, or third generation. In this article, a description is presented on the main characteristics of the latest generation of anti-epileptic drugs (lacosamide, eslicarbazepine acetate, brivaracetam, perampanel, retigabine, everolimus and cannabidiol). These, with the exception of retigabine (is not yet on the market), are considered safe and effective in the paediatric population. Everolimus and cannabidiol have very specific indications (tuberous sclerosis, Dravet syndrome, and Lennox Gastaut syndrome), while the rest are indicated in the management of seizures of focal origin in children from 4 years-old. These new molecules have been developed in order to provide a pharmaceutical profile and tolerance superior to the previously available drugs, and it is forecast that as their use increases, their true potential and profile will widen. Furthermore, for the first time in Paediatric Epileptology, the extrapolation of the efficacy data in adults have been used (together with specific safety and pharmacokinetic studies in the paediatric population), in order to speed up their approval for use in the child population.

It is estimated that about 70 million people all over the world suffer from epilepsy, half of which are children, in whom the prevalence is around 0.5–0.8%. Although there are several therapies, the treatment of epilepsy is based mainly on drugs, which, depending on the year of coming onto the market are classified as first, second, or third generation. In this article, a description is presented on the main characteristics of the latest generation of anti-epileptic drugs (lacosamide, eslicarbazepine acetate, brivaracetam, perampanel, retigabine, everolimus and cannabidiol). These, with the exception of retigabine (is not yet on the market), are considered safe and effective in the paediatric population. Everolimus and cannabidiol have very specific indications (tuberous sclerosis, Dravet syndrome, and Lennox Gastaut syndrome), while the rest are indicated in the management of seizures of focal origin in children from 4 years-old. These new molecules have been developed in order to provide a pharmaceutical profile and tolerance superior to the previously available drugs, and it is forecast that as their use increases, their true potential and profile will widen. Furthermore, for the first time in Paediatric Epileptology, the extrapolation of the efficacy data in adults have been used (together with specific safety and pharmacokinetic studies in the paediatric population), in order to speed up their approval for use in the child population. Resumen: Se estima que unos 70 millones de personas padecen epilepsia a nivel mundial de los cuales más de la mitad son niños, en los que la prevalencia estimada se sitúa en torno al 0,5-0,8%. Aunque existen diversas terapias, el tratamiento de la epilepsia se basa mayoritariamente en fármacos, que en función de su año de comercialización se clasifican como de primera, segunda o tercera generación. En el presente artículo se revisan las principales características de los fármacos antiepilépticos de última generación (lacosamida, acetato de eslicarbazepina, brivaracetam, perampanel, retigabina, everolimus y cannabidiol) que, con excepción de la retigabina (ya no está comercializada), se consideran seguros y efectivos en población pediátrica. El everolimus y el cannabidiol tienen indicaciones muy concretas (esclerosis tuberosa, síndrome de Dravet y síndrome de Lennox Gastaut) mientras que el resto están indicados en el manejo de crisis de origen focal en niños a partir de 4 años. Estas nuevas moléculas han sido desarrolladas para aportar un perfil farmacocinético y de tolerancia superior a los fármacos previamente disponibles y es previsible que a medida que aumente su uso, se vaya perfilando y ampliando su verdadero potencial. Además, por primera vez en epileptología pediátrica, se ha utilizado la extrapolación de datos de efectividad en adultos (junto con estudios de seguridad y farmacocinética específicos en población pediátrica), para acelerar la aprobación de uso en población infantil.

Objective To develop recommendations for the management of patients with primary or secondary generalized tonic-clonic seizures (GTCS) based on best evidence and experience. Methods The Delphi methodology was followed. A multidisciplinary panel of 10 experts was established, who defined the scope, users and preliminary recommendations. Systematic and narrative reviews of the current literature were performed to assess data on the risk of sudden unexpected death in epilepsy and the efficacy and safety of add-on therapy in patients with GTCS. Twenty-five definitive recommendations were generated which were then graded on a scale of 1 (totally disagree) to 10 (totally agree) by the experts and 45 neurologists. Consensus was reached if at least 70% of the participants applied a score of ≥7. Each recommendation was then assigned a level of evidence, a grade of agreement and a grade of recommendation. The entire process was supervised by an expert methodologist. Results Overall, 24 out of 25 recommendations achieved consensus. These included specific recommendations on diagnosis, evaluation and treatment. The recommendations also emphasized the importance of proper psychological evaluation and effective communication between patients and health professionals, and the importance of patient and family education and support. Significance The recommendations generated by this consensus can be used as a guide for the diagnosis and management of patients with GTCS.

Objective: This study was aimed to analyze the effectiveness of sodium channel blockers (SCBs) in CDKL5 deficiency disorder (CDD)-related epilepsy. Methods: A retrospective, observational study was performed, including patients with CDD diagnosis evaluated between 2016 and 2019 at three tertiary Epilepsy Centers. Demographic, electroclinical and genetic features, as well as ASM treatments and their outcomes were analyzed, with special focus on SCBs. Results: Twenty-one patients evaluated at three tertiary Epilepsy Centers were included, of which 19 presented with epilepsy (90.5%); all had pathogenic mutations of CDKL5. Six patients (31.6%) were classified as SCB responders (more than 50% reduction), four being currently seizure free (mean seizure-free period of 8 years). Most frequent SCB drugs were oxcarbazepine (OXC), carbamazepine (CBZ), and lacosamide (LCM). None of them presented relevant adverse events. In contrast, three patients showed seizure aggravation in the non-responder group. When comparing both groups, responders had statistically significant younger age at SCB treatment and epilepsy onset, higher proportion of focal epileptiform activity and less frequent history of West syndrome. Conclusions: The results of this study indicate that treatment with SCBs might be effective and safe in a subset of patients with CDD-related epilepsy. (C) 2021 Elsevier Inc. All rights reserved.

Paroxysmal episodes are one of the most common neurological disorders in children. It is important to distinguish between paroxysmal non-epileptic events, symptomatic seizures, febrile seizures, and unprovoked seizures. Patient's history is the key to proper diagnosis in most of the cases. A single unprovoked seizure is a frequent phenomenon in the pediatric population. Studies of recurrence after a first unprovoked seizure show percentages between 23% and 96% over a median follow-up of two years. The aim of this study is to define how to evaluate the first unprovoked epileptic seizure in a child and to review the weight of the different recurrence risk factors. Several factors enable us to predict the recurrence risk after a first unprovoked seizure including family history of epilepsy, prior history of febrile seizures, age at onset, type of seizure, prolonged seizures at onset, multiple seizures in a single day, sleep state, neurological abnormalities, etiology, and abnormalities in the electroencephalogram. The most important of these risk factors are the etiology of the seizures and the evidence of epileptiform abnormalities in the electroencephalogram.

ObjectiveTo analyze the effectiveness and tolerability of perampanel across different seizure types in routine clinical care of patients with idiopathic generalized epilepsy (IGE). MethodsThis multicenter, retrospective, 1-year observational study collected data from patient records at 21 specialist epilepsy units in Spain. All patients who were aged 12 years, prescribed perampanel before December 2016, and had a confirmed diagnosis of IGE were included. ResultsThe population comprised 149 patients with IGE (60 with juvenile myoclonic epilepsy, 51 generalized tonic-clonic seizures [GTCS] only, 21 juvenile absence epilepsy, 10 childhood absence epilepsy, 6 adulthood absence epilepsy, and one Jeavons syndrome). Mean age was 36 years. The retention rate at 12 months was 83% (124/149), and 4 mg was the most common dose. At 12 months, the seizure-free rate was 59% for all seizures (88/149); 63% for GTCS (72/115), 65% for myoclonic seizures (31/48), and 51% for absence seizures (24/47). Seizure frequency was reduced significantly at 12 months relative to baseline for GTCS (78%), myoclonic (65%), and absence seizures (48%). Increase from baseline seizure frequency was seen in 5.2% of patients with GTCS seizures, 6.3% with myoclonic, and 4.3% with absence seizures. Perampanel was effective regardless of epilepsy syndrome, concomitant antiepileptic drugs (AEDs), and prior AEDs, but retention and seizure freedom were significantly higher when used as early add-on (after 2 prior AEDs) than late (3 prior AEDs). Adverse events were reported in 50% of patients over 12 months, mostly mild or moderate, and irritability (23%), somnolence (15%), and dizziness (14%) were most frequent. SignificanceIn routine clinical care of patients with IGE, perampanel improved seizure outcomes for GTCS, myoclonic seizures, and absence seizures, with few discontinuations due to adverse events. This is the first real-world evidence with perampanel across different seizure types in IGE.

Resumen: El síndrome afectivo-cognitivo cerebeloso se caracteriza por alteración en funciones ejecutivas, problemas de organización y memoria visuoespacial, alteración en la producción del lenguaje y trastorno de conducta.Niño de 11 años con dificultades de aprendizaje, trastorno de conducta y problemas de interacción social. En la exploración física destaca conducta inmadura, escaso contacto visual, dificultad para mantener la atención, lenguaje expresivo pobre y disabilidad motriz global con dispraxia para las variantes de la marcha, sin signos cerebelosos definidos. Valoración neuropsicológica: cociente intelectual 84 con datos compatibles con síndrome afectivo-cognitivo cerebeloso. RM cerebral: proceso expansivo en vermis cerebeloso inferior, que permanece estable tras 5 años de seguimiento.El cerebelo participa como centro coordinador de funciones cognitivas y emocionales. Ante un niño con un trastorno de aprendizaje con componente conductual y afectivo asociado debe incluirse la patología cerebelosa en el diagnóstico diferencial y descartar una lesión a este nivel. Abstract: Cerebellar cognitive affective syndrome is characterized by disturbances of executive function, impaired spatial cognition, linguistic difficulties, and personality change.The case of an 11 year old boy is presented, with behavior problems, learning difficulties and social interaction problems. In the physical examination he had poor visual contact, immature behavior, reduced expressive language and global motor disability with gait dyspraxia, with no defined cerebellar motor signs. In the neuropsychological evaluation he has a full scale overall intellectual quotient of 84, with signs of cerebellar cognitive affective syndrome. A tumour affecting inferior cerebellar vermis was observed in the magnetic resonance imaging, which had not significantly grown during 5 years of follow up.The cerebellum participates in controlling cognitive and affective functions. Cerebellar pathology must be considered in the differential diagnosis of children with cognitive or learning disorder with associated behavioral and emotional components.

Resumen: Introducción: La invaginación intestinal es una enfermedad obstructiva potencialmente grave que se produce cuando un segmento del intestino se introduce en el interior de otro segmento intestinal distal vecino. La tríada clásica de vómitos, dolor abdominal y hematoquecia aparece en menos de un 25% de los casos. Existen formas de presentación atípica, con clínica sistémica y/o neurológica predominante. La alteración brusca de la consciencia puede ser el único signo clínico en lactantes. Objetivos: Conocer la frecuencia y la naturaleza de las manifestaciones neurológicas de la invaginación intestinal y describir las características específicas de este subgrupo de pacientes. Pacientes y métodos: Revisión retrospectiva de las historias clínicas de 351 niños diagnosticados de invaginación intestinal entre los años 2000 y 2012. En todos los pacientes analizamos: datos epidemiológicos generales, sintomatología digestiva y neurológica, duración del cuadro clínico y eficacia del tratamiento. Resultados: En 15 de los 351 pacientes totales (4,27%) se recogieron distintos síntomas y signos neurológicos, destacando la letargia (66,66%), seguida por los episodios paroxísticos, hipotonía global, debilidad aguda y fluctuación del nivel de consciencia. Un 60% de estos pacientes tenían solo clínica neurológica y un 73,3% de ellos necesitaron cirugía. Conclusiones: Se debe considerar la invaginación intestinal en el diagnóstico diferencial de los lactantes y niños pequeños que acuden al Servicio de Urgencias con cuadros de letargia, hipotonía, debilidad aguda, alteración brusca del nivel de conciencia y/o episodios paroxísticos, aunque no exista ninguno de los signos clásicos de presentación de la enfermedad. Un diagnóstico precoz en estos casos puede evitar el desarrollo de complicaciones vasculares intestinales irreversibles. Abstract: Introduction: Intussusception is a potentially severe obstructive disease that occurs when a more proximal portion of bowel invaginates into a more distal part of the bowel. Patients with intussusception often present with a wide range of non-specific systemic symptoms, with less than one quarter presenting with the classic triad of vomiting, abdominal pain, and bloody stools. An acute change in level of consciousness could be the only clinical symptom of this disorder. Objectives: To ascertain the frequency and nature of the neurological symptoms in children with intussusception, and to describe the characteristics of the patients presenting in this atypical way. Patients and methods: We retrospectively reviewed the records of 351 children presenting with intussusception from 2000 to 2012. General epidemiological data, abdominal and neurological signs and symptoms, duration of symptoms and effectiveness of treatment, were analysed in all patients. Results: Of the 351 patients studied, 15 (4.27%) had one or more neurological symptoms recorded at presentation, with lethargy being the most frequent (66.66%), followed by hypotonia, generalized weakness, paroxysmal events, and fluctuating consciousness. Sixty per cent of these fifteen patients showed isolated neurological symptomatology, and eleven of them (73.3%) needed a laparotomy to reduce the intussusception. Conclusions: Intussusception should be considered in the differential diagnosis in infants and young children presenting as a pediatric emergency with lethargy, hypotonia, generalized weakness, paroxysmal events and/or sudden changes in consciousness, even in the absence of the classical symptoms of intussusception. An early recognition of intussusception may improve the global prognosis and avoid ischaemic intestinal sequelae.

Malignant atrophic papulosis, or Degos' disease, is a severe systemic vasculopathy extremely rare in children. The skin, gastrointestinal tract, and central nervous system are most frequently affected. We report a 5-year-old girl with malignant atrophic papulosis who presented with widespread skin lesions from early infancy and severe visual and neurological impairment.

School failure, learning and behavioral problems are more common in children with epilepsy than the general population. The aim of this study is to examine the different factors which can affect the school performance of children with epilepsy.Various psychosocial, medication-related, and epilepsy-related factors may be associated with learning disorders in epilepsy. The age of onset of epilepsy, the type of syndrome, its aetiology, and the response to treatment are some of the most important epilepsy-related factors. All of the established antiepileptic drugs can produce cognitive side effects, which are increased with polypharmacy and with increasing dosage and anticonvulsant blood levels.Judicious management of all related factors is essential for an optimal outcome. Recent onset of educational problems in a child with epilepsy deserves immediate and exhaustive evaluation and management.Fracaso escolar y epilepsia infantil.Introduccion. El fracaso escolar, los trastornos de aprendizaje y las alteraciones de conducta son mas frecuentes en el niño epileptico que en la poblacion general. El objetivo de este trabajo es estudiar los diversos factores que pueden afectar al rendimiento escolar del niño con epilepsia. Desarrollo. Los aspectos que condicionan el fracaso escolar y las alteraciones de aprendizaje en el niño epileptico son muy heterogeneos, e incluyen factores propios de la epilepsia, factores de indole psicosocial y factores derivados del tratamiento antiepileptico. La edad de comienzo de la epilepsia, el tipo de sindrome epileptico, la etiologia de la epilepsia y la respuesta al tratamiento antiepileptico son algunos de los factores mas importantes. Todos los farmacos antiepilepticos disponibles pueden producir efectos adversos cognitivos, que son mas frecuentes en politerapia, con dosis totales altas y niveles sericos elevados. Conclusiones. Una buena valoracion de cada uno de los posibles factores implicados es fundamental para garantizar un mejor pronostico. El desarrollo de alteraciones en el rendimiento escolar en un niño con epilepsia debe conducir a una inmediata y exhaustiva evaluacion diagnostica y terapeutica.

Macrophagic myofasciitis is an unusual inflammatory myopathy, which has been almost exclusively reported in French adults with diffuse arthromyalgias and asthenia. It is characterized by an infiltrate of densely packed macrophages, with granular periodic-acid-Schiff positive content, on muscle biopsies at the site of vaccination. The presence of aluminum inclusions in these macrophages points to an inappropriate reaction to aluminum used as an adjuvant in some vaccines. Although in adults this entity is well defined, less than 15 cases have been reported in children. This study describes seven children, younger than 3 years of age, with typical lesions of macrophagic myofasciitis on quadriceps muscle biopsy. In five cases, biopsies were performed to exclude mitochondrial pathology. All the children developed hypotonia and motor or psychomotor delay, associated with others symptoms. Abnormal neuroimaging was evident in six cases. Spectrometry studies detected elevated levels of aluminum in muscle in three of four cases tested. Despite the wide use of vaccines in childhood, macrophagic myofasciitis was rarely observed in children and its characteristic histologic pattern could not be correlated with a distinctive clinical syndrome.

Introduccion. Las encefalopatias epilepticas del lactante constituyen un grupo de entidades donde la actividad epileptica mantenida contribuye por si misma al deterioro neurologico y cognitivo del paciente. Entre ellas se incluyen el sindrome de Ohtahara, la encefalopatia mioclonica precoz, el sindrome de West, el sindrome de Dravet y la epilepsia migratoria maligna del lactante. Estos sindromes se originan por etiologias variadas, incluyendo lesiones estructurales cerebrales, enfermedades metabolicas y heredodegenerativas, y alteraciones geneticas, entre otras. Objetivo. Presentar y discutir el conocimiento actual sobre los hallazgos geneticos en las encefalopatias epilepticas del lactante, el potencial correlato genotipo-fenotipo en las distintas formas de encefalopatias epilepticas y el impacto de estos nuevos hallazgos en la practica clinica. Desarrollo. En los lactantes con encefalopatias epilepticas, sin una etiologia definida tras realizar una resonancia magnetica cerebral, debe considerarse un abordaje etiologico que excluya patologias geneticas. En la actualidad, mas de 50 genes se han asociado con la etiologia de las encefalopatias epilepticas del lactante. Los paneles de multiples genes analizados por tecnicas de secuenciacion masiva son una herramienta util para el diagnostico genetico de estos pacientes. Conclusiones. El conocimiento sobre la genetica de las encefalopatias epilepticas del lactante ha revolucionado el abordaje diagnostico y cada vez se implican mas genes y distintos tipos de mutaciones en la patogenia de estas patologias. El desarrollo de clasificaciones especificas para las encefalopatias epilepticas geneticas puede contribuir a un mejor correlato genotipo-fenotipo, a orientar mejor el consejo genetico y a considerar terapias especificas.

Introduccion. Los deficits neurocognitivos y las dificultades de aprendizaje representan las complicaciones neurologicas mas frecuentes de la neurofibromatosis tipo 1 (NF1) en la edad pediatrica y son responsables de una importante morbilidad evolutiva. Los ninos con NF1 muestran alteraciones en atencion, percepcion visual, lenguaje, funciones ejecutivas, logros academicos y conducta. Los estudios en modelos animales sugieren que las alteraciones de aprendizaje en la NF1 se relacionan con una potenciacion de la actividad Ras que conduce a un incremento de la inhibicion mediada por el acido gamma-aminobutirico (GABA) y a una disminucion de la potenciacion sinaptica a largo plazo. Objetivo. Describir la frecuencia, gravedad, tipologia y evolucion natural de los deficits neurocognitivos especificos de la NF1. Desarrollo. Los trastornos neurocognitivos y conductuales afectan al 50-80% de los ninos con NF1. Se pueden definir tres subtipos de perfiles cognitivos en la NF1, incluyendo trastorno de aprendizaje global, trastorno especifico de aprendizaje y trastorno por deficit de atencion/hiperactividad aislado. Los deficits cognitivos mas frecuentes se relacionan con la alteracion visuoespacial, aunque tambien son importantes las alteraciones de la memoria de trabajo y de la funcion ejecutiva asociadas con la disfuncion de la corteza prefrontal. Conclusiones. Existe una gran frecuencia global de problemas cognitivos en la NF1, lo cual implica que la disfuncion neurocognitiva sea la mayor complicacion medica que afecta la calidad de vida de estos pacientes. El diagnostico y el tratamiento precoces de los trastornos de aprendizaje en estos ninos son basicos para conseguir un mejor desempeno academico.

Multiple factors underlie the cognitive changes associated with epilepsy, including the effect of antiepileptic drug (AED) therapy itself. The use of AEDs in the management of epilepsy requires an ongoing risk-benefit analysis that attempts to maximize seizure control while minimizing adverse cognitive side-effects.This review focuses on the global and specific cognitive effects of the classic and the new AEDs.All of the established AEDs can produce cognitive side effects, which are increased with polypharmacy and with increasing dosage and anticonvulsant blood levels. The main disorders are a diminished reaction and information processing time with alterations affecting memory, attention and language. Further, there is much debate concerning the existence and clinical importance of differential AED cognitive side effects and a large portion of the literature examining the comparative cognitive effects of AEDs is limited by inadequate study designs.Cognitive side effects of antiepileptic drugs are common and can negatively affect tolerability, compliance, and long-term retention of the treatment. The role of cognitive side effects should be kept in proper perspective when choosing AED therapy. It is important to be able to recognize early these effects and to put them into perspective as to how they affect our patients.Epilepsia y cognicion: el papel de los farmacos antiepilepticos.Introduccion. Multiples y muy diversos factores se relacionan con la alteracion cognitiva en la epilepsia, incluyendo el efecto adverso directo de los farmacos antiepilepticos (FAE). El uso de los FAE requiere de un riguroso equilibrio entre riesgo y beneficio para conseguir asi el mejor control de las crisis con el menor numero de efectos adversos neurocognitivos. Objetivo. Analizar los efectos adversos cognitivos generales y especificos de los FAE de primera, segunda y tercera generacion. Desarrollo. Todos los FAE disponibles pueden producir efectos adversos cognitivos, que son mas frecuentes en politerapia, con dosis totales altas y niveles sericos elevados. Las alteraciones mas comunes son el descenso de la capacidad de reaccion y de la velocidad de procesamiento con afectacion concomitante de la memoria, la atencion y el lenguaje. Sin embargo, hay gran controversia sobre la existencia o no de perfiles cognitivos especificos para cada uno de los distintos FAE y se dispone de una informacion contradictoria al respecto por la inadecuada metodologia de los estudios comparativos. Conclusiones. Los efectos adversos cognitivos de los FAE son frecuentes y pueden afectar negativamente la tolerabilidad, el cumplimiento y el mantenimiento a largo plazo del tratamiento antiepileptico. Se debe considerar el potencial efecto adverso cognitivo de los distintos FAE a la hora de elegir un tratamiento y es importante reconocer e identificar precozmente estos efectos adversos y saber como pueden afectar a los pacientes.

A benign prognosis has been claimed in benign familial infantile seizures (BFIS). However, few studies have assessed the long-term evolution of these patients. The objective of this study is to describe atypical courses and presentations in BFIS families with mutations in PRRT2 gene. We studied clinically affected individuals from five BFIS Spanish families. We found mutations in PRRT2 in all 5 families. A non-BFIS phenotype or an atypical BFIS course was found in 9/25 (36%) patients harbouring a PRRT2 mutation. Atypical features included neonatal onset, mild hemiparesis, learning difficulties or mental retardation, and recurrent seizures during adulthood. We also report a novel PRRT2 mutation (c.121_122delGT). In BFIS families an atypical phenotype was present in a high percentage of the patients. These findings expand the clinical spectrum of PRRT2 mutations including non-benign epileptic phenotypes.

Benign myoclonic epilepsy in infancy (BMEI) is a well-defined electro-clinical syndrome, classically associated with a good prognosis. However, in the last years several studies have been published with variable results of neuropsychological outcome in BMEI. AIM. To analyze the natural history and the cognitive and behavioral outcome in BMEI patients.We report a long-term follow-up of 10 patients with BMEI. During the follow-up, all the patients underwent neurocognitive and behavioral evaluations.Sixty percent of patients became seizure free on valproic acid. The intelligence quotient of the whole cohort was between 74 and 93, with three patients in the range of borderline intelligence and six in the range of medium-to-low intelligence. Nine of the 10 patients met criteria for attention deficit hyperactivity disorder, and two patients associated another learning disorder. All patients showed poor motor and visuospatial coordination signs and three patients had a behavior disorder.The term 'benign' in BMEI has to be used with caution in refer to its behavioral and cognitive outcome. Early onset of seizures and a worse epilepsy control may be risk factors of a poor neuropsychological outcome.Epilepsia mioclonica benigna del lactante: evolucion natural y pronostico neurocognitivo y conductual.Introduccion. La epilepsia mioclonica benigna del lactante (EMBL) es un sindrome electroclinico de caracteristicas homogeneas y bien definidas, considerado clasicamente de buen pronostico. Sin embargo, en los ultimos años se han publicado estudios con resultados variables en cuanto a evolucion neuropsicologica. Objetivo. Analizar la evolucion natural y el pronostico neurocognitivo y conductual de los pacientes con EMBL. Pacientes y metodos. Estudio retrospectivo de 10 pacientes con EMBL, con un periodo de seguimiento de mas de cinco años, durante los cuales se realizo una evaluacion neurocognitiva y conductual. Resultados. En el 60% de los pacientes las crisis se controlaron con acido valproico en monoterapia, y el 80% no presento nuevas crisis durante su seguimiento. El cociente intelectual de la cohorte se situo entre 74 y 93; tres pacientes tuvieron un cociente intelectual en rango de inteligencia limite, y seis, en rango de inteligencia media-baja. Nueve pacientes cumplieron criterios de trastorno por deficit de atencion/hiperactividad y dos asociaban otro trastorno del aprendizaje, uno de ellos trastorno de aprendizaje no verbal, y el otro, trastorno especifico de la lectoescritura. Todos los pacientes presentaron datos de pobre coordinacion motriz y visuoespacial, y tres fueron diagnosticados de trastorno de conducta. Conclusiones. El termino 'benigno' en la EMBL debe utilizarse con precaucion en cuanto a su pronostico neurocognitivo y conductual. El inicio precoz y un peor control de las crisis podrian suponer factores de riesgo de evolucion neuropsicologica desfavorable.

Described here is the case of a girl with a reticulated capillary malformation on the right side of her face, along with Dyke-Davidoff-Masson syndrome, as evidenced by microphthalmia and severe associated anomalies in the right eye, and right cerebral hemispheric atrophy and cerebral arteries malformations. Capillary malformations are a novel finding for children with Dyke-Davidoff-Masson syndrome.

Fundamento y objetivo: La hemiplejia alternante de la infancia (HAI) es una enfermedad rara y de etiologia desconocida. Se caracteriza por episodios recurrentes de hemiplejia, crisis tonicas y/o distonicas y trastornos de la motilidad ocular de inicio precoz, que evolucionan hacia una encefalopatia grave. Nuestro objetivo ha sido describir los sintomas clinicos, los desencadenantes, el resultado de examenes complementarios, la evolucion a largo plazo y la respuesta al tratamiento en una serie de pacientes con HAI. Pacientes y metodo: Se ha realizado un estudio descriptivo, retrospectivo y multicentrico en 17 pacientes espanoles de 1-24 anos de edad que cumplian criterios diagnosticos de HAI. Resultados: Un total de 12 casos cumplian criterios de HAI tipica y 5 de HAI atipica. La edad media en el momento del diagnostico fue de 26 meses y un 47% tenia historia familiar de migrana. La edad media de inicio de la hemiplejia fue 9,3 meses. Los sintomas desaparecian durante el sueno en todos los casos y en el 94% habia algun desencadenante de las crisis. La enfermedad evoluciono a retraso cognitivo con dificultades en la marcha y disartria. Los examenes realizados (bioquimicos, neurofisiologicos, neurorradiologicos) resultaron normales o inespecificos. En 3 pacientes se descartaron mutaciones en los genes CACNA1A y ATP1A2. En un 81% se observo respuesta a la flunaricina. Conclusiones: Los sintomas clinicos caracteristicos siguen siendo la clave para el diagnostico de esta entidad, en ausencia de marcadores geneticos, bioquimicos, radiologicos y neurofisiologicos. El diagnostico precoz evita la realizacion de pruebas invasivas, la repeticion de examenes y el uso de farmacos ineficaces y potencialmente toxicos, y permite iniciar el tratamiento con flunaricina. Es necesaria la realizacion de estudios geneticos en series amplias de pacientes, aunque hay limitaciones por la baja frecuencia de HAI y porque la mayoria de los casos corresponden a formas esporadicas

We report on a child with multiple lesions of membranous aplasia cutis congenita of the scalp since birth who developed an extensive intracranial arteriovenous malformation several years later. Even in the absence of other clues to suggest intracranial anomalies, children with multiple scalp defects should be carefully surveyed and followed up in the long term.

We studied 10 patients with a variable degree of mtDNA depletion in muscle. Seven patients showed a clear-cut myopathic pattern, while the three remaining had brain involvement. There was no relationship between age at onset and relative mtDNA copy number in muscle, but we found an apparent correlation between clinical severity and degree of muscle mtDNA depletion. Muscle morphology showed that mtDNA depletion was associated with mitochondrial proliferation and cytochrome c oxidase negative fibers. Biochemical studies revealed single or combined defects of mtDNA-dependent respiratory chain complexes. Our data indicate that patients with mtDNA depletion may have a more variable age at onset and clinical evolution and wider phenotype than previously thought. The diagnosis of this condition, so far regarded as rare, may have been overlooked to some extent.

Acute inflammation of a single cerebellar hemisphere (hemicerebellitis) is a rare disorder of unknown origin. The clinical presentation is mainly characterized by headache, ataxia, dysmetria, and vomiting. In addition, some children may develop severe intracranial hypertension. The neuroimaging of hemicerebellitis raises a challenging differential diagnosis, particularly with posterior fossa tumours. Although there is no standard treatment for hemicerebellitis, its outcome is usually favourable. However, ipsilateral hemicerebellar atrophy develops in up to half of cases, and a minority of children may show persisting fine motor and/or neurocognitive sequelae. In this article, we contribute with three new reports and review a total of 35 cases of hemicerebellitis.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that results from mutations in the TSC1 or TSC2 genes and is associated with hamartoma formation in multiple organ systems. Brain disorders are the origin of more frequent and severe problems and include infantile spasms, intractable epilepsy, brain tumors, cognitive disabilities, and autism. TSC1 or TSC2 encoded proteins modulate cell function via the mTOR signaling cascade and serve as keystones in regulating cell growth and proliferation. AIM. To review the etiopathogenic mechanisms and the natural course of the association of autism and epilepsy in TSC.Both the clinical and the neuroimaging findings of TSC, including early onset epilepsy and the localization of cortical tubers in the temporal lobes, and the molecular understanding of the mTOR signaling pathway, not only involved in cell growth, but also in synaptogenesis, synaptic plasticity and neuronal functioning, have suggested a multimodal origin of autism in these patients.A greater understanding of the pathogenetic mechanisms underlying autism in TSC could help in devising targeted and potentially more effective treatment strategies. Antagonism of the mTOR pathway with rapamycin and everolimus may provide new therapeutic options for these TSC patients.

Introduccion. Se define siringomielia como una cavidad que contiene liquido cefalorraquideo dispuesta en el interior de la medula espinal. Objetivo. Describir las caracteristicas clinicas de una serie de pacientes con siringomielia, su diagnostico y tratamiento. Pacientes y metodos. Estudio descriptivo retrospectivo realizado mediante la revision de historias clinicas en nuestro centro. Resultados. Se revisaron 25 pacientes diagnosticados de siringomielia. En cinco el diagnostico fue casual y ocho presentaban una patologia grave previa (tumoral, osea o vascular). Dos pacientes comenzaron con hidrocefalia y clinica de hipertension intracraneal y unicamente dos destacaban cefalea como unico sintoma. Cuatro presentaron escoliosis progresiva, dos de ellos como queja inicial, y precisaron cirugia con artrodesis y uso de corse, respectivamente. Destaca la precocidad del diagnostico. La mayoria presentaba unicamente perdida de fuerza leve, con potenciales somatosensoriales y electromiograma normales. En todos se hicieron controles con resonancia magnetica. Ocho pacientes precisaron craniectomia descompresiva con laminectomia posterior C1-C2, con drenaje de la cavidad siringomielica en cuatro. Nueve requirieron valvula de derivacion y dos precisaron, ademas, ventriculostomia. Conclusiones. La presencia de siringomielia en pediatria es rara, y se asocia generalmente a malformaciones en la fosa posterior y antecedentes de disrafismo espinal. Destaca la escoliosis progresiva como posible manifestacion aislada. Un abordaje multidisciplinar con controles radiologicos seriados y la valoracion por servicios de neurologia y neurocirugia pediatricos son mandatorios para su seguimiento.

The social, language, and behavioural problems that occur with autism suggest that this syndrome affects a functionally diverse and widely distributed set of neural systems.To review the molecular pathways involved in synaptic growth, development, and stability of human synapses. We also examine the genes implicated in synaptogenesis which have been associated with autism. In particular, we highlight the role of these genes in synaptic cell adhesion, organization of presynaptic and postsynaptic specializations, growth signaling pathways, and endosomal function.Proper brain function requires stringent balance of excitatory and inhibitory synapse formation during neural circuit assembly. Mutation of genes that normally sculpt and maintain this balance results in severe dysfunction, causing neurodevelopmental disorders including autism, epilepsy, Angelman syndrome, fragile X syndrome, and Rett syndrome. Such mutations may result in defective architectural structuring of synaptic connections, molecular assembly of synapses and/or functional synaptogenesis.Increased knowledge of abnormal mechanisms of human synaptogenesis may lead to define different etio-pathogenic models of autism and to understand how far abnormal cell/synaptic growth and synaptic function could be reversed.

Malignant atrophic papulosis, or Degos' disease, is a severe systemic vasculopathy extremely rare in children. The skin, gastrointestinal tract, and central nervous system are most frequently affected. We report a 5-year-old girl with malignant atrophic papulosis who presented with widespread skin lesions from early infancy and severe visual and neurological impairment.

Antiepileptic hypersensitivity syndrome (AHS) is a potentially life-threatening syndrome in pediatric cases. It is associated with aromatic anticonvulsivant drugs and others antibiotics with or without associated reactivation of virus. The pathogenesis of the process is not clear. Clinical feature of this syndrome include cutaneous reactions, fever and lymphadenopathies, but different organs can be involved. In laboratory analyses we can find leucocytosis, eosinophilia, and increase in transaminase levels. Significant elevation of procalcitonin (PCT) has been described in two adults patients. This study we report two cases of a 14-year-old male and a 13-year-old female with a AHS and a high level of the PCT. These are the first cases described in pediatric age. Establishing a diagnosis of AHS is important to avoid the use of the involved drug. The treatment is based on the withdrawal of the drugs that are supposed and if there is no improvement or a deterioration of the patient, the use of systemic corticosteroids is often useful.

Alternating hemiplegia of childhood (AHC) is a rare disease of unknown etiology characterized by early onset of recurrent episodes of hemiplegia, tonic or dystonic attacks and abnormal ocular movements with a fatal outcome to severe encephalopathy. Our aim was to describe the clinical manifestations, precipitating factors, complementary studies results, long-term outcome and response to treatment in a series of AHC patients.Descriptive, retrospective and multicenter study in 17 Spanish patients aged between 1-24 years who fulfilled diagnostic criteria of AHC.Twelve cases fulfilled criteria of typical AHC and 5 were atypical. Mean age at diagnosis was 26 months and 47% cases had a family history of migraine. Mean age at onset of hemiplegic attacks was 9.3 months. Symptoms disappeared during sleep and precipitating factors were present in 94% cases. Most patients developed mental retardation with ataxia and dysarthria. Work-up tests (metabolic, neurophysiologic and radiologic) were normal or nonspecific. In 3 patients mutations in CACNA1A, ATP1A2 were ruled out. Positive responses to flunarizine was observed in 81%.The characteristic clinical symptoms are still the clue to make the diagnosis of this disease, with a lack of genetic, biochemical or radiological specific studies. Early diagnosis avoids invasive tests, repeating procedures, using ineffective and potentially toxic treatments, and allows to start treatment with flunarizine without delay. More genetic studies are needed in broader series of patients.

Status Epilepticus (SE) is a potential and relatively common complication of epileptic seizures. Traditionally, SE was defined as 30 minutes of continuous seizure activity or a series of seizures without return to full consciousness between the seizures. As a practical rule, it is admitted that all patients arriving at the emergency room suffering from epileptic seizures could have SE and should be treated accordingly. It is well known that the longer an attack has lasted, the more difficult it is to control in the next 5 to 10 minutes. On the other hand, once an attack has lasted for over 5 to 10 minutes, it is unlikely to cease spontaneously. Ambulatory intervention should focus on this "therapeutic interval" in acute attacks with the use of first-line drugs such as the intramuscular, rectal, oral, and/or intranasal application of benzodiazepines (BZD). Treatment of SE is a medical emergency, which should include 3 priority objectives: (1) to stop the seizures; (2) to maintain internal homeostasis; and (3) to treat possible complications. Current consensus is that a BZD, notably lorazepam or diazepam, is the initial class of drug for the treatment of SE. Phenytoin, fosphenytoin, or valproate generally is agreed upon as the next drugs to be administered. Failure to respond to optimal BZD and phenytoin loading operationally defines refractory SE.