Epileptogénesis y corteza piriforme: entendiendo a la epilepsia del lóbulo temporal más allá del hipocampo / Epileptogenesis and the piriform cortex: understanding temporal lobe epilepsy beyond the hippocampus

Introducción: Con la experiencia de los registros electroencefalográficos invasivos y el fracaso quirúrgico después de la cirugía, se ha hecho evidente que la epilepsia del lóbulo temporal es mucho más compleja de lo que se creía, y en la actualidad es considerada una enfermedad de redes anatomofuncionales y no de lesiones estructurales. Contenido: La información neurofisiológica e imagenológica actual permite concluir que en esta epilepsia están involucradas varias redes neuronales temporales y extratemporales que contribuyen a la extensión de la zona epileptógena. Una forma de entender el concepto de red epiléptica en la epilepsia del lóbulo temporal es a partir del conocimiento de la corteza piriforme. Varios estudios clínicos han mostrado que en pacientes con epilepsia del lóbulo temporal asociada a esclerosis hipocampal existe una disfunción interictal del procesamiento olfatorio que es más significativa, en comparación con pacientes con epilepsia focal extrahipocampal y controles sanos. Esta alteración es, probablemente, la consecuencia de una red neuronal disfuncional que se extiende más allá del hipocampo y que afecta a otras estructuras cercanas, incluida la corteza piriforme. Conclusión: En este artículo llevamos a cabo una revisión narrativa de la literatura con el objetivo de establecer un vínculo entre la corteza piriforme y la epileptogénesis del lóbulo temporal, y demostramos que esta enfermedad es la consecuencia de una disfunción de redes neuronales que no depende exclusivamente de una anormalidad estructural en el hipocampo o en estructuras cercanas.

Introduction: With the experience of invasive EEG recordings and surgical failure after surgery, it has become clear that temporal lobe epilepsy is much more complex than previously thought, and currently, is conceptualized as a disease of anatomical networks instead of structural lesions. Content: The current neurophysiological and imaging information allows us to conclude that several temporal and extratemporal anatomical networks are involved in this type of epilepsy. One way of understanding the concept of the epileptic network in temporal lobe epilepsy is from the knowledge of the piriform cortex. Several clinical studies have shown that in patients with temporal lobe epilepsy associated with hippocampal sclerosis exists an interictal dysfunction of olfactory processing that is more significant compared to patients with focal extra-hippocampal epilepsy and healthy controls. This alteration is probably the consequence of a dysfunctional neural network that extends beyond the hippocampus and affects other nearby structures, including the piriform cortex. Conclusion: In this article, we carry out a narrative review of the literature with the aim of establishing a link between the piriform cortex and temporal lobe epileptogenesis, demonstrating that this disease is the consequence of a dysfunctional network that does not depend exclusively of a hippocampal structural abnormality.

Change in intestinal flora after treatment in children with focal epilepsy / 中国当代儿科杂志

OBJECTIVES@#To study the difference in intestinal flora between children with focal epilepsy and healthy children and the change in intestinal flora after treatment in children with epilepsy.@*METHODS@#A total of 10 children with newly diagnosed focal epilepsy were recruited as the case group and were all treated with oxcarbazepine alone. Their clinical data were recorded. Fecal specimens before treatment and after 3 months of treatment were collected. Fourteen aged-matched healthy children were recruited as the control group. Total bacterial DNA was extracted from the fecal specimens for 16S rDNA sequencing and bioinformatics analysis.@*RESULTS@#After 3 months of carbamazepine treatment, the seizure frequency was reduced by >50% in the case group. At the phylum level, the abundance of Actinobacteria in the case group before treatment was significantly higher than that in the control group (P<0.05), and it was reduced after treatment (P<0.05). At the genus level, the abundances of Escherichia/Shigella, Streptococcus, Collinsella, and Megamonas in the case group before treatment were significantly higher than those in the control group (P<0.05), and the abundances of these bacteria decreased significantly after treatment (P<0.05).@*CONCLUSIONS@#There is a significant difference in intestinal flora between children with focal epilepsy and healthy children. Oxcarbazepine can significantly improve the symptoms and intestinal flora in children with epilepsy.

Predictive factors of quality of life in temporal and extratemporal lobe epilepsy: association with affective temperament profiles and psychiatric comorbidities / Factores predictivos de la calidad de vida en la epilepsia del lóbulo temporal y extratemporal: asociación con perfiles de temperamento afectivo y comorbilidades psiquiátricas

ABSTRACT Background: Investigating predictive factors of reduced quality of life (QOL) of patients and their association with focal epilepsy can improve management and treatment strategies. Objective: This study aimed to investigate the relationship between affective temperaments, depression, anxiety, disease characteristics, and QOL and to explore the predictors of QOL in patients with temporal lobe epilepsy (TLE) and extratemporal lobe epilepsy (ETLE). Methods: A total of 50 patients with TLE, 51 patients with ETLE, and 70 controls were enrolled. Affective temperaments were evaluated using the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire (TEMPS-A). QOL was assessed by the Short-Form Health Survey (SF-36). Beck Depression Inventory and Beck Anxiety Inventory were used to explore depression and anxiety severity, respectively. Results: Compared with the controls, patients with TLE and ETLE had significantly higher scores on all TEMPS-A scales, except on hyperthymic temperament. All the SF-36 subscale scores were lower in the TLE and ETLE groups. Linear regression analysis revealed that depressive symptoms, anxiety, depressive and irritable temperament, and seizure frequency were significant predictors of QOL in TLE. Patients with ETLE with temperamental disturbances, depressive symptoms, and polytherapy had a poorer QOL. Conclusions: Affective temperaments, psychiatric disorders, and clinical factors may predict impaired QOL in patients with TLE and ETLE. Further studies are needed to identify predictors of QOL in various epilepsy subtypes.

RESUMEN Antecedentes: Explorar los factores asociados y predictivos que reducen la calidad de vida en la epilepsia focal produce un efecto beneficioso en las estrategias de gestión y tratamiento. Objetivo: Investigar la relación entre temperamentos afectivos, depresión, ansiedad, características de la enfermedad y calidad de vida (QOL) y explorar los predictores de QOL en pacientes con epilepsia del lóbulo temporal (TLE) y epilepsia del lóbulo extratemporal (ETLE). Métodos: Se inscribieron un total de 50 pacientes con TLE, 51 pacientes con ETLE y 70 controles. Los temperamentos afectivos se evaluaron mediante el cuestionario de autoevaluación de Temperamento de Memphis, Pisa, París y San Diego (TEMPS-A). La calidad de vida se evaluó mediante la encuesta de salud de formato corto (SF-36). También se realizó a todos los participantes el Inventario de Depresión de Beck (BDI) y el Inventario de Ansiedad de Beck (BAI). Resultados: Los pacientes con TLE y ETLE tuvieron puntuaciones significativamente más altas en todas las escalas TEMPS-A que los controles, excepto la hipertimia . En la comparación de las puntuaciones del SF-36 dentro de cada grupo, todas las subescalas fueron más bajas en los pacientes con TLE y ETLE. El análisis de regresión lineal reveló que la depresión y la ansiedad, el temperamento depresivo e irritable y la frecuencia de las convulsiones fueron predictores significativos de la calidad de vida en el TLE. Además, los pacientes con ETLE con desequilibrios de temperamento afectivo, depresión comórbida y politerapia tenían una peor calidad de vida. Conclusiones: Los temperamentos afectivos, los trastornos psiquiátricos y los factores clínicos pueden predecir el deterioro de la calidad de vida en pacientes con TLE y ETLE. Se necesitan más estudios para descubrir los predictores de la calidad de vida en varios subtipos de epilepsia.

Efficacy and safety of levetiracetam as adjunctive therapy for refractory focal epilepsy / Eficácia e segurança do levetiracetam como terapia adjunta na epilepsia focal refratária

ABSTRACT Background: Epilepsy affects about 50 million people worldwide and around 30% of these patients have refractory epilepsy, with potential consequences regarding quality of life, morbidity and premature mortality. Objective: The aim of treatment with antiseizure medications (ASMs) is to allow patients to remain without seizures, with good tolerability. Levetiracetam is a broad-spectrum ASM with a unique mechanism of action that differs it from other ASMs. It has been shown to be effective and safe for treating adults and children with epilepsy. Methods: This was a phase III, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of levetiracetam in children and adults (4-65 years) as an adjuvant treatment for focal-onset seizures. It was conducted among 114 patients undergoing treatment with up to three ASMs. The primary efficacy analysis was based on the proportion of patients who achieved a reduction of ≥ 50% in the mean number of focal seizures per week, over a 16-week treatment period. The patients were randomized to receive placebo or levetiracetam, titrated every two weeks from 20 mg/kg/day or 1,000 mg/day up to 60 mg/kg/day or 3,000 mg/day. Results: Levetiracetam was significantly superior to placebo (p = 0.0031); 38.7% of the participants in the levetiracetam group and 14.3% in the control group shows reductions in focal seizures. Levetiracetam was seen to have a favorable safety profile and an adverse event rate similar to that of placebo. Conclusion: Corroborating the results in the literature, levetiracetam was shown to be effective and safe for children and adults with refractory focal-onset epilepsy.

RESUMO Introdução: A epilepsia afeta cerca de 50 milhões de pessoas em todo o mundo e aproximadamente 30% desses pacientes apresentam epilepsia refratária, com possíveis consequências na qualidade de vida, morbidade e mortalidade prematura. Objetivo: O objetivo do tratamento com fármacos antiepilépticos (FAEs) é permitir que os pacientes permaneçam sem crises epilépticas com boa tolerabilidade. O levetiracetam (LEV) é um FAE de amplo espectro, com mecanismo de ação único, diferente dos demais e que demonstra ser eficaz e seguro no tratamento de adultos e crianças. Métodos: Estudo de fase III, multicêntrico, randomizado, duplo-cego e controlado por placebo avalia a eficácia e a segurança do LEV em crianças e adultos (4-65 anos) como tratamento adjuvante para crises de início focal em 114 pacientes já tratados com até três FAEs. A análise de eficácia primária foi baseada na proporção de pacientes que apresentaram redução ≥50% no número médio de crises epilépticas focais semanais, durante 16 semanas. Os pacientes foram randomizados para receber placebo ou LEV, titulado a cada duas semanas de 20 mg/kg/dia ou 1.000 mg/dia até 60 mg/kg/dia ou 3.000 mg/dia. Resultados: LEV foi significativamente superior ao placebo (p=0,0031), com 38,7% dos participantes no grupo LEV e 14,3% no grupo controle que apresentaram redução das crises focais. LEV apresenta bom perfil de segurança com eventos adversos semelhantes ao placebo. Conclusão: Corroborando com os resultados da literatura, o levetiracetam mostra-se eficaz e seguro para crianças e adultos com epilepsia focal refratária.

Vinpocetina de liberación prolongada: un posible tratamiento adyuvante en crisis epiléptica de inicio focal / Extended-release vinpocetine: a possible adjuvant treatment for focal onset epileptic seizures

Resumen Introducción: La vinpocetina de liberación prolongada ha demostrado ser efectiva en el control de crisis de inicio focal en pacientes epilépticos con una baja frecuencia de eventos adversos. Se realizó un estudio clínico para evaluar la eficacia y tolerabilidad de la vinpocetina como tratamiento adyuvante en pacientes con este padecimiento. Métodos: Se realizó un estudio clínico, doble ciego, de grupos paralelos. Se reclutaron 87 pacientes con diagnóstico de epilepsia focal tratados con uno a tres fármacos antiepilépticos. Los pacientes se aleatorizaron para ser tratados con vinpocetina (n = 41) o placebo (n = 46) de manera adyuvante a su tratamiento, e ingresaron a la fase basal (4 semanas), a la fase de titulación (4 semanas) y a la fase de evaluación (8 semanas) conservando estables las dosis de la vinpocetina y de los fármacos antiepilépticos. Resultados: La vinpocetina fue más efectiva que el placebo en la reducción de las crisis al finalizar la fase de evaluación (p < 0.0001). El 69% de los pacientes tratados con vinpocetina presentaron una reducción mayor al 50% en las crisis en comparación con el 13% de los pacientes tratados con placebo. No se presentaron diferencias significativas en cuanto a la presencia de efectos adversos en los pacientes tratados con vinpocetina comparados con los tratados con placebo. Los eventos adversos más frecuentes observados con vinpocetina fueron cefalea (7.9%) y diplopía (5.2%). Conclusiones: Como tratamiento adyuvante, la vinpocetina (2 mg/kg/día) redujo eficazmente la frecuencia de crisis epilépticas y demostró ser bien tolerada. Presenta un amplio perfil de seguridad y eventos adversos conocidos, que son transitorios y sin secuelas.

Abstract Background: Extended-release vinpocetine is effective to control focal onset epileptic seizures with a low rate of adverse events. A clinical study was performed to evaluate the efficacy and tolerability of vinpocetine as an adjuvant treatment in patients with this condition. Methods: A double-blind clinical study of parallel groups was conducted, in which 87 patients with a diagnosis of focal epilepsy treated with one to three antiepileptic drugs were recruited. Patients were randomized to receive vinpocetine (n = 41) or placebo (n = 46) adjuvant to their treatment. Patients entered the baseline phase (4 weeks), the titration phase (4 weeks) and the evaluation phase (8 weeks), maintaining stable doses of vinpocetine and their respective antiepileptic drug treatment. Results: Vinpocetine was more effective than placebo in reducing seizures at the end of the evaluation phase (p < 0.0001). Sixty-nine percent of the vinpocetine-treated patients had a 50% reduction in seizures compared to 13% of placebo-treated patients. No significant differences in the presence of adverse effects in patients treated with vinpocetine compared to those treated with placebo were observed. The most frequent adverse events observed with vinpocetine were headache (7.9%) and diplopia (5.2%). Conclusions: As an adjuvant treatment, vinpocetine (2 mg/kg/day) effectively reduced the frequency of epileptic seizures and proved to be well tolerated. Vinpocetine has a wide safety profile and well-known adverse events, which are transient and with no sequelae.

Evolución atípica del síndrome de Panayiotopoulos a síndrome de punta-ondas continuas durante el sueño lento / Atypical evolution of Panayiotopoulos syndrome to continuous spikes and wave's syndrome during slow sleep

Introducción: Las epilepsias focales idiopáticas constituyen uno de los grupos de epilepsias más frecuentes en la infancia. Excepcionalmente los pacientes con este tipo de epilepsias tienen evoluciones atípicas que constituyen un reto diagnóstico y terapéutico. Objetivo: Ilustrar la evolución atípica de la epilepsia focal idiopática tipo Panayiotopoulos. Presentación del caso: Adolescente de 13 años que presentó su primera crisis epiléptica a los 5 años de edad, de breve duración, mientras dormía tuvo apertura ocular, desviación de los ojos a la izquierda, abundante salivación y presentó un vómito. En tres años tuvo solo tres crisis. No recibió tratamiento con fármacos antiepilépticos hasta después de la tercera crisis, que fue más prolongada. Tras iniciar tratamiento con carbamazepina comenzó a presentar dificultades en el aprendizaje y marcada hiperactividad. Un electroencefalograma interictal de sueño demostró descargas de punta-ondas continuas en el sueño lento. Después de dos años de tratamiento se alcanzó la normalidad en el estudio electroencefalográfico de sueño, con retirada inicial de la carbamazepina, e introducción progresiva de clobazam y valproato de magnesio. Evolutivamente el paciente mantuvo las dificultades en el aprendizaje, con mejoría notable de su hiperactividad, sin recurrencia de crisis epilépticas. Conclusiones: El caso presentado constituye un ejemplo infrecuente de un paciente con una epilepsia focal idiopática con evolución atípica, probablemente inducida por la carbamazepina, con cuadro clínico-electroencefalográfico de más de dos años de duración, con mejoría favorecida por el tratamiento finalmente empleado, la evolución natural del síndrome o el efecto de ambos (AU)

Introduction: Idiopathic focal epilepsies are one of the most frequent epilepsy groups in childhood. Exceptionally, patients with this type of epilepsy have atypical evolutions that constitute a diagnostic and therapeutic challenge. Objective: To illustrate the atypical evolution of idiopathic focal epilepsy, type Panayiotopoulos. Case presentation: A 13-year-old adolescent who presented his first epileptic seizure at 5 years old, of short duration, while he slept had an eye opening, deviation of the eyes to the left, abundant salivation and vomiting. In three years he had only three seizures. He did not receive treatment with antiepileptic drugs until after the third seizure, which was longer. After starting treatment with carbamazepine, he began to have learning difficulties and marked hyperactivity. A sleep's interictal electroencephalogram showed continuous spikes and wave's discharges during the slow sleep. After two years of treatment, the normalization of the sleep electroencephalogram was achieved, with withdrawal of carbamazepine, and progressive introduction of clobazam and magnesium valproate. The patient remained evolutionarily with learning difficulties, with significant improvement in hyperactivity, without recurrence of seizures. Conclusions: The case presented is an infrequent example of a patient with idiopathic focal epilepsy with atypical evolution, probably induced by carbamazepine, with clinical-electroencephalographic symptoms during more than two years, with improvement favored by the final treatment used, the natural evolution of the syndrome or the effect of both(AU)

Prosopometamorphopsia and Visual Field Defect Improved by Valproic acid in a CADASIL Patient

Persistent aura without infarction is defined as an aura persisting for 1 week or more without evidence of infarction on neuroimaging. It is difficult to differentiate persistent visual aura without infarction from occipital lobe epilepsy. We report a Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy patient with prosopometamorphopsia and visual field defect improved by valproic acid. We also review ambiguity between visual aura in migraine and occipital lobe epilepsy.

Mechanistic Target of Rapamycin Pathway in Epileptic Disorders

The mechanistic target of rapamycin (mTOR) pathway coordinates the metabolic activity of eukaryotic cells through environmental signals, including nutrients, energy, growth factors, and oxygen. In the nervous system, the mTOR pathway regulates fundamental biological processes associated with neural development and neurodegeneration. Intriguingly, genes that constitute the mTOR pathway have been found to be germline and somatic mutation from patients with various epileptic disorders. Hyperactivation of the mTOR pathway due to said mutations has garnered increasing attention as culprits of these conditions : somatic mutations, in particular, in epileptic foci have recently been identified as a major genetic cause of intractable focal epilepsy, such as focal cortical dysplasia. Meanwhile, epilepsy models with aberrant activation of the mTOR pathway have helped elucidate the role of the mTOR pathway in epileptogenesis, and evidence from epilepsy models of human mutations recapitulating the features of epileptic patients has indicated that mTOR inhibitors may be of use in treating epilepsy associated with mutations in mTOR pathway genes. Here, we review recent advances in the molecular and genetic understanding of mTOR signaling in epileptic disorders. In particular, we focus on the development of and limitations to therapies targeting the mTOR pathway to treat epileptic seizures. We also discuss future perspectives on mTOR inhibition therapies and special diagnostic methods for intractable epilepsies caused by brain somatic mutations.

The Surgical and Cognitive Outcomes of Focal Cortical Dysplasia

Focal cortical dysplasia (FCD) is the major cause of intractable focal epilepsy in childhood leading to epilepsy surgery. The overall seizure freedom after surgery ranges between 50–75% at 2 years after surgery and the long-term seizure freedom remain relatively stable. Seizure outcome after surgery depends on a various factors such as pathologic etiologies, extent of lesion, and types of surgery. Therefore, seizure outcome after surgery for FCD should be analyzed carefully considering cohorts' characteristics. Studies of pediatric epilepsy surgery emphasize the early surgical intervention for a better cognition. Early surgical intervention and cessation of seizure activity are important for children with intractable epilepsy. However, there are limited data on the cognitive outcome after surgery in pediatric FCD, requiring further investigation. This paper reviews the seizure and cognitive outcomes of epilepsy surgery for FCD in children. Several prognostic factors influencing seizure outcome after surgery will be discussed in detail.

Epilepsy Surgery in 2019: A Time to Change

Epilepsy has been known to humankind since antiquity. The surgical treatment of epilepsy began in the early days of neurosurgery and has developed greatly. Many surgical procedures have stood the test of time. However, clinicians treating epilepsy patients are now witnessing a huge tide of change. In 2017, the classification system for seizure and epilepsy types was revised nearly 36 years after the previous scheme was released. The actual difference between these systems may not be large, but there have been many conceptual changes, and clinicians must bid farewell to old terminology. Paradigms in drug discovery are changing, and novel antiseizure drugs have been introduced for clinical use. In particular, drugs that target genetic changes harbor greater therapeutic potential than previous screening-based compounds. The concept of focal epilepsy has been challenged, and now epilepsy is regarded as a network disorder. With this novel concept, stereotactic electroencephalography (SEEG) is becoming increasingly popular for the evaluation of dysfunctioning neuronal networks. Minimally invasive ablative therapies using SEEG electrodes and neuromodulatory therapies such as deep brain stimulation and vagus nerve stimulation are widely applied to remedy dysfunctional epilepsy networks. The use of responsive neurostimulation is currently off-label in children with intractable epilepsy.

Clinical Significance of Asymmetric Minimum Intensity Projection Images of Brain Magnetic Resonance Imaging in Children

BACKGROUND AND PURPOSE: The susceptibility-weighted imaging form of brain MRI using minimum intensity projection (mIP) is useful for assessing traumatic brain injuries because it readily reveals deoxyhemoglobin or paramagnetic compounds. We investigated the efficacy of using this methodology in nontraumatic patients. METHODS: We retrospectively analyzed the asymmetric mIP findings in nontraumatic patients. Asymmetric mIP images were first verified visually and then using ImageJ software. We enrolled patients with a difference of >5% between hemispheres in ImageJ analysis. All patients underwent detailed history-taking and EEG, and asymmetric mIP findings were compared. RESULTS: The visual analysis identified 54 pediatric patients (37 males and 17 females) with asymmetric mIP findings. Ten patients were excluded because they did not meet the ImageJ verification criteria. The 44 patients with asymmetry comprised 36 with epilepsy, 6 with headache, and 2 with cerebral infarction. Thirty-one of the 36 epileptic patients showed definite partial seizure activities in semiology, while the remaining patients did not demonstrate a history of partial seizure manifestations. The MRI findings were normal in all patients except for five with periventricular leukomalacia unrelated to seizure symptoms. There was agreement between mIP images and semiology in 29 (93.5%) of the 31 epileptic patients with focal signs, while the other 2 demonstrated discordance. Twenty (64.5%) of the 31 patients showed consistent EEG abnormalities. CONCLUSIONS: Our data suggest that asymmetric mIP findings are an excellent lateralizing indicator in pediatric patients with partial epilepsy.

Mechanistic Target of Rapamycin Pathway in Epileptic Disorders

The mechanistic target of rapamycin (mTOR) pathway coordinates the metabolic activity of eukaryotic cells through environmental signals, including nutrients, energy, growth factors, and oxygen. In the nervous system, the mTOR pathway regulates fundamental biological processes associated with neural development and neurodegeneration. Intriguingly, genes that constitute the mTOR pathway have been found to be germline and somatic mutation from patients with various epileptic disorders. Hyperactivation of the mTOR pathway due to said mutations has garnered increasing attention as culprits of these conditions : somatic mutations, in particular, in epileptic foci have recently been identified as a major genetic cause of intractable focal epilepsy, such as focal cortical dysplasia. Meanwhile, epilepsy models with aberrant activation of the mTOR pathway have helped elucidate the role of the mTOR pathway in epileptogenesis, and evidence from epilepsy models of human mutations recapitulating the features of epileptic patients has indicated that mTOR inhibitors may be of use in treating epilepsy associated with mutations in mTOR pathway genes. Here, we review recent advances in the molecular and genetic understanding of mTOR signaling in epileptic disorders. In particular, we focus on the development of and limitations to therapies targeting the mTOR pathway to treat epileptic seizures. We also discuss future perspectives on mTOR inhibition therapies and special diagnostic methods for intractable epilepsies caused by brain somatic mutations.

The Surgical and Cognitive Outcomes of Focal Cortical Dysplasia

Focal cortical dysplasia (FCD) is the major cause of intractable focal epilepsy in childhood leading to epilepsy surgery. The overall seizure freedom after surgery ranges between 50–75% at 2 years after surgery and the long-term seizure freedom remain relatively stable. Seizure outcome after surgery depends on a various factors such as pathologic etiologies, extent of lesion, and types of surgery. Therefore, seizure outcome after surgery for FCD should be analyzed carefully considering cohorts' characteristics. Studies of pediatric epilepsy surgery emphasize the early surgical intervention for a better cognition. Early surgical intervention and cessation of seizure activity are important for children with intractable epilepsy. However, there are limited data on the cognitive outcome after surgery in pediatric FCD, requiring further investigation. This paper reviews the seizure and cognitive outcomes of epilepsy surgery for FCD in children. Several prognostic factors influencing seizure outcome after surgery will be discussed in detail.

Epilepsy Surgery in 2019: A Time to Change

Epilepsy has been known to humankind since antiquity. The surgical treatment of epilepsy began in the early days of neurosurgery and has developed greatly. Many surgical procedures have stood the test of time. However, clinicians treating epilepsy patients are now witnessing a huge tide of change. In 2017, the classification system for seizure and epilepsy types was revised nearly 36 years after the previous scheme was released. The actual difference between these systems may not be large, but there have been many conceptual changes, and clinicians must bid farewell to old terminology. Paradigms in drug discovery are changing, and novel antiseizure drugs have been introduced for clinical use. In particular, drugs that target genetic changes harbor greater therapeutic potential than previous screening-based compounds. The concept of focal epilepsy has been challenged, and now epilepsy is regarded as a network disorder. With this novel concept, stereotactic electroencephalography (SEEG) is becoming increasingly popular for the evaluation of dysfunctioning neuronal networks. Minimally invasive ablative therapies using SEEG electrodes and neuromodulatory therapies such as deep brain stimulation and vagus nerve stimulation are widely applied to remedy dysfunctional epilepsy networks. The use of responsive neurostimulation is currently off-label in children with intractable epilepsy.

Pivotal Role of Subcortical Structures as a Network Hub in Focal Epilepsy: Evidence from Graph Theoretical Analysis Based on Diffusion-Tensor Imaging

BACKGROUND AND PURPOSE: There is accumulating evidence that epilepsy is caused by network dysfunction. We evaluated the hub reorganization of subcortical structures in patients with focal epilepsy using graph theoretical analysis based on diffusion-tensor imaging (DTI). In addition, we investigated differences in the values of diffusion tensors and scalars, fractional anisotropy (FA), and mean diffusivity (MD) of subcortical structures between patients with focal epilepsy and healthy subjects. METHODS: One hundred patients with focal epilepsy and normal magnetic resonance imaging (MRI) findings and 80 age- and sex-matched healthy subjects were recruited prospectively. All subjects underwent DTI to obtain data suitable for graph theoretical analysis. We investigated the differences in the node strength, cluster coefficient, eigenvector centrality, page-rank centrality measures, FA, and MD of subcortical structures between patients with epilepsy and healthy subjects. RESULTS: After performing multiple corrections, the cluster coefficient and the eigenvector centrality of the globus pallidus were higher in patients with epilepsy than in healthy subjects (p=0.006 and p=0.008, respectively). In addition, the strength and the page-rank centrality of the globus pallidus tended to be higher in patients with epilepsy than in healthy subjects (p=0.092 and p=0.032, respectively). The cluster coefficient of the putamen was lower in patients with epilepsy than in healthy subjects (p=0.004). The FA values of the caudate nucleus and thalamus were significantly lower in patients with epilepsy than in healthy subjects (p=0.009 and p=0.007, respectively), whereas the MD value of the thalamus was higher than that in healthy subjects (p=0.005). CONCLUSIONS: We discovered the presence of hub reorganization of subcortical structures in focal epilepsy patients with normal MRI findings, suggesting that subcortical structures play a pivotal role as a hub in the epilepsy network. These findings further reinforce the idea that epilepsy is a network disease.

Síndrome de sensibilidad a fármacos con eosinofilia y síntomas sistémicos debido a la carbamazepina: Caso pediátrico / Drug reaction with eosinophilia and systemic symptoms due to carbamazepine: Pediatric case

Entre las reacciones medicamentosas graves en la piel, se encuentran el síndrome de Stevens-Johnson, la necrólisis epidérmica tóxica y el síndrome de sensibilidad a fármacos con eosinofilia y síntomas sistémicos (drug reaction with eosinophilia and systemic symptoms; DRESS, por sus siglas en inglés), que son poco comunes en la población pediátrica (incidencia: 1/1000-10 000 niños), sin embargo, tienen mal pronóstico. El síndrome de sensibilidad a fármacos con eosinofilia y síntomas sistémicos consiste en erupciones cutáneas, alteraciones hematológicas, linfadenopatía y afectación de órganos. Se presenta el caso de un paciente masculino de 12 años que desarrolló esta patología después de iniciar el tratamiento anticonvulsivo con carbamazepina. Se considera que es importante que el personal de la salud tenga conocimiento de esta enfermedad para que sea incluida entre los diagnósticos diferenciales de pacientes con afecciones similares, ya que este síndrome es potencialmente mortal.

Severe skin reactions include Stevens-Johnson Syndrome, toxic epidermal necrolysis and Drug reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome, which are uncommon in the pediatric population (incidence 1/1000-10 000 children), but they have bad prognosis. Drug-sensitive Syndrome with eosinophilia and systemic symptoms consists in rash, hematological abnormalities, lymphadenopathy and organ involvement. We report the case of a 12-year-old male patient who developed this pathology after initiating anticonvulsant therapy with carbamazepine. We consider that it is important to be aware of this disease and to include it among the differential diagnoses in patients with similar conditions because this syndrome is life-threatening.

Cognitive Function and Neuropsychological Comorbidities in Children with Newly Diagnosed Idiopathic Epilepsy

BACKGROUND: In this study, we aimed to identify cognitive function and neuropsychological comorbidities in children with newly diagnosed idiopathic epilepsy. METHODS: We retrospectively reviewed the records of 97 antiepileptic drug-naïve children (9.7 ± 2.9 years; 54 males and 43 females) with newly diagnosed idiopathic epilepsy, all of whom underwent a neuropsychological battery. The battery consisted of the Korean Wechsler Intelligence Scale, Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale, ADHD Diagnostic System, Children's Depression Inventory, and State-Trait Anxiety Inventory for Children. We investigated association between scores of the neuropsychological battery and epilepsy classification, lateralization of interictal epileptiform discharges (IEDs) on electroencephalography (EEG), and variables related to seizures. RESULTS: Thirteen patients (14.3%) had ADHD symptoms. Three patients (4.1%) had depressive symptoms, and 9 (12.3%) had anxiety symptoms. Patients with idiopathic generalized epilepsy (IGE) had significantly lower full-scale intelligence and performance intelligence quotient scores than patients with idiopathic localization-related epilepsy (ILRE) (89.0 ± 17.6 vs. 96.3 ± 14.8; P = 0.030 and 88.9 ± 16.3 vs. 97.0 ± 16.4; P = 0.016, respectively). Patients with ILRE having unilateral IEDs had significantly higher full-scale intelligence quotient scores than patients with ILRE having bilateral IEDs and patients with IGE (99.9 ± 12.2 vs. 93.7 ± 16.1 vs. 89.0 ± 17.6; P = 0.039, respectively). CONCLUSION: Our results suggest that idiopathic epilepsy may be accompanied by various neuropsychological comorbidities even at initial diagnosis. Patients with IGE and ILRE having bilateral IEDs on EEG appear more likely to be at high risk of decreased cognitive function.

Alteraciones en las ejecuciones viso-perceptuales en pacientes con síndromes electro-clínicos de epilepsias del lóbulo temporal y frontal / Visuoperceptual performances impairments in patients with electro-clinical syndromes of temporal lobe and frontal lobe epilepsies

RESUMEN INTRODUCCIÓN: Según el modelo de actividad modular encapsulada del foco epiléptico (FE), las epilepsias del lóbulo temporal (ELI) y del frontal (ELF) se asocian con alteraciones cognitivas de memoria, atención, lenguaje y función ejecutiva. Por eso la mayoría de los protocolos neuropsicológicos se centran en la evaluación de estas funciones. Las habilidades viso-perceptuales se evaluarían en los pacientes con epilepsias del cuadrante posterior (ECP). OBJETIVO: Establecer las alteraciones viso-perceptuales en pacientes adultos con síndrome electro-clínico compatible con ELT y ELF de Medellín, Colombia, al compararse con un grupo de personas sin epilepsia. Pacientes y métodos: la muestra estuvo conformada por 19 pacientes, 10 (52,6 %) mujeres, edad de 43,0±12,3 (IC 95 %:37,1-48,9) años, con síndromes electro-clínicos por video-telemetría compatibles con ELT o ELF, con capacidad intelectual total estimada 107,2±14,1 (IC95 %:100,3-114,0). Se compararon con 16 personas sin epilepsia, 9(56,2 %) mujeres, edad 41,8±12,7 (IC95 %:35,1-48,6) y capacidad intelectual de 117±17,5 (IC95 %:108,6-127,2). Se les aplicó un protocolo para evaluación de procesos viso-perceptuales. RESULTADOS: Los pacientes presentaron un rendimiento significativamente inferior (p<0,05) en discriminación de figura-fondo, orientación viso-espacial de líneas y en el reconocimiento diferido de la memoria visual de puntos. Estas dificultades fueron mayores en los pacientes con ELF. CONCLUSIONES: Se observan alteraciones en ejecuciones viso-perceptuales y de almacenamiento de memoria visual más severas en pacientes con ELF. Esto apoya el modelo de redes complejas (no modulares y no encapsuladas), tanto para la actividad epiléptica como para la cognitiva. Por esto, los procesos viso-perceptuales deben ser evaluados en los pacientes con síndromes de ELT o ELF.

SUMMARY INTRODUCTION: According to modular encapsulated activity model of the epileptic focus (EF), Temporal lobe epilepsies (TLE) and Frontal lobe epilepsies (FLE) are associated to memory, attention, language and executive function impairments. For this reason most of the neuropsychological protocols are focused in the assessment of these functions. Visuoperceptual skills only would be assessed in patients with posterior quadrant epilepsies (PQE). OBJECTIVE: To establish visuoperceptual impairment in a sample of electro-clinical syndromes compatibles with TLE and FLE from Medellín-Colombia, compared with a group of healthy people without epilepsy. Patients and methods: sample was constituted by 19 patients, 10 women (52,6%), aged 43,0±12,3 (CI95%:37,1-48,9), with electro-clinical syndromes compatible with TLE or FLE, median estimated IQ 107,2±14,1 (CI95%:100,3-114,0). They were compared with 16 healthy people without epilepsy, 9(56,2%) women, median age 41,8±12,7 (CI95%:35,1-48,6) and 117±17,5 (IC95%:108,6-127,2). A visuoperceptual protocol was administered to both groups. RESULTS: Patients presented significant lower (p<0,05) on figure-background discrimination, visuospatial line orientations, and delayed recall by recognition of dots visual memory. These impairments were significant worst in FLE patients. CONCLUSIONS: TLE and FLE patients have visuoperceptual and delayed visual memory store impairments, which were significant worst in FLE patients. These findings support the complex network (non-modular and non-encapsulated) model to explain EF and cognitive functioning in patient with TLE and FLE. Visuoper-ceptual processes should be always assessed in these patients.

Estimulador del nervio vago, ¿se puede quedar libre de crisis?, presentación de un caso y revisión de la literatura / Vagus nerve stimulator, is it possible to be free of crisis ?, presentation of a case and review of the literature

RESUMEN La estimulación del nervio vago es una técnica aprobada por la FDA, para epilepsia focal refractaria. Presentamos un caso de un paciente, con epilepsia de probable origen frontal, el cual cumplió criterios para epilepsia refractaria, y fue llevado a implantación de estimulador del nervio vago, quedando libre de crisis.

SUMMARY Vagal nerve stimulation is an FDA-approved technique for focal refractory epilepsy. We present the case of a patient, with epilepsy of probable frontal origin, who met criteria for refractory epilepsy, and was taken to implantation of vagus nerve stimulator, currently free of crisis.