Trends in pediatric epilepsy surgery in Europe between 2008 and 2015: Country-, center-, and age-specific variation.

OBJECTIVE: To profile European trends in pediatric epilepsy surgery (<16 years of age) between 2008 and 2015. METHODS: We collected information on volumes and types of surgery, pathology, and seizure outcome from 20 recognized epilepsy surgery reference centers in 10 European countries. RESULTS: We analyzed retrospective aggregate data on 1859 operations. The proportion of surgeries significantly increased over time (P < .0001). Engel class I outcome was achieved in 69.3% of children, with no significant improvement between 2008 and 2015. The proportion of histopathological findings consistent with glial scars significantly increased between the ages of 7 and 16 years (P for trend = .0033), whereas that of the remaining pathologies did not vary across ages. A significant increase in unilobar extratemporal surgeries (P for trend = .0047) and a significant decrease in unilobar temporal surgeries (P for trend = .0030) were observed between 2008 and 2015. Conversely, the proportion of multilobar surgeries and unrevealing magnetic resonance imaging cases remained unchanged. Invasive investigations significantly increased, especially stereo-electroencephalography. We found different trends comparing centers starting their activity in the 1990s to those whose programs were developed in the past decade. Multivariate analysis revealed a significant variability of the proportion of the different pathologies and surgical approaches across countries, centers, and age groups between 2008 and 2015. SIGNIFICANCE: Between 2008 and 2015, we observed a significant increase in the volume of pediatric epilepsy surgeries, stability in the proportion of Engel class I outcomes, and a modest increment in complexity of the procedures.

Seizure and developmental outcomes after hemispherectomy in children and adolescents with intractable epilepsy.

PURPOSE: The aim of this study is to describe a series of pediatric hemispherectomies, reviewing pathologic substrate, epilepsy characteristics and seizure outcome as well as developmental profiles, before and after surgery, in different domains. METHODS: Seventeen patients with full pre-surgical work-up, minimum follow-up of 12 months, and at least one post-surgical neuropsychological evaluation were selected. Three had Rasmussen encephalitis (RE), five hemispheric malformations of cortical development (MCD), and nine hemispheric vascular lesions. RESULTS: At latest follow-up, all patients with RE and 66.7 % of those with vascular lesions are in Engel's class I; in the latter group, pre-surgical independent contralateral EEG discharges statistically correlated with a worse seizure outcome. Patients with MCD showed the worst seizure outcome. Pre-surgical language transfer to the right hemisphere was confirmed in a boy with left RE, operated on at 6 years of age. Patients with MCD and vascular lesions already showed severe global developmental delay before surgery, which persists afterwards. A linear correlation was found between earlier age at surgery and better outcome in personal-social, gross motor, and adaptive domains, in the vascular lesions group. The case with highest cognitive improvement had continuous spike and wave during sleep on pre-surgical EEG. CONCLUSIONS: Pathologic substrate was the main factor related with seizure outcome. In children with MCD and vascular lesions, although developmental progression is apparent, significant post-surgical improvements are restricted by the severity of pre-surgical neuropsychological disturbances and a slow maturation. Early surgery assessment is recommended to enhance the possibilities for a better quality of life in terms of seizure control, as well as better autonomy and socialization.

Epilepsy surgery in children with developmental tumours.

We report our experience regarding evaluation, surgical treatment and outcomes in a population of 21 children with histopathologically confirmed developmental tumours [nine dysembryoplastic neuroepithelial tumours (DNET), ten gangliogliomas (GG) and two gangliocytomas (GC)] and related epilepsy, analyzing video-EEG, MRI and neuropsychological data, before and after surgery. Most children had focal epilepsy correlating well with lesion location. One patient had epileptic spasms and generalized discharges. Tumours were located in the temporal lobe in 13 patients. Mean age at surgery was 11.16 years. Postsurgical MRI showed residual tumour growth in one DNET. One child had a recurrent ganglioglioma with anaplastic transformation. At latest follow-up (mean 4.68 years) 95.2% of patients were seizure-free and no significant neuropsychological declines were observed. Evidence from our study suggests that, in this setting, surgery should be performed before criteria for refractory epilepsy are met, particularly in cases with early seizure onset, in order to optimize cognitive outcome.

[Panayiotopoulos syndrome: academic difficulties and behavioural disorders]. / Síndrome de Panayiotopoulos: dificultades académicas y alteraciones comportamentales.

INTRODUCTION: Panayiotopoulos syndrome (PS) is one of the benign epilepsies found in childhood. Some papers have shown that patients can present behavioural disorders and learning difficulties. AIMS: To review patients diagnosed with PS in our hospital and to check whether they display evidence of such disorders and if there is any specific feature that allows high-risk patients to be identified. PATIENTS AND METHODS: A retrospective review of the medical records of patients diagnosed with PS was carried out. An electroencephalogram (EEG) or video-EEG-polygraph recordings were performed on all patients during sleep. The Weschler Intelligence Scale for Children was used to evaluate intelligence. RESULTS: Data were collected for 33 patients, 17 of whom were children. The mean age at onset was 3.2 years and the follow-up was 4.9 years (range: 1-12 years). Irritative EEG phenomena were detected in the occipital (67.7%), temporal (45.2%) or parietal regions (22.5%) in 31 patients. Furthermore, 72.7% of patients presented more than two seizures. Twenty-three patients required treatment with antiepileptic drugs. Two patients were diagnosed with attention deficit hyperactivity disorder. Additionally, 30.3% reported dispersed attention and 27.3% had an impulsive character. It was found that 51.1% had a good level of academic achievement, in 26.5% it was regular and in 17.6% poor. A total of 39.4% needed assistance in the form of after-school classes. The level of intelligence was evaluated in 11 patients. CONCLUSION: PS is a condition with a good prognosis, but seems to be associated to learning and behavioural disorders.

Evaluación neuropsicológica prequirúrgica en epilepsias focales pediátricas / Presurgery neuropsychological evaluation in pediatric focal epilepsies

Introducción. La evaluación neuropsicológica está incorporada a los protocolos de valoración de un paciente candidato a cirugía de la epilepsia, proporciona información de las disfunciones cognitivas presentes en cada paciente, permite predecir los posibles riesgos cognitivos de la cirugía y proporciona medidas objetivas de cambio postquirúrgico. Las alteraciones neuropsicológicas son una importante comorbilidad de la epilepsia resistente a los fármacos. Su aparición precoz en la infancia puede determinar que las disfunciones cognitivas con las que cursa puedan ser atípicas con respecto a los principios de localización cerebral, debido a procesos de plasticidad y reorganización del cerebro inmaduro; el análisis de los perfiles neuropsicológicos con los que cursan las epilepsias focales pediátricas es mucho más complejo que en adultos. Desarrollo y conclusiones. En el presente trabajo se revisan las alteraciones neuropsicológicas que acompañan a las epilepsias focales de córtex posterior, temporales y frontales, señalando la escasez de trabajos publicados a pesar de que la evaluación neuropsicológica forma parte indispensable de la evaluación prequirúrgica (AU)

Introduction. Neuropsychological assessment is included in the protocols for evaluation of epilepsy surgery candidates, providing information about the patient’s cognitive dysfunctions, allowing for prediction of possible cognitive deficits derived from surgery and yielding objective measures of any post-surgical changes. Neuropsychological disturbances constitute an important co-morbidity of medically intractable epilepsy. An early epilepsy onset in infancy may lead to cognitive dysfunctions that are atypical in terms of brain localization, due to the inherent plasticity and reorganization processes of the immature brain. The analysis of the neuropsychological profiles of paediatric focal epilepsies is much more complex than in the adult population. Development and conclusions. In this paper, we review the neuropsychological disturbances associated to focal epilepsies (posterior cortex, temporal and frontal epilepsies), stressing the point that there is a considerable lack of rigorous studies on the topic in the literature, in spite of this being an essential part of the presurgical work-up in epilepsy patients (AU)

A somatic NLRP3 mutation as a cause of a sporadic case of chronic infantile neurologic, cutaneous, articular syndrome/neonatal-onset multisystem inflammatory disease: Novel evidence of the role of low-level mosaicism as the pathophysiologic mechanism underlying mendelian inherited diseases.

OBJECTIVE: Chronic infantile neurologic, cutaneous, articular syndrome (CINCA), also known as neonatal-onset multisystem inflammatory disease (NOMID), is a severe, early-onset autoinflammatory disease characterized by an urticaria-like rash, arthritis/arthropathy, variable neurologic involvement, and dysmorphic features, which usually respond to interleukin-1 blockade. CINCA/NOMID has been associated with dominant Mendelian inherited NLRP3 mutations. However, conventional sequencing analyses detect true disease-causing mutations in only approximately 55-60% of patients, which suggests the presence of genetic heterogeneity. We undertook the current study to assess the presence of somatic, nongermline NLRP3 mutations in a sporadic case of CINCA/NOMID. METHODS: Clinical data, laboratory results, and information on treatment outcomes were gathered through direct interviews. Exhaustive genetic studies, including Sanger method sequencing, subcloning, restriction fragment length polymorphism assay, and pyrosequencing, were performed. RESULTS: The patient's CINCA/NOMID was diagnosed based on clinical features (early onset of the disease, urticaria-like rash, knee arthropathy, and dysmorphic features). The patient has exhibited a successful response to anakinra within the last 28 months. Analysis of NLRP3 identified a novel heterozygous variant (p.D303H) that was detected in approximately 30-38% of circulating leukocytes. The absence of this variant in healthy controls and in the patient's parents suggested a de novo true disease-causing mutation. Additional analyses showed that this novel mutation was present in both leukocyte subpopulations and epithelial cells. CONCLUSION: Our findings identify the novel p.D303H NLRP3 variant in a Spanish patient with CINCA/NOMID as a new disease-causing mutation, which was detected as a somatic, nongermline mutation in hematopoietic and nonhematopoietic cell lineages. Our data provide new insight into the role of low-level mosaicism in NLRP3 as the pathophysiologic mechanism underlying cryopyrin-associated periodic syndrome.