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Paediatric epilepsy surgery is an increasingly used evidence-based management option with low risks for complications. Developments in neuroimaging techniques and other advanced diagnostics have widened the spectrum of children who could benefit from the procedure, and surgery is now considered a standard management approach for epilepsy. Available data indicate that early surgery improves outcomes. Despite these considerable advances, epilepsy surgery in children is still underused. In this Review, we summarise the indications, patient selection, principles of presurgical investigations, optimal timing, and types of epilepsy surgery. We also examine comprehensive outcomes after surgery, including seizure outcomes, complications, cognition, neurodevelopment, vocational outcome, and health-related quality of life of children and their parents. Successful epilepsy surgery could lead to improvement in all these areas. Children should, therefore, be referred early for evaluation in an appropriately competent centre.

Background Surgery is a widely accepted treatment option for drug-resistant focal epilepsy. A detailed analysis of longitudinal postoperative seizure outcomes and use of antiepileptic drugs for different brain lesions causing epilepsy is not available. We aimed to analyse the association between histopathology and seizure outcome and drug freedom up to 5 years after epilepsy surgery, to improve presurgical decision making and counselling.Methods In this retrospective, multicentre, longitudinal, cohort study, patients who had epilepsy surgery between Jan 1, 2000, and Dec 31, 2012, at 37 collaborating tertiary referral centres across 18 European countries of the European Epilepsy Brain Bank consortium were assessed. We included patients of all ages with histopathology available after epilepsy surgery. Histopathological diagnoses and a minimal dataset of clinical variables were collected from existing local databases and patient records. The primary outcomes were freedom from disabling seizures (Engel class 1) and drug freedom at 1, 2, and 5 years after surgery. Proportions of individuals who were Engel class 1 and drug-free were reported for the 11 main categories of histopathological diagnosis. We analysed the association between histopathology, duration of epilepsy, and age at surgery, and the primary outcomes using random effects multivariable logistic regression to control for confounding.Findings 9147 patients were included, of whom seizure outcomes were available for 8191 (89.5%) participants at 2 years, and for 5577 (61.0%) at 5 years. The diagnoses of low-grade epilepsy associated neuroepithelial tumour (LEAT), vascular malformation, and hippocampal sclerosis had the best seizure outcome at 2 years after surgery, with 77.5% (1027 of 1325) of patients free from disabling seizures for LEAT, 74.0% (328 of 443) for vascular malformation, and 71.5% (2108 of 2948) for hippocampal sderosis. The worst seizure outcomes at 2 years were seen for patients with focal cortical dysplasia type I or mild malformation of cortical development (50.0%, 213 of 426 free from disabling seizures), those with malformation of cortical development-other (52.3%, 212 of 405 free from disabling seizures), and for those with no histopathological lesion (53.5%, 396 of 740 free from disabling seizures). The proportion of patients being both Engel class 1 and drug-free was 0-14% at 1 year and increased to 14-51% at 5 years. Children were more often drug-free; temporal lobe surgeries had the best seizure outcomes; and a longer duration of epilepsy was associated with reduced chance of favourable seizure outcomes and drug freedom. This effect of duration was evident for all lesions, except for hippocampal sclerosis.Interpretation Histopathological diagnosis, age at surgery, and duration of epilepsy are important prognostic factors for outcomes of epilepsy surgery. In every patient with refractory focal epilepsy presumed to be lesional, evaluation for surgery should be considered. Copyright (C) 2020 Elsevier Ltd. All rights reserved.

Familial partial epilepsy with variable foci (FPEVF) is an autosomal dominant form of partial epilepsy characterized by the presence of epileptic seizures originating from different cerebral lobes in different members of the same family. Linkage to chromosomes 22q12 and 2q36 has been reported, although only six families have been published. We studied a new FPEVF family including nine affected individuals. The phenotype in this family was similar to that previously described and consisted of nocturnal and daytime seizures with semiology suggesting a frontal lobe origin. A video-EEG (electroencephalography) recording of the proband's seizures is presented and revealed hyperkinetic seizures of frontal lobe origin preceded by left frontal spikes. We excluded linkage to chromosome 2q36 and found a suggestion of linkage to chromosome 22q12 with a lod score of 2.64 (h = 0) for marker D22S689.

Purpose of review This article reviews the most significant advances in the field of genetics of the epilepsies during the past year, with emphasis on newly identified genes and functional studies leading to new insights into the pathophysiology of epilepsy. Recent findings Mutations in the chloride channel gene CLCN2 have been associated with the most common forms of idiopathic generalized epilepsies. A mutation in the ATP1A2 sodium potassium ATPase pump gene has been described in a family in which familial hemiplegic migraine and benign familial infantile convulsions partly co-segregate. The leucine-rich, glioma-inactivated 1 gene (LGI1) (also known as epitempin) was found to be responsible for autosomal-dominant lateral temporal lobe epilepsy in additional families. The serine-threonine kinase 9 gene (STK9) was identified as the second gene associated with X-linked infantile spasms. Mutations in the Aristaless-related homeobox gene (ARX) have been recognized as a cause of X-linked infantile spasms and sporadic cryptogenic infantile spasms. A second gene underlying progressive myoclonus epilepsy of Lafora, NHLRC1, was shown to code for a putative E3 ubiquitin ligase. Summary Genes associated with idiopathic generalized epilepsies remain within the ion channel family. Mutations in non-ion channel genes are responsible for autosomal-dominant lateral temporal lobe epilepsy, a form of idiopathic focal epilepsy, malformations of cortical development, and syndromes that combine X-linked mental retardation and epilepsy. Most genetic epilepsies have a complex mode of inheritance, and genes identified so far account only for a minority of families and sporadic cases. Functional studies are leading to a better understanding of the mechanisms underlying hyperexcitability and seizures.

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.

Paroxysmal dyskinesia due to a subthalamic lesion is a rare finding. We describe a patient with paroxysmal tonic spasms due to a well-defined lesion in the subthalamic area. In this case, we confirm the nonepileptic nature of the episode and collect with detail the clinical features by means of a video-electroencephalographic recording. We also report an excellent response to carbamazepine in subthalamic paroxysmal dyskinesias. © 2003 Movement Disorder Society

5 páginas, 2 figuras -- PAGS nros. 1369-1373, Background: Lafora disease (LD; progressive myoclonus epilepsy type 2; EPM2) is an autosomal recessive disorder caused by mutations in the EPM2A and EPM2B genes. LD is characterized by the presence of strongly PAS-positive intracellular inclusions (Lafora bodies) in several tissues. Glycogen storage disease type IV (GSD-IV; Andersen disease) is an autosomal recessive disorder characterized by cirrhosis leading to severe liver failure. GSD-IV has been associated with mutations in the glycogen branching enzyme gene (GBE). Histopathologic changes of the liver in both diseases show an identical appearance, although cirrhosis has never been described in patients with LD. We report a LD family in which the proband presented severe liver failure at onset of the disease. Methods: Clinical histories, physical and neurologic examination, laboratory tests, EEGs, MRI of the brain, and liver or axillary skin biopsies were performed in the two affected siblings. The diagnosis was confirmed by molecular genetic analysis of the EPM2A, EPM2B, and GBE genes and loci. Results: During the first decade of life, abnormalities in liver function tests were detected in the two affected siblings. The proband's liver dysfunction was severe enough to require liver transplantation. Subsequently, both sibs developed LD. Mutation analysis of EPM2A revealed a homozygous Arg241stop mutation in both patients. Conclusions: This is the first description of severe hepatic dysfunction as the initial clinical manifestation of LD. The phenotypic differences between the two affected siblings suggest that modifier genes must condition clinical expression of the disease outside the CNS

Background: The Ehlers-Danlos syndrome (EDS) comprises a group of hereditary connective tissue disorders. Periventricular nodular heterotopia (PNH) is a human neuronal migration disorder characterised by seizures and conglomerates of neural cells around the lateral ventricles of the brain, caused by FLNA mutations. FLNA encodes filamin A, an actin binding protein involved in cytoskeletal organisation. The amino-terminal actin binding domain (ABD) of filamins contains two tandem calponin homology domains, CHD1 and CHD2. Objective: To report clinical and genetic analyses in a Spanish family affected by a connective tissue disorder suggestive of EDS type III and PNH. Methods: A clinical and molecular study was undertaken in the three affected women. Clinical histories, physical and neurological examinations, brain magnetic resonance imaging studies, and skin biopsies were done. Genetic analysis of the FLNA gene was undertaken by direct sequencing and restriction fragment length polymorphism analysis. Results: Mutation analysis of the FLNA gene resulted in the identification of a novel mutation in exon 3 (c.383C→T) segregating with the combination of both syndromes. This mutation results in a substitution of an alanine residue (A128V) in CHD1. Conclusions: The findings suggest that the Ala128Val mutation causes the dual EDS-PNH phenotype. This association constitutes a new variant within the EDS spectrum. This is the first description of a familial EDS-PNH association with a mutation in FLNA .

5 p.-2 tab., Objective: To study EPM2B gene mutations and genotype-phenotype correlations in patients with Lafora disease. Methods: The authors performed a clinical and mutational analysis of 25 patients, from 23 families, diagnosed with Lafora disease who had not shown mutations in the EPM2A gene. Results: The authors identified 18 mutations in EPM2B, including 12 novel mutations: 4 nonsense mutations (R265X, C26X, W219X, and E67X), a 6-base pair (bp) microdeletion resulting in a two amino acid deletion (V294_K295del), a 4-bp insertion resulting in a frameshift mutation (S339fs12), and 6 missense mutations (D308A, I198N, C68Y, E67Q, P264H, and D233A). In our data set of 77 families with Lafora disease, 54 (70.1%) tested probands have mutations in EPM2A, 21 (27.3%) in EPM2B, and 2 (2.6%) have no mutations in either gene. The course of the disease was longer in patients with EPM2B mutations vs patients with EPM2A mutations. Conclusions: Genetic allelic heterogeneity is present in Lafora disease associated with mutations in EPM2B. Patients with mutations in EPM2A and EPM2B express similar clinical manifestation, although patients with EPM2B-associated Lafora disease seem to have a slightly milder clinical course. The lack of mutations in EPM2A and EPM2B in two families could be because of the presence of mutations in noncoding, nontested regions or the existence of an additional gene associated with Lafora disease.