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• Machine learning was used to predict seizure recurrence with electrical status epilepticus (ESES) in idiopathic focal epilepsy. • The partial directed coherence is a reliable feature for predicting seizure recurrence with ESES via machine learning. • Among 6 machine learning algorithms, the Xgboost Classifier model achieved a classification accuracy up to 0.85. Some individuals with idiopathic focal epilepsy (IFE) experience recurring seizures accompanied by the evolution of electrical status epilepticus during sleep (ESES). Here, we aimed to develop a predictor for the early detection of seizure recurrence with ESES in children with IFE using resting state electroencephalogram (EEG) data. The study group included 15 IFE patients who developed seizure recurrence with ESES. There were 17 children in the control group who did not experience seizure recurrence with ESES during at least 2-year follow-up. We used the degree value of the partial directed coherence (PDC) from the EEG data to predict seizure recurrence with ESES via 6 machine learning (ML) algorithms. Among the models, the Xgboost Classifier (XGBC) model achieved the highest specificity of 0.90, and a remarkable sensitivity and accuracy of 0.80 and 0.85, respectively. The CATC showed balanced performance with a specificity of 0.85, sensitivity of 0.73, and an accuracy of 0.80, with an AUC equal to 0.78. For both of these models, F4, Fz and T4 were the overlaps of the top 4 features. Considering its high classification accuracy, the XGBC model is an effective and quantitative tool for predicting seizure recurrence with ESES evolution in IFE patients. We developed an ML-based tool for predicting the development of IFE using resting state EEG data. This could facilitate the diagnosis and treatment of patients with IFE. [ABSTRACT FROM AUTHOR]

• Children with resolved Rolandic epilepsy have increased median nerve somatosensory conduction time compared to controls. • Ventral thalamic volume positively correlated with N20 conduction time. • Focally decreased Rolandic thalamocortical connectivity may support symptom resolution in Rolandic epilepsy. Median nerve somatosensory evoked fields (SEFs) conduction times reflect the integrity of neural transmission across the thalamocortical circuit. We hypothesized median nerve SEF conduction time would be abnormal in children with Rolandic epilepsy (RE). 22 children with RE (10 active; 12 resolved) and 13 age-matched controls underwent structural and diffusion MRI and median nerve and visual stimulation during magnetoencephalography (MEG). N20 SEF responses were identified in contralateral somatosensory cortices. P100 were identified in contralateral occipital cortices as controls. Conduction times were compared between groups in linear models controlling for height. N20 conduction time was also compared to thalamic volume and Rolandic thalamocortical structural connectivity inferred using probabilistic tractography. The RE group had slower N20 conduction compared to controls (p = 0.042, effect size 0.6 ms) and this difference was driven by the resolved RE group (p = 0.046). There was no difference in P100 conduction time between groups (p = 0.83). Ventral thalamic volume positively correlated with N20 conduction time (p = 0.014). Children with resolved RE have focally decreased Rolandic thalamocortical connectivity. These results identify a persistent focal thalamocortical circuit abnormality in resolved RE and suggest that decreased Rolandic thalamocortical connectivity may support symptom resolution in this self-limited epilepsy. [ABSTRACT FROM AUTHOR]

Seizures occur in approximately one-third of children with cerebral palsy. This study aimed to determine epilepsy syndromes in children with seizures and cerebral palsy due to vascular injury, anticipating that this would inform treatment and prognosis. We studied a population-based cohort of children with cerebral palsy due to prenatal or perinatal vascular injuries, born 1999–2006. Each child's MRI was reviewed to characterize patterns of grey and white matter injury. Children with syndromic or likely genetic causes of cerebral palsy were excluded, given their inherent association with epilepsy and our aim to study a homogeneous cohort of classical cerebral palsy. Chart review, parent interview and EEGs were used to determine epilepsy syndromes and seizure outcomes. Of 256 children, 93 (36%) had one or more febrile or afebrile seizures beyond the neonatal period and 87 (34%) had epilepsy. Children with seizures were more likely to have had neonatal seizures, have spastic quadriplegic cerebral palsy and function within Gross Motor Function Classification System level IV or V. Fifty-six (60%) children with seizures had electroclinical features of a self-limited focal epilepsy of childhood; we diagnosed these children with a self-limited focal epilepsy-variant given the current International League Against Epilepsy classification precludes a diagnosis of self-limited focal epilepsy in children with a brain lesion. Other epilepsy syndromes were focal epilepsy—not otherwise specified in 28, infantile spasms syndrome in 11, Lennox–Gastaut syndrome in three, genetic generalized epilepsies in two and febrile seizures in nine. No epilepsy syndrome could be assigned in seven children with no EEG. Twenty-one changed syndrome classification during childhood. Self-limited focal epilepsy-variant usually manifested with a mix of autonomic and brachio-facial motor features, and occipital and/or centro-temporal spikes on EEG. Of those with self-limited focal epilepsy-variant, 42/56 (75%) had not had a seizure for >2 years. Favourable seizure outcomes were also seen in some children with infantile spasms syndrome and focal epilepsy-not otherwise specified. Of the 93 children with seizures, at last follow-up (mean age 15 years), 61/91 (67%) had not had a seizure in >2 years. Children with cerebral palsy and seizures can be assigned specific epilepsy syndrome diagnoses typically reserved for normally developing children, those syndromes commonly being age-dependent and self-limited. Compared to typically developing children with epilepsy, self-limited focal epilepsy-variant occurs much more commonly in children with cerebral palsy and epilepsy. These findings have important implications for treatment and prognosis of epilepsy in cerebral palsy, and research into pathogenesis of self-limited focal epilepsy. [ABSTRACT FROM AUTHOR]

IntroductionIdiopathic focal epilepsy (IFE) is a group of self-limited epilepsies. The etiology for the majority of the patients with IFE remains elusive. We thus screened disease-causing variants in the patients with IFE.MethodsWhole-exome sequencing was performed in a cohort of 323 patients with IFE. Protein modeling was performed to predict the effects of missense variants. The genotype–phenotype correlation of the newly defined causative gene was analyzed.ResultsFour novel heterozygous variants in PGM3, including two de novo variants, were identified in four unrelated individuals with IFE. The variants included one truncating variant (c.1432C > T/p.Q478X) and three missense variants (c.478C > T/p.P160S, c.1239C > G/p.N413K, and c.1659T > A/p.N553K), which had no allele frequency in the gnomAD database. The missense variants were predicted to be damaging and affect hydrogen bonds with surrounding amino acids. Mutations Q478X, P160S, and N413K were associated with benign childhood epilepsy with centrotemporal electroencephalograph (EEG) spikes. P160S and N413K were located in the inner side of the enzyme active center. Mutation N553K was associated with benign occipital epilepsy with incomplete penetrance, located in the C-terminal of Domain 4. Further analysis demonstrated that previously reported biallelic PGM3 mutations were associated with severe immunodeficiency and/or congenital disorder of glycosylation, commonly accompanied by neurodevelopmental abnormalities, while monoallelic mutations were associated with milder symptoms like IFE.ConclusionThe genetic and molecular evidence from the present study implies that the PGM3 variants identified in IFE patients lead to defects of the PGM3 gene, suggesting that the PGM3 gene is potentially associated with epilepsy. The genotype–phenotype relationship of PGM3 mutations suggested a quantitative correlation between genetic impairment and phenotypic severity, which helps explain the mild symptoms and incomplete penetrance in individuals with IFE.

Introduction: Idiopathic focal epilepsy (IFE) is a group of self-limited epilepsies. The etiology for the majority of the patients with IFE remains elusive. We thus screened disease-causing variants in the patients with IFE. Methods: Whole-exome sequencing was performed in a cohort of 323 patients with IFE. Protein modeling was performed to predict the effects of missense variants. The genotype–phenotype correlation of the newly defined causative gene was analyzed. Results: Four novel heterozygous variants in PGM3 , including two de novo variants, were identified in four unrelated individuals with IFE. The variants included one truncating variant (c.1432C > T/p.Q478X) and three missense variants (c.478C > T/p.P160S, c.1239C > G/p.N413K, and c.1659T > A/p.N553K), which had no allele frequency in the gnomAD database. The missense variants were predicted to be damaging and affect hydrogen bonds with surrounding amino acids. Mutations Q478X, P160S, and N413K were associated with benign childhood epilepsy with centrotemporal electroencephalograph (EEG) spikes. P160S and N413K were located in the inner side of the enzyme active center. Mutation N553K was associated with benign occipital epilepsy with incomplete penetrance, located in the C-terminal of Domain 4. Further analysis demonstrated that previously reported biallelic PGM3 mutations were associated with severe immunodeficiency and/or congenital disorder of glycosylation, commonly accompanied by neurodevelopmental abnormalities, while monoallelic mutations were associated with milder symptoms like IFE. Conclusion: The genetic and molecular evidence from the present study implies that the PGM3 variants identified in IFE patients lead to defects of the PGM3 gene, suggesting that the PGM3 gene is potentially associated with epilepsy. The genotype–phenotype relationship of PGM3 mutations suggested a quantitative correlation between genetic impairment and phenotypic severity, which helps explain the mild symptoms and incomplete penetrance in individuals with IFE. [ABSTRACT FROM AUTHOR]

Basic properties of Levetiracetam (LEV) were described and own experience of its application at the dose of 500–4000 mg/day in 95 patients at the age of 17–69 years (mean age 34 ± 13 years) with various epileptic syndromes was analyzed. The overall effect of LEV made 69.1%, remission at least a year was achieved in 43.6%, in 17% – for 3 years or more. The best result was observed in juvenile myoclonic epilepsy an improvement in 83.3% of patients, remission on LEV monotherapy in 75% of patients. High efficiency was also noted in idiopathic and symptomatic generalized epilepsy – an improvement making up 78.6 and 81.3%, respectively. Idiopathic focal epilepsy LEO showed less efficiency – about 51.5%. Adverse effects were observed in 12 patients (12,8%), of which only in 3 the LEV was replaced because of the development of apathy, fatigue and the appearance of efficiency violations as a result of aggravate focal seizures. In other cases drowsiness, irritability and increased unprovoked aggression were observed, these side effects passed within the first month of treatment. The obtained results confirm the high efficacy and good tolerability of LEV.

The structure of idiopathic focal forms of epilepsy was investigated on 1118 patients with diagnosis of epilepsy, and aged from the first days of life to 18 years. Their age enabled to monitor the debut of seizures. The methods of investigation included clinical examination, video EEG-monitoring, testing by neuropsychologist and, when necessary, neurovisualization. In 189 cases (16.9% of the total number of patients with the debut of seizures before 18) the idiopathic focal epilepsy forms were diagnosed. In 99 cases (8.8% of patients) the diagnosis was Idiopathic focal epilepsy (IFE) with central temporal spikes. The idiopathic occipital lobe epilepsy (IOE) was found in 47 patients (4.2 % of cases). IFE with pseudo-generalized seizures (IFEPGS) was observed in 31 patients (2.8% of cases). The idiopathic focal epilepsy of infancy (IFEI) was seen in 5 cases which equals to 0.5% of the total patient group. The idiopathic focal epilepsy with affective symptoms (IFEAS) was diagnosed in 7 patients (0.6%). Rolandic epilepsy was most frequently found in the IFE group (52.4% of cases). The idiopathic occipital lobe epilepsy was diagnosed in 24.9% of cases. The IFE-PGS was seen in 16.4% of patients, IFEAS - in 3.7% of cases, and IFEI - in 2.6% of cases. By and large, the results are in line with those obtained in the majority of foreign studies on the incidence rate of the idiopathic focal epilepsy forms.

The structure of idiopathic focal epilepsy was studied with 1118 patients who have diagnosis «epilepsy» with debut of seizures at the age from first days of life to 18 years. The methods included clinical examination, video-EEG monitoring, neuropsychological testing and neurovisualization methods if necessary. Idiopathic forms of focal epilepsy were observed in 189 cases, which rated 16.9% of the total group of patients with debut of seizures. A diagnosis of «idiopathic focal epilepsy (IFE) with central temporal spikes» was arrived in 99 cases (8.8% of patients). Idiopathic occipital epilepsy (IOE) was detected in 47 patients (4.2% of cases). IFE with pseudo generalized attacks (IFE-PGA) - 31 patients (2.8% of cases). Idiopathic focal epilepsy of infancy (IFEI) was observed in 5 cases, which rated 0.5% of the total patients group. Idiopathic focal epilepsy with affective symptoms (IFEAS) was observed in 7 patients (0.6%). In IFE most often detected rolandic epilepsy (in 52.4% of cases). Idiopathic occipital epilepsy was diagnosed in 24.9% of cases. IFE-PGA was observed in 16.4% of patients, IFEAS - in 3.7% of cases and IFEI - in 2.6%. Overall, the results correspond to data obtained in the majority of foreign studies the incidence of idiopathic local forms of epilepsy.

Idiopathic childhood focal epilepsy with centrotemporal spikes, which is more known as rolandic epilepsy (RE), is age- and localization-related epilepsy with childhood onset, which is characterized mainly by short-lasting hemifacial and oropharyngeal seizures generally occurring when awakening or falling asleep, by the normal neurological status of patients, by specific electroencephalographic changes and complete arrest of seizures during therapy or when achieving puberty.RE is the most common epilepsy in childhood. Its prevalence is 21 per 100,000 healthy children. It is characterized by an onset that is clearly related to age. In 85 % of cases, RE occurs at 4–10 years of age with its peak at about 9 years. The clinical manifestations of this form of epilepsy are several types of seizures, such as oropharyngolaryngeal, hemifacial, faciobrachial, secondarily generalized convulsive, unilateral seizures with the possible development of short duration Todd’s paresis. Other types of seizures (absence, atonic, and myoclonic ones) are uncharacteristic of RE. They may occur occasionally on aggravation resulting from the use of carbamazepine or oxcarbazepine or permanently on transformation into pseudo-Lennox syndrome. According to the definition, focal neurological symptoms and behavioral and intellectual disorders are absent in patients with RE. However, there have been recent observations suggesting that speech, cognitive, and behavioral disorders may occur (at the same time rarely) in children with RE. Magnetic resonance imaging (MRI) fails to reveal the abnormality in the vast majority of cases. The described MRI changes in nearly 10 % of the patients with RE are an incidental finding and irrelevant to the course of the disease. Valproate in small doses is a first-choice drug; if it is inefficient, levetiracetam, topiramate, or a combination of valproate and ethosuximide are administered. Sulthiame (ospolot) as monotherapy is used in Germany.Based on their findings and the data available in the literature, the authors consider the etiology, pathogenesis, clinical manifestations of RE and its diagnosis, treatment principles, and prognosis. The specific features of the electroencephalographic pattern in this disease are detailed.

Results of research of efficacy and tolerability of lamitor (lamotrigine) in the treatment of idiopathic focal and generalized forms of epilepsy as monotherapy or in polytherapy in children and adolescents are presented. 25 patients were included in our research, aged from 2 till 18 years, with idiopathic focal (n=10) and generalized (n=15) epilepsy, which received lamitor in monotherapy (5 patients) or in polytherapy (20 patients). As a whole, remission was reached at 18 of 25 patients (72%), significant improvement – at 5 of 25 (20%), the effect was absent – 1 patient (4%), deterioration was noted only in 1 case (4%). Efficiency of lamitor in dependence on epilepsy form was considered. Good tolerability of lamitor is noted. Thus, our research demonstrated high efficiency and good tolerability of lamitor as an additional antiepileptic drug and in monotherapy in the treatment of idiopathic epilepsies in children and adolescents.

The childhood epilepsy with occipital paroxysms and early onset or Panayiotopoulos syndrome is a benign focal epileptic syndrome,a benign disease, developing at infants. The disease has been described in 1989 by S. Panayiotopoulos on the basis of results of own observations, who has called this syndrome “benign night childhood occipital lobe epilepsy”. In 1996 N. Fejerman et al. offered the new name of the syndrome – benign childhood occipital lobe epilepsy, with earlier onset (Panayiotopoulos type), versus the childhood occipital lobe epilepsy, starting later in childhood (Gastaut type). The Panayiotopoulos syndrome occurs only at children, develops at healthy children without neurological disorders, the pick of disease falls on 4–5 years. The morbidity of boys and girls is almost the same. In most cases of the syndrome seizures take place during the sleep, 2 / 3 of patients report seizures only during sleep. As a rule, seizures last for more than 5 min, in 40 % of cases it last for more than 30 min, what corresponds (according to the consciousness level) to focal or generalized epileptic status criteria. To typical clinical syndromes at Panayiotopoulos syndrome are referred the ictal vomiting, as well as different vegetative symptoms. So, theictal vomiting, which, generally, is not typical for epilepsy, takes place in about 80 % of cases at Panaytopululos syndrome. Authors describe their own observation of the Panayiotopoulos syndrome at 5 years old girl.

The term idiopathic focal epilepsies of childhood (IFE) is not formally recognised by the ILAE in its 2010 revision (Berg et al., ), nor are its members and boundaries precisely delineated. The IFEs are amongst the most commonly encountered epilepsy syndromes affecting children. They are fascinating disorders that hold many 'treats' for both clinicians and researchers. For example, the IFEs pose many of the most interesting questions central to epileptology: how are functional brain networks involved in the manifestation of epilepsy? What are the shared mechanisms of comorbidity between epilepsy and neurodevelopmental disorders? How do focal EEG discharges impact cognitive functioning? What explains the age-related expression of these syndromes? Why are EEG discharges and seizures so tightly locked to slow-wave sleep? In the last few decades, the clinical symptomatology and the respective courses of many IFEs have been described, although they are still not widely appreciated beyond the specialist community. Most neurologists would recognise the core syndromes of IFE to comprise: benign epilepsy of childhood with centro-temporal spikes or Rolandic epilepsy (BECTS/RE); Panayiotopoulos syndrome; and the idiopathic occipital epilepsies (Gastaut and photosensitive types). The Landau-Kleffner syndrome and the related (idiopathic) epilepsy with continuous spikes and waves in sleep (CSWS or ESES) are also often included, both as a consequence of the shared morphology of the interictal discharges and their potential evolution from core syndromes, for example, CSWS from BECTS. Atypical benign focal epilepsy of childhood also has shared electro-clinical features warranting inclusion. In addition, a number of less well-defined syndromes of IFE have been proposed, including benign childhood seizures with affective symptoms, benign childhood epilepsy with parietal spikes, benign childhood seizures with frontal or midline spikes, and benign focal seizures of adolescence. The term 'benign' is often used in connection with the IFEs and is increasingly being challenged. Certainly most of these disorders are not associated with the devastating cognitive and behavioural problems seen with early childhood epileptic encephalopathies, such as West or Dravet syndromes. However, it is clear that specific, and sometimes persistent, neuropsychological deficits in attention, language and literacy accompany many of the IFEs that, when multiplied by the large numbers affected, make up a significant public health problem. Understanding the nature, distribution, evolution, risk and management of these is an important area of current research. A corollary to such questions regarding comorbidities is the role of focal interictal spikes and their enduring impact on cognitive functioning. What explains the paradox that epilepsies characterised by abundant interictal epileptiform abnormalities are often associated with very few clinical seizures? This is an exciting area in both clinical and experimental arenas and will eventually have important implications for clinical management of the whole child, taking into account not just seizures, but also adaptive functioning and quality of life. For several decades, we have accepted an evidence-free approach to using or not using antiepileptic drugs in IFEs. There is huge international variation and only a handful of studies examining neurocognitive outcomes. Clearly, this is a situation ready for an overhaul in practice. Fundamental to understanding treatment is knowledge of aetiology. In recent years, there have been several significant discoveries in IFEs from studies of copy number variation, exome sequencing, and linkage that prompt reconsideration of the 'unknown cause' classification and strongly suggest a genetic aetiology. The IFE are strongly age-related, both with regards to age of seizure onset and remission. Does this time window solely relate to a similar age-related gene expression, or are there epigenetic factors involved that might also explain low observed twin concordance? The genetic (and epigenetic) models for different IFEs, their comorbidities, and their similarities to other neurodevelopmental disorders deserve investigation in the coming years. In so doing, we will probably learn much about normal brain functioning. This is because these disorders, perhaps more than any other human brain disease, are disorders of functional brain systems (even though these functional networks may not yet be fully defined). In June 2012, an international group of clinical and basic science researchers met in London under the auspices of the Waterloo Foundation to discuss and debate these issues in relation to IFEs. This Waterloo Foundation Symposium on the Idiopathic Focal Epilepsies: Phenotype to Genotype witnessed presentations that explored the clinical phenomenology, phenotypes and endophenotypes, and genetic approaches to investigation of these disorders. In parallel, the impact of these epilepsies on children and their families was reviewed. The papers in this supplement are based upon these presentations. They represent an updated state-of-the-art thinking on the topics explored. The symposium led to the formation of international working groups under the umbrella of 'Luke's Idiopathic Focal Epilepsy Project' to investigate various aspects of the idiopathic focal epilepsies including: semiology and classification, genetics, cognition, sleep, high-frequency oscillations, and parental resources (see ). The next sponsored international workshop, in June 2014, was on randomised controlled trials in IFEs and overnight learning outcome measures. [ABSTRACT FROM AUTHOR]

Sultiame is recommended for the treatment of benign epilepsy of childhood with centrotemporal spikes, electrical status epilepticus during slow-wave sleep, as well as other genetic (idiopathic) focal epilepsies. Sultiame is not traditionally considered a treatment choice for idiopathic generalised epilepsy, and it does not appear on the list of drugs recommended for treatment of absence seizures. We report the efficacy of sultiame in treating three children with drug-resistant absence seizures and discuss the potential use of sultiame beyond the idiopathic focal epilepsies. [ABSTRACT FROM AUTHOR]

Foram estudadas as características evolutivas clínico-eletrencefalográficas de 14 crianças com epilepsia occipital benigna da infância de início precoce (tipo Panayiotopoulos). O tempo médio de segmento foi 50,5 meses. A idade média na primeira crise foi 3,7 anos. O número total de crises foi até 3 crises em 11 casos, numerosas em 3; o período médio entre a primeira e a última crise foi 14,5 meses. Em 4 casos as crises tiveram duração prolongada, constituindo estado de mal parcial. Atividade epileptiforme (AE) occipital foi observada em todos os casos no primeiro EEG e, foi também, extra-occipital, em 3 casos. Houve bloqueio da AE occipital, pela abertura dos olhos, em 4 casos; em 3 casos foram observadas, também, pontas evocadas. O EEG normalizou-se em 9 casos, em um período médio de 29 meses.We studied clinical and electroencephalographic features of 14 children, age range of 2 -8 years, with no neurological or neuroradiological evidence of brain damage and with occipital epileptiform activity in the EEG. Seizures were numerous in 3 cases. Age at onset was between 1-7 years. In 4 cases the seizures last for more than 20 min. Spikes were observed in 6 cases and spike and slow-wave complex in 8. Discharges blocking by eyes opening were confirmed in 4 cases. Somatosensory evoked spikes by foot stimulation were observed in 2 cases. Autonomic and versive seizures are the main clinical manifestations of Panayiotopoulos syndrome. Discharges blocking by eyes opening are a less frequent feature.

Foram estudadas as características clínico-eletrencefalográficas de 63 crianças com crises epilépticas, atividade epileptiforme occipital ao EEG e sem elementos sugestivos de lesão cerebral. As crises foram únicas em 16 casos e numerosas em 16. A idade na primeira crise variou de 1-12 anos. As crises foram focais em 49 casos, com manifestações autonômicas em 25, versivas em 24, visuais em 10 e exclusivamente tônico-clônicas generalizadas em 14 casos. Ocorreram durante o sono em 37 e foram prolongadas em 15 crianças. O EEG evidenciou pontas em 27 casos e complexos de ponta-onda lenta em 36; houve bloqueio pela abertura dos olhos em 15. Pontas evocadas foram observadas em 9,5% dos casos. Os diagnósticos de epilepsias idiopáticas foram: occipital precoce - tipo-Panayiotopoulos (EIOP), 32 casos; occipital tardia - tipo-Gastaut (EIOT), 8; rolândica em 7. A EIOP foi mais freqüente que a EIOT e em 63,4% dos casos foi possível a classificação nas síndromes occipitais reconhecidas.We studied clinical-EEG features of 63 children, age range of 2-14 years, with occipital epileptiform activity in the EEG, with epileptic seizures and no evidences of brain damage. Age at onset was between 1-12 years. In 15 cases the seizures last for more than 30 min up to 6 h. Seizures occurred during sleep in 28 children. Autonomic symptoms were apparent in 25, head deviation in 24 and hemiconvulsion or generalization in 17 cases. Ten children reported visual symptoms. In 14 children the seizures were exclusively generalised convulsions. Spikes were observed in 27 cases and spike and slow-wave complex in 36. Discharges blocking by eyes opening were confirmed in 15 cases. Somatosensory evoked spikes by foot stimulation were observed in 9.5% cases. The cases were classified in the following idiopathic epileptic syndromes: early-onset occipital - Panayiotopoulos-type (EOO), 32 cases; late-onset occipital - Gastaut type (LOO), 8; rolandic epilepsy in 7. Conclusion: EOO occurred more frequently than LOO. Idiopathic occipital syndromes diagnosis was possible in 63.4% of the cases.

We recently showed genomewide linkage of centrotemporal sharp waves (CTS) in classic Rolandic epilepsy (RE) families to chromosome 11p13, and fine-mapped this locus to variants in the ELP4 gene. Speech sound disorder (SSD) is a common comorbidity in RE subjects, of unknown etiology, which co-aggregates in family members in a manner that could hypothetically be explained by shared underlying genetic riskwith CTS. Furthermore, the neuralmechanismof SSD is unknown, although individuals with rare, Mendelian forms of RE are described with severe verbal and oromotor apraxia. We therefore first performed genomewide linkage analysis for SSD, operationally defined as clinical history consistent with ICD-10 speech articulation disorder, in 38 families singly ascertained through a proband with RE. We tested the hypothesis of shared genetic risk with CTS at the 11p13 locus. In the second part of the study we used computerized acoustic analysis of recorded speech to test the hypothesis of dyspraxia as a mechanism for SSD in a smaller subset of RE probands and relatives. In two-point and multipoint LOD score analysis, we found that evidence for linkage to the 11p13 locus increased substantially when the phenotype was broadened from CTS to CTS/SSD. In multipoint analysis, the LOD score rose by 3.2 to HLOD 7.54 at D11S914 for CTS/SSD, the same marker at which multipoint linkage maximized for CTS alone. Non-parametric, affected-only methods in a sub-set of the data provide further confirmatory evidence for pleiotropy. In acoustic analysis there were voice-onset time abnormalities in 10/18 RE probands, 8/16 siblings and 5/15 parents, providing evidence of breakdown in the spatial/temporal properties of speech articulation consistent with a dyspraxic mechanism. The results from genetic and physiological studies suggest a pleiotropic role for the 11p13 locus in the development of both SSD and CTS, and also indicate a dyspraxic mechanism for the SSD linked to 11p13. Taken together, these data strongly support a neurodevelopmental origin for classic RE. [ABSTRACT FROM AUTHOR]

Purpose: We have studied the clinical differences between early-onset benign epilepsy with centro-temporal spikes (early-onset BECT) and Panayiotopoulos syndrome (PS) to investigate the hypothesis that BECT and PS nosologically constitute age-dependent benign childhood seizure susceptibility syndromes based on a common etiopathogenesis. Subjects and Methods: The subjects were 24 patients with BECT and 62 patients with PS, who satisfied the following definitions: 1) onset of epilepsy before 5 years of age; 2) the BECT and PS seizures started mainly with orofacial focal motor attacks and emetic symptoms followed by focal seizures, respectively; 3) follow-up examinations for longer than 2 years. We compared the various clinical features between these two groups. Results: In children with early-onset BED', the seizures at times manifested with hypersalivation, vomiting, and focal motor seizures, but the vomiting that developed in the middle of seizures was different from the initial vomiting observed in patients with PS. Although the seizures recurred more frequently in patients with early-onset BECT, the incidence of status epilepticus as well as prolonged seizures was higher in those with PS. The patients demonstrating below borderline IQ scores and mild developmental behavioral disorders were more frequently seen in early-onset BECT than PS, accounting for 37.5 and 14.6%(P<0.05), and for 8% and 21%, respectively (P<0.05). Discussion: Early-onset BECT and PS have heterogeneous clinical characteristics, except for the same onset age, and appear to be nosologically different epileptic syndromes. The former seems to develop in combination with other acquired disturbances based on a BECT predisposition, while the latter develops based on a PS predisposition and involves a better prognosis. [ABSTRACT FROM AUTHOR]

Abstract: The role of neuronal acetylcholine receptors (nAChRs) in epilepsy has been clearly established by the finding of mutations in a subset of genes coding for subunits of the nAChRs in a form of sleep-related epilepsy with familial occurrence in about 30% of probands and dominant inheritance, named autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). Sporadic and familial forms have similar clinical and EEG features. Seizures begin in middle childhood as clusters of sleep-related attacks with prominent motor activity, and sustained dystonic posturing. In addition to nocturnal seizures, psychosis or schizophrenia, behavioral disorders, memory deficits and mental retardation were described in some individuals. Although over hundred families are on record, only a minority of them have been linked to mutations in the genes coding for the α4, α2 and β2 (CHRNA4, CHRNA2, and CHRNB2) subunits of the nAChRs, indicating that ADNFLE is genetically heterogeneous despite a relatively homogeneous clinical picture. Functional characterization of some mutations suggests that gain of the receptor function might be the basis for epileptogenesis. In vitro and in vivo studies have shown high density of nAChRs in the thalamus, over activated brainstem ascending cholinergic pathway and enhanced GABAergic function, reinforcing the hypothesis that cortico-subcortical networks, regulating arousal from sleep, play a central role in seizure precipitation in ADNFLE. [Copyright &y& Elsevier]

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Objective: Declarative memory is consolidated during sleep in healthy children. We tested the hypothesis that consolidation processes are impaired in idiopathic focal epilepsies (IFE) of childhood in association with frequent interictal epileptiform discharges (IEDs) during sleep., Methods: A verbal (word-pair association) and a nonverbal (2D object location) declarative memory task were administrated to 15 children with IFEs and 8 control children 6-12 years of age. Patients had either centrotemporal (11 patients) or occipital (4 patients) IEDs. All but 3 patients had a history of unprovoked seizures, and 6 of them were treated with valproate (VPA). The learning procedure (location of object pairs presented on a grid; association of word pairs) was executed in the evening. Retrieval was tested immediately after learning and on the next morning after a night of sleep. Participants were tested twice, once in natural home conditions and one month later in the unfamiliar conditions of the sleep unit under EEG monitoring., Results: Overnight recall performance was lower in children with IFE than in control children on both tasks (ps<0.05). Performance in home conditions was similar to that in hospital conditions. Higher spike-wave index (SWI) during nonrapid eye movement (NREM) sleep was associated with poorer performance in the nonverbal task (p<0.05). Valproate treatment was not associated with overnight recall performance for both tasks (ps>0.05)., Conclusion: Memory consolidation is impaired in IFE of childhood. The association between higher SWI during NREM sleep and poorer nonverbal declarative memory consolidation supports the hypothesis that interictal epileptic activity could disrupt sleep memory consolidation., (Copyright © 2014 Elsevier Inc. All rights reserved.)