Childhood Idiopathic Epilepsy Research Articles

Assessment of serum complement level in a sample of patients of idiopathic childhood epilepsy

BackgroundThe etiology of epilepsy is still unknown in over a third of cases and a third of patients have seizures resistant to current antiseizure drugs. Most antiseizure drugs work on suppressing seizures, not targeting the underlying pathophysiological mechanisms because these mechanisms are incompletely understood. Understanding the process of epileptogenesis may lead to pathophysiology-driven drug development of more effective treatment. The aim of this study is to assess the role of the immune system in children with epilepsy, using complement as an immune marker.ResultsThe serum complement level in the cases group ranged from 1.8 to 4.5 mg/ml, with mean value 2.850 ± 0.646 mg/ml. While in the control group ranged from 2.7 to 26 mg/ml, with mean value 9.208 ± 4.805 mg/ml. The study showed a statistically significant decrease in C3 serum level in cases compared to control group with P-value < 0.001. Also, there was no statistically significant relation between seizure control and serum C3 level.ConclusionTo conclude, it was found that complement component C3 levels are significantly lower in idiopathic childhood epilepsy patients in relation to control group.

Evaluation of Acetylcholinesterase and Acetylcholine Levels in Children with Idiopathic Epilepsy

Objective of this work was to assess whether acetylcholinesterase and acetylcholine, levels that can be used as biomarkers for drug-resistant epilepsy in children with idiopathic epilepsy. Acetylcholinesterase and acetylcholine levels were measured in three groups of children, 30 children with drug resistant epilepsy,30 with seizures free and30 age and sex matched healthy children. Significant lower acetylcholinesterase was found in drug resistant epilepsy compared to seizure free epilepsy and healthy controls. Higher acetylcholine levels was found in seizure free epilepsy compared to drug resistant epilepsy and healthy controls. Stepwise linear regression analysis showed that low ACHE, high ACH, high severity score are significant independent factors associated with idiopathic epilepsy. Moreover, Receiver Operating Characteristic (ROC) analysis showed that severity score at cutoff of Chalfont score&gt;60 had the highest sensitivity 86.7% and specificity 80% followed by serum ACHE at cutoff &lt;3.212(ng/ml) with sensitivity 70% and specificity 100% and then serum ACH at cutoff &gt;18.410(ng/ml)with sensitivity 70% and specificity 83.3% as predictors for idiopathic epilepsy. Increased circulating level of ACHand decreased ACHE may predict idiopathic epilepsy suggesting their role in the childhood idiopathic epilepsy’spathogenesis.

Short-Term and Long-Term Effects of Levetiracetam Monotherapy On Hematological Parameters in Children with Idiopathic Epilepsy.

Levetiracetam (LEV) is a broad-spectrum anti-seizure drug (ASD) that has been widely used in recent years. It is thought to have an effect on the release of neurotransmitters that occur as a result of vesicle fusion and exocytosis by binding to synaptic vesicle glycoprotein 2A. The study enrolled patients diagnosed in the Pediatric Neurology Outpatient Clinic who were being followed with the diagnosis of childhood idiopathic epilepsy and were receiving LEV as ASD monotherapy. Sixty-four patients with complete blood count data from the pretreatment (Pre-T) period, the short-term period of 3 to 6 months after treatment (Post-TS), and the long-term period after 12 months (Post-TL) were included in the study. The demographic data of the patients included in the study were retrospectively analyzed for seizure frequency, seizure type, initial and subsequent EEG results, starting date of the treatment, and complete blood count data. Of 64 patients, 36 were male and 28 were female. The mean age of patients was 8.7±3.8 (2.5-16) years. In the whole population, post-TL lymphocyte counts were found to be decreased compared to pre-TL lymphocyte counts. This decrease was statistically significant for patients over 6 years of age (n=46) (p<0.075). In the post-TL period, hematocrit, hemoglobin, mean corpuscular volume, and mean platelet (PLT) volume increased, while white blood cell, PLT, neutrophil, and monocyte counts decreased (p<0.05). Seizure-free status was achieved in 92.2% of cases. Frequent seizures were observed only in five patients who were older than 6 years. Pre-treatment EEG findings were normal for 15 (23.4%) patients, generalized for 8 (12.5%) patients, and focal for 41 (64.1%) patients. According to the pretreatment EEG findings, all of the patients with improvement in EEG were those whose findings were focal (p<0.001). In children with idiopathic epilepsy, long-term LEV monotherapy may cause significant changes in hematological parameters. LEV seems to have effects on the counts and perhaps functions of PLTs, lymphocytes, monocytes, and neutrophils, particularly in the long-term.

Computational Evidence for a Competitive Thalamocortical Model of Spikes and Spindle Activity in Rolandic Epilepsy.

Rolandic epilepsy (RE) is the most common idiopathic focal childhood epilepsy syndrome, characterized by sleep-activated epileptiform spikes and seizures and cognitive deficits in school age children. Recent evidence suggests that this disease may be caused by disruptions to the Rolandic thalamocortical circuit, resulting in both an abundance of epileptiform spikes and a paucity of sleep spindles in the Rolandic cortex during non-rapid eye movement sleep (NREM); electrographic features linked to seizures and cognitive symptoms, respectively. The neuronal mechanisms that support the competitive shared thalamocortical circuitry between pathological epileptiform spikes and physiological sleep spindles are not well-understood. In this study we introduce a computational thalamocortical model for the sleep-activated epileptiform spikes observed in RE. The cellular and neuronal circuits of this model incorporate recent experimental observations in RE, and replicate the electrophysiological features of RE. Using this model, we demonstrate that: (1) epileptiform spikes can be triggered and promoted by either a reduced NMDA current or h-type current; and (2) changes in inhibitory transmission in the thalamic reticular nucleus mediates an antagonistic dynamic between epileptiform spikes and spindles. This work provides the first computational model that both recapitulates electrophysiological features and provides a mechanistic explanation for the thalamocortical switch between the pathological and physiological electrophysiological rhythms observed during NREM sleep in this common epileptic encephalopathy.

CHD4 variants are associated with childhood idiopathic epilepsy with sinus arrhythmia

AimsCHD4 gene, encoding chromodomain helicase DNA‐binding protein 4, is a vital gene for fetal development. In this study, we aimed to explore the association between CHD4 variants and idiopathic epilepsy.MethodsTrios‐based whole‐exome sequencing was performed in a cohort of 482 patients with childhood idiopathic epilepsy. The Clinical Validity Framework of ClinGen and an evaluating method from five clinical‐genetic aspects were used to determine the association between CHD4 variants and epilepsy.ResultsFour novel heterozygous missense mutations in CHD4, including two de novo mutations (c.1597A>G/p.K533E and c.4936G>A/p.E1646K) and two inherited mutations with co‐segregation (c.856C>G/p.P286A and c.4977C>G/p.D1659E), were identified in four unrelated families with eight individuals affected. Seven affected individuals had sinus arrhythmia. From the molecular sub‐regional point of view, the missense mutations located in the central regions from SNF2‐like region to DUF1087 domain were associated with multisystem developmental disorders, while idiopathic epilepsy‐related mutations were outside this region. Strong evidence from ClinGen Clinical Validity Framework and evidences from four of the five clinical‐genetic aspects suggested an association between CHD4 variants and epilepsy.ConclusionsCHD4 was potentially a candidate pathogenic gene of childhood idiopathic epilepsy with arrhythmia. The molecular sub‐regional effect of CHD4 mutations helped explaining the mechanisms underlying phenotypic variations.

Sleep and Epilepsy Link by Plasticity.

We aimed to explore the link between NREM sleep and epilepsy. Based on human and experimental data we propose that a sleep-related epileptic transformation of normal neurological networks underlies epileptogenesis. Major childhood epilepsies as medial temporal lobe epilepsy (MTLE), absence epilepsy (AE) and human perisylvian network (PN) epilepsies - made us good models to study. These conditions come from an epileptic transformation of the affected functional systems. This approach allows a system-based taxonomy instead of the outworn generalized-focal classification. MTLE links to the memory-system, where epileptic transformation results in a switch of normal sharp wave-ripples to epileptic spikes and pathological high frequency oscillations, compromising sleep-related memory consolidation. Absence epilepsy (AE) and juvenile myoclonic epilepsy (JME) belong to the corticothalamic system. The burst-firing mode of NREM sleep normally producing sleep-spindles turns to an epileptic working mode ejecting bilateral synchronous spike-waves. There seems to be a progressive transition from AE to JME. Shared absences and similar bilateral synchronous discharges show the belonging of the two conditions, while the continuous age windows - AE affecting schoolchildren, JME the adolescents - and the increased excitability in JME compared to AE supports the notion of progression. In perisylvian network epilepsies - idiopathic focal childhood epilepsies and electrical status epilepticus in sleep including Landau-Kleffner syndrome - centrotemporal spikes turn epileptic, with the potential to cause cognitive impairment. Postinjury epilepsies modeled by the isolated cortex model highlight the shared way of epileptogenesis suggesting the derailment of NREM sleep-related homeostatic plasticity as a common step. NREM sleep provides templates for plasticity derailing to epileptic variants under proper conditions. This sleep-origin explains epileptiform discharges' link and similarity with NREM sleep slow oscillations, spindles and ripples. Normal synaptic plasticity erroneously overgrowing homeostatic processes may derail toward an epileptic working-mode manifesting the involved system's features. The impact of NREM sleep is unclear in epileptogenesis occurring in adolescence and adulthood, when plasticity is lower. The epileptic process interferes with homeostatic synaptic plasticity and may cause cognitive impairment. Its type and degree depends on the affected network's function. We hypothesize a vicious circle between sleep end epilepsy. The epileptic derailment of normal plasticity interferes with sleep cognitive functions. Sleep and epilepsy interconnect by the pathology of plasticity.

The effect of interictal epileptiform discharges on cognitive and academic performance in children with idiopathic epilepsy

BackgroundInterictal epileptiform discharges (IEDs) have been proven to impair cognitive function. However, it is not clear whether IEDs disrupt academic performance in children with idiopathic epilepsy, and the contribution of cognitive function deficits to impaired academic performance has not been clarified. This study aimed to examine the cognitive deficits and academic impairment in childhood idiopathic epilepsy with IEDs.MethodsNinety-seven childhood idiopathic epilepsy with IEDs, 77 childhood idiopathic epilepsy without IEDs, and 71 healthy controls completed a series of cognitive tests. We analyzed the cognitive performance in several domains including language, mathematics, psychomotor speed, spatial ability, memory, general intelligence, attention and executive functioning. Analysis of variance was conducted to compare the performance on all tests between the three groups.ResultsChildhood idiopathic epilepsy with IEDs exhibited not only general cognitive deficits in processing speed, spatial ability, and attention, but also arithmetic impairment. Furthermore, general cognitive deficits could account for the impaired arithmetic performance in childhood idiopathic epilepsy with IEDs.ConclusionsOur study suggested that IEDs in children with idiopathic epilepsy affected both cognitive function and academic performance, and that the cognitive deficits may be responsible for arithmetic performance impairment.

Expertise, giftedness and insight in mathematics

Absence epilepsy (AE) and nocturnal frontal lobe epilepsy (NFLE) are system epilepsies of the sleep–wake system.1. Absence epilepsy is a well-known idiopathic childhood epilepsy. The spike–wake pattern of absence epilepsy and the non–rapid eye movement (NREM) sleep-related burst-firing mode of the corticothalamic system share the same functional structures in the brain. Absences occur when vigilance decreases, during the transition from waking to NREM sleep, whereas they are inhibited by wakefulness and rapid eye movement sleep. The sensory stimuli reaching the brain during the transition state [cyclic alternating pattern (CAP) A1 phase] elicit “reactive” slow-wave responses and may activate spike–wave responses, whereas those arriving in other states (CAP 2 or 3 NREM sleep) evoke “regular” desynchronization–arousal responses and do not trigger spike–waves.In other words, in terms of states and functions, absence epilepsy seems to be linked to the periods of initiation and shifts toward NREM sleep.2. Autosomal dominant nocturnal frontal lobe epilepsy, the genetic variation of NFLE, is underlain by mutations of the nicotinic acetylcholine receptor system.The acetylcholine receptor (AChE) gene mutations render the cholinergic ascending arousal system oversensitive to arousals during NREM sleep, resulting in arousal-linked seizure fragments and full-blown seizures with different degrees of behavioral manifestations, from plain arousal behaviors to alarm reactions with hypermotor features. The semiology and the occurrence pattern of seizures can be explained by an increased propensity to arousal and a dissociation between the partially activated brain and a sleeping (dysfunctional) dorsofrontal cortical system. The clinical semiology of the genetic variations and the sporadic cases does not differ.Therefore, NFLE seems to be linked to the epileptically facilitated cholinergic arousal system, underlain by a genetic or a suspected genetic origin.Arousal parasomnia (AP) manifests behaviors similar to those of NFLE, caused by a nonepileptic mechanism. The two conditions (AP and NFLE) show a familial clustering, with patients and families suffering in both conditions and probably sharing the pathomechanisms related to a dissociation background.We can see that NFLE and AP (the epileptic and nonepileptic counterparts) may both be linked to a disorder of the frontal part of the ascending arousal system.

Circulating irisin and chemerin levels as predictors of seizure control in children with idiopathic epilepsy.

Irisin and chemerin peptides expression are triggered by hypoxia and involved in activation of inflammatory cascades in various organs including the brain; however, their role in epilepsy is not fully illustrated. This study aims to explore the predictive role of irisin and chemerin for seizure control in children with idiopathic epilepsy. This cross-sectional comparative study included 50 children with idiopathic epilepsy; 25 of them had controlled seizures over the previous 6months and 30 age- and sex-matched healthy children as controls. Epilepsy characteristics, seizure severity Chalfont score, and response to medications were assessed in relation to serum irisin and chemerin levels. In comparison to healthy controls, serum chemerin and irisin levels were significantly higher in children with idiopathic epilepsy especially those with uncontrolled seizures. Serum chemerin and irisin levels had significant positive correlation with seizure severity Chalfont score and the duration of epilepsy. Elevated Chalfont score (OR 3.19), serum chemerin (OR 2.01), and irisin (OR 2.03) are predictors of uncontrolled seizures. Circulating chemerin and irisin have 80% and 76% sensitivity and 88% and 92% specificity at cutoff point > 191.38 ng/ml and > 151.2ng/ml respectively for prediction of uncontrolled seizures in children with idiopathic epilepsy. Elevated circulating level of irisin and chemerin may predict poor seizure control in children with idiopathic epilepsy suggesting the role of hypoxia-triggered neuroinflammation in the pathogenesis of childhood idiopathic epilepsy.

Contribution of Family Relatedness to Neurobehavioral Comorbidities in Idiopathic Childhood Epilepsies.

Rates of cognitive, academic and behavioral comorbidities are elevated in children with epilepsy. The contribution of environmental and genetic influences to comorbidity risk is not fully understood. This study investigated children with epilepsy, their unaffected siblings, and controls to determine the presence and extent of risk associated with family relatedness across a range of epilepsy comorbidities. Participants were 346 children (8-18 years), n=180 with recent-onset epilepsy, their unaffected siblings (n=67), and healthy first-degree cousin controls (n=99). Assessments included: (1) Child Behavior Checklist/6-18 (CBCL), (2) Behavior Rating Inventory of Executive Function (BRIEF), (3) history of education and academic services, and (4) lifetime attention deficit hyperactivity disorder (ADHD) diagnosis. Analyses consisted of linear mixed effect models for continuous variables, and logistic mixed models for binary variables. Differences were detected between the three groups of children across all measures (p<.001). For ADHD, academic problems, and executive dysfunction, children with epilepsy exhibited significantly more problems than unaffected siblings and controls; siblings and controls did not differ statistically significantly from each other. For social competence, children with epilepsy and their unaffected siblings displayed more abnormality compared with controls, with no statistically significant difference between children with epilepsy and unaffected siblings. For behavioral problems, children with epilepsy had more abnormality than siblings and controls, but unaffected siblings also exhibited more abnormalities than controls. The contribution of epilepsy and family relatedness varies across specific neurobehavioral comorbidities. Family relatedness was not significantly associated with rates of ADHD, academic problems and executive dysfunction, but was associated with competence and behavioral problems. (JINS, 2018, 24, 653-661).

Language function in childhood idiopathic epilepsy syndromes

PurposeTo examine the impact of diverse syndromes of focal and generalized epilepsy on language function in children with new and recent onset epilepsy. Of special interest was the degree of shared language abnormality across epilepsy syndromes and the unique effects associated with specific epilepsy syndromes. MethodsParticipants were 136 youth with new or recent-onset (diagnosis within past 12 months) epilepsy and 107 healthy first-degree cousin controls. The participants with epilepsy included 20 with Temporal Lobe Epilepsy (TLE; M age = 12.99 years, SD = 3.11), 41 with Benign Epilepsy with Centrotemporal Spikes (BECTS; M age = 10.32, SD = 1.67), 42 with Juvenile Myoclonic Epilepsy (JME; M age = 14.85, SD = 2.75) and 33 with absence epilepsy (M age = 10.55, SD = 2.76). All children were administered a comprehensive test battery which included multiple measures of language and language-dependent abilities (i.e., verbal intelligence, vocabulary, verbal reasoning, object naming, reception word recognition, word reading, spelling, lexical and semantic fluency, verbal list learning and delayed verbal memory). Test scores were adjusted for age and gender and analyzed via MANCOVA. ResultsLanguage abnormalities were found in all epilepsy patient groups. The most broadly affected children were those with TLE and absence epilepsy, whose performance differed significantly from controls on 8 of 11 and 9 of 11 tests respectively. Although children with JME and BECTS were less affected, significant differences from controls were found on 4 of 11 tests each. While each group had a unique profile of language deficits, commonalities were apparent across both idiopathic generalized and localization-related diagnostic categories. DiscussionThe localization related and generalized idiopathic childhood epilepsies examined here were associated with impact on diverse language abilities early in the course of the disorder.

Abnormal asymmetry in benign epilepsy with unilateral and bilateral centrotemporal spikes: A combined fMRI and DTI study

Benign epilepsy with centrotemporal spikes (BECTS) is the most common idiopathic focal childhood epilepsy associated with either unilateral or bilateral epileptic discharge. Asymmetry as an important characteristic of the human brain is beneficial for brain functions. However, little is known about on asymmetry of BECTS patients with different epileptic spikes pattern. In the present study, we investigated functional and structural asymmetries in unilateral spikes BECTS (U_BECTS) patients and bilateral spikes BECTS (B_BECTS) patients using resting state functional magnetic resonance images and diffusion tensor imaging. Compared with the controls, we observed a decreased voxel-mirrored interhemispheric functional connectivity (FC) in primary sensorimotor cortex (SM1) in U_BECTS and B_BECTS groups, and reduced fractional anisotropy (FA) values of the corpus callosum (CC) connecting bilateral SM1 were also observed in B_BECTS group. Further region-based FC map analysis of SM1 demonstrated increased functional asymmetry with ipsilateral hemisphere, contralateral hemisphere and the whole brain in U_BECTS and increased functional asymmetry with the contralateral hemisphere and the whole brain in B_BECTS groups. The correlation between functional asymmetry of SM1 and intelligence quotient scores was found in the U_BECTS group. The altered asymmetries of the SM1 further indicated the important role of SM1 in the pathophysiology of the BECTS. Furthermore, the B_BECTS group also showed abnormal voxel-mirrored interhemispheric FC in the temporal pole, the lobule IX of the cerebellum, the caudate and the occipital cortex relative to the controls. Altogether, our findings provide additional insight into the neuronal mechanism of BECTS with different epileptic spikes pattern and cognitive impairments with BECTS patients.

Childhood absence epilepsy and benign epilepsy with centro-temporal spikes: a narrative review analysis

Recent studies have shown a possible coexistence of absence seizures with other forms of epilepsy. The purpose of this study was to ascertain the possible contemporary or subsequent presence of childhood absence epilepsy (CAE) and benign epilepsy with centro-temporal spikes (BECTS) in pediatric epileptic patients. A PubMed systematic search indexed for MEDLINE, PubMed and EMBASE was undertaken to identify studies in children including articles written between 1996 and 2015. Retrospective studies, meta-analysis and case reports were included. The list of references of all the relevant articles was also studied. The date of our last search was December 2015. Review of the literature revealed 19 cases, 8 females and 11 males, reporting a consecutive or contemporary coexistence of CAE and BECTS within the same patients. Patient's age ranged between 4 and 12 years. Three out of 19 patients presented concomitant features of both syndromes, whereas 16 patients experienced the two syndromes at different times. BECTS and CAE may be pathophysiologically related, and the two epileptic phenotypes may indicate a neurobiological continuum. Further studies are needed to elucidate a probable genetic or functional link between partial and primarily generalized electro-clinical patterns in idiopathic childhood epilepsies.

Cognitive phenotypes in childhood idiopathic epilepsies.

The objective of this study was to identify cognitive phenotypes in children with new-onset focal and generalized idiopathic epilepsies and determine their relationship with epilepsy syndrome, brain structure, neurodevelopmental history, and family characteristics. One hundred thirty-eight children with new-onset epilepsy and 95 controls (age: 8-18) underwent neuropsychological, clinical, and quantitative MR evaluations. Control participants' neuropsychological data were subjected to confirmatory factor analysis and then resultant factor scores were applied to participants with epilepsy and subjected to latent class analysis. Identified cognitive phenotypes were examined in relation to epilepsy syndrome, quantitative neuroimaging, and familial and neurodevelopmental variables. Confirmatory factor analysis identified five cognitive factors (verbal, perceptual, speed, attention, executive), and latent class analysis identified three clusters of participants with epilepsy: 1) average and similar to controls, 2) mild impairment across multiple cognitive domains, and 3) impairment across all domains with severe attentional impairment, representing 44%, 44%, and 12% of the epilepsy sample, respectively. Cognitive phenotype membership was not associated with epilepsy syndrome but was associated with increasing abnormalities in brain structure, parental IQ, and features of early developmental history. Cognitive phenotypes are present in idiopathic childhood epilepsies that are unassociated with traditional epilepsy syndromes but are associated with measures of brain structure, family history, and neurodevelopmental features.

Long-Term Clinical and Electroencephalography (EEG) Consequences of Idiopathic Partial Epilepsies.

BackgroundIdiopathic partial epilepsies of childhood (IPE) affect a considerable proportion of children. Three main electroclinical syndromes of IPE are the Benign Childhood Epilepsy with Centro-temporal Spikes (BECTS), Panayiotopoulos Syndrome (PS), and Childhood Epilepsy with Occipital Paroxysms (CEOP). In this study we investigated the long-term prognosis of patients with IPE and discussed the semiological and electroencephalography (EEG) data in terms of syndromic characteristics.Material/MethodsThis study included a group of consecutive patients with IPE who had been followed since 1990. Demographic and clinical variables were investigated. Patients were divided into 3 groups – A: Cases suitable for a single IPE (BECTS, PS and CEOP); B: cases with intermediate characteristics within IPEs; and C: cases with both IPE and IGE characteristics. Long-term data regarding the individual seizure types and EEG findings were re-evaluated.ResultsA total of 61 patients were included in the study. Mean follow-up duration was 7.8±4.50 years. The mean age at onset of seizures was 7.7 years. There were 40 patients in group A 40, 14 in group B, and 7 in group C. Seizure and EEG characteristics were also explored independently from the syndromic approach. Incidence of autonomic seizures is considerably high at 2–5 years and incidence of oromotor seizures is high at age 9–11 years. The EEG is most abnormal at 6–8 years. The vast majority (86%) of epileptic activity (EA) with parietooccipital is present at 2–5 years, whereas EA with fronto-temporal or multiple sites become more abundant between ages 6 and 11.ConclusionsResults of the present study provide support for the age-related characteristics of the seizures and EEGs in IPE syndromes. Acknowledgement of those phenomena may improve the management of IPEs and give a better estimate of the future consequences.

Praxis-induced seizures in a patient with juvenile myoclonic epilepsy: MEG-EEG coregistration study

PurposeJuvenile myoclonic epilepsy (JME) is one of the most common generalized idiopathic epilepsies of childhood and adolescence. In some patients with JME, mathematical calculus and praxis may induce myoclonic seizures.MethodsA reflex myoclonic seizure was recorded by simultaneous magnetoencephalography (MEG) and electroencephalography (EEG) when a generalized spike–wave synchronous pattern at 3 Hz was observed.ResultsSource reconstruction localized the epileptogenic area to the right premotor frontal cortex.ConclusionsThe present study demonstrates that the origin of epileptiform activity in JME can be localized in brain areas associated with the premotor frontal cortex.

EEG resting state analysis of cortical sources in patients with benign epilepsy with centrotemporal spikes.

Benign epilepsy with centrotemporal spikes (BECTS) is the most common idiopathic childhood epilepsy, which is often associated with developmental disorders in children. In the present study, we analyzed resting state EEG spectral changes in the sensor and source spaces in eight BECTS patients compared with nine age-matched controls. Using high-resolution scalp EEG data, we assessed statistical differences in spatial distributions of EEG power spectra and cortical sources of resting state EEG rhythms in five frequency bands: δ (0.5–3.5 Hz), θ (4–8 Hz), α (8.5–13 Hz), β1 (13.5–20 Hz) and β2 (20.5–30 Hz) under the eyes-closed resting state condition. To further investigate the impact of centrotemporal spikes on EEG spectra, we split the EEG data of the patient group into EEG portions with and without spikes. Source localization demonstrated the homogeneity of our population of BECTS patients with a common epileptic zone over the right centrotemporal region. Significant differences in terms of both spectral power and cortical source densities were observed between controls and patients. Patients were characterized by significantly increased relative power in θ, α, β1 and β2 bands in the right centrotemporal areas over the spike zone and in the right temporo-parieto-occipital junction. Furthermore, the relative power in all bands significantly decreased in the bilateral frontal and parieto-occipital areas of patients regardless of the presence or absence of spikes in EEG segments. However, the spectral differences between patients and controls were more pronounced in the presence of spikes. This observation emphasized the impact of benign epilepsy on cortical source power, especially in the right centrotemporal regions. Spectral changes in bilateral frontal and parieto-occipital areas may also suggest alterations in the default mode network in BECTS patients.

16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy.

Rolandic epilepsy (RE) is the most common idiopathic focal childhood epilepsy. Its molecular basis is largely unknown and a complex genetic etiology is assumed in the majority of affected individuals. The present study tested whether six large recurrent copy number variants at 1q21, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 previously associated with neurodevelopmental disorders also increase risk of RE. Our association analyses revealed a significant excess of the 600 kb genomic duplication at the 16p11.2 locus (chr16: 29.5-30.1 Mb) in 393 unrelated patients with typical (n = 339) and atypical (ARE; n = 54) RE compared with the prevalence in 65,046 European population controls (5/393 cases versus 32/65,046 controls; Fisher's exact test P = 2.83 × 10(-6), odds ratio = 26.2, 95% confidence interval: 7.9-68.2). In contrast, the 16p11.2 duplication was not detected in 1738 European epilepsy patients with either temporal lobe epilepsy (n = 330) and genetic generalized epilepsies (n = 1408), suggesting a selective enrichment of the 16p11.2 duplication in idiopathic focal childhood epilepsies (Fisher's exact test P = 2.1 × 10(-4)). In a subsequent screen among children carrying the 16p11.2 600 kb rearrangement we identified three patients with RE-spectrum epilepsies in 117 duplication carriers (2.6%) but none in 202 carriers of the reciprocal deletion. Our results suggest that the 16p11.2 duplication represents a significant genetic risk factor for typical and atypical RE.

Clinical course and seizure outcome of idiopathic childhood epilepsy: determinants of early and long-term prognosis

BackgroundIdiopathic epilepsies and epileptic syndromes predominate childhood and adolescence epilepsy. The aim of the present study was to investigate the clinical course and outcome of idiopathic childhood epilepsy and identify variables determining both early and long-term prognosis.MethodsWe followed 303 children with newly diagnosed idiopathic epilepsy aged 1–14 years old, both prospectively and retrospectively. Outcome was defined at one, 2 and 4 years of follow-up, as well as at the end of the study period for all patients. Based on the data collected, patients were classified in four patterns of clinical course: “excellent”, “improving”, “relapsing” and “poor”. Variables defined at intake and after the initial year of treatment were analyzed for their prognostic relevance towards the clinical course and outcome of the patients.ResultsThe mean age at seizure onset was 6,7 years and the mean duration of follow-up was 8,3 years (range 2,0-22,0,SD 4,24). During the initial year of treatment, 70,3% of patients were seizure-free. The course of epilepsy was “excellent” in 53,1% of the subjects, “improving” in 22,8%, “relapsing” in 22,1% whereas only 6 children with idiopathic epilepsy (2%) had a “poor” clinical course exhibiting drug-resistance. After multivariate analysis, variables predictive of a poor initial response to therapy were early seizure onset, multiple seizure types and history of status epilepticus. At the end of follow-up, early response to treatment was of significant positive predictive value, while the presence of multiple seizure types and the history of migraine had a negative impact on prognosis.ConclusionsIn the vast majority of children, the long-term prognosis of idiopathic epilepsy is favorable. More than half of the patients attain seizure freedom immediately and their clinical course is considered “excellent”. About one fifth exhibit either an improving or a fluctuating course. Early seizure onset, multiple seizure types and status epilepticus are predictive of an initial poor response to treatment in children with idiopathic epilepsy. Initial non-response to treatment, multiple seizure types and history of migraine are determinants of a less favorable final outcome after long-term follow-up.

Aberrant functional connectivity between motor and language networks in rolandic epilepsy

Rolandic epilepsy (RE) is an idiopathic focal childhood epilepsy with a well-established neuropsychological profile of language impairment. The aim of this study is to provide a functional correlate that links rolandic (sensorimotor) pathology to language problems using functional MRI. Twenty-three children with RE (8-14 years old) and 21 matched controls underwent extensive language assessment (Clinical Evaluation of Language Fundamentals). fMRI was performed at rest and using word generation, reading, and finger tapping paradigms. Since no activation group differences were found, regions of interest (ROIs) were defined at pooled (patients and controls combined) activation maxima and in contralateral homotopic cortex, and used to assess language lateralization as well as for a resting-state connectivity analysis. Furthermore, the association between connection strength and language performance was investigated. Reduced language performance was found in the children with RE. Bilateral activation was found for both language tasks with some predominance of the left hemisphere in both groups. Compared to controls, patient connectivity was decreased between the left sensorimotor area and right inferior frontal gyrus (p<0.01). For this connection, lower connectivity was associated with lower language scores in the patient group (r=0.49, p=0.02), but not in the controls. Language laterality analysis revealed bilateral language representation in the age range under study (8-14 years). As a consequence, the connection of reduced functional connectivity we found represents an impaired interplay between motor and language networks, and aberrant functional connectivity associated with poorer language performance. These findings provide a first neuronal correlate in terms of aberrant resting-state functional connectivity for language impairment in RE.