Individual-based morphological brain network changes in children with Rolandic epilepsy.

OBJECTIVE: To investigate the local cortical morphology and individual-based morphological brain networks (MBNs) changes in children with Rolandic epilepsy (RE). METHODS: Based on the structural MRI data of 56 children with RE and 56 healthy controls (HC), we constructed four types of individual-based MBNs using morphological indices (cortical thickness [CT], fractal dimension [FD], gyrification index [GI], and sulcal depth [SD]). The global and nodal properties of the brain networks were analyzed using graph theory. The between-group difference in local morphology and network topology was estimated, and partial correlation analysis was further analyzed. RESULTS: Compared with the HC, children with RE showed regional GI increases in the right posterior cingulate gyrus and SD increases in the right anterior cingulate gyrus and medial prefrontal cortex. Regarding the network level, RE exhibited increased characteristic path length in CT-based and FD-based networks, while decreased FD-based network node efficiency in the right inferior frontal gyrus. No significant correlation between altered morphological features and clinical variables was found in RE. CONCLUSIONS: These findings indicated that children with RE have disrupted morphological brain network organization beyond local morphology changes. SIGNIFICANCE: The present study could provide more theoretical basis for exploring the neuropathological mechanisms in RE.

Cognitive development in children with new-onset Rolandic epilepsy and Rolandic discharges without seizures: Focusing on intelligence, visual perception, working memory and the role of parents' education.

PURPOSE: Our aim was to assess intelligence, visual perception and working memory in children with new-onset Rolandic epilepsy (RE) and children with Rolandic discharges without seizures (RD). METHODS: The participants in the study were 12 children with RE and 26 children with RD aged 4 to 10 years (all without medication and shortly after diagnosis) and 31 healthy controls. Their cognitive performance was assessed using the German versions of the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III), the Wechsler Intelligence Scale for Children (WISC-IV), the Developmental Test of Visual Perception-2 (DTVP-2), the Developmental Test of Visual Perception-Adolescent and Adult (DTVP-A) (each according to age) and the Word Order, Hand Movements and Spatial Memory subtests of the German version of the Kaufman Assessment Battery for Children (K-ABC). RESULTS: The comparison of the entire group of children with RE/RD and the control group conducted in the first step of our analysis revealed a weaker performance of the children with RE/RD in all cognitive domains. Significant deficits, however, were found exclusively in the RD group. Compared to the controls, they performed significantly weaker regarding IQ (full scale IQ: p < 0.001; verbal IQ: p < 0.001; performance IQ: p = 0.002; processing speed: p = 0.005), visual perception (general visual perception: p = 0.005; visual-motor integration: p = 0.002) and working memory (WISC working memory: p = 0.002 and K-ABC Word Order (p = 0.010) and Hand Movements (p = 0.001) subtests. Also, the children without seizures scored significantly lower than those with seizures on the WISC Working Memory Index (p = 0.010) and on the K-ABC Word Order (p = 0.021) and Hand Movements (p = 0.027) subtests. Further analysis of our data demonstrated the particular importance of the family context for child development. Significant cognitive deficits were found only in children with RD from parents with lower educational levels. This group consistently scored lower compared to the control group regarding IQ (full scale IQ: p < 0.001; verbal IQ: p < 0.001; performance IQ: p = 0.012; processing speed: p = 0.034), visual perception (general visual perception: p = 0.018; visual-motor integration: p = 0.010) and auditory working memory (WISC working memory: p = 0.014). Furthermore, compared to the children with RE, they performed significantly weaker on verbal IQ (p = 0.020), auditory working memory consistently (WISC working memory: p = 0.027; K-ABC: Word Order: p = 0.046) as well as in one of the K-ABC spatial working memory subtests (Hand Movements: p = 0.029). Although we did not find significant deficits in children with new-onset RE compared to healthy controls, the performance of this group tended to be weaker more often. No statistically significant associations were observed between selected clinical markers (focus types: centrotemporal/other foci/laterality of foci and spread of Rolandic discharges) and cognitive test results. Except for spatial working memory, we also found no evidence that the age of our patients at the time of study participation was of significant importance to their cognitive performance. CONCLUSIONS: Our study provides some evidence that children with Rolandic discharges, with and without seizures, may be at higher risk of cognitive impairment. In addition to medical care, we emphasise early differentiated psychosocial diagnostics to provide these children and their families with targeted support if developmental problems are present.

Distinct manifestations and potential mechanisms of seizures due to cortical versus white matter injury in children.

PURPOSE: To study seizure manifestations and outcomes in children with cortical versus white matter injury, differences potentially explaining variability of epilepsy in children with cerebral palsy. METHODS: In this population-based retrospective cohort study, MRIs of children with cerebral palsy due to ischemia or haemorrhage were classified according to presence or absence of cortical injury. MRI findings were then correlated with history of neonatal seizures, seizures during childhood, epilepsy syndromes, and seizure outcomes. RESULTS: Of 256 children studied, neonatal seizures occurred in 57 and seizures during childhood occurred in 93. Children with neonatal seizures were more likely to develop seizures during childhood, mostly those with cortical injury. Cortical injury was more strongly associated with (1) developing seizures during childhood, (2) more severe epilepsy syndromes (infantile spasms syndrome, focal epilepsy, Lennox-Gastaut syndrome), and (3) less likelihood of reaching > 2 years without seizures at last follow-up, compared to children without cortical injury. Children without cortical injury, mainly those with white matter injury, were less likely to develop neonatal seizures and seizures during childhood, and when they did, epilepsy syndromes were more commonly febrile seizures and self-limited focal epilepsies of childhood, with most achieving > 2 years without seizures at last follow-up. The presence of cortical injury also influenced seizure occurrence, severity, and outcome within the different predominant injury patterns of the MRI Classification System in cerebral palsy, most notably white matter injury. CONCLUSIONS: Epileptogenesis is understood with cortical injury but not well with white matter injury, the latter potentially related to altered postnatal white matter development or myelination leading to apoptosis, abnormal synaptogenesis or altered thalamic connectivity of cortical neurons. These findings, and the potential mechanisms discussed, likely explain the variability of epilepsy in children with cerebral palsy and epilepsy following early-life brain injury in general.

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

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

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

A prospective 5-year longitudinal study detects neurocognitive and imaging correlates of seizure remission in self-limiting Rolandic epilepsy.

OBJECTIVE: Self-limiting Rolandic epilepsy (RE) is the most common epilepsy in school-age children. Seizures are generally infrequent, but cognitive, language, and motor coordination problems can significantly impact the child's life. To better understand brain structure and function changes in RE, we longitudinally assessed neurocognition, cortical thickness, and subcortical volumes. METHODS: At baseline, we recruited 30 participants diagnosed with RE and 24-healthy controls and followed up for 4.94 ± 0.8 years when the participants with RE were in seizure remission. Measures included were as follows: T1-weighted magnetic resonance brain imaging (MRI) with FreeSurfer analysis and detailed neuropsychological assessments. MRI and neuropsychological data were compared between baseline and follow-up in seizure remission. RESULTS: Longitudinal MRI revealed excess cortical thinning in the left-orbitofrontal (p = 0.0001) and pre-central gyrus (p = 0.044). There is a significant association (p = 0.003) between a reduction in cortical thickness in the left-orbitofrontal cluster and improved processing of filtered words. Longitudinal neuropsychology revealed significant improvements in the symptoms of developmental coordination disorder (DCD, p = 0.005) in seizure remission. CONCLUSIONS: There is evidence for altered development of neocortical regions between active seizure state and seizure remission in RE within two clusters maximal in the left-orbitofrontal and pre-central gyrus. There is significant evidence for improvement in motor coordination between active seizures and seizure remission and suggestive evidence for a decline in fluid intelligence and gains in auditory processing.

Comprehensive Dental Management of a Rolandic Epilepsy Patient Under Local Anesthesia: A Case Report.

Dental treatment of epilepsy patients is often challenging and requires careful consideration of their sudden movements. Epilepsy patients often require sedation (e.g., nitrous oxide or intravenous sedation) to receive their required dental treatments. Rolandic epilepsy (RE) is a specific type of epilepsy in children with certain electroencephalogram (EEG) abnormalities and motor focal seizures with no signs of neurological deficits. This report discusses a case of an RE patient who was treated comprehensively under local anesthesia with careful evaluation of the patient's medical conditions.

The fate of spikes in self-limited epilepsy with centrotemporal spikes: Are clinical and baseline EEG features effective?

OBJECTIVE: The aim of this study is to evaluate the effects of clinical and electroencephalographic features on spike reduction with a focus on the first EEG characteristics in self-limited epilepsy with centrotemporal spikes (SeLECTS). METHODS: This retrospective study was conducted on SeLECTS patients of with at least five years follow-up and at least two EEG recordings in which spike wave indexes (SWI) were calculated. RESULTS: 136 patients were enrolled. Median SWI in the first and last EEGs were 39% (7.6-89%) and 0 (0-112%). Gender, seizure onset age, psychiatric diseases, seizure characteristics (semiology, duration, and relationship to sleep), last EEG time, and spike lateralization in the first EEG did not have a statistically significant effect on the SWI change. Multinomial logistic regression analysis revealed that presence of phase reversal, interhemispheric generalization, and SWI percentage had a significant effect on spike reduction. The frequency of seizures was also significantly decreased in patients with a greater decrease in SWI. Both valproate and levetiracetam were statistically superior in suppressing SWI, with no significant difference between them. CONCLUSION: Interhemispheric generalization and phase reversal in the first EEG in SeLECTS had negative effects on the spike reduction. The most effective ASMs in reducing spikes were valproate and levetiracetam.

Children with Rolandic epilepsy have micro- and macrostructural abnormalities in white matter constituting networks necessary for language function.

INTRODUCTION: Self-limited epilepsy with centrotemporal spikes is a transient developmental epilepsy with a seizure onset zone localized to the centrotemporal cortex that commonly impacts aspects of language function. To better understand the relationship between these anatomical findings and symptoms, we characterized the language profile and white matter microstructural and macrostructural features in a cohort of children with SeLECTS. METHODS: Children with active SeLECTS (n = 13), resolved SeLECTS (n = 12), and controls (n = 17) underwent high-resolution MRIs including diffusion tensor imaging sequences and multiple standardized neuropsychological measures of language function. We identified the superficial white matter abutting the inferior rolandic cortex and superior temporal gyrus using a cortical parcellation atlas and derived the arcuate fasciculus connecting them using probabilistic tractography. We compared white matter microstructural characteristics (axial, radial and mean diffusivity, and fractional anisotropy) between groups in each region, and tested for linear relationships between diffusivity metrics in these regions and language scores on neuropsychological testing. RESULTS: We found significant differences in several language modalities in children with SeLECTS compared to controls. Children with SeLECTS performed worse on assessments of phonological awareness (p = 0.045) and verbal comprehension (p = 0.050). Reduced performance was more pronounced in children with active SeLECTS compared to controls, namely, phonological awareness (p = 0.028), verbal comprehension (p = 0.028), and verbal category fluency (p = 0.031), with trends toward worse performance also observed in verbal letter fluency (p = 0.052), and the expressive one-word picture vocabulary test (p = 0.068). Children with active SeLECTS perform worse than children with SeLECTS in remission on tests of verbal category fluency (p = 0.009), verbal letter fluency (p = 0.006), and the expressive one-word picture vocabulary test (p = 0.045). We also found abnormal superficial white matter microstructure in centrotemporal ROIs in children with SeLECTS, characterized by increased diffusivity and fractional anisotropy compared to controls (AD p = 0.014, RD p = 0.028, MD p = 0.020, and FA p = 0.024). Structural connectivity of the arcuate fasciculus connecting perisylvian cortical regions was lower in children with SeLECTS (p = 0.045), and in the arcuate fasciculus children with SeLECTS had increased diffusivity (AD p = 0.007, RD p = 0.006, MD p = 0.016), with no difference in fractional anisotropy (p = 0.22). However, linear tests comparing white matter microstructure in areas constituting language networks and language performance did not withstand correction for multiple comparisons in this sample, although a trend was seen between FA in the arcuate fasciculus and verbal category fluency (p = 0.047) and the expressive one-word picture vocabulary test (p = 0.036). CONCLUSION: We found impaired language development in children with SeLECTS, particularly in those with active SeLECTS, as well as abnormalities in the superficial centrotemporal white matter as well as the fibers connecting these regions, the arcuate fasciculus. Although relationships between language performance and white matter abnormalities did not pass correction for multiple comparisons, taken together, these results provide evidence of atypical white matter maturation in fibers involved in language processing, which may contribute to the aspects of language function that are commonly affected by the disorder.

Spike height improves prediction of future seizure risk.

OBJECTIVE: We evaluated whether interictal epileptiform discharge (IED) rate and morphological characteristics predict seizure risk. METHODS: We evaluated 10 features from automatically detectable IEDs in a stereotyped population with self-limited epilepsy with centrotemporal spikes (SeLECTS). We tested whether the average value or the most extreme values from each feature predicted future seizure risk in cross-sectional and longitudinal models. RESULTS: 10,748 individual centrotemporal IEDs were analyzed from 59 subjects at 81 timepoints. In cross-sectional models, increases in average spike height, spike duration, slow wave rising slope, slow wave falling slope, and the most extreme values of slow wave rising slope each improved prediction of an increased risk of a future seizure compared to a model with age alone (p < 0.05, each). In longitudinal model, spike rising height improved prediction of future seizure risk compared to a model with age alone (p = 0.04) CONCLUSIONS: Spike height improves prediction of future seizure risk in SeLECTS. Several other morphological features may also improve prediction and should be explored in larger studies. SIGNIFICANCE: Discovery of a relationship between novel IED features and seizure risk may improve clinical prognostication, visual and automated IED detection strategies, and provide insights into the underlying neuronal mechanisms that contribute to IED pathology.

Does Electrical Status Epilepticus in Sleep Adversely Affect Language in Self-Limiting Focal Epilepsies of Childhood?

Introduction: The electrical status epilepticus in sleep (ESES) accompanies a wide spectrum of focal and generalized epilepsies, which manifest with cognitive-linguistic regression. Both ESES and language impairment can be seen in self-limited focal epileptic syndromes of childhood (SFEC). The association between the presence of ESES pattern on the EEG and the severity of the language impairment has not been adequately clarified. Methods: Twenty-eight SFEC cases without intellectual and motor disabilities and 32 healthy children were recruited. Cases with active ESES (A-ESES, n=6) and without ESES pattern on EEG (non-ESES, n=22) were compared in terms of clinical features and linguistic parameters by both standard and descriptive assessment tools. Results: The only significantly different clinical feature in the A-ESES group was the increased prevalence of polytherapy. While most of the linguistic parameters were impaired in A-ESES and non-ESES groups compared to healthy controls, A-ESES patients differed from non-ESES patients only in terms of decreased complex sentence production, which was assessed by narrative analysis. A-ESES patients also showed trends toward producing lower numbers of words, nouns, verbs, and adverbs during narrative analysis. There were no differences among patients under polytherapy and monotherapy in terms of these language parameters. Conclusion: Our results show that ESES increases the negative effect of chronic epilepsy on complex sentence and word production. Linguistic distortions that are not reflected in objective tests can be detected by narrative tools. Complex syntactic production obtained by narrative analysis is an important parameter that extensively characterizes language skills in school-age children with epilepsy.

18 F-FDG PET Brain Findings in a Case of Idiopathic Benign Rolandic Epilepsy of Childhood.

Idiopathic benign rolandic epilepsy, also known as benign childhood epilepsy with centrotemporal spikes (BCECTS), is one of the commonly seen electroclinical epilepsy syndromes of childhood with a generally favorable long-term prognosis. We describe a 5-year-old female child who presented with recurrent focal seizures involving right side of face since the age of 6 months. She had no perinatal or postnatal insults, had normal development, and her neurological examination was unremarkable. Electroencephalogram showed rolandic spikes, suggesting BCETCS. Her seizures remained refractory to two appropriately dosed antiepileptic drugs. Magnetic resonance imaging of the brain did not reveal any structural lesion. Interictal fluorodeoxyglucose 18 F-positron emission tomography brain showed hypometabolism in the left lower rolandic region.

Poor School Academic Performance and Benign Epilepsy with Centro-Temporal Spikes.

BACKGROUND: Poor academic performance of students with epilepsy seems to be a multifactorial problem related to difficulties in reading, writing, math, and logic skills. Poor school and academic performances refer to learning problems in a specific academic area due to learning disorders and learning difficulties not excluding the ability to learn in a different manner during school and academic life. Sometimes, school, academic difficulties, and Rolandic epilepsy can coexist together, and there may be comorbidities. Consequently, the risk of impaired academic performance in people with epilepsy is high. METHODS: This review analyzed the relationship between Benign Epilepsy with Centro-Temporal Spikes (BECTS) and poor school and academic performance (PSAP) in children and adolescents (aged 6 to 19), and in adults (aged 20 to no age limit). The PRISMA guideline was used to guide our review strategy. RESULTS: This research shows that Benign Epilepsy with Centro-Temporal Spikes (BECTS) and poor school and academic performances are strongly correlated. An early onset age, as well as a long persistence of seizures, correlate more closely with PSAP. On the other hand, it appears that good pharmacological control of seizures and remission from the acute phase of the pathology support better school performance. CONCLUSIONS: This review highlights how neuropsychological aspects are also involved in patients with BECTS and PSAP, both in the greater predisposition to the establishment of other neuropsychiatric conditions and in the possibility that stigma conditions and poor academic results may have repercussions on the adaptation and functioning of these subjects. Global management of the subject with BECTS and PSAP is essential, which also pays attention to the aspects of social and scholastic inclusion, both to achieve age-appropriate educational and behavioral objectives, to give the necessary tools for the growth of the individual, and to allow a serene transition to adulthood, favoring autonomous learning and better outcomes.

GRIN2A-related epilepsy and speech disorders: A comprehensive overview with a focus on the role of precision therapeutics.

Language dysfunction is a common and serious comorbidity of epilepsy, especially in individuals with epilepsy aphasia spectrum syndromes. Childhood epilepsy with centrotemporal spikes is on the mild end of the spectrum, while epileptic encephalopathy with continuous spike-and-wave during sleep syndrome is on the severe end. Traditional antiseizure medicines and immunotherapy are currently used to treat severely affected patients, but the results are usually disappointing. The discovery that GRIN2A is the primary monogenic etiology of these diseases has opened the door to precision treatments. The GRIN2A gene encodes GluN2A protein, which constitutes a subunit of the NMDA receptor (NMDAR). The GRIN2A pathogenic variants cause gain or loss of function of NMDAR; the former can be treated with uncompetitive NMDAR antagonists, such as memantine, while the latter with NMDAR co-agonist serine. Hyper-precision therapies with various other effective agents are likely to be developed shortly to target the diverse functional effects of different variants. Precision treatments for GRIN2A-related disorders will benefit those who suffer from the condition and pave the way for new therapeutic approaches to a variety of other NMDAR-linked neurodegenerative and psychiatric diseases (schizophrenia, Parkinson's disease, Alzheimer's disease, and so on). Furthermore, more research into GRIN2A-related disorders will help us better understand the neuroinflammatory and neuroimmunological basis of epilepsy, as well as the pathological and physiological network activation mechanisms that cause sleep activation of central-temporal spikes and language impairment.

Epilepsy syndromes in cerebral palsy: varied, evolving and mostly self-limited.

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.

Genotype and phenotype analysis of epilepsy caused by ADGRV1 mutations in Chinese children.

OBJECTIVE: To investigate the genotype and phenotype of epilepsy caused by ADGRV1 variants in Chinese children. METHODS: A total of 625 patients with epilepsy who had undergone whole-exon gene sequencing or epilepsy and related paroxysmal disease gene panel sequencing were recruited. Variants were evaluated for susceptibility pathogenicity based on their frequency in the Genome Aggregation Database (≤ 0.001). We used six algorithms (sorting intolerant from tolerant (SIFT), PolyPhen-2, Mutation Taster, CADD, REVEL and Splice AI) that predicted that the ADGRV1 variant would have a harmful impact on the function of genes and gene products. We retrospectively reviewed the clinical information of patients with susceptible pathogenic ADGRV1 variants. The relationship between the genotype and phenotype was also analyzed. RESULTS: Eighteen patients with epilepsy were found to have likely pathogenic variants in ADGRV1. The rate of ADGRV1 variants in patients with epilepsy in this cohort was 2.88%. A total of 19 ADGRV1 variants were found, of which 13 were novel and 6 had been previously reported. Eleven out of the 18 children (61.1%) had febrile and afebrile seizures (FS and AS), two children had only FS, one child had infantile spasms, and the other four children had only AS that occurred during sleep (Rolandic epilepsy or atypical Rolandic epilepsy). SIGNIFICANCE: Our study showed a statistically significant association between ADGRV1 variants and FS and AS (p < 0.05), supporting the hypothesis that ADGRV1 is a susceptibility gene for Rolandic epilepsy and infantile spasms. Most epilepsy cases caused by ADGRV1 variants have a good prognosis.

Connectivity increases during spikes and spike-free periods in self-limited epilepsy with centrotemporal spikes.

OBJECTIVE: To understand the impact of interictal spikes on brain connectivity in patients with Self-Limited Epilepsy with Centrotemporal Spikes (SeLECTS). METHODS: Electroencephalograms from 56 consecutive SeLECTS patients were segmented into periods with and without spikes. Connectivity between electrodes was calculated using the weighted phase lag index. To determine if there are chronic alterations in connectivity in SeLECTS, we compared spike-free connectivity to connectivity in 65 matched controls. To understand the acute impact of spikes, we compared connectivity immediately before, during, and after spikes versus baseline, spike-free connectivity. We explored whether behavioral state, spike laterality, or antiseizure medications affected connectivity. RESULTS: Children with SeLECTS had markedly higher connectivity than controls during sleep but not wakefulness, with greatest difference in the right hemisphere. During spikes, connectivity increased globally; before and after spikes, left frontal and bicentral connectivity increased. Right hemisphere connectivity increased more during right-sided than left-sided spikes; left hemisphere connectivity was equally affected by right and left spikes. CONCLUSIONS: SeLECTS patient have persistent increased connectivity during sleep; connectivity is further elevated during the spike and perispike periods. SIGNIFICANCE: Testing whether increased connectivity impacts cognition or seizure susceptibility in SeLECTS and more severe epilepsies could help determine if spikes should be treated.

Childhood Absence Epilepsy Associated With Concomitant Centrotemporal Spikes.

Objectives The coexistence of generalized epileptiform discharges of 3Hz spike-and-wave complexes, which are the hallmark of childhood absence epilepsy (CAE), and centrotemporal spikes, which are characteristic of benign epilepsy with centrotemporal spikes (BECTs) in the same or subsequent EEGs appears to be very rare. Only a few published reports have shown a possible concomitance of CAE and BECTs electrographic changes. The study aimed to analyze electrographic and clinical features of patients with CAE who had concomitant or subsequent EEG features of BECTs. Method During a five-year analysis period (2014-2018), 277 children with BECTs and 93 children with CAE were diagnosed and treated at the pediatric neurology unit of Sultan Qaboos University Hospital (SQUH) in Muscat, Oman. Nine patients were identified to have overlapping EEG findings of both epileptic syndromes. We then analyzed the nine children's clinical features, outcomes, and EEG findings in detail. Results The clinical onset of all our patients aged 5-14 years (six boys, three girls) was characterized by the absence of seizures, either typical (seven children) or atypical (two children). Six out of nine patients presented with concomitant electrographic features of both syndromes, whereas three patients experienced the EEG pattern of two syndromes at different times. All nine children were treated with valproate as the first-line medication, with reasonable seizure control. However, three patients required a second add-on medication. Despite good seizure control, six of our patients had poor school performance and five children had comorbid conditions such as ADHD and learning disability. Conclusion The coexistence of CAE and BECTS is described in the literature albeit rare. This overlap is mostly in electrographic features with or without the clinical features seen in both syndromes.

Alterations in the default mode network in rolandic epilepsy with mild spike-wave index in non-rapid eye movement sleep.

Purpose: Rolandic epilepsy (RE) is one of the most common epilepsy syndromes during childhood. The aim of this study was to investigate the alterations in the default mode network (DMN) of RE patients whose spike-wave index (SWI) was within the 50-85% range during non-rapid eye movement (NREM) during sleep, as well as to detect early neuroimaging markers. Methods: Resting-state data was recorded for each subject using magnetoencephalography (MEG). DMN-related brain regions were chosen as regions of interest. The spectral power and functional connectivity (FC) of the DMN were estimated through the use of minimum norm estimation (MNE) combined with Welch technique and corrected amplitude envelope correlation (AEC-c). Results: The patient group included 20 patients with NREM phase 50% ≤ SWI < 85% (mild SWI group), and 18 typical RE patients (SWI < 50% group). At the regional level, the mild SWI group exhibited enhanced spectral power in the delta band of the bilateral posterial cingulate cortex and attenuated the spectral power in the alpha band of the bilateral posterial cingulate cortex. Enhanced spectral power in the bilateral precuneus (PCu) in the delta band and attenuated spectral power in the right lateral temporal cortex (LTC) in the alpha band were common across all RE patients. At the FC level, patients in the mild SWI group indicated increased AEC-c values between the bilateral posterial cingulate cortex in the delta band and between the left medial frontal cortex (MFC) and bilateral posterial cingulate cortex in the alpha band. Increased AEC-c values between the right PCu and left MFC in the delta band, and between the left PCu and right MFC in the theta band, were common across all RE patients. Moreover, the spectral power in the bilateral posterial cingulate cortex in the alpha band and the AEC-c value between the bilateral posterial cingulate cortex in the delta band demonstrated good discrimination ability. Conclusion: The spectral power of the bilateral posterior cingulate cortex (PCC) in the alpha band and the AEC-c value between the bilateral PCC in the delta band may be promising indicators of early differentiation between mild SWI and typical RE.

Brain magnetic resonance imaging findings and brain volumetric differences in a large series of benign rolandic epilepsy.

BACKGROUND: Several studies with a small sample size have investigated the relationship between structural and functional changes on MRI and the clinical and natural history of BRE. We aim to assess the frequency of incidental epileptogenic lesions on brain MRI in a large cohort of patients diagnosed with BRE and to assess the difference in volumetric brain measurements in BRE patients compared to healthy controls. METHODS: The case-control study includes 214 typical BRE cases and 197 control children with non-epileptic spells. Brain MRIs were evaluated for abnormalities which were classified into normal and abnormal with or without epileptogenic lesions with categorization of epileptogenic lesions. Brain segmentation was also performed for a smaller group of BRE patients and another healthy control group. Pearson's chi-squared test and two-tailed independent samples t-test were used. RESULTS: In patients with BRE, 7% had an epileptogenic lesion on their MRI. The frequency of epileptogenic lesion in the control group was 10.2% and not significantly different from those with BRE (p= 0.2). Significantly higher intracranial and white matter volumes were found in BRE patients compared to the healthy group while lower gray matter volume was found in BRE patients. Cortical and subcortical regions showed either higher or lower volumes with BRE. Interestingly, altered subcallosal cortex development which has a known association with depression was also found in BRE. CONCLUSIONS: Our findings confirm the absence of any association between specific brain MRI abnormalities and BRE. However, the altered cortical and subcortical development in BRE patients suggests a microstructural-functional correlation.