Centrotemporal Spikes Research Articles

Language Performance and Disruption of Brain Connectivity in Children with Epilepsy

Abstract Objective To explore the correlation between brain connectivity and language difficulties in children with epilepsy. We hypothesize that the epileptic cortex (where seizures arise) becomes hyperconnected to left frontal and temporal language regions thus suppressing connectivity between language regions. We expect that connectivity is associated with language performance. Method Right-handed children with Self-Limited Epilepsy with Centrotemporal Spikes (SeLECTS) recruited from a specialty clinic, and typically developing age and sex-matched controls (63 children, 9.3+/−2 years, 37% female) recruited from the community completed a language task (verb generation) and a resting task while undergoing an electroencephalogram. Phonological awareness was measured with the CTOPP-2. Connectivity between four regions – left frontal & temporal language regions and bilateral motor regions (epileptic cortices) – was measured using the weighted Phase Lag Index. We tested for group differences in connectivity in either task and for associations between connectivity and phonological awareness. Results SeLECTS had higher left frontal to left temporal connectivity than controls during verb generation (group difference = 0.07, 95% CI 0.02–0.11, p = 0.003) but not at rest. Right motor to left temporal connectivity was elevated in SeLECTS during verb generation (difference = 0.04, 95% CI 0.01–0.07, p = 0.008) and rest (difference = 0.03, 95% CI 0.01–0.05, p = 0.001). Higher right motor to left temporal (−55.8, 95% CI -81.5 to −30.1, p < 0.0001) connectivity during verb generation was associated with poorer phonological awareness in SeLECTS but not controls. Resting connectivity was not associated with phonological awareness in either group. Conclusions Hyperconnectivity may contribute to language difficulties and electroencephalogram may be a biomarker for phonological awareness in children with epilepsy.

Epidemiology of self-limited epilepsy with centrotemporal spikes (SeLECTS): A population study using primary care records

Background and objectiveInformation on self-limited epilepsy with centrotemporal spikes (SeLECTS) epidemiology is limited. We aimed to determine the incidence of SeLECTS in children, its association with socioeconomic deprivation and the prevalence of neurodevelopmental comorbidities. MethodWe performed a retrospective cohort study (2004–2017) using anonymised, linked, routinely collected, primary care and demographic data for children in Wales. We used primary care diagnosis codes to identify children (aged 0–16 years) with SeLECTS and other epilepsies and to record antiseizure medication (ASM) prescriptions and neurodevelopmental comorbidities. We used a mixed effects Poisson regression model to determine temporal trends of SeLECTS incidence and its association with socioeconomic deprivation. ResultsWe identified 6,732 children with epilepsy, 186 (3%) with SeLECTS. In 2017, epilepsy and SeLECTS prevalence was 0.55% and 0.02% respectively with corresponding crude incidence of 51.2/100,000/year and 1.1/100,000/year. The incidence of epilepsy in children decreased with decreasing deprivation with an adjusted incidence rate ratio (AIRR) of 0.72 (95% CI 0.64–0.82) in the least deprived compared with the most deprived quintile. The corresponding AIRR for children with SeLECTS was 1.35 (95% CI 0.46–1.99). 34% of children with epilepsy, 18% of children with SeLECTS and 3% of all children in Wales had a neurodevelopmental disorder and or school problems. Half of children with SeLECTS were treated with ASM. ConclusionsWe identified a lower than previously reported incidence of SeLECTS, which may be due to under-recording of SeLECTS. There was no change in the incidence of SeLECTS over time, whilst the incidence of childhood epilepsy overall was decreasing. There was no significant association between incidence of SeLECTS and deprivation but the modest sample size needs to be considered. Children with SeLECTS should be screened for neurodevelopmental and or learning comorbidities. Treatment for SeLECTS remains debatable.

Repetitive Transcranial Magnetic Stimulation Modulates Brain Connectivity in Children with Self-limited Epilepsy with Centrotemporal Spikes.

Interictal epileptiform discharges (IEDs) alter brain connectivity in children with epilepsy; this connectivity change may be a mechanism by which epilepsy induces cognitive deficits. Here, we test whether repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique, modulates connectivity and reduces IEDs in children with epilepsy. Nineteen children with self-limited epilepsy with centrotemporal spikes (SeLECTS) participated in a cross-over study comparing the impact of active vs. sham rTMS on IEDs and brain connectivity. SeLECTS is an epilepsy syndrome affecting the motor cortex, and prior studies show that motor cortices become pathologically hyper-connected to frontal and temporal language cortices. Using a crossover design, we compared the effect of single doses of active versus sham motor cortex rTMS. Connectivity, which was quantified by the weighted phase lag index (wPLI), was measured before and after rTMS using single pulses of TMS combined with EEG (spTMS-EEG). Analyses focused on six regions: bilateral motor cortices and bilateral inferior frontal and superior temporal regions. IEDs were counted in the five minutes before and after rTMS. Active, but not sham, rTMS significantly and globally decreased wPLI connectivity between multiple regions, with the greatest reductions seen in the superior temporal region connections in the stimulated hemisphere. Additionally, there was a trend suggesting that rTMS decreases IED frequency. These findings underscore the potential of low-frequency rTMS to target pathologic hyperconnectivity and reduce IEDs in children with SeLECTS and potentially other pediatric epilepsy syndromes, offering a promising avenue for therapeutic intervention.

Sudden unexpected death in epilepsy (SUDEP) in childhood—occurrence in association with self-limiting epilepsy with centrotemporal spikes (seLECTS)

Sudden unexpected death in epilepsy (SUDEP) in childhood—occurrence in association with self-limiting epilepsy with centrotemporal spikes (seLECTS)

Sleep, cognitive functions, behavioral, and emotional disturbance in self-limited focal childhood epilepsies

BackgroundSelf-limited focal epilepsies of childhood, including self-limited epilepsy with centrotemporal spikes (SeLECTS), idiopathic childhood occipital epilepsy of Gastaut (ICOE-G), and self-limited epilepsy with autonomic seizures (SeLEAS), were considered benign conditions. However, recent research assumed potential adverse impacts on sleep, cognition, behavior, and emotional well-being. Our aim was to investigate the effects of self-limited focal epilepsies on sleep architecture, cognitive functions, behavior, and emotional disturbances in drug naive children. A cross-sectional study was conducted on 46 newly diagnosed children (ages 6–12) with SeLECTS (n = 22), ICOE-G (n = 12), SeLEAS (n = 12), and 20 healthy controls. Overnight polysomnography was performed. Cognitive assessments included intelligence scales, executive function tests, verbal fluency, visuospatial abilities, and memory. Behavioral and emotional problems were evaluated using standardized questionnaires and psychiatric interviews.ResultsChildren with epilepsy exhibited significant disturbances in sleep architecture, impairments in cognitive domains (executive functions, verbal fluency, visuospatial skills, and memory), and higher rates of internalizing/externalizing problems, social issues, attention deficit hyperactive disorder, depression, and anxiety compared to controls. No significant differences were found among the three epilepsy subtypes.ConclusionSelf-limited focal epilepsies in childhood are associated with sleep disruption, cognitive deficits, behavioral issues, and psychiatric comorbidities, challenging their traditional "benign" perception. Comprehensive management approaches addressing these multidimensional impacts are warranted.

From brain connectivity to cognitive function: Dissecting the salience network in pediatric BECTS-ESES

BackgroundBenign childhood epilepsy with centrotemporal spikes (BECTS), a common pediatric epilepsy, may lead to cognitive decline when compounded by Electrical Status Epilepticus during Sleep (ESES). Emerging evidence suggests that disruptions in the Salience Network (SN) contribute significantly to the cognitive deficits observed in BECTS-ESES. Our study rigorously investigates the dynamic functional connectivity (dFC) within the SN and its correlation with cognitive impairments in BECTS-ESES, employing advanced neuroimaging and neuropsychological assessments. MethodsIn this research, 45 patients diagnosed with BECTS-ESES and 55 age-matched healthy controls (HCs) participated. We utilized resting-state functional magnetic resonance imaging (fMRI) and Independent Component Analysis (ICA) to identify three fundamental SN nodes: the right Anterior Insula (rAI), left Anterior Insula (lAI), and the Anterior Cingulate Cortex (ACC). A two-sample t-test facilitated the comparison of dFC between these pivotal regions and other brain areas. ResultsSignificantly, the BECTS-ESES group demonstrated increased dFC, particularly between the ACC and the right Middle Occipital Gyrus, and from the rAI to the right Superior Parietal Gyrus and Cerebellum, and from the lAI to the left Postcentral Gyrus. Such dFC augmentations provide neural insights potentially explaining the neuropsychological deficits in BECTS-ESES children. Employing comprehensive neuropsychological evaluations, we mapped these dFC disruptions to specific cognitive impairments encompassing memory, executive functioning, language, and attention. Through multiple regression analysis and path analysis, a preliminary but compelling association was discovered linking dFC disturbances directly to cognitive impairments. These findings underscore the critical role of SN disruptions in BECTS-ESES cognitive dysfunctions. LimitationOur cross-sectional design and analytic methods preclude definitive mediation models and causal inferences, leaving the precise nature of dFC's mediating role and its direct impact by BECTS-ESES partially unresolved. Future longitudinal and confirmatory studies are needed to comprehensively delineate these associations. ConclusionOur study heralds dFC within the SN as a vital biomarker for cognitive impairment in pediatric epilepsy, advocating for targeted cognitive-specific interventions in managing BECTS-ESES. The preliminary nature of our findings invites further studies to substantiate these associations, offering profound implications for the prognosis and therapeutic strategies in BECTS-ESES, thereby underlining the importance of this research in the field of pediatric neurology and epilepsy management.

Neurocognitive effects and electrophysiological findings in ADHD and self-limiting centrotemporal spike wave epilepsy (SeLECTS) − A prospective tertiary care study

ObjectiveThe study aimed to determine the prevalence of attention deficit hyperactivity disorder (ADHD) in patients with self-limiting epilepsy with centrotemporal spike wave (SeLECTS), as well as the electroclinical features associated with this comorbid condition and the neurocognitive effects using psychometric tests. Additionally, we analysed the electrophysiological findings and neurocognitive status of patients with ADHD to estimate the prevalence of epilepsy and neurocognitive effects in the ADHD population and evaluate their clinical features. MethodThe study included patients diagnosed with SeLECTS and ADHD who were matched for age and gender. Electrophysiological tests, psychometric tests, demographic and clinical characteristics of SeLECTS patients aged 7–13 years and ADHD patients of similar age were analysed. The study examined electrophysiological and psychometric tests, as well as demographic and clinical characteristics. Both groups underwent testing using the Wechsler Intelligence Scale for Children (WISC-R), Stroop Colour and Word Test (SCWT), and EEG (Electroencephalogram). The SeLECTS group also underwent the Bender Visual-Motor Gestalt Test. ResultsNo significant relationship was found between the SeLECTS and ADHD groups in terms of age and gender. The rate of epileptiform discharge in EEG findings without a diagnosis of epilepsy was 5.6 % (n = 2) in the ADHD group. The rate of ADHD in the SeLECTS group was 28 % (n = 11).Although all subsections of the WISCR test were higher in the ADHD patient group than in the SeLECTS patient group, only verbal IQ and total IQ showed a significant difference. No significant differences were found between the completion times, error rates, and correction averages of the SCWT sections in both groups.There was no significant correlation found between the performance IQ, verbal IQ, and total intelligence scores in either the isolated SeLECTS patient group or the SeLECTS + ADHD patient group (p > 0.05). However, it is worth noting that verbal IQ was below normal in both groups and slightly lower in the SeLECT + ADHD group. Additionally, the mean SCWT completion time was significantly longer in the SeLECT + ADHD group than in the isolated SeLECTS group. However, no significant difference was found in the Bender Gestalt Visual Motor Perception Test.In the psychometric analyses comparing the isolated SeLECTS, SeLECT + ADHD, and ADHD patient groups, the SCWT completion times were significantly longer in the SeLECT + ADHD group than in the other two groups. The verbal IQ score was significantly higher in the ADHD group than in the other two groups. ConclusionIn conclusion, although SeLECTS is commonly considered a benign form of epilepsy, our study found a high rate of comorbidity with ADHD. This condition has a negative impact on verbal intelligence and sustained attention, highlighting the importance of a complete neuropsychological evaluation at the stage of epilepsy diagnosis. It is crucial not to overlook the possibility of an ADHD diagnosis.

Genetik und genetische Diagnostik fokaler Epilepsien des Kindesalters

AbstractSelf-limiting focal epilepsies are among the most common forms of epilepsy in children. Based on family studies, a genetic basis is assumed for the epilepsy as well as the typical electroencephalographic (EEG) feature of centrotemporal spikes, although complex inheritance and possibly additional influencing factors must be considered. Variants in GRIN2A, encoding the GluN2A subunit of the N‑methyl-D-aspartate (NMDA) glutamate receptor, represent the most important genetic risk factor to date. With memantine for variants with a gain-of-function effect and L‑serine for loss-of-function variants, two personalized therapeutic approaches are potentially available. Their effectiveness and significance need to be clarified in further investigations and clinical trials.

Epilepsy, EEG and chromosomal rearrangements.

Chromosomal abnormalities are associated with a broad spectrum of clinical manifestations, one of the more commonly observed of which is epilepsy. The frequency, severity, and type of epileptic seizures vary according to the macro- and microrearrangements present. Even within a single chromosomal anomaly, we most often deal with a phenotypic spectrum. The aim of the study was to look for chromosomal rearrangements with a characteristic electroencephalographic pattern. Only a few disorders have peculiar electroclinical abnormalities: 1p36, 4p16, 6q terminal or trisomy 12p, Angelman syndrome, inv dup 15, 15q13.3 deletions, ring 20, Down syndrome, or Xp11.22-11.23 duplication. We also reviewed studies on epileptic seizures and typical electroencephalographic patterns described in certain chromosomal rearrangements, focusing on the quest for potential electroclinical biomarkers. The comprehensive review concludes with clinical presentations of the most common micro and macro chromosomal rearrangements, such as 17q21.31 microdeletion, 6q terminal deletion, 15q inv dup syndrome, 2q24.4 deletion, Xp11.22-11.23 duplication, 15q13.3 microdeletion, 1p36 terminal deletion, 5q14.3 microdeletion, and Xq28 duplication. The papers reviewed did not identify any specific interictal electroencephalographic patterns that were unique and significant biomarkers for a given chromosomal microrearrangement. The types of seizures described varied, with both generalized and focal seizures of various morphologies being reported. Patients with chromosomal anomalies may also meet the criteria for specific epileptic syndromes such as Infantile Epilepsy Spasms Syndrome (IESS, West syndrome): 16p13.11, 15q13.3 and 17q21.31 microdeletions, 5q inv dup. syndrome; Dravet syndrome (2q24.4 deletion), Lennox-Gastaut syndrome (15q11 duplication. 1q13.3, 5q inv dup.); or Self-Limited Epilepsy with Autonomic Features (SeLEAS, Panayiotopoulos syndrome: terminal deletion of 6q.n), Self-Limited Epilepsy with Centrotemporal Spikes (SeLECT): fragile X syndrome. It is essential to better characterize groups of patients to more accurately define patterns of epilepsy and EEG abnormalities. This could lead to new treatment strategies. Future research is required to better understand epileptic syndromes and chromosomal rearrangements. PLAIN LANGUAGE SUMMARY: This paper presents EEG recording abnormalities in patients with various gene abnormalities that can cause epilepsy. The authors summarize these EEG variations based on a literature review to see if they occur frequently enough in other chromosomal abnormalities (in addition to those already known) to be a clue for further diagnosis.

Associations of glymphatic function with structural network and cognition in self-limited epilepsy with centrotemporal spikes

PurposeTo investigate glymphatic function by Virchow-Robin space (VRS) counts and volume in patients with newly diagnosed self-limited epilepsy with centrotemporal spikes (SeLECTS) and evaluate its relationship with structural connectivity and cognitive impairment. MethodsThirty-two children with SeLECTS and thirty-two age- and sex-matched typically developing (TD) children were enrolled in this study. VRS counts and volume were quantified. Structural networks were constructed and the topological metrics were analyzed. Wechsler Intelligence Scale (WISC) was used to assess cognitive function in all participants. Correlation analysis assessed the association between VRS counts and volume, network connectivity, and cognitive impairment. Mediation effects of topological metrics of the structural networks on the relationship between glymphatic function and cognitive impairment were explored. ResultsPatients with SeLECTS showed a higher VRS counts, VRS volume, and global shortest path length (Lp); they also showed a lower global efficiency (Eg). VRS counts and volume were significantly correlated with full-scale intelligence quotient (FIQ) (r_VRS counts = -0.520, r_VRS volume = -0.639), performance intelligence quotient (PIQ) (r_VRS counts = -0.693, r_VRS volume = -0.597), verbal intelligence quotient (VIQ) (r_VRS counts = -0.713, r_VRS volume = -0.699), Eg (r_VRS counts = -0.499, r_VRS volume = -0.490), and Lp (r_VRS volume = 0.671) in patients with SeLECTS. Eg mediated 24.59% of the effects for the relationship between VRS volume and FIQ. ConclusionGlymphatic function may be impaired in SeLECTS reflected by VRS counts and volume. Glymphatic dysfunction may result in cognitive impairment by disrupting structural connectivity in SeLECTS.

The Association Between Sleep Problems and Attentional Network Functions in Patients with Self-Limited Epilepsy with Centrotemporal Spikes.

To investigate sleep problems in children with self-limited epilepsy with central temporal spiking (SeLECTS) and to assess the relationship between sleep problems and attention network dysfunction. 107 children 6-14 years of age with SeLECTS and 90 age- and sex-matched healthy controls were recruited for this study. The sleep status of these participants was evaluated using the Children's Sleep Habits Questionnaire (CSHQ), while attentional network function was assessed with the attention network function test (ANT). Together, these analyses revealed that children with SeLECTS exhibited higher total CSHQ scores and sleep disorder incidence relative to healthy controls (P< 0.001). Children with SeLECTS had higher scores in delayed sleep onset, sleep duration, night awakenings, parasomnias, daytime sleepiness and sleep anxiety (P<0.01). Total CSHQ scores were negatively correlated with average ANT correct rates (ρ= -0.253, P<0.01), while they were positively correlated with total reaction time (ρ=0.367, P<0.01) and negatively correlated with the efficiency of the alerting and executive control networks (ρ=-0.344 P<0.01; ρ=-0.418 P<0.01). Children with SeLECTS face a higher risk of experiencing sleep disorders relative to age-matched healthy children, while also demonstrating that the magnitude of the impairment of attentional network function in these children is positively correlated with sleep disorder severity. Thus, the prognosis and quality of life of children with SeLECTS can be improved by interventions addressing sleep disorders.

Sulthiame use in children with pharmacoresistant epilepsies: A retrospective study.

This retrospective study aimed to assess the efficacy and tolerability of sulthiame as an add-on treatment in children with pharmacoresistant epilepsies. All patients with epilepsy who received sulthiame at Montreal Children's Hospital over an 11-year period were included. Medical charts were reviewed, and extracted data included patient age and sex, seizure types, epilepsy syndrome, electroencephalography (EEG) reports, brain imaging reports, antiseizure treatments trialed, starting and final dose of sulthiame, duration of sulthiame treatment, adverse events attributed to sulthiame, and seizure frequency before and after sulthiame treatment. EEG studies were also analyzed and spike-wave index (SWI) in the first 10 min of sleep was calculated. Sixteen patients were included, all of whom had pharmacoresistant epilepsies (mean of 9.9 trials of other antiseizure treatments). Six had genetic diagnoses, four had in utero/perinatal acquired brain injury, one had a suspected focal cortical dysplasia, and five were idiopathic. Ten patients had developmental and epileptic encephalopathy with spike-wave activation in sleep, three had Lennox-Gastaut syndrome, and one each had sleep-related hyperkinetic epilepsy, self-limited epilepsy with centrotemporal spikes, and mixed generalized and multifocal epilepsy. Of the 12 patients with uncontrolled seizures at the time of sulthiame initiation, 4 had improvement in seizure frequency, including 2 who became seizure free. Eight patients had EEG data available that allowed calculation of sleep SWI; from this group, SWI decreased from 81.1% +/- 17.6% to 45.1% +/- 36.5% (p = .007). The most common adverse events reported were somnolence/drowsiness, aggression, and increased seizure frequency. Of the patients with genetic etiologies, significant positive responses were seen in patients with pathogenic variants in NDUFS1 and SATB1. These data demonstrate the therapeutic potential of sulthiame, even in patients with highly pharmacoresistant epilepsy. Improvements may be seen in both seizure frequency and sleep SWI.

The influence of wakefulness fluctuations on brain networks involved in centrotemporal spike occurrence

ObjectiveDrowsiness has been implicated in the modulation of centro-temporal spikes (CTS) in Self-limited epilepsy with Centro-Temporal Spikes (SeLECTS). Here, we explore this relationship and whether fluctuations in wakefulness influence the brain networks involved in CTS generation. MethodsFunctional MRI (fMRI) and electroencephalography (EEG) was simultaneously acquired in 25 SeLECTS. A multispectral EEG index quantified drowsiness (‘EWI’: EEG Wakefulness Index). EEG (Pearson Correlation, Cross Correlation, Trend Estimation, Granger Causality) and fMRI (PPI: psychophysiological interactions) analytic approaches were adopted to explore respectively: (a) the relationship between EWI and changes in CTS frequency and (b) the functional connectivity of the networks involved in CTS generation and wakefulness oscillations. EEG analyses were repeated on a sample of routine EEG from the same patient’s cohort. ResultsNo correlation was found between EWI fluctuations and CTS density during the EEG-fMRI recordings, while they showed an anticorrelated trend when drowsiness was followed by proper sleep in routine EEG traces. According to PPI findings, EWI fluctuations modulate the connectivity between the brain networks engaged by CTS and the left frontal operculum. ConclusionsWhile CTS frequency per se seems unrelated to drowsiness, wakefulness oscillations modulate the connectivity between CTS generators and key regions of the language circuitry, a cognitive function often impaired in SeLECTS. SignificanceThis work advances our understanding of (a) interaction between CTS occurrence and vigilance fluctuations and (b) possible mechanisms responsible for language disruption in SeLECTS.

Minor Neurological Dysfunction: A Comparative Study in Pediatrics with Different Types of Focal Epilepsy

AbstractEpilepsy is a disorder that occurs as a result of abnormal neuronal discharges in the brain and affects approximately 1% of children. Sensorimotor function impairments that are related to minor neurological deficits may be seen even in children diagnosed with epilepsy solely. This study aims to determine the type and areas of minor neurological dysfunction (MND) in children with Self-Limited Focal Epilepsy (SeLFE) and to compare the children with Self-Limited Epilepsy with Centrotemporal Spikes (SeLECTS) and SeLFE without SeLECTS. Fifty-six children diagnosed with epilepsy (28 SeLECTS and 28 SeLFE without SeLECTS) were included in the study. Both groups consisted of 13 girls and 15 boys. The mean ages of SeLECTS and SeLFE without SeLECTS groups were 9.68 ± 1.63 and 9.32 ± 1.62, respectively. A Modified Touwen Neurological Examination was performed to determine the type and areas of MND. There were no differences between the groups regarding MND type, coordination, fine manipulation, sensory, and involuntary movement areas (p &gt; 0.05). It should be considered that children with SeLECTS may be neurologically affected as much as children with other types of epilepsy. Long-term problems due to epilepsy may be minimized by short-term neurodevelopmental follow-ups.

Efficacy and safety of adjunctive perampanel treatment in pediatric patients with epilepsy aged 4-12years: a real-world study.

To determine the efficacy and safety of perampanel (PER) as an adjunctive therapy in children aged 4-12years with epilepsy. We performed a non-randomized, open-label, placebo-uncontrolled, real-world self-controlled study that included 216 young children (aged 4-12years) with epilepsy who received PER as adjunctive therapy at the children's hospital affiliated with Chongqing Medical University from July 4, 2020, to September 20, 2023. (1) The efficacy rates of adjunctive PER therapy at 3, 6, 9, and 12months were 62.8%, 67.8%, 65.3%, and 61.2%, respectively. PER showed efficacy in alleviating focal seizures, generalized tonic-clonic seizures, myoclonic seizures, and absence seizures. The efficacy rates for variants of self-limited epilepsy with centrotemporal spikes (SeLECTS) and Lennox-Gastaut syndrome (LGS) were 89.5% and 66.7%, respectively. (2) Focal non-motor onset seizures with or without impaired awareness, focal to bilateral tonic-clonic seizures (FBTCS), LGS, variants of SeLECTS, the number of concomitant antiseizure medications (ASMs), a family history of epilepsy, and focal lesions on cranial magnetic resonance imaging were independent factors affecting efficacy. The order of PER addition did not affect efficacy. The retention rates at 3, 6, 9, and 12months were 90.7%, 84.7%, 74.7%, 64.9%, respectively. (3) Adverse reactions occurred in 45 patients (45/216, 20.8%), with irritability/aggressive behavior (18/216, 8.3%) and somnolence (14/216, 6.5%) being the most common. Twelve patients (12/216, 5.6%) withdrew from the study because of adverse reactions. In young Chinese children with epilepsy, PER is effective, safe, and well-tolerated as an adjunctive therapy, making it a viable option for use with broad-spectrum ASMs.

A novel splicing variant in MICAL-1 gene is associated with epilepsy

Germline MICAL1 defects have been rarely reported in patients with epilepsy and the genotype-phenotype association remains unclear. In this study, the patient was a 4.6 years old girl who presented with onset of recurrent focal seizures with onset at age 3.4 years. EEG showed abnormal δ-wave activity in the right central and middle temporal lobe. Trio WES showed a novel heterozygous variant c.-43-1G > A in the MICAL1 gene in the patient and her normal mother. Minigene verified two abnormal transcripts due to the mutation, which was predicted to interrupt 5′UTR structures of MICAL1. The patient was clinically diagnosed with benign childhood epilepsy with centrotemporal spike (BECTS). As far as we know, this is the first BECTS case with documented MICAL1 mutation. Novel MICAL1 variant c.-43-1G > A putatively interrupted MICAL1 translation by changing 5′UTR structures and, however, further functioning study is needed.

Combined diffusion tensor imaging and quantitative susceptibility mapping to characterize normal-appearing white matter in self-limited epilepsy with centrotemporal spikes.

In brain development, Myelination is the characteristic feature of white matter maturation, which plays an important role in efficient information transmitting. The white matter abnormality has been reported to be associated with self-limited epilepsy with centrotemporal spikes (SeLECTS). This study aimed to detect the altered white matter region in the SeLECTS patients by the combination of diffusion tensor imaging (DTI) and quantitative susceptibility mapping (QSM) technique. 27 children with SeLECTS and 23 age- and gender-matched healthy children were enrolled. All participants were scanned with 3.0-T MRI to acquire the structure, diffusion and susceptibility-weighted data. The susceptibility and diffusion weighted data were processed to obtain quantitative susceptibility map and fraction anisotropy (FA) map. Then voxel-wise tract-based spatial statistics (TBSS) were used to analyze quantitative susceptibility and FA data. Both DTI and QSM revealed extensive white matter alterations in the frontal, parietal, and temporal lobes in SeLECTS patients. The overlapped region of DTI and QSM analyses was located in the fiber tracts of the corona radiata. The FA values in this overlapped region were negatively correlated with the magnetic susceptibility values. Our results suggest that TBSS-based QSM can be employed as a novel approach for characterizing alterations in white matter in SeLECTS. And the combination of QSM and DTI can provide a more comprehensive evaluation of white matter integrity by utilizing different biophysical features.

Stability of transcranial magnetic stimulation electroencephalogram evoked potentials in pediatric epilepsy

Transcranial magnetic stimulation paired with electroencephalography (TMS–EEG) can measure local excitability and functional connectivity. To address trial-to-trial variability, responses to multiple TMS pulses are recorded to obtain an average TMS evoked potential (TEP). Balancing adequate data acquisition to establish stable TEPs with feasible experimental duration is critical when applying TMS–EEG to clinical populations. Here we aim to investigate the minimum number of pulses (MNP) required to achieve stable TEPs in children with epilepsy. Eighteen children with Self-Limited Epilepsy with Centrotemporal Spikes, a common epilepsy arising from the motor cortices, underwent multiple 100-pulse blocks of TMS to both motor cortices over two days. TMS was applied at 120% of resting motor threshold (rMT) up to a maximum of 100% maximum stimulator output. The average of all 100 pulses was used as a “gold-standard” TEP to which we compared “candidate” TEPs obtained by averaging subsets of pulses. We defined TEP stability as the MNP needed to achieve a concordance correlation coefficient of 80% between the candidate and “gold-standard” TEP. We additionally assessed whether experimental or clinical factors affected TEP stability. Results show that stable TEPs can be derived from fewer than 100 pulses, a number typically used for designing TMS-EEG experiments. The early segment (15–80 ms) of the TEP was less stable than the later segment (80–350 ms). Global mean field amplitude derived from all channels was less stable than local TEP derived from channels overlying the stimulated site. TEP stability did not differ depending on stimulated hemisphere, block order, or antiseizure medication use, but was greater in older children. Stimulation administered with an intensity above the rMT yielded more stable local TEPs. Studies of TMS-EEG in pediatrics have been limited by the complexity of experimental set-up and time course. This study serves as a critical starting point, demonstrating the feasibility of designing efficient TMS–EEG studies that use a relatively small number of pulses to study pediatric epilepsy and potentially other pediatric groups.

A novel RyR2 mutation associated with co-morbid catecholaminergic polymorphic ventricular tachycardia (CPVT) and benign epilepsy with centrotemporal spikes (BECTS)

In this case report, we describe a 14-year-old patient with a novel RyR2 gene mutation (c.6577G > T/p.Val2193Leu), identified through a comprehensive review of medical history, examination findings, and follow-up data. The pathogenic potential of this mutation, which results in the loss of some interatomic forces and compromises the closure of the RyR2 protein pore leading to calcium leakage, was analyzed using the I-TASSER Suite to predict the structural changes in the protein. This mutation manifested clinically as co-morbid catecholaminergic polymorphic ventricular tachycardia (CPVT) and benign epilepsy with centrotemporal spikes (BECTS), a combination not previously documented in the same patient. While seizures were successfully managed with levetiracetam, the patient's exercise-induced syncope episodes could not be controlled with metoprolol, highlighting the complexity and challenge in managing CPVT associated with this novel RyR2 variation.

Antiseizure Medications Normalize Electroencephalographic Functional Connectivity and Power in Children With Benign Epilepsy With Centrotemporal Spikes

BackgroundThe decision to treat children with benign epilepsy with centrotemporal spikes (BECTS) using antiseizure medications (ASM) is controversial. Our goal is to compare the effect of ASM treatment on the alteration of electroencephalographic (EEG) functional connectivity and power across four frequency bands in children with BECTS. MethodsChildren with BECTS with two-year follow-up were retrospectively divided into ASM versus non-ASM groups. The network properties of the EEGs as based on network-based statistic and graph theory were evaluated by the following indices: global efficiency, clustering coefficient, betweenness centrality, and nodal strength in four frequency bands (delta, theta, alpha, and beta). EEG power including absolute power (AP) and relative power (RP) was analyzed in four frequency bands. ResultsIn children with BECTS with ASM treatment, there was no significant change in EEG connectivity across all bands before and after two years of ASM. In children with BECTS without ASM treatment, there was a significant increase of global efficiency, clustering coefficient, and nodal strength but not the betweenness centrality in the delta band after two years of follow-up. A decrease in AP in the delta and theta bands and a decrease in RP in the theta band were found in the ASM group after two years of treatment. ConclusionsOur results suggest that ASM may play a role in modulating the development of increasing overall brain connectivity and in downregulating overt synaptic activity, but not intrinsic focal connectivity, in the early years of BECTS. The changes in the EEG power indicate that ASM significantly normalized slow-wave band power.