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

OBJECTIVE: Drowsiness 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. METHODS: Functional 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. RESULTS: No 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. CONCLUSIONS: While 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. SIGNIFICANCE: This work advances our understanding of (a) interaction between CTS occurrence and vigilance fluctuations and (b) possible mechanisms responsible for language disruption in SeLECTS.

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

BACKGROUND: The 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. METHODS: Children 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. RESULTS: In 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. CONCLUSIONS: Our 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.

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.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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.

Recognition memory deficits detected through eye-tracking in well-controlled children with self-limited epilepsy with centrotemporal spikes.

OBJECTIVE: Children with self-limited epilepsy characterized by centrotemporal spikes (SeLECTS) exhibit cognitive deficits in memory during the active phase, but there is currently a lack of studies and techniques to assess their memory development after well-controlled seizures. In this study, we employed eye-tracking techniques to investigate visual memory and its association with clinical factors and global intellectual ability, aiming to identify potential risk factors by examining encoding and recognition processes. METHODS: A total of 26 recruited patients diagnosed with SeLECTS who had been seizure-free for at least 2 years, along with 24 control subjects, underwent Wechsler cognitive assessment and an eye-movement-based memory task while video-electroencephalographic (EEG) data were recorded. Fixation and pupil data related to eye movements were utilized to detect distinct memory processes and subsequently to compare the cognitive performance of patients exhibiting different regression patterns on EEG. RESULTS: The findings revealed persistent impairments in visual memory among children with SeLECTS after being well controlled, primarily observed in the recognition stage rather than the encoding phase. Furthermore, the age at onset, frequency of seizures, and interictal epileptiform discharges exhibited significant correlations with eye movement data. SIGNIFICANCE: Children with SeLECTS exhibit persistent recognition memory impairment after being well controlled for the disease. Controlling the frequency of seizures and reducing prolonged epileptiform activity may improve memory cognitive development. The application of the eye-tracking technique may provide novel insights into exploring memory cognition as well as underlying mechanisms associated with pediatric epilepsy.

Connectivity Disturbances in Self-Limited Epilepsy with Centrotemporal Spikes: A Partial Directed Coherence Analysis of Electroencephalogram.

Although the remission of self-limited epilepsy with centrotemporal spikes (SeLECTS) usually occurs by adolescence, deficits in cognition and behavior are not uncommon. Several functional magnetic resonance imaging (fMRI) studies have revealed connectivity disturbances in patients with SeLECTS associated with cognitive impairment. However, the disadvantages of fMRI are expensive, time-consuming, and motion sensitive. In the current study, we used a partial directed coherence (PDC) method to analyze electroencephalogram (EEG) for exploring brain connectivity in patients with SeLECTS. This study enrolled 38 participants (19 patients with SeLECTS and 19 healthy controls) for PDC analysis. Our results demonstrated that the controls had significantly higher PDC inflow connectivity in the F7, T3, FP1, and F8 channels than patients with SeLECTS. By contrast, the patients with SeLECTS demonstrated significantly higher PDC inflow connectivity than did the controls in the T5, Pz, and P4 channels. We also compared the PDC connectivity in different Brodmann areas between the patients with SeLECTS and the controls. The results revealed that the inflow connectivity in the BA9_46_L area was significantly higher in the controls than in the patients with SeLECTS, whereas the inflow connectivity in the MIF_L area 4 was significantly higher in the patients with SeLECTS than in the controls. Our proposed approach of combining EEG with PDC provides a convenient and useful tool for investigating functional connectivity in patients with SeLECTS. This approach is time-saving and inexpensive compared with fMRI, but it achieves similar results to fMRI.

The Prevalence and Risk Factors of Electrical Status Epilepticus During Slow-Wave Sleep in Self-Limited Epilepsy With Centrotemporal Spikes.

Objective. To investigate the prevalence and risk factors for electrical status epilepticus during slow-wave sleep (ESES) in patients with self-limited epilepsy with centrotemporal spikes (SeLECTS). Methods. The clinical and follow-up data of children with SeLECTS were collected between 2017 and 2021. Patients were divided into typical ESES, atypical ESES, and non-ESES groups according to spike-wave indices (SWI). Clinical and electroencephalography characteristics were retrospectively analyzed. Logistic regression was used to identify risk factors for ESES. Results. A total of 95 patients with SeLECTS were enrolled. Seven patients (7.4%) developed typical ESES, 30 (31.6%) developed atypical ESES, 25 (26.3%) developed ESES at the first visit, and 12 (12.6%) developed ESES during treatment and follow-up. Multivariate logistic regression analysis showed that the risk factors for SeLECTS combined with ESES were Rolandic double or multiple spikes (OR = 8.626, 95% CI: 2.644-28.147, P < .001) and Rolandic slow waves (OR = 53.550, 95% CI: 6.339-452.368, P < .001). There were no significant differences in seizure characteristics, electroencephalogram (EEG) findings, or cognitive impairment between the atypical and typical ESES groups. Conclusion. More than one-third of the SeLECTS patients combined with ESES. Both atypical and typical ESES scores can affect cognitive function. On electroencephalography, interictal Rolandic double/multiple spikes and slow-wave abnormalities may indicate SeLECTS with ESES.

Interictal magnetic signals in new-onset Rolandic epilepsy may help with timing of treatment selection.

OBJECTIVE: With research progress on Rolandic epilepsy (RE), its "benign" nature has been phased out. Clinicians are exhibiting an increasing tendency toward a more assertive treatment approach for RE. Nonetheless, in clinical practice, delayed treatment remains common because of the "self-limiting" nature of RE. Therefore, this study aimed to identify an imaging marker to aid treatment decisions and select a more appropriate time for initiating therapy for RE. METHODS: We followed up with children newly diagnosed with RE, classified them into medicated and non-medicated groups according to the follow-up results, and compared them with matched healthy controls. Before beginning follow-up visits, interictal magnetic data were collected using magnetoencephalography in treatment-naïve recently diagnosed patients. The spectral power of the whole brain during initial diagnosis was determined using minimum normative estimation combined with the Welch technique. RESULTS: A difference was observed in the magnetic source intensity within the left caudal anterior cingulate and precentral and postcentral gyri in the delta band between the medicated and non-medicated groups. The results revealed good discriminatory ability within the receiver operator characteristic curve. In the medicated group, there was a specific change in the frontotemporal magnetic source intensity, which shifted from high to low frequencies, compared with the healthy control group. SIGNIFICANCE: The intensity of the precentral gyrus magnetic source within the delta band showed good specificity. Considering the rigor of initial treatment, the intensity of the precentral gyrus magnetic source can provide some help as an imaging marker for initial RE treatment, particularly for the timing of treatment initiation.

Care and three-year outcomes of children with Benign Epilepsy with Centro-Temporal Spikes in England.

PURPOSE: Benign Epilepsy with Centro-Temporal Spikes (BECTS) is a pediatric epilepsy with typically good seizure control. Although BECTS may increase patients' risk of developing neurological comorbidities, their clinical care and short-term outcomes are poorly quantified. METHODS: We retrospectively assessed adherence to National Institute for Health and Care Excellence (NICE) guidelines relating to specialist referral, electroencephalogram (EEG) conduct and annual review in the care of patients with BECTS, and measured their seizure, neurodevelopmental and learning outcomes at three years post-diagnosis. RESULTS: Across ten centers in England, we identified 124 patients (74 male) diagnosed with BECTS between 2015 and 2017. Patients had a mean age at diagnosis of 8.0 (95% CI = 7.6-8.4) years. 24/95 (25%) patients were seen by a specialist within two weeks of presentation; 59/100 (59%) received an EEG within two weeks of request; and 59/114 (52%) were reviewed annually. At three years post-diagnosis, 32/114 (28%) experienced ongoing seizures; 26/114 (23%) had reported poor school progress; 15/114 (13%) were diagnosed with a neurodevelopmental disorder (six autism spectrum disorder, six attention-deficit/hyperactivity disorder); and 10/114 (8.8%) were diagnosed with a learning difficulty (three processing deficit, three dyslexia). Center-level random effects models estimated neurodevelopmental diagnoses in 9% (95% CI: 2-16%) of patients and learning difficulty diagnoses in 7% (95% CI: 2-12%). CONCLUSIONS: In this multicenter work, we found variable adherence to NICE guidelines in the care of patients with BECTS and identified a notable level of neurological comorbidity. Patients with BECTS may benefit from enhanced cognitive and behavioral assessment and monitoring.

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.

Self-limited epilepsy with centrotemporal spikes.

Self-limited epilepsy with centrotemporal spikes (SeLECTS) is one of the most frequent epilepsies in childhood, characterised by typical clinical presentation with characteristic EEG findings. This review investigates the existing knowledge regarding cognitive function, the potential effect of anti-seizure medicines on cognitive development as well as prognosis of SeLECTS based on recent studies. There is evidence supporting that SeLECTS may not be as benign as previously assumed due to the possible neurocognitive comorbidities.

Konservativ behandling af læbelæsioner med substanstab.

Self-limited epilepsy with centrotemporal spikes (SeLECTS) is one of the most frequent epilepsies in childhood, characterised by typical clinical presentation with characteristic EEG findings. This review investigates the existing knowledge regarding cognitive function, the potential effect of anti-seizure medicines on cognitive development as well as prognosis of SeLECTS based on recent studies. There is evidence supporting that SeLECTS may not be as benign as previously assumed due to the possible neurocognitive comorbidities.

Atypical functional connectivity hierarchy in Rolandic epilepsy.

Functional connectivity hierarchy is an important principle in the process of brain functional organization and an important feature reflecting brain development. However, atypical brain network hierarchy organization in Rolandic epilepsy have not been systematically investigated. We examined connectivity alteration with age and its relation to epileptic incidence, cognition, or underlying genetic factors in 162 cases of Rolandic epilepsy and 117 typically developing children, by measuring fMRI multi-axis functional connectivity gradients. Rolandic epilepsy is characterized by contracting and slowing expansion of the functional connectivity gradients, highlighting the atypical age-related change of the connectivity hierarchy in segregation properties. The gradient alterations are relevant to seizure incidence, cognition, and connectivity deficit, and development-associated genetic basis. Collectively, our approach provides converging evidence for atypical connectivity hierarchy as a system-level substrate of Rolandic epilepsy, suggesting this is a disorder of information processing across multiple functional domains, and established a framework for large-scale brain hierarchical research.

Perampanel and lacosamide monotherapy in pediatric patients with newly diagnosed focal epilepsy: A prospective study evaluating efficacy, tolerability, and behavior.

PURPOSE: Perampanel (PER) and lacosamide (LCM) are the new third-generation anti-seizure medications (ASMs) that were approved for the monotherapy of focal epilepsy in children over four years of age in China, in 2021. Very few studies have analyzed the application of PER monotherapy among pediatric patients aged ≥four years, and no study compared the efficacy and tolerability of PER monotherapy with LCM monotherapy in pediatric patients with focal epilepsy. The present study aimed to investigate the efficacy, tolerability, and effect on behavior and emotion of PER and LCM as monotherapy in pediatric patients with newly diagnosed focal epilepsy, which is beneficial for clinicians to have more choices to treat pediatric patients with focal epilepsy. METHODS: This was a prospective, single-center, observational study that involved pediatric patients (disease onset age ≥four years) with newly diagnosed focal epilepsy treated with PER or LCM as primary monotherapy. Outcomes included retention, being responders, and seizure-free rates after 3, 6, and 12 months. Adverse events (AEs) were noticed throughout the follow-up period. Behavioral outcomes were evaluated with Achenbach Child Behavior Checklist (CBCL/4-16) at baseline and after three and six months. RESULTS: Using randomization, 60 patients receiving PER (31 females, 29 males, median age: 7.79 [5.34, 10.16] years, median dose: 3.0 [2.0, 4.0] mg/day) and 60 patients receiving LCM (25 females, 35 males, median age: 7.72 [5.91, 10.72] years, median dose: 150.0 [100.0, 200.0] mg/day) were enrolled in the study. At the 12-month follow-up, the retention rates in the PER and LCM groups, both were 90.4%, and the responder rates were 65.4% and 71.2%, while seizure-free rates were 57.7% and 67.3%, respectively. There were no significant differences in the retention, responder and seizure-free rates between the two groups (P > 0.05). There were no significant differences in the responder rates between patients with BECTS, abnormal brain magnetic resonance imaging (MRI), or types of seizure in the two groups (P > 0.05). In the PER group, 28.8% (15/52) of patients experienced AEs, of which the most frequently reported were irritability (n = 7; 13.5%), dizziness (n = 5; 9.6%), somnolence (n = 3; 5.8%), ataxia (n = 1; 1.9%), headache (n = 1; 1.9%), and rash (n = 1; 1.9%). In the LCM group, 15.4% (8/52) of the patients had AEs, including headache (n = 4; 7.5%), dizziness (n = 4; 7.5%), nausea (n = 2; 3.8%), somnolence (n = 2; 3.8%), irritability (n = 1; 1.9%), stomach ache (n = 1; 1.9%), and vomiting (n = 1; 1.9%). The incidence of irritability was significantly higher in the PER group than in the LCM group (13.5% vs. 1.9%, P = 0.031), which occurred mainly within eight weeks after drug administration. Patients with irritability were not dangerous to surrounding people by the assessment of parental observation in the life. And the symptoms were relieved spontaneously within a few months. The outcomes of total scores, internalizing scores, and externalizing scores of the CBCL did not show statistically significant differences in the PER and LCM groups between baseline and three and six months. Characteristics of behavior and emotion did not have substantial changes in patients treated with PER and LCM monotherapy. CONCLUSIONS: The present study documented similar good effectiveness and good tolerance of PER and LCM as monotherapy in pediatric patients with newly diagnosed focal epilepsy and showed no behavioral or emotional impact, as assessed by the CBCL. Though the incidence of irritability with PER monotherapy may be higher than that with LCM monotherapy soon after medication initiation, this side effect appears to resolve spontaneously within a few months. At present, this study was the first research about PER and LCM monotherapy in pediatric patients with newly diagnosed focal epilepsy evaluating efficacy, tolerability, and behavior in China.

Trends and hotspots in gene research of epilepsy in children: A review and bibliometric analysis from 2010 to 2022.

BACKGROUND: About 70% to 80% of epilepsy cases are related to genetic factors. Genetic research has revealed the genetic etiology and molecular mechanisms of childhood epilepsy, which has increased our understanding of childhood epilepsy. METHODS: We searched the core collection of Web of Science for relevant papers on genetic research on childhood epilepsy published since 2010 on November 30, 2022. In this study, original articles and reviews in English were included. Using CiteSpace and VOSviewer online tools, we conducted a bibliometric analysis of the countries, institutions, journals, co-cited journals, co-cited references, keywords, and research hotspots. RESULTS: We evaluated 2500 literatures on epilepsy genomics in children. Among them, 96 countries published relevant articles, with the United States ranking the most. A total of 389 institutions have contributed relevant publications, and the University of Melbourne has published the most papers. Epilepsy journals were the most commonly cited. The references of papers were clustered into 9 categories: gene testing, epileptic encephalopathy, Dravet syndrome, focal cortical dysplasia, Rolandic epilepsy, copy number variation, ketogenic diet, monogenic epilepsy, and ptt2 mutation. Burst keywords represent the frontier of research, including developmental and epileptic encephalopathy (2021-2022), neurodevelopmental disorders (2020-2022), gene testing (2020-2022), and whole-exome sequencing (2019-2022). CONCLUSION: This study conducted a systematic and objective bibliometric analysis of the literature on epilepsy gene research in children. More importantly, it revealed the hot spot, frontier, and future developmental trends in the field. It will help pediatricians and geneticists further understand the dynamic evolution of genetic research on pediatric epilepsy.

Decreased thalamocortical connectivity in resolved Rolandic epilepsy.

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

WISC-IV intellectual profiles in Italian children with self-limited epilepsy with centrotemporal spikes.

OBJECTIVE: This study aimed to describe the intellectual profile based on the Wechsler Intelligence Scale for Children 4th edition (WISC-IV) in children with self-limited epilepsy with centrotemporal spikes (SeLECTS), with an attempt to define possible predictive epilepsy-related variables of cognitive performance. METHODS: The WISC-IV was assessed in 161 children with SeLECTS and their cognitive profiles were compared to a matched sample of healthy control children. RESULTS: Children with SeLECTS performed within normal range across all indices, demonstrating particular strength based on the Perceptual Reasoning Index. Compared to healthy control children, we observed a significant difference in performance based on the Full Scale Intelligence Quotient, Verbal Comprehension Index and Processing Speed Index. Regarding epilepsy-related variables, earlier onset of epilepsy, use of anti-seizure medications, the presence of neurodevelopmental disorders, a higher frequency of seizures, and a longer treatment duration were associated with an overall lower level of performance. SIGNIFICANCE: Children with SeLECTS performed within the average range for cognitive assessment based on the WISC-IV, demonstrating that children had normal levels of global intelligence. However, compared to healthy control children, children with SeLECTS showed a slightly lower level of performance. Reasoning skills represented the relative strengths in children with SeLECTS. Predictors of intellectual performance in patients with SeLECTS include epilepsy-related variables and neurodevelopmental comorbidities.

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.

Language-related brain areas in childhood epilepsy with centrotemporal spikes studied with MEG.

OBJECTIVE: Children with self-limited epilepsy with centrotemporal spikes (SeLECTS) typically indicate cognitive impairment with widespread speech impairment. We explored how epilepsy affects language-related brain areas and areas in their vicinity. METHODS: Twenty-two children with SeLECTS and declined verbal comprehension (DVC), 21 with SeLECTS and normal verbal comprehension (NVC), and 23 healthy controls (HCs) underwent high-sampling magnetoencephalography recordings. According to a previous study, 24 language-related regions of interest were selected bilaterally, and the relative spectral power was estimated using a minimum norm estimate. RESULTS: The highest mean power spectral density was observed in the delta band for the DVC group, in the theta band for the NVC group, and in the alpha band for HCs within language-specific brain regions. The distinctions between the DVC and NVC groups in the delta and theta frequency bands were primarily concentrated in the right linguistic brain area. CONCLUSIONS: Children with SeLECTS may have developmental problems in language-related brain areas, with different developmental levels observed in the DVC, NVC, and HC groups. The DVC group could have inferior speech comprehension due to a more significant number of seizures and more left-sided spike locations. SIGNIFICANCE: Children having SeLECTS showed impaired brain maturation, leading to associated language impairment.