Factors associated with poor sleep in children with drug-resistant epilepsy.

OBJECTIVE: We aimed to investigate sleep in children with drug-resistant epilepsy (DRE), including developmental and epileptic encephalopathies (DEEs). Next, we examined differences in sleep macrostructure and microstructure and questionnaire outcomes between children with well-controlled epilepsy (WCE) and children with DRE. Furthermore, we wanted to identify factors associated with poor sleep outcome in these children, as some factors might be targets to improve epilepsy and neurodevelopmental outcomes. METHODS: A cross-sectional study was conducted in children 4 to 18-years-old. Children without epilepsy, with WCE, and with DRE were included. Overnight electroencephalography (EEG), including chin electromyography and electrooculography, to allow sleep staging, was performed. Parents were asked to fill out a sleep questionnaire. Classical five-stage sleep scoring was performed manually, spindles were automatically counted, and slow wave activity (SWA) in the first and last hour of slow wave sleep was calculated. RESULTS: One hundred eighty-two patients were included: 48 without epilepsy, 75 with WCE, and 59 with DRE. We found that children with DRE have significantly lower sleep efficiency (SE%), less time spent in rapid eye movement (REM) sleep, fewer sleep spindles, and a lower SWA decline over the night compared to children with WCE. Subjectively more severe sleep problems were reported by the caregivers and more daytime sleepiness was present in children with DRE. Least absolute shrinkage and selection operator (LASSO) regression showed that multifocal interictal epileptiform discharges (IEDs), benzodiazepine treatment, and longer duration of epilepsy were associated with lower SE% and lower REM sleep time. The presence of multifocal discharges and cerebral palsy was associated with fewer spindles. Benzodiazepine treatment, drug resistance, seizures during sleep, intellectual disability, and older age were associated with lower SWA decline. SIGNIFICANCE: Both sleep macrostructure and microstructure are severely impacted in children with DRE, including those with DEEs. Epilepsy parameters play a distinct role in the disruption REM sleep, spindle count, and SWA decline.

Efficacy and safety of corticosteroids and ACTH in epileptic syndromes beyond Infantile Epileptic Spasms Syndrome (IESS): A systematic review and meta-analysis.

We conducted a systematic review investigating the efficacy and tolerability of adrenocorticotropic hormone (ACTH) and corticosteroids in children with epilepsies other than infantile epileptic spasm syndrome (IESS) that are resistant to anti-seizure medication (ASM). We included retrospective and prospective studies reporting on more than five patients and with clear case definitions and descriptions of treatment and outcome measures. We searched multiple databases and registries, and we assessed the risk of bias in the selected studies using a questionnaire based on published templates. Results were summarized with meta-analyses that pooled logit-transformed proportions or rates. Subgroup analyses and univariable and multivariable meta-regressions were performed to examine the influence of covariates. We included 38 studies (2 controlled and 5 uncontrolled prospective; 31 retrospective) involving 1152 patients. Meta-analysis of aggregate data for the primary outcomes of seizure response and reduction of electroencephalography (EEG) spikes at the end of treatment yielded pooled proportions (PPs) of 0.60 (95% confidence interval [CI] 0.52-0.67) and 0.56 (95% CI 0.43-0.68). The relapse rate was high (PP 0.33, 95% CI 0.27-0.40). Group analyses and meta-regression showed a small benefit of ACTH and no difference between all other corticosteroids, a slightly better effect in electric status epilepticus in slow sleep (ESES) and a weaker effect in patients with cognitive impairment and "symptomatic" etiology. Obesity and Cushing's syndrome were the most common adverse effects, occurring more frequently in trials addressing continuous ACTH (PP 0.73, 95% CI 0.48-0.89) or corticosteroids (PP 0.72, 95% CI 0.54-0.85) than intermittent intravenous or oral corticosteroid administration (PP 0.05, 95% CI 0.02-0.10). The validity of these results is limited by the high risk of bias in most included studies and large heterogeneity among study results. This report was registered under International Prospective Register of Systematic Reviews (PROSPERO) number CRD42022313846. We received no financial support.

Structure-function interrelationships and associated neurotransmitter profiles in drug-naïve benign childhood epilepsy with central-temporal spikes patients.

OBJECTIVES: To explore the interrelationships between structural and functional changes as well as the potential neurotransmitter profile alterations in drug-naïve benign childhood epilepsy with central-temporal spikes (BECTS) patients. METHODS: Structural magnetic resonance imaging (sMRI) and resting-state functional MRI data from 20 drug-naïve BECTS patients and 33 healthy controls (HCs) were acquired. Parallel independent component analysis (P-ICA) was used to identify covarying components among gray matter volume (GMV) maps and fractional amplitude of low-frequency fluctuations (fALFF) maps. Furthermore, we explored the spatial correlations between GMV/fALFF changes derived from P-ICA and neurotransmitter maps in JuSpace toolbox. RESULTS: A significantly positive correlation (p < 0.001) was identified between one structural component (GMV_IC6) and one functional component (fALFF_IC4), which showed significant group differences between drug-naïve BECTS patients and HCs (GMV_IC6: p < 0.01; fALFF_IC4: p < 0.001). GMV_IC6 showed increased GMV in the frontal lobe, temporal lobe, thalamus, and precentral gyrus as well as fALFF_IC4 had enhanced fALFF in the cerebellum in drug-naïve BECTS patients compared to HCs. Moreover, significant correlations between GMV alterations in GMV_IC6 and the serotonin (5HT1a: p < 0.001; 5HT2a: p < 0.001), norepinephrine (NAT: p < 0.001) and glutamate systems (mGluR5: p < 0.001) as well as between fALFF alterations in fALFF_IC4 and the norepinephrine system (NAT: p < 0.001) were detected. CONCLUSION: The current findings suggest co-altered structural/functional components that reflect the correlation of language and motor networks as well as associated with the serotonergic, noradrenergic, and glutamatergic neurotransmitter systems. CLINICAL RELEVANCE STATEMENT: The relationship between anatomical brain structure and intrinsic neural activity was evaluated using a multimodal fusion analysis and neurotransmitters which might provide an important window into the multimodal neural and underlying molecular mechanisms of benign childhood epilepsy with central-temporal spikes. KEY POINTS: Structure-function relationships in drug-naïve benign childhood epilepsy with central-temporal spikes (BECTS) patients were explored. The interrelated structure-function components were found and correlated with the serotonin, norepinephrine, and glutamate systems. Co-altered structural/functional components reflect the correlation of language and motor networks and correlate with the specific neurotransmitter systems.

Reading and language profiles among children with epilepsy.

This study evaluated the profile of language and reading skills among children with epilepsy. We utilized a sample of children from an epilepsy database who were administered a measure of reading comprehension, excluding those whose intellectual skills were in the impaired range (N=147; age range 4-20 years, 52 % female). Additional measures that were considered within the sample included broad language skills, pre-reading skills (phonological processing, rapid naming, decoding), and basic reading skills (sight word reading, reading fluency). We further considered associations between these skills and seizure characteristics (age of onset, number of anti-seizure medications, seizure type, seizure frequency, and localization). We found that our sample performed significantly lower on all language and reading skills, on average, than normative expectations. Within our sample, relative strengths were noted in broad language skills, and relative weaknesses were found in phonological processing, rapid naming, reading fluency, word reading, and reading comprehension. We further identified a subgroup of our sample (31 %) who were characterized as struggling in reading comprehension (performing one standard deviation below the normative mean); these children exhibited a profile more consistent with non-epilepsy samples with reading disabilities/ dyslexia. Seizure variables that were associated with language and reading skills included age of onset, number of anti-seizure medications, seizure frequency, and having generalized (versus focal) seizures. These results have important implications for the identification and treatment of reading problems in children with epilepsy.

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.

Risk factors of electrical status epilepticus during sleep in children with benign childhood epilepsy with centro-temporal spikes.

Objective: To explore risk factors of electrical status epilepticus during sleep in children with benign childhood epilepsy with centro-temporal spikes (BECT). Methods: This is a clinical comparative study. The subjects of study were 67 children with BECT from the Outpatient Department of Pediatric Neurology in Xingtai People's Hospital from January 2019 to January 2022. According to the occurrence of ESES, the enrolled children were divided into control group which included BECT children without ESES and the observation group which included BECT children with ESES. Compared differences of the two groups in the age of first seizure, the frequency of seizures before treatment, the classification of treatment drugs, cranial MRI, and discharge side of electroencephalogram (EEG). Results: There was no statistical difference between the two groups in the frequency of seizures before treatment, the classification of treatment drugs, cranial MRI, and the distribution of EEG discharges in the left and right cerebral areas(P>0.05). Statistical differences were observed in the age of the first seizure, whether the seizures occurred after treatment, and EEG discharges in unilateral/bilateral cerebral areas (P<0.05). Furthermore, the collinearity test and Logistic regression analysis showed that the age of the first seizure, the frequency of seizures before treatment, and whether the seizures occurred after treatment were independent risk factors for the occurrence of ESES in BECT (P<0.05). Conclusion: Clinically, the occurrence of ESES in children with BECT may be related to the younger age of the first seizure, higher frequency of seizures before treatment, and the occurrence of seizures after treatment.

Wearable detection of tonic seizures in childhood epilepsy: An exploratory cohort study.

OBJECTIVE: To investigate the performance of a multimodal wearable device for the offline detection of tonic seizures (TS) in a pediatric childhood epilepsy cohort, with a focus on patients with Lennox-Gastaut syndrome. METHODS: Parallel with prolonged video-electroencephalography (EEG), the Plug 'n Patch system, a multimodal wearable device using the Sensor Dot and replaceable electrode adhesives, was used to detect TS. Multiple biosignals were recorded: behind-the-ear EEG, surface electromyography, electrocardiography, and accelerometer/gyroscope. Biosignals were annotated blindly by a neurologist. Seizure characteristics were described, and performance was assessed by sensitivity, positive predictive value (PPV), F1 score, and false alarm rate (FAR) per hour. Performance was compared to seizure diaries kept by the caretaker. RESULTS: Ninety-nine TS were detected in 13 patients. Seven patients (54%) had Lennox-Gastaut syndrome and six patients (46%) had other forms of (developmental) epileptic encephalopathies or drug-resistant epilepsy. All but one patient had intellectual disability. Overall sensitivity was 41%, with a PPV of 9%, an F1 score of 14%, and a median FAR per hour of 0.75. Performance increased to an F1 score of 66% for nightly seizures lasting at least 10 s (sensitivity 66%, PPV 66%) and 71% for nightly seizures lasting at least 20 s (sensitivity 62%, PPV 82%). For these seizures there were no false alarms in 10 of 13 patients. Sensitivity of seizure diaries reached a maximum of 52% for prolonged (≥20 s) nightly seizures, even though caretakers slept in the same room. SIGNIFICANCE: We showed that it is feasible to use a multimodal wearable device with multiple adhesive sites in children with epilepsy and intellectual disability. For prolonged nightly seizures, offline manual detection of TS outperformed seizure diaries. The recognition of seizure-specific signatures using multiple modalities can help in the development of automated TS detection algorithms.

Developing and maintaining health literacy: A continuous emotional, cognitive, and social process for parents of children with epilepsy-A qualitative study.

Childhood epilepsy is often complicated by neurobehavioral comorbidities, and parents are expected to actively engage in managing the condition. Insufficient parental health literacy (HL) has been associated with reduced health outcomes for children with epilepsy. Little is known about the parents' experiences of information seeking, social support, navigating the healthcare system, and interactions with healthcare professionals and how these skills may contribute to the development of sufficient HL. This study explored parents' experiences of their caregiver responsibility and the development of their HL in relation to caring for their child with epilepsy. Ten parents of children under 12 years of age with epilepsy were purposedly sampled and interviewed individually, using semi-structured interviews. The interviews were analyzed using qualitative content analysis, in line with Graneheim & Lundman. The analyses resulted in three themes, each comprising two sub-themes. The themes were: (1) Alone with the responsibility, (2) The combat for information and support, and (3) Developing vigilance and distrust in system competence. Lack of flexibility in healthcare services, insufficient multidisciplinary collaboration, and unclear treatment provider responsibility made the parents feel alone in the caregiver's responsibility. Poor local provider competence related to childhood epilepsy was a barrier to developing sufficient HL. A trusting relationship with professionals and timely access to competent health services were facilitators for developing HL. Higher HL made the parents more critical for the healthcare services, which triggered vigilance and reduced their trust in the professionals' information. For the parents, developing and maintaining HL was a continuous emotional, cognitive, and social process. Health information and care support need to be adjusted to the severity of the child's condition, the resources are available, and the parent's HL. The results of this study may contribute to the development of future interventions for strengthening parental HL in the childhood epilepsy context.

The association between early childhood onset epilepsy and attention-deficit hyperactivity disorder (ADHD) in 3237 children and adolescents with Autism Spectrum Disorder (ASD): a historical longitudinal cohort data linkage study.

Children and young people with Autism Spectrum Disorder (ASD) have an increased risk of comorbidities, such as epilepsy and Attention-Deficit/Hyperactivity Disorder (ADHD). However, little is known about the relationship between early childhood epilepsy (below age 7) and later ADHD diagnosis (at age 7 or above) in ASD. In this historical cohort study, we examined this relationship using an innovative data source, which included linked data from routinely collected acute hospital paediatric records and childhood community and inpatient psychiatric records. In a large sample of children and young people with ASD (N = 3237), we conducted a longitudinal analysis to examine early childhood epilepsy as a risk factor for ADHD diagnosis while adjusting for potential confounders, including socio-demographic characteristics, intellectual disability, family history of epilepsy and associated physical conditions. We found that ASD children and young people diagnosed with early childhood epilepsy had nearly a twofold increase in risk of developing ADHD later in life, an association which persisted after adjusting for potential confounders (adjusted OR = 1.72, CI95% = 1.13-2.62). This study suggests that sensitive monitoring of ADHD symptoms in children with ASD who have a history of childhood epilepsy may be important to promote early detection and treatment. It also highlights how linked electronic health records can be used to examine potential risk factors over time for multimorbidity in neurodevelopmental conditions.

The Central Noradrenergic System in Neurodevelopmental Disorders: Merging Experimental and Clinical Evidence.

The aim of this article is to highlight the potential role of the locus-coeruleus-noradrenergic (LC-NA) system in neurodevelopmental disorders (NdDs). The LC is the main brain noradrenergic nucleus, key in the regulation of arousal, attention, and stress response, and its early maturation and sensitivity to perinatal damage make it an interesting target for translational research. Clinical data shows the involvement of the LC-NA system in several NdDs, suggesting a pathogenetic role in the development of such disorders. In this context, a new neuroimaging tool, LC Magnetic Resonance Imaging (MRI), has been developed to visualize the LC in vivo and assess its integrity, which could be a valuable tool for exploring morphological alterations in NdD in vivo in humans. New animal models may be used to test the contribution of the LC-NA system to the pathogenic pathways of NdD and to evaluate the efficacy of NA-targeting drugs. In this narrative review, we provide an overview of how the LC-NA system may represent a common pathophysiological and pathogenic mechanism in NdD and a reliable target for symptomatic and disease-modifying drugs. Further research is needed to fully understand the interplay between the LC-NA system and NdD.

Surgical evaluation in children <3 years of age with drug-resistant epilepsy: Patient characteristics, diagnostic utilization, and potential for treatment delays.

OBJECTIVE: Drug-resistant epilepsy (DRE) occurs at higher rates in children <3 years old. Epilepsy surgery is effective, but rarely utilized in young children despite developmental benefits of early seizure freedom. The present study aims to identify unique patient characteristics and evaluation strategies in children <3 years old who undergo epilepsy surgery evaluation as a means to assess contributors and potential solutions to health care disparities in this group. METHODS: The Pediatric Epilepsy Research Consortium Epilepsy Surgery Database, a multicentered, cross-sectional collaboration of 21 US pediatric epilepsy centers, collects prospective data on children <18 years of age referred for epilepsy surgery evaluation. We compared patient characteristics, diagnostic utilization, and surgical treatment between children <3 years old and those older undergoing initial presurgical evaluation. We evaluated patient characteristics leading to delayed referral (>1 year) after DRE diagnosis in the very young. RESULTS: The cohort included 437 children, of whom 71 (16%) were <3 years of age at referral. Children evaluated before the age of 3 years more commonly had abnormal neurological examinations (p = .002) and daily seizures (p = .001). At least one ancillary test was used in 44% of evaluations. Fifty-nine percent were seizure-free following surgery (n = 34), with 35% undergoing limited focal resections. Children with delayed referrals more often had focal aware (p < .001) seizures and recommendation for palliative surgeries (p < .001). SIGNIFICANCE: There are relatively few studies of epilepsy surgery in the very young. Surgery is effective, but may be disproportionally offered to those with severe presentations. Relatively low utilization of ancillary testing may contribute to reduced surgical therapy for those without evident lesions on magnetic resonance imaging. Despite this, a sizeable portion of patients have favorable outcome after focal epilepsy surgery resections.

International League Against Epilepsy classification and definition of epilepsy syndromes with onset in childhood: Position paper by the ILAE Task Force on Nosology and Definitions.

The 2017 International League Against Epilepsy classification has defined a three-tier system with epilepsy syndrome identification at the third level. Although a syndrome cannot be determined in all children with epilepsy, identification of a specific syndrome provides guidance on management and prognosis. In this paper, we describe the childhood onset epilepsy syndromes, most of which have both mandatory seizure type(s) and interictal electroencephalographic (EEG) features. Based on the 2017 Classification of Seizures and Epilepsies, some syndrome names have been updated using terms directly describing the seizure semiology. Epilepsy syndromes beginning in childhood have been divided into three categories: (1) self-limited focal epilepsies, comprising four syndromes: self-limited epilepsy with centrotemporal spikes, self-limited epilepsy with autonomic seizures, childhood occipital visual epilepsy, and photosensitive occipital lobe epilepsy; (2) generalized epilepsies, comprising three syndromes: childhood absence epilepsy, epilepsy with myoclonic absence, and epilepsy with eyelid myoclonia; and (3) developmental and/or epileptic encephalopathies, comprising five syndromes: epilepsy with myoclonic-atonic seizures, Lennox-Gastaut syndrome, developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep, hemiconvulsion-hemiplegia-epilepsy syndrome, and febrile infection-related epilepsy syndrome. We define each, highlighting the mandatory seizure(s), EEG features, phenotypic variations, and findings from key investigations.

Academic attainment following pediatric epilepsy surgery: A systematic review.

Academic skills, such as reading, spelling and arithmetic, are central to meaningful engagement with society throughout adolescence and into adulthood. The disruption caused by on-going seizure activity places children with drug-resistant epilepsy at a particularly high risk of poor academic attainment. Though epilepsy surgery during childhood has long-been associated with various cognitive changes, less is known of the extent to which pediatric epilepsy surgery impacts academic attainment. The aim of the present systematic review was to identify the nature of the effect of pediatric epilepsy surgery on the core academic skills of reading, writing, and arithmetic. The electronic databases Embase, Medline, PubMed, PsychInfo, OpenAire, and the ISRCTN registry were searched for studies examining academic attainment following epilepsy surgery in childhood, over the last three decades. Two thousand three-hundred and sixty-eight articles were screened for relevance. Thirteen studies met the inclusion criteria. Study quality and reliability were independently assessed by two reviewers. Results indicate that academic attainment primarily stabilizes in the first year following epilepsy surgery. Though changes to learning ability would not be expected in this early recovery phase, this review indicates that children do not, at least, lose the academic skills they have acquired before surgery. Postoperative declines in performance were most notably recorded in assessments of arithmetic, suggesting an area of potential vulnerability in this cohort. These declines were noted in cohorts with the longest periods between seizure onset and surgery. While older age at onset and seizure freedom correlated with improved academic attainment, further research is necessary to fully understand the specific effect of epilepsy surgery on academic attainment. Still, the present review provides valuable information regarding the likely academic outcomes in the early years following surgical treatment for drug-resistant epilepsy.

Operational diagnosis of epilepsy in children at undetermined risk: A meta-analysis of prognostic factors for seizure recurrence.

PURPOSE: According to the operational epilepsy definition adopted by the International League Against Epilepsy (ILAE) in 2014, in patients with one unprovoked seizure, clinicians must stratify the recurrence risk to determine if the criteria for diagnosis of epilepsy have been met and if antiseizure medications (ASM) are required. A remote symptomatic etiology was considered to be one of the best predictors for seizure recurrence, also according to the available prediction tools, but in children with a previously negative history and a normal neurological examination, estimating the probability of seizure relapse remains less obvious. This meta-analysis aimed to fill this gap of knowledge. METHODS: The PubMed, Embase, and Scopus databases were searched from January 2000 to December 2020. We selected studies reporting children (1 month-18 years old) presenting a first unprovoked seizure. The absence of a known remote neurological pathology had to be clearly stated in the paper or the idiopathic/cryptogenic group data were used; the finding of epileptogenic structural brain MRI abnormalities during the diagnostic workup at the moment of the first unprovoked seizure was not an exclusion criterion. Factors analyzed, as possible predictors of recurrence, included: age at onset, sex, family history of epilepsy, type of seizure (focal or generalized), epileptiform abnormalities on EEG, and epileptogenic structural brain MRI abnormalities. RESULTS: Four studies met the inclusion criteria and the sample size consisted of 741 children. The estimated recurrence rate within 3 years was 50% (95%CI:33.9%-66.0%). Among the predictors of recurrence, focal seizure (OR = 1.52; 95%CI = 1.05-2.19), epileptiform abnormalities on EEG (OR = 1.97; 95%CI = 1.31-2.96), and positive family history for epilepsy (OR = 2.37; 95%CI = 1.56-3.59) were associated with a statistically significant increased risk. CONCLUSION: The analysis of data available until now cannot adequately assess the risk of recurrence after a first unprovoked seizure in neurotypical children. Prospective and multicenter cohort studies are expected.

Primary school teachers' health literacy levels, knowledge, and attitudes toward childhood epilepsy.

OBJECTIVE: The aim of this study was to determine primary school teachers' health literacy levels, knowledge and attitudes towards childhood epilepsy in the province of Igdir in the east of Turkey. METHOD: This descriptive and cross-sectional study involved 247 primary school teachers in the province of Igdir in the east of Turkey between March and April 2021. The questionnaire form, the social attitude towards childhood epilepsies scale (SATCES), and the European health literacy scale (EHLS) were used in data collection. Normal distribution of data was evaluated by analytical methods (Kolmogorov-Smirnov/Shapiro-Wilk tests). An independent sample t-test, one-way analysis of variance (ANOVA), and Pearson correlation analysis were used to analyze the data. RESULTS: During an epileptic seizure, 63.1% of the teachers stated that they would try to open locked jaw by putting something between teeth. A statistically significant difference was found between the age of the teachers and the total mean score of SATCES (p < 0.05). A statistically significant difference was found between the gender of the teachers and the mean score of the affective and behavioral attitudes sub-dimension of the SATCES (p < 0.05). A statistically significant difference was found between the age of the teachers and the total mean score of the EHLS (p < 0.05). The health literacy scores of the teachers between the ages of 31 and 38 were significantly higher than the teachers over the age of 46. CONCLUSION: The main findings of this study indicated the inadequate and wrong information of the teachers, and a positive attitude about epilepsy among primary school teachers. IMPLICATIONS: It is recommended that health professionals organize training programs to In order to correct the inadequate and erroneous knowledge of teachers about epilepsy.

Parents of children with epilepsy: Characteristics associated with high and low levels of health literacy.

Parents of children with epilepsy play a key role in the management of their child's condition. Their level of health literacy (HL), which refers to their ability to seek, understand, assess, remember, and utilize health information, is essential for handling the child optimally. The aim of this study was to investigate characteristics associated with high and low levels of different dimensions of HL in parents. HL was assessed with the multidimensional Health Literacy Questionnaire (parents' version) and the electronic Health Literacy Scale, using data from a cohort of 254 parents of children <12 years. Bivariate correlation and multiple hierarchal linear regression (STATA version 16 SE) were used to investigate variables associated with HL. Self-efficacy (St. ß = 0.14-0.34) was the only variable that predicted higher scores on every HL scale. Being older than 35 years (St. ß = 0.18-0.21), level of education (St. ß = 0.16-0.27), and the child having a coordinator of services (St. ß = 0.16-0.28) were associated with higher scores, while sick leave due to the child's epilepsy (St. ß = -0.13 to -0.16), child comorbidities (St. ß = -0.15 to -0.19), and higher levels of mental distress (St. ß = -0.13 to -0.19) were associated with lower scores in several of the different HL dimensions. A total of 44.8% of the parents scored over the cutoff (≥1.85) predicting a mental disorder on the Hopkins symptom checklist. This is the first study to investigate multidimensional parental HL in a childhood epilepsy context. Our results highlight the need to investigate multiple variables, especially mental distress, to determine characteristics that may predict low parental HL. Further qualitative studies are needed to explore the underlying reasons for the parents' HL scores and to develop inventions tailored to meet different HL needs.

Functional connectivity differences in speech production networks in Chinese children with Rolandic epilepsy.

Previous studies have demonstrated that language impairments are frequently observed in patients with benign epilepsy with centrotemporal spikes (BECTS). However, how BECTS affects language processing in the Chinese population remains unclear. With the use of functional magnetic resonance imaging (fMRI) in an overt picture-naming task, the present study examined functional connectivity in 27 children with BECTS and 26 healthy controls. The results indicated that children with BECTS showed altered functional connectivity associated with speech production between the left precuneus and the right cerebellum, between the right precuneus and the bilateral thalamus and the left superior temporal gyrus, between the right cuneus and the right postcentral gyrus and the right inferior parietal lobule, and between the right cerebellum and right middle frontal gyrus. Collectively, the findings in this study demonstrate the abnormal functional connectivity basis of speech production in Chinese children with BECTS, providing clues to understanding the brain mechanisms of language-related network in patients with BECTS.

Involvement of brain structures in childhood epilepsy with centrotemporal spikes.

BACKGROUND: We aimed to investigate electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) findings to elucidate the interictal epileptiform discharge (IED)-related functional alterations in deep brain structures and the neocortex in childhood epilepsy with centrotemporal spikes (CECTS). METHODS: Ten children with CECTS (median age 8.2 years), referred to our hospital within a year of onset, were eligible for inclusion. They underwent EEG-fMRI recording during sleep. Llongitudinal evaluations, including medical examinations, intelligence tests, and questionnaires about developmental disabilities, were performed. The initial evaluation was performed at the same time as the EEG-fMRI, and the second evaluation was performed over 2 years after the initial evaluation. RESULTS: Three children were unable to maintain sleep during the EEG-fMRI recording, and the remaining seven children were eligible for further assessment. All patients showed unilateral-dominant centrotemporal spikes during scans. One patient had only positive hemodynamic responses, while the others had both positive and negative hemodynamic responses. All patients showed IED-related hemodynamic responses in the bilateral neocortex. For deep brain structures, IED-related hemodynamic responses were observed in the cingulate gyrus (n = 4), basal ganglia (n = 3), thalamus (n = 2), and default mode network (n = 1). Seizure frequencies at the second evaluation were infrequent or absent, and the longitudinal results of intelligence tests and questionnaires were within normal ranges. CONCLUSIONS: We demonstrated that IEDs affect broad brain areas, including deep brain structures such as the cingulate gyrus, basal ganglia, and thalamus. Deep brain structures may play an important role in the pathophysiology of CECTS.

An analysis of breakthrough seizures and related factors in paediatric epilepsy patients.

OBJECTIVE: To determine the frequency of breakthrough seizures among paediatric patients suffering from epilepsy, and factors related to the precipitation of these seizures. METHODS: The cross-sectional study was conducted from July 1, 2018, to July 1, 2020, at the Combined Military Hospital Lahore and the Military Hospital, Rawalpindi, Pakistan, and comprised children of either gender aged 2-12 years diagnosed with any type of epilepsy presenting at the children outpatient department. Diagnosis of epilepsy was established by either a consultant adult neurophysician or a consultant paediatrician. The presence of breakthrough seizures was assessed by obtaining detailed history from the patient and the primary caregiver. Socio-demographic profile, duration of epilepsy and poly-pharmacy were noted. Data was analysed using SPSS 23. RESULTS: Of the 450 subjects, 259(57.6%) were boys and 191(42.4%) were girls. The overall mean age was 6.353±4.732 years. The presence of breakthrough seizures was noted in 227(50.4%) subjects. Children with young age, with low family income, and those in need of poly-pharmacy showed significantly higher odds for breakthrough seizures (p<0.05). CONCLUSIONS: The incidence of breakthrough seizures in epileptic children was high despite the anticonvulsant agents that were previously effective in controlling seizures.

Early 17ß-estradiol treatment reduces seizures but not abnormal behaviour in mice with expanded polyalanine tracts in the Aristaless related homeobox gene (ARX).

Children with severe intellectual disability have an increased prevalence of refractory seizures. Steroid treatment may improve seizure outcomes, but the mechanism remains unknown. Here we demonstrate that short term, daily delivery of an exogenous steroid 17ß-estradiol (40 ng/g) in early postnatal life significantly reduced the number and severity of seizures, but did not improve behavioural deficits, in mice modelling mutations in the Aristaless-related homeobox gene (ARX), expanding the first (PA1) or second (PA2) polyalanine tract. Frequency of observed seizures on handling (n = 14/treatment/genotype) were significantly reduced in PA1 (32% reduction) and more modestly reduced in PA2 mice (14% reduction) with steroid treatment compared to vehicle. Spontaneous seizures were assessed (n = 7/treatment/genotype) at 7 weeks of age coinciding with a peak of seizure activity in untreated mice. PA1 mice treated with steroids no longer present with the most severe category of prolonged myoclonic seizures. Treated PA2 mice had an earlier onset of seizures coupled with a subsequent reduction in seizures later in postnatal life, with a complete absence of any seizures during the analysis at 7 weeks of age. Despite the reduction in seizures, 17ß-estradiol treated mice showed no improvement in behavioural or cognitive outcomes in adulthood. For the first time we show that these deficits due to mutations in Arx are already present before seizure onset and do not worsen with seizures. ARX is a transcription factor and Arx PA mutant mice have deregulated transcriptome profiles in the developing embryonic brain. At postnatal day 10, treatment completion, RNAseq identified 129 genes significantly deregulated (Log2FC > ± 0.5, P-value<0.05) in the frontal cortex of mutant compared to wild-type mice. This list reflects genes deregulated in disease and was particularly enriched for known genes in neurodevelopmental disorders and those involved in signalling and developmental pathways. 17ß-estradiol treatment of mutant mice significantly deregulated 295 genes, with only 23 deregulated genes overlapping between vehicle and steroid treated mutant mice. We conclude that 17ß-estradiol treatment recruits processes and pathways to reduce the frequency and severity of seizures in the Arx PA mutant mice but does not precisely correct the deregulated transcriptome nor improve mortality or behavioural and cognitive deficits.