Abstract To date, FBRSL1 -related disorder has been reported in five individuals with congenital abnormalities and severe postnatal impairment with or without epilepsy; however, the full extent of the phenotypic and genotypic spectrum remains unclear. Previously reported cases involved small truncating variants apparently escaping nonsense-mediated decay, suggesting either a haploinsufficiency or a dominant-negative mechanism. We report the first case of a complex structural variant at the FBRSL1 locus, resulting in an additional, partially truncated copy of the gene, providing strong evidence for a dominant-negative mechanism. RNA-Seq supported the expression of the additional truncated gene copy. The patient is an infant girl with a profound developmental and epileptic encephalopathy (DEE). The child presented at birth with intrauterine growth restriction, respiratory insufficiency, severe swallowing dysfunction, spasticity, contractures, optic nerve hypoplasia, facial dysmorphism, and atrial septal defect. She developed severe postnatal growth restriction with microcephaly and profound developmental impairment. She has a DEE with frequent neonatal focal seizures evolving to infantile epileptic spasms syndrome (IESS). Our patient has congenital abnormalities in common with previously reported cases, along with a profound DEE, not associated previously with FBRSL1 . Our case expands both the phenotypic and genotypic spectrum of FBRSL1 -related disorder.

BACKGROUND:Early-life exposure to chronic and unpredictable stress is a major risk factor for affective disorders, yet the neurodevelopmental mechanisms linking such exposure to emotional vulnerability remain unclear. War-related environments represent an extreme form of environmental unpredictability and may shape how children's attachment-related characteristics relate to the organization of cognitive-limbic brain systems. Here we test whether war-related exposure moderates this brain-behavior association, rather than producing uniform group-level differences. METHODS:Seventy-nine children (42 war-exposed; 37 non-exposed) underwent behavioral assessment and resting-state fMRI. Executive functions (EF) were assessed via parent report, attachment-related characteristics via the Experiences in Close Relationships questionnaire, and war exposure via a structured exposure index. Functional connectivity analyses focused on large-scale executive-control networks and limbic circuits. RESULTS:The war-exposed and non-exposed groups did not differ significantly in attachment-related characteristics, and group differences in parent-reported EF were no longer significant after adjustment for scan timing and nonverbal ability. At the neural level, the two groups showed divergent patterns of association between attachment-related characteristics and limbic connectivity. Critically, attachment-related difficulties were associated with distinct connectivity patterns depending on exposure status: in the war-exposed group, greater attachment-related anxiety and avoidance were associated with reduced cingulate-amygdala connectivity, whereas in the non-exposed group the same characteristics were associated with reduced amygdala-hippocampal connectivity. For large-scale networks, the direction of the attachment-connectivity association shifted across exposure levels, from negative at lower exposure to positive at higher exposure; these within-level simple slopes did not survive correction for multiple comparisons and are interpreted with caution. CONCLUSIONS:War-related exposure was associated with distinct patterns of association between children's attachment-related characteristics and cognitive-limbic connectivity, rather than with uniform group-level differences in attachment or connectivity. These findings provide preliminary evidence that environmental adversity may moderate brain-behavior coupling in childhood; longitudinal studies with validated exposure and symptom measures are needed to clarify causal mechanisms.

INTRODUCTION:Liver transplantation (LT) is a curative treatment for end-stage liver diseases. There is a paucity of data regarding early neurological complications after liver transplantation in the pediatric population. Our aim is to present the characteristics and clinical findings of pediatric patients with early neurological complications (NC) following liver transplantation. METHODS:We conducted a retrospective study conducted in a tertiary pediatric referral center which serves as a national liver transplant center. All children who underwent liver transplantation between 2017 and 2021 were included. Data were collected from medical files during the first 3 months after transplantation, and risk factor analysis for neurological complications was carried out. RESULTS:Of 79 patients who underwent LT, 17 (21.5%) experienced NC. Forty five (57%) were males and the mean age was 2.8 years (range 4 months to 18 years). The most common indication for transplantation was biliary atresia (n = 29, 37.2%), followed by metabolic disorders (n = 16, 20.5%). Living donor liver transplantation was performed in 39 cases (49.4%). The most common neurologic manifestations were seizures (n = 5, 29% of NC), followed by neuropathy (n = 4, 24%), encephalopathy (n = 3, 18%), myoclonus, tremors, and headaches (n = 2, 12%). There was no significant difference in the presence of NC between gender, underlying disease, type of transplant, neurological symptoms pre-transplantation and coagulopathy post transplantation. Age was not found to be an independent risk factor, however there was a trend of higher NC in older patients. Type of immunosuppression protocol, was surprisingly not associated with NC. CONCLUSIONS:Early NC are common (21.5%) in pediatric LT recipients, with seizures being the most frequent manifestation. While predisposing factors were not identified in this cohort, this study characterizes the clinical spectrum of these serious complications.

Abstract Acquiring reading proficiency, unlike spoken language, requires the brain to engage several specialized neural systems to map visual symbols (letters) to their corresponding phonological sounds (audiovisual integration), laying the foundation for fluent reading. This study investigates the neural and behavioral trajectory of developing audiovisual (AV) integration during the first year of learning to read. Thirty-two healthy Hebrew-speaking first-grade children were assessed at 3 time points across the school year: beginning, middle, and end of first grade. Participants underwent behavioral testing and brain fMRI scans while performing a block-design fMRI task involving AV matching or non-matching letters and sounds. Together with improvement in behavioral test scores related to general abilities, working memory, cognitive flexibility, and phonemic abilities, a Drift Diffusion Modeling (DDM) analysis of the accuracy and reaction time across sessions suggested faster and more efficient responses as the year progressed. fMRI results showed a significant increase in activation, from the beginning to the end of the first grade, in the left superior temporal gyrus (STG), frontal cortices and parietotemporal cortices, with a shift towards left-lateralization in the fusiform gyrus at the end of the year. These findings point towards the second half of the first grade as the time window for neural specialization and lateralization to phonological and orthographic information. A significant positive correlation between the fusiform gyrus activation and naming objects and colors scores across all sessions links this neural specialization to cognitive flexibility behavioral skills. Key points Significant increase, predominantly between the middle and end of the first grade, in activation in fusiform, left superior temporal, frontal, and parietotemporal cortices across the first grade. Significant left lateralization in the fusiform gyrus at the end of first grade. Positive correlation between naming skills and a bilateral fusiform gyrus activation throughout the first grade.

The expanded Simple View of Reading model suggests language processing and word reading as contributors to reading comprehension and points at the participation of executive functions as supporting these abilities. Switching and inhibition are both executive functions (EF) contributing to reading, especially in languages with two writing systems-shallow and deep, such as Hebrew. Here, we aimed to determine the specific role of switching/inhibition both cognitively and neurobiologically in the Simple View of Reading model among 49 eight- to 12-year-old Hebrew-speaking children. Children underwent reading and cognitive behavioural testing as well as a five-min resting-state fMRI scan. Functional connectivity of the fronto-parietal network related to switching/inhibition was determined and included in a moderation model. Results suggest that both switching/inhibition abilities and functional connectivity within the fronto-parietal network moderate the relations between word reading and reading comprehension. This strengthens the contribution of switching/inhibition to facilitating reading comprehension and supports the need to include it as part of the expanded SVR model.

This study aimed to determine the involvement of neural circuits associated with executive functions (EF) during Hebrew reading in its two forms, deep and shallow, on a word and contextual level in children. Functional MRI data was collected employing 49 8-12-year-old Hebrew-speaking children performing the n-back task. Functional connectivity within and between EF networks (i.e. the cingulo-opercular; CO and fronto-parietal; FP networks) was calculated and included in prediction models for single word as well as contextual reading measures on a deep and shallow orthographic level. Working memory was positively associated with single word reading in Hebrew-speaking children. Functional connectivity between CO-FP networks better predicted deep orthography reading in single word reading compared to shallow orthography. Results highlight the utilisation of EF networks during the deep form of Hebrew in single word reading.

BackgroundCaregivers shape children's reading abilities and neural networks. While joint reading is well-studied, the impact of parental storytelling on reading-related networks (executive function [EF], attention, sensory processing) before and at the early stages of reading acquisition remains unclear. This study examines whether parental storytelling differentially influences these networks compared to an experimenter's narration.MethodsTwenty-four Hebrew-speaking children (5.0-7.11 years; six females) and their parents participated. Pre-literacy and cognitive skills were assessed, and parents completed cognitive control and language questionnaires. Functional MRI data were collected as children listened to their parent narrate a picture-book story and an experimenter read an age-matched story. Functional connectivity within and between attention, EF, language, and sensory networks was analyzed and correlated with behavioral measures.ResultsParental storytelling elicited stronger connectivity across all networks. Increased EF, attention, and sensory network connectivity correlated positively with book exposure and negatively with reading hours. Stronger sensory processing connectivity during parental narration was linked to better pre-literacy skills. Enhanced audiovisual integration correlated with home literacy, pre-literacy, and later reading abilities.ConclusionsParental storytelling engages reading-related networks, supporting pre-literacy and future reading skills beyond exposure to an unfamiliar reader.ImpactThe literature in the field of parent-child interaction and language development repeatedly points to the benefit of book reading to the child with respect to language development.However, whether there is a particular benefit specifically for parental reading is unknown and whether the child's brain is stimulated differently when the parent is reading a book (vs an experimenter) is also unknown.Our results show that parental reading engages brain regions related to cognitive abilities, attention, language abilities and future reading skills in children even prior to reading age. Parental reading is important for the development of these brain regions.

Pseudotumor cerebri (PTC) is a relatively common cause of headaches in children. In order to exclude secondary causes, an extensive laboratory workup is generally recommended. This assessment causes blood loss, discomfort and a financial burden. To our knowledge, the diagnostic significance of such workup is unclear. We aimed to evaluate the clinical yield of PTC laboratory workup in a pediatric tertiary medical center. This is a retrospective study in a tertiary pediatric hospital. Included were children hospitalized between 2010–2020 with new diagnosis of definite PTC, as confirmed by a certified pediatrician and ophthalmologist. Abnormal results were reviewed by two pediatricians for clinical significance. 75 children (58.7

Neural fingerprinting is a method to identify individuals from a group of people. Here, we established a new connectome-based identification model and used diffusion maps to show that biological parent–child couples share functional connectivity patterns while listening to stories. These shared fingerprints enabled the identification of children and their biological parents from a group of parents and children. Functional patterns were evident in both cognitive and sensory brain networks. Defining “typical” shared biological parent–child brain patterns may enable predicting or even preventing impaired parent–child connections that develop due to genetic or environmental causes. Finally, we argue that the proposed framework opens new opportunities to link similarities in connectivity patterns to behavioral, psychological, and medical phenomena among other populations. To our knowledge, this is the first study to reveal the neural fingerprint that represents distinct biological parent–child couples.

Epilepsy, a prevalent neurological disorder, profoundly affects patients’ quality of life due to the unpredictable nature of seizures. The development of a reliable and user-friendly wearable EEG system capable of detecting and predicting seizures has the potential to revolutionize epilepsy care. However, optimizing electrode configurations for such systems, which is crucial for balancing accuracy and practicality, remains to be explored. This study addresses this gap by developing a systematic approach to optimize electrode configurations for a seizure detection machine-learning algorithm. Our approach was applied to an extensive database of prolonged annotated EEG recordings from 158 epilepsy patients. Multiple electrode configurations ranging from one to eighteen were assessed to determine the optimal number of electrodes. Results indicated that the performance was initially maintained as the number of electrodes decreased, but a drop in performance was found to have occurred at around eight electrodes. Subsequently, a comprehensive analysis of all eight-electrode configurations was conducted using a computationally intensive workflow to identify the optimal configurations. This approach can inform the mechanical design process of an EEG system that balances seizure detection accuracy with the ease of use and portability. Additionally, this framework holds potential for optimizing hardware in other machine learning applications. The study presents a significant step towards the development of an efficient wearable EEG system for seizure detection.

BRAT1 biallelic variants are associated with rigidity and multifocal seizure syndrome, lethal neonatal (RMFSL), and neurodevelopmental disorder associating cerebellar atrophy with or without seizures syndrome (NEDCAS). To date, forty individuals have been reported in the literature. We collected clinical and molecular data from 57 additional cases allowing us to study a large cohort of 97 individuals and draw phenotype-genotype correlations. Fifty-nine individuals presented with BRAT1-related RMFSL phenotype. Most of them had no psychomotor acquisition (100%), epilepsy (100%), microcephaly (91%), limb rigidity (93%), and died prematurely (93%). Thirty-eight individuals presented a non-lethal phenotype of BRAT1-related NEDCAS phenotype. Seventy-six percent of the patients in this group were able to walk and 68% were able to say at least a few words. Most of them had cerebellar ataxia (82%), axial hypotonia (79%) and cerebellar atrophy (100%). Genotype-phenotype correlations in our cohort revealed that biallelic nonsense, frameshift or inframe deletion/insertion variants result in the severe BRAT1-related RMFSL phenotype (46/46; 100%). In contrast, genotypes with at least one missense were more likely associated with NEDCAS (28/34; 82%). The phenotype of patients carrying splice variants was variable: 41% presented with RMFSL (7/17) and 59% with NEDCAS (10/17).

Deficits in executive functions (EF) are a common comorbidity among adolescents with epilepsy. EF deficits were previously correlated with altered connectivity of the fronto-parietal and cingulo-opercular neural networks. The current study investigated white matter integrity in adolescents with epilepsy (n = 29) relative to healthy controls (n = 19). Participants completed questionnaires, neuropsychological testing, and brain magnetic resonance imaging (MRI) that included diffusion tensor imaging (DTI) sequences. On BRIEF parent-report questionnaires, adolescents with epilepsy demonstrated lower working memory and planning abilities than healthy controls. Among adolescents with epilepsy, DTI measurements revealed lower fractional anisotropy (FA) within the right superior longitudinal fasciculus, forceps minor, and the superior frontal segment of the corpus callosum, and higher FA in the left uncinate fasciculus, compared to healthy controls. Better working memory ability in the epilepsy group was associated with higher FA in the superior frontal segment of the corpus callosum. Only in healthy controls, working memory and planning were positively associated with FA values in the left UF, forceps minor and the superior frontal segment of the corpus callosum. The current study complements previous functional studies on the same cohort and suggests that EF impairments among adolescents with epilepsy may be related to the altered anatomical organization of white matter tracts. Combining structural and functional data could potentially enrich the neuropsychological assessment of executive functioning in adolescents with epilepsy.

This specific review aims to expose clinicians, researchers and administrators in hospitals to the importance, procedures and safety of fMRI studies to promote the increased utilisation of such studies in different geographical places worldwide. The child's brain is developing rapidly, both structurally and functionally. These functional changes can only be detected using functional scans generated from an MRI machine and referred to as a functional MRI (fMRI). This method may be used clinically in complex medical and surgical conditions (e.g., epilepsy surgery), but these days are often used for research purposes. However, due to ethical and logistical considerations, fMRI in the paediatric population is not widely and equally used in different geographical places.

OBJECTIVE:The aim of the study was to describe focal epilepsy in patients with Laron syndrome (LS).METHODS:Data were retrieved from medical records of a single-center cohort of 75 patients with LS.RESULTS:We describe for the first time 4 patients with concomitant focal epilepsy and LS. Two of them experienced episodes of status epilepticus. Electroencephalogram examination in all 4 patients showed interictal epileptiform discharges in the temporal regions. Three achieved long-term seizure freedom on antiseizure medications.CONCLUSION:Patients with LS may be at risk of developing focal epilepsy, which seems to be unrelated to hypoglycemic episodes in childhood.

This specific review aims to expose clinicians, researchers and administrators in hospitals to the importance, procedures and safety of fMRI studies to promote the increased utilisation of such studies in different geographical places worldwide. The child's brain is developing rapidly, both structurally and functionally. These functional changes can only be detected using functional scans generated from an MRI machine and referred to as a functional MRI (fMRI). This method may be used clinically in complex medical and surgical conditions (e.g., epilepsy surgery), but these days are often used for research purposes. However, due to ethical and logistical considerations, fMRI in the paediatric population is not widely and equally used in different geographical places. The benefits of using this method to define the functional changes occurring in the developing brain are discussed in this review, along with desensitisation methods recommended when working with this vulnerable population in research and even in a clinical setting.

The authors would like to inform you that in the statistical analysis section of their paper, which appears on page 87, the Chi-square test is mentioned in place of the be Fishers' exact test. The corrected text is as follows: Continuous variables were compared by the Wilcoxon non-parametric test, nominal parameters were compared by Fisher's exact test. The authors apologise for any inconvenience caused. Absence seizure provocation during routine EEG: Does position of the child during hyperventilation affect the diagnostic yield?Seizure - European Journal of EpilepsyVol. 79PreviewAbsence seizures are generalized epileptic seizures with a characteristic ictal electroencephalographic (EEG) pattern of generalized, 3 Hertz (Hz) spike-and wave discharges.1,2 The mean duration of an absence seizure is 4-20 seconds (range 3-40 seconds), and it begins and ends abruptly, manifesting as cessation of activity, unresponsiveness, and staring with/without eye flutter, lip-smacking or head dropping. Full-Text PDF Open Archive

This study aimed to define whether individuals with drug-resistant focal epilepsy also used regions related to cognitive control to facilitate reading. We focused on patients with drug-resistant focal epilepsy in 2011-2014, who were aged 8-20 years and were being treated at the Cincinnati Children's Hospital, USA. They performed a verb generation functional magnetic resonance imaging task known to involve language and cognitive control, as well as a formal reading assessment. The reading scores were correlated with functional connectivity of the anterior cingulate cortex (ACC) using seed-to-voxel analysis. There were 81 potential patients and 13 (seven females) met the inclusion criteria. Their age at seizure onset was 0-13 years, and they had a mean age of 12.66 ± 3.17 years at the time of the study. Individuals with epilepsy demonstrated average intelligence and word reading ability. Their reading scores were positively correlated with functional connectivity between the ACC and regions related to emotional processing (right amygdala), learning and language processing (left cerebellum) and visual processing. Our results support the role that the ACC plays in proficient reading among children with drug-resistant epilepsy, even in those with epileptogenic foci in areas related to language.

AIM:This study aimed to define whether individuals with drug-resistant focal epilepsy also used regions related to cognitive control to facilitate reading. METHODS:We focused on patients with drug-resistant focal epilepsy in 2011-2014, who were aged 8-20 years and were being treated at the Cincinnati Children's Hospital, USA. They performed a verb generation functional magnetic resonance imaging task known to involve language and cognitive control, as well as a formal reading assessment. The reading scores were correlated with functional connectivity of the anterior cingulate cortex (ACC) using seed-to-voxel analysis. RESULTS:There were 81 potential patients and 13 (seven females) met the inclusion criteria. Their age at seizure onset was 0-13 years, and they had a mean age of 12.66 ± 3.17 years at the time of the study. Individuals with epilepsy demonstrated average intelligence and word reading ability. Their reading scores were positively correlated with functional connectivity between the ACC and regions related to emotional processing (right amygdala), learning and language processing (left cerebellum) and visual processing. CONCLUSION:Our results support the role that the ACC plays in proficient reading among children with drug-resistant epilepsy, even in those with epileptogenic foci in areas related to language.

Triclofos sodium (TFS) has been used for many years in children as a sedative for painless medical procedures. It is physiologically and pharmacologically similar to chloral hydrate, which has been censured for use in children with neurocognitive disorders. The aim of this study was to investigate the safety and efficacy of TFS sedation in a pediatric population with a high rate of neurocognitive disability. The database of the neurodiagnostic institute of a tertiary academic pediatric medical center was retrospectively reviewed for all children who underwent sedation with TFS in 2014. Data were collected on demographics, comorbidities, neurologic symptoms, sedation-related variables, and outcome. The study population consisted of 869 children (58.2% male) of median age 25 months (range 5–200 months); 364 (41.2%) had neurocognitive diagnoses, mainly seizures/epilepsy, hypotonia, or developmental delay. TFS was used for routine electroencephalography in 486 (53.8%) patients and audiometry in 401 (46.2%). Mean (± SD) dose of TFS was 50.2 ± 4.9 mg/kg. Median time to sedation was 45 min (range 5–245), and median duration of sedation was 35 min (range 5–190). Adequate sedation depth was achieved in 769 cases (88.5%). Rates of sedation-related adverse events were low: apnea, 0; desaturation ≤ 90%, 0.2% (two patients); and emesis, 0.35% (three patients). None of the children had hemodynamic instability or signs of poor perfusion. There was no association between desaturations and the presence of hypotonia or developmental delay. TFS, when administered in a controlled and monitored environment, may be safe for use in children, including those with underlying neurocognitive disorders.