OBJECTIVE:The long-term relationship between breakfast habits in early childhood and academic performance remains unclear. Therefore, this study aimed to investigate the association between breakfast habits at age 3 years and academic performance in the first grade of elementary school. METHODS:We conducted a retrospective analysis of a population-based cohort in Amagasaki City that followed children from birth until entry into elementary school. Academic outcomes included performance in the national language and math, as well as subdomains within each subject. RESULTS:Among 7847 children, regular breakfast consumption at age 3 years was associated with higher academic performance. Children who ate breakfast daily had higher mean scores in national language (73.12 ± 19.19 vs 66.16 ± 22.33) and math (81.09 ± 19.19 vs 73.31 ± 24.71). In multivariable regression analyses, daily breakfast consumption at age 3 years was modestly associated with higher first-grade academic performance, specifically with overall math scores (β = 2.46, 95% confidence interval [CI]: 0.07-4.85), calculation-related skills (β = 1.94, 95% CI: 0.29-3.59), and language-related skills (β = 1.74, 95% CI: 0.02-3.46). Associations with other domains were not significant. These associations remained significant after adjusting for economic status, suggesting an independent association between early childhood breakfast habits and academic performance. Children who did not eat breakfast daily were more likely to have financial difficulties and irregular lifestyles. CONCLUSION:Regular breakfast consumption during early childhood was associated with higher subsequent academic achievement. However, the observed association may reflect underlying social and environmental factors.

Background Status epilepticus (SE) is a neurological emergency requiring rapid, stepwise treatment. In Japan, the Guidelines for the Treatment of Pediatric Status Epilepticus 2023 (GL2023) were published; however, real-world practice following their publication remains unclear. Methods We conducted a nationwide, cross-sectional web-based survey of pediatric neurologists between January and March 2025. One representative from each institution reported institutional practices for the in-hospital management of pediatric SE. Institutions were stratified by annual SE case volume (≥20 vs. ≤19 cases). General management strategies, antiseizure medication selection, electroencephalography (EEG) utilization, and approaches to refractory and super-refractory SE (RSE and SRSE) were analyzed. Results A total of 136 institutions responded. Most institutions reported referring to GL2023 and initiating first-line treatment within 10 min of hospital arrival. Midazolam was the most commonly used first-line drug, with widespread use of non-intravenous routes. Phenytoin or fosphenytoin remained the most commonly selected second-line drug, followed by phenobarbital. For RSE, anesthetic coma therapy with midazolam and barbiturates was used at comparable frequencies. Overall, antiseizure medication selection did not differ by institutional case volume. In contrast, institutions managing ≥20 cases annually more frequently reported having institution-specific protocols, utilizing EEG in the emergency department, administering repeat doses of benzodiazepines, and having experience with advanced therapies for SRSE. Conclusions Pediatric SE management in Japan emphasizes rapid treatment and flexible administration routes. Institutional experience is associated with differences in EEG utilization, protocol development, and SRSE management. Further improvement will require continued evidence generation, timely treatment implementation, and reduction of institutional disparities.

BACKGROUND:Status epilepticus (SE) is a neurological emergency requiring rapid treatment. While prehospital management is critical, practices regarding rescue medication use and caregiver guidance, including emergency service activation, remain unclear. METHODS:We conducted a nationwide, web-based survey of pediatric neurologists between January and March 2025. One representative from each institution reported on rescue medication prescribing and caregiver instructions for prehospital seizure management. The survey assessed indications for buccal midazolam, scenario-based recommendations, and post-administration guidance. RESULTS:Of 136 responses, 134 respondents who were aware of buccal midazolam were included; 118 had prescribing experience. A history of prolonged convulsive seizures, particularly ≥30 min (95.5% high-priority), was consistently identified as a high-priority indication. Seizures lasting 5-30 min were also considered appropriate (57.5% high-priority, 38.1% low-priority), with greater variability. In contrast, frequent seizures alone were often regarded as appropriate (44.8% low-priority) but rarely high-priority (16.4%). Diagnostic categories such as epilepsy or febrile seizures themselves were not regarded as appropriate indications. Environmental factors, including distance from medical facilities, were also relevant. Similar patterns were observed in scenario-based recommendations, with consistent findings across epilepsy and febrile seizure scenarios. Caregiver instructions varied widely, particularly regarding emergency service activation. In-hospital management was generally unchanged regardless of prehospital rescue medication use. CONCLUSIONS:Prehospital rescue medication prescribing is primarily guided by seizure duration rather than diagnostic categories. Variability in caregiver instructions highlights the need for clearer guidance to optimize prehospital seizure management.

ABSTRACT Introduction Social restrictions during the coronavirus (COVID‐19) pandemic have resulted in children spending more time with their families and having fewer opportunities to attend nursery schools or therapeutic facilities. Few studies have examined the impact of the COVID‐19 pandemic on the development and parenting environments of 3‐year‐old children. In this study, we aimed to examine the impact of the COVID‐19 pandemic on fine and gross motor skills and language development, including comprehension and communication, in 3‐year‐old children. The secondary objective was to investigate their impact on caregiving environments. Methods This repeated cross‐sectional study was conducted at age 3 years using data from a longitudinal birth cohort. We analyzed data from routine 3‐year‐old health examinations conducted in Kobe City, Japan, between April 2014 and March 2021. Multivariable logistic regression models were used to assess the association between COVID‐19 birth cohorts and developmental and caregiving outcomes among 3‐year‐old children. In total, 62,192 children (3 years, 51.4% males; majority Japanese) were categorized into three birth cohorts: pre‐ (from 4/1/2014 to 3/31/2017; n = 29,421), partial‐ (from 4/1/2017 to 3/31/2020; n = 25,202), and post‐COVID‐19 (from 4/1/2020 to 3/31/2021; n = 7569). Results The prevalence of impaired gross motor skills and language comprehension was significantly higher in the post‐COVID‐19 group than in the pre‐COVID‐19 group (gross motor skill: 0.7% vs. 0.5%, OR 1.41, 95% CI 1.02–1.95, p = 0.04; language comprehension abnormalities: 3.6% vs. 2.1%, OR 1.72, 95% CI 1.49–1.99, p < 0.001). However, medical evaluations conducted by physicians showed no differences in fine motor skills. Caregiver questionnaires showed impaired verbal and communication skills, as well as reduced interactions with peers and relatives, in the post‐COVID‐19 group (limited vocabulary growth: 1.0% vs. 0.7%, OR 1.32, 95% CI 1.01–1.72, p = 0.04; inability to formulate three‐word sentences: 4.4% vs. 3.4%, OR 1.26, 95% CI 1.11–1.43, p < 0.001; inability to state the names of their playmates: 5.5% vs. 3.9%, OR 1.40, 95% CI 1.25–1.57, p = 0.003). However, no definitive conclusions regarding motor skills could be drawn from our findings. Although caregiving assistance decreased significantly in the COVID‐19 group, comparable trends were observed in the pre‐COVID‐19 group. Conclusion These findings indicate that the COVID‐19 pandemic was associated with changes in language development and social interactions, possibly reflecting decreased opportunities for social engagement outside the family.

BACKGROUND:Febrile status epilepticus (FSE) is associated with the development of acute encephalopathy (AE), and delays in the administration of antiseizure medications have been linked to worse outcomes. However, the effect of treatment timing on subsequent in-hospital management and short-term outcomes in pediatric patients with FSE remains inadequately elucidated. METHODS:We conducted a single-center retrospective cohort study involving children with FSE admitted to our hospital between January 2020 and April 2023. Patients who received benzodiazepines (BZDs) within 80 min of seizure onset were included. Patients were categorized into an early group (EG) (≤40 min) and a late group (LG) (41-80 min) based on the timing of initial BZD administration. Outcomes assessed included impaired consciousness at 6 h, induction of anesthetic coma therapy (ACT), development of AE, and neurological sequelae. RESULTS:A total of 93 children with FSE were analyzed. Impaired consciousness at 6 h was observed in 33 (35.4%) patients, and 16 (17.2%) required ACT. Neurological sequelae occurred in 7 (7.5%) patients, including one death (1.1%). The induction rate of ACT was significantly higher in the LG than in the EG (22.7% vs. 3.7%). Although no statistically significant differences were observed in the incidence of AE or neurological sequelae, the ACT rate increased in a time-dependent manner with delays in BZD administration. CONCLUSIONS:Delayed BZD administration may be associated with an increased likelihood of requiring intensive neurocritical care, including ACT, among children with FSE.

Background Mohr-Tranebjaerg syndrome (MTS) is an X-linked recessive neurodegenerative disorder caused by pathogenic variants in TIMM8A. Of the 39 previously reported disease-causing variants in the TIMM8A, five are splice site variants; however, none of these variants have been evaluated by transcript analysis. Methods We performed panel-based targeted exome analysis in a Japanese boy with sensorineural hearing loss and rapidly progressive dystonia. To assess the effect of the identified splice donor site variant, transcript analysis was performed using RNA derived from peripheral blood. Result A novel hemizygous splice donor site variant in TIMM8A (NM_004085.4:c.132+5G>A) was identified. Transcript analysis revealed three aberrant transcripts: two transcripts with partial intron 1 inclusion of 606 bp or 492 bp (INS606bp and INS492bp) and one transcript with a 60 bp partial deletion of exon 1 (Δ60bp), with no detectable normal transcript. Both INS606bp and INS492bp transcripts contain premature stop codons due to the inserted intronic sequences, leading to the loss of 53 amino acids, whereas the Δ60bp transcript leads to the loss of 20 amino acids. All aberrant transcripts lacked part of the Tim10/DDP family zinc finger domain, which is essential for TIM8A function. Conclusion This study provides the first transcript analysis elucidating the pathogenic mechanism of a splice donor site variant in TIMM8A. The findings suggest that splice donor site variants may share a common disease mechanism involving the production of functionally defective TIM8A protein.

PURPOSE:While prolonged impaired consciousness is often attributed to encephalopathy or meningitis, its occurrence and associated factors in patients with febrile status epilepticus without these conditions remain unclear. This study investigated the duration and determinants of impaired consciousness following febrile status epilepticus lasting ≥ 30 min in children treated with antiseizure medications. METHODS:This retrospective multicenter study used data from the Febrile Acute Convulsion and Encephalopathy registry, a prospective multicenter consecutive case registry for acute encephalopathy and febrile convulsive status epilepticus in Japan. Children aged 6-60 months with febrile status epilepticus lasting ≥ 30 min who received antiseizure medication were analyzed. Clinical data and early laboratory results were compared between prolonged (≥4 h) and non-prolonged (<4 h) impaired consciousness groups. RESULTS:Among 227 children with febrile status epilepticus lasting ≥ 30 min, the median time to recovery of consciousness was 176 min, and 79 (34.8%) had prolonged impaired consciousness (≥4 h). The two groups did not differ in age, sex, seizure duration, body temperature, history of febrile seizures, or number of antiseizure medications. Phenobarbital use was more frequent in the prolonged group. Laboratory abnormalities, including lower pH, lower base excess, higher creatinine, higher glucose, and higher ammonia were associated with prolonged impairment. Low pH was the only independent factor. CONCLUSION:In children with febrile status epilepticus ≥ 30 min, prolonged unconsciousness (≥4 h) was associated with phenobarbital use and laboratory abnormalities, with acidosis as the sole independent predictor. Early recognition of delayed recovery may support timely clinical decision making and optimize emergency care.

OBJECTIVE:This population-based cohort study in Kobe, Japan, investigated the impact of the COVID-19 pandemic on infant neurodevelopment by comparing children born before and during the pandemic. DESIGN:Retrospective population-based cohort study of 63 703 children born between 1 April 2014 and 31 October 2020, who underwent an 18-month health check-up. SETTING:Kobe, Japan. PATIENT:Children born between April 2014 and March 2018 (pre-COVID-19 group) or April-October 2020 (during-COVID-19 group). INTERVENTION:None MAIN OUTCOME MEASURES: Neurodevelopmental outcomes assessed by trained paediatricians, including language, social and behavioural indicators. RESULTS:The abnormal neurodevelopment prevalence was higher in the during-COVID-19 group (12.8%) than in the pre-COVID-19 group (10.2%) (OR, 1.30; 99% CI 1.16 to 1.46). Similarly, the rate of children without meaningful words was higher during the pandemic (7.1% vs 4.8%; OR, 1.52; 99% CI 1.31 to 1.78), indicating delayed language development. Intergroup differences in other outcomes were minimal. CONCLUSIONS:The COVID-19 pandemic may have negatively influenced early neurodevelopment, particularly language acquisition. These findings suggest that infant language development is affected by social changes, such as pandemics. Further research is required to explore the underlying causes and the long-term effects.

BACKGROUND:Previous national studies of acute encephalopathy in Japan were conducted in 2007-2010 and 2014-2017. In this third study (April 1, 2020-October 31, 2023), spanning the coronavirus disease 2019 (COVID-19) outbreak, we compared results to assess trends in pediatric viral infections and therapeutic practices. METHODS:Questionnaires were sent to 430 hospitals of the Japanese Pediatric Society, yielding 241 responses and 1197 cases. A secondary survey to 151 facilities received 110 responses (72.8 %), identifying 622 eligible patients (604 for treatment, 544 for outcome analysis). Data on patient background, syndrome classification, causative virus, treatment, and prognosis were collected. RESULTS:Among 622 cases (54.6 % boys), the highest incidence was in 1-year-olds, with case numbers peaking during COVID-19 and influenza outbreaks. The frequency of clinical syndromes was: acute encephalopathy with biphasic seizures and late reduced diffusion, 35.1 %; clinically mild encephalitis/encephalopathy with a reversible splenial lesion, 17.8 %; hemorrhagic shock and encephalopathy syndrome (HSES), 6.9 %; acute encephalitis with refractory, repetitive partial seizures, 3.7 %; acute fulminant cerebral edema (AFCE), 2.2 %; acute necrotizing encephalopathy, 1.6 %; and unclassifiable, 31.4 %. Notably, the combined HSES/AFCE rate increased from 1.9 % in the 2014-2017 survey to 9.1 %, likely due to enhanced diagnosis and COVID-19 impact. Pathogens were exanthem subitum (16.1 %), severe acute respiratory syndrome coronavirus 2 (15.9 %), and influenza (7.7 %). Treatments included steroid pulse therapy (68.9 %), mitochondrial cocktails (42.5 %), and targeted temperature management (31.0 %). CONCLUSION:This study provides a comprehensive overview of pediatric acute encephalopathy during COVID-19 outbreaks, shows increases in the incidence of HSES/AFCE, and presents current treatment.

PURPOSE:Status epilepticus associated with fever (SEF) is often encountered in pediatric emergency departments, and some patients develop neurological emergencies, such as acute encephalopathy (AE). Although numerous genetic variants of developmental and epileptic encephalopathy (DEE) have been reported, the frequency of these disease-associated variants of SEF is unknown. The first aim of this study was to investigate the associated genetic variants of SEF. The second aim was to compare the variations in genes between SEF and DEE. METHOD:This retrospective, clinical observational study included patients with SEF or DEE who visited Kobe University Hospital or Kobe University affiliated hospitals and provided consent for a genetic diagnosis of SEF or DEE between January 1, 2021, and December 31, 2022. FINDING:Fifteen patients with SEF and 27 patients with DEE consented to a genetic diagnosis and were included in the study. The detection rate of genetic variants was lower in patients with SEF (26.7%) than in those with DEE (63.0%), although there is no statistically significant difference (p = 0.05, Fisher's exact test). Analysis of patients with DEE revealed a wide variety of causative genes for DEE (16 different genes), whereas in SEF cases, only SCN1A variants were detected. CONCLUSION:Our study is the first to clarify the detection rates of different genetic variants in SEF. Patients with SEF may have less genetic involvement in the onset of epileptic seizures, compared to those with DEE.

Trisomy of the short arm of chromosome 12 (trisomy 12p) is a rare chromosomal abnormality causing dysmorphic features, congenital anomalies, intellectual disabilities, developmental delays, and seizures. Detailed information regarding the types of seizures is scarce owing to the low incidence of seizures. In contrast, 18p deletions and seizures are rare. Previous reports on trisomy 12p or monosomy 18p are limited, and little is known about epilepsy in children with trisomy 12p or monosomy 18p. Here, we report a case of 46,XX,der(18)t(12;18)(p11.2;p11.2) with repeatedly disturbed consciousness accompanied with alternating hemiplegia, corresponding to the electroencephalogram findings. G-banding of the parents showed balanced translocation of the mother. The last hospitalization occurred when our patient was 12 years old. She presented with disturbed consciousness and left-sided hemiplegia. Electroencephalography showed continuous 1-2 Hz slow waves in the right hemisphere and a theta burst in the left hemisphere. Based on the genes on chromosomes 12 and 18, the symptoms seemed to be related to partial trisomy 12p. Our case suggests the possibility of a novel seizure phenotype associated with trisomy 12p.

BACKGROUND:Acute encephalopathy is a severe condition predominantly affecting children with viral infections. The purpose of this study was to elucidate the epidemiology, treatment, and management of acute encephalopathy. The study also aimed to understand how the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has affected epidemiological trends. METHODS:This retrospective study used the database of the Febrile Acute Convulsion and Encephalopathy registry, a prospective multicenter consecutive case registry for acute encephalopathy and febrile convulsive status epilepticus. Pediatric patients aged 0-18 years hospitalized and diagnosed with acute encephalopathy between January 2020 and August 2023 were included in this study. RESULTS:Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) was the most common syndrome (36 cases, 27.5 %). SARS-CoV-2 was the most common pathogen (19 cases, 14.5 %), followed by influenza virus type A (15 cases, 11.5 %). Targeted temperature management was performed for 25 (69.4 %) of 36 patients with AESD; 5 (50.0 %) of 10 patients with hemorrhagic shock and encephalopathy; and only 1 (5.9 %) of 17 patients with mild encephalitis or encephalopathy with a reversible splenial lesion (MERS). High-dose corticosteroids were administered to 9 (90.0 %) of 10 patients with hemorrhagic shock and encephalopathy and 11 (30.6 %) of 36 patients with AESD. CONCLUSIONS:The primary causative pathogen of acute encephalopathy has changed to SARS-CoV-2. AESD remains the most common syndrome. Targeted temperature management is more, whereas high-dose corticosteroid therapy is less, frequently used. No specific treatment for mild encephalitis or encephalopathy with a reversible splenial lesion has been established.

Background Rapid and reliable diagnostic methods are essential to ensure appropriate management of acute gastroenteritis. The BioFire FilmArray® Gastrointestinal Panel (FGP) rapidly and accurately identifies various pathogens. However, previous studies on FGP lacked detailed descriptions of its utility in clinical practice. Additionally, pediatric data from Japan are limited. Therefore, we aimed to evaluate the clinical utility of the FGP and identify the characteristics of patients with positive FGP results. Methods We retrospectively reviewed the records of pediatric patients (aged ≤ 18 years) who underwent FGP testing at Kobe University Hospital in 2024. The pathogens detected and clinical characteristics of FGP-positive and FGP-negative patients were compared. Subgroup analyses were conducted by bacterial- and viral-positive status. Results The median time from FGP testing to the confirmation of results was 82 min. Of the 67 patients who underwent FGP testing, 28 (42%) were FGP-positive. The most frequently detected pathogen was norovirus (18%), followed by Clostridioides difficile toxin A/B (12%), Campylobacter spp. (4.5%), Yersinia enterocolitica (4.5%), Enteroaggregative Escherichia coli (4.5%), Enteropathogenic Escherichia coli (3%), astrovirus (3%), sapovirus (1.5%), Shiga -like toxin producing Escherichia coli (1.5%), and Salmonella spp. (1.5%). No significant differences in clinical findings were observed between FGP-positive and FGP-negative cases. Subgroup analysis revealed frequent vomiting, and significantly shorter fever in patients with viral-positive FGP results than in those with bacterial-positive FGP results. Conclusion FGP aids clinical decision-making by enabling the early detection of pathogens, such as Campylobacter spp. and Yersinia enterocolitica, which typically require several days for stool culture results.

PURPOSE:To investigate association between magnetic resonance imaging (MRI)-defined cortical tuber subtypes and interictal epileptiform discharges (IEDs) in Tuberous sclerosis complex (TSC). METHODS:Twenty-three patients with TSC underwent brain MRI and scalp electroencephalogram (EEG). We analyzed total of 184 cerebral lobes (bilateral frontal, temporal, parietal, occipital). Tubers were classified into Types A, B, and C based on their signal intensity on MRI with T1-weighted (T1W), T2-weighted (T2W), and fluid-attenuated inversion recovery (FLAIR) images. Type A was isointense on T1W and subtly hyperintense on T2W/FLAIR, while Type B was hypointense on T1W and homogeneously hyperintense on T2W/FLAIR. Meanwhile, Type C was hypointense on T1W, hyperintense on T2W, and heterogeneous on FLAIR, characterized by a hypointense central region surrounded by a hyperintense rim. IEDs were detected using automated software and confirmed by expert visual inspection. The association between tuber subtypes and IED presence was assessed using multivariable generalized estimating equations (GEE). A negative binomial generalized linear mixed model (GLMM) was used to assess the association between tuber counts and IED frequency. RESULTS:Multivariable analyses revealed that Type C tubers were the only subtype independently associated with both the presence of IEDs (Adjusted odds ratio = 1.417, p = 0.011) and a higher frequency of IEDs (p < 0.001). The presence or number of Type A and B tubers were not significantly associated with either outcome. CONCLUSIONS:Type C tubers demonstrate significantly higher cortical irritability than other subtypes, providing insights into varying irritability potential of different tuber types in TSC.

The updated definition of status epilepticus (SE) by the International League Against Epilepsy in 2015 included two critical time points (t1: at which the seizure should be regarded as an “abnormally prolonged seizure”; and t2: beyond which the ongoing seizure activity can pose risk of long-term consequences) to aid in diagnosis and management and highlights the importance of early treatment of SE more clearly than ever before. Although Japan has witnessed an increasing number of pre-hospital drug treatment as well as first- and second-line treatments, clinical issues have emerged regarding which drugs are appropriate. To address these clinical concerns, a revised version of the “Japanese Guidelines for the Treatment of Pediatric Status Epilepticus 2023” (GL2023) was published. For pre-hospital treatment, buccal midazolam is recommended. For in-hospital treatment, if an intravenous route is unobtainable, buccal midazolam is also recommended. If an intravenous route can be obtained, intravenous benzodiazepines such as midazolam, lorazepam, and diazepam are recommended. However, the rates of seizure cessation were reported to be the same among the three drugs, but respiratory depression was less frequent with lorazepam than with diazepam. For established SE, phenytoin/fosphenytoin and phenobarbital can be used for pediatric SE, and levetiracetam can be used in only adults in Japan. Coma therapy is recommended for refractory SE, with no recommended treatment for super-refractory SE. GL2023 lacks adequate recommendations for the treatment of nonconvulsive status epilepticus (NCSE). Although electrographic seizure and electrographic SE may lead to brain damages, it remains unclear whether treatment of NCSE improves outcomes in children. We plan to address this issue in an upcoming edition of the guideline.

Background Au-Kline syndrome (AKS) is characterized by moderate-to-severe intellectual disability, hypotonia, and distinctive characteristic facies. Other features, such as cardiac malformations, feeding difficulties, hydronephrosis, high pain tolerance, recurrent fever, abnormal sweating, and heat intolerance, have also been reported. However, our understanding of the heat tolerance of AKS remains limited. Objective We present a rare case of AKS in a 3-year old girl who presented with poor oral intake during the summer due to heat intolerance. Furthermore, we conducted a detailed review of AKS and investigated the extent to which heat intolerance was reported in patients with AKS. Methods To evaluate the “heat intolerance” in patients with HNRNPK variants, the literature in English was reviewed for cases reported as patients with HNRNPK variants by searching the PubMed database. Results A total of 456 articles were identified. We thoroughly reviewed the abstracts and selected articles describing cases with variants in HNRNPK, including two original articles, eight clinical case reports, and two letters to the editor. The cohort consisted of 23 male and 23 female patients with HNRNPK variants. Seventeen patients harbored missense variants, 27 harbored a truncating variant, and two harbored an intron variant. All variants in all the cases were de novo. In this review, we found no reported cases of heat intolerance. Conclusion We identified a novel HNRNPK variant of AKS associated with heat intolerance symptoms caused by abnormal sweating. Whether heat intolerance in AKS is extremely rare or underreported remains unclear, and further investigation is required.

BACKGROUND:This study aimed to analyze and describe reduced-lead electroencephalographic (EEG) data for suspected electrographic seizure (ESz) in pediatric patients presenting with altered mental status (AMS) in the emergency department (ED) according to standardized EEG terminology. The secondary aim was to compare the characteristics of these EEG patterns across febrile seizure (FS), acute encephalopathy/encephalitis (AE/AES), and epilepsy. METHODS:Epileptologists retrospectively analyzed the medical records and findings of reduced-lead EEG performed for suspected ESz in pediatric patients with AMS in ED between March 1, 2019, and February 28, 2023. Fifty-one EEG results with few artifacts were extracted; these patterns were described according to the American Clinical Neurophysiology Society's Standardized Critical Care EEG Terminology 2021. The obtained clinical diagnoses were categorized into three groups: FS, AE/AES, and epilepsy, and the characteristics of EEG patterns were compared. RESULTS:Clinical seizure types were not significantly different between FS, AE/AES, and epilepsy. In terms of EEG, there was no difference in Main term 1 (localization) among the groups. With regard to Main term 2 (morphology), patients with FS and AE/AES had commonly rhythmic delta activity, whereas patients with epilepsy had significantly more spikes and waves. ESz was observed in 25 patients; their incidence was significantly higher in the epilepsy group. CONCLUSIONS:This is the first study to describe patterns in reduced-lead EEG performed for suspected ESz in pediatric patients with AMS due to disorders commonly encountered in the ED by using standardized EEG terminology and to compare EEG patterns among these disorders.

"Infantile spasms syndrome (IS)," previously known as "West syndrome (WS)," is characterized by epileptic spasms (ES), abnormal electroencephalography (EEG) patterns such as hypsarrhythmia, and developmental stagnation or regression in infancy. IS has various etiologies, including genetic abnormalities. SCN8A variants are associated with developmental and epileptic encephalopathy, characterized by developmental delay, seizures starting from infancy, and refractory epilepsy with multiple seizure types. However, previous studies have not focused on the treatment of IS caused by SCN8A variants. We report a case of a previously healthy boy who presented ES and developmental regression at 6 months of age. His EEG revealed hypsarrhythmia, leading to the diagnosis of IS. After admission, the patient was treated with hormonal therapy using intravenous methylprednisolone pulse therapy (MPT). ES and hypsarrhythmia on EEG disappeared in the early stages of MPT administration with no observed treatment complications. Furthermore, we observed no recurrence of EEG abnormalities or seizures at 17 months of age. Genetic testing revealed a novel de novo SCN8A variant (NM_001177984.2:c.2882T > G:p. M961R). The literature review confirmed that 13 patients, including our described patient, were reported to have ES owing to missense variants of SCN8A . While the previous articles do not mention intravenous MPT for ES with SCN8A , our case findings suggest that intravenous MPT therapy may be effective for short-term suppression of ES caused by the SCN8A variant in IS.

OBJECTIVE:This study aimed to measure and compare cerebrospinal fluid neuronal injury biomarkers in the acute phase of complex febrile seizure (CFS) and infection-triggered acute encephalopathy (AE). Furthermore, we determined the pathogenesis of AE with biphasic seizures and late reduced diffusion (AESD). METHODS:Pediatric patients with febrile status epilepticus who visited Hyogo Prefectural Kobe Children's Hospital from November 1, 2016, to December 31, 2022, and whose cerebrospinal fluid samples were collected within 24 h of neurological symptom onset were included. Patients were classified as having CFS or infection-triggered AE according to their definitions. Patients with AE were further categorized into AESD or unclassified AE. Cerebrospinal fluid biomarkers (neuron-specific enolase, growth differentiation factor 15 [GDF-15], S100 calcium-binding protein B [S100B], glial fibrillary acidic protein, and tau protein were measured and compared among the groups. RESULTS:Total of 63 patients (45 with CFS and 18 with AE) were included. Among the AE patients, nine were classified as having AESD and nine as having unclassified AE. S100B levels were significantly higher in patients with AESD than in patients with CFS (485 pg/ml vs. 175.3 pg/ml) and were even higher in patients with AESD and neurological sequelae (702.4 pg/ml). GDF-15 levels were significantly elevated in patients with AE compared to patients with CFS (85.8 pg/ml vs. 23.6 pg/ml). CONCLUSIONS:The elevation of S100B suggests that activated astrocytes may be closely associated with the early pathology of AESD. Elevated GDF-15 levels in infection-triggered AE suggest the activation of defense mechanisms caused by stronger neurological injury.

Although the causes of neurodevelopmental disorders remain unknown, several environmental risk factors have attracted considerable attention. We conducted a retrospective, longitudinal, population-based cohort study using data from infant health examinations of children born to mothers with pregnancies between April 1, 2014 and March 31, 2016 in Kobe City to identify the perinatal factors associated with neurodevelopmental referrals in 3-year-old children. There were 15,223 and 1283 children in the normal and referral groups, respectively. Neurodevelopmental referrals at the health checkup for 3-year-old children were significantly associated with the lack of social support during pregnancy (adjusted odds ratio [aOR] 1.99, 99% CI 1.14–3.45, p = 0.001), history of psychiatric consultation (aOR 1.56, 99% CI 1.10–2.22, p = 0.001), no social assistance post-delivery (aOR 1.49, 99% CI 1.03–2.16, p = 0.006), Edinburgh Post-natal Depression Scale (EPDS) score ≥ 9 (aOR 1.36, 99% CI 1.01–1.84, p = 0.008), infant gender (male) (aOR 2.51, 99% CI 2.05–3.06, p < 0.001), and cesarean delivery (aOR 1.39, 99% CI 1.11–1.75, p < 0.001). In conclusion, this exploratory study in the general Japanese population identified six perinatal factors associated with neurodevelopmental referrals in 3-year-old children: infant gender (male), cesarean section, maternal history of psychiatric consultation, EPDS score ≥ 9, lack of social support during pregnancy, and no social assistance post-delivery.