Brain Dev. [JOURNAL]
Sun
200 papers
Emerging disease-modifying therapies for Angelman syndrome: A comprehensive review for pediatric neurologists.
Samanta D
Brain Dev · 2026 Jun · PMID 41864145 · Publisher ↗
Angelman syndrome (AS), a rare neurogenetic disorder affecting approximately 1 in 15,000 live births, results from loss of functional UBE3A gene expression and manifests with severe developmental delay, intellectual disa...
Angelman syndrome (AS), a rare neurogenetic disorder affecting approximately 1 in 15,000 live births, results from loss of functional UBE3A gene expression and manifests with severe developmental delay, intellectual disability, absent speech, ataxia, epilepsy, and distinctive behavioral features. Until recently, only symptomatic management was available. This review provides pediatric neurologists with a comprehensive, practice-oriented overview of emerging disease-modifying therapies for AS, focusing on therapeutic approaches advancing through clinical development. The molecular pathophysiology of AS, natural history considerations critical for trial interpretation, and the current evidence for antisense oligonucleotide (ASO) therapies (ION582, GTX-102/apazunersen, rugonersen), gene replacement approaches (MVX-220), and next-generation strategies including CRISPR-based gene editing, artificial transcription factors, small molecules, and novel delivery platforms are reviewed. ASO therapies targeting the UBE3A antisense transcript represent the most clinically advanced approach, with three candidates showing proof-of-concept efficacy in Phase 1/2 studies and two advancing to pivotal Phase 3 trials. Gene replacement therapy offers potential single-administration treatment but faces challenges regarding safety, immune responses, and durability. Next-generation approaches including CRISPR activation, epigenetic editing, and blood-brain barrier-penetrating delivery systems show preclinical promise. Critical challenges include outcome measurement limitations, genotype stratification, long-term safety monitoring, and ensuring equitable access. These advances herald a transformation in AS clinical care and represent a milestone in precision pediatric neurology.
From a caregiver perspective: Quality of life of children with epilepsy and autism spectrum disorder - a single site case-control study.
Fonseca LD, Carnes S, Kumar G
Brain Dev · 2026 Jun · PMID 41855821 · Publisher ↗
BACKGROUND: We aim to investigate the quality of life (QoL) in children with idiopathic generalized epilepsy (IGE) compared to children with epilepsy and autism spectrum disorder (ASD) and their respective caregiver's QO...
BACKGROUND: We aim to investigate the quality of life (QoL) in children with idiopathic generalized epilepsy (IGE) compared to children with epilepsy and autism spectrum disorder (ASD) and their respective caregiver's QOL. METHODS: We conducted a case-control study from a single pediatric hospital in Ohio. Inclusion criteria for the epilepsy group included children with a diagnosis of IGE; the ASD group included diagnosis of epilepsy and ASD. Both groups included children aged 2-18 years. To capture patient QoL, adult caregivers completed the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55), and to capture caregiver QoL, adult caregivers completed the Health-Related Social Needs (HRSN) and the CarerQoL-7D instrument. RESULTS: A total of 43 caregivers completed the surveys. There was a greater distribution of female patients in the IGE group (57.1%) versus the ASD group which had higher distribution of males (86.4%). Cognitive functioning (M = 33.0), emotional functioning (M = 57.4), physical functioning (M = 33.6) and overall QOLCE-55 mean score (M = 45.2) revealed a statistically significant lower QoL in the ASD group (n = 22), compared to the IGE group (n = 21) (M = 76.8, M = 75.4, M = 61.8, M = 75.3 respectively). The overall CarerQol-7D score mirrored these results with a lower score in the ASD group (M = 68.8) compared to the IGE group (M = 80.3). The individual dimensions in the CarerQol and HRSN revealed no differences. CONCLUSIONS: The QoL as assessed by caregivers for the patients and the caregivers themselves was lower in the ASD group compared to the IGE group. QoL assessment should be integrated in clinical care for comprehensive health management.
Management of febrile seizures in Türkiye: A nationwide survey of pediatricians and pediatric neurologists.
Akıncı Göktaş Ö, Coşkun AN
Brain Dev · 2026 Jun · PMID 41849953 · Publisher ↗
OBJECTIVE: To compare treatment preferences and decision-making patterns of pediatricians and pediatric neurologists in Türkiye regarding febrile seizure (FS) management. METHODS: This cross-sectional survey was conducte...
OBJECTIVE: To compare treatment preferences and decision-making patterns of pediatricians and pediatric neurologists in Türkiye regarding febrile seizure (FS) management. METHODS: This cross-sectional survey was conducted between June and December 2024 using an online questionnaire distributed nationwide to pediatricians and pediatric neurologists. The 34-item survey assessed demographics, clinical experience, FS encounter frequency, and management strategies for simple febrile seizures (SFS), complex febrile seizures (CFS), and febrile status epilepticus (FSE). Statistical analyses were performed using SPSS, with categorical variables compared using chi-square tests. RESULTS: A total of 184 physicians participated (97 pediatric neurologists, 87 pediatricians). Pediatric neurologists reported higher monthly FS encounter rates (p < 0.001). In SFS, both groups avoided continuous antiseizure medication (ASM) and preferred rescue therapy. In CFS, pediatric neurologists more often used intermittent prophylaxis, mainly oral diazepam or clobazam, whereas pediatricians more frequently initiated continuous therapy, most commonly levetiracetam (p < 0.05). For FSE, most participants initiated treatment after the first episode, with continuous levetiracetam as the preferred agent. Family history of afebrile seizures and seizure duration most strongly influenced treatment decisions. Over half of respondents reported difficulty explaining intermittent prophylaxis to caregivers and suggested educational materials as helpful. CONCLUSION: FS management differs between pediatricians and pediatric neurologists in Türkiye, particularly for complex cases. Pediatric neurologists favor guideline-consistent intermittent benzodiazepine-based strategies, whereas pediatricians more often prescribe continuous ASMs. Clearer guidance and improved caregiver education are needed to support evidence-based practice.
Management of pediatric status epilepticus after hospital arrival in Japan: A nationwide questionnaire survey.
Nishiyama M, Ueda Y, Matsuura R … +11 more , Shiohama T, Motobayashi M, Fukuoka M, Oikawa S, Kanai S, Torio M, Kuki I, Nagase H, Akiyama T, Kikuchi K, Maegaki Y
Brain Dev · 2026 Jun · PMID 41849952 · Publisher ↗
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-...
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.
Post-stimulus rebound of EEG power in response to vocal and non-vocal sounds in children with and without autism spectrum disorder: An exploratory study.
Gunji A, Takeichi H, Suzuki K … +7 more , Kobayashi T, Kokubo N, Yasumura A, Yamamoto H, Inoue Y, Kaga M, Inagaki M
Brain Dev · 2026 Jun · PMID 41833206 · Publisher ↗
INTRODUCTION: This hypothesis-generating study examined voice perception to find a straightforward measure of communication difficulties associated with autism spectrum disorder (ASD). Whereas face and voice are the most...
INTRODUCTION: This hypothesis-generating study examined voice perception to find a straightforward measure of communication difficulties associated with autism spectrum disorder (ASD). Whereas face and voice are the most characteristic social stimulus in human visual and auditory perception, studies on the latter are sparse compared with the former. METHODS: The post-stimulus power rebound (PSPR) in response to vocal and non-vocal sounds was characterized in children with ASD. Electroencephalograms were obtained from 11 recording sites in 18 male children with ASD and 18 age-matched typically developing male children. Stimuli included eight degraded human voice sounds, eight degraded non-voice sounds and sixteen control noise sounds. Scores differentiating ASD children from typically developing children were calculated using stepwise regression in each frequency band for both the voice and non-voice stimuli. RESULTS: Between ASD and typically developing children (N = 17 + 17 after artifact rejection), stimulus-dependent PSPR at a right temporal site (T8) in the alpha band was significantly different in response to non-voice sounds, but not in response to voice sounds, showing that PSPR could differentiate the two groups. DISCUSSION: The results show atypical right-lateralized processing of degraded vocal and non-vocal sounds among children with ASD, with less impairment for vocal sounds as indicated by PSPR. This difference may underlie atypical auditory processing and behavior among children with ASD, and suggests the feasibility of PSPR as an index of difficulties in communication during development.
Outcomes of combination therapy with nusinersen, onasemnogene abeparvovec, and risdiplam over 3.5 years in a patient with prenatally diagnosed spinal muscular atrophy type 0: A case report.
Okubo Y, Togashi N, Morishita Y … +13 more , Yoshida S, Kawaji T, Kawashima A, Katata Y, Uneoka S, Yagi Y, Endo W, Inui T, Kato T, Yokomura M, Otsuki N, Saito K, Haginoya K
Brain Dev · 2026 Apr · PMID 41795276 · Publisher ↗
BACKGROUND: Recently introduced disease-modifying therapies have markedly improved survival and motor outcomes, particularly when initiated presymptomatically or in the early symptomatic stage. However, reports on treatm...
BACKGROUND: Recently introduced disease-modifying therapies have markedly improved survival and motor outcomes, particularly when initiated presymptomatically or in the early symptomatic stage. However, reports on treatment of the most severe form, SMA type 0, remain extremely limited. CASE REPORT: We report a patient with prenatally diagnosed spinal muscular atrophy type 0 who was treated with nusinersen and onasemnogene abeparvovec as early and as safely as possible, followed by risdiplam, for further motor acquisition. With continuous physiotherapy, the patient achieved independent walking at 2 years 11 months and showed sustained development without swallowing or respiratory difficulties up to 3.5 years of age. DISCUSSION: Early intervention with combined use of disease-modifying therapies may be beneficial for patients with severe spinal muscular atrophy phenotypes. However, since evidence of efficacy and safety of combination therapy is still lacking, great caution should be paid to this treatment strategy, taking the patient's clinical status into account.
The impact of gestational diabetes mellitus on fetal neural development: A systematic review.
Safwan Z, Ijaz E, Shamim H … +3 more , Fatima A, Ahmad A, Khalid AM
Brain Dev · 2026 Apr · PMID 41791210 · Publisher ↗
OBJECTIVE: To synthesise existing research on the impact of gestational diabetes mellitus (GDM) on fetal neural development and subsequent cognitive function in offspring. METHODS: A systematic review was conducted follo...
OBJECTIVE: To synthesise existing research on the impact of gestational diabetes mellitus (GDM) on fetal neural development and subsequent cognitive function in offspring. METHODS: A systematic review was conducted following PRISMA guidelines. PubMed, Cochrane Library, and ClinicalTrials.gov were searched from January 1964 to October 2024. Studies comparing offspring of mothers with GDM to those without were included. Quality was assessed using the Newcastle-Ottawa Scale (NOS). RESULTS: Seventeen studies met the inclusion criteria. The findings suggest that GDM is linked to subtle yet significant neurodevelopmental modifications, encompassing delays in communication and language proficiency, behavioural dysregulation, as well as heightened susceptibility to autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). Electrophysiological investigations revealed alterations in cortical activity and extended auditory responses, while neuroimaging studies documented structural variations, including changes in the dimensions of the corpus callosum, ventricular size, and sulcal maturation. Molecular investigations uncovered dysregulated microRNAs that play a role in neurogenesis. Numerous studies emphasised the dose-dependent effects of maternal glucose concentrations and the protective impact of effective glycemic control. CONCLUSION: Maternal GDM is associated with alterations in fetal brain structure and function, which may predispose offspring to neurodevelopmental risks. While not all deficits persist, these findings highlight the potential value of early glycemic control and postnatal monitoring for at-risk infants. Further longitudinal research is needed to distinguish causal GDM effects from environmental confounders.
Incidence of new onset neurological disorders due to convulsive status epilepticus in children: A long-term population-based study in Tottori prefecture, Japan.
Kawaguchi T, Okanishi T, Ohta K … +11 more , Arai Y, Urushibara M, Okada S, Tamasaki A, Togawa M, Kinoshita T, Kawaba Y, Nagaishi JI, Morita M, Fujimoto A, Maegaki Y
Brain Dev · 2026 Apr · PMID 41759490 · Publisher ↗
BACKGROUND: Convulsive status epilepticus (CSE) is a type of severe seizure associated with significant neurological sequelae. However, the extent to which CSE causes novel-onset neurological disorders in children remain...
BACKGROUND: Convulsive status epilepticus (CSE) is a type of severe seizure associated with significant neurological sequelae. However, the extent to which CSE causes novel-onset neurological disorders in children remains unclear. This retrospective study aimed to assess long-term neurological outcomes after pediatric CSE, determine the incidence ratios of new-onset neurological conditions, and identify prognostic factors. METHODS: This study enrolled patients with CSE onset between 2006 and 2009 in any of nine hospitals in Tottori Prefecture, Japan, that potentially treated the condition in this area. We collected clinical data from the medical records, analyzed the incidence ratios of CSE, etiologies, and incidences of new-onset neurological diseases/conditions after CSE, and statistically analyzed the prognostic factors. RESULTS: A total of 140 pediatric patients developed new-onset CSE during the study period. The study found an CSE incidence ratio of 43.4 per 100,000 child-years. Febrile CSE was the most common cause. The incidence rates of new-onset neurological diseases/conditions after CSE were 8.6 per 100,000 child-years for epilepsy, 3.4 for intellectual disabilities, 2.8 for motor disabilities and 1.2 for acute mortality per 100,000 child-years. Multivariate analyses revealed that a history of afebrile seizures (p = 0.014), pre-existing structural brain abnormalities (p < 0.001) and acute symptomatic etiology (p = 0.032) were risk factors for new-onset intellectual disability, whereas pre-existing developmental/intellectual delay (p < 0.001) was risk factors for new-onset epilepsy. CONCLUSIONS: In this study, we determined the incidence of new-onset neurological problems due to CSE in children. These results may help to enhance the efficacy of CSE management strategies and improve prognosis.
Response inhibition and working memory in children with attention deficit hyperactivity disorders: An event-related potential study.
Gao X, Zhong L, He H … +2 more , Zhang J, Yang W
Brain Dev · 2026 Apr · PMID 41740334 · Publisher ↗
BACKGROUND: To assess the combined N-back/Nogo paradigm applicability in the measurement of cognitive functions of response inhibition and working memory and to further determine the mechanisms underlying the occurrence...
BACKGROUND: To assess the combined N-back/Nogo paradigm applicability in the measurement of cognitive functions of response inhibition and working memory and to further determine the mechanisms underlying the occurrence of response inhibition and working memory deficits in children with ADHD. MATERIAL AND METHODS: This study used a two-phase design. In Experiment 1, 30 healthy children were recruited via convenience sampling. They performed single N-back, single Go/Nogo, and combined N-back/Nogo tasks while ERPs and behavioral data were recorded. In Experiment 2, 41 children with ADHD were screened using a convenience whole-group sampling method, and 34 healthy controls were matched by sex and age. Both groups completed the combined N-back/Nogo task while ERPs and behavioral performance were assessed. RESULTS: Experiment 1: Comparisons between single and combined tasks in healthy children. There was no significant difference between the single and combined N-back/Nogo tasks on measures of accuracy rate, omission rate, or ERPs (all P > 0.05). Experiment 2: Compared the ADHD and healthy control groups using the combined N-back/Nogo task. The ADHD group demonstrated significantly lower accuracy on both N-back and Nogo components, alongside a higher omission rate specifically on the Nogo component (P < 0.05). The ERP results further revealed reductions in the N-back P300 peak amplitude at sites F4, C3, Cz, C4, and P3 in the ADHD group. Additionally, the ADHD group exhibited prolonged latency of the Nogo-N200 peak at the F3 and C4 sites (all P < 0.05). CONCLUSION: The study revealed working memory and response inhibition deficits in children with ADHD from Xinjiang, using a combined N-back/Nogo paradigm. This also demonstrates the paradigm's applicability in measuring these cognitive functions.
Human herpesvirus 6 and non-human herpesvirus 6 limbic encephalitis in children with allogeneic stem cell transplantation: A case series.
Yoshimura T, Natsume J, Muramatsu H … +14 more , Sajiki D, Narita H, Kumai S, Sawamura F, Suzui R, Shiraki A, Ito Y, Yamamoto H, Nakata T, Shibata T, Ozasa S, Kidokoro H, Kawada JI, Takahashi Y
Brain Dev · 2026 Apr · PMID 41734634 · Publisher ↗
BACKGROUND: Post-transplant acute limbic encephalitis (PALE) has been reported, and human herpesvirus 6 (HHV-6) is one of the causes. Reports of PALE in children are still limited. In the present study, the detailed clin...
BACKGROUND: Post-transplant acute limbic encephalitis (PALE) has been reported, and human herpesvirus 6 (HHV-6) is one of the causes. Reports of PALE in children are still limited. In the present study, the detailed clinico-radiological findings of PALE and the neurological outcomes of four children are reported. CASES: Four patients aged three to twelve years of 142 patients who underwent allogeneic hematopoietic stem cell transplantation developed PALE. Underlying disorders were neuroblastoma in three patients and acute lymphoblastic leukemia in one. All four patients showed disorientation, behavioral changes, emotional dysregulation, anterograde amnesia, or decreased level of consciousness between 12 and 22 days after transplantation. None had clinical seizures. In all patients, MRI showed hyperintense signals in unilateral or bilateral hippocampi, especially in the CA1 area, on diffusion-weighted imaging (DWI), with a decreased apparent diffusion coefficient. Though the hippocampi were also hyperintense on T2-weighted and fluid-attenuated inversion recovery imaging, signal intensity was higher on DWI by visual inspection. Electroencephalograms showed poorly organized posterior dominant rhythm in all patients and left occipito-centro-parietal slow waves in one without epileptiform discharges. HHV-6 DNA was positive in both cerebrospinal fluid and whole blood by polymerase chain reaction in three of the four patients. Two patients had pharmaco-resistant epilepsy and cognitive impairment three years after PALE, but the other two recovered neurologically from PALE. CONCLUSION: A DWI abnormality of the hippocampal CA1 area is a good biomarker for the diagnosis of HHV-6-positive or -negative PALE in children. Glutamatergic dysregulation and hippocampal cytotoxic edema may be involved in PALE.
Arterial spin labeling reveals cerebral perfusion changes associated with involuntary movements in acute encephalopathy with biphasic seizures and late reduced diffusion: A case report.
Asahara R, Enokizono M, Ogawa E … +4 more , Kawakami A, Miyama S, Takanashi JI, Kono T
Brain Dev · 2026 Apr · PMID 41722127 · Publisher ↗
BACKGROUND: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is characterized by a biphasic seizure pattern with distinct neuroimaging findings. While involuntary movements during the recover...
BACKGROUND: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is characterized by a biphasic seizure pattern with distinct neuroimaging findings. While involuntary movements during the recovery phase may be a marker of an unfavorable neurological outcome, their relationship with cerebral perfusion changes remains poorly understood. Arterial spin labeling (ASL) is a non-invasive method of assessing changes in perfusion without using contrast agents that can provide valuable insight into the pathophysiology of the disease. We report herein the first case of AESD demonstrating a correlation between involuntary movements and concurrent abnormalities of cerebral perfusion on ASL. CASE REPORT: A 13-month-old female patient was admitted for fever and status epilepticus. Magnetic resonance imaging (MRI) on day of illness (DOI) 6 revealed frontal lobe diffusion restriction on diffusion-weighted imaging (DWI) and hyperperfusion on ASL. H-MR spectroscopy demonstrated metabolic changes consistent with excitotoxic encephalopathy. By DOI 20, myoclonic movements and ballism had developed, and ASL demonstrated a characteristic pattern of frontal hypoperfusion concurrent with basal ganglia hyperperfusion. The involuntary movements resolved over two months. Follow-up MRI performed 8 months after initial presentation revealed recovery of brain volume and improvement in perfusion abnormalities of the basal ganglia. At the age of 5 years, the patient demonstrated mild developmental delay with well-controlled epilepsy. CONCLUSION: The perfusion abnormalities detected on ASL correlated with the involuntary movements of AESD, which suggests dysregulation of cerebral autoregulation propagation via cortico-basal ganglia circuits. ASL can provide valuable insight into the pathophysiology of AESD and may facilitate assessment of prognosis and therapeutic decision-making by enabling real-time monitoring of changes in cerebral perfusion during the recovery phase.
Cyclic vomiting syndrome.
Hikita T
Brain Dev · 2026 Apr · PMID 41719916 · Publisher ↗
Cyclic vomiting syndrome (CVS) is characterized by recurrent vomiting episodes. In this study, the mean ages at the onset of symptoms and at the diagnosis of children with cyclic vomiting pattern were 5.7 and 8.0 years,...
Cyclic vomiting syndrome (CVS) is characterized by recurrent vomiting episodes. In this study, the mean ages at the onset of symptoms and at the diagnosis of children with cyclic vomiting pattern were 5.7 and 8.0 years, respectively. On average 2.3 years elapsed between the onset and diagnosis, suggesting the difficulty of diagnosing CVS. However, the prevalence of CVS ranges from approximately 0.3% to 2%. Its pathophysiology, prognosis, and natural history need to be further investigated. Various abortive and prophylactic therapies that have been applied in CVS cases were reported. To date, no randomized control study on abortive therapy (i.e., treatment intended to stop a migraine once it starts) for CVS has yet been conducted. Current treatment recommendations are detailed in the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) 2025 guidelines for the management of CVS in children. The NASPGHAN 2025 guidelines for the management of CVS in children recommend non-steroidal anti-inflammatory drugs, triptans, ondansetron, aprepitant, and fosaprepitant for acute medicine. The NASPGHAN 2025 guidelines for the management of CVS in children recommend coenzyme Q10, riboflavin, and magnesium as preventive treatments. The recommended medications include propranolol, cyproheptadine, aprepitant, and amitriptyline. The guidelines also recommend not using the antiseizure medications topiramate and valproic acid. However, antiseizure medications are recommended only for patients who are unresponsive to the aforementioned preventive medications and who have frequent vomiting and severe symptoms.
An increase in cerebrospinal fluid macrophage migration inhibitory factor levels in pediatric patients with acute neuroinflammatory diseases: A preliminary study.
Nasuno M, Motobayashi M, Yamazaki K … +4 more , Ito M, Kobayashi J, Fukuyama T, Inaba Y
Brain Dev · 2026 Apr · PMID 41707435 · Publisher ↗
BACKGROUND: Macrophage migration inhibitory factor (MIF) is a multifaceted cytokine involved in both the innate and adaptive immune systems. The roles of MIF in neuroinflammatory diseases have been described in adults, b...
BACKGROUND: Macrophage migration inhibitory factor (MIF) is a multifaceted cytokine involved in both the innate and adaptive immune systems. The roles of MIF in neuroinflammatory diseases have been described in adults, but remain unclear in the pediatric population. METHODS: We herein retrospectively investigated the cerebrospinal fluid (CSF) levels of MIF and 19 types of related cytokines in pediatric patients with acute neuroinflammatory diseases, i.e., bacterial meningitis (n = 6), aseptic meningitis/encephalitis (n = 8), and febrile infection-related epilepsy syndrome (FIRES) (n = 5), and in patients with febrile seizure (n = 15). RESULTS: CSF MIF levels were significantly higher in the three neuroinflammatory disease groups, particularly in the bacterial meningitis group, than in the febrile seizure group. CSF MIF levels were significantly higher in the bacterial meningitis group than in the FIRES group. CSF MIF levels were higher in the FIRES group than in the febrile seizure group, and this result was independent of age. CSF MIF levels correlated more strongly with interleukin-10, an M2 promoter, than with interferon-γ, an M1 promoter. CONCLUSIONS: CSF MIF levels were elevated in pediatric patients with acute neuroinflammatory diseases. This is the first study to compare differences in CSF MIF levels among neuroinflammatory diseases and to show relationships between MIF and related cytokines.
Senescence markers in peripheral blood mononuclear cells in pediatric drug-resistant epilepsy.
Günbey C, Muratoğlu B, Özdemir C … +2 more , Çetinkaya DU, Yalnızoğlu D
Brain Dev · 2026 Apr · PMID 41698292 · Publisher ↗
BACKGROUND: Senescence, a steady loss of proliferative capacity triggered by complex pathways, has received attention in neurodegenerative diseases but remains obscure in epilepsy. This study aims to investigate whether...
BACKGROUND: Senescence, a steady loss of proliferative capacity triggered by complex pathways, has received attention in neurodegenerative diseases but remains obscure in epilepsy. This study aims to investigate whether the stress of frequent seizures in children triggers cellular senescence. METHODS: Peripheral blood mononuclear cells (PBMC) from children under 12 years of age were analyzed for senescence-associated β-galactosidase (SA-βgal) activity, telomere length, expression of cell cycle arrest genes [p53, p16, p21, retinoblastoma (RB)] along with telomerase reverse transcriptase (TERT), insulin-like growth factors (IGF), and interleukin-6 (IL-6)/tumor necrosis factor-alpha (TNF-alpha) levels. We compared these markers in drug-resistant epilepsy patients with malformations of cortical development (MCD) to those in drug-responsive epilepsy patients and healthy controls (n = 10 each). RESULTS: Our study showed similar PBMC SA-βgal levels across all groups. CD8+ T cell subgroup analysis from the drug-resistant epilepsy group exhibited higher SA-βgal activity. Drug-resistant epilepsy group was associated with the longest telomeres and high TERT expression. p53 and RB expressions were similar to healthy controls in drug-resistant epilepsy group, whereas p21 and p16 expressions were higher. Children with drug-resistant epilepsy with MCD showed significantly higher levels of IL-6 and TNF-alpha than healthy controls or children with drug-responsive epilepsy. CONCLUSION: We observed no evidence of established stress-induced premature or replicative senescence in drug-resistant epilepsy patients. However, elevated proinflammatory cytokines and high p21/p16 expression in the drug-resistant group may suggest ongoing seizures cause cellular stress which could increase susceptibility to senescence in drug-resistant pediatric epilepsy patients over time.
Clinical profiles of tuberous sclerosis complex: A regionally based survey.
Yamada M, Natsume J, Maki Y … +16 more , Ishimaru S, Numoto S, Kobayashi S, Hattori A, Matsukawa Y, Wakahara K, Ishihara N, Sasaki H, Ito Y, Yamamoto H, Nakata T, Kidokoro H, Yoshikawa T, Saitoh S, Okumura A, Takahashi Y
Brain Dev · 2025 Dec · PMID 41693132 · Publisher ↗
BACKGROUND: This study aimed to clarify the clinical profiles of patients with tuberous sclerosis complex (TSC) in the general population by a regionally based survey of medical facilities in a region with 7.5 million re...
BACKGROUND: This study aimed to clarify the clinical profiles of patients with tuberous sclerosis complex (TSC) in the general population by a regionally based survey of medical facilities in a region with 7.5 million residents, and investigate differences in clinical profiles according to medical facility size and type. METHODS: A survey was sent to 146 hospitals and clinics regarding clinical profiles of patients with TSC who lived in Aichi Prefecture, Japan, between 2013 and 2018. Medical facilities were classified as large hospitals (≥750 beds or a children's hospital), small hospitals (<750 beds), institutions for handicapped children, and private clinics. RESULTS: Information was obtained of 232 patients (median age, 25 years; range, 1-81 years). Estimated prevalence of TSC was 3.1 per 100,000. Cortical tubers were present in 88 %, epilepsy in 81 %, autism spectrum disorder in 44 %, and subependymal giant cell astrocytoma in 17 %. Hypomelanotic macules, facial angiofibroma, renal angiomyolipoma, and cardiac rhabdomyoma were present in >50 % of patients. Rates of epilepsy with frequent seizures and autism spectrum disorder were both higher in patients in institutions for handicapped children. In more than half of patients in institutions for handicapped children information on cranial MRI findings was not obtained. CONCLUSIONS: Our regionally based study confirmed the clinical profiles previously reported in specialized hospitals for TSC and found that clinical characteristics differed among the types and sizes of medical facilities. Multicenter information sharing and collaboration between general hospitals and institutions for handicapped children are important for the comprehensive care of patients with TSC.
Child neurology: Early neuroprotective and immunomodulatory intervention in acute shock with encephalopathy and multiorgan failure: Cytokine-storm encephalopathy-case report.
Tsuiki N, Aihara T, Hayakawa I … +7 more , Moriwaki T, Tomita K, Takahashi T, Irie S, Matsumoto S, Uematsu S, Abe Y
Brain Dev · 2026 Apr · PMID 41679242 · Publisher ↗
BACKGROUND: Acute shock with encephalopathy and multiorgan failure (ASEM)-within the infection-triggered encephalopathy syndromes (ITES)-is a fulminant para-infectious encephalopathy that can progress to diffuse cerebral...
BACKGROUND: Acute shock with encephalopathy and multiorgan failure (ASEM)-within the infection-triggered encephalopathy syndromes (ITES)-is a fulminant para-infectious encephalopathy that can progress to diffuse cerebral edema within hours. Guidance on time-critical immunomodulation remains limited. CASE: An 8-year-old girl developed abrupt altered mental status on day 2 of an influenza A respiratory illness. Glasgow Coma Scale score was E4V1M5 with hyperpyrexia, hypoxemia, and circulatory instability, prompting intubation. Head CT at 120 min showed early diffuse cerebral edema. At 180 min (transport-team arrival), systolic blood pressure was 60 mmHg; a neuroprotective bundle with vasoactive agents achieved partial stabilization. Methylprednisolone pulse therapy began at 200 min; therapeutic plasma exchange (TPE) at 430 min. Continuous EEG showed diffuse slowing in the 0.5-2 Hz band without suppression or electrographic seizures. Steroid pulses plus TPE were continued for five days, with adjunct intravenous immunoglobulin on days 5-6. Vasopressors were weaned by day 3; renal replacement therapy ended by day 5. Brain MRI on day 7 showed no new abnormalities. She was extubated on day 7; blood cultures remained negative. Neurologic status steadily improved. At 3.5 months, full-scale IQ was 111; at 6 months, only mild truncal ataxia persisted without functional limitation. CONCLUSIONS: This ASEM case illustrates parallel diagnosis and treatment within a narrow window. Simple triggers-shock with multiorgan failure/disseminated intravascular coagulation and early imaging red flags-can support rapid transfer and early immunomodulation (e.g., steroid pulses and TPE) alongside neuroprotective care, potentially averting irreversible brain injury.
Association between left precuneus functional connectivity and early neurodevelopment in preterm infants.
Feng Y, Li X, Bi S … +5 more , Wang L, Wang Y, Zhang C, Dai L, Zhang J
Brain Dev · 2026 Apr · PMID 41671832 · Publisher ↗
OBJECTIVE: Preterm birth is associated with an increased risk of functional brain network alterations, which may contribute to long-term motor and neurocognitive deficits. However, the underlying neural mechanisms remain...
OBJECTIVE: Preterm birth is associated with an increased risk of functional brain network alterations, which may contribute to long-term motor and neurocognitive deficits. However, the underlying neural mechanisms remain incompletely understood. This study aimed to investigate functional brain activity changes in preterm infants and their correlation with early neurobehavioral development. METHODS: Fifteen preterm infants and 15 full-term infants underwent scanning using a 3.0T Philips MRI scanner. Three resting-state functional magnetic resonance imaging (rs-fMRI) data-driven approaches, amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo), and seed-based functional connectivity (FC) were used to comprehensively evaluate functional brain alterations in preterm infants at term-equivalent age (TEA). Correlations between Neonatal Behavioral Neurological Assessment (NBNA) scores and FC values of abnormally connected brain regions were further analyzed in preterm infants at TEA. RESULTS: Compared with full-term infants, preterm infants exhibited significantly higher ALFF and ReHo values in the left precuneus. Using the left precuneus as a seed region for FC analysis, preterm infants showed reduced FC with the left Rolandic operculum, right putamen, and left hippocampus. Additionally, FC values between the left precuneus and left Rolandic operculum, as well as between the left precuneus and right putamen, were positively correlated with NBNA scores in preterm infants. CONCLUSIONS: Preterm infants may present early functional connectivity impairments of the left precuneus, which may be a potential neural correlate of neurobehavioral abnormalities. These findings provide insights into the neurodevelopmental mechanisms underlying preterm birth-related deficits and may inform early clinical assessment strategies.
Clinical and molecular profiles of patients with Xia-Gibbs syndrome: a cohort in Japan.
Shirai H, Oitani Y, Nishi E … +13 more , Haraguchi K, Nakamura T, Ichinose F, Sanefuji M, Hattori A, Yanagi K, Shimojima Yamamoto K, Okamoto N, Matsuo M, Saitoh S, Yoshiura KI, Kaname T, Yamamoto T
Brain Dev · 2026 Apr · PMID 41653504 · Publisher ↗
BACKGROUND: Xia-Gibbs syndrome (XGS) is a rare neurodevelopmental disorder caused by pathogenic variants in the AT-hook DNA binding motif containing 1 (AHDC1) gene. More than 100 patients with XGS have been reported. In...
BACKGROUND: Xia-Gibbs syndrome (XGS) is a rare neurodevelopmental disorder caused by pathogenic variants in the AT-hook DNA binding motif containing 1 (AHDC1) gene. More than 100 patients with XGS have been reported. In this study, we describe the findings from a Japanese cohort of patients with XGS. To enhance understanding, we also conducted a systematic literature review of XGS. METHODS: We collected clinical and genetic information from seven new Japanese patients with XGS which were diagnosed through comprehensive genetic analysis. A systematic literature review was also conducted using PubMed. RESULTS: All Japanese patients carried premature truncation variants or deletions. The core clinical features were global developmental delay and hypotonia, which were consistent with those observed in the 106 previously reported patients identified in our literature review. In one patient with a frameshift variant, escape from nonsense-mediated mRNA decay was confirmed using the patient's sample. CONCLUSION: The clinical and molecular profiles of Japanese patients with XGS were analyzed and compared with those of previously reported patients from other countries, confirming the consistent characteristics of XGS. This study provides direct evidence of nonsense-mediated mRNA decay escape. A comprehensive understanding of this expanding phenotype is crucial for accurate diagnosis and management.
A scoping review of functional near-infrared spectroscopy studies of reading development in children aged 6-12.
Bode DA, Rankaduwa SS, Elliott LM … +1 more , Newman AJ
Brain Dev · 2026 Apr · PMID 41628521 · Publisher ↗
SIGNIFICANCE: Functional near-infrared spectroscopy (fNIRS) offers several advantages for neuroimaging in children, yet its use in research on cognitive development, particularly reading, remains limited. AIM: This scopi...
SIGNIFICANCE: Functional near-infrared spectroscopy (fNIRS) offers several advantages for neuroimaging in children, yet its use in research on cognitive development, particularly reading, remains limited. AIM: This scoping review focuses on fNIRS studies examining reading development in school-aged children (6-12 years), with four goals: (1) characterize methodological parameters, including stimuli and tasks; (2) identify brain regions showing fNIRS signal changes during reading and across development; (3) document technical fNIRS methods; (4) assess adherence to best practice in fNIRS reporting. APPROACH: We searched PubMed, Embase, PsycINFO, Scopus, gray literature, and reference lists. RESULTS: Reading-related fNIRS activation was most frequently observed in the inferior frontal gyrus, superior temporal gyrus, and middle frontal gyrus. However, only seven studies directly examined developmental changes in reading using fNIRS. A consistent issue across studies was underreporting of technical methods and incomplete adherence to recommended best practices for fNIRS data collection and analysis. CONCLUSIONS: To advance the field, future fNIRS research on reading development should (1) follow established reporting guidelines, (2) ensure adequate brain region coverage when designing probe arrays, and (3) prioritize longitudinal and developmental investigations to better capture changes in brain function during reading development.
Toward etiology-specific and radiomics-based approaches in cytotoxic lesions of the corpus callosum.
Tekgül H, Ataş Y, Kanmaz S … +1 more , Eraslan C
Brain Dev · 2026 Apr · PMID 41621374 · Publisher ↗
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