Brain Dev. [JOURNAL]
Sun
200 papers
Exercise-induced muscle injury in Duchenne muscular dystrophy: impaired mitophagy and altered PINK1-PARKIN pathway in mdx mice.
Li J, Zhao Q, He H … +1 more , Song X
Brain Dev · 2026 Jun · PMID 42143857 · Publisher ↗
OBJECTIVE: Duchenne muscular dystrophy (DMD) is a severe hereditary disorder characterized by dystrophin deficiency, leading to progressive muscle weakness. Mitochondrial dysfunction and impaired quality control, particu...
OBJECTIVE: Duchenne muscular dystrophy (DMD) is a severe hereditary disorder characterized by dystrophin deficiency, leading to progressive muscle weakness. Mitochondrial dysfunction and impaired quality control, particularly via the PTEN-induced putative kinase 1 (PINK1)-E3 ubiquitin ligase PARK2 (PARKIN) mitophagy pathway, are implicated in DMD pathogenesis, but the impact of exercise remains unclear. This study investigated the effects of short-term high-intensity exercise on skeletal muscle pathology and mitophagy in mdx mice. METHODS: Skeletal muscle from DMD patients and non-dystrophic controls (CTR) was analyzed for mitochondrial content and PINK1-PARKIN expression. Eight-week-old male mdx and C57 control mice underwent a 5-day rotarod exercise protocol. Muscle pathology was assessed using hematoxylin and eosin (HE), acid phosphatase (ACP), and succinate dehydrogenase (SDH) staining. Mitophagy was evaluated via immunofluorescence for microtubule-associated protein 1 light chain 3 (LC3), cytochrome c oxidase subunit IV (COXIV), and voltage-dependent anion channel (VDAC), as well as western blotting for PINK1 and PARKIN. Transmission electron microscopy (TEM) was used to visualize mitochondrial ultrastructure. RESULTS: In DMD patients, skeletal muscle showed reduced mitochondrial content and dysregulated PINK1-PARKIN expression. In mdx mice, basal mitophagy markers were elevated. Short-term high-intensity exercise exacerbated muscle necrosis and inflammation in mdx mice while impairing the activation of PINK1-PARKIN-mediated mitophagy, contrasting with the adaptive response in wild-type mice. CONCLUSION: Short-term high-intensity exercise exacerbates skeletal muscle pathology in mdx mice, which is associated with impaired activation of PINK1-PARKIN-mediated mitophagy, underscoring the critical role of mitochondrial quality control in DMD and the need for tailored exercise regimens.
Genotype-dependent response to combined levodopa/benserazide and trihexyphenidyl in pediatric genetic dystonia.
Zhou X, Li Y, Luo X … +3 more , He Z, Liu M, Li P
Brain Dev · 2026 Jun · PMID 42119286 · Publisher ↗
BACKGROUND: Genetic etiologies underlie a substantial proportion of pediatric dystonia, but whether treatment response to combined dopaminergic and anticholinergic therapy varies by genotype remains unknown. METHODS: Thi...
BACKGROUND: Genetic etiologies underlie a substantial proportion of pediatric dystonia, but whether treatment response to combined dopaminergic and anticholinergic therapy varies by genotype remains unknown. METHODS: This retrospective cohort study analyzed 36 children with genetically confirmed dystonia, classified into three subgroups: PANK2 (n = 7), channelopathies (SCN1A/SCN2A/SCN3A/SCN1B, KCNQ2; n = 6), and other monogenic etiologies (n = 23; 19 distinct genes). All received levodopa/benserazide and trihexyphenidyl combination therapy for 16 weeks. Outcomes included Barry-Albright Dystonia Scale (BADS), Gross Motor Function Measure-88 (GMFM-88), Quality of Upper Extremity Skills Test (QUEST), and Cerebral Palsy Quality of Life Questionnaire (CP-QOL). RESULTS: Treatment response was genotype-dependent. PANK2 patients showed excellent improvement (ΔBADS -6.6 ± 3.0; ΔGMFM-88 + 49.6 ± 45.8). Other monogenic patients showed moderate improvement comparable to our cerebral palsy cohort (ΔBADS -6.1 ± 1.9; ΔGMFM-88 + 32.2 ± 26.5). Channelopathy patients derived minimal benefit (ΔBADS -3.5 ± 1.2; ΔGMFM-88 + 6.2 ± 2.9; p < 0.001 compared to both other groups). All six patients with status dystonicus (all in the other monogenic group) responded excellently. Adverse event rates were comparable across groups (p = 0.61). CONCLUSIONS: Genotype determines treatment response to levodopa/benserazide and trihexyphenidyl in pediatric genetic dystonia. PANK2 and most other monogenic etiologies respond well, while channelopathies derive minimal benefit. Genotype, not severity, guides therapy.
Daily administration of long-acting adrenocorticotropic hormone (ACTH) alters the developmental pattern of plasma fibrinogen in juvenile rats.
Takeda Y, Sakakibara T, Horiuchi K … +2 more , Ogiwara K, Nogami K
Brain Dev · 2026 Jun · PMID 42114184 · Publisher ↗
BACKGROUND: We previously reported that adrenocorticotropic hormone (ACTH) therapy for infantile epileptic spasm syndrome (IESS) decreases plasma fibrinogen (Fbg) levels. However, the underlying mechanism(s) has not been...
BACKGROUND: We previously reported that adrenocorticotropic hormone (ACTH) therapy for infantile epileptic spasm syndrome (IESS) decreases plasma fibrinogen (Fbg) levels. However, the underlying mechanism(s) has not been elucidated. An animal model approximating early childhood in humans uses juvenile rats at postnatal days (P)21-P35, but its applicability to this question has not been examined. AIM: To determine the effects of the daily long-acting ACTH administration on plasma Fbg levels in juvenile rats. METHODS: Wistar rats were intramuscularly injected daily with normal saline (NS), low-dose ACTH (LD), or high-dose ACTH (HD) daily from P21 to P35. Blood samples were collected before administration (P21), 7 days (P28) and 14 days (P35) after treatment initiation. Body weight and plasma corticosterone and Fbg levels were assessed. RESULTS: ACTH administration increased plasma corticosterone levels and suppressed weight gain. Fbg levels showed a transient increase at P28 in the HD group, but this was not sustained at P35. In the LD group, Fbg levels did not show developmental increases as observed in controls. No significant decrease in absolute plasma Fbg levels was detected. Repeated-measures correlation analysis revealed no association between corticosterone and Fbg levels. CONCLUSION: Daily ACTH administration in juvenile rats did not reduce absolute plasma Fbg levels but altered the developmental trajectory of Fbg levels. These findings suggest that the decrease in Fbg levels observed during ACTH therapy in human infants may reflect the developmental regulation of fibrinogen production rather than a direct glucocorticoid-mediated effect.
Th1-Th17 immune signature in children with autism spectrum disorder.
Naranjo-Galvis CA, Zuluaga-Valencia JB, Sánchez-López JV … +3 more , Zuluaga-Arroyave T, Delgado-Reyes AC, Salamanca-Duque LM
Brain Dev · 2026 Jun · PMID 42096802 · Publisher ↗
BACKGROUND: Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by substantial inter-individual variability in clinical presentation and underlying biology. Increasing evidence im...
BACKGROUND: Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by substantial inter-individual variability in clinical presentation and underlying biology. Increasing evidence implicates immune dysregulation in ASD; however, well-defined Th1-Th17 immune signatures in pediatric populations remain incompletely characterized using rigorous analytical approaches. METHODS: We conducted a cross-sectional case-control study including 40 children with ASD and 25 neurotypical controls. The plasma concentrations of nine cytokines were quantified using a multiplex immunoassay. Cytokine differences were evaluated using false discovery rate correction, standardized effect size estimation, and generalized linear models adjusted for sex and age of the participants. In parallel, targeted next-generation sequencing of 236 ASD-implicated genes was performed as an exploratory approach to contextualize the immune findings within neurodevelopmental and immune-related pathways. RESULTS: Children with ASD exhibited a consistent Th1-Th17 immune signature, characterized by significantly higher plasma levels of IL-2, IL-12, and IL-17 than neurotypical controls. These differences remained robust after correction for multiple testing and covariate adjustment, with large standardized effect sizes. No group differences were observed for IL-4, IL-6, IL-10, TNF-α, IFN-γ, or IL-1β, indicating a selective rather than generalized inflammatory profile. Sex-stratified analyses revealed higher IL-2 and IL-17 levels in females with ASD, suggesting a quantitative sex-related modulation of Th1-Th17 immune responses. Exploratory genetic analyses identified rare variants in genes involved in chromatin remodeling, synaptic organization, and immune-related processes, converging on pathways related to transcriptional regulation and immune signaling. CONCLUSIONS: This study provides an exploratory yet analytically robust characterization of the Th1-Th17 immune signature in children with ASD. The consistency and specificity of the immune findings support their biological relevance and underscore the value of integrative immune-informed approaches to understand the biological heterogeneity in pediatric ASD.
Therapeutic effects of tDCS on behavioral symptoms of autism spectrum disorders in children and adolescents: A systematic review and meta-analysis of randomized sham-controlled trials.
Tung CB, Lu YC, Sun CK … +3 more , Cheng YS, Chen CM, Hung KC
Brain Dev · 2026 Jun · PMID 42092376 · Publisher ↗
OBJECTIVE: This study aimed at investigating the effectiveness of transcranial direct current stimulation (tDCS) in improving autism spectrum disorder (ASD)-related behavioral symptoms in children and adolescents. METHOD...
OBJECTIVE: This study aimed at investigating the effectiveness of transcranial direct current stimulation (tDCS) in improving autism spectrum disorder (ASD)-related behavioral symptoms in children and adolescents. METHODS: Randomized placebo-controlled trials (RCTs) recruiting children/adolescents were identified from major databases using the keywords "tDCS" and "ASD". Outcomes included improvement in ASD-related overall/core symptoms and treatment acceptability. Effect sizes of continuous and categorical data were expressed as standardized mean difference (SMD) and odds ratios (ORs), respectively, with 95% confidence intervals. RESULTS: Meta-analysis of nine RCTs (278 participants, mean age = 8.1) showed improvement in overall behavioral symptoms, social function, and communication in the tDCS group compared with sham-controls [SMD = -0.50, p < 0.01; SMD = -0.40, p = 0.02 (seven studies) and SMD = -0.34, p = 0.04 (six studies), respectively] without difference in symptoms of restricted and repetitive behaviors (SMD = -0.36, p = 0.06). Subgroup analysis revealed greater improvement in studies enrolling only children than those that also recruited adolescents (SMD = -0.70 vs. -0.06, respectively, p = 0.03). No difference was noted in treatment acceptability (i.e., the number of participants withdrawing from a study) between the tDCS and sham-controlled groups. CONCLUSIONS: Our study supported tDCS use for improving overall behavioral symptoms of ASD in children and adolescents, mainly those pertinent to socio-communication, with fair treatment acceptability.
Role of NMDAR-NMNAT in sevoflurane exposure-induced learning memory deficits.
Hu N, Ji W, Dou J … +1 more , Chen X
Brain Dev · 2026 Jun · PMID 42081862 · Publisher ↗
OBJECTIVE: This study investigated the roles of CREB and NMNATs in sevoflurane-induced cognitive deficits and synaptic alterations in developing hippocampal neurons. METHODS: 160 postnatal day-7 male SD rats were randomi...
OBJECTIVE: This study investigated the roles of CREB and NMNATs in sevoflurane-induced cognitive deficits and synaptic alterations in developing hippocampal neurons. METHODS: 160 postnatal day-7 male SD rats were randomized into four groups: Control; Sevo (3% sevoflurane for 6 h); Sevo+D-cycloserine (DCS, an NMDA receptor agonist); and AP-5 (an NMDA receptor antagonist). Cognitive function was assessed at 8 weeks using the Morris water maze. Dendritic spine density/morphology in hippocampal CA1 was analyzed via Golgi-Cox Staining. Protein levels of NMNAT1, NMNAT2, CREB, and p-CREB were measured by western blot and immunofluorescence. RESULTS: Compared to controls, sevo-exposed rats exhibited significant spatial memory impairment, demonstrated by increased escape latency, longer path length, and fewer platform crossings. This group also showed reduced dendritic spine density and altered morphology in CA1, alongside decreased p-CREB and NMNAT1/2 expression. In contrast, DCS pretreatment before sevo exposure reversed these deficits, restoring cognitive performance, spine density/morphology, and p-CREB/NMNAT1/2 levels. CONCLUSION: Sevoflurane induces learning/memory deficits and dendritic spine pathology in neonatal rats, likely via NMDA receptor-mediated downregulation of p-CREB and NMNAT1/2. DCS pretreatment effectively mitigates these effects, highlighting that enhancing NMDA receptor activity can counteract sevoflurane-induced neurotoxicity. NMDA receptor modulation represents a promising therapeutic strategy for postoperative cognitive dysfunction.
Successful management of withdrawal symptoms from long-term intravenous dexmedetomidine using guanfacine in a pediatric patient: a case report.
Okada K, Okanishi T, Yoshino G … +2 more , Okuda T, Maegaki Y
Brain Dev · 2026 Jun · PMID 42070379 · Publisher ↗
INTRODUCTION: Dose reduction or discontinuation of dexmedetomidine, an alpha-2 adrenergic agonist sedative, after prolonged continuous administration may be associated with withdrawal syndrome. In adults, the adjunctive...
INTRODUCTION: Dose reduction or discontinuation of dexmedetomidine, an alpha-2 adrenergic agonist sedative, after prolonged continuous administration may be associated with withdrawal syndrome. In adults, the adjunctive use of guanfacine, another alpha-2 adrenergic agonist, has been reported to facilitate the tapering and discontinuation of dexmedetomidine. Herein, we report the first pediatric patient in whom this approach was successfully used. CASE REPORT: A previously healthy 8-year-7-month-old girl developed febrile infection-related epilepsy syndrome and subsequently developed drug-resistant epilepsy and severe intellectual disability. She required tube feeding in the acute phase and underwent a gastrostomy at 9 years and 10 months of age. Continuous dexmedetomidine infusion was initiated immediately after surgery to maintain postoperative rest. Although tapering of dexmedetomidine was attempted starting on postoperative day 25, withdrawal syndrome, characterized predominantly by vomiting, fever, and agitation, occurred on three occasions each time the dose was reduced, necessitating re-escalation of dexmedetomidine to its original dose. When adjunctive guanfacine was introduced and dexmedetomidine tapering resumed on postoperative day 43, dexmedetomidine was successfully discontinued on postoperative day 49 without withdrawal symptoms. No adverse effects attributable to guanfacine such as hypotension or bradycardia were observed. DISCUSSION: Even in pediatric patients, adjunctive guanfacine may enable effective tapering and discontinuation of long-term dexmedetomidine while preventing withdrawal syndrome.
Spinal hypomyelination in a child with classic hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC): expanding the neuroradiological spectrum, a case report.
Sugiyama R, Baba S, Kagaya R … +3 more , Sato N, Murakami N, Komaki H
Brain Dev · 2026 Jun · PMID 42061272 · Publisher ↗
BACKGROUND: Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a progressive hypomyelinating leukodystrophy caused by pathogenic variants in the tubulin beta-4A gene (TUBB4A). Some patients exhib...
BACKGROUND: Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a progressive hypomyelinating leukodystrophy caused by pathogenic variants in the tubulin beta-4A gene (TUBB4A). Some patients exhibit clinical symptoms suggestive of spinal cord involvement; however, spinal cord magnetic resonance imaging (MRI) findings have rarely been described. CASE PRESENTATION: We performed spinal cord MRI in an 11-year-old boy carrying the most common, prototypical H-ABC-associated TUBB4A variant (p.D249N) and identified hypomyelinating changes in the spinal cord. In addition to the typical motor symptoms, he exhibited impaired vibration and joint position sense in the lower limbs, suggestive of posterior column involvement of the spinal cord. On somatosensory evoked potential (SEP) testing, spinal segmental responses were preserved, whereas the more rostral components were absent. DISCUSSION/CONCLUSION: Our case indicates that spinal hypomyelination can also be present in H-ABC. The concordant clinical findings, spinal MRI abnormalities, and SEP results in our patient suggest involvement of the dorsal column pathways and indicate that spinal cord pathology could contribute to the clinical manifestations and disease severity.
Four-year neurodevelopmental outcomes in infants with symptomatic congenital cytomegalovirus disease treated with oral valganciclovir: A prospective follow-up study in Japan.
Kakei Y, Morioka I, Imai T … +9 more , Okahashi A, Fujioka K, Nozu K, Yoshikawa T, Moriuchi H, Kakimoto Y, Ito Y, Oka A, Japanese Congenital Cytomegalovirus Study Group
Brain Dev · 2026 Jun · PMID 42044599 · Publisher ↗
BACKGROUND: Congenital cytomegalovirus (CMV) infection is a leading cause of neurodevelopmental disabilities. Although oral valganciclovir (VGCV) treatment has shown short-term benefits, long-term outcomes beyond 3 years...
BACKGROUND: Congenital cytomegalovirus (CMV) infection is a leading cause of neurodevelopmental disabilities. Although oral valganciclovir (VGCV) treatment has shown short-term benefits, long-term outcomes beyond 3 years remain unclear. OBJECTIVE: To evaluate 4-year neurodevelopmental outcomes in infants with symptomatic congenital CMV (SCCMV) disease treated with VGCV and identify predictors of adverse outcomes. METHODS: This prospective follow-up study (VGCV-2) included 24 infants with SCCMV disease who received oral VGCV (16 mg/kg, twice daily for 6 months). Neurodevelopmental assessments were performed at 1, 2, 3, and 4 years of age using the Kyoto Scale of Psychological Development (KSPD). The primary outcome was developmental delay (developmental quotient [DQ] < 70) at 4 years. Secondary outcomes included diagnoses of neurodevelopmental disorders and results of autism spectrum disorder (ASD) screening. RESULTS: Twenty-one participants (87.5%) completed the 4-year follow-up. Developmental delay was evident in 28.6% (6/21) of patients at 4 years. Neurodevelopmental disorders, including intellectual disability (28.6%), ASD (19.0%), and cerebral palsy (14.3%), were diagnosed in 42.9% (9/21) of patients. A poorer best-ear hearing assessment at baseline was a significant predictor of developmental delay. Shorter body length, smaller head circumference at birth, and poorer baseline hearing were significantly associated with the diagnosis of neurodevelopmental disorders. Early positive Modified Checklist for Autism in Toddlers screening at 2 and 3 years strongly predicted the diagnosis of neurodevelopmental disorders. CONCLUSION: Despite VGCV treatment, substantial neurodevelopmental impairment persisted for 4 years in children with SCCMV disease. Early clinical markers can help identify high-risk infants who require intensive developmental support. (Clinical trial registration: jRCT2051190075).
Gait analysis of children with neurodevelopmental disorders using gait profile score.
Takahashi K, Mizukami M, Yoshikawa K … +4 more , Miyata K, Ohguro H, Nakai A, Nakayama T
Brain Dev · 2026 Jun · PMID 42025278 · Publisher ↗
BACKGROUND: Neurodevelopmental disorders (NDDs) are a group of disorders that become evident early in development. Recently, gait disorders in NDDs have been the focus of increasing attention; however, no unified view ha...
BACKGROUND: Neurodevelopmental disorders (NDDs) are a group of disorders that become evident early in development. Recently, gait disorders in NDDs have been the focus of increasing attention; however, no unified view has been attained. Gait Profile Score (GPS) is an index that combines three-dimensional gait analysis (3DGA) data into a single numerical value. This study aimed to characterize gait disorders in children with NDD using GPS. METHODS: Children aged 5-15 years with various NDDs were included in this study. The reference group included children with the same conditions as those with typical development (TD). Participants walked along a 14-m walking path at a self-selection speed, and gait data were assessed using Internal Measurement Unit-based 3DGA to calculate the GPS and Gait Variable Scores (GVS). RESULTS: GPS was significantly higher in the NDD group than in the reference group. Additionally, the GVS of each joint was significantly greater in the NDD group for right ankle dorsiflexion and plantar flexion. Furthermore, the right ankle kinematic curve during the gait cycle revealed that the children with NDD demonstrated greater plantar flexion during the swing phase than the reference group. CONCLUSION: GPS revealed substantial differences between children with TD and those with NDD. The difference in GPS between children with TD and those with NDD was extremely small. GPS use allowed us to quantify small differences in gait patterns between children with NDD and those with TD. Furthermore, the gait pattern of children with NDD was characterized by dorsiflexion and plantar flexion of the ankle joints.
Screening for serum antineuronal antibodies in pediatric epilepsy.
Bektas H, Tagiyev A, Gunbey C … +4 more , Konuskan B, Sener B, Yalnizoglu D, Anlar B
Brain Dev · 2026 Jun · PMID 42025277 · Publisher ↗
OBJECTIVE: Autoimmunity has been associated with epilepsy, either as the cause or consequence of seizures. This study evaluated serum neuronal autoantibodies in pediatric focal epilepsy and assessed the utility of the An...
OBJECTIVE: Autoimmunity has been associated with epilepsy, either as the cause or consequence of seizures. This study evaluated serum neuronal autoantibodies in pediatric focal epilepsy and assessed the utility of the Antibody Prevalence in Epilepsy (APE) score in identifying potential immune-mediated cases. METHODS: Forty-four pediatric patients with focal epilepsy were tested for serum antibodies against NMDA-R, LGI1, CASPR2, GABABR, AMPAR, and GAD65. Two etiological groups were formed according to clinical and neuroimaging features: Group-1 (n = 20) with known structural/genetic etiologies; Group-2 (n = 24) with acquired/remote symptomatic epilepsy with possible secondary autoimmune mechanisms (e.g., hippocampal sclerosis, history of encephalitis/hypoxia). APE scores were calculated using clinical, electroencephalographic, neuroimaging data; cerebrospinal fluid (CSF) parameters were not included. RESULTS: The age at seizure onset and evaluation and epilepsy duration were similar between groups. No specific neuronal antibodies were identified in any patient. Low-titer anti-GAD antibodies were observed in five patients across both groups and were considered clinically irrelevant. The median APE score was significantly higher in Group-2 (p = 0.030). Four patients (16.7%) in Group-2 had an APE score ≥ 4 whereas none in Group-1. CONCLUSION: Routine serum screening with standard commercial antibody panel did not identify neuronal antibodies in this pediatric cohort with chronic focal epilepsy. APE score distinguished patients with possible immune etiologies, suggesting that validated clinical scoring systems assist in selecting patients who may benefit from antibody screening in clinical practice.
Validity of bioelectrical impedance analysis to estimate body composition in patients with severe motor and intellectual disabilities.
Kurima T, Shimizu Y, Hada Y … +1 more , Nakayama T
Brain Dev · 2026 Jun · PMID 42019160 · Publisher ↗
OBJECTIVE: Assessing nutritional status in patients with severe motor and intellectual disabilities (SMID) is essential but challenging. While dual-energy X-ray absorptiometry (DXA) is the standard method for body compos...
OBJECTIVE: Assessing nutritional status in patients with severe motor and intellectual disabilities (SMID) is essential but challenging. While dual-energy X-ray absorptiometry (DXA) is the standard method for body composition analysis, its clinical utility is limited by logistical constraints. This study aimed to evaluate the concurrent validity and agreement of bioelectrical impedance analysis (BIA) compared with DXA in patients with SMID. METHODS: Twelve patients with SMID (median age: 11 years) underwent body composition measurements using a multi-frequency BIA device and DXA. Agreement between the two methods for fat-free mass (FFM), body fat mass (BF), percentage body fat (%BF), and regional lean mass was assessed using intraclass correlation coefficients (ICCs) and Bland-Altman analysis. RESULTS: BIA demonstrated excellent concurrent validity for whole-body absolute mass parameters, with ICCs of 0.981 for FFM and 0.978 for BF. Mean bias was minimal for FFM (0.3 kg) and BF (-0.3 kg). However, %BF showed lower validity (ICC = 0.813) and was substantially underestimated (mean bias -7.1%). Bland-Altman analysis revealed wide limits of agreement for all parameters and a significant proportional bias for BF, indicating overestimation as adiposity increased. Regional analysis showed high validity for the trunk but poor agreement for limb measurements. CONCLUSION: IA is a useful non-invasive alternative for assessing FFM and BF at the group level in patients with SMID. However, caution is warranted for individual assessment, particularly for %BF, which BIA tends to underestimate in this population.
Dynamic thalamo-cortical perfusion changes in myoclonic-atonic seizures captured by ictal technetium-99m ethyl cysteinate dimer single-photon emission computed tomography: A case report.
Matsuura R, Hamano SI, Oba A … +6 more , Horita H, Daida A, Hirata Y, Koichihara R, Kikuchi K, Oka A
Brain Dev · 2026 Jun · PMID 42019159 · Publisher ↗
PURPOSE: Ictal and interictal single-photon emission computed tomography (SPECT) has not been used to characterize myoclonic-atonic seizures. However, monitoring changes in cerebral blood flow (CBF) may help determine th...
PURPOSE: Ictal and interictal single-photon emission computed tomography (SPECT) has not been used to characterize myoclonic-atonic seizures. However, monitoring changes in cerebral blood flow (CBF) may help determine the pathogenetic mechanisms of this condition. METHODS: We evaluated myoclonic-atonic seizures using technetium-99m ethylene cysteinate dimer (ECD)-SPECT and ictal SPECT subtraction co-registered with magnetic resonance imaging (SISCOM). RESULTS: A 3-year-old boy with normal development presented with truncal ataxia caused by acute cerebellitis at 1 year and 10 months, followed by atonic seizures at 2 years and 1 month and myoclonic-atonic seizures at 2 years and 6 months. Seizures could not be controlled by valproate, lamotrigine, or clonazepam. By 3 years of age, he experienced up to 40 myoclonic-atonic seizures per day, confirmed using ictal electroencephalography. Interictal electroencephalography showed diffuse spike-and-wave complexes. Ictal ECD-SPECT demonstrated increased CBF in the right precentral gyrus and temporal lobe and decreased CBF in both thalami. The patient was diagnosed with epilepsy with myoclonic-atonic seizures. Seizure control was achieved after adrenocorticotropic hormone therapy. Following treatment, interictal ECD-SPECT images demonstrated no difference in CBF between the left and right precentral gyri and temporal lobes, and resolution of hypoperfusion in both thalami. SISCOM revealed hyperperfusion in the right centroparietal region. CONCLUSION: Adrenocorticotropic hormone therapy successfully treated myoclonic-atonic seizures and resolved bilateral thalamic hypoperfusion. Thalamic dysfunction may also be involved in myoclonic-atonic seizures. This case uniquely demonstrates CBF changes in the motor cortex and thalamus and provides insight into the mechanisms underlying myoclonic-atonic seizures.
Cognitive functioning in children with both epilepsy and ADHD: A systematic review and meta-analysis.
Wickens S, Gummersall P, Brown T
Brain Dev · 2026 Jun · PMID 41967398 · Publisher ↗
There is a well-known bidirectional association between epilepsy and attention deficit hyperactivity disorder (ADHD) in children. The aim of the current systematic review and meta-analysis was to investigate neuropsychol...
There is a well-known bidirectional association between epilepsy and attention deficit hyperactivity disorder (ADHD) in children. The aim of the current systematic review and meta-analysis was to investigate neuropsychological functioning of children with epilepsy (CWE) and ADHD. The systematic search of two databases revealed 22 observational studies that comprised samples of CWE + ADHD and cognitive outcomes as compared to CWE alone, ADHD alone, and/or healthy controls. Neuropsychological data was organised with respect to Cattell-Horn-Carroll (CHC) taxonomy. Random effects meta-analyses across all measured cognitive domains showed small to moderate effect sizes indicating poorer cognitive outcomes in the CWE + ADHD group as compared to either condition alone (standardised mean difference [SMD] -0.30 to -0.72), with moderate to large effect sizes compared to healthy controls (SMD -0.61 to -1.12). Confidence intervals were wide and overlapping, suggesting a broad heterogenous profile of neuropsychological functioning in children with both conditions. These findings underscore the breadth, magnitude and vulnerability of cognitive dysfunction in children with comorbid neurobehavioral conditions, thus highlighting the need for comprehensive assessment and targeted intervention in this vulnerable population.
Clinical validation of CD16b as a standardized biomarker for inherited GPI deficiencies.
Tanigawa J, Imanishi K, Umeshita S … +5 more , Nabatame S, Kitabatake Y, Kinoshita T, Inoue N, Murakami Y
Brain Dev · 2026 Jun · PMID 41967397 · Publisher ↗
OBJECTIVES: Inherited glycosylphosphatidylinositol (GPI) deficiencies (IGDs) impair the expression of GPI-anchored proteins and produce diverse clinical phenotypes that complicate diagnosis. Since we had previously ident...
OBJECTIVES: Inherited glycosylphosphatidylinositol (GPI) deficiencies (IGDs) impair the expression of GPI-anchored proteins and produce diverse clinical phenotypes that complicate diagnosis. Since we had previously identified CD16b as a useful diagnostic biomarker, we aimed to establish a standardized flow cytometric assay suitable for routine clinical application. METHODS: We analyzed granulocyte expression of CD16b in 29 IGD patients and 101 controls (21 non-IGD and 80 healthy adults). Granulocyte CD16b expression was quantified as geometric mean fluorescence intensity (gMFI) by flow cytometry in our laboratory and a commercial testing company. Receiver operating characteristic (ROC) analysis was used to define diagnostic cut-offs. RESULTS: CD16b on granulocytes showed the largest decrease (approximately 85%) among GPI-anchored proteins in IGD patients. Mean gMFI was 41,660 ± 36,286 in IGD versus 88,370 ± 24,856 in healthy controls (p < 0.001). ROC analysis yielded an optimal cut-off of 53,431 (sensitivity 0.73, specificity 0.96, area under the curve (AUC) 0.84, Youden index 0.69). We defined 40,000 as the definitive diagnostic threshold and 60,000 as the borderline value. These cut-offs were validated with the commercial assay, which provides results within 2-3 days and is reimbursed by Japan's national health insurance. CONCLUSIONS: Measurement of granulocyte CD16b provides a reliable and rapid screening method for IGD that complements genetic testing. Implementation of this assay by a commercial provider, together with validated cutoffs, enables nationwide, insurance-covered diagnostic testing and functional confirmation of GPI pathway gene variants, representing a significant advance in IGD diagnosis.
Utility of the Rett syndrome behavior questionnaire (RSBQ) for Japanese patients with Rett syndrome: A pilot study.
Sato M, Yamaki H, Kawano G … +7 more , Tanaka Y, Isooka A, Yamashita D, Akita Y, Eshima N, Takahashi T, Matsuishi T
Brain Dev · 2026 Jun · PMID 41936323 · Publisher ↗
BACKGROUND: Rett syndrome (RTT) is a neurodevelopmental disorder caused by MECP2 gene mutations. It mainly affects females and is characterized by age-dependent neurological and behavioral abnormalities. The Rett Syndrom...
BACKGROUND: Rett syndrome (RTT) is a neurodevelopmental disorder caused by MECP2 gene mutations. It mainly affects females and is characterized by age-dependent neurological and behavioral abnormalities. The Rett Syndrome Behavior Questionnaire (RSBQ) is a caregiver-completed tool accepted by the US Food and Drug Administration as a primary outcome measure in RTT clinical trials. However, its reliability remains uncertain, and few Japanese studies have used it. METHODS: In this study, 18 female RTT patients aged 4-44 years who regularly visited our hospital were assessed using the 45-item RSBQ through physician-guided, face-to-face caregiver interviews to ensure accurate understanding of each question. RSBQ scores were analyzed across nine behavioral domains and compared between patients aged <15 years (n = 8) and those aged ≥15 years (n = 10). Correlations between age and domain scores were examined using Spearman's rank test. Multiple regression was conducted to identify independent predictors of RTT-characteristic domains, which we defined as Domain 2 (breathing abnormalities) and Domain 3 (hand stereotypies) total scores. RESULT: Among patients aged ≥15 years, Domain 2 scores showed a strong negative correlation with age (r = -0.936, p < 0.001). Multiple regression showed that age was an independent factor associated with lower total scores on Domains 2 and 3. CONCLUSION: Breathing abnormalities and hand stereotypies tended to decrease with age. The RSBQ appears useful for evaluating symptom profiles in Japanese RTT patients. Future comparative and multicenter validation studies including female patients with intellectual disabilities are warranted. (242 words).
The Turkish version of neurological disorders depression inventory epilepsy for youth (NDDI-E-Y); validity and reliability study.
Aydin S, Öz Tunçer G, Bayir GK … +1 more , Aksoy A
Brain Dev · 2026 Jun · PMID 41916022 · Publisher ↗
INTRODUCTION: Although depression is one of the most common comorbidities in patients with epilepsy, it is often undiagnosed. The aim of this study was to verify the validity and reliability of the Turkish version of the...
INTRODUCTION: Although depression is one of the most common comorbidities in patients with epilepsy, it is often undiagnosed. The aim of this study was to verify the validity and reliability of the Turkish version of the Neurological Disorders Depression Inventory-Epilepsy for Youth (NDDI-E-Y), which is used to determine depressive symptoms in children with epilepsy. METHODS: Children with epilepsy aged between 12 and 17 years were included. The Turkish versions of the Child Depression Inventory (CDI) and NDDI-E-Y were applied to the participants. RESULTS: All of the 116 participants were able to complete the scale without any difficulty in understanding the Turkish version of the NDDI-E-Y. Cronbach's α coefficient was 0.88. Receiver operator characteristics (ROC) analysis was performed and the area under the curve (AUC) for NDDI-E-Y was 0.983 (95% CI 0.940-0.998), the optimum cut-off score was >32 with 90.5% sensitivity and 96.8% specificity. NDDI-E-Y Turkish version scores showed a significant positive correlation with CDI (p < 0.05). CONCLUSION: The Turkish version of the NDDI-E-Y can be used as a valid and reliable measurement tool for children with epilepsy. We believe that the routine use of this short, self-administered scale in intensive clinical settings will contribute to the diagnosis and treatment of depression in children with epilepsy.
Association of weather with seizure incidence in children with drug-resistant epilepsy: A multicenter prospective observational study.
Arai Y, Okanishi T, Noma H … +9 more , Sunada H, Kanai S, Togawa M, Ohno T, Hiraiwa R, Fujii Y, Maeda M, Matsushige T, Maegaki Y
Brain Dev · 2026 Jun · PMID 41903422 · Publisher ↗
PURPOSE: We investigated the correlation of atmospheric pressure, temperature, and humidity with seizures in children with drug-resistant epilepsy (DRE). METHODS: This multicenter prospective observational study enrolled...
PURPOSE: We investigated the correlation of atmospheric pressure, temperature, and humidity with seizures in children with drug-resistant epilepsy (DRE). METHODS: This multicenter prospective observational study enrolled children with DRE who experienced at least one seizure per week. During 60 days, the participants' parents recorded the number of daily seizures and other seizure-triggering risk factors. A Poisson mixed-effects model, after adjustment for other seizure risk factors and the children's demographics (sex and age), was used to estimate the relative risk (RR) of seizure incidence. RESULTS: The 3214 seizures (mean: 3.4 seizures per day) showed negative associations of seizure incidence (RR [95% confidence interval, CI]) with the mean atmospheric pressure on the day of (0.988 [0.981-0.996], p = 0.002), the day before (0.989 [0.981-0.996], p = 0.003), and 2 days preceding (RR, 0.986; 95% CI, 0.978-0.993; p < 0.001) the seizure, but positive associations with atmospheric variations on the day before (1.020 [1.004-1.035], p = 0.012) and 2 days prior (1.022 [1.006-1.037], p = 0.005). Mean temperatures on the day of (0.990 [0.981-0.999], p = 0.027) and day before (0.991 [0.981-1.000], p = 0.047) the seizure were negatively associated with seizure incidence. The mean humidity on the day of (1.006 [1.003-1.010], p = 0.001), day before (1.006 [1.002-1.009], p = 0.003), and 2 days before (1.007 [1.003-1.010], p < 0.001) the seizure were positively associated with seizure incidence. CONCLUSION: Lower atmospheric pressure, greater atmospheric variations, lower temperatures, and higher humidity may increase seizure risk in DRE. Incorporating these factors into the preventive education of parents of patients with DRE could improve self-management.
A novel splice site variant in TIMM8A induced abnormal mRNA splicing resulting in Mohr-Tranebjaerg syndrome.
Hanafusa H, Ishida Y, Bo R … +4 more , Nishiyama M, Nozu K, Nagase H, Awano H
Brain Dev · 2026 Jun · PMID 41880689 · Publisher ↗
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 spli...
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.
Executive function deficits among Malaysian children with epilepsy.
Hamidun Majid NA, Fong CY, Jayanath S … +4 more , Li L, Lim WK, Mardiah WH, Ong LC
Brain Dev · 2026 Jun · PMID 41875528 · Publisher ↗
BACKGROUND: Children with epilepsy (CWE) are at risk of executive function (EF) deficits that may affect their behaviour, parenting stress and health related quality of life (HRQOL). This study aimed to i) determine the...
BACKGROUND: Children with epilepsy (CWE) are at risk of executive function (EF) deficits that may affect their behaviour, parenting stress and health related quality of life (HRQOL). This study aimed to i) determine the prevalence of EF deficits among Malaysian CWE and its associated factors, ii) explore the relationship between EF deficits, behaviour, parenting stress and HRQOL. METHOD: Cross-sectional study of all mainstream school-going CWE seen at University Malaya Medical Centre, Kuala Lumpur from July 2023-January 2024. Children with learning disorders, neurodevelopmental disorders, or additional chronic medical conditions were excluded from the study. Questionnaires included the Behaviour Rating Inventory of Executive Function (BRIEF-2), Health Related QOL Measure for CWE (CHEQOL-25), Strengths and Difficulties Questionnaire (SDQ), and Parenting Stress Index-short form (PSI-SF) questionnaire. RESULTS: Total of 115 participants (72 male) participated in the study with age range 6-18 years (mean 12.4 years). The prevalence of EF deficits ranged from 14.8 to 24.3% across different domains of BRIEF-2. The mean scores for BRIEF-2 scales were: Global Executive Composite (GEC) 56.1 (SD 9.57), Behaviour Regulating Index (BRI) 53.8 (SD 9.76), Emotion Regulation Index (ERI) 56.6 (SD 9.90) and Cognitive Regulation Index (CRI) 55.6 (SD 9.40). Multivariate logistic regression analysis identified hyperactivity/inattention as a significant factor for all domains of EF deficits, parent-child dysfunctional interaction (PCDI) for EF deficits in BRI and CRI subdomains and Chinese ethnicity for EF deficits in BRI and ERI subdomains. Scores from the hyperactivity/inattention domain of the SDQ were strongly correlated with GEC (r 0.73), BRI (r 0.64) and CRI (r 0.67) scores. Difficult child domain scores of the PSI-SF were moderately correlated with GEC scores (r 0.45). There was a significant but weak negative correlation between GEC scores and the total CHEQOL-25 scores (r - 0.24). CONCLUSION: Twenty percent of Malaysian CWE were reported to have EF deficits. EF deficits were more prevalent among those with behavioural hyperactivity/inattention, Chinese ethnicity and elevated parenting stress levels. CWE with EF deficits were also at risk of lower HRQOL. Interventions for EF deficits should take into account ethnic differences, and address issues of associated behavioural problems and parenting stress.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe