BACKGROUND: Children with autism spectrum disorder (ASD) often face difficulties in parent-child relationships and exhibit problematic behaviors. This study retrospectively examines the effects of standard Parent-Child I...BACKGROUND: Children with autism spectrum disorder (ASD) often face difficulties in parent-child relationships and exhibit problematic behaviors. This study retrospectively examines the effects of standard Parent-Child Interaction Therapy (PCIT) for children with ASD and their caregivers in Japan, focusing on reducing parental stress and children's problematic behaviors. METHODS: Eight parent-child dyads with children aged 2.5-7 years with ASD underwent standard PCIT. Measures included the Eyberg Child Behavior Inventory (ECBI), Beck Depression Inventory-II (BDI-II), Parenting Stress Index-Short Form (PSI-SF), and Child Behavior Checklist for Ages 4-18 (CBCL/4-18), assessed pre- and post-treatments. RESULTS: For parents, ECBI problem score decreased from 16.8 (SD ± 4.4) to 3.0 (SD ± 4.1) pre- and post-treatment (p < 0.05, effect size 1.9). PSI-SF parent section scores dropped from 28.7 (SD ± 7.1) to 22.1 (SD ± 6.2) (p < 0.01, effect size 2.0). The total PSI-SF score from 58.1 (SD ± 10.9) to 45.0 (SD ± 11.1), (p < 0.01, effect size 1.7). For children, ECBI intensity scores decreased from 147.9 (SD ± 20.3) to 85.5 (SD ± 17.7) (p < 0.01, effect size 3.4). PSI-SF child section scores fell from 29.4 (SD ± 4.8) to 22.9 (SD ± 5.8) (p < 0.05, effect size of 1.2), and total CBCL from 70.3 (SD ± 5.9) to 62.0 (SD ± 8.4) (p < 0.05, effect size of 1.5). CONCLUSION: The standard PCIT for children with ASD and their parents in Japan significantly reduces parental stress and children's problematic behaviors, improving parent-child interactions.
INTRODUCTION: Cerebral palsy (CP) is the most common motor disorder in childhood that causes lifelong disabilities. Studies suggest that administration of autologous cord blood (CB) or sibling cord blood (SCB) may improv...INTRODUCTION: Cerebral palsy (CP) is the most common motor disorder in childhood that causes lifelong disabilities. Studies suggest that administration of autologous cord blood (CB) or sibling cord blood (SCB) may improve gross motor function and brain connectivity in CP. In this pilot study, we evaluated the safety and efficacy of allogeneic SCB in Japanese children with CP. METHODS: A single-arm pilot study of a single intravenous dose of HLA-matched or partially matched (at least 4/6 HLA molecular matches) SCB was conducted in five Japanese patients with CP (5.0-6.3 years old). The primary endpoint was to measure the safety profiles and assessment of motor function and neurodevelopmental behaviors as the secondary endpoint. RESULTS: No serious side effects or concerning infusion reactions were observed. All patients showed a mean improvement of 4.89 ± 4.01 points in Gross Motor Function Measure-66 (GMFM-66) score at 6 months, which was better than predicted by age and severity of disease. In addition, GMFM-66 scores at 1 and 2 years was further improved by a mean of 6.49 ± 3.58 and 7.93 ± 4.26 points, respectively. One case showed improvement in the Developmental Quotient (DQ) overall and language/social scales and another case showed improvement in the Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV) overall, language. No significant correlations were found between GMFM-66 scores, DQ scales, WISC-IV scores and HLA concordance or number of cells administered. CONCLUSION: Allogeneic SCB administration is safe and feasible in Japanese CP patients and may offer therapeutic potential in clinical practice. Future study is needed to clarify several unclear issues.
AIM: To clarify the association between characteristics of early infantile general movements (GMs) and clinical background factors, including brain morphological characteristics, in very-low-birth-weight infants (VLBWIs)...AIM: To clarify the association between characteristics of early infantile general movements (GMs) and clinical background factors, including brain morphological characteristics, in very-low-birth-weight infants (VLBWIs). METHODS: GMs were scored using the motor optimality score revised (MOS-R) at a post-term age of 9-20 weeks. The MOS-R is composed of the following five subscales: quality of fidgety movements (Quality FMs), movement patterns (MP), age-adequate movement repertoire (AMR), postural patterns (PP), and movement character (MC). Brain magnetic resonance imaging (MRI) at term-equivalent age was scored using a validated scoring system (MRI score). Factors affecting the MOS-R were investigated using a multiple regression analysis. SUBJECTS: Ninety-five VLBWIs managed at Oita University Hospital in 2012-2023, who underwent brain MRI and GMs assessment, were included. The median gestational age at birth and birth weight were 28 weeks, 6 days and 997 g, respectively. RESULTS: The multiple regression analysis revealed that MRI score, patent ductus arteriosus (PDA) drug therapy, and sex were associated with MOS-R. In an analysis using the MOS-R subscales as dependent variables, Quality FMs were associated with MRI score and sex; MP was associated with MRI score; AMR was associated with PDA drug therapy, sex, and postnatal steroid use; PP was associated with height at the estimated date of confinement (EDC); and MC was associated with PDA drug therapy and body weight at EDC. CONCLUSION: MOS-R is associated with brain morphological development. Its subscales are influenced by different clinical factors.
OBJECTIVE: To compare parenting stress between parents of children with autism spectrum disorder (ASD) and other developmental disabilities (DDs) and to examine ASD's influence on parenting stress through mediation analy...OBJECTIVE: To compare parenting stress between parents of children with autism spectrum disorder (ASD) and other developmental disabilities (DDs) and to examine ASD's influence on parenting stress through mediation analysis. METHODS: We retrospectively analyzed 48 children with ASD (ASD group) and 77 with non-ASD DDs (non-ASD group), along with one of their parents, at the Gyeongsang National University Hospital between May 2021 and August 2024. All underwent developmental assessments and completed the Korean version of the Parenting Stress Index-4 and the Child Interactive Behavior Test (CIBT). RESULTS: The ASD group's median age was 37.5 months, with 37 boys (77.1 %). No significant difference was found in child age, sex, or parental demographics between the groups. Total parenting stress was significantly higher in the ASD group (p = 0.01), primarily due to higher child domain scores (p<0.01) than in the non-ASD group. Among the child domain subscales, Distractibility/Hyperactivity, Adaptability, Reinforces Parent, and Acceptability were significantly higher in the ASD group, while only the Attachment subscale differed in the parent domain. For high parenting stress (>85th percentile), Initiative Interaction-a CIBT subscale-was the only independent predictor, rather than ASD diagnosis. Mediation analysis showed no direct effect of ASD on parenting stress (β = 4.28, p = 0.42) but an indirect effect via reduced initial interaction (β = 3.68, p<0.05). CONCLUSIONS: Parenting stress was higher in the ASD group, mainly due to child-related factors. ASD influenced parenting stress indirectly through reduced initiative interaction. These findings provide further insight into parenting stress in families of children with ASD.
Fukuyama congenital muscular dystrophy (FCMD, a severe form of muscular dystrophy characterized by brain structural anomalies and ocular complications due to neuronal migration disorders, is notably limited mainly to Jap...Fukuyama congenital muscular dystrophy (FCMD, a severe form of muscular dystrophy characterized by brain structural anomalies and ocular complications due to neuronal migration disorders, is notably limited mainly to Japan. Ninety percent of patients are unable to walk throughout their lives and die before the age of 20 due to respiratory failure and cardiomyopathy. At present, there is no cure. The founder variant, a 3-kb insertion in FKTN, is an SVA (SINE-VNTR-Alu) retrotransposon, and FCMD is a splicing disorder attributable the exon trapping function of this retrotransposon. A splicing modulation therapy targeting exon-trapping based on using antisense nucleic acids to block abnormal splicing is under development, and clinical trials have begun. Additionally, it was clarified that the gene product of FKTN is a glycosyltransferase that transfers ribitol-5-phosphate from cytidine diphosphate ribitol, a precursor for the synthesis of the O-mannosyl glycans of α-dystroglycan, a cell membrane component. This finding raises hopes for a prodrug therapy. Though patient numbers were small, previous clinical studies suggested that steroids are effective in FCMD. Thus, phase II clinical trials are underway with the aim of obtaining insurance approval. This review provides an overview of the clinical course and current status of treatments being developed for FCMD.
Hypomyelinating leukodystrophies (HLDs) are a group of inherited disorders characterized by impaired myelin formation in the central nervous system. Among them, Pelizaeus-Merzbacher disease (PMD) is a well-defined X-link...Hypomyelinating leukodystrophies (HLDs) are a group of inherited disorders characterized by impaired myelin formation in the central nervous system. Among them, Pelizaeus-Merzbacher disease (PMD) is a well-defined X-linked leukodystrophy caused by mutations in the PLP1 gene, including duplications, missense variants, and null mutations. Recent studies have revealed that different types of PLP1 mutations lead to distinct pathomechanisms: while missense mutations induce endoplasmic reticulum stress and activate the unfolded protein response (UPR), PLP1 duplications cause aberrant intracellular trafficking and cholesterol accumulation without UPR activation. Additionally, mutations in other genes such as GJC2, SOX10, TUBB4A, and POLR3A/B have been implicated in various forms of HLD, each with unique clinical and imaging features. Advances in neuroimaging and next-generation sequencing have enabled more accurate and earlier diagnosis, expanding the clinical spectrum and deepening our understanding of disease mechanisms. This review summarizes the current knowledge on the molecular pathogenesis, genotype-phenotype correlations, and diagnostic approaches in HLDs, with an emphasis on recent biological insights that may inform future therapeutic strategies.
PURPOSE: We aimed to explore the potential prognostic factors associated with poorer outcomes in pediatric patients presenting with acute-onset ataxia to guide early intervention. METHODS: This single-center retrospectiv...PURPOSE: We aimed to explore the potential prognostic factors associated with poorer outcomes in pediatric patients presenting with acute-onset ataxia to guide early intervention. METHODS: This single-center retrospective cohort study was conducted at the National Center for Child Health and Development between January 2014 and May 2024. Pediatric patients aged 0-18 years who presented with acute-onset ataxia within 7 days of symptom onset were included, excluding those with pre-diagnosed causes of ataxia. Patients were divided into two groups based on their final diagnosis and prognosis: the benign acute cerebellar ataxia (ACA) group for low-risk patients and the clinically urgent neurological pathology (CUNP) group for high-risk patients. Statistical analyses, including chi-square tests and multivariate logistic regression, were performed to identify prognostic factors. RESULTS: In total, 59 children were included: 34 in the benign ACA group and 25 in the CUNP group. Univariate analysis showed significant differences in headache, vomiting, tremors or dysmetria, age ≥ 5 years, and symptom persistence beyond 3 days between the two groups. Multivariate analysis indicated that age ≥ 5 years (odds ratio [OR] 22.2, 95 % confidence interval [CI] 1.8-640.2) and symptom persistence over 3 days (OR 8.1, 95 % CI 1.5-68.6) were significantly associated with poorer outcomes. CONCLUSION: Pediatric patients aged ≥5 years with symptoms persisting for more than 3 days are more likely to require treatment or develop sequelae. Early diagnostic evaluation is important in such cases to avoid delayed intervention.
Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disorder caused by variants of the DMD that leads to progressive muscle degeneration. Recent advances in gene therapy have opened new therapeutic avenues, pa...Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disorder caused by variants of the DMD that leads to progressive muscle degeneration. Recent advances in gene therapy have opened new therapeutic avenues, particularly through the use of adeno-associated virus (AAV)-mediated micro-dystrophin delivery. Delandistrogene moxeparvovec, the first FDA-approved gene therapy for DMD, has demonstrated transgene expression and potential functional improvement in early phase trials, although its long-term efficacy, durability, and safety remain unconfirmed. Immune-mediated toxicities including myositis, myocarditis, and liver injury present significant clinical challenges, prompting the need for careful patient selection, immunoprophylaxis, and post-treatment monitoring. In addition to micro-dystrophin replacement, novel gene therapy approaches such as endogenous dystrophin upregulation, exon skipping, and adjunctive muscle-enhancement strategies are being explored. Future studies focus on overcoming vector size limitations by using dual/triple AAV systems or non-viral platforms, improving muscle tropism through capsid and promoter engineering, and expanding eligibility through desensitization protocols. This review provides an integrated overview of the current progress, challenges, and future perspectives in gene therapy for DMD, with the aim of supporting its safe and effective clinical implementation.