Journal of Neurodevelopmental Disorders最新文献

{"title":"Disrupted visual attention relates to cognitive development in infants with Neurofibromatosis Type 1.","authors":"Jannath Begum-Ali, Luke Mason, Tony Charman, Mark H Johnson, Jonathan Green, Shruti Garg, Emily J H Jones","doi":"10.1186/s11689-025-09599-4","DOIUrl":"10.1186/s11689-025-09599-4","url":null,"abstract":"<p><strong>Background: </strong>Neurofibromatosis Type 1 is a genetic condition diagnosed in infancy that substantially increases the likelihood of a child experiencing cognitive and developmental difficulties, including Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD). Children with NF1 show clear differences in attention, but whether these differences emerge in early development and how they relate to broader difficulties with cognitive and learning skills is unclear. To address this question requires longitudinal prospective studies from infancy, where the relation between domains of visual attention (including exogenous and endogenous shifting) and cognitive development can be mapped over time.</p><p><strong>Methods: </strong>We report data from 28 infants with NF1 tested longitudinally at 5, 10 and 14 months compared to cohorts of 29 typical likelihood infants (with no history of NF1 or ASD and/or ADHD), and 123 infants with a family history of ASD and/or ADHD. We used an eyetracking battery to measure both exogenous and endogenous control of visual attention.</p><p><strong>Results: </strong>Infants with NF1 demonstrated intact social orienting, but slower development of endogenous visual foraging. This slower development presented as prolonged engagement with a salient stimulus in a static display relative to typically developing infants. In terms of exogenous attention shifting, NF1 infants showed faster saccadic reaction times than typical likelihood infants. However, the NF1 group demonstrated a slower developmental improvement from 5 to 14 months of age. Individual differences in foraging and saccade times were concurrently related to visual reception abilities within the full infant cohort (NF1, typical likelihood and those with a family history of ASD/ADHD).</p><p><strong>Conclusions: </strong>Our results provide preliminary evidence that alterations in saccadic reaction time and visual foraging may contribute to learning difficulties in infants with NF1.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"17 1","pages":"12"},"PeriodicalIF":4.1,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in sleep EEG coherence and spindle metrics in toddlers with and without receptive/expressive language delay: a prospective observational study.","authors":"Xinyi Hong, Cristan Farmer, Nataliia Kozhemiako, Gregory L Holmes, Lauren Thompson, Stacy Manwaring, Audrey Thurm, Ashura Buckley","doi":"10.1186/s11689-024-09586-1","DOIUrl":"10.1186/s11689-024-09586-1","url":null,"abstract":"<p><strong>Background: </strong>Changes in brain connectivity during development are thought to reflect organizational and maturational processes that correspond to skill acquisition in domains like motor, language, and cognition. This theory is supported by findings in typically developing children as well as observations of abnormal connectivity among children with neurodevelopmental differences. However, few coherence studies have capitalized on the potential of sleep electroencephalogram (EEG) to examine the developing brain, especially among very young children for whom formal neurodevelopmental diagnosis is not yet possible. Sleep microarchitecture in young children may offer key insights into neurophysiological abnormalities associated with neurodevelopmental trajectories and potentially aid in early detection and intervention. In this study, we explored sleep EEG coherence and sleep spindles in typically developing toddlers and toddlers at increased risk of later neurodevelopmental diagnoses.</p><p><strong>Methods: </strong>We investigated EEG coherence and sleep spindles in 16 toddlers with receptive and expressive language delay (LangD) and 39 typically developing (TD) toddlers. Participants were aged 12-22 months at baseline, and 34 (LangD, n=11; TD, n=23) participants were evaluated again at 36 months of age.</p><p><strong>Results: </strong>Average EEG coherence was stronger in the LangD group than the TD group, with differences most prominent during slow-wave sleep. Some age-related increases in coherence were observed, but these did not differ between groups. Sleep spindle density, duration, and frequency changed between baseline and follow-up for both groups, with the LangD group demonstrating a smaller magnitude of change than the TD group. The direction of change was frequency band-dependent for both groups.</p><p><strong>Conclusions: </strong>These findings indicate that atypical sleep EEG connectivity and sleep spindle development can be detected in toddlers at risk of later neurodevelopmental diagnoses.</p><p><strong>Trial registration: </strong>https://clinicaltrials.gov/study/NCT01339767 ; Registration date: 4/20/2011.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"17 1","pages":"11"},"PeriodicalIF":4.1,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA methylation biomarkers of intellectual/developmental disability across the lifespan.","authors":"Janine M LaSalle","doi":"10.1186/s11689-025-09598-5","DOIUrl":"10.1186/s11689-025-09598-5","url":null,"abstract":"<p><p>Epigenetic mechanisms, including DNA methylation, act at the interface of genes and environment by allowing a static genome to respond and adapt to a dynamic environment during the lifespan of an individual. Genome-wide DNA methylation analyses on a wide range of human biospecimens are beginning to identify epigenetic biomarkers that can predict risk of intellectual/developmental disabilities (IDD). DNA methylation-based epigenetic signatures are becoming clinically useful in categorizing benign from pathogenic genetic variants following exome sequencing. While DNA methylation marks differ by tissue source, recent studies have shown that accessible perinatal tissues, such as placenta, cord blood, newborn blood spots, and cell free DNA may serve as accessible surrogate tissues for testing epigenetic biomarkers relevant to understanding genetic, environmental, and gene by environment interactions on the developing brain. These DNA methylation signatures may also provide important information about the biological pathways that become dysregulated prior to disease progression that could be used to develop early pharmacological interventions. Future applications could involve preventative screenings using DNA methylation biomarkers during pregnancy or the newborn period for IDDs and other neurodevelopmental disorders. DNA methylation biomarkers in adolescence and adulthood are also likely to be clinically useful for tracking biological aging or co-occurring health conditions that develop across the lifespan. In conclusion, DNA methylation biomarkers are expected to become more common in clinical diagnoses of IDD, to improve understanding of complex IDD etiologies, to improve endpoints for clinical trials, and to monitor potential health concerns for individuals with IDD as they age.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"17 1","pages":"10"},"PeriodicalIF":4.1,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atypical audio-visual neural synchrony and speech processing in early autism.","authors":"Xiaoyue Wang, Sophie Bouton, Nada Kojovic, Anne-Lise Giraud, Marie Schaer","doi":"10.1186/s11689-025-09593-w","DOIUrl":"10.1186/s11689-025-09593-w","url":null,"abstract":"<p><strong>Background: </strong>Children with Autism Spectrum disorder (ASD) often exhibit communication difficulties that may stem from basic auditory temporal integration impairment but also be aggravated by an audio-visual integration deficit, resulting in a lack of interest in face-to-face communication. This study addresses whether speech processing anomalies in young autistic children (mean age 3.09-year-old) are associated with alterations of audio-visual temporal integration.</p><p><strong>Methods: </strong>We used high-density electroencephalography (HD-EEG) and eye tracking to record brain activity and gaze patterns in 31 children with ASD (6 females) and 33 typically developing (TD) children (11 females), while they watched cartoon videos. Neural responses to temporal audio-visual stimuli were analyzed using Temporal Response Functions model and phase analyses for audiovisual temporal coordination.</p><p><strong>Results: </strong>The reconstructability of speech signals from auditory responses was reduced in children with ASD compared to TD, but despite more restricted gaze patterns in ASD it was similar for visual responses in both groups. Speech reception was most strongly affected when visual speech information was also present, an interference that was not seen in TD children. These differences were associated with a broader phase angle distribution (exceeding pi/2) in the EEG theta range in children with ASD, signaling reduced reliability of audio-visual temporal alignment.</p><p><strong>Conclusion: </strong>These findings show that speech processing anomalies in ASD do not stand alone and that they are associated already at a very early development stage with audio-visual imbalance with poor auditory response encoding and disrupted audio-visual temporal coordination.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"17 1","pages":"9"},"PeriodicalIF":4.1,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11837391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The striatal matrix compartment is expanded in autism spectrum disorder.","authors":"Jeff L Waugh, Asim O A Hassan, Adrian T Funk, Joseph A Maldjian","doi":"10.1186/s11689-025-09596-7","DOIUrl":"10.1186/s11689-025-09596-7","url":null,"abstract":"<p><strong>Background: </strong>Autism spectrum disorder (ASD) is the second-most common neurodevelopmental disorder in childhood. This complex developmental disorder manifests with restricted interests, repetitive behaviors, and difficulties in communication and social awareness. The inherited and acquired causes of ASD impact many and diverse brain regions, challenging efforts to identify a shared neuroanatomical substrate for this range of symptoms. The striatum and its connections are among the most implicated sites of abnormal structure and/or function in ASD. Striatal projection neurons develop in segregated tissue compartments, the matrix and striosome, that are histochemically, pharmacologically, and functionally distinct. Immunohistochemical assessment of ASD and animal models of autism described abnormal matrix:striosome volume ratios, with an possible shift from striosome to matrix volume. Shifting the matrix:striosome ratio could result from expansion in matrix, reduction in striosome, spatial redistribution of the compartments, or a combination of these changes. Each type of ratio-shifting abnormality may predispose to ASD but yield different combinations of ASD features.</p><p><strong>Methods: </strong>We developed a cohort of 426 children and adults (213 matched ASD-control pairs) and performed connectivity-based parcellation (diffusion tractography) of the striatum. This identified voxels with matrix-like and striosome-like patterns of structural connectivity.</p><p><strong>Results: </strong>Matrix-like volume was increased in ASD, with no evident change in the volume or organization of the striosome-like compartment. The inter-compartment volume difference (matrix minus striosome) within each individual was 31% larger in ASD. Matrix-like volume was increased in both caudate and putamen, and in somatotopic zones throughout the rostral-caudal extent of the striatum. Subjects with moderate elevations in ADOS (Autism Diagnostic Observation Schedule) scores had increased matrix-like volume, but those with highly elevated ADOS scores had 3.7-fold larger increases in matrix-like volume.</p><p><strong>Conclusions: </strong>Matrix and striosome are embedded in distinct structural and functional networks, suggesting that compartment-selective injury or maldevelopment may mediate specific and distinct clinical features. Previously, assessing the striatal compartments in humans required post mortem tissue. Striatal parcellation provides a means to assess neuropsychiatric diseases for compartment-specific abnormalities. While this ASD cohort had increased matrix-like volume, other mechanisms that shift the matrix:striosome ratio may also increase the chance of developing the diverse social, sensory, and motor phenotypes of ASD.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"17 1","pages":"8"},"PeriodicalIF":4.1,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An exploratory fetal MRI study examining the impact of 22q11.2 microdeletion syndrome on early brain growth.","authors":"Daniel Cromb, Tom Finck, Alexandra F Bonthrone, Alena Uus, Milou Van Poppel, Johannes Steinweg, David F Lloyd, Kuberan Pushparajah, Reza Razavi, Serena J Counsell, Mary Rutherford","doi":"10.1186/s11689-025-09594-9","DOIUrl":"10.1186/s11689-025-09594-9","url":null,"abstract":"<p><strong>Background: </strong>Improved long-term outcomes, related to advances in surgical and clinical care of infants with congenital heart disease (CHD), has shifted focus onto the accompanying and later-onset cognitive and neuropsychiatric disorders in those who also have 22q11.2 deletion syndrome (22qDS). 22qDS is itself associated with neurodevelopmental impairments and altered brain growth. However, when brain growth in 22qDS first deviates from normal is unknown, and whether impaired brain development is primarily genetics-driven or a secondary consequence of the underlying CHD remains incompletely understood.</p><p><strong>Methods: </strong>In this small, exploratory study, we use fetal MRI to assess volumetric brain development in 22qDS by comparing fetal brain morphometry to a set of gestation and sex-matched healthy controls, and a cohort of gestation and sex-matched fetuses with the same CHD diagnoses but without 22q11.2 deletion. Structural T2-weighted fetal brain images were acquired using a 1.5T MRI scanner. MR scanner and sequence parameters were identical in all cohorts. Motion-corrected images underwent segmentation using an automated pipeline developed for fetal brain MRI. Total brain tissue volumes, volumes for four different tissue regions (cortical grey matter, white matter, deep grey matter and cerebellum), cerebrospinal fluid and total intracranial volumes were calculated.</p><p><strong>Results: </strong>Antenatal imaging was acquired between 29 and 35 weeks gestation. Thirty-three fetuses were included (7 22qDS; 14 isolated CHD; 12 healthy control). White matter volumes were significantly reduced in fetuses with 22qDS compared to control fetuses (p = 0.028), but not to those with CHD without 22q11.2 deletion (p = 0.09). Large effect-sizes were seen between the 22qDS and isolated CHD cohorts (D_Cohen = 0.81), and between the 22qDS and control cohorts (D_Cohen = 1.2) for white matter volumes. No significant differences were seen in volumes of other brain regions between groups.</p><p><strong>Conclusions: </strong>This exploratory study expands our existing knowledge on neurodevelopmental impairments in 22qDS to the fetal period by highlighting reduced white matter volumes compared to gestation and sex-matched control fetuses during this time-period. Our findings suggest that impaired white matter growth in fetuses with both 22qDS and CHD may not be fully explained by any underlying CHD.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"17 1","pages":"7"},"PeriodicalIF":4.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11817260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of the Food Safe Zone questionnaire for families of individuals with Prader-Willi syndrome.","authors":"Elisabeth M Dykens, Elizabeth Roof, Hailee Hunt-Hawkins, Theresa V Strong","doi":"10.1186/s11689-024-09589-y","DOIUrl":"10.1186/s11689-024-09589-y","url":null,"abstract":"<p><strong>Background: </strong>Prader-Willi syndrome (PWS), a genetic neurodevelopmental disorder, is characterized by hyperphagia and significant behavioral problems. Hyperphagic individuals with PWS are chronically hungry yet rarely feel sated, and often engage in food-seeking behaviors. To avoid life-threatening obesity in their children, families implement food security strategies (e.g., locking food sources, constant supervision around food, alerting others). Although widely used, these strategies have yet to be systematically examined. We thus developed and analyzed the psychometric properties of a new measure of these diverse strategies, the Food Safe Zone, and evaluated them in relation to hyperphagic symptoms and demographic variables. In doing so, we also shine a light on the extraordinary efforts of families in managing their children's hyperphagia.</p><p><strong>Methods: </strong>Our team developed 20 FSZ items that were revised for clarity and completeness in an iterative feedback process with stakeholders, including parents, PWS specialists, and individuals with PWS. The FSZ was pilot tested, descriptive findings were reviewed by additional stakeholders, and then administered to 624 parents in a large-scale study. Based on an open-ended question, \"Is there anything else you do to ensure food safety?\" two additional items were added and evaluated in a follow-up study.</p><p><strong>Results: </strong>Principal component analyses revealed that 21 FSZ items loaded onto 5 factors that were readily interpretable, accounting for 67% of test variance: Alerting Others and Food Supervision in the Community; Locking or Restricting Food Sources; Checking for Food; At Home Supervision and Meals; and Avoiding Food Settings. Internal consistency and test-rest reliability were robust. Convergent validity analyses revealed that parents implemented FSZ strategies in response to the severity of their child's hyperphagia, and not their child's age, gender or PWS genetic subtype.</p><p><strong>Conclusions: </strong>The psychometrically sound FSZ holds promise for future research, especially on the effects of food safety tactics on family members. In future clinical trials, the FSZ could also be used to help parents think critically about their food safety tactics in relation to their child's hyperphagia, or as an exploratory endpoint; if hyperphagia is lessened, so too may food safety tactics, thereby enhancing familial quality of life.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"17 1","pages":"6"},"PeriodicalIF":4.1,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regional hippocampal thinning and gyrification abnormalities and associated cognition in children with prenatal alcohol exposure.","authors":"Blake A Gimbel, Jeffrey R Wozniak, Bryon A Mueller, Kent A Tuominen, Abigail M Ernst, Mary E Anthony, Erik de Water, Donovan J Roediger","doi":"10.1186/s11689-025-09595-8","DOIUrl":"10.1186/s11689-025-09595-8","url":null,"abstract":"<p><strong>Background: </strong>Prenatal alcohol exposure (PAE) impacts hippocampal structure and function, contributing to deficits in memory and decision-making in affected individuals. Here, we evaluate hippocampal anomalies in children with PAE and an unexposed comparison group using advanced MRI methods that characterize hippocampal curvature and thickness.</p><p><strong>Methods: </strong>Participants, ages 8 to 16 years, included children with PAE (n = 48) and an unexposed comparison group (n = 46) who underwent a dysmorphology exam, neuropsychological assessment, and an MRI scan. Height, weight, head circumference, and dysmorphic facial features were evaluated. Of those with PAE, 4.2% had fetal alcohol syndrome (FAS), 22.9% had partial FAS, and 72.9% had alcohol-related neurodevelopmental disorder. Neuropsychological testing included measures of intelligence and memory functioning. T1-weighted anatomical data were processed with the Hippunfold pipeline, which \"unfolds\" the complex hippocampal structure onto a template surface and provides measures of thickness and gyrification/curvature at each vertex. Permutation Analysis of Linear Models (PALM) was used to test for group differences (PAE vs. comparison) in hippocampal thickness and gyrification at each vertex and also to assess correlations with cognitive functioning.</p><p><strong>Results: </strong>There were significant regional differences in thickness and gyrification across bilateral hippocampi, with the PAE group showing substantially thinner tissue and less curvature than the comparison group, especially in CA1 and subiculum regions. For those with PAE, thinner subicular tissue (bilateral) was associated with lower IQ. Also in the PAE group, lower episodic memory performance was associated with thinness in the right hippocampus, especially in the subiculum region. There were no significant regional hippocampal patterns that were associated with cognitive functioning for individuals in the unexposed comparison group.</p><p><strong>Conclusions: </strong>We used a novel MRI method to evaluate hippocampal structure in children with PAE and an unexposed comparison group. The data suggest that PAE disrupts hippocampal development, impacting both the early-stage folding of the structure and its ultimate thickness. The data also demonstrate that these developmental anomalies have functional consequences in terms of core memory functions as well as global intellectual functioning in children with PAE.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"17 1","pages":"5"},"PeriodicalIF":4.1,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11796126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A randomized, placebo-controlled, cross-over trial of ketamine in Rett syndrome.","authors":"Kathleen Campbell, Jeffrey L Neul, David N Lieberman, Elizabeth Berry-Kravis, Tim A Benke, Cary Fu, Alan Percy, Bernhard Suter, David Morris, Randall L Carpenter, Eric D Marsh, Jana von Hehn","doi":"10.1186/s11689-025-09591-y","DOIUrl":"10.1186/s11689-025-09591-y","url":null,"abstract":"<p><strong>Background: </strong>Preclinical studies and anecdotal case reports support the potential therapeutic benefit of low-dose oral ketamine as a treatment of clinical symptoms in Rett syndrome (RTT); however, no controlled studies have been conducted in RTT to evaluate safety, tolerability and efficacy.</p><p><strong>Design: </strong>This was a sequentially initiated, dose-escalating cohort, placebo-controlled, double blind, randomized sequence, cross-over study of oral ketamine in 6-12-year-old girls with RTT to evaluate short-term safety and tolerability and explore efficacy.</p><p><strong>Methods: </strong>Participants were randomized to either five days treatment with oral ketamine or matched placebo, followed by a nine-day wash-out period and then crossed-over to the opposite treatment. Ketamine was dosed twice daily at 0.75 mg/kg/dose (Cohort 1) or 1.5 mg/kg/dose (Cohort 2). An independent safety monitoring committee evaluated safety and approved proceeding to the next dose cohort. Caregivers, participants, outcome assessors, and study staff except pharmacists were blinded to allocation. The primary endpoint was safety and tolerability. Exploratory efficacy endpoints included change in clinician- and caregiver-rated measures of RTT features, brain activity on electroencephalography, and wearable biosensors to measure respiration, heart rate, sleep, and activity.</p><p><strong>Results: </strong>Twenty-three participants enrolled (11 in Cohort 1, 12 in Cohort 2) from 3/12/2019-11/22/2021. One participant was excluded from analysis due to not meeting inclusion criteria on blinded review prior to analysis. One participant was withdrawn from the study due to an adverse event (vomiting) after the first dose of ketamine. Although planned for four dose cohorts, the trial was stopped after Cohort 2 due to enrollment challenges associated with the COVID-19 pandemic. Ketamine was safe and tolerated in both cohorts, with 1 related treatment emergent adverse event of vomiting. No difference was observed in efficacy between ketamine and placebo. Electroencephalography showed the expected increase in high frequency power with ketamine.</p><p><strong>Conclusions: </strong>Short-term, low-dose oral ketamine was safe and well tolerated in girls with RTT. No clinical efficacy of ketamine in treating symptoms of RTT was observed with 5 days of treatment, despite electroencephalography evidence of ketamine target engagement during the first dose. Further studies are needed to evaluate safety and efficacy of higher dose and longer exposure to ketamine in RTT.</p><p><strong>Trial registration: </strong>Registered at clinicaltrials.gov NCT03633058.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"17 1","pages":"4"},"PeriodicalIF":4.1,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143039422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced white matter integrity and disrupted brain network in children with type 2 and 3 spinal muscular atrophy.","authors":"Huirong Nie, Shasha Lan, Huan Wang, Pei Xiang, Mengzhen Yan, Yang Fan, Wanqing Shen, Yijuan Li, Wen Tang, Zhiyun Yang, Yujian Liang, Yingqian Chen","doi":"10.1186/s11689-025-09592-x","DOIUrl":"10.1186/s11689-025-09592-x","url":null,"abstract":"<p><strong>Background: </strong>Spinal muscular atrophy (SMA) is caused by reduced expression of survival motor neuron (SMN) protein. Previous studies indicated SMA causes not only lower motor neuron degeneration but also extensive brain involvement. This study aimed to investigate the changes of brain white matter and structural network using diffusion tensor imaging (DTI) in children with type 2 and 3 SMA.</p><p><strong>Methods: </strong>Forty-two type 2 and 3 pediatric SMA patients and 42 age- and gender-matched healthy controls (HC) were prospectively enrolled in this study. The tract-based spatial statistics (TBSS) was used to assess white matter integrity and the structural network properties were calculated based on DTI white matter fiber tracking and the graph theory approach. A partial correlation was performed to explore the relationship between white matter parameters and clinical characteristics.</p><p><strong>Results: </strong>In total, 42 patients (mean age, 10.86 ± 4.07 years; 23 men) were included. TBSS analysis revealed widespread white matter changes in SMA patients. The SMA patients showed changes in multiple small-world and network efficiency parameters. Compared to the HC group, SMA showed increased characteristic path length (L_p), normalized clustering coefficient (γ), small-world characteristic (σ), and decreased global efficiency (E_glob) (all p < 0.05). In the node properties, right supramarginal gyrus, right orbital part of superior frontal gyrus, right supplementary motor area, and left median cingulate and paracingulate gyri changed in SMA patients. A decreased axial diffusivity (AD) value was associated with lower Hammersmith Functional Motor Scale-Expanded scores (r = 0.45, p = 0.02), which means that the symptoms of SMA patients are more severe.</p><p><strong>Conclusions: </strong>This study found white matter and DTI-based brain network abnormalities in SMA patients, suggesting SMN protein deficiency may affect white matter development.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"17 1","pages":"3"},"PeriodicalIF":4.1,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143039432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}