Beth R Piscopo, Amy E Sutherland, Atul Malhotra, Beth J Allison, Suzanne L Miller
{"title":"Pathogenesis of Preterm Intraventricular Haemorrhage.","authors":"Beth R Piscopo, Amy E Sutherland, Atul Malhotra, Beth J Allison, Suzanne L Miller","doi":"10.1159/000546607","DOIUrl":"10.1159/000546607","url":null,"abstract":"<p><strong>Background: </strong>Intraventricular haemorrhage (IVH) is the primary neuropathology in infants born very preterm. IVH describes bleeding into the ventricular space of the newborn brain, originating from the germinal matrix, termed germinal matrix haemorrhage. IVH is diagnosed at a rate of 1 in 5 infants born very preterm (less than 32 weeks' gestation), but the incidence increases with earlier gestation at birth. IVH is graded in severity (I to IV), and the neurological sequelae of IVH in infants born very preterm are significant, with more than 1 in 4 infants with any grade of IVH subsequently diagnosed with a moderate to severe neurodevelopmental deficit, increasing to more than half of infants diagnosed with severe IVH (grade III/IV).</p><p><strong>Summary: </strong>The high susceptibility to IVH in infants born at less than 32 weeks' arises in part to the presence of the germinal matrix. The germinal matrix is a transient brain region that produces neural stem and progenitor cells. The germinal matrix region is rich in angiogenic blood vessels that have a low density of pericyte and astrocyte coverage to provide structural stability, and it is a border zone for vascular endpoints that are highly fragile to haemodynamic instability. In addition to immaturity, antenatal complications may also adversely impact cerebrovascular development, pericyte and astrocyte coverage, and subsequently the structural integrity of the blood-brain barrier that might increase the risk for IVH.</p><p><strong>Key messages: </strong>Here, we will report the maturational profile of cerebrovascular development in the extremely preterm neonate, and implications for susceptibility to IVH, the complications that may contribute to the risk of haemorrhage, and neurodevelopmental deficits that primarily arise from IVH. We aimed to elucidate the cellular foundations of IVH to provide insight into neuroprotective targets.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-12"},"PeriodicalIF":2.3,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Costs of Underfunding Brain Development.","authors":"Masahiro Tsuji, Zoltán Molnár","doi":"10.1159/000546688","DOIUrl":"10.1159/000546688","url":null,"abstract":"<p><strong>Background: </strong>Healthcare costs are rising at an exponential rate. Given the constraints of limited resources, it is essential to make informed decisions about priorities to ensure the best possible health outcomes globally. The history of medicine illustrates how these priorities have shifted over time - from early focus on infectious diseases to later emphasis on noncommunicable conditions such as metabolic disorders. Today, neurodegenerative diseases and aging brain are the forefront of medical research, as these conditions profoundly affect individuals, families, and society.</p><p><strong>Summary: </strong>One in three people will experience a mental health disorder in their lifetime, yet it is not widely recognized that many of these conditions may have origins in pre-birth experiences and early life influences. Disruptions in progenitor proliferation, neuronal and glial migration, and differentiation during prenatal development can contribute to lifelong neurodevelopmental abnormalities. Despite the fundamental importance of brain development, most of the neuroscience funding is allocated to studying neurodegeneration, such as dementia and Parkinson's disease, while early life influences remain underexplored. Crucially, the impact of developmental factors begins even before conception. Environmental risks extend beyond direct maternal exposures during pregnancy; they include cumulative parental exposure to teratogenic agents affecting both male and female gametes, as well as early life environmental exposures affecting newborns, infants, and children. These influences are complex yet highly relevant to long-term health outcomes.</p><p><strong>Key messages: </strong>We urge greater recognition of the developmental origins of disease and advocate for increased investment in preventive strategies. These include lifestyle modifications, dietary improvements, targeted supplementation, regular exercise, and minimizing exposure to environmental pollutants. Addressing these factors proactively could yield profound benefits for both individual and public health.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-13"},"PeriodicalIF":2.3,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pediatric Post-Infectious Neuroinflammatory Syndromes Come to the Fore.","authors":"Samuel J Pleasure","doi":"10.1159/000546082","DOIUrl":"10.1159/000546082","url":null,"abstract":"","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-2"},"PeriodicalIF":2.3,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Bioinformatic Investigation into a Unique Human FOXM1 Exon Variant and Its Relevance to Gyrencephaly.","authors":"Mikaela Barresi, Alice Johnstone, Mary Tolcos","doi":"10.1159/000545713","DOIUrl":"10.1159/000545713","url":null,"abstract":"<p><strong>Introduction: </strong>Gyrification is a shared phenotype of brain development across many species. The identification of human- and primate-specific genes is a topic of great research interest to uncover the genetic mechanisms that drive human gyrification. Here we investigated a human transcript variant of FOXM1 with a unique ninth exon proposed to have a crucial role in primate gyrification.</p><p><strong>Method: </strong>We performed comprehensive bioinformatic analyses, including several BLASTs and multiple sequence alignment, utilising available deposited sequencing data. We aimed to determine the degree of conservation of human FOXM1 exon 9 across a wide range of species, with a particular focus on gyrencephalic primates. Furthermore, we aimed to determine the degree of conservation of the remaining regions of FOXM1 across a subset of gyrencephalic and lissencephalic species.</p><p><strong>Results: </strong>Our results revealed that the exon is only partially detected in four other primates, challenging its presumed conservation in humans, apes, and other primates. The remaining regions of FOXM1 had a remarkably high level of conservation, and, given its role in regulating proliferation and differentiation, the results suggested that FOXM1 may be required for early brain development across all species. However, the sporadic presence of the exon 9 sequence even in other gyrencephalic primates raises questions about its indispensability in the process of gyrification.</p><p><strong>Conclusion: </strong>Therefore, we conclude that the FOXM1 transcript variant comprising the exon 9 sequence in its entirety could be more appropriately reclassified as a human-specific cortical folding variant not found in other species. This research lays the foundation for further investigating the role of FOXM1 exon 9 in human gyrification and brain development.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-9"},"PeriodicalIF":2.3,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Erin E Masterson, Kate Miles, Noelle Schlenk, Cindy Manko, Meiqian Ma, Bahare Farhadian, Kiki Chang, Melissa Silverman, Margo Thienemann, Jennifer Frankovich
{"title":"Defining Clinical Course of Patients Evaluated for Pediatric Acute-Onset Neuropsychiatric Syndrome: Phenotypic Classification Based on 10 Years of Clinical Data.","authors":"Erin E Masterson, Kate Miles, Noelle Schlenk, Cindy Manko, Meiqian Ma, Bahare Farhadian, Kiki Chang, Melissa Silverman, Margo Thienemann, Jennifer Frankovich","doi":"10.1159/000545598","DOIUrl":"10.1159/000545598","url":null,"abstract":"<p><strong>Introduction: </strong>Establishing clear and standardized terminology regarding disease state and course is crucial for enhancing communication, research, and treatment decisions, particularly when there are no clearly identified biological markers, as in the case of pediatric acute-onset neuropsychiatric syndrome (PANS). We aim to propose terminology for assessing disease state and classifying long-term clinical courses in individuals evaluated for PANS, advancing standardization in clinical care and research.</p><p><strong>Methods: </strong>We drew upon clinical expertise, insights from similar conditions, and a decade of longitudinal clinical data from the Stanford University Immune Behavioral Health (IBH) Clinic to devise terminology for characterizing patient status and clinical progression among patients evaluated for PANS. Utilizing parent- and clinician-reported data spanning from 2012 to 2023, we constructed a comprehensive dataset documenting patients' disease trajectory from initial flare to latest clinical encounter, encompassing intervening recovery periods. This allowed us to apply the proposed terminology to the IBH Clinic patient cohort, offering a detailed phenotypic analysis of PANS flares and clinical courses.</p><p><strong>Results: </strong>We analyzed 264 patients evaluated for PANS at the IBH Clinic and stratified them based on whether they met PANS criteria at initial flare (51%), after initial flare (24%), or had not met criteria at the time of analysis (25%). The average age at the initial flare ranged from 6.1 to 8.3 years across these patient subgroups. Among patients with PANS, the average isolated flare lasted 3.7-4.1 months and 95% of flares resolved within 1 year. Five years after initial flare, most (77%) patients with PANS had had multiple flares, and nearly half (43%) had experienced a flare that lasted >12 months, approximately half of which occurred at the initial flare.</p><p><strong>Conclusions: </strong>Patients evaluated for PANS at the IBH Clinic showed diverse clinical presentations and illness courses over the long term, with most experiencing a relapsing-remitting clinical course but some exhibiting persistent symptoms. Many experienced neuropsychiatric flares before meeting PANS classification criteria. This underscores the importance of clinicians being vigilant for new neuropsychiatric symptoms in pediatric patients, even if they do not immediately meet PANS criteria. Based on these data, we propose terms and definitions for characterizing patient status, flares, and clinical course, which we hope the clinical and research communities will build on and refine.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-17"},"PeriodicalIF":2.3,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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