Annals of the Child Neurology Society最新文献

{"title":"Expanding the Phenotype of CYFIP2-Related Developmental Epileptic Encephalopathy: Case Report and Literature Review","authors":"Michaela Squire,&nbsp;Jenna K. Lea,&nbsp;Zheng (Jane) Fan,&nbsp;Senyene E. Hunter","doi":"10.1002/cns3.70036","DOIUrl":"https://doi.org/10.1002/cns3.70036","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Pathogenic <i>CYFIP2</i> variants cause developmental and epileptic encephalopathy (DEE), characterized by early-onset intractable epilepsy and developmental delay. The disease course has not been delineated. Codon Arg87 is a de novo mutational hotspot associated with a severe DEE phenotype via gain-of-function mechanisms. Currently, there are no targeted therapies for <i>CYFIP2</i>-related DEE. Genetic therapies initiated at early symptomatic stages have demonstrated benefit in other disorders and may be an important consideration for this patient population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We describe a child with a de novo <i>CYFIP2</i> Arg87Cys variant and a unique clinical course, along with a comprehensive literature review of reported cases. We identified 41 additional patients with pathogenic or likely pathogenic <i>CYFIP2</i> variants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The Arg87Cys variant was present in 12/42 (29%) patients. An additional 27 variants are described across 30 patients. All individuals had global developmental delay, 32/42 (76%) developed epilepsy, and 25/42 (60%) experienced seizure onset in the first year of life. Of those with seizures, 16/32 (50%) had epileptic spasms, and 5/32 (16%), including our patient, developed other seizure types before epileptic spasm onset. Interestingly, our patient is the only report of developmental and electroencephalographic (EEG) normalization after initial seizure onset and before spasms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our patient expands the phenotype of <i>CYFIP2</i>-related DEE by demonstrating developmental and EEG normalization after seizure onset and before onset of epileptic spasms and global developmental delay. Given the growing field of genetic therapies and other precision medicines, this period of normalization may represent a window of opportunity for future early intervention.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"3 4","pages":"314-323"},"PeriodicalIF":0.0,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.70036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145761478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Speed-Dependent Visual-Motor Tracking Differences in Children With Autism Relate to Core Symptoms","authors":"Daniel E. Lidstone,&nbsp;Stewart H. Mostofsky","doi":"10.1002/cns3.70043","DOIUrl":"https://doi.org/10.1002/cns3.70043","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background and Objectives&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Children with autism spectrum disorder (ASD) often experience challenges integrating visual information to guide motor behavior, particularly in dynamic (speeded) contexts. We investigated the effects of varying stimulus tracking speed on visual-motor integration (VMI), addressing our hypothesis that ASD diagnosis and symptom severity would be associated with impaired performance on dynamic, speeded (vs. slow/static) VMI.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Fifty-four children aged 8–12 years (ASD: &lt;i&gt;n&lt;/i&gt; = 16; typically developing [TD] controls: &lt;i&gt;n&lt;/i&gt; = 38) successfully completed a continuous grip-force tracking task involving three conditions: static, slow, and fast visual trajectories. A linear mixed-effects model was used to examine the effects of ASD (vs. TD) diagnosis on speeded VMI. We further examined the correlation between speeded VMI and both clinician-rated (Autism Diagnostic Observation Schedule, Second Edition [ADOS-2]) and parent-reported Social Responsiveness Scales, Second Edition (SRS-2) autism symptoms.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A significant interaction between diagnosis and condition was observed (&lt;i&gt;p&lt;/i&gt; = 0.03), indicating that group differences in tracking accuracy varied by stimulus speed. Children with ASD showed significantly greater tracking error than TD peers in the fast condition (ASD: 13.5 ± 1.0 [95% CI: 11.3–15.7]; TD: 10.5 ± 0.7 [95% CI: 9.1–12.0]; &lt;i&gt;p&lt;/i&gt; = 0.02), but not in the static (&lt;i&gt;p&lt;/i&gt; = 0.80) or slow (&lt;i&gt;p&lt;/i&gt; = 0.55) conditions. Both groups showed increased error as speed increased, but the ASD group showed greater impairment under speeded conditions. Higher ADOS-2 Total scores predicted greater error in the fast versus slow (&lt;i&gt;p&lt;/i&gt; = 0.009) and fast versus static (&lt;i&gt;p&lt;/i&gt; = 0.06) contrasts and in the fast condition alone (&lt;i&gt;p&lt;/i&gt; = 0.02). Elevated SRS-2 Total scores were similarly associated with greater error in the fast versus slow (&lt;i&gt;p&lt;/i&gt; = 0.02) and fast versus static (&lt;i&gt;p&lt;/i&gt; = 0.02) comparisons, though not in the fast condition alone (&lt;i&gt;p&lt;/i&gt; = 0.23).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Discussion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The findings support difficulty with speeded dynamic VMI as a scalable autism biomarker. Further development of these biomarkers could be helpful to guiding behavioral interventions, for instance, identifying children who would best respond to slowing visual cues during therapy. Future studies should refine assessment tools to extend assessments of dynamic VMI to younger and more affected children and ","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"3 4","pages":"274-281"},"PeriodicalIF":0.0,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.70043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145761212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Rare and Treatable Cause for Generalized Epilepsy: Biotinidase Deficiency","authors":"Sammie Lai,&nbsp;Fernando N. Galan","doi":"10.1002/cns3.70042","DOIUrl":"https://doi.org/10.1002/cns3.70042","url":null,"abstract":"&lt;p&gt;Biotin is an essential cofactor for four carboxylase enzymes that participate in glucose, amino acid, and fatty acid catabolism [&lt;span&gt;1&lt;/span&gt;]. Biotin recycling is essential since humans cannot synthesize this molecule &lt;i&gt;de novo&lt;/i&gt;, and it is mediated by the enzyme biotinidase. Deficiency of this enzyme leads to the disturbance of metabolic homeostasis with clinical features including seizures, ataxia, hypotonia, developmental delay, eczema, alopecia, and occasional ophthalmologic and auditory symptoms [&lt;span&gt;2&lt;/span&gt;]. Biotinidase deficiency (BD) is an autosomal recessive disorder. Mild BD refers to the form of the disease with 10%–30% of enzyme activity, and these patients can be asymptomatic until triggered by metabolic stress [&lt;span&gt;2&lt;/span&gt;]. We describe a teenager with well-controlled generalized epilepsy who was eventually diagnosed with mild BD.&lt;/p&gt;&lt;p&gt;This 14-year-old previously healthy girl was diagnosed with idiopathic generalized epilepsy. She had normal development and was noted to be intellectually gifted. She was socially appropriate and participated in competitive cheerleading at school. Her physical examination was normal, including symmetric reflexes in the extremities and a thorough motor and sensory examination. Electroencephalogram indicated generalized, posterior-predominant epileptiform discharges. As part of her epilepsy evaluation, magnetic resonance imaging (MRI) of the brain showed a hyperintense T2-weighted signal in the right cerebral peduncle (Figure 1a) with no abnormal postcontrast enhancement on FLAIR (fluid-attenuated inversion recovery). Whole-exome sequence revealed compound heterozygosity for two pathogenic variants in the &lt;i&gt;BTD&lt;/i&gt; gene, confirming a diagnosis of BD.&lt;/p&gt;&lt;p&gt;Her regimen included levetiracetam 750 mg twice daily and biotin 5 mg daily. MRI brain at 8 months after initial scan showed interval decrease in signal intensity and size of the right cerebral peduncle lesion (Figure 1b). At 20 months after initial imaging, the lesion was barely detectable on imaging (Figure 1c). No further seizure episodes were observed, although the relationship to her epilepsy is unknown. We are currently evaluating when to stop her antiseizure medication.&lt;/p&gt;&lt;p&gt;This report showcases a rare but treatable cause for epilepsy. The vast majority of BD occurs in the first few months of life and usually before 5 years of age [&lt;span&gt;3&lt;/span&gt;]. When the deficiency presents late, it most commonly involves the central nervous system and can mimic acquired neuroinflammatory disorders [&lt;span&gt;2, 3&lt;/span&gt;]. In one study, neurological problems occurred in 31% of adult-onset BD and 43% of mild BD, with seizures being one of the most frequent symptoms [&lt;span&gt;2&lt;/span&gt;]. While MRI of the brain and spinal cord can be normal, both white matter lesions within the brain and spinal cord have been reported. In one study, the most common imaging abnormalities in children with BD included the optic pathway, fornices, mamillary bodies, hipp","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"3 4","pages":"324-325"},"PeriodicalIF":0.0,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.70042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145761165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Walking Capacity in Children With Ataxia Telangiectasia From the Global Ataxia Telangiectasia Family Data Platform","authors":"Biljana Horn,&nbsp;Alex Smith,&nbsp;Jennifer Thornton,&nbsp;Tara Symonds,&nbsp;Maureen Roden,&nbsp;Dirk Thye,&nbsp;William P. Whitehouse","doi":"10.1002/cns3.70039","DOIUrl":"https://doi.org/10.1002/cns3.70039","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Walking capacity declines prematurely in individuals with ataxia telangiectasia. However, granular data on walking capacity loss in ataxia telangiectasia are scarce. In this large cross-sectional cohort, we describe age-related walking capacity loss reported by participants and compare categories of a subjective walking capacity scale with the International Cooperative Ataxia Rating Scale (ICARS) walking categories.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Children with ataxia telangiectasia who presented with neurological symptoms at 5 years of age or younger and were 18 years of age or younger at the time of walking capacity reporting were included. Descriptive statistics, Spearman's rank correlations, and simple linear regression of score versus age were used to analyze the data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Mean walking capacity scores from 372 participants remained stable until age 5, followed by progressive worsening between ages 5 and 14, with persistently high scores thereafter. Categories from the subjective walking capacity scale were mapped to ICARS and its abbreviated, more functional version, Rescored modified ICARS (RmICARS) walking categories. Correlation with age was similar across all three scales (Spearman's rho: 0.711, 0.713, and 0.714). Linear regression in participants aged 5–14 years (<i>N</i> = 220) showed consistent <i>R</i>² values (~0.45) across all scales and confirmed a statistically significant relationship between age and diminished walking capacity (<i>p</i> &lt; 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Although age-related loss of ambulation was statistically significant, it accounted for just under half of the variability in walking capacity progression. Controlling for disease severity, i.e., classical or the mild variant of ataxia telangiectasia, and capturing more granular data on walking with assistance may improve the prediction of age-associated walking capacity loss.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"3 4","pages":"299-307"},"PeriodicalIF":0.0,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.70039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145761311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Essential Components of Child Neurology Training: Program Director Consensus Recommendations","authors":"Danny Rogers,&nbsp;Robert Thompson Stone,&nbsp;Margie Ream,&nbsp;Rachel Pearson,&nbsp;Lindsay M. Pagano,&nbsp;Miya Elizabeth Bernson-Leung,&nbsp;Elizabeth Troy,&nbsp;Scott I. Otallah,&nbsp;Eric Heath Kossoff,&nbsp;Sudha Kilaru Kessler,&nbsp;Clarimar Borrero-Mejias,&nbsp;Daniel Crowder,&nbsp;Kathryn Idol Xixis,&nbsp;Salvatore C. Rametta,&nbsp;Stephen Deputy,&nbsp;Kapil Arya,&nbsp;Aaron Nelson,&nbsp;Jenny L. Wilson,&nbsp;Amy McGregor,&nbsp;Tara Mangum,&nbsp;Jennifer M. Bain,&nbsp;Yael Shiloh-Malawsky,&nbsp;Meghan S. Candee,&nbsp;Donald L. Gilbert,&nbsp;Jan B. Wollack,&nbsp;Sharoon Qaiser,&nbsp;Rinat Jones,&nbsp;Jeffrey Strelzik,&nbsp;Emmanuelle Tiongson,&nbsp;Charu Venkatesan,&nbsp;Jessica Goldstein,&nbsp;Anna Thamann,&nbsp;Latanya D. Agurs,&nbsp;Teri L. Schreiner,&nbsp;Adam Wallace,&nbsp;Audrey Foster-Barber,&nbsp;Rachel Gottlieb-Smith","doi":"10.1002/cns3.70038","DOIUrl":"https://doi.org/10.1002/cns3.70038","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We aimed to develop a program director–derived model of essential components of child neurology residency training.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>All 79 child neurology residency programs in the United States were invited to submit a block diagram with 48 months of required rotations, the minimum clinical requirement across all approved pathways. These block diagrams were then analyzed for consensus. Program directors were anonymously surveyed regarding whether a child neurology resident could be adequately trained using the consensus curriculum if implemented in either a 4- or a 5-year training program, and whether 4 years of residency could provide adequate training.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fifty of 79 residency programs (63%) submitted a block diagram (54% in pediatrics departments, 46% in neurology departments). Greater than 75% of program directors recommended the following rotations with the average number of months recommended across all program directors in parentheses: pediatric inpatient/hospital medicine (3), pediatric non-consult intensive care (3), healthy newborn (0.5), pediatric acute/emergency care (1), genetics (1), child development (1), child neurology inpatient/consults (8), child neurology general outpatient (4), child psychiatry (1), adult neurology inpatient/consults (3), neurology specialties outpatient (4), electroencephalography (2), neuroradiology (1), and electives (7). Of the program directors (53 of 79, 67%) who completed the post-survey, 87% agreed that these requirements would be adequate, and 89% agreed that child neurologists could be adequately trained for independent practice within 4 years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The program director consensus supports modification of existing child neurology training requirements, with general agreement that 4 years of clinical training would be adequate.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"3 4","pages":"282-291"},"PeriodicalIF":0.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.70038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145761305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unilateral Task, Bilateral Response: An Acquired Movement Disorder in a Child With Chiari Malformation Type III and Syringomyelia","authors":"Aysha Arshad,&nbsp;John R. Crawford","doi":"10.1002/cns3.70033","DOIUrl":"https://doi.org/10.1002/cns3.70033","url":null,"abstract":"<p>This teenaged girl with a Chiari malformation type III that was diagnosed and surgically repaired at birth presented with an 8-year history of involuntary movements of the left arm during right-handed tasks (Video 1). These mirrored movements interfered with fine motor skills such as writing, grooming, and dressing. She denied visual changes, nausea, vomiting, or developmental regression. Her neurological examination revealed involuntary left-hand movements during right-hand activity (Video 1), decreased vibratory sensation in her arms and legs, and impaired tandem gait. Magnetic resonance imaging showed a repaired occipital encephalocele, severe untreated ventriculomegaly, and a syrinx extending from C4 to L1 (Figure 1).</p><p>Mirror movements are involuntary movements that replicate voluntary actions of the contralateral limb and are most often seen in the arms [<span>1</span>]. They represent a type of motor overflow and are considered pathologic when persistent beyond early childhood [<span>2</span>]. Proposed mechanisms include aberrant ipsilateral corticospinal projections, where motor fibers fail to decussate, as well as impaired interhemispheric inhibition, resulting in bilateral cortical activation during unimanual movement [<span>3</span>]. These abnormalities may reflect incomplete development of corticospinal and callosal pathways. Mirror movements are recognized in congenital and midline disorders such as Kallmann and Klippel–Feil syndromes [<span>1, 3, 4</span>] but are rarely reported in association with Chiari malformation type III. This patient underscores the importance of a detailed neurological examination in individuals with congenital hindbrain anomalies and highlights how structural disruption of motor systems may manifest as clinically observable motor overflow.</p><p><b>Aysha Arshad:</b> writing – original draft, writing – review and editing, visualization. <b>John R. Crawford:</b> supervision, writing – review and editing, conceptualization, visualization.</p><p>Written consent was obtained from the parent and patient before submission.</p><p>John R. Crawford, MD, MS, serves as an associate editor of <i>Annals of the Child Neurology Society</i>.</p>","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"3 3","pages":"251-252"},"PeriodicalIF":0.0,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.70033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145100985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fetal and Perinatal Brain MRI Findings in Adaptor Protein Complex 4–Associated Hereditary Spastic Paraplegia","authors":"Alexandra K. Brooks,&nbsp;Vicente Quiroz,&nbsp;Luca Schierbaum,&nbsp;Julian E. Alecu,&nbsp;Katerina Bernardi,&nbsp;Nicole Battaglia,&nbsp;Amy Tam,&nbsp;Joshua Rong,&nbsp;Gregor Kasprian,&nbsp;Edward Yang,&nbsp;Darius Ebrahimi-Fakhari","doi":"10.1002/cns3.70035","DOIUrl":"https://doi.org/10.1002/cns3.70035","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Adaptor protein complex 4–associated hereditary spastic paraplegia (AP-4-HSP) is a rare childhood-onset neurogenetic disorder. With gene replacement therapies advancing, early—potentially prenatal—diagnosis holds significant clinical promise. We aimed to characterize fetal and perinatal brain MRI features of AP-4-HSP to assess whether early imaging can prompt timely diagnosis, counseling, and interventions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this retrospective analysis, we reviewed prenatal imaging from 303 individuals with genetically confirmed AP-4-HSP enrolled in the Registry and Natural History Study for Early Onset Hereditary Spastic Paraplegia (NCT04712812). Four patients (covering SPG47, SPG50, SPG52) with fetal, perinatal, or early postmortem imaging available were selected for detailed neuroradiologic evaluation. Systematic assessment documented several structural anomalies, correlated with genotype and clinical progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fetal imaging between 22 and 38 weeks' gestation revealed ventriculomegaly, corpus callosum hypoplasia, reduced periventricular white matter, and hippocampal under-rotation across all subtypes. The SPG52 patient exhibited additional severe features, including gyral immaturity and pontine/vermis hypoplasia. Postnatal follow-up demonstrated progressive white matter volume reduction and delayed myelination.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study demonstrates that fetal and perinatal brain MRI can detect early, consistent neurodevelopmental abnormalities in AP-4-HSP, reinforcing its classification as both a neurodevelopmental and neurodegenerative disorder. Integration of prenatal neuroimaging with molecular diagnostics could enable earlier recognition, family counseling, and access to emerging gene therapies. These findings support the incorporation of fetal brain MRI into diagnostic protocols for suspected neurogenetic conditions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"3 3","pages":"226-231"},"PeriodicalIF":0.0,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.70035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145101013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Use of Synaptic Extracellular Myo-Inositol to Treat Developmental and Epileptic Encephalopathy","authors":"E. Naomi Vos,&nbsp;Didem Demirbas,&nbsp;Lance Rodan,&nbsp;Edward Yang,&nbsp;Sanjay P. Prabhu,&nbsp;Jie Chen,&nbsp;Xiaoping Huang,&nbsp;Wanshu Qi,&nbsp;Robin L. Haynes,&nbsp;Maria K. Lehtinen,&nbsp;Michael J. Bennett,&nbsp;Miao He,&nbsp;Phillip L. Pearl,&nbsp;M. Estela Rubio-Gozalbo,&nbsp;Annapurna Poduri,&nbsp;Gerard T. Berry","doi":"10.1002/cns3.70029","DOIUrl":"10.1002/cns3.70029","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The developmental and epileptic encephalopathies (DEE) are associated with serious and lifelong neurological conditions and risk of early mortality. Here, we describe the chronic treatment of a boy with <i>PLCB1</i>-related DEE with enteral myo-inositol supplementation as an add-on therapy to standard antiseizure medications that had been ineffective, and present novel findings in our lethal <i>Slc5a3</i> knockout mouse model to substantiate our hypothesis for a novel role of myo-inositol in prenatal life.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Myo-inositol levels were measured in plasma, urine, and cerebrospinal fluid (CSF) using stable isotope dilution and selected ion monitoring gas chromatography/mass spectrometry. Brain function and structure were monitored with magnetic resonance spectroscopy, magnetic resonance imaging, and electroencephalograms. Safety studies were performed according to Food and Drug Administration requirements.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Treatment was well tolerated without any adverse events. There was an improvement in seizure burden and stabilization of brain atrophy that was most evident in the first and second years of life. Myo-inositol administration to the pregnant <i>Slc5a3</i> carrier mice increased the myo-inositol content in the CSF of the <i>Slc5a3</i> knockout pups, which prevented their death.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>High-dose enteral myo-inositol supplementation was safely used in a patient with epileptic encephalopathy due to <i>PLCB1</i> deletion, increasing CSF levels and improving seizures and brain atrophy. The hypothesized mechanism involves restoring a fetal-like state with increased membrane potential, thereby reducing neuronal firing. Based on our experience, we encourage the exploration of high-dose myo-inositol in clinical trials involving infants with severe epileptic encephalopathy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"3 3","pages":"201-207"},"PeriodicalIF":0.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12381637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arthur L. Prensky, 1930–2025","authors":"Christina A. Gurnett,&nbsp;Seth J. Perlman,&nbsp;Steven M. Rothman","doi":"10.1002/cns3.70034","DOIUrl":"https://doi.org/10.1002/cns3.70034","url":null,"abstract":"&lt;p&gt;Arthur Prensky, who profoundly influenced two generations of pediatric neurologists, died on June 16, 2025, after a short illness. He was 94 and Professor Emeritus of Neurology at Washington University School of Medicine at the time of his death. His career spanned the evolution of pediatric neurology from a descriptive specialty to a field anchored in modern genetics and neuroscience.&lt;/p&gt;&lt;p&gt;After early childhood trauma, including some time in foster care, he attended the highly selective Bronx High School of Science and then graduated Phi Beta Kappa from Cornell. He went on to New York University Medical School and then came to Washington University and Barnes Hospital for medical internship and a 1-year research neurophysiology fellowship. This was followed by service in the Air Force School of Aviation Medicine, ironic since he was phobic of flying. He went on to neurology residency at the Massachusetts General Hospital and an additional 3 years of laboratory research focused on leukodystrophies.&lt;/p&gt;&lt;p&gt;In 1967 he “metamorphized” (his own word) into a child neurologist and returned to Washington University to direct a new division of pediatric neurology (Figure 1). In 1974 he was named the first Allen P. and Josephine B. Green Professor of Pediatric Neurology. He had wide-ranging interests and wrote on a variety of topics, including brain lipid metabolism and disorders of myelination; amino acidopathies; epilepsy; toxicity of antiseizure medications; peripheral neuropathies; and Sydenham's chorea. He had an exemplary approach to complicated patients—he tried to formulate as accurate a differential diagnosis as possible but at the end of this process inverted his thinking and asked: Could any treatable condition be present? In this way, he pulled out all stops to make sure his patients did not miss out on potential therapies. He emphasized this approach with residents.&lt;/p&gt;&lt;p&gt;In his later years he was especially interested in pediatric headache, with two of his former trainees becoming national authorities on this topic (Andrew Hershey and Kenneth Mack). With several Washington University colleagues, he coauthored books on nutrition and the brain, caring for children with handicaps, and neurological pathophysiology. His skills were recognized by awards and honors, including the Hower Award of the Child Neurology Society, presidency of the Child Neurology Society, and the Faculty Achievement Award of the Washington University Alumni Association.&lt;/p&gt;&lt;p&gt;Arthur's formal résumé, however, fails to capture the attributes and eccentricities that gained him such notoriety among child neurologists. He was more than six feet tall and, while physically imposing, was noticeably awkward. He frequently mentioned not only that he walked late but that he only learned to ride a bicycle at 12, with the latter milestone achieved because his success became a neighborhood project. This information was often shared with parents of his motor-delayed patients to give ","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"3 3","pages":"132-134"},"PeriodicalIF":0.0,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.70034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chylolymphatic Mesenteric Cyst as a Possible Ketogenic Diet Complication","authors":"Siefaddeen Sharayah,&nbsp;Jennifer Griffith,&nbsp;Brad W. Warner,&nbsp;Liu Lin Thio","doi":"10.1002/cns3.70028","DOIUrl":"https://doi.org/10.1002/cns3.70028","url":null,"abstract":"<p>The ketogenic diet (KD) is a high-fat, low-carbohydrate, adequate-protein diet used for a century to treat drug-resistant epilepsy. It has relatively mild adverse effects. We highlight a patient who developed severe gastrointestinal (GI) symptoms related to a chylolymphatic mesenteric cyst (CMC) after KD initiation.</p><p>This boy was born at 39 weeks weighing 3490 g after an uneventful term gestation. Growth and development were initially appropriate. At 6 months of age he developed seizures manifested by episodes of right head-turning, rightward gaze deviation, impaired responsiveness, sometimes with chewing movements, decreased tone on the left, and/or shaking of the right extremities. These episodes had an ictal electrographic correlate with a diffuse onset but better evolution on the right on continuous video electroencephalography (EEG). Interictally, EEG showed epileptiform discharges in multiple areas on the right, resulting in a diagnosis of focal seizures with impaired consciousness. An epilepsy gene panel identified a heterozygous, paternally inherited, autosomal recessive, pathogenic variant in the biotinidase gene (<i>BTD</i>) (c.1368A&gt;C, p.Q456H). A chromosomal microarray showed a maternally inherited, 329 kb duplication within 11p14.3 (arr[GRCh37]11p14.3(21897259_22226105)x3 mat). Brain magnetic resonance imaging was normal.</p><p>Levetiracetam, zonisamide, and clobazam failed to control seizures. Biotin therapy was not trialed. Oxcarbazepine reduced seizures but was limited by diarrhea and poor sleep. At 22 months, he began a 3:1 KD but was discharged on 2:1 due to acidosis and hypoglycemia. His abdominal examination was unremarkable. His seizure burden decreased from two to four seizures per day to a few times per week within the first 3 months, during which his KD ratio was gradually increased to 2.75:1.</p><p>Three months after starting the KD, he experienced intermittent severe abdominal pain, vomiting, and diarrhea for 5 days. An abdominal computed tomography scan revealed a predominantly hypoattenuating soft tissue mass measuring 35 × 43 × 41 mm arising from the root of the mesentery, causing mass effect on small bowel loops and abutting on branches of the superior mesenteric vein and artery with mesenteric lymphadenopathy (Figure 1). He underwent exploratory laparotomy with resection of a 5 cm chylous-appearing cystic mass in the mesenteric root, along with an 11 cm segment of adjacent small bowel, followed by re-anastomosis (Figure 2). Postoperatively, symptoms resolved, and tolerance to a 2.75:1 KD improved. His last seizures occurred immediately after surgery. He was weaned off oxcarbazepine 10 months after diet initiation, and he was weaned off the diet 2 years after surgery. Now 7 years of age, he remains seizure-free with near-normal development and no cyst recurrence. He has had three normal EEGs, including one overnight on the diet and one after diet discontinuation.</p><p>We classified the abdominal mass in o","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"3 3","pages":"240-241"},"PeriodicalIF":0.0,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.70028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}