Annals of the Child Neurology Society最新文献

{"title":"Epilepsy Phenotypic Spectrum of NUS1-Related Disorder: A Case Series","authors":"Saumel Ahmadi,&nbsp;Natalie Fulton,&nbsp;Michael Morrissey,&nbsp;Rebekah Landre,&nbsp;Stuart Tomko,&nbsp;Fumihiko Urano,&nbsp;Réjean M Guerriero","doi":"10.1002/cns3.70056","DOIUrl":"10.1002/cns3.70056","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Epilepsy with myoclonic and atonic seizures (EMAtS), also known as Doose syndrome, accounts for 1%–2% of childhood epilepsies, and various genes have been implicated in causing this epilepsy syndrome. <i>NUS1</i> encodes for Nogo-B receptor (NgBR), which stabilizes the dehydrodolichyl-diphosphate synthase complex in the endoplasmic reticulum, promoting its enzymatic activity (cis-IPTase) and thereby regulating cholesterol biosynthesis. Pathogenic variants in <i>NUS1</i> have been associated with movement disorder and epilepsy; however, the spectrum of epilepsy and electroencephalogram (EEG) phenotype has not been well characterized.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We describe a single-center case series of five patients with <i>NUS1</i>-related disorder.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In our cohort, three patients met the diagnostic criteria of EMAtS, and the remainder had a milder form of generalized epilepsy. Four patients had a pathogenic variant in <i>NUS1</i> on one allele, and one patient had a missense change of unclear significance but fit the phenotype of <i>NUS1</i>-related disorder. All patients bearing the pathogenic variants in <i>NUS1</i> had normal to mild developmental delay at the onset of epilepsy, with normal brain magnetic resonance imaging. Age of seizure onset in these patients was 1–7 years, and patients responded to levetiracetam and/or valproic acid. The EEG findings for these patients included the presence of spike and slow wave discharges, as well as the presence of generalized, invariant monomorphic theta range activity in the awake state, which was seen in four out of the five patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Taken together, <i>NUS1</i> variants are associated with generalized epilepsy phenotype and an invariant EEG pattern of monomorphic theta activity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"4 1","pages":"95-100"},"PeriodicalIF":0.0,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12914875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146229673","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 Pain Perception: Legislative Assertions and Developmental Neuroscience","authors":"William D. Graf,&nbsp;Timothy M. Crombleholme,&nbsp;Leon G. Epstein,&nbsp;Dawn Gano,&nbsp;Phillip L. Pearl,&nbsp;Timothy V. Salomons,&nbsp;Mark S. Scher,&nbsp;Elise Turk,&nbsp;Klaus-Peter Zimmer,&nbsp;Harvey B. Sarnat","doi":"10.1002/cns3.70057","DOIUrl":"https://doi.org/10.1002/cns3.70057","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Pain perception is a conscious experience, but neither pain nor consciousness is defined in the developing human fetus. Emergent consciousness may be regarded as a phenomenon that ultimately arises from an essential minimum of functional neuronal connectivity. Proposed U.S. federal legislation asserts that a functioning cerebral cortex is not necessary to experience pain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We assess the scientific premise of the 13 assertions in the “Pain-Capable Unborn Child Protection Act” with analysis and interpretation from a developmental neuroscience perspective. We review the biological requisites of fetal sentience, the emergence of involuntary spinal cord and brainstem reflexes, the early appearance of autonomic homeostatic stress reactions, and measures of synaptogenesis and neuronal connectivity through immunocytochemistry and fetal functional neuroimaging.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The formation of functional synapses can be demonstrated by synaptophysin immunoreactivity in the receptive sensory layers of fetal cerebral cortex at around 25 weeks' gestation, but immunoreactivity is not uniformly intense until after 35 weeks. In vivo, fetal functional magnetic resonance imaging confirms immunocytochemical results by showing complex, interconnected brain networks developing at similar gestational ages. Fetal magnetoencephalography detects magnetic fields from fetal brain activity and demonstrates second-order rule learning in fetuses over 35 weeks' gestation. The neural pathways required for the emotional and evaluative aspects of pain processing in the brain are still incomplete in term newborns.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Given the limitations of reductionism to explain the subjective nature of consciousness, evidence from developmental neuroanatomy, neurophysiology, and functional neuroimaging infers that fetal pain perception requires the emergence of conscious cortical processing beginning with weak functional thalamocortical connectivity well after the age of fetal viability.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"4 1","pages":"15-28"},"PeriodicalIF":0.0,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.70057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147570231","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 Digital Diagnostic Odyssey: Artificial Intelligence and Social Media Crowdsourcing Amid Pediatric Neurology Access Gaps","authors":"Audrey M. Smith,&nbsp;Rachel Vassar","doi":"10.1002/cns3.70048","DOIUrl":"https://doi.org/10.1002/cns3.70048","url":null,"abstract":"&lt;p&gt;Child neurology continues to face a workforce shortage in the United States. The average wait time to see a pediatric neurologist is 45 days, and 30% of children wait more than 8 weeks [&lt;span&gt;1&lt;/span&gt;]. Because three-quarters of child neurologists work in urban settings [&lt;span&gt;1&lt;/span&gt;], access to care is even more restricted for families in rural areas. The situation has left an access gap that is already partially being filled by artificial intelligence (AI)-assisted diagnosis and social media crowdsourcing for information. AI has also helped children with rare neurological conditions who did have access to pediatric neurologists but remained undiagnosed. Such tools can yield impressive breakthroughs for some families but also pose significant risks.&lt;/p&gt;&lt;p&gt;One striking example of AI's use in pediatric neurology comes from a mother who spent 3 years seeking answers for her son's gross motor delay and back pain [&lt;span&gt;2&lt;/span&gt;]. After consultations with 17 medical professionals yielded no diagnosis, the mother entered his symptoms and magnetic resonance imaging (MRI) report into ChatGPT (OpenAI). It suggested tethered cord syndrome, which was later confirmed by a pediatric neurosurgeon and quickly repaired. This patient demonstrates AI's potential as a diagnostic partner when traditional care pathways fail or are unavailable, particularly for rare conditions.&lt;/p&gt;&lt;p&gt;Emerging AI-based clinical diagnostic tools also show promise. One AI model trained on several thousand video clips of infantile spasms was able to identify a seizure with 85% accuracy [&lt;span&gt;3&lt;/span&gt;]. Another AI tool analyzed caregiver questionnaires and home videos to identify behaviors consistent with autism spectrum disorder (ASD) with more than 98% sensitivity [&lt;span&gt;4&lt;/span&gt;]. This suggests a potential role for AI in streamlining pediatric neurological diagnoses and partially filling the child neurologist access gap. Streamlined diagnosis for many pediatric neurological conditions leads to earlier treatment and provides an undeniable benefit in conditions such as ASD, infantile spasms, and other forms of epilepsy [&lt;span&gt;5-7&lt;/span&gt;]. However, because AI is new, we do not have data on how many families trust and act upon these AI-assisted diagnoses, nor can we identify instances of unnecessary or harmful treatment of a child due to an incorrect AI-assisted diagnosis.&lt;/p&gt;&lt;p&gt;It is also important to consider the potential complexities of AI-assisted diagnoses on healthcare coverage. For example, many insurance providers require a formal evaluation for ASD using the Autism Diagnostic Observation Schedule or other gold-standard assessment for service eligibility [&lt;span&gt;8&lt;/span&gt;]. Policy change would be required before AI-based care can fully translate into earlier access to therapies for children. AI may speed diagnosis for some children, but this does not guarantee earlier therapy if families cannot access the necessary resources.&lt;/p&gt;&lt;p&gt;Another success story for AI in pediatric neu","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"4 1","pages":"12-14"},"PeriodicalIF":0.0,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.70048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147570118","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":"Infant Monitoring Devices in Infants With or at Risk for Sturge–Weber Syndrome: Analysis of Clinical Questionnaire Supports Reduced Parent Anxiety","authors":"Katharine E. Joslyn,&nbsp;Ashley N. Eisenberg,&nbsp;Veronica M. Lee,&nbsp;Linda Rozell-Shannon,&nbsp;Anne M. Comi","doi":"10.1002/cns3.70046","DOIUrl":"https://doi.org/10.1002/cns3.70046","url":null,"abstract":"<p>Diagnosis and treatment of Sturge–Weber syndrome (SWS) brain involvement in infants born with a port-wine birthmark who are at risk of seizures requires close neurological monitoring [<span>1, 2</span>]. In 90% of patients with SWS brain involvement, seizures will occur before 2 years of age [<span>2</span>]. Early seizures in patients with SWS are typically focal or partial, prolonged, and often associated with tachycardia. Less commonly, they may present with bradycardia and desaturations, which are often not detectable on seizure-specific devices [<span>3</span>]. There has been a notable increase in parents using infant monitoring devices (IMDs) in the Hunter Nelson Sturge–Weber Center. The present study analyzed parental experience using commercially available IMDs and assessed whether these devices may be useful for detecting clinically diagnosed seizures in patients with SWS.</p><p>We sent a clinical questionnaire developed in Qualtrics via a secure email link to parents of patients &lt; 5 y of age diagnosed or at risk for SWS and seen between August 31, 2021, and August 31, 2024 (<i>N</i> = 118) at Kennedy Krieger (KK). Twenty-two research-consented patients responded to the questionnaire. We shared the questionnaire with the Vascular Birthmarks Foundation (VBF), who posted it on SurveyMonkey on Facebook pages between February 7, 2025, and April 21, 2025 (<i>N</i> = 37 respondents). See Figures S1a,b for questionnaire and Tables S1a–S2b for demographic information and SWS characteristics.</p><p>While the data from the clinical site came from a closely followed patient population, the data from the advocacy site came from participants without a well-characterized clinical presentation. In addition, it is not certain whether the two groups could have generated multiple responses from the same individuals. Each site yielded the same conclusions, supporting broader generalization.</p><p>Parents reported having an overall positive experience using an IMD. See Figure S4 for the combined parental Likert scale data. This initial study supports the use of IMDs to aid in decreasing anxiety in parents of infants with SWS brain involvement and epilepsy, and the need for future research, including larger and more diverse sample sizes and retrospective and prospective studies, to determine if the use of IMDs in these patients can detect epileptic seizures.</p><p><b>Katharine E. Joslyn:</b> writing – original draft, writing–review and editing, data visualization. <b>Ashley N. Eisenberg and Veronica M. Lee:</b> data curation, writing–review and editing. <b>Linda Rozell-Shannon:</b> conceptualization, data curation, writing–review and editing. <b>Anne M. Comi:</b> conceptualization, supervision, writing–review and editing.</p><p>A.M.C. is an editorial board member of ACNS. The other authors declare no conflicts of interest.</p>","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"3 4","pages":"326-329"},"PeriodicalIF":0.0,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.70046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145761114","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":"Preserved Limbic White Matter Predicts Favorable 2-Year Outcomes in Neonatal Hypoxic-Ischemic Encephalopathy","authors":"Xingyu Chen,&nbsp;Shuhei Tomoshige,&nbsp;Ria Wright,&nbsp;Vera J. Burton,&nbsp;Gwendolyn Gerner,&nbsp;Nathanael Kuo,&nbsp;Jill S. Chotiyanonta,&nbsp;Raul Chavez-Valdez,&nbsp;Ernest M. Graham,&nbsp;Frances J. Northington,&nbsp;Kenichi Oishi","doi":"10.1002/cns3.70047","DOIUrl":"https://doi.org/10.1002/cns3.70047","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Accurate prediction of both favorable and unfavorable long-term neurodevelopmental outcomes of neonatal hypoxic-ischemic encephalopathy (HIE) is essential for clinical care, yet the brain structures underlying a favorable prognosis remain unclear. This study aimed to identify diffusion magnetic resonance imaging (MRI) measures that can predict the 2-year outcomes in neonates with HIE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed whole-brain diffusion MRI scans from a retrospective cohort of 40 neonates with HIE, acquired within 14 days of birth. Diffusion measures were quantified across 16 cerebrum regions covering the whole cerebrum. We used the area under the Receiver Operating Characteristic curve (AUC) to evaluate the performance of regional fractional anisotropy (FA) and mean diffusivity (MD) values in predicting neurodevelopmental outcomes assessed at 2 years of age.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Reduced FA in the thalamus (AUC = 0.990), basal ganglia (AUC = 0.961), basal forebrain (AUC = 0.951), and limbic white matter (AUC = 0.961) strongly predicted severe disability or death, whereas preserved limbic white matter FA uniquely predicted favorable outcomes (AUC = 0.811).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>While FA reduction in the thalamus, basal ganglia, and basal forebrain is a robust marker for severe outcomes, the limbic white matter demonstrated sensitivity to mild hypoxic-ischemic injury. Therefore, the preservation can be a potential marker for predicting favorable neurodevelopmental trajectories.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"3 4","pages":"308-313"},"PeriodicalIF":0.0,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.70047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145761230","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":"Landscape of Advanced Practice Provider Responsibilities in Pediatric Neurology","authors":"Chelsey F. Stillman,&nbsp;Mona P. Jacobson,&nbsp;Jill M. Marks,&nbsp;Craig A. Press,&nbsp;Kelly G. Knupp,&nbsp;Kevin C. Ess","doi":"10.1002/cns3.70041","DOIUrl":"https://doi.org/10.1002/cns3.70041","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>A worldwide shortage of pediatric neurologists, combined with increased demand, increased wait times, and clinician burnout, have led to substantial access limitations. Given these challenges, we need to ensure advanced practice providers (APPs) in pediatric neurology are utilized effectively. Our results provide a framework for optimizing modern pediatric neurology practice through a thoughtful consideration of APP integration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A survey was sent through two large neurology academic organizations. Emails were also sent to known professional contacts across 59 practice sites. An electronic survey in REDCap with 31 open-ended or multiple-choice questions about demographics, supervision, inpatient and outpatient clinical processes, procedures, and scholarly activities was sent.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Surveys were completed from 29 sites. Sixteen of these sites (55%) reported APPs do not have demographic restrictions in their outpatient practice. At many practice sites APPs perform inpatient consultations, with variable models for independence and partnership with attending neurologists. APPs subspecialize frequently and perform a variety of procedures including lumbar punctures and headache treatment injections.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Most US-based APPs in outpatient pediatric neurology practice autonomously and also frequently perform procedures. APP independence in the inpatient setting should be expanded. As pediatric neurology practices evolve, information regarding the landscape of APP clinical responsibilities will aid in increasing access to care.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"3 4","pages":"292-298"},"PeriodicalIF":0.0,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.70041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145754653","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":"Natural History of Alternating Hemiplegia of Childhood: Vulnerabilities in Early Childhood and Predictive Factors for Long-Term Outcomes","authors":"Shital H. Patel,&nbsp;Eleni Panagiotakaki,&nbsp;Beiyu Liu,&nbsp;Carmen Fons,&nbsp;Lyndsey Prange,&nbsp;Maria T. Papadopoulou,&nbsp;April Boggs,&nbsp;Elisa De Grandis,&nbsp;Aikaterini Vezyroglou,&nbsp;Francesco Fortunato,&nbsp;Simona Balestrini,&nbsp;Francesca Ragona,&nbsp;Eugenia Julia Tosi,&nbsp;Claudio Zucca,&nbsp;Giacomo Garone,&nbsp;Andrey Megvinov,&nbsp;Giosuè Lo Bosco,&nbsp;Michela Stagnaro,&nbsp;Julie Uchitel,&nbsp;Marion Comajuan,&nbsp;Matthildi Athina Papathanasiou Terzi,&nbsp;Jennifer Anticona,&nbsp;Joan M. Jasien,&nbsp;Jeffrey Wuchich,&nbsp;Sigurdur H. Johannesson,&nbsp;J. Narayan,&nbsp;J. Helen Cross,&nbsp;Sanjay M. Sisodiya,&nbsp;Hwanhee Hong,&nbsp;Alexis Arzimanoglou,&nbsp;Rosaria Vavassori,&nbsp;Mohamad A. Mikati","doi":"10.1002/cns3.70037","DOIUrl":"https://doi.org/10.1002/cns3.70037","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The natural history of the most common <i>ATP1A3</i>-related disease, alternating hemiplegia of childhood (AHC), has not been determined. We investigated three hypotheses: (1) AHC worsens over time; (2) several novel factors correlate with long-term outcomes; and (3) AHC manifests high mortality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In a large cross-sectional study with a nested period of prospective 1–3-year follow-up, 115 patients (0.3–46.0 years old, 9 centers/5 countries) were evaluated using across-center-standardized protocol and validated scales. Univariable and multivariable linear-mixed-effects models with random intercepts and random slopes for age, adjusted for confounding variables, allowed for the determination of the effect of age throughout the total age range of patients studied.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><b>Course:</b> We identified a distinction between two periods, namely the period of early childhood (age 1–5 years) and the period of later childhood to mid-adulthood. Intellectual and non-paroxysmal disability indexes (IDS, NPDI) scores as well as the Vineland Adaptive Behavior Composite and its subscales worsened during early childhood, but not in the period after that. The extent of motor skills impairment did not differ with age in either period. Within the PDI (paroxysmal disability index) scores, dystonia severity scores did not differ with age in either period; however, plegia severity scores did improve with age after 5 years of age. <b>Prognostic variables</b> included the following: (1) Epilepsy was associated with worse NPDI, intellectual, and fine and gross motor skills. (2) Worse early life PDI and NPDI scores were significantly associated with worse respective scores at the latest follow-up. (3) Worse early life NPDI scores were also associated with worse IDS and fine and gross motor scores at the latest follow-up. (4) <i>D801N</i> mutation was associated with worse PDI. (4) <i>E815K</i> mutation was associated with worse IDS. <b>Mortality was</b> 1.12 deaths/100 patient-years and 6.5 sudden unexpected death in epilepsy (SUDEP) deaths/1000 patient-years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>AHC is a progressive disease, and early childhood is the vulnerable period. We identified several novel prognostic indicators and a mortality rate, which provide critical information not only regarding prognostication, counseling, and underlying pathophysiology but also for planning therapeutic studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"3 4","pages":"260-273"},"PeriodicalIF":0.0,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.70037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145761483","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":"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}