Annals of the Child Neurology Society最新文献

{"title":"Increased Extra-Axial Cerebrospinal Fluid Volume in Children With Angelman Syndrome: Links to Sleep Problems and Seizures","authors":"Zumin Chen,&nbsp;Dea Garic,&nbsp;Yinuo Xu,&nbsp;Rachel G. Smith,&nbsp;Leigh Anne H. Weisenfeld,&nbsp;Sun Hyung Kim,&nbsp;Martin A. Styner,&nbsp;Joseph Piven,&nbsp;Benjamin D. Philpot,&nbsp;Heather C. Hazlett,&nbsp;Mark D. Shen","doi":"10.1002/cns3.70024","DOIUrl":"10.1002/cns3.70024","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Previous studies demonstrated that children with autism have enlarged volumes of extra-axial cerebrospinal fluid (EA-CSF) and an increased ratio of EA-CSF to brain volume, indicating that EA-CSF is disproportionally increased beyond macrocephaly often observed in autism. It is unknown whether EA-CSF is disproportionally enlarged in Angelman syndrome (AS), which shares phenotypic features with autism (sleep problems, seizures) but is characterized by microcephaly. This study examined EA-CSF and total cerebral volume (TCV) in AS children compared with neurotypical (NT) controls to test whether EA-CSF is disproportionally enlarged and is associated with sleep problems and seizures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Magnetic resonance imaging scans were acquired in <i>n</i> = 29 AS (M[SD] = 6.95 ± 2.83 years) and <i>n</i> = 27 NT children (M[SD] = 7.96 ± 2.24). EA-CSF and TCV were compared using analysis of covariance (ANCOVA), controlling for age, sex, and group interactions. In AS, associations between EA-CSF, sleep quality, and seizure severity were evaluated by linear regression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Children with AS had 22% smaller TCV (<i>p</i> &lt; 0.0001) yet nearly identical EA-CSF volumes (<i>p</i> = 0.35). The ratio of EA-CSF to TCV was 48% higher in AS (<i>p</i> &lt; 0.0001). Increased EA-CSF ratio in AS was associated with sleep initiation problems (<i>p</i> = 0.002) and seizure severity (<i>p</i> = 0.032).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Children with AS have disproportionally higher EA-CSF volume than would be predicted by their smaller brain size. EA-CSF was associated with sleep problems and seizures, which impact quality of life and are target endpoints of current AS clinical trials. Excessive CSF suggests that CSF circulation might be perturbed in AS, which could have implications for brain waste clearance and impact the biodistribution of AS therapies delivered via CSF.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"3 3","pages":"165-175"},"PeriodicalIF":0.0,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12356226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980725","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":"Difficult-to-Treat Epilepsy With Developmental Implications","authors":"Samuel Kamoroff,&nbsp;Harry Abram,&nbsp;Fernando Galan","doi":"10.1002/cns3.70022","DOIUrl":"https://doi.org/10.1002/cns3.70022","url":null,"abstract":"<p>This 5-year-old girl presented with approximately 1 year of recurrent episodes of staring with rhythmic eye movements and upper extremity twitching. Development and cognition were normal. Electroencephalogram (EEG) captured typical events of behavioral arrest with staring associated with rhythmic upper body myoclonic jerks time-locked to generalized spike-wave discharges (Video 1/Figure 1). Photic stimulation induced events. Magnetic resonance imaging was normal. An epilepsy gene panel revealed a variant of unknown significance in <i>ADAR</i>/<i>TREX1</i>. Initial treatment with valproic acid (VPA) was unsuccessful, but adding clobazam resolved her seizures. Attempted simplification to monotherapy clobazam was unsuccessful, but she remained seizure-free when combination VPA and clobazam therapy was reintroduced.</p><p>Epilepsy with myoclonic absences (EMA) is an epilepsy syndrome characterized by absence seizures accompanied by myoclonic jerks and tonic abduction in the arms often appearing as a ratcheting movement [<span>1</span>]. The condition typically begins in early childhood and can persist into adulthood [<span>2</span>]. Cognitive and developmental impairments may arise from the interplay between the underlying epileptic condition and the effects of frequent seizures [<span>3</span>]. VPA is generally the first-line treatment, often combined with other antiepileptic drugs such as ethosuximide, benzodiazepines, or levetiracetam [<span>1, 4</span>]. However, age, metabolic conditions, and sex may impact first-line medication choice. Zonisamide, levetricetam, clobazam, and several others can be considered as second line or if VPA is not recommended [<span>1, 2</span>]. Primary sodium channel blockers, such as carbamazepine, oxcarbazepine, and phenytoin, should be avoided to prevent exacerbating seizures [<span>5</span>]. Early diagnosis and treatment is crucial for better outcomes, as delayed therapy and the presence of generalized tonic-clonic seizures may indicate a poorer prognosis [<span>2</span>]. Proper medication management of EMA requires consideration of potential side effects and comorbidities.</p><p><b>Samuel Kamoroff:</b> conceptualization, writing – original draft, writing – review and editing, data curation. <b>Harry Abram:</b> writing – review and editing, supervision. <b>Fernando Galan:</b> writing – review and editing, visualization, supervision.</p><p>Parental consent was obtained due to the patient being a minor with identifiable physical features included in the video.</p><p>The authors declare no conflicts of interest.</p>","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"3 3","pages":"249-250"},"PeriodicalIF":0.0,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.70022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145101125","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":"Delayed Neuropsychiatric Syndrome Due to Unrecognized Carbon Monoxide Toxicity: A Case Report","authors":"Alexandria Valdrighi,&nbsp;Greta Peng,&nbsp;Andreas Rauschecker,&nbsp;Mary Karalius","doi":"10.1002/cns3.70021","DOIUrl":"https://doi.org/10.1002/cns3.70021","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Carbon monoxide (CO) is a leading cause of poison-related deaths in children and frequently results in nonspecific neurological symptoms and imaging findings. Rarely, pediatric patients develop a delayed neuropsychiatric syndrome (DNS) following a lucid interval. Although imaging findings of early bilateral globi pallidi injury and white matter demyelination in association with DNS are most common, these findings are not always present. It is important to consider CO toxicity in patients found unresponsive without a clear etiology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Patient Presentation</h3>\u0000 \u0000 <p>This 16-year-old boy was found unresponsive at his workplace with initial labs notable for end-organ injury. After stabilization, he had deficits in language, attention, memory, and left-sided dysmetria on neurological assessment. Imaging demonstrated injury in the bilateral caudate, putamen, hippocampi, and cerebellum, concerning for anoxic injury. His symptoms initially improved, but he developed new agitation and dyskinetic movements 6 days after presentation. His imaging continued to evolve with late enhancement in areas of prior injury and the bilateral globi pallidi. Ultimately, it was discovered that he had CO toxicity from a leaky workplace water heater.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion and Conclusions</h3>\u0000 \u0000 <p>We highlight a rare presentation of DNS in a pediatric patient with CO toxicity. Our patient demonstrates the spectrum of clinical and imaging findings associated with CO toxicity and DNS. The clinical and neuroimaging features of CO toxicity are variable, making diagnosis challenging without a known exposure. It is important to maintain CO toxicity on the differential for patients presenting with unexplained neurological symptoms.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"3 3","pages":"220-225"},"PeriodicalIF":0.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.70021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145101331","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":"Novel Pathogenic Variant in Exon 31 of the TSC2 Gene Associated With a Severe Phenotype of Tuberous Sclerosis","authors":"Tabitha D'souza,&nbsp;Laura Davids,&nbsp;Prabhumallikarjun Patil","doi":"10.1002/cns3.70026","DOIUrl":"https://doi.org/10.1002/cns3.70026","url":null,"abstract":"&lt;p&gt;Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disorder caused by variants of the &lt;i&gt;TSC1&lt;/i&gt; (tuberous sclerosis complex 1) or &lt;i&gt;TSC2&lt;/i&gt; (tuberous sclerosis complex 2) tumor suppressor genes, which regulate cellular proliferation through the mTOR (mammalian target of rapamycin) pathway [&lt;span&gt;1, 2&lt;/span&gt;]. TSC has complete genetic penetrance but variable expressivity between patients, which leads to a broad phenotype [&lt;span&gt;1, 3&lt;/span&gt;]. Diagnosis is based on major and minor clinical criteria, but identification of a pathogenic genetic variant can be sufficient for early diagnosis in the absence of clinical features [&lt;span&gt;4, 5&lt;/span&gt;]. Pathogenic variants are those that prevent protein synthesis or lead to loss of protein function; these are commonly nonsense or frameshift mutations or large deletions [&lt;span&gt;5&lt;/span&gt;]. Pathogenic variants have been identified in all other &lt;i&gt;TSC2&lt;/i&gt; exons in the literature; however, variants in exons 25 and 31 have not been associated with loss of protein function or severe symptoms of disease. It has been hypothesized that this occurrence is due to alternative splicing mechanisms in these exons [&lt;span&gt;2&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;This 2-month-old boy completed genetic testing shortly after birth due to a family history of TSC. A paternal aunt with hypomelanotic macules was previously diagnosed with TSC, and additional family members had cutaneous features of the disease. Genetic testing of our patient showed a heterozygous frameshift variant in exon 31 of &lt;i&gt;TSC2&lt;/i&gt; (NM_000548.5) c.3786dupA p.Pro1263ThrfsTer59, classified as a likely pathogenic variant (based on the understanding that a frameshift variant is predicted to lead to loss of protein function) although no patients with this variant leading to clinical disease have been documented. Frameshift variants disrupt the reading frame, changing the downstream amino acid codons and resulting in a truncated protein or a protein that is subject to nonsense-mediated decay.&lt;/p&gt;&lt;p&gt;Our patient's paternal aunt had molecular confirmation of the same variant, and the father was considered an obligate carrier with a milder phenotype of the disease. However, parental testing was not completed due to a loss of follow-up. Within the next few months, this patient developed infantile spasms, which were treated with vigabatrin and adrenocorticotropic hormone. Magnetic resonance imaging of the brain at 5 months of age revealed left-sided subependymal nodules, without other abnormalities (Figures 1 and 2). Additional screening (echocardiogram, renal ultrasound, and ophthalmologic evaluation) was completed, and there were no signs of systemic involvement.&lt;/p&gt;&lt;p&gt;The diagnosis of TSC can be challenging during early life due to broad phenotypic variability. Genetic testing can be useful as a screening tool in patients at risk for disease. Our patient, who was diagnosed with TSC by genetic testing, was initially asymptomatic and later developed severe manifesta","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"3 3","pages":"238-239"},"PeriodicalIF":0.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.70026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145101049","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":"Clinically Important Endpoints in Individuals With Leukodystrophy: A Multisite Study","authors":"Emma R. Kotes,&nbsp;Sarah Woidill,&nbsp;Russell D'Aiello,&nbsp;Amina Khan,&nbsp;Jacob McCann,&nbsp;Mark Ramos,&nbsp;Francesco Gavazzi,&nbsp;Stephanie Keller,&nbsp;Keith Van Haren,&nbsp;Ali Fatemi,&nbsp;Florian Eichler,&nbsp;Joshua Bonkowsky,&nbsp;Jamie Fraser,&nbsp;Lisa Emrick,&nbsp;Omar Sherbini,&nbsp;Ashley Hackett,&nbsp;Jeilo Gauna,&nbsp;Dandre Amos,&nbsp;Jordan Goodman,&nbsp;Amena Smith Fine,&nbsp;Amanda Nagy,&nbsp;Seungil Lee,&nbsp;Nicole Page,&nbsp;Johanna Schmidt,&nbsp;Amy Pizzino,&nbsp;Kayla Muirhead,&nbsp;Mariko Bennett,&nbsp;Amy Waldman,&nbsp;Justine Shults,&nbsp;Laura Adang,&nbsp;Robert Grundmeier,&nbsp;Adeline Vanderver","doi":"10.1002/cns3.70025","DOIUrl":"10.1002/cns3.70025","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Importance&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Leukodystrophies are a diverse group of rare disorders that disrupt central myelination. These disorders present with a broad spectrum of neurological severity and are associated with a range of potential secondary complications, such as scoliosis and failure of independent feeding.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We explore real-world data of leukodystrophy complications to inform future evidence-based care guidelines across these rare diseases.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Design&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;In a cross-sectional observational study, we use a leukodystrophy-specific research consortium and the availability of electronic health records (EHR) to capture a cross-section of real-world data.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Setting&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Study participants were identified using EHR data from five hospital systems with established expertise in leukodystrophies.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Participants&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Principal investigators or genetic counselors confirmed leukodystrophy diagnoses in all participants.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Exposures&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Time-to-event measures were collected, including orthopedic complications (scoliosis, hip subluxation/dislocation), loss of ambulation, artificial ventilation, gastrostomy tube placement, and urinary tract infections (UTIs). Maximum motor milestones, including gain of ambulation by 2 years of age, were captured to stratify cohorts by neurological severity.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Main Outcome and Measure&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A primary outcome was not prespecified, as this was an observational study.&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;In total, 1203 participants were identified across 42 leukodystrophies (age range of 9 days to 89 years at last encounter). The most common event was feeding tube placement, and the median time to any first complication varied between disorders (Fleming–Harrington weighted log-rank test). The specific diagnosis correlated with maximum gross motor milestone attainment (chi-square test of independence). When all disorders were stratified by maximum motor milestone attainment (not specific diagnosis), the median time ","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"3 3","pages":"176-187"},"PeriodicalIF":0.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12369899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980688","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":"Considerations in Transition of Pediatric Neurology Patients to Adult Care","authors":"Asif Doja,&nbsp;Katherine Muir,&nbsp;Megan E. Harrison,&nbsp;Sarah Healy,&nbsp;Ashley Vandermorris,&nbsp;Alene Toulany","doi":"10.1002/cns3.70019","DOIUrl":"https://doi.org/10.1002/cns3.70019","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Transition refers to the planned, coordinated movement of adolescents from the child- and family-centered environment of pediatric care to the adult healthcare system. A well-structured transition process is essential for ensuring adolescents with chronic health conditions continue to thrive in young adulthood. Poor transitions can lead to negative health outcomes, worsening of comorbidities such as anxiety and depression, and poorer psychosocial well-being.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This topical review combines literature from general pediatrics, adolescent medicine, general child neurology, and child neurology subspecialities to provide holistic recommendations for the transition of pediatric patients to adulthood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Core principles of transition include starting transition planning early, creating individualized transition plans, providing support before transition, and ensuring ongoing support after transition to adult care. For adolescents with neurological conditions, additional considerations include recognizing that many childhood neurological disorders are now lifelong conditions, addressing the impact of varying levels of intellectual disability, reevaluating the diagnosis at the time of transfer, and establishing emergency care planning.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"3 3","pages":"145-151"},"PeriodicalIF":0.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.70019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145101047","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":"Variation in Neurodegeneration-Linked Brain Regions in Young Adult APOE E4 Carriers With Spina Bifida","authors":"Joan M. Jasien,&nbsp;Jacques A. Stout,&nbsp;Mohamad A. Mikati,&nbsp;Robert J. Anderson,&nbsp;Brittany G. Nave,&nbsp;Herbert E. Fuchs,&nbsp;Brian Smith,&nbsp;Alexandra Badea,&nbsp;Jeffrey N. Browndyke","doi":"10.1002/cns3.70016","DOIUrl":"https://doi.org/10.1002/cns3.70016","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Possible pleiotropic effects of apolipoprotein E4 (APOE E4) in individuals with congenital brain malformations are relatively unknown. Our goal was to determine if neurodegeneration-linked brain region volumes differ significantly between E4 carriers and noncarriers in young adults with spina bifida (SB).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Eleven individuals ( &gt; 18 years), genotyped for APOE, underwent neuroimaging and neurocognitive evaluation. Primary analysis: Magnetic resonance imaging (MRI) data from 10 a priori neurodegeneration-risk regions of interest were compared between E4 carriers and noncarriers, adjusting for age, sex, and total intracranial volume (FDR-adjusted <i>p</i> &lt; 0.05). Secondary analyses: Age-adjusted neurocognitive standard scores were compared between groups (<i>p</i> &lt; 0.05). Post hoc analyses of NeuroQuant-derived regional brain volumes were examined for combined group differences in young adults with SB.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Comparison of a priori risk region volumes revealed significantly lower left amygdala volumes (FDR-adjusted <i>p</i> = 0.04) in young adult E4 carriers (<i>n</i> = 4) relative to noncarriers (<i>n</i> = 7). Neurocognitive data were not significantly different between the groups. A possible trend was detected for enlarged parietal volumes in E4 carriers (<i>p</i> = 0.07), while volumetric extremes ( &gt; 95% or &lt; 5%) were detected for the anterior cingulate (100% of cases; <i>p</i> = 0.001), frontal cortices (90% of cases), hippocampus (80% of cases), and entorhinal cortices (70% of cases).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Early left amygdala volumetric reduction was found in E4 carriers; combined group volume comparisons revealed frontal and temporal lobe differences in young adults with SB relative to age- and sex-matched volumetric estimates. This pilot investigation does not appear to support E4 conferring a pleiotropic benefit in young adults with SB but rather supports further investigation of MRI volumetrics as a possible biomarker for this population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"3 3","pages":"208-219"},"PeriodicalIF":0.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.70016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145100850","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":"White Matter Disease in a Toddler With New-Onset Seizures","authors":"Olivia Viscuso,&nbsp;Bhairav Patel,&nbsp;James B. Gibson,&nbsp;Louisa G. Keith","doi":"10.1002/cns3.70009","DOIUrl":"https://doi.org/10.1002/cns3.70009","url":null,"abstract":"<p>This 19-month-old boy with tetralogy of Fallot, repaired at age 6 months, and mild gross motor and language developmental delays presented with new-onset generalized tonic-clonic seizures. Following a brief postictal state, he returned to baseline. Neurological examination was unremarkable. Initial imaging showed diffuse, confluent T2 white matter hyperintensity with associated diffusion restriction and T1 hypointensity. Follow-up imaging at 25 months (Figure 1) revealed progression involving the central corpus callosum. Differential diagnosis for leukodystrophy with diffuse white matter involvement is broad and includes vanishing white matter disease, metachromatic leukodystrophy, and certain mitochondrial disorders. A leukodystrophy gene panel demonstrated homozygous pathogenic sequence variants in <i>EIF2B3</i>, establishing a diagnosis of vanishing white matter disease 3 (VWM3).</p><p>VWM is an inherited leukodystrophy that most commonly presents in early childhood with motor deficits following a provoking event (e.g., febrile illness) [<span>1</span>]. VWM3 is caused by biallelic pathogenic variants in the <i>EIF2B3</i> gene, which encodes a subunit of the enzyme eukaryotic initiation factor 2B (eIF2B). Pathogenic variants in any of the subunit genes lead to reduction in eIF2B activity, causing aberrant activation of the cellular response to physiologic stressors and downstream white matter pathology [<span>2</span>]. Unprovoked seizures and lack of motor manifestations are not typical initial presenting features in this age group [<span>3</span>]. Three-years after his VWM diagnosis, he was also diagnosed with autism.</p><p><b>Olivia Viscuso:</b> conceptualization, writing – original draft, writing – review and editing, resources. <b>Bhairav Patel:</b> conceptualization, writing – review and editing; visualization. <b>James B. Gibson:</b> writing – review and editing. <b>Louisa G. Keith:</b> resources, supervision, writing – review and editing, writing – original draft, conceptualization.</p><p>Written consent for publication of clinical details and images was obtained from the patient's legal guardian.</p><p>The authors declare no conflicts of interest.</p>","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"3 3","pages":"245-246"},"PeriodicalIF":0.0,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102102","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":"Impaired Copper Metabolism in a Patient With Short Gut and IDEDNIK Syndrome","authors":"Stephen Deputy","doi":"10.1002/cns3.70020","DOIUrl":"https://doi.org/10.1002/cns3.70020","url":null,"abstract":"&lt;p&gt;IDEDNIK syndrome (intellectual disability, enteropathy, deafness, neuropathy, ichthyosis, and keratoderma; OMIM: 242150, MEDNIK syndrome: 609313, KIDAR: 242150) is a recently recognized autosomal recessive neurocutaneous disorder resulting from pathogenic variants of either &lt;i&gt;AP1S1&lt;/i&gt; or &lt;i&gt;AP1B1&lt;/i&gt; [&lt;span&gt;1&lt;/span&gt;]. It is associated with low serum copper and ceruloplasmin levels secondary to perturbations of intracellular copper transport. Patients with short bowel syndrome can also develop hypocupremia from impaired copper absorption in the small intestine [&lt;span&gt;2&lt;/span&gt;]. Disorders of copper transport should be considered in any infant presenting with hypocupremia.&lt;/p&gt;&lt;p&gt;This 30-month-old girl was delivered at 32 weeks gestational age by Caesarean section for absent fetal movements, though she required minimal resuscitation. She did not tolerate feedings, and laparotomy confirmed small bowel ischemia requiring resection of 26 cm of the terminal small intestine. She exhibited erythematous scaling plaques with hyperpigmented borders, consistent with erythrokeratodermia variabilis. Profound bilateral sensorineural hearing was discovered at 4 months of age. At 11 months of age, she began experiencing recurrent episodes of febrile status epilepticus. She remained TPN-dependent secondary to intestinal failure. Elevated serum transaminase levels and depressed serum copper and ceruloplasmin levels were initially attributed to short bowel syndrome and TPN-induced hepatopathy (see Table 1).&lt;/p&gt;&lt;p&gt;Magnetic resonance imaging of the brain at 22 months of age documented supratentorial global white matter loss with retained myelin maturation (see Figure 1). Nerve conduction studies at 24 months of age revealed an axonal polyneuropathy predominantly affecting sensory nerves. Epidermal nerve fiber density studies were normal.&lt;/p&gt;&lt;p&gt;Examination at 30 months of age revealed a normocephalic head size, lack of dysmorphic features, depressed deep tendon reflexes, and profound developmental delay.&lt;/p&gt;&lt;p&gt;At 10 months of age, genetic evaluation included chromosome microarray, which demonstrated 2.06% regions of homozygosity due to parental consanguinity but was otherwise uninformative. Subsequently, proband exome sequencing identified homozygous, likely pathogenic variants: AP1S1(NM_001283.5):c291+2T&gt;A (p.=?), ClinVarID:851525 in intron 3 of &lt;i&gt;AP1S1&lt;/i&gt; confirming the diagnosis of IDEDNIK syndrome. Both parents were confirmed to be heterozygous carriers of this variant. Enteral zinc acetate supplementation, starting at 15 months of age, resulted in modestly improved serum transaminase, copper, and ceruloplasmin levels (see Table 1), though she remains profoundly delayed.&lt;/p&gt;&lt;p&gt;Differential diagnosis for developmental delay in the setting of hypocupremia includes Wilson's disease, Menkes disease, short bowel syndrome, and IDEDNIK syndrome. Wilson's disease is a copper transport disorder causing reduced secretion of copper from the liver into bile for subsequ","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"3 3","pages":"235-237"},"PeriodicalIF":0.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.70020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145101899","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":"Fenfluramine's Broader Potential: A Second Notable Electroencephalogram Response in Developmental Epileptic Encephalopathy With Spike-Wave Activation in Sleep","authors":"Abigail Arroyo,&nbsp;Douglas R. Nordli III,&nbsp;Fernando Galan","doi":"10.1002/cns3.70013","DOIUrl":"https://doi.org/10.1002/cns3.70013","url":null,"abstract":"&lt;p&gt;Fenfluramine, a serotonergic agent, was first identified in the 1980s for its potential antiseizure properties, particularly in photosensitive epilepsy and later in Dravet syndrome [&lt;span&gt;1&lt;/span&gt;]. Although it was withdrawn from the market in the 1990s due to concerns over cardiovascular adverse effects, including pulmonary arterial hypertension associated with high doses, subsequent studies have demonstrated that low-dose fenfluramine can be both efficacious and well-tolerated in managing refractory epilepsies [&lt;span&gt;2, 3&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;We present a second pediatric patient with developmental and epileptic encephalopathy with spike-wave activation in sleep (DEE-SWAS) in which fenfluramine was associated with marked electroencephalographic and clinical improvements, supporting its potential role as an adjunctive therapy in this challenging epilepsy phenotype.&lt;/p&gt;&lt;p&gt;This 6-year-old right-handed boy with DEE-SWAS was admitted to the epilepsy monitoring unit for further evaluation. He had been experiencing seizures since age 2 years, occurring multiple times daily and lasting only a few seconds. The seizure semiology was consistent with myoclonic seizures, characterized by eyelid myoclonia and bilateral arm jerks.&lt;/p&gt;&lt;p&gt;Initial electroencephalography (EEG) revealed a diffusely slowed background with abundant multifocal epileptiform discharges, most prominent in the bilateral temporal regions. During wakefulness, several electroclinical seizures with eyelid myoclonia were recorded. In sleep, EEG demonstrated bilaterally synchronous spike-and-wave discharges, with a spike-wave index exceeding 85% during non–rapid eye movement (NREM) sleep.&lt;/p&gt;&lt;p&gt;Comprehensive genetic testing—including chromosomal microarray analysis, mitochondrial DNA analysis, and whole-exome sequencing—did not identify any pathogenic variants. Magnetic resonance imaging (MRI) of the brain was also unremarkable.&lt;/p&gt;&lt;p&gt;At the time of admission, the patient was receiving levetiracetam, valproic acid, clobazam, and diazepam. Despite this regimen, he exhibited significant developmental regression, particularly in motor and language skills, accompanied by severe sleep disturbances that negatively impacted his overall quality of life. Previous treatments, including high-dose intravenous methylprednisolone, intravenous immunoglobulin (IVIG), and acetazolamide, had been discontinued due to ineffectiveness or uncertain benefit.&lt;/p&gt;&lt;p&gt;During his epilepsy monitoring unit stay, fenfluramine was initiated at a dose of 0.2 mg/kg/day, divided into two daily administrations, as an adjunct to his ongoing antiseizure medications. In parallel, the ketogenic diet was introduced as an additional therapeutic strategy for seizure control. Within 24–48 h of initiating fenfluramine, the patient's EEG exhibited a marked improvement compared with baseline (Figure 1).&lt;/p&gt;&lt;p&gt;This second pediatric patient with refractory epilepsy and DEE-SWAS demonstrated significant EEG improvement following initiation of fe","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"3 3","pages":"232-234"},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.70013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145101416","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}