Annals of the Child Neurology Society最新文献

{"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}

{"title":"Influenza-Associated Encephalopathy","authors":"Andrew Silverman,&nbsp;Chrisoula Cheronis","doi":"10.1002/cns3.70010","DOIUrl":"https://doi.org/10.1002/cns3.70010","url":null,"abstract":"<p>This previously healthy and vaccinated (except for the seasonal influenza vaccine) 12-year-old boy developed acute neurological symptoms following 3 days of fever and gastrointestinal distress. His symptoms progressed from headache and transient left-arm paresthesias to expressive aphasia, prompting emergency evaluation. He was febrile, tachycardic, and hypertensive on arrival, with fluctuating neurological deficits. Serum investigations, including blood counts, glucose, metabolic panel, urine toxicology, and anti-MOG, were normal. Influenza B was detected via nasopharyngeal swab. Magnetic resonance imaging/magnetic resonance angiography revealed confluent white matter signal changes with restricted diffusion (Figure 1) with normal vessels, consistent with an infection-triggered encephalopathy syndrome, specifically mild encephalopathy with a reversible splenial lesion (MERS) [<span>2</span>]. The patient's rapid clinical improvement within 24 h without treatment supported a diagnosis of influenza-associated encephalopathy (IAE), for which neuroimaging is paramount. Diffusion restriction was thought to be related to intramyelinic edema and/or inflammatory infiltrate, comparable to prior reports [<span>1, 3</span>]. At 3-month follow-up, he remained neurologically intact, had returned to age-appropriate schooling, and had normal repeat imaging. IAE is a rare but severe complication of influenza; the pathogenesis is not fully understood but is believed to involve dysregulated host inflammatory response to influenza, leading to varying degrees of brain dysfunction and inflammation [<span>4, 5</span>]. This patient with MERS with focal neurological deficits and extensive white matter involvement illustrates the variable presentation and rapid reversibility of IAE in some individuals. In contrast, more severe types of IAE require immediate neuroprotective measures in intensive care and prompt immunotherapy (namely, acute necrotizing encephalopathy) [<span>2, 6</span>]. Given the significant proportion of pediatric influenza-associated deaths involving IAE in the 2024-25 influenza season, prevention strategies, including seasonal influenza vaccination, remain critical [<span>7, 8</span>].</p><p><b>Andrew Silverman:</b> conceptualization, investigation, visualization, writing – review and editing, writing – original draft. <b>Chrisoula Cheronis:</b> conceptualization, visualization, writing – review and editing, writing – original draft, investigation.</p><p>The authors declare no conflicts of interest.</p>","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"3 3","pages":"247-248"},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.70010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145101415","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":"Symptom Onset in Classic Rett Syndrome: Analysis of Initial Clinical Severity Scale Entries","authors":"Alan K. Percy,&nbsp;Jeffrey L. Neul,&nbsp;Amitha Ananth,&nbsp;Timothy A. Benke,&nbsp;Eric D. Marsh","doi":"10.1002/cns3.70017","DOIUrl":"10.1002/cns3.70017","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We aim to assess the clinical features of Rett syndrome (RTT) at registration into the National Institutes of Health–sponsored natural history study (NHS) using the Clinical Severity Scale (CSS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The CSS was established in 2000 to assess characteristics of individuals with RTT and related disorders. We analyzed the CSS at enrollment into the NHS of all individuals with classic RTT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The CSS of 1258 individuals was used to examine three historical items (age at regression, age at onset of hand stereotypies, and head growth) and 10 clinical features at initial enrollment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among historical items, age at regression was most prominent after age 12 months with 8% regressing before this, hand stereotypies were most common after 18 months with 30% occurring before, and head growth was substantially lower overall. Hand use, ambulation, and communication skills were reduced in most individuals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion and Conclusion</h3>\u0000 \u0000 <p>These findings reflect core clinical criteria for classic RTT and mirror the top concerns registered independently by parents or caregivers. The CSS is an important analytic tool for the association of relative differences in clinical outcome with specific <i>MECP2</i> variant groups and has been important in establishing entrance criteria in RTT clinical trials. The range of age-specific CSS features will continue to inform the RTT natural natural history as well as provide stratification and selection in future clinical trials, especially those involving younger participants.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"3 3","pages":"152-157"},"PeriodicalIF":0.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12380397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980717","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":"Manganese Neurotoxicity and Familial Disorders of Manganese Transport","authors":"Sidney M. Gospe Jr.","doi":"10.1002/cns3.70015","DOIUrl":"https://doi.org/10.1002/cns3.70015","url":null,"abstract":"<p>Manganese is the 12th most common element in the Earth's crust and is an essential industrial component. Biologically, this metal plays an important role as a constituent of numerous enzymes. While manganese is required for normal biochemical and physiological processes, manganese excess can lead to significant toxicity, particularly to the central nervous system. Over the past 25 years, three inherited disorders of manganese transport have been described, leading to a model of how this essential metal is absorbed, distributed to tissues, and eliminated. The first part of this review describes the clinical features and cellular mechanisms of manganese toxicity due to occupational and environmental exposure. The remainder of the review discusses the familial disorder associated with hypomagnesemia, SLC39A8 deficiency, and the two genetic diseases resulting in hypermanganesemia, SLC30A10 deficiency and SLC39A14 deficiency. These latter two disorders are treatable, and the early recognition and institution of chelation therapy and iron supplementation can improve neurological disability. Ongoing research regarding the tissue-specific role of each transporter and their regulatory interplay, the varied mechanisms of manganese toxicity, and its treatment are also described.</p>","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"3 3","pages":"135-144"},"PeriodicalIF":0.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.70015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145101039","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":"Epilepsy of Infancy With Migrating Focal Seizures","authors":"Samuel Kamoroff,&nbsp;Harry Abram,&nbsp;Fernando Galan","doi":"10.1002/cns3.70014","DOIUrl":"https://doi.org/10.1002/cns3.70014","url":null,"abstract":"<p>This 3-month-old boy had frequent recurrent events of right-arm stiffening and right head turn suggestive of focal seizures. Continuous electroencephalogram (EEG) showed subclinical focal seizures arising independently from the right occipital and left posterior head regions. These events persisted despite escalating use of lacosamide, levetiracetam, and phenobarbital. Given the patient's age, epilepsy of infancy with migrating focal seizures (EIMFS) was suspected. Early investigation with whole-exome sequencing revealed homozygous pathogenic variants in <i>SLC12A5</i> (c.986C &gt; A, p.Ala329Asp). Early recognition is vital in this epilepsy syndrome due to the difficulty in treating and subsequent prognosis. Given the expected drug resistance, early or urgent initiation of the ketogenic diet should be considered. The overall prognosis is not favorable, as poor developmental outcomes are expected.</p><p>EIMFS is a severe infantile-onset epilepsy syndrome characterized by refractory seizures, developmental delay, and migrating focal discharges [<span>1</span>]. <i>SLC12A5</i> mutations have been identified as a cause of EIMFS, with nine patients reported to date, but <i>KCNT1</i> remains responsible for about 50% of cases [<span>2</span>] (Figure 1). <i>SLC12A5</i> encodes the potassium-chloride cotransporter KCC2, which is crucial for maintaining synaptic inhibition [<span>3</span>]. Mutations in <i>SLC12A5</i> lead to decreased KCC2 surface expression, impaired chloride extrusion, and reduced protein glycosylation, resulting in neuronal hyperexcitability [<span>3</span>]. EIMFS typically presents before 6 months of age with focal motor seizures that become multifocal and intractable [<span>2</span>]. Treatment options are limited, but the ketogenic diet and potassium bromide have shown potential efficacy [<span>2</span>]. <i>SLC12A5</i>-related EIMFS is inherited in an autosomal recessive manner, with both de novo and inherited mutations reported [<span>4</span>].</p><p><b>Samuel Kamoroff:</b> conceptualization, writing – original draft, writing – review and editing, data curation. <b>Harry Abram:</b> writing – review and editing, data curation, supervision. <b>Fernando Galan:</b> conceptualization, writing – review and editing, data curation, supervision.</p><p>The authors declare no conflicts of interest.</p>","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"3 2","pages":"125-126"},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.70014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299539","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":"Child Neurology Workforce Shortage: Challenges and Recommendations for Researching and Recruiting the Next Generation of Child Neurologists","authors":"Sara A. Rubin,&nbsp;Peter E. Davis,&nbsp;Miya E. Bernson-Leung","doi":"10.1002/cns3.70011","DOIUrl":"https://doi.org/10.1002/cns3.70011","url":null,"abstract":"<p>For subspecialities like child neurology in which demand is predicted to increase and further exceed supply, understanding what attracts individuals to the field and deters individuals from it is particularly valuable. To explore this, we recently surveyed medical students and residents who had completed child neurology clerkships at US medical schools within the last approximately 7 years to investigate the antecedent factors that led to interest in these clerkships and the factors that subsequently impacted residency choice, child neurology or otherwise. Current child neurology and neurodevelopmental disabilities residents (postgraduate years [PGY] 1 through 5) and current medical students who completed at least one child neurology clerkship at a US medical institution were invited to complete an online survey through their residency program coordinators/directors or clerkship coordinators/directors. While our 38 respondents gave us useful insights, our difficulty reaching a larger sample of the population of interest (likely ~1000−5000 individuals) highlights several barriers to conducting workforce research. Here, we share relevant literature and our observations on the pipeline for careers in child neurology, current research challenges, and potential paths forward.</p><p>Early exposure to child neurology is critical for sparking interest in the field. Although studies have used different definitions of “early,” frequently referring to college and medical school [<span>1</span>], it is becoming more apparent that no exposure is too early for igniting interest. In our study, the most common timeframe for initial exposure to neurology was during college at 39%; however, exposure in high school or earlier was almost equally as common (37%). Popular media such as books by Oliver Sacks and fictional characters like Sherlock Holmes have been cited in residency personal statements as motivating interest in neurology [<span>2</span>]. These exposures along with chance encounters with neurologists through personal or family experience with neurological conditions, pediatric or otherwise, appear to be relevant when medical students are planning their career paths. It remains to be explored whether the specific exposure (pediatric, e.g., a sibling with autism, or adult, e.g., a grandparent with Alzheimer's disease) influences whether one decides to go into child neurology or adult neurology, especially given the lack of awareness among premedical and medical students that child neurology is its own specialty. Studying these types of “early” exposures could be fruitful for understanding how early lifeexperiences influence motivation to enter medicine and eventual specialty choice.</p><p>Undergraduate neuroscience courses are another crucial early exposure to the field. At present, there are inequities in access to such courses, which has implications for recruiting a diverse workforce [<span>3</span>]. In our survey, 24% of participants indicated tha","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"3 2","pages":"68-70"},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.70011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299652","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}