Annals of the Child Neurology Society最新文献

{"title":"Questionnaire-Based Experimental Study of the Diagnostic Process in Suspected Shaken Baby Syndrome","authors":"N. Lynøe,&nbsp;A. Castor,&nbsp;N. Juth,&nbsp;A. Eriksson","doi":"10.1002/cns3.70031","DOIUrl":"https://doi.org/10.1002/cns3.70031","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The objective of this study was to examine the correctness of the statement that the diagnosis of shaken baby syndrome (SBS) is a “medical conclusion.”</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Design</h3>\u0000 \u0000 <p>If the outcome of an event is considered bad, people tend to attribute intent or responsibility. Against this backdrop, a randomized, blinded trial was applied using two case-based questionnaires of possible violent shaking of an infant, identical except for the outcome: fatal or nonfatal.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Setting</h3>\u0000 \u0000 <p>We used a report of a 2-month-old baby who had suddenly stopped breathing and was subsequently shaken by the father with the intention to resuscitate him. After admission, encephalopathy, subdural hemorrhages, and retinal hemorrhages were detected.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Participants</h3>\u0000 \u0000 <p>A total of 1269 randomly selected physicians received the questionnaire, whose distribution was randomized and blinded. The participants were not informed about the existence of two versions of the questionnaire.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The participants who responded to the fatal version considered in a significantly higher proportion (79% [95% CI: 73−85]) that shaking caused the triad findings than those who responded to the nonfatal version (68% [95% CI: 61−75]) (<i>p</i> = 0.01). When pediatricians and ophthalmologists are merged, the corresponding proportions were (91% [95% CI: 86−96]) versus (74% [95% CI: 66−82]) (<i>p</i> = 0.001). Radiologists and forensic pathologists did not distinguish significantly between fatal and nonfatal outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The study indicates that among pediatricians and ophthalmologists, the diagnostic process in suspected SBS is more value-based than evidence-based. As these two specialties dominate the SBS diagnostic procedure, the SBS diagnosis is, in this sense, not strictly a “medical conclusion.”</p>\u0000 </section>\u0000 </div>","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"3 3","pages":"158-164"},"PeriodicalIF":0.0,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.70031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145101710","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":"Focal Cerebral Arteriopathy and Stroke Secondary to Tuberculous Meningitis","authors":"Mahesh Chikkannaiah,&nbsp;Sarah G. Yu,&nbsp;Laura D. Fonseca,&nbsp;Ajay Goenka,&nbsp;Gogi Kumar","doi":"10.1002/cns3.70032","DOIUrl":"https://doi.org/10.1002/cns3.70032","url":null,"abstract":"&lt;p&gt;In countries where tuberculosis (TB) is endemic, children with tuberculous meningitis (TBM) commonly present with cerebrovascular complications such as stroke [&lt;span&gt;1&lt;/span&gt;]. Herein, we present a patient from the United States with stroke associated with focal cerebral arteriopathy (FCA) secondary to TBM.&lt;/p&gt;&lt;p&gt;This 11-month-old girl presented with left hemiparesis and seizure. About 1.5 weeks before presentation, her parents noticed fatigue and decreased appetite and that she was not crawling as usual. Two days before presentation, her parents noticed decreased strength in her left arm and leg. Computed tomography of the head showed an area of hypoattenuation in the right basal ganglia and loss of gray and white matter differentiation in the right frontal cortex. While en route to our hospital, she had a seizure described as bilateral upper extremity shaking lasting 1 min, which self-resolved. On examination, she had right preferential gaze and left hemiparesis. Laboratory findings were significant for hyponatremia of 126 mEq/L. Magnetic resonance imaging of the brain (Figure 1) showed a right middle cerebral artery (MCA) distribution ischemic stroke. Magnetic resonance angiography (Figure 2) showed decreased flow in the right supraclinoid portion of the right internal carotid artery (ICA), A1 segment of the right anterior cerebral artery (ACA), and M1 segment of the right MCA and mild narrowing involving the petrous portion of the right carotid artery and carotid siphon. Her evaluation included cerebrospinal fluid (CSF) evaluation, which showed pleocytosis (235 cells/μL) with hypoglycorrhachia (11 mg/dL) and an elevated CSF protein (272 mg/dL).&lt;/p&gt;&lt;p&gt;Additional evaluation included CSF testing (bacterial culture, viral meningitis/encephalitis panel, herpes simplex virus polymerase chain reaction [PCR], and varicella virus PCR and antibodies) and respiratory panel for COVID-19, which were all negative. Chest computed tomography showed mediastinal and right hilar lymphadenopathy as well as nodular opacities in bilateral upper lobes with a miliary pattern.&lt;/p&gt;&lt;p&gt;Further family history included exposure to grandfather 1 month before his diagnosis of active TB; her grandfather had recently traveled to his native country, where TB is endemic. An interferon-gamma release assay and gastric aspirate culture were positive for &lt;i&gt;Mycobacterium tuberculosis&lt;/i&gt;. The TB skin test was also positive. A CSF acid-fast bacilli culture was negative. She was diagnosed with FCA with right MCA stroke secondary to TBM and disseminated TB. She was treated with steroids and antitubercular therapy. Her seizures were controlled with levetiracetam and phenobarbital, which were weaned off as an outpatient. Upon the most recent follow-up at 3 years of age, she had spastic left hemiplegia, and she was able to sit independently but was not walking yet.&lt;/p&gt;&lt;p&gt;TB affects 1.2 million children worldwide, with an estimated 4% of TB diagnoses progressing to TBM [&lt;span&gt;1-3&lt;/span","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"3 3","pages":"242-244"},"PeriodicalIF":0.0,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.70032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145100995","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":"Factors Influencing the Duration From the Initiation of Surgical Evaluation to Final Intervention in Pediatric Epilepsy Surgery","authors":"Ruba Al-Ramadhani,&nbsp;Ann Hyslop,&nbsp;Avery R. Caraway,&nbsp;Edward J. Novotny,&nbsp;Adam P. Ostendorf,&nbsp;Krista L. Eschbach,&nbsp;Allyson L. Alexander,&nbsp;Lily C. Wong-Kisiel,&nbsp;Dewi F. Depositario-Cabacar,&nbsp;Chima O. Oluigbo,&nbsp;Cemal Karakas,&nbsp;Samir R. Karia,&nbsp;Priyamvada Tatachar,&nbsp;Jeffrey Bolton,&nbsp;Pilar D. Pichon,&nbsp;Daniel W. Shrey,&nbsp;Erin Fedak Romanowski,&nbsp;Nancy A. McNamara,&nbsp;Ernesto Gonzalez-Giraldo,&nbsp;Kurtis Auguste,&nbsp;Danilo Bernardo,&nbsp;Rani K. Singh,&nbsp;Pradeep K. Javarayee,&nbsp;Jenny J. Lin,&nbsp;Jason C. Coryell,&nbsp;Shilpa B. Reddy,&nbsp;Abhinaya Ganesh,&nbsp;Michael A. Ciliberto,&nbsp;Debopam Samanta,&nbsp;Kristen H. Arredondo,&nbsp;Ahmad Marashly,&nbsp;Zachary M. Grinspan,&nbsp;Dallas Armstrong,&nbsp;Taylor J. Abel,&nbsp;Janelle Wagner,&nbsp;Derryl J. Miller,&nbsp;Fernando N. Galan,&nbsp;Michael Scott Perry","doi":"10.1002/cns3.70027","DOIUrl":"https://doi.org/10.1002/cns3.70027","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Rationale&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Longer duration of epilepsy before surgery is a predictor of poor outcome. While referral delays of surgical candidates are well documented, factors causing delay during the presurgical evaluation remain unclear and may vary depending on institutional characteristics. By benchmarking the duration of presurgical evaluation across multiple centers and identifying patient and evaluation characteristics contributing to duration, we can ascertain best practices and address modifiable contributors to reduce delays.&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;We queried the Pediatric Epilepsy Research Consortium Surgery Database, a prospective, observational multicenter study enrolling children 0–18 years at 27 US pediatric epilepsy centers, for all patients undergoing initial presurgical evaluation for drug-resistant epilepsy (DRE). We included patients with completed evaluations and data on duration from initiation of presurgical evaluation to final surgical decision. We compared patient characteristics and evaluation components between those with long duration evaluations (&gt; 75% quartile) and those with short evaluations (&lt; 25% quartile). Akaike information criteria selection identified variables associated with longer duration. From these, we developed a logistic prediction model for evaluation duration, using a random 80/20 training/testing split of the entire cohort. The model was tested among institutions with ≥ 10 patients in the cohort to assess its accuracy in predicting long durations. Linear models for each site assessed each variable's impact on duration. Variables with &lt; 10% of the patient population at each site were excluded. Beta values were compared to identify intra- and inter-institution variability and to delineate institutions with the shortest added duration for each variable.&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;Of 2318 patients undergoing surgical evaluation, 1655 (71%) from 23 sites had complete data. Median evaluation duration was 8 weeks (interquartile range 3–22); 453 (27%) were short-duration evaluations and 414 (25%) were long-duration evaluations. Multiple patient and evaluation characteristics were associated with duration (Table 1). Table 6 provides the average duration each variable contributes to evaluation by site, highlighting the shortest durations compared with other groups.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Duration of presurgical evaluation for DRE can be accurately modeled using multiple patient characteristics and testing strategies commo","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"3 3","pages":"188-200"},"PeriodicalIF":0.0,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.70027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145100832","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":"Response to Comment on Witnessing Abusive Head Trauma: Accidents Show Higher Rates of Intracranial Pathologies Than Shaking","authors":"Chris B. Brook","doi":"10.1002/cns3.70018","DOIUrl":"https://doi.org/10.1002/cns3.70018","url":null,"abstract":"&lt;p&gt;I thank Drs. Greeley and Anderst for taking the time to comment1 on my article “Witnessing abusive head trauma: Accidents show higher rates of intracranial pathologies than shaking.”2&lt;/p&gt;&lt;p&gt;The authors raise issues regarding the validity of comparing different data sets. They claim that “pediBIRN is a prospective, cohort study.” In fact, pediBIRN starts with an outcome (child with brain injury), then looks backward (using a clinician's judgment) to decide exposure (accident versus abuse). The PediBIRN authors themselves refer to the data as “strictly observational.”3 So whilst the registry of head injury cases is prosepective, it is &lt;i&gt;not&lt;/i&gt; a prospective cohort study of exposures. The studies used in my article all have directionality of outcome to exposure.&lt;/p&gt;&lt;p&gt;Further, the base rate for shaking in my study is “witnessed shaking events,” regardless of which of the four studies4 the data were drawn from. I compiled a list of witnessed cases of shaking from the literature, and the number of such witnessed cases became the base rate in my study. I have not incorporated different base rates from the different studies into my study.&lt;/p&gt;&lt;p&gt;Nevertheless, the authors raise a central, crucial point regarding selection bias. Abusive head trauma (AHT) encompasses a spectrum—from a slap to violent shaking to forceful impact—just as accidental injury ranges from minor bumps to severe falls. Comparing rates of findings in all AHT cases versus all accidents is intractable. Any comparison of rates will be subject to selection bias, particularly selections that influence how severe was the accident and how severe was the abuse.&lt;/p&gt;&lt;p&gt;This is demonstrated in my previous article, “Retino-dural hemorrhages in infants are markers of degree of intracranial pathology not of violent shaking,”5 which shows that when studies claim certain findings are more common in AHT (i.e., specific for AHT), this apparent specificity stems from selection bias. Such studies typically compare severe cases of AHT with less severe accidental injuries. By contrast, when cases are matched for severity (as reflected by hypoxic brain injury), the findings supposedly associated with AHT instead correlate with the degree of brain injury—independent of cause or intent.&lt;/p&gt;&lt;p&gt;The other problem with articles that claim certain findings to be specific to AHT is the methods used for classification of cases as AHT, which are biased towards selecting cases with certain pathologies, creating a self-fulfilling prophecy. The motivation for my article was to restrict comparisons to cases that were witnessed, providing a more robust classification that does not suffer from such circular reasoning.&lt;/p&gt;&lt;p&gt;Unfortunately there is a paucity of such data, and my study required assembling data from different sources. This was explained as a limitation of the study, so I agree with the authors that a degree of caution is warranted in assessing the quoted rates, and I once again reiterate that it will be v","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"3 3","pages":"255-256"},"PeriodicalIF":0.0,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.70018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145100940","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":"Commentary on Witnessing Abusive Head Trauma: Accidents Show Higher Rates of Intracranial Pathologies Than Shaking—Caution Is Warranted","authors":"Christopher Greeley,&nbsp;Jim Anderst","doi":"10.1002/cns3.70030","DOIUrl":"https://doi.org/10.1002/cns3.70030","url":null,"abstract":"&lt;p&gt;As the topic of abusive head trauma (AHT) has become a cause célèbre in some nonpediatric academic circles, we read the research article by Brook [&lt;span&gt;1&lt;/span&gt;] with great interest. The research article reports on an effort to compare some of the findings typically associated with AHT between cases in which shaking was witnessed or admitted to those in which accidents were confirmed. Initially, it appears to be similar to prior studies comparing witnessed accidents with witnessed/admitted abuse [&lt;span&gt;2, 3&lt;/span&gt;] but particularly focused on shaking as a reported mechanism. The author takes a unique approach in attempting to answer the question about the rate of findings between accidental and inflicted head injuries due to shaking. The author's chosen methodology contains several flaws, which are quite puzzling. We chose to specifically highlight two fundamental flaws that we feel undermine meaningful conclusions: the study designs of the chosen data sets and the populations being compared between the categories of cases.&lt;/p&gt;&lt;p&gt;The first concern is the data sets that were constructed. The author used four independent sources from which he has grouped participants into three categories: unconflicted witnessed accident, witnessed shaking, and unconflicted witnessed shaking. The first data set assembled (unconflicted witnessed accident) was of participants extracted from the PediBIRN study (www.pedibirn.com) and as reported in Hymel et al. [&lt;span&gt;4&lt;/span&gt;]. PediBIRN is a prospective, cohort study of children younger than 3 years admitted to pediatric intensive care units for traumatic head injury. Children who are injured in accidents and admitted to an intensive care unit represent the most severe accidents only. The second data set assembled (unconflicted witnessed shaking) was from the Swedish National Patient Register and reported by Thiblin et al. [&lt;span&gt;5&lt;/span&gt;]. This is a retrospective case series of infant victims of abuse identified by ICD-10 codes. In this data set, shaking is not an explicit variable, and the author only includes those participants in which shaking was expressly reported in the medical records. Records that did not include a reference to shaking (i.e., missing data) were treated the same as those in which shaking was specifically denied (i.e., shaking = “no”), likely resulting in undercounting of shaking. The author apparently includes the same 36 participants identified by Thiblin et al. [&lt;span&gt;5&lt;/span&gt;]. If so, it is important to note that Thiblin et al. [&lt;span&gt;5&lt;/span&gt;] has since received an “Expression of Concern” (similar to a “black box warning”) by the editors of &lt;i&gt;PLoS One&lt;/i&gt;, in part due to “suitability of the study design to support the conclusions” [&lt;span&gt;6&lt;/span&gt;]. The last category assembled (witnessed shaking) was from two separate sources, both reported in Feldman et al. [&lt;span&gt;7&lt;/span&gt;]. The ExSTRA study was a prospective, multicenter, observational study of children younger than 10 years referred","PeriodicalId":72232,"journal":{"name":"Annals of the Child Neurology Society","volume":"3 3","pages":"253-254"},"PeriodicalIF":0.0,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns3.70030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102379","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":"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":"<p>Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disorder caused by variants of the <i>TSC1</i> (tuberous sclerosis complex 1) or <i>TSC2</i> (tuberous sclerosis complex 2) tumor suppressor genes, which regulate cellular proliferation through the mTOR (mammalian target of rapamycin) pathway [<span>1, 2</span>]. TSC has complete genetic penetrance but variable expressivity between patients, which leads to a broad phenotype [<span>1, 3</span>]. 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 [<span>4, 5</span>]. 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 [<span>5</span>]. Pathogenic variants have been identified in all other <i>TSC2</i> 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 [<span>2</span>].</p><p>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 <i>TSC2</i> (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.</p><p>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.</p><p>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}