Pediatric neurology最新文献

{"title":"MECP2 Variants in Males: More Common than Previously Appreciated","authors":"Amitha Ananth MD ,&nbsp;Cary Fu MD ,&nbsp;Jeffrey L. Neul MD, PhD ,&nbsp;Tim Benke MD, PhD ,&nbsp;Eric Marsh MD, PhD ,&nbsp;Bernhard Suter MD, PhD ,&nbsp;Kathleen Ferdinandsen LCSW, MS ,&nbsp;Steven A. Skinner MD ,&nbsp;Fran Annese MSW ,&nbsp;Alan K. Percy MD","doi":"10.1016/j.pediatrneurol.2024.09.022","DOIUrl":"10.1016/j.pediatrneurol.2024.09.022","url":null,"abstract":"<div><h3>Background</h3><div>To assess the age and <em>MECP2</em> variants of recently identified males and set the stage for further study of clinical features in males.</div></div><div><h3>Methods</h3><div>Genetic information on the specific <em>MECP2</em> variant was acquired from the coordinator (K.F.) of the Parent Group for Males. Data were collected indicating whether these variants were <em>de novo</em> or transmitted from the mother and whether males who appeared to meet the diagnostic criteria for Rett syndrome had mosaicism for the <em>MECP2</em> variant.</div></div><div><h3>Results</h3><div>Fifty-nine males were identified through the parent group. Their ages ranged from 2 to 28 years, with the median age being 7.0 years and the mean age being 10.8 years. Of these variants, 46 (78.0%) were <em>de novo</em>, nine (15.3%) were maternally inherited, and for four (6.8%) inheritance was not known. Eleven (18.6%) were mosaic, 10 with somatic mosaicism and one with Klinefelter syndrome (47XXY). Together with males reported previously from the US Natural History Study, the total group represents 85 males, of whom 27 are deceased.</div></div><div><h3>Conclusions</h3><div>These data on males with <em>MECP2</em> variants are important to caregivers, physicians, and researchers to begin to characterize their historical and clinical features, improve diagnostic recognition and overall care, and accelerate access to therapeutic studies including gene replacement strategies. Equal access to such therapies for males is critical.</div></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"161 ","pages":"Pages 263-267"},"PeriodicalIF":3.2,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142538016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Febrile Seizures, Ongoing Epileptiform Activity, and the Resulting Long-Term Consequences: Lessons From Animal Models","authors":"Sydney A. Harris MSc ,&nbsp;Emily E. Gordon BSc ,&nbsp;Karlene T. Barrett PhD ,&nbsp;Morris H. Scantlebury MBBS, MD ,&nbsp;G. Campbell Teskey PhD","doi":"10.1016/j.pediatrneurol.2024.09.026","DOIUrl":"10.1016/j.pediatrneurol.2024.09.026","url":null,"abstract":"<div><div>Febrile seizures affect 2% to 14% of children. Prospective studies indicate that following a relatively prolonged febrile seizure there are long-term consequences. Although controlled experiments in children have ethical limitations, nonhuman animal models give us the ability to discover new phenomena, determine their mechanisms, and test treatments that can potentially translate to the human clinical population. Rat models of febrile seizures show two temporally distinct phases: (1); behavioral seizures and (2); ongoing epileptiform activity associated with hyperoxia. The behavioral seizures mimic those displayed by children including tonic-clonic convulsions and loss of postural control. Recordings show classic spiking discharges from cortical regions during the behavioral seizures. Following behavioral seizure termination electrical recordings in rodent models reveal that there is ongoing epileptiform activity that lasts longer than the duration of the behavioral seizures themselves. This ongoing epileptiform activity is also associated with hyperoxia—levels of brain tissue oxygen well above the normoxic zone (typical oxygen levels)—and can last more than an hour. When this hyperoxia, but not the epileptiform activity, is prevented in febrile rat pups the long-term learning impairments are also prevented. This leaves important questions unanswered, “Do children also have ongoing and long-lasting epileptiform activity and associated hyperoxia following termination of their febrile behavioral seizures and does this second phase have long-term consequences”? Here we discuss appropriate animal models of febrile seizures that replicate much of the human condition with special attention to the long-term effects of occult epileptiform activity following termination of a behavioral febrile seizure.</div></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"161 ","pages":"Pages 216-222"},"PeriodicalIF":3.2,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to Hamid et al., “Equitable Access of Delandistrogene Moxeparvovec for Patients With Duchenne Muscular Dystrophy”","authors":"David K. Urion MD,&nbsp;Juan Francisco Cabello MD,&nbsp;Rodrigo Salinas MD","doi":"10.1016/j.pediatrneurol.2024.09.019","DOIUrl":"10.1016/j.pediatrneurol.2024.09.019","url":null,"abstract":"","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"161 ","pages":"Pages 227-228"},"PeriodicalIF":3.2,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do Vaccines Cause Postural Orthostatic Tachycardia Syndrome (POTS)? Review of Cases in the National Vaccine Injury Compensation Program","authors":"Waqar Waheed MD,&nbsp;Gregory L. Holmes MD","doi":"10.1016/j.pediatrneurol.2024.09.025","DOIUrl":"10.1016/j.pediatrneurol.2024.09.025","url":null,"abstract":"<div><h3>Purpose</h3><div>The National Childhood Vaccine Injury Act of 1986 created the National Vaccine Injury Compensation Program (VICP), a no-fault alternative to the traditional tort system. Since 1988, the total compensation paid exceeds $6 billion. While postural orthostatic tachycardia syndrome (POTS) is a frequent reason for filing a claim, there has been no review of the process and validity of the legal outcomes given current medical information. The purpose of this study was to review vaccine-related POTS and assess the rationale behind decisions made by the court.</div></div><div><h3>Methods</h3><div>We identified 102 unique cases with POTS. All published reports were reviewed for petitioner’s theories supporting vaccine-induced POTS, respondent’s counterarguments, the final decision regarding compensation and the rationale underlying these decisions. The primary goal was to determine which factors went into decisions regarding whether vaccines cause POTS.</div></div><div><h3>Results</h3><div>In deciding the cases the Special Masters hearing the cases places a high reliance on expert witnesses for both the petitioners and respondents. Petitioners’ experts frequently implicated vaccines, primarily human papillomavirus vaccine (HPV) as causing POTS through autoimmunity induced by molecular mimicry. However, in none of the 102 cases was POTS considered to be directly caused by a vaccine.</div></div><div><h3>Conclusion</h3><div>Despite the lack of epidemiological or mechanistic evidence indicating that childhood vaccines covered by the VICP result in POTS, these cases continue to be adjudicated, at considerable cost to the government. Unless there is emerging scientific support for implicating vaccines in POTS it is time that the VICP stop considering these cases.</div></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"161 ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dengue-Associated Acute Necrotizing Encephalopathy Is an Acute Necrotizing Encephalopathy Variant Rather than a Mimic: Evidence From a Systematic Review","authors":"Sophie Barron MD ,&nbsp;Velda X. Han MD, PhD ,&nbsp;Juhi Gupta MD ,&nbsp;Lokesh Lingappa MD ,&nbsp;Naveen Sankhyan MD ,&nbsp;Terrence Thomas MD","doi":"10.1016/j.pediatrneurol.2024.09.021","DOIUrl":"10.1016/j.pediatrneurol.2024.09.021","url":null,"abstract":"<div><h3>Background</h3><div>Bilateral hemorrhagic thalamic lesions in dengue encephalitis resemble lesions seen in acute necrotizing encephalopathy (ANE). We investigate whether dengue-associated ANE (DANE) should be considered an ANE variant or a mimic.</div></div><div><h3>Methods</h3><div>Systematic review of dengue encephalitis literature from PubMed and SCOPUS (inception to December 31, 2022). Diagnostic criteria for ANE, acute encephalitis (AE), acute disseminated encephalomyelitis (ADEM), and infection-triggered encephalopathy syndromes were applied.</div></div><div><h3>Results</h3><div>Data on 162 patients (median age 20 [0.4 to 79] years; 69 [42.3%] female; 72 [44.4%] aged ≤18 years) from 103 articles were analyzed. DANE (62, 38.3%) was the commonest, followed by AE (56, 34.6%) and ADEM (27, 16.7%). The main clinical features were fever (100%), thrombocytopenia (79.0%), headache (57.8%), and seizures (43.7%). Patients with DANE had earlier neurological deterioration (3.5 [1 to 8] vs 5 [1 to 14] days in other encephalitis syndromes, <em>P</em> = 0.0127), seizures (54.2% vs 37.4%, <em>P</em> = 0.0471), higher cerebrospinal fluid (CSF) protein (0.92 [0.18 to 4.8] vs 0.73 [1 to 16] g/L, <em>P</em> = 0.0469), thalamic (100% vs 8.0%) and hemorrhagic brain lesions (73.3% vs 7.5%, <em>P</em> &lt; 0.0001). CSF pleocytosis and positive CSF dengue IgM/viral polymerase chain reaction were reported in 66.7% and 78.6% with DANE. Mortality was 16.1% in DANE, and 40.6% of survivors had disability. High-risk ANE severity scores predicted poor outcomes (positive predictive value 64.3% [95% confidence interval 38.8% to 83.7%]).</div></div><div><h3>Conclusion</h3><div>DANE differs from other dengue encephalitis syndromes and is clinicoradiologically indistinguishable from sporadic ANE with sufficient evidence to be considered an ANE variant.</div></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"161 ","pages":"Pages 208-215"},"PeriodicalIF":3.2,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cenobamate's Efficacy for Seizure Treatment in Tuberous Sclerosis Complex","authors":"Gewalin Aungaroon MD ,&nbsp;Alexander Cooke BS ,&nbsp;David Ritter MD, PhD ,&nbsp;Darcy Krueger MD, PhD ,&nbsp;Paul Horn PhD ,&nbsp;David N. Franz MD","doi":"10.1016/j.pediatrneurol.2024.09.023","DOIUrl":"10.1016/j.pediatrneurol.2024.09.023","url":null,"abstract":"<div><h3>Background</h3><div>Epilepsy is prevalent, and seizure control is challenging in patients with tuberous sclerosis complex (TSC). Cenobamate (CBM) has proven efficacy in several studies; however, its benefit in the TSC population is not known.</div></div><div><h3>Methods</h3><div>We performed a retrospective review of patients with TSC who received adjunctive CBM for seizure treatments. We assessed treatment efficacy by comparing seizure frequencies three months before CBM (baseline) and those at 3-, 6-, 12-, and 18- month follow-ups.</div></div><div><h3>Results</h3><div>We identified 70 patients with TSC receiving CBM and excluded 16 with insufficient data. Fifty-four patients aged 2 to 39 years, with an average baseline seizure of 66.1 ± 88.9 per month, were analyzed. Treatment retention rates at 3, 6, 12, and 18 months were 94.4%, 79.6%, 66.7%, 44.4%, and responder rates (proportions of patients who remained on treatment and had ≥50% seizure reduction) were 38.1%, 51.7%, 53.1%, and 59.1%, respectively. Seizure-free rates at these respective follow-ups were 7.1%, 13.8%, 6.3%, and 9.1%. For patients experiencing reduced seizures, the mean percentage of change ranged from 61.5% to 74.6%. Side effects were common (64.8%), particularly sedation (42.6%), behavioral disturbance (24.1%), and gastrointestinal disturbance (22.2%).</div></div><div><h3>Conclusions</h3><div>Most patients in this study showed seizure reduction; however, the overall responder and seizure-free rates were lower than the literature, likely due to the unique underlying epileptogenesis in TSC and the challenges of tolerating CBM. The lower treatment retention rates signal areas for improvement in concurrent medication adjustment practices.</div></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"161 ","pages":"Pages 201-207"},"PeriodicalIF":3.2,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond Numbers: A Call to Action for Accurate Estimation of Spinal Muscular Atrophy in the Middle East and North Africa Region","authors":"Maryam Bemanalizadeh MD ,&nbsp;Vahid Mansouri MD","doi":"10.1016/j.pediatrneurol.2024.09.024","DOIUrl":"10.1016/j.pediatrneurol.2024.09.024","url":null,"abstract":"","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"161 ","pages":"Pages 182-184"},"PeriodicalIF":3.2,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142426937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebrovascular Injury From Early-Onset Neonatal Escherichia coli Meningitis: Expanding the Clinical-Radiologic Phenotype","authors":"Francesca G. García MD ,&nbsp;Yi Li MD ,&nbsp;Rachel Vassar MD ,&nbsp;Cheryl Hawkins MD ,&nbsp;Mark Petersen MD ,&nbsp;Dawn Gano MD, MAS","doi":"10.1016/j.pediatrneurol.2024.09.020","DOIUrl":"10.1016/j.pediatrneurol.2024.09.020","url":null,"abstract":"","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"161 ","pages":"Pages 167-169"},"PeriodicalIF":3.2,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Genetic Landscape of Epilepsy With Eyelid Myoclonia: A Comprehensive Review on Clinical Features and Diagnostic Challenges","authors":"Samia Aziz Sulaiman MD ,&nbsp;Ihda Bani Khalaf MD ,&nbsp;Ahmad E. Saeed MD ,&nbsp;Waseem Hoshan MD ,&nbsp;Ahmed W. Hageen MBBCh ,&nbsp;Jatin Motwani MBBS ,&nbsp;Aman Goyal MBBS","doi":"10.1016/j.pediatrneurol.2024.09.018","DOIUrl":"10.1016/j.pediatrneurol.2024.09.018","url":null,"abstract":"<div><div>Jeavons syndrome (JS), also known as epilepsy with eyelid myoclonia (EEM), is an idiopathic epileptic syndrome that primarily affects children. JS constitutes a significant portion of idiopathic generalized epilepsies and overall epileptic conditions and is characterized by frequent eyelid myoclonia. JS is often triggered by factors such as eyelid closure and exposure to light, leading to absence seizures with photoparoxysmal responses. Although previous studies indicate that some genes have demonstrated an association with the syndrome, no definitive causative gene has yet been identified. The current review therefore aims to shed emphasis on the potential value genetic testing holds in the context of EEM, as well as the need to investigate potential early diagnosis and management strategies in future research.</div></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"161 ","pages":"Pages 176-181"},"PeriodicalIF":3.2,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Severe Epilepsy in an Individual With a TSC2 R905Q Variant Prompting Late Diagnosis in Affected Family Members","authors":"Alice Man BSc ,&nbsp;Matteo Di Scipio BSc ,&nbsp;Breanne Dale MSc, CGC ,&nbsp;Paula Teixeira Marques MD ,&nbsp;Cynthia Sloan Birbeck BScN, RN, MN ,&nbsp;Puneet Jain MBBS, MD, DM ,&nbsp;Elisabetta Trinari MD, MSc ,&nbsp;Resham Ejaz MD ,&nbsp;Robyn Whitney MD","doi":"10.1016/j.pediatrneurol.2024.09.014","DOIUrl":"10.1016/j.pediatrneurol.2024.09.014","url":null,"abstract":"<div><h3>Background</h3><div>Tuberous sclerosis complex (TSC) is a multisystemic disorder caused by inactivating variants in the mTOR pathway inhibitor genes <em>TSC1</em> and <em>TSC2</em>. Individuals with TSC are predisposed to benign tumors in multiple organs as well as TSC-associated neuropsychiatric disorders (TAND) and epilepsy. Pathogenic variants in <em>TSC2</em> are typically associated with a more severe phenotype compared with <em>TSC1</em>; the <em>TSC2</em> R905Q variant has been shown to be an exception, where patients have been reported to present with unusually mild TSC features that may be undetected.</div></div><div><h3>Methods</h3><div>We studied the TSC phenotype of a 13-year-old individual and three family members with a <em>TSC2</em> c.2714G&gt;A (R905Q) pathogenic variant.</div></div><div><h3>Results</h3><div>Patient 1 presented with severe medically refractory epilepsy without tubers or subependymal nodules and only mild dermatologic features of TSC missed on virtual examinations. Her mother and maternal aunt (Patients 2 and 3–diagnosed after age 50 years) presented with a mild phenotype, with dermatologic features and TAND. Her maternal uncle (Patient 4–diagnosed at age 47 years) displayed the most severe phenotype, presenting with intellectual disability, medically refractory epilepsy, obsessive-compulsive disorder, post-traumatic stress disorder, and psychosis.</div></div><div><h3>Conclusions</h3><div>This study expands the possible phenotypic spectrum of <em>TSC2</em> R905Q variant, demonstrating an association with severe epilepsy without associated neuroradiological stigmata. This presentation highlights the possibility of occult focal cortical dysplasia in TSC and emphasizes the importance of genetic testing in individuals with severe epilepsy. Moreover, a late adult diagnosis was subsequently made in other family members allowing for appropriate TSC surveillance to occur.</div></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"161 ","pages":"Pages 158-161"},"PeriodicalIF":3.2,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}