Pediatric neurology最新文献

{"title":"Intellectual Profile in Myotonic Dystrophy Type 1 and Its Association With Its Onset: A Systematic Review and Meta-Analysis","authors":"","doi":"10.1016/j.pediatrneurol.2024.08.002","DOIUrl":"10.1016/j.pediatrneurol.2024.08.002","url":null,"abstract":"<div><h3>Background</h3><p>Myotonic dystrophy type 1 (DM1) is caused by mutations in the <em>DMPK</em> gene, and it is associated with cognitive deficits and intelligence below normative values. The objective of this systematic review and meta-analysis was to estimate the overall intelligence and proportion of intellectual development disorder (IDD) in the population with DM1 and its association with its onset.</p></div><div><h3>Methods</h3><p>Systematic searches of Medline, Scopus, Web of Science, and Cochrane Library were performed from inception to January 2023. Studies that determined the full intelligence quotient (FIQ) or the IDD proportion in populations with DM1 were included. Meta-analyses of the FIQ and IDD and the FIQ mean difference and IDD prevalence ratios (PRs) by disease onset, inheritance, and genotype were conducted.</p></div><div><h3>Results</h3><p>Forty-five studies were included in the meta-analyses, and all were performed in the DM1 population. The FIQ and IDD in DM1 were 77.90 (71.98, 83.81) and 0.44 (0.27, 0.60), respectively. Furthermore, DM1 onset was negatively associated with intelligence. Thus, the comparison “Congenital versus Adult” onsets resulted in an intelligence quotient of −41.61 (−47.81, −35.40) points and a PR of IDD of 9.49 (3.23, 27.89). Finally, maternal inheritance was also negatively associated, but the genotype did not have a statistically significant association.</p></div><div><h3>Conclusions</h3><p>The alterations in intelligence in DM1 are highly associated with the onset of the disease. However, the genotype did not explain these alterations well and there may be other genetic or epigenetic factors that should be considered.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142129910","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":"Editorial Board and Masthead","authors":"","doi":"10.1016/S0887-8994(24)00266-2","DOIUrl":"10.1016/S0887-8994(24)00266-2","url":null,"abstract":"","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141962834","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":"An Evaluation of an Australian Pediatric Neuromuscular Transition Model","authors":"","doi":"10.1016/j.pediatrneurol.2024.07.020","DOIUrl":"10.1016/j.pediatrneurol.2024.07.020","url":null,"abstract":"<div><h3>Background</h3><p>After receiving a diagnosis of a neuromuscular condition, patients have to make their way through a convoluted network of community and state resources as health care shifts from being family and child centered to adult focused. This study examined the barriers to successful transition from patient and clinician perspectives.</p></div><div><h3>Methods</h3><p>Adolescents with a primary diagnosis of a neuromuscular condition who were aged 16 years and over in Queensland, Australia, and who had started the transition process were eligible. Surveys were collected over six months and statistics used to characterize survey responses.</p></div><div><h3>Results</h3><p>There was a high degree of anxiety reported about the transition, with almost 50% of patients and families surveyed reporting concerns about moving across to the adult hospital system. The main barriers to effective transition identified by clinicians were limited time (84%), clinic space (58%), and a lack of an identified transition coordinator (79%).</p></div><div><h3>Conclusions</h3><p>This study has provided a checklist to assist patients with neuromuscular disorders in transitioning from pediatric to adult care. A new model has been developed to enable a slow, personalized transition that is led by a multidisciplinary team.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142076740","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":"The Genetic Puzzle of Cerebral Palsy: Results of a Monocentric Study","authors":"","doi":"10.1016/j.pediatrneurol.2024.07.019","DOIUrl":"10.1016/j.pediatrneurol.2024.07.019","url":null,"abstract":"<div><h3>Background</h3><p>Cerebral palsy (CP) is the most frequent cause of motor impairment in children. Although perinatal asphyxia was long considered to be the leading cause of CP, recent studies demonstrate its causation in only around one in 10 individuals with CP. Instead, genetic causes are increasingly demonstrated. We systematically performed clinical phenotyping and genetic investigations in a monocentric CP cohort, aiming to gain insight into the contribution of genetic variants in CP and its different subtypes.</p></div><div><h3>Methods</h3><p>Chromosomal microarray and/or trio exome sequencing were systematically performed in 337 individuals with CP between September 2017 and August 2022. Deep phenotyping was performed through clinical multidisciplinary evaluation and review of medical files.</p></div><div><h3>Results</h3><p>Genetic analyses resulted in an overall diagnostic yield of 38.3% (129 of 337). In cases with one or more comorbidities (intellectual disability, epilepsy, autism spectrum disorder), the yield increased to almost 50%. Functional enrichment analysis showed over-representation of the following pathways: genetic imprinting, DNA modification, liposaccharide metabolic process, neuron projection guidance, and axon development.</p></div><div><h3>Conclusions</h3><p>Genetic analyses in our CP cohort, the largest monocentric study to date, demonstrated a diagnostic yield of 38.3%, highlighting the importance of genetic testing in CP. The diagnosis of a genetic disorder is essential for prognosis and clinical follow-up, as well as for family counseling. Pathway analysis points to dysregulation of general developmental and metabolic processes as well as neuronal development and function. Unraveling the role of these pathways in CP pathogenesis is instrumental for the identification of CP candidate genes as well as potential therapeutic targets.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142096216","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":"Identification of Putative Biomarkers in Cerebral Palsy: A Meta-Analysis and Meta-Regression","authors":"","doi":"10.1016/j.pediatrneurol.2024.07.016","DOIUrl":"10.1016/j.pediatrneurol.2024.07.016","url":null,"abstract":"<div><h3>Background</h3><p>Cerebral palsy (CP) is a neurological disorder that impairs motor abilities. Identifying maternal biomarker derangements can facilitate further evaluation for early diagnosis, potentially leading to improved clinical outcomes. This study investigates the association between maternal biomarker derangements and CP development during the antenatal period.</p></div><div><h3>Methods</h3><p>A systematic search was conducted in MEDLINE, EMBASE, and Cochrane databases, following MOOSE guidelines. Data on participants exceeding biomarker thresholds (95th and 5th percentiles) were extracted for combined odds ratio estimation. Geometric mean differences, reported as multiples of the median (MoMs), were used to analyze changes in marker levels. Trimesterwise subgroup analysis and metaregression assessed the impact of variables on outcomes.</p></div><div><h3>Results</h3><p>Five observational studies (1552 cases, 484,985 controls) revealed lower maternal pregnancy-associated plasma protein A levels were associated with CP (pooled odds ratio [OR] = 1.60, 95% confidence interval [CI] = 1.22 to 2.09; I = 0%), with a −0.04 MoM geometric mean difference. Lower maternal beta-human chorionic gonadotropin (HCG) levels in first and second trimesters indicated a pooled OR = 1.18 (95% CI = 0.85 to 1.63; I = 57%). Sensitivity analysis showed an OR = 1.40 (95% CI = 1.08 to 1.82; I = 0%), with a −0.07 MoM geometric mean difference. Metaregression identified primigravida status as negatively influencing beta-HCG levels. Elevated nuchal translucency values and CP presented a pooled OR = 1.06 (95% CI = 0.77 to 1.44; I = 0%).</p></div><div><h3>Conclusion</h3><p>Lower maternal pregnancy-associated plasma protein A levels during the first trimester and lower beta-HCG levels in the first and second trimesters are associated with CP development in children. Future research should validate the predictive utility of these biomarkers and explore novel ones through large-scale cohort studies.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142168438","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":"Categorizing Monogenic Epilepsies by Genetic Mechanisms May Predict Efficacy of the Ketogenic Diet","authors":"","doi":"10.1016/j.pediatrneurol.2024.07.014","DOIUrl":"10.1016/j.pediatrneurol.2024.07.014","url":null,"abstract":"<div><h3>Background</h3><p>The ketogenic diet (KD) is an effective treatment for epilepsy. In recent years, studies have shown favorable efficacy of KD in epilepsy from genetic disorders. In this study, we propose an approach to KD in monogenic epilepsy: we evaluate the utility of categorizing genetic variants based on rational associations with the known mechanisms of KD.</p></div><div><h3>Methods</h3><p>Patients with monogenic epilepsy treated with KD were reviewed. The genetic etiologies were categorized into five groups: (1) conditions causing cellular energy impairment, (2) GABA-pathies, (3) mToR-pathies, (4) ion channelopathies, and (5) no known mechanisms associated with KD mechanisms. Treatment response was defined as a median reduction in seizure frequency of greater than 50%.</p></div><div><h3>Results</h3><p>Of 35 patients, 24 (69%) were responders at three months. Based on categories, Group 1 had the highest response rate with seven of seven (100%), followed by Group 2, six of seven (86%), and Group 3, two of three (67%). Patients in Groups 4 and 5 had poorer responses with three of seven (43%) and four of 11 (36%) response rates, respectively (<em>P</em> &lt; 0.01). Median percentage of seizure reduction showed Group 1 with the highest reduction of 97.5%, Group 2 at 94%, and Groups 3, 4, and 5 at 62.5%, 30%, and 40%, respectively (<em>P</em> = 0.036).</p></div><div><h3>Conclusion</h3><p>Our findings show a favorable response to KD in patients with monogenic epilepsy (69% at three months) with the highest response in patients with conditions involving cellular energy impairment and GABA-pathies. The KD, therefore, should be considered early in patients with monogenic epilepsy, especially those involving genes associated with cellular energy impairment or GABA-pathies.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036619","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":"Clinician Stakeholder Experience With Telemedicine Consults to Assess Neonatal Encephalopathy in a Rural State","authors":"","doi":"10.1016/j.pediatrneurol.2024.07.013","DOIUrl":"10.1016/j.pediatrneurol.2024.07.013","url":null,"abstract":"<div><h3>Background</h3><p>Serial neonatal encephalopathy (NE) examinations are difficult to perform in rural community hospitals as on-site experts are not readily available. We implemented a synchronous, acute care model of teleconsultation—the Maine Neonatal Encephalopathy Teleconsultation program (Maine NET)—to provide remote, joint assessment of NE by pediatric neurology and neonatology at nine community hospitals and one tertiary care center. We performed a qualitative study to interview clinicians about their experience of this program.</p></div><div><h3>Methods</h3><p>From April 2018 to October 2022, we employed a semistructured interview format with 16 clinicians representing all participating hospitals. We utilized deductive analysis to assign a set of predefined codes to the transcribed interviews.</p></div><div><h3>Results</h3><p>Thematic analysis supported the anticipated benefits of Maine NET, demonstrating that clinicians felt resource utilization, collaborative decision making, communication, and continuity of care were improved. Clinicians overwhelmingly supported the program: “This program has truly saved babies' lives and future function. I have not met any parents through this journey, who aren't incredibly grateful for the care that is provided” and emphasized the benefit of collaboration between all care team members. Teleconsultation was felt to be “more than adequate to [assess] NE.” Connectivity issues were cited as a limitation.</p></div><div><h3>Conclusions</h3><p>Maine NET has positively impacted care delivery for newborns with clinical concerns for NE. Additionally, the program has improved resource allocation, collaborative decision making, communication, and equity of care. Addressing technological challenges will be vital to the success and sustainability of the planned Maine NET expansion.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036620","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":"Developmental, Cognitive, Ocular Motor, and Neuroimaging Findings Related to SUFU Haploinsufficiency: Unraveling Subtle and Highly Variable Phenotypes","authors":"","doi":"10.1016/j.pediatrneurol.2024.07.015","DOIUrl":"10.1016/j.pediatrneurol.2024.07.015","url":null,"abstract":"<div><h3>Background</h3><p>Biallelic <em>SUFU</em> variants have originally been linked to Joubert syndrome, comprising cerebellar abnormalities, dysmorphism, and polydactyly. In contrast, heterozygous truncating variants have recently been associated with developmental delay and ocular motor apraxia, but only a limited number of patients have been reported. Here, we aim to delineate further the mild end of the phenotypic spectrum related to <em>SUFU</em> haploinsufficiency.</p></div><div><h3>Methods</h3><p>Nine individuals (from three unrelated families) harboring truncating <em>SUFU</em> variants were investigated, including two previously reported individuals (from one family). We provide results from a comprehensive assessment comprising neuroimaging, neuropsychology, video-oculography, and genetic testing.</p></div><div><h3>Results</h3><p>We identified three inherited or <em>de novo</em> truncating variants in <em>SUFU</em> (NM_016169.4): c.895C&gt;T p.(Arg299∗), c.71dup p.(Ala25Glyfs∗23), and c.71del p.(Pro24Argfs∗72). The phenotypic expression showed high variability both between and within families. Clinical features include motor developmental delay (seven of nine), axial hypotonia (five of nine), ocular motor apraxia (three of nine), and cerebellar signs (three of nine). Four of the six reported children had macrocephaly. Neuropsychological and developmental assessments revealed mildly delayed language development in the youngest children, whereas general cognition was normal in all variant carriers. Subtle but characteristic <em>SUFU</em>-related neuroimaging abnormalities (including superior cerebellar dysplasia, abnormalities of the superior cerebellar peduncles, rostrally displaced fastigium, and vermis hypoplasia) were observed in seven of nine individuals.</p></div><div><h3>Conclusions</h3><p>Our data shed further light on the mild but recognizable features of <em>SUFU</em> haploinsufficiency and underline its marked phenotypic variability, even within families. Notably, neurodevelopmental and behavioral abnormalities are mild compared with Joubert syndrome and seem to be well compensated over time.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0887899424002790/pdfft?md5=76ceb9fd27326b717fad6aee95d40970&pid=1-s2.0-S0887899424002790-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047775","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":"Equitable Access of Delandistrogene Moxeparvovec for Patients With Duchenne Muscular Dystrophy: A Call for Discussion","authors":"","doi":"10.1016/j.pediatrneurol.2024.07.017","DOIUrl":"10.1016/j.pediatrneurol.2024.07.017","url":null,"abstract":"","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889931","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":"Long-Term Neurodevelopmental Outcome of Children With Mild Traumatic Brain Injury","authors":"","doi":"10.1016/j.pediatrneurol.2024.07.011","DOIUrl":"10.1016/j.pediatrneurol.2024.07.011","url":null,"abstract":"<div><h3>Background</h3><p>To investigate the long-term outcome of pediatric mild traumatic brain injury (mTBI) in terms of neurocognitive, behavioral, and school functioning and to identify clinical risk factors for adverse outcomes.</p></div><div><h3>Methods</h3><p>This study describes the follow-up of a prospective multicenter sample of 89 children with mTBI 3.6 years postinjury and 89 neurologically healthy children matched for sex, age, and socioeconomic status. Neurodevelopmental outcomes were assessed using an intelligence test, behavioral questionnaires, computerized neurocognitive tests, and longitudinal (pre- and postinjury) standardized school performance data.</p></div><div><h3>Results</h3><p>Children with mTBI exhibited intelligence in the average range but had more behavioral problems related to inattentiveness (<em>P</em> = 0.004, <em>d</em> = 0.47) and hyperactive impulsivity (<em>P</em> = 0.01, <em>d</em> = 0.40) and showed poorer neurocognitive performance in information processing stability (<em>P</em> = 0.003, <em>d</em> = −0.55) and Visual Working Memory (<em>P</em> = 0.04, <em>d</em> = −0.39) compared with matched peers. Longitudinal school performance data revealed poorer performance in Technical Reading up to two years postinjury (<em>P</em> = 0.005, <em>d</em> = −0.42) when compared with normative data. Clinical risk factors did not reveal predictive value for adverse outcomes in children with mTBI.</p></div><div><h3>Conclusions</h3><p>This study indicates that children with mTBI are at risk of long-term deficits in neurocognitive and behavioral functioning, with longitudinal evidence suggesting shortfalls in school performance up to two years postinjury. Clinical risk factors do not provide a solid basis for long-term neurodevelopmental prognosis. Findings emphasize the importance of, and challenges for, early identification of children at risk for adverse neurodevelopmental outcome after mTBI.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0887899424002625/pdfft?md5=ce84bad74163f7b90e406ea38c96fef3&pid=1-s2.0-S0887899424002625-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141846204","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}