Pub Date : 2024-07-20DOI: 10.1016/j.pediatrneurol.2024.07.010
Maria Carla Borroto , Heena Patel PharmD , Siddharth Srivastava MD , Lindsay C. Swanson MS , Boris Keren MD, PhD , Sandra Whalen MD , Cyril Mignot MD, PhD , Xiaodong Wang PhD , Qian Chen MSc, PhD , Jill A. Rosenfeld MS , Scott McLean MD , Rebecca O. Littlejohn MS
Background
GTPases of the Rab family are important orchestrators of membrane trafficking, and their dysregulation has been linked to a variety of neuropathologies. In 2017, we established a causal link between RAB11A variants and developmental and epileptic encephalopathy. In this study, we expand the phenotype of RAB11A-associated neurodevelopmental disorder and explore genotype-phenotype correlations.
Methods
We assessed 16 patients with pathogenic or likely pathogenic RAB11A variants, generally de novo, heterozygous missense variants. One individual had a homozygous nonsense variant, although concomitant with a pathogenic LAMA2 variant, which made their respective contributions to the phenotype difficult to discriminate.
Results
We reinforce the finding that certain RAB11A missense variants lead to intellectual disability and developmental delays. Other clinical features might include gait disturbances, hypotonia, magnetic resonance imaging abnormalities, visual anomalies, dysmorphisms, early adrenarche, and obesity. Epilepsy seems to be less common and linked to variants outside the binding sites. Individuals with variants in the binding sites seem to have a more multisystemic, nonepileptic phenotype.
Conclusions
Similar to other Rab-related disorders, RAB11A-associated neurodevelopmental disorder can also impact gait, tonus, brain anatomy and physiology, vision, adrenarche, and body weight and structure. Epilepsy seems to affect the minority of patients with variants outside the binding sites.
{"title":"Cohort Expansion and Genotype-Phenotype Analysis of RAB11A-Associated Neurodevelopmental Disorder","authors":"Maria Carla Borroto , Heena Patel PharmD , Siddharth Srivastava MD , Lindsay C. Swanson MS , Boris Keren MD, PhD , Sandra Whalen MD , Cyril Mignot MD, PhD , Xiaodong Wang PhD , Qian Chen MSc, PhD , Jill A. Rosenfeld MS , Scott McLean MD , Rebecca O. Littlejohn MS","doi":"10.1016/j.pediatrneurol.2024.07.010","DOIUrl":"10.1016/j.pediatrneurol.2024.07.010","url":null,"abstract":"<div><h3>Background</h3><p>GTPases of the Rab family are important orchestrators of membrane trafficking, and their dysregulation has been linked to a variety of neuropathologies. In 2017, we established a causal link between <em>RAB11A</em> variants and developmental and epileptic encephalopathy. In this study, we expand the phenotype of <em>RAB11A</em>-associated neurodevelopmental disorder and explore genotype-phenotype correlations.</p></div><div><h3>Methods</h3><p>We assessed 16 patients with pathogenic or likely pathogenic <em>RAB11A</em> variants, generally <em>de novo</em>, heterozygous missense variants. One individual had a homozygous nonsense variant, although concomitant with a pathogenic <em>LAMA2</em> variant, which made their respective contributions to the phenotype difficult to discriminate.</p></div><div><h3>Results</h3><p>We reinforce the finding that certain <em>RAB11A</em> missense variants lead to intellectual disability and developmental delays. Other clinical features might include gait disturbances, hypotonia, magnetic resonance imaging abnormalities, visual anomalies, dysmorphisms, early adrenarche, and obesity. Epilepsy seems to be less common and linked to variants outside the binding sites. Individuals with variants in the binding sites seem to have a more multisystemic, nonepileptic phenotype.</p></div><div><h3>Conclusions</h3><p>Similar to other Rab-related disorders, <em>RAB11A</em>-associated neurodevelopmental disorder can also impact gait, tonus, brain anatomy and physiology, vision, adrenarche, and body weight and structure. Epilepsy seems to affect the minority of patients with variants outside the binding sites.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"160 ","pages":"Pages 45-53"},"PeriodicalIF":3.2,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0887899424002613/pdfft?md5=12ef8cd00d03d472149d57d6339d53d7&pid=1-s2.0-S0887899424002613-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141848373","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}
Pub Date : 2024-07-17DOI: 10.1016/j.pediatrneurol.2024.07.009
Grace Gombolay MD, MSc , J. Nicholas Brenton MD , Jennifer H. Yang MD , Coral M. Stredny MD , Ryan Kammeyer MD , Kristen S. Fisher MD , Alexander J. Sandweiss MD, PhD , Timothy A. Erickson MD , Varun Kannan MD , Catherine Otten MD , Claude Steriade MD , NgocHanh Vu MD , Jonathan D. Santoro MD , Karla Robles-Lopez MD , Robert Goodrich MD , Scott Otallah MD , Janetta Arellano MD , Andrew Christiana MD , Morgan Morris MS , Mark P. Gorman MD , Duriel Hardy MD
Background
Isolated psychiatric symptoms can be the initial symptom of pediatric anti-N-methyl-d-aspartate (NMDA) receptor autoimmune encephalitis (pNMDARE). Here we report on the prevalence of isolated psychiatric symptoms in pNMDARE. We also assess whether initial neurodiagnostic tests (brain magnetic resonance imaging [MRI], electroencephalography [EEG], and/or cerebrospinal fluid [CSF] white blood cell count) are abnormal in children with isolated psychiatric symptoms and pNMDARE.
Methods
This multicenter retrospective cohort study from CONNECT (Conquering Neuroinflammation and Epilepsies Consortium) from 14 institutions included children under age 18 years who were diagnosed with pNMDARE. Descriptive statistics using means, medians, and comparisons for continuous versus discrete data was performed.
Results
Of 249 children included, 12 (5%) had only psychiatric symptoms without other typical clinical features of autoimmune encephalitis at presentation. All but one (11 of 12 = 92%) had at least one abnormal finding on initial ancillary testing: eight of 12 (67%) had an abnormal EEG, six of 12 (50%) had an abnormal MRI, and five of 12 (42%) demonstrated CSF pleocytosis. The single patient with a normal MRI, EEG, and CSF profile had low positive CSF NMDA antibody (titer of 1:1), and symptoms improved without immunotherapy.
Conclusions
Isolated first-episode psychiatric symptoms in pNMDARE are uncommon, and the majority of children will exhibit additional neurodiagnostic abnormalities. Delaying immunotherapy in a child with isolated psychiatric symptoms and normal neurodiagnostic testing may be warranted while awaiting confirmatory antibody testing.
{"title":"Isolated Psychiatric Symptoms in Children With Anti-N-Methyl-d Aspartate Receptor Encephalitis","authors":"Grace Gombolay MD, MSc , J. Nicholas Brenton MD , Jennifer H. Yang MD , Coral M. Stredny MD , Ryan Kammeyer MD , Kristen S. Fisher MD , Alexander J. Sandweiss MD, PhD , Timothy A. Erickson MD , Varun Kannan MD , Catherine Otten MD , Claude Steriade MD , NgocHanh Vu MD , Jonathan D. Santoro MD , Karla Robles-Lopez MD , Robert Goodrich MD , Scott Otallah MD , Janetta Arellano MD , Andrew Christiana MD , Morgan Morris MS , Mark P. Gorman MD , Duriel Hardy MD","doi":"10.1016/j.pediatrneurol.2024.07.009","DOIUrl":"10.1016/j.pediatrneurol.2024.07.009","url":null,"abstract":"<div><h3>Background</h3><p>Isolated psychiatric symptoms can be the initial symptom of pediatric anti-<em>N</em>-methyl-d-aspartate (NMDA) receptor autoimmune encephalitis (pNMDARE). Here we report on the prevalence of isolated psychiatric symptoms in pNMDARE. We also assess whether initial neurodiagnostic tests (brain magnetic resonance imaging [MRI], electroencephalography [EEG], and/or cerebrospinal fluid [CSF] white blood cell count) are abnormal in children with isolated psychiatric symptoms and pNMDARE.</p></div><div><h3>Methods</h3><p>This multicenter retrospective cohort study from CONNECT (Conquering Neuroinflammation and Epilepsies Consortium) from 14 institutions included children under age 18 years who were diagnosed with pNMDARE. Descriptive statistics using means, medians, and comparisons for continuous versus discrete data was performed.</p></div><div><h3>Results</h3><p>Of 249 children included, 12 (5%) had only psychiatric symptoms without other typical clinical features of autoimmune encephalitis at presentation. All but one (11 of 12 = 92%) had at least one abnormal finding on initial ancillary testing: eight of 12 (67%) had an abnormal EEG, six of 12 (50%) had an abnormal MRI, and five of 12 (42%) demonstrated CSF pleocytosis. The single patient with a normal MRI, EEG, and CSF profile had low positive CSF NMDA antibody (titer of 1:1), and symptoms improved without immunotherapy.</p></div><div><h3>Conclusions</h3><p>Isolated first-episode psychiatric symptoms in pNMDARE are uncommon, and the majority of children will exhibit additional neurodiagnostic abnormalities. Delaying immunotherapy in a child with isolated psychiatric symptoms and normal neurodiagnostic testing may be warranted while awaiting confirmatory antibody testing.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"159 ","pages":"Pages 12-15"},"PeriodicalIF":3.2,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141843740","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}
Pub Date : 2024-07-16DOI: 10.1016/j.pediatrneurol.2024.07.008
Alice Yun BS , Amanda M. Griffin AuD, PhD , Hae-Young Kim DrPH , Nicole J. Ullrich MD, PhD , Greg R. Licameli MD, MHCM
Background
Hearing loss has not been thoroughly investigated as a comorbidity in larger cohorts with neurofibromatosis type 1 (NF1).
Methods
Available audiometric data were reviewed from patients with NF1 seen at a tertiary pediatric hospital to assess prevalence and risk factors for hearing loss.
Results
Of 1172 patients with NF1 seen between 2010 and 2022, 90 had available audiometric data and 48 of 90 patients (53%) had one or more audiogram revealing hearing loss. Those not referred to audiology were presumed to have normal hearing, resulting in a conservative hearing loss estimate of 4% for children and young adults with NF1. Of 90 patients with audiograms, 29 (32%) had conductive loss (CHL), 15 (17%) had sensorineural loss (SNHL), and 3 (3%) had mixed hearing loss. Hearing loss type was undetermined for one patient. For children with CHL, six had permanent CHL secondary to plexiform neurofibroma, 19 CHL were transient due to active middle ear dysfunction, and four CHL cases were indeterminate in etiology. For three children with SNHL or mixed hearing loss, etiology included history of ototoxic chemotherapy and/or family history of SNHL. In the 16 patients with SNHL or mixed hearing loss with more than one audiogram over time, progressive hearing decline was noted in eight of 16, and 26 of 178 hearing thresholds (15%) progressed.
Conclusions
Our findings suggest that audiometric evaluations should be considered for at least a subset of children with NF1, given the higher-than-expected rate of hearing loss in patients with NF1 compared with the general population.
{"title":"Incidence of Hearing Loss in Patients With Neurofibromatosis Type 1 at a Tertiary Care Pediatric Hospital","authors":"Alice Yun BS , Amanda M. Griffin AuD, PhD , Hae-Young Kim DrPH , Nicole J. Ullrich MD, PhD , Greg R. Licameli MD, MHCM","doi":"10.1016/j.pediatrneurol.2024.07.008","DOIUrl":"10.1016/j.pediatrneurol.2024.07.008","url":null,"abstract":"<div><h3>Background</h3><p>Hearing loss has not been thoroughly investigated as a comorbidity in larger cohorts with neurofibromatosis type 1 (NF1).</p></div><div><h3>Methods</h3><p>Available audiometric data were reviewed from patients with NF1 seen at a tertiary pediatric hospital to assess prevalence and risk factors for hearing loss.</p></div><div><h3>Results</h3><p>Of 1172 patients with NF1 seen between 2010 and 2022, 90 had available audiometric data and 48 of 90 patients (53%) had one or more audiogram revealing hearing loss. Those not referred to audiology were presumed to have normal hearing, resulting in a conservative hearing loss estimate of 4% for children and young adults with NF1. Of 90 patients with audiograms, 29 (32%) had conductive loss (CHL), 15 (17%) had sensorineural loss (SNHL), and 3 (3%) had mixed hearing loss. Hearing loss type was undetermined for one patient. For children with CHL, six had permanent CHL secondary to plexiform neurofibroma, 19 CHL were transient due to active middle ear dysfunction, and four CHL cases were indeterminate in etiology. For three children with SNHL or mixed hearing loss, etiology included history of ototoxic chemotherapy and/or family history of SNHL. In the 16 patients with SNHL or mixed hearing loss with more than one audiogram over time, progressive hearing decline was noted in eight of 16, and 26 of 178 hearing thresholds (15%) progressed.</p></div><div><h3>Conclusions</h3><p>Our findings suggest that audiometric evaluations should be considered for at least a subset of children with NF1, given the higher-than-expected rate of hearing loss in patients with NF1 compared with the general population.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"159 ","pages":"Pages 35-40"},"PeriodicalIF":3.2,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0887899424002595/pdfft?md5=277a79c825d41c1def31f5b3c596627e&pid=1-s2.0-S0887899424002595-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141698704","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}
Pub Date : 2024-07-15DOI: 10.1016/j.pediatrneurol.2024.07.007
Sarah Baer MD , Audrey Schalk MD , Marguerite Miguet MD , Élise Schaefer MD, PhD , Salima El Chehadeh MD, PhD , Emmanuelle Ginglinger MD , Anne de Saint Martin MD, PhD , Marie-Thérèse Abi Wardé MD , Vincent Laugel MD, PhD , Yvan de Feraudy MD , Lucas Gauer MD , Edouard Hirsch MD, PhD , Clotilde Boulay MD , Claire Bansept MD , Anamaria Bolocan MD , Ismini Kitadinis MD , Aurélie Gouronc MD , Bénédicte Gérard pharmD, PhD , Amélie Piton PhD , Sophie Scheidecker MD, PhD
Background
Genetic epilepsy diagnosis is increasing due to technological advancements. Although the use of molecular diagnosis is increasing, chromosomal microarray analysis (CMA) remains an important diagnostic tool for many patients. We aim to explore the role and indications of CMA in epilepsy, given the current genomic advances.
Methods
We obtained data from 378 epileptic described patients, who underwent CMA between 2015 and 2021. Different types of syndromic or nonsyndromic epilepsy were represented.
Results
After excluding patients who were undertreated or had missing data, we included 250 patients with treated epilepsy and relevant clinical information. These patients mostly had focal epilepsy or developmental and epileptic encephalopathy, with a median start age of 2 years. Ninety percent of the patients had intellectual disability, more than two thirds had normal head size, and 60% had an abnormal magnetic resonance imaging. We also included 10 patients with epilepsy without comorbidities. In our cohort, we identified 35 pathogenic copy number variations (CNVs) explaining epilepsy with nine recurrent CNVs enriched in patients with epilepsy, 12 CNVs related to neurodevelopmental disorder phenotype with possible epilepsy, five CNVs including a gene already known in epilepsy, and nine CNVs based on size combined with de novo occurrence. The diagnosis rate in our study reached 14% (35 of 250) with first-line CMA, as previously reported. Although targeted gene panel sequencing could potentially diagnose some of the reported epilepsy CNVs (34% [12 of 35]).
Conclusions
CMA remains a viable option as the first-line genetic test in cases where other genetic tests are not available and as a second-line diagnostic technique if gene panel or exome sequencing yields negative results.
{"title":"Copy Number Variation and Epilepsy: State of the Art in the Era of High-Throughput Sequencing—A Multicenter Cohort Study","authors":"Sarah Baer MD , Audrey Schalk MD , Marguerite Miguet MD , Élise Schaefer MD, PhD , Salima El Chehadeh MD, PhD , Emmanuelle Ginglinger MD , Anne de Saint Martin MD, PhD , Marie-Thérèse Abi Wardé MD , Vincent Laugel MD, PhD , Yvan de Feraudy MD , Lucas Gauer MD , Edouard Hirsch MD, PhD , Clotilde Boulay MD , Claire Bansept MD , Anamaria Bolocan MD , Ismini Kitadinis MD , Aurélie Gouronc MD , Bénédicte Gérard pharmD, PhD , Amélie Piton PhD , Sophie Scheidecker MD, PhD","doi":"10.1016/j.pediatrneurol.2024.07.007","DOIUrl":"10.1016/j.pediatrneurol.2024.07.007","url":null,"abstract":"<div><h3>Background</h3><p>Genetic epilepsy diagnosis is increasing due to technological advancements. Although the use of molecular diagnosis is increasing, chromosomal microarray analysis (CMA) remains an important diagnostic tool for many patients. We aim to explore the role and indications of CMA in epilepsy, given the current genomic advances.</p></div><div><h3>Methods</h3><p>We obtained data from 378 epileptic described patients, who underwent CMA between 2015 and 2021. Different types of syndromic or nonsyndromic epilepsy were represented.</p></div><div><h3>Results</h3><p>After excluding patients who were undertreated or had missing data, we included 250 patients with treated epilepsy and relevant clinical information. These patients mostly had focal epilepsy or developmental and epileptic encephalopathy, with a median start age of 2 years. Ninety percent of the patients had intellectual disability, more than two thirds had normal head size, and 60% had an abnormal magnetic resonance imaging. We also included 10 patients with epilepsy without comorbidities. In our cohort, we identified 35 pathogenic copy number variations (CNVs) explaining epilepsy with nine recurrent CNVs enriched in patients with epilepsy, 12 CNVs related to neurodevelopmental disorder phenotype with possible epilepsy, five CNVs including a gene already known in epilepsy, and nine CNVs based on size combined with <em>de novo</em> occurrence. The diagnosis rate in our study reached 14% (35 of 250) with first-line CMA, as previously reported. Although targeted gene panel sequencing could potentially diagnose some of the reported epilepsy CNVs (34% [12 of 35]).</p></div><div><h3>Conclusions</h3><p>CMA remains a viable option as the first-line genetic test in cases where other genetic tests are not available and as a second-line diagnostic technique if gene panel or exome sequencing yields negative results.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"159 ","pages":"Pages 16-25"},"PeriodicalIF":3.2,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141691364","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}
Anti-Purkinje cell cytoplasmic antibody type 2 (PCA-2) is associated with various neurological conditions in adults. However, related studies have not been conducted in children. The present study aimed to characterize the clinical features and outcomes of PCA-2-related autoimmune cerebellar degeneration in pediatric patients.
Methods
A total of 357 pediatric patients with acute or subacute cerebellar ataxia were recruited for the study from June 2015 to September 2022. Of these, PCA-2 was identified in four patients. Information on the clinical manifestations, patient response to treatment, and outcomes was collected and analyzed.
Results
The patient cohort in the present study included two boys and two girls, with the age of onset from six to 12 years. Axial ataxia was the most remarkable symptom observed in the entire patient cohort (four of four), followed by dysmetria in 75% (three of four), dysarthria in 50% (two of four), and nystagmus in 25% (one of four) of patients. Cognitive impairment was present in one patient. Peripheral neuropathy, which is an extracerebellar symptom, was found in two patients. One patient was diagnosed with a pelvic neuroblastoma before the onset of ataxia. The presence of oligoclonal bands was confirmed in the cerebrospinal fluid, and cerebellar atrophy was observed. Immunotherapy, including glucocorticoids and/or intravenous immunoglobulin, was administered to all four patients immediately following diagnosis, and mycophenolate mofetil was administered to three patients. Three patients responded to immunotherapy.
Conclusions
In children, PCA2-associated autoimmune cerebellar degeneration is rare, and they show comparatively fewer symptoms than adults. Timely and appropriate immunotherapy is beneficial.
{"title":"Anti-Purkinje Cell Cytoplasmic Antibody Type 2-Associated Autoimmune Cerebellar Degeneration in Children: A Different Phenotype From Adults","authors":"Anna Zhou MD , Haitao Ren MD , Libing Fu MD , Changhong Ren MD , Ji Zhou MD , Hongzhi Guan MD , Xiaotun Ren MD , Weihua Zhang MD","doi":"10.1016/j.pediatrneurol.2024.07.004","DOIUrl":"10.1016/j.pediatrneurol.2024.07.004","url":null,"abstract":"<div><h3>Background</h3><p>Anti-Purkinje cell cytoplasmic antibody type 2 (PCA-2) is associated with various neurological conditions in adults. However, related studies have not been conducted in children. The present study aimed to characterize the clinical features and outcomes of PCA-2-related autoimmune cerebellar degeneration in pediatric patients.</p></div><div><h3>Methods</h3><p>A total of 357 pediatric patients with acute or subacute cerebellar ataxia were recruited for the study from June 2015 to September 2022. Of these, PCA-2 was identified in four patients. Information on the clinical manifestations, patient response to treatment, and outcomes was collected and analyzed.</p></div><div><h3>Results</h3><p>The patient cohort in the present study included two boys and two girls, with the age of onset from six to 12 years. Axial ataxia was the most remarkable symptom observed in the entire patient cohort (four of four), followed by dysmetria in 75% (three of four), dysarthria in 50% (two of four), and nystagmus in 25% (one of four) of patients. Cognitive impairment was present in one patient. Peripheral neuropathy, which is an extracerebellar symptom, was found in two patients. One patient was diagnosed with a pelvic neuroblastoma before the onset of ataxia. The presence of oligoclonal bands was confirmed in the cerebrospinal fluid, and cerebellar atrophy was observed. Immunotherapy, including glucocorticoids and/or intravenous immunoglobulin, was administered to all four patients immediately following diagnosis, and mycophenolate mofetil was administered to three patients. Three patients responded to immunotherapy.</p></div><div><h3>Conclusions</h3><p>In children, PCA2-associated autoimmune cerebellar degeneration is rare, and they show comparatively fewer symptoms than adults. Timely and appropriate immunotherapy is beneficial.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"160 ","pages":"Pages 26-29"},"PeriodicalIF":3.2,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141692860","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}
Pub Date : 2024-07-11DOI: 10.1016/j.pediatrneurol.2024.07.005
Dr. Abdul Aziz Al-Garni MD (Clinical Fellow) , Avneet Mazara BSc (Life Sciences) , Nina Stein MD, MSc (Associate Professor) , Lawrence Mbuagbaw MD, PhD (Associate Professor) , Olufemi Ajani MD (Associate Professor) , Ipsita Goswami MD, MSc (Assistant Professor)
Background
Posthemorrhagic ventricular dilatation (PHVD) is a major complication of intraventricular hemorrhage (IVH); it is associated with high risks of cerebral palsy and cognitive deficits compared with infants without PHVD. This study aims to explore the early perinatal risk factors-associated with the risk of progressive PHVD.
Methods
Neonates ≤29 weeks gestational age (GA) with Grade II-III IVH and periventricular hemorrhagic infarct (PVHI) between 2015 and 2021 were retrospectively reviewed. All cranial ultrasounds done within 14 days postnatal age (PNA) were assessed for grade of IVH, anterior horn width (AHW), ventricular index (VI), and thalamo-occipital index (TOD). The outcome was defined as death of any cause or VI and/or AHW and/or TOD ≥ moderate-risk zone based on an ultrasound done beyond two weeks PNA.
Results
A total of 146 infants with a mean GA of 26 ± 1.8 weeks, birth weight 900 ± 234 g were included, 46% were females. The primary outcome occurred in 56 (39%) infants; among them 17 (30%) and 11 (20%) needed ventricular reservoir and shunt insertion, respectively. The risk factors present within 14 days PNA that significantly increased the odds of developing PHVD were hemodynamically significant patent ductus arteriosus (odds ratio [OR] 6.1, 95% confidence interval [CI] 1.9 to 22), culture-proven sepsis (OR 5.4, 95% CI 1.8 to 18), Grade III IVH (OR 4.6, 95% CI 1.1 to 22), PVHI (OR 3.0, 95% CI 0.9 to 10), and VI (OR 2.1, 95% CI 1.6 to 2.9).
Conclusions
Clinical predictors such as significant ductus arteriosus and bacterial septicemia, along with risk levels of AHW and VI measured with early cranial ultrasounds, are potential predictors of subsequent onset of PHVD.
背景出血性脑室扩张（PHVD）是脑室内出血（IVH）的主要并发症；与无PHVD的婴儿相比，它与脑瘫和认知障碍的高风险相关。本研究旨在探讨与进展性 PHVD 风险相关的围产期早期风险因素。方法回顾性研究了 2015 年至 2021 年期间胎龄（GA）小于 29 周、患有 II-III 级 IVH 和脑室周围出血性梗死（PVHI）的新生儿。所有在产后14天（PNA）内进行的头颅超声检查均评估了IVH的等级、前角宽度（AHW）、脑室指数（VI）和丘脑-枕骨指数（TOD）。结果共纳入146名婴儿，平均孕期（26±1.8周），出生体重（900±234克），46%为女性。56名婴儿（39%）出现了主要结果；其中分别有17名（30%）和11名（20%）需要插入心室蓄水池和分流管。PNA 14 天内出现的风险因素会显著增加 PHVD 的发病几率，这些因素包括：血液动力学显著的动脉导管未闭（几率比 [OR] 6.1，95% 置信区间 [CI] 1.9 至 22）、培养证实的败血症（OR 5.4，95% CI 1.8 至 18）、IVH III 级（OR 4.6，95% CI 1.结论临床预测因素，如明显的动脉导管未闭和细菌性败血症，以及早期头颅超声检查测得的 AHW 和 VI 风险水平，都是随后 PHVD 发病的潜在预测因素。
{"title":"Integrating Clinical and Neuroimaging Markers to Predict the Onset of Posthemorrhagic Ventricular Dilatation in Preterm Neonates","authors":"Dr. Abdul Aziz Al-Garni MD (Clinical Fellow) , Avneet Mazara BSc (Life Sciences) , Nina Stein MD, MSc (Associate Professor) , Lawrence Mbuagbaw MD, PhD (Associate Professor) , Olufemi Ajani MD (Associate Professor) , Ipsita Goswami MD, MSc (Assistant Professor)","doi":"10.1016/j.pediatrneurol.2024.07.005","DOIUrl":"10.1016/j.pediatrneurol.2024.07.005","url":null,"abstract":"<div><h3>Background</h3><p>Posthemorrhagic ventricular dilatation (PHVD) is a major complication of intraventricular hemorrhage (IVH); it is associated with high risks of cerebral palsy and cognitive deficits compared with infants without PHVD. This study aims to explore the early perinatal risk factors-associated with the risk of progressive PHVD.</p></div><div><h3>Methods</h3><p>Neonates ≤29 weeks gestational age (GA) with Grade II-III IVH and periventricular hemorrhagic infarct (PVHI) between 2015 and 2021 were retrospectively reviewed. All cranial ultrasounds done within 14 days postnatal age (PNA) were assessed for grade of IVH, anterior horn width (AHW), ventricular index (VI), and thalamo-occipital index (TOD). The outcome was defined as death of any cause or VI and/or AHW and/or TOD ≥ moderate-risk zone based on an ultrasound done beyond two weeks PNA.</p></div><div><h3>Results</h3><p>A total of 146 infants with a mean GA of 26 ± 1.8 weeks, birth weight 900 ± 234 g were included, 46% were females. The primary outcome occurred in 56 (39%) infants; among them 17 (30%) and 11 (20%) needed ventricular reservoir and shunt insertion, respectively. The risk factors present within 14 days PNA that significantly increased the odds of developing PHVD were hemodynamically significant patent ductus arteriosus (odds ratio [OR] 6.1, 95% confidence interval [CI] 1.9 to 22), culture-proven sepsis (OR 5.4, 95% CI 1.8 to 18), Grade III IVH (OR 4.6, 95% CI 1.1 to 22), PVHI (OR 3.0, 95% CI 0.9 to 10), and VI (OR 2.1, 95% CI 1.6 to 2.9).</p></div><div><h3>Conclusions</h3><p>Clinical predictors such as significant ductus arteriosus and bacterial septicemia, along with risk levels of AHW and VI measured with early cranial ultrasounds, are potential predictors of subsequent onset of PHVD.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"159 ","pages":"Pages 4-11"},"PeriodicalIF":3.2,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S088789942400256X/pdfft?md5=80934d85da97829a0969599155a943f0&pid=1-s2.0-S088789942400256X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141708645","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}
Pub Date : 2024-07-10DOI: 10.1016/j.pediatrneurol.2024.07.003
S. Zeynep Kaşka MSc , Gülsen Sırtbaş Işık PhD , H. Tolga Çelik MD , Akmer Mutlu PhD
Background
High birth weight (HBW) describes fetal birth weight of more than 4000 g. Infants with HBW have a high risk of developing neurological and developmental problems. Until recently, there were no studies in the literature that investigated the quality of spontaneous movements and the integrity of the developing nervous system in infants with HBW. The aims of this study were (1) to describe age-specific detailed early spontaneous movements in infants with HBW and (2) to compare the detailed early spontaneous movements of infants with HBW and normal birth weight (NBW).
Methods
Twenty-two infants with HBW (median birth weight = 4190 g) and 22 infants with NBW (median birth weight = 3255 g) were included at 10 to 19 weeks post-term age (median = 13 weeks). All infants were assessed according to General Movement Assessment using three- to five-minute video recordings. Video recordings of each infant were evaluated using Motor Optimality Score for three- to five-month-old infants-Revised score sheet.
Results
Motor Optimality Score-Revised (MOS-R) (P < 0.001), observed postural patterns (P < 0.001), and age-adequate movement repertoire (P = 0.005) were significantly lower in the infants with HBW. Infants with HBW had more aberrant (abnormal or absent) fidgety movements (18%) than those with NBW (0%).
Conclusions
The results of this study demonstrated that the motor repertoire of infants with HBW tended to decrease more than that of those with NBW. To enable the follow-up of progression as a result of these assessments infants in need should be referred to age-adequate early intervention programs.
{"title":"General Movements Assessment in Infants with High Birth Weight","authors":"S. Zeynep Kaşka MSc , Gülsen Sırtbaş Işık PhD , H. Tolga Çelik MD , Akmer Mutlu PhD","doi":"10.1016/j.pediatrneurol.2024.07.003","DOIUrl":"10.1016/j.pediatrneurol.2024.07.003","url":null,"abstract":"<div><h3>Background</h3><p>High birth weight (HBW) describes fetal birth weight of more than 4000 g. Infants with HBW have a high risk of developing neurological and developmental problems. Until recently, there were no studies in the literature that investigated the quality of spontaneous movements and the integrity of the developing nervous system in infants with HBW. The aims of this study were (1) to describe age-specific detailed early spontaneous movements in infants with HBW and (2) to compare the detailed early spontaneous movements of infants with HBW and normal birth weight (NBW).</p></div><div><h3>Methods</h3><p>Twenty-two infants with HBW (median birth weight = 4190 g) and 22 infants with NBW (median birth weight = 3255 g) were included at 10 to 19 weeks post-term age (median = 13 weeks). All infants were assessed according to General Movement Assessment using three- to five-minute video recordings. Video recordings of each infant were evaluated using Motor Optimality Score for three- to five-month-old infants-Revised score sheet.</p></div><div><h3>Results</h3><p>Motor Optimality Score-Revised (MOS-R) (<em>P</em> < 0.001), observed postural patterns (<em>P</em> < 0.001), and age-adequate movement repertoire (<em>P</em> = 0.005) were significantly lower in the infants with HBW. Infants with HBW had more aberrant (abnormal or absent) fidgety movements (18%) than those with NBW (0%).</p></div><div><h3>Conclusions</h3><p>The results of this study demonstrated that the motor repertoire of infants with HBW tended to decrease more than that of those with NBW. To enable the follow-up of progression as a result of these assessments infants in need should be referred to age-adequate early intervention programs.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"159 ","pages":"Pages 26-32"},"PeriodicalIF":3.2,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141695083","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}
Pub Date : 2024-07-09DOI: 10.1016/j.pediatrneurol.2024.07.002
Sarah Mohajeri MD, MPH , Michael Potchen MD , Izukanji Sikazwe MD , Samuel Kampondeni MD , Colleen Hoffman ARRT , David Bearden MD , Lisa Kalungwana MSc , Namwiya Musonda MS , Manoj Mathews MD , Musaku Mwenechanya MD , Ifunanya Dallah MPH , Brent Johnson PhD , Christopher Bositis MD , Jessie Huang BSc , Gretchen L. Birbeck MD, MPH
Background
There are an estimated 1.5 million children living with human immunodeficiency virus (CLHIV), most residing in sub-Saharan Africa. A common hospital presentation of CLHIV is new-onset seizure, for which imaging is helpful but not routinely performed due to scarce resources. We present imaging findings and their association with clinical risk factors and outcomes in a cohort of Zambian CLHIV presenting with new-onset seizure.
Methods
In this prospective cohort study, participants were recruited at the University Teaching Hospital in Lusaka, Zambia. Various clinical and demographic characteristics were obtained. Computed tomography (CT), magnetic resonance imaging (MRI), or both were obtained during admission or shortly after discharge. If both studies were available, MRI data was used. Two neuroradiologists interpreted images using REDCap-based NeuroInterp, a tool that quantifies brain imaging findings. Age-dependent neuropsychologic assessments were administered.
Results
Nineteen of 39 (49%) children had a brain MRI, 16 of 39 (41%) had CT, and four of 39 (10%) had both. Mean age was 6.8 years (S.D. = 4.8). Children with advanced HIV disease had higher odds of atrophy (odds ration [OR] 7.2, 95% confidence interval [CI] 1.1 to 48.3). Focal abnormalities were less likely in children receiving antiretroviral therapy (ART) (OR 0.22, 95% CI 0.05 to 1.0). Children with neurocognitive impairment were more likely to have atrophy (OR 8.4, 95% CI 1.3 to 55.4) and less likely to have focal abnormalities (OR 0.2, 95% CI 0.03 to 0.9).
Conclusions
Focal brain abnormalities on MRI were less likely in CLHIV on ART. Brain atrophy was the most common imaging abnormality, which was linked to severe neurocognitive impairment.
{"title":"Brain Imaging in New-Onset Seizure of Children Living With Human Immunodeficiency Virus in Zambia","authors":"Sarah Mohajeri MD, MPH , Michael Potchen MD , Izukanji Sikazwe MD , Samuel Kampondeni MD , Colleen Hoffman ARRT , David Bearden MD , Lisa Kalungwana MSc , Namwiya Musonda MS , Manoj Mathews MD , Musaku Mwenechanya MD , Ifunanya Dallah MPH , Brent Johnson PhD , Christopher Bositis MD , Jessie Huang BSc , Gretchen L. Birbeck MD, MPH","doi":"10.1016/j.pediatrneurol.2024.07.002","DOIUrl":"10.1016/j.pediatrneurol.2024.07.002","url":null,"abstract":"<div><h3>Background</h3><p>There are an estimated 1.5 million children living with human immunodeficiency virus (CLHIV), most residing in sub-Saharan Africa. A common hospital presentation of CLHIV is new-onset seizure, for which imaging is helpful but not routinely performed due to scarce resources. We present imaging findings and their association with clinical risk factors and outcomes in a cohort of Zambian CLHIV presenting with new-onset seizure.</p></div><div><h3>Methods</h3><p>In this prospective cohort study, participants were recruited at the University Teaching Hospital in Lusaka, Zambia. Various clinical and demographic characteristics were obtained. Computed tomography (CT), magnetic resonance imaging (MRI), or both were obtained during admission or shortly after discharge. If both studies were available, MRI data was used. Two neuroradiologists interpreted images using REDCap-based NeuroInterp, a tool that quantifies brain imaging findings. Age-dependent neuropsychologic assessments were administered.</p></div><div><h3>Results</h3><p>Nineteen of 39 (49%) children had a brain MRI, 16 of 39 (41%) had CT, and four of 39 (10%) had both. Mean age was 6.8 years (S.D. = 4.8). Children with advanced HIV disease had higher odds of atrophy (odds ration [OR] 7.2, 95% confidence interval [CI] 1.1 to 48.3). Focal abnormalities were less likely in children receiving antiretroviral therapy (ART) (OR 0.22, 95% CI 0.05 to 1.0). Children with neurocognitive impairment were more likely to have atrophy (OR 8.4, 95% CI 1.3 to 55.4) and less likely to have focal abnormalities (OR 0.2, 95% CI 0.03 to 0.9).</p></div><div><h3>Conclusions</h3><p>Focal brain abnormalities on MRI were less likely in CLHIV on ART. Brain atrophy was the most common imaging abnormality, which was linked to severe neurocognitive impairment.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"159 ","pages":"Pages 41-47"},"PeriodicalIF":3.2,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0887899424002534/pdfft?md5=7c954a9d958771bb5198164d5d9ebe55&pid=1-s2.0-S0887899424002534-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141693494","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}
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