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Purpose: To conduct a costing study comparing orthoptist-led with consultant-led clinics screening for optic pathway gliomas (OPGs) in children with neurofibromatosis Type 1 (NF1) attending the Royal Children's Hospital (RCH), Melbourne. Methods: Patients with NF1 examined in the orthoptist-led NF1 screening clinic and/or consultant-led clinics during the study period were identified. The workflow management software Q-Flow 6® provided data documenting patient's time spent with the orthoptist, nurse, and ophthalmologist. Time points were converted into minutes and multiplied by the cost-per-minute for each profession. A bottom-up micro-costing approach was used to estimate appointment level costs. Bootstrap simulations with 1000 replications were used to estimate 95% confidence intervals (CIs) for the difference in mean appointment time and cost between clinics. Results: Data for 130 consultant-led clinic appointments and 234 orthoptist-led clinic appointments were extracted for analysis. The mean time per appointment for the consultant-led clinic was 45.11 minutes, and the mean time per appointment for the orthoptist-led clinic was 25.85 minutes. The mean cost per appointment for the consultant-led clinic was A $84.15 (GBP £39.60) compared to the orthoptist-led clinic at A $20.40 (GBP £9.60). This represents a mean reduction of 19.25 minutes per appointment (95% CI, -24.85 to -13.66) and a mean reduction of A $63.75 (GBP £30.00) per appointment (95% CI, (A $-75.40 to $-52.10 [GBP £ -35.48 to £ -24.52]). Conclusion: An orthoptist-led clinic screening for OPGs in patients with NF1 can be a more cost-efficient model of care for ophthalmic screening in this patient group.
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OBJECTIVES: Despite the prevalence of cognitive symptoms in the idiopathic generalized epilepsies (IGEs), cognitive dysfunction in juvenile absence epilepsy (JAE), a common yet understudied IGE subtype, remains poorly understood. This descriptive study provides a novel, comprehensive characterization of cognitive functioning in a JAE sample and examines the relationship between cognition and 24-h epileptiform discharge load. METHOD: Forty-four individuals diagnosed with JAE underwent cognitive assessment using Woodcock Johnson III Test of Cognitive Abilities with concurrent 24-h ambulatory EEG monitoring. Generalized epileptiform discharges of any length, and prolonged generalized discharges ≥3 s were quantified across wakefulness and sleep. The relationship between standardized cognitive scores and epileptiform discharges was assessed through regression models. RESULTS: Cognitive performances in overall intellectual ability, acquired comprehension-knowledge, processing speed, long-term memory storage and retrieval, and executive processes were 0.63-1.07 standard deviation (SD) units lower in the JAE group compared to the population reference mean, adjusted for educational attainment. Prolonged discharges (≥3 s) were recorded in 20 patients (47.6%) from 42 available electroencephalography (EEG) studies and were largely unreported. Duration and number of prolonged discharges were associated with reduced processing speed and long-term memory storage and retrieval. SIGNIFICANCE: Cognitive dysfunction is seen in patients with JAE across various cognitive abilities, including those representing more stable processes like general intellect. During 24-h EEG, prolonged epileptiform discharges are common yet underreported in JAE despite treatment, and they show moderate effects on cognitive abilities. If epileptiform burden is a modifiable predictor of cognitive dysfunction, therapeutic interventions should consider quantitative 24-h EEG with routine neuropsychological screening. The growing recognition of the spectrum of neuropsychological comorbidities of IGE highlights the value of multidisciplinary approaches to explore the causes and consequences of cognitive deficits in epilepsy.
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Epilepsia Tipo Ausência , Humanos , Estudos Transversais , Eletroencefalografia , Cognição , Imunoglobulina ERESUMO
This study investigated sex and age differences in autistic behaviours in children with neurofibromatosis type 1 (NF1) who scored within the clinical range on the Social Responsiveness Scale - Second Edition (T score ≥ 60). Thirty-four males and 28 females (3-16 years) were assessed with the Autism Diagnostic Observation Schedule - Second Edition and Autism Diagnostic Interview - Revised. Across both measures, males exhibited greater social communication deficits relative to females. Age-related abatement of social communication difficulties was observed for males but not females. Conversely, no sex differences were found for restricted/repetitive behaviours, which were stable over time for both males and females. The findings are discussed within the context of broader neurodevelopmental considerations that are common in NF1.
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Transtorno do Espectro Autista , Transtorno Autístico , Neurofibromatose 1 , Masculino , Humanos , Criança , Transtorno Autístico/diagnóstico , Neurofibromatose 1/complicações , Neurofibromatose 1/diagnóstico , Comunicação , IdiomaRESUMO
Childhood apraxia of speech (CAS), the prototypic severe childhood speech disorder, is characterized by motor programming and planning deficits. Genetic factors make substantive contributions to CAS aetiology, with a monogenic pathogenic variant identified in a third of cases, implicating around 20 single genes to date. Here we aimed to identify molecular causation in 70 unrelated probands ascertained with CAS. We performed trio genome sequencing. Our bioinformatic analysis examined single nucleotide, indel, copy number, structural and short tandem repeat variants. We prioritised appropriate variants arising de novo or inherited that were expected to be damaging based on in silico predictions. We identified high confidence variants in 18/70 (26%) probands, almost doubling the current number of candidate genes for CAS. Three of the 18 variants affected SETBP1, SETD1A and DDX3X, thus confirming their roles in CAS, while the remaining 15 occurred in genes not previously associated with this disorder. Fifteen variants arose de novo and three were inherited. We provide further novel insights into the biology of child speech disorder, highlighting the roles of chromatin organization and gene regulation in CAS, and confirm that genes involved in CAS are co-expressed during brain development. Our findings confirm a diagnostic yield comparable to, or even higher, than other neurodevelopmental disorders with substantial de novo variant burden. Data also support the increasingly recognised overlaps between genes conferring risk for a range of neurodevelopmental disorders. Understanding the aetiological basis of CAS is critical to end the diagnostic odyssey and ensure affected individuals are poised for precision medicine trials.
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Apraxias , Distúrbios da Fala , Criança , Humanos , Distúrbios da Fala/genética , Apraxias/genética , Mapeamento Cromossômico , Causalidade , Encéfalo , Histona-Lisina N-MetiltransferaseRESUMO
BACKGROUND: A high proportion of patients with neurofibromatosis type 1 (NF1) present with functional hearing deficiency as a result of neural abnormality in the late auditory brainstem. METHODS: In this randomized, two-period crossover study, we investigated the hypothesis that remote-microphone listening devices can ameliorate hearing and communication deficits in affected school-aged children (7-17 years). Speech perception ability in background noise was evaluated in device-active and inactive conditions using the CNC-word test. Participants were then randomized to one of two treatment sequences: (1) inactive device for two weeks (placebo), followed by active device use for two weeks, or (2) active device for 2 weeks, followed by inactive device for 2 weeks. Listening and communication ratings (LIFE-R Questionnaire) were obtained at baseline and at the end of each treatment phase. RESULTS: Each participant demonstrated functional hearing benefits with remote-microphone use. All showed a speech perception in noise increase when the device was activated with a mean phoneme-score difference of 16.4% (p < 0.001) and reported improved listening/communication abilities in the school classroom (mean difference: 23.4%; p = 0.017). DISCUSSION: Conventional hearing aids are typically ineffective as a treatment for auditory neural dysfunction, making sounds louder, but not clearer for affected individuals. In this study, we demonstrate that remote-microphone technologies are acceptable/tolerable in pediatric patients with NF1 and can ameliorate their hearing deficits. CONCLUSION: Remote-microphone listening systems offer a viable treatment option for children with auditory deficits associated with NF1.
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Auxiliares de Audição , Neurofibromatose 1 , Percepção da Fala , Percepção Auditiva , Criança , Estudos Cross-Over , Humanos , Neurofibromatose 1/complicações , Neurofibromatose 1/terapia , Percepção da Fala/fisiologiaRESUMO
BACKGROUND: Existing research has demonstrated elevated autistic behaviours in children with neurofibromatosis type 1 (NF1), but the autistic phenotype and its relationship to other neurodevelopmental manifestations of NF1 remains unclear. To address this gap, we performed detailed characterisation of autistic behaviours in children with NF1 and investigated their association with other common NF1 child characteristics. METHODS: Participants were drawn from a larger cross-sectional study examining autism in children with NF1. The population analysed in this study scored above threshold on the Social Responsiveness Scale-Second Edition (T-score ≥ 60; 51% larger cohort) and completed the Autism Diagnostic Interview-Revised (ADI-R) and/or the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2). All participants underwent evaluation of their intellectual function, and behavioural data were collected via parent questionnaires. RESULTS: The study cohort comprised 68 children (3-15 years). Sixty-three per cent met the ADOS-2 'autism spectrum' cut-off, and 34% exceeded the more stringent threshold for 'autistic disorder' on the ADI-R. Social communication symptoms were common and wide-ranging, while restricted and repetitive behaviours (RRBs) were most commonly characterised by 'insistence on sameness' (IS) behaviours such as circumscribed interests and difficulties with minor changes. Autistic behaviours were weakly correlated with hyperactive/impulsive attention deficit hyperactivity disorder (ADHD) symptoms but not with inattentive ADHD or other behavioural characteristics. Language and verbal IQ were weakly related to social communication behaviours but not to RRBs. LIMITATIONS: Lack of genetic validation of NF1, no clinical diagnosis of autism, and a retrospective assessment of autistic behaviours in early childhood. CONCLUSIONS: Findings provide strong support for elevated autistic behaviours in children with NF1. While these behaviours were relatively independent of other NF1 comorbidities, the importance of taking broader child characteristics into consideration when interpreting data from autism-specific measures in this population is highlighted. Social communication deficits appear similar to those observed in idiopathic autism and are coupled with a unique RRB profile comprising prominent IS behaviours. This autistic phenotype and its relationship to common NF1 comorbidities such as anxiety and executive dysfunction will be important to examine in future research. Current findings have important implications for the early identification of autism in NF1 and clinical management.
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Transtorno Autístico , Neurofibromatose 1 , Transtorno Autístico/genética , Pré-Escolar , Estudos Transversais , Humanos , Neurofibromatose 1/complicações , Neurofibromatose 1/diagnóstico , Fenótipo , Estudos RetrospectivosRESUMO
Importance: Neurofibromatosis type 1 (NF1) affects hearing through disruption of central auditory processing. The mechanisms, functional severity, and management implications are unclear. Objective: To investigate auditory neural dysfunction and its perceptual consequences in individuals with NF1. Design, Setting, and Participants: This case-control study included children and adults with NF1 and control participants matched on age, sex, and hearing level. Patients were recruited through specialist neurofibromatosis and neurogenetic outpatient clinics between April and September 2019. An evaluation of auditory neural activity, monaural/binaural processing, and functional hearing was conducted. Diffusion-weighted magnetic resonance imaging (MRI) data were collected from a subset of participants (10 children with NF1 and 10 matched control participants) and evaluated using a fixel-based analysis of apparent fiber density. Main Outcomes and Measures: Type and severity of auditory dysfunction evaluated via laboratory testing and questionnaire data. Results: A total of 44 participants (18 [41%] female individuals) with NF1 with a mean (SD) age of 16.9 (10.7) years and 44 control participants (18 [41%] female individuals) with a mean (SD) age of 17.2 (10.2) years were included in the study. Overall, 11 participants (25%) with NF1 presented with evidence of auditory neural dysfunction, including absent, delayed, or low amplitude electrophysiological responses from the auditory nerve and/or brainstem, compared with 1 participant (2%) in the control group (odds ratio [OR], 13.03; 95% CI, 1.59-106.95). Furthermore, 14 participants (32%) with NF1 showed clinically abnormal speech perception in background noise compared with 1 participant (2%) in the control group (OR, 20.07; 95% CI, 2.50-160.89). Analysis of diffusion-weighted MRI data of participants with NF1 showed significantly lower apparent fiber density within the ascending auditory brainstem pathways. The regions identified corresponded to the neural dysfunction measured using electrophysiological assessment. Conclusions and Relevance: The findings of this case-control study could represent new neurobiological and clinical features of NF1. Auditory dysfunction severe enough to impede developmental progress in children and restrict communication in older participants is a common neurobiological feature of the disorder.
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Potenciais Evocados Auditivos/fisiologia , Transtornos da Audição/diagnóstico , Transtornos da Audição/etiologia , Neurofibromatose 1/complicações , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Feminino , Transtornos da Audição/fisiopatologia , Humanos , Masculino , Neurofibromatose 1/fisiopatologia , Testes Neuropsicológicos , Adulto JovemRESUMO
PURPOSE: The leading cause of early death in patients with neurofibromatosis type 1 (NF1) is malignant peripheral nerve sheath tumor (MPNST). The principles of management include early diagnosis, surgical clearance and close monitoring for tumor recurrence. Current methods for diagnosis, detection of residual disease and monitoring tumor burden are inadequate, as clinical and radiological features are non-specific for malignancy in patients with multiple tumors and lack the sensitivity to identify early evidence of malignant transformation or tumor recurrence. Circulating tumor DNA (ctDNA) is a promising tool in cancer management and has the potential to improve the care of patients with NF1. In the following article we summarise the current understanding of the genomic landscape of MPNST, report on the previous literature of ctDNA in MPNST and outline the potential clinical applications for ctDNA in NF1 associated MPNST. Finally, we describe our prospective cohort study protocol investigating the utility of using ctDNA as an early diagnostic tool for MPNSTs in NF1 patients.
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Neurofibromatose 1 , Neurofibrossarcoma , DNA Tumoral Circulante/genética , Humanos , Recidiva Local de Neoplasia , Neoplasias de Bainha Neural/diagnóstico , Neoplasias de Bainha Neural/genética , Neurofibromatose 1/complicações , Neurofibromatose 1/diagnóstico , Neurofibromatose 1/genética , Neurofibrossarcoma/diagnóstico por imagem , Neurofibrossarcoma/etiologia , Neurofibrossarcoma/genética , Estudos ProspectivosRESUMO
RNA sequencing (RNAseq) is emerging as a complementary tool to DNA sequencing, providing utility in diagnosis for disorders such as neuronal ceroid lipofuscinosis CLN2 disease. We describe an individual with a presentation suggestive of an attenuated CLN2 phenotype, including a history of regression, recent-onset microcephaly and spasticity from age five years. Exome sequencing revealed two variants inherited in trans in TPP1, NM_000391.4:c.225A>G; p.(Gln75 = ) and NM_000391.4:c.1012C>G; p.(Gln338Glu), both classified as variants of uncertain significance. TPP1 activity was found to be significantly reduced in fibroblasts of the affected individual. RNAseq was performed to assess the impact of compound heterozygous variants in TPP1 and enabled the identification of three aberrant splicing events. The c.225A>G variant introduces a 5 nucleotide truncation of exon 3 and a loss of reading frame. The majority of CLN2 transcripts exclude either exon 8 or exons 7-8, resulting in large in-frame deletions. Isoform specific RT-PCR confirmed the aberrant splicing events are mutually exclusive, suggesting that the paternal exon 8 c.1012C>G variant results in exon skipping. This case study demonstrates how RNAseq can be used as an orthogonal test to inform the interpretation of some variants of unknown significance and its particular importance in disorders where effective disease management requires early diagnosis.
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Aminopeptidases/genética , Dipeptidil Peptidases e Tripeptidil Peptidases/genética , Mutação , Lipofuscinoses Ceroides Neuronais/genética , Splicing de RNA , Serina Proteases/genética , Aminopeptidases/metabolismo , Células Cultivadas , Criança , Dipeptidil Peptidases e Tripeptidil Peptidases/metabolismo , Feminino , Humanos , Lipofuscinoses Ceroides Neuronais/patologia , Serina Proteases/metabolismo , Tripeptidil-Peptidase 1RESUMO
OBJECTIVE: We investigated the possible significance of rare genetic variants to response to valproic acid (VPA) and ethosuximide (ETX) in patients with absence epilepsy. Our primary hypothesis was that rare CACNA1H variants are more frequent in ETX-non-responsive patients compared to ETX-responsive. Our secondary hypothesis was that rare variants in GABA-receptor genes are more frequent in VPA-non-responsive patients compared to VPA-responsive. METHODS: We recruited patients with absence epilepsy treated with both VPA and ETX, and performed whole exome sequencing in order to investigate the potential role of rare variants in CACNA1H, other voltage-gated calcium channel (VGCC) genes, or GABA-receptor genes in predicting response to ETX or VPA. RESULTS: Sixty-two patients were included; 12 were ETX-responsive, 14 VPA-responsive, and 36 did not have a clear positive response to either medication. We did not find significant enrichment inCACNA1H rare variants in ETX-responsive patients (odds ratio 3.43; 0.43-27.65; p = 0.20), nor was there enrichment for other VGCC genes. No significant enrichment of GABA-receptor gene rare variants was seen for VPA-non-responsive patients versus VPA-responsive. We found enrichment of rare GABA-receptor variants in our absence cohort compared to controls (odds ratio 3.82; 1.68-8.69). There was no difference in frequency of CACNA1H rs61734410 and CACNA1I rs3747178 polymorphisms between ETX-responsive and ETX-non-responsive groups; these polymorphisms have previously been reported to predict lack of response to ETX in absence epilepsy. SIGNIFICANCE: We conclude that if CACNA1H rare variants predict lack of response to ETX, a larger sample is necessary to test this with sufficient power. Increased GABA-receptor gene rare variant frequency in absence epilepsy patients who fail initial anti-seizure therapy suggests subtle GABA receptor dysfunction may contribute to the underlying pathophysiology.
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Epilepsia Tipo Ausência , Anticonvulsivantes/uso terapêutico , Epilepsia Tipo Ausência/tratamento farmacológico , Epilepsia Tipo Ausência/genética , Etossuximida/uso terapêutico , Humanos , Preparações Farmacêuticas , Ácido Valproico/uso terapêutico , Ácido gama-AminobutíricoRESUMO
OBJECTIVE: To study the epilepsy syndromes among the severe epilepsies of infancy and assess their incidence, etiologies, and outcomes. METHODS: A population-based cohort study was undertaken of severe epilepsies with onset before age 18 months in Victoria, Australia. Two epileptologists reviewed clinical features, seizure videos, and electroencephalograms to diagnose International League Against Epilepsy epilepsy syndromes. Incidence, etiologies, and outcomes at age 2 years were determined. RESULTS: Seventy-three of 114 (64%) infants fulfilled diagnostic criteria for epilepsy syndromes at presentation, and 16 (14%) had "variants" of epilepsy syndromes in which there was one missing or different feature, or where all classical features had not yet emerged. West syndrome (WS) and "WS-like" epilepsy (infantile spasms without hypsarrhythmia or modified hypsarrhythmia) were the most common syndromes, with a combined incidence of 32.7/100 000 live births/year. The incidence of epilepsy of infancy with migrating focal seizures (EIMFS) was 4.5/100 000 and of early infantile epileptic encephalopathy (EIEE) was 3.6/100 000. Structural etiologies were common in "WS-like" epilepsy (100%), unifocal epilepsy (83%), and WS (39%), whereas single gene disorders predominated in EIMFS, EIEE, and Dravet syndrome. Eighteen (16%) infants died before age 2 years. Development was delayed or borderline in 85 of 96 (89%) survivors, being severe-profound in 40 of 96 (42%). All infants with EIEE or EIMFS had severe-profound delay or were deceased, but only 19 of 64 (30%) infants with WS, "WS-like," or "unifocal epilepsy" had severe-profound delay, and only two of 64 (3%) were deceased. SIGNIFICANCE: Three quarters of severe epilepsies of infancy could be assigned an epilepsy syndrome or "variant syndrome" at presentation. In this era of genomic testing and advanced brain imaging, diagnosing epilepsy syndromes at presentation remains clinically useful for guiding etiologic investigation, initial treatment, and prognostication.
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Deficiências do Desenvolvimento/epidemiologia , Epilepsias Mioclônicas/epidemiologia , Espasmos Infantis/epidemiologia , Anticonvulsivantes/uso terapêutico , Pré-Escolar , Estudos de Coortes , Deficiências do Desenvolvimento/etiologia , Deficiências do Desenvolvimento/fisiopatologia , Progressão da Doença , Eletroencefalografia , Epilepsias Mioclônicas/tratamento farmacológico , Epilepsias Mioclônicas/etiologia , Epilepsias Mioclônicas/fisiopatologia , Síndromes Epilépticas/tratamento farmacológico , Síndromes Epilépticas/epidemiologia , Síndromes Epilépticas/etiologia , Síndromes Epilépticas/fisiopatologia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Síndrome de Lennox-Gastaut/tratamento farmacológico , Síndrome de Lennox-Gastaut/epidemiologia , Síndrome de Lennox-Gastaut/etiologia , Síndrome de Lennox-Gastaut/fisiopatologia , Masculino , Malformações do Desenvolvimento Cortical/complicações , Malformações do Desenvolvimento Cortical/epidemiologia , Malformações do Desenvolvimento Cortical/cirurgia , Mortalidade , Índice de Gravidade de Doença , Espasmos Infantis/tratamento farmacológico , Espasmos Infantis/etiologia , Espasmos Infantis/fisiopatologia , Vitória/epidemiologiaRESUMO
INTRODUCTION: Children with epilepsy report lower health-related quality of life (QOL) compared with healthy children and those with other chronic disorders. This study piloted the recently published Pediatric Quality of Life Inventory (PedsQL) Epilepsy Module (PedsQL-EM) in an ambulatory setting and studied epilepsy-related factors contributing to QOL in children with epilepsy. METHODS: Children with epilepsy aged 8-18â¯years who were ambulant and verbal were recruited from pediatric neurology clinics. Children and their caregivers completed age-appropriate versions of the PedsQL-EM (8-12 or 13-18â¯years) in the clinic waiting area. Treating neurologists completed medical questionnaires about their patients' epilepsy. RESULTS: We collected 151 parent-report and 127 self-report PedsQL-EMs. Administration time was 5-10â¯min with some children receiving assistance from the researcher. Mean age of children was 12.9+/-3.0, with 77 females (51%). Parents reported lower mean QOL scores across all subdomains compared with their children. Parents reported significantly lower QOL for children with earlier age at epilepsy onset, longer epilepsy duration, presence of seizures during the last month, more severe epilepsy, increased number of antiepileptic drugs (AEDs), and cognitive comorbidity. The same factors impacted on child self-reporting, but with more variability across subdomains. CONCLUSIONS: The PedsQL-EM is an epilepsy-specific measure of QOL that is quick and easy to administer and is sensitive to the clinical factors reported to impact on QOL in pediatric epilepsy.
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Assistência Ambulatorial/normas , Epilepsia/psicologia , Pais/psicologia , Qualidade de Vida/psicologia , Autorrelato/normas , Inquéritos e Questionários/normas , Adolescente , Assistência Ambulatorial/métodos , Cuidadores/psicologia , Criança , Epilepsia/diagnóstico , Epilepsia/terapia , Feminino , Humanos , Masculino , Neurologistas/normas , Pediatras/normasRESUMO
INTRODUCTION: Children with the single-gene disorder neurofibromatosis type 1 (NF1) appear to be at an increased risk for autism spectrum disorder (ASD) and exhibit a unique social-cognitive phenotype compared with children with idiopathic ASD. A complete framework is required to better understand autism in NF1, from neurobiological levels through to behavioural and functional outcomes. The primary aims of this study are to establish the frequency of ASD in children with NF1, examine the social cognitive phenotype, investigate the neuropsychological processes contributing to ASD symptoms and poor social functioning in children with NF1, and to investigate novel structural and functional neurobiological markers of ASD and social dysfunction in NF1. The secondary aim of this study is to compare the neuropsychological and neurobiological features of ASD in children with NF1 to a matched group of patients with idiopathic ASD. METHODS AND ANALYSIS: This is an international, multisite, prospective, cross-sectional cohort study of children with NF1, idiopathic ASD and typically developing (TD) controls. Participants will be 200 children with NF1 (3-15 years of age), 70 TD participants (3-15 years) and 35 children with idiopathic ASD (7-15 years). Idiopathic ASD and NF1 cases will be matched on age, sex and intelligence. All participants will complete cognitive testing and parents will rate their child's behaviour on standardised questionnaires. Neuroimaging will be completed by a subset of participants aged 7 years and older. Children with NF1 that screen at risk for ASD on the parent-rated Social Responsiveness Scale 2nd Edition will be invited back to complete the Autism Diagnostic Observation Scale 2nd Edition and Autism Diagnostic Interview-Revised to determine whether they fulfil ASD diagnostic criteria. ETHICS AND DISSEMINATION: This study has hospital ethics approval and the results will be disseminated through peer-reviewed publications and international conferences.
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Transtorno do Espectro Autista/etiologia , Comportamento Infantil , Cognição , Neurofibromatose 1/complicações , Fenótipo , Comportamento Social , Adolescente , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/fisiopatologia , Transtorno do Espectro Autista/psicologia , Transtorno Autístico/psicologia , Criança , Desenvolvimento Infantil , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Sistema Nervoso/fisiopatologia , Neurofibromatose 1/fisiopatologia , Neurofibromatose 1/psicologia , Estudos Prospectivos , Projetos de PesquisaRESUMO
BACKGROUND: Focal areas of T2 hyperintensity are seen on magnetic resonance imaging (MRI) in patients with neurofibromatosis type 1 (NF1). These lesions are commonly known as "unidentified bright objects" of the brain. We have seen similar lesions in the spinal cord of the same patient population. Our aim was to determine the prevalence and characterize the imaging features of these T2 hyperintense spinal cord lesions in children with NF1. METHODS: A search of our hospital's medical imaging database yielded all children with NF1 and MRI of the brain and/or spine between February 2014 and April 2017. Medical imaging was reviewed for T2 hyperintense signal changes and medical records were reviewed of those children with T2 hyperintense spinal cord lesions. RESULTS: During the study period 155 children underwent a brain MRI and 72 had a spine MRI. One hundred twenty-three (79%) showed multiple cerebral T2 hyperintense lesions and six (8%) had non-contrast enhancing spinal cord T2 hyperintensities with five children having had a follow-up scan. The one child without follow-up imaging was not further pursued. Interval scanning showed stable appearance of the spinal cord lesions in four children and signal reduction in one child. All five children with T2 hyperintense changes in the spinal cord had an MRI brain and all (100%) also exhibited cerebral T2 hyperintensities. CONCLUSIONS: Focal areas of signal hyperintensity in the spinal cord are the corollary of the better described cerebral T2 hyperintensities in individuals with NF1.
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Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Neurofibromatose 1/diagnóstico por imagem , Medula Espinal/diagnóstico por imagem , Adolescente , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/epidemiologia , Criança , Pré-Escolar , Seguimentos , Humanos , Neurofibromatose 1/epidemiologia , Prevalência , Neoplasias da Medula Espinal/diagnóstico por imagem , Neoplasias da Medula Espinal/epidemiologiaRESUMO
PURPOSE: Status epilepticus (SE) is a paediatric emergency with significant morbidity and mortality. Recommendations beyond first line care are not based on high quality evidence. Emergency physicians and neurologists are key stakeholders in managing this condition. A collaborative, widely consulted approach to identifying priorities can help direct limited research funds appropriately. The objectives of this study are to identify consensus research priorities in paediatric SE among experts and health consumers. METHODS: A three-stage Delphi process was conducted. Paediatric Neurologists and Emergency Physicians in Australia and New Zealand participated. Round one asked participants to generate three research questions important for further research in paediatric status epilepticus. Responses were refined into unique individual questions. Rounds two and three required participants to rate questions on a seven point ordinal scale. Health consumers were invited to participate by providing up to three problem areas that could be addressed by research. RESULTS: 54 experts and 76 health consumers participated in the process. Nine questions reached our definition of consensus "high priority", 21 questions achieved consensus "low priority" and seven questions did not achieve consensus. High priority areas included second line management including levetiracetam (efficacy, dose and timing), use of third line agents, induction of anaesthesia (timing and best agent), management of focal SE, and indicators of "subtle SE". Consumer priority areas included themes of treatment efficacy, aetiology, and community education. CONCLUSION: We identified nine priority research questions in paediatric SE, congruent with the health consumer theme of treatment efficacy. Future research efforts should be directed towards these priority areas.
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Consenso , Relações Profissional-Paciente , Pesquisa/normas , Estado Epiléptico/diagnóstico , Inquéritos e Questionários , Adolescente , Adulto , Distribuição por Idade , Idoso , Austrália/epidemiologia , Técnica Delphi , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Pediatria/métodos , Pediatria/normas , Estado Epiléptico/epidemiologia , Estado Epiléptico/psicologia , Adulto JovemAssuntos
Hidróxidos/intoxicação , Hiperemia/complicações , Compostos de Potássio/intoxicação , Doenças da Medula Espinal/etiologia , Doença Aguda , Adolescente , Humanos , Hiperemia/diagnóstico por imagem , Hiperemia/tratamento farmacológico , Masculino , Doenças da Medula Espinal/diagnóstico por imagem , Doenças da Medula Espinal/tratamento farmacológico , SíndromeRESUMO
A 5-year-old boy with standard-risk B-cell acute lymphoblastic anemia developed fever during induction chemotherapy. The patient had no neurological symptoms. Blood cultures grew Bacillus cereus and neuroimaging studies demonstrated a cerebral abscess. Imaging changes resolved after completion of antibiotics. Bacillus cereus bacteremia is increasingly implicated as the cause of life-threatening infections, including cerebral abscesses, in compromised patients. Positive blood cultures for this organism should prompt neuroimaging and consideration of cerebrospinal fluid sampling, as well as catheter removal. Given the worse outcome with central nervous system involvement, there is a need for increased awareness and early diagnosis, particularly in immunocompromised individuals.