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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]