-Related Developmental and Epileptic Encephalopathy: Expanding the Clinical Spectrum and Deciphering the Genotype-Phenotype.

Background And Objectives: developmental and epileptic encephalopathy (-DEE), also known as -related epileptic encephalopathy, is characterized by drug-resistant epilepsy with onset within the first year of life and severe psychomotor developmental delay. The condition is poorly understood, posing significant challenges to clinical management and prognosis. This study investigated genotype and phenotype correlations of individuals with -DEE to inform clinical care.

Cerebrospinal fluid metabolomics in autistic regression reveals dysregulation of sphingolipids and decreased β-hydroxybutyrate.

Background: Autism is highly heritable, however actionable genetic findings are only found in a minority of patients. Many people with autism suffer loss of neurodevelopmental skills, known as autistic regression. The cause of regression is poorly understood, and the diagnostic and therapeutic pathways are lacking.

Clinician Understanding, Acceptance and utilization of Ketogenic diet therapy for epilepsy in Australia and New Zealand: An online survey.

Ketogenic diet therapy (KDT) is an established treatment for people with epilepsy. As increasing evidence demonstrates effectiveness and safety of KDT on seizure reduction, cognition and behaviour, it is essential to evaluate factors hindering and supporting neurologists in prescribing KDT to strengthen quality, evidence-based, appropriate and equitable care. A study of Australian and New Zealand (ANZ) neurologists was undertaken via an online survey.

Solving the Etiology of Developmental and Epileptic Encephalopathy with Spike-Wave Activation in Sleep (D/EE-SWAS).

Objective: To understand the etiological landscape and phenotypic differences between 2 developmental and epileptic encephalopathy (DEE) syndromes: DEE with spike-wave activation in sleep (DEE-SWAS) and epileptic encephalopathy with spike-wave activation in sleep (EE-SWAS).

Methods: All patients fulfilled International League Against Epilepsy (ILAE) DEE-SWAS or EE-SWAS criteria with a Core cohort (n = 91) drawn from our Epilepsy Genetics research program, together with 10 etiologically solved patients referred by collaborators in the Expanded cohort (n = 101). Detailed phenotyping and analysis of molecular genetic results were performed.

Ketogenic diet modifies ribosomal protein dysregulation in KMT2D Kabuki syndrome.

Background: Kabuki syndrome (KS) is a genetic disorder caused by DNA mutations in KMT2D, a lysine methyltransferase that methylates histones and other proteins, and therefore modifies chromatin structure and subsequent gene expression. Ketones, derived from the ketogenic diet, are histone deacetylase inhibitors that can 'open' chromatin and encourage gene expression. Preclinical studies have shown that the ketogenic diet rescues hippocampal memory neurogenesis in mice with KS via the epigenetic effects of ketones.

Ketogenic Diets in Children With Intractable Epilepsy and its Effects on Gastrointestinal Function, Gut Microbiome, Inflammation, and Quality of Life.

Objectives: The ketogenic diet (KD) is a treatment for children with intractable epilepsy (IE), can cause gastrointestinal symptoms, and have an adverse effect on growth, nutrition and quality of life (QOL). This study investigated the extent of these side effects by comparing children with IE on KDs to their counterparts on normal diets.

Methods: Patients with IE were categorized into patients with KD or control groups.

Integration of EpiSign, facial phenotyping, and likelihood ratio interpretation of clinical abnormalities in the re-classification of an ARID1B missense variant.

Heterozygous ARID1B variants result in Coffin-Siris syndrome. Features may include hypoplastic nails, slow growth, characteristic facial features, hypotonia, hypertrichosis, and sparse scalp hair. Most reported cases are due to ARID1B loss of function variants.

Intraoperative Fluorescein Angiography Can Efficiently Identify Biomarkers and Guide Surgical Decision-Making.

Purpose: We sought to develop an efficient method for fluorescein angiography (FA) during digitally assisted vitreoretinal surgery (DAVS).

Methods: A 485-nm bandpass filter was placed into the filter holder of the accessory light sources of the Constellation Vision System with steel modified washers to produce an exciter source. A barrier filter was placed into the blank slot of a switchable laser filter with a 535-nm bandpass filter and another washer or created digitally with a specific color channel using NGENUITY software version 1.

Treatment of severe acute necrotizing encephalopathy of childhood with interleukin-6 receptor blockade in the first 24 h as add-on immunotherapy shows favorable long-term outcome at 2 years.

Background: Acute necrotizing encephalopathy (ANE) of childhood is a rare and devastating infection-associated acute encephalopathy. While there are no consensus treatments for ANE, recent case reports suggest a beneficial role for the use of tocilizumab, a recombinant humanized monoclonal antibody against the interleukin-6 (IL-6) receptor. The correlation of the timing of add-on tocilizumab in relation to long-term outcome has not been reported.

WWOX developmental and epileptic encephalopathy: Understanding the epileptology and the mortality risk.

Objective: WWOX is an autosomal recessive cause of early infantile developmental and epileptic encephalopathy (WWOX-DEE), also known as WOREE (WWOX-related epileptic encephalopathy). We analyzed the epileptology and imaging features of WWOX-DEE, and investigated genotype-phenotype correlations, particularly with regard to survival.

Methods: We studied 13 patients from 12 families with WWOX-DEE.

Urgent computed tomography angiography in paediatric stroke.

Aim: To improve delivery of acute therapies for acute ischaemic stroke (AIS).

Method: We identified factors influencing the speed of diagnosis and delivery of acute therapies in a prospective cohort of 21 children with suspected AIS (eight with AIS, 13 stroke mimics) and explored them in a retrospective cohort with confirmed AIS.

Results: Approximately half of the prospective and total AIS cohorts presented with acute, sustained hemiparesis, and were diagnosed relatively quickly.

The need for improved management of status epilepticus in children in Australia: Time from seizure onset to treatment is consistently delayed.

Aim: To determine if the management of paediatric status epilepticus (SE) follows accepted clinical practice guidelines.

Methods: Retrospective, consecutive series of patients with SE who attended the emergency departments from two NSW sites over a 12-month period. SE was defined as a convulsive seizure, 5 min or more in duration.

Diagnostic Yield of Whole Genome Sequencing After Nondiagnostic Exome Sequencing or Gene Panel in Developmental and Epileptic Encephalopathies.

Objective: To assess the benefits and limitations of whole genome sequencing (WGS) compared to exome sequencing (ES) or multigene panel (MGP) in the molecular diagnosis of developmental and epileptic encephalopathies (DEE).

Methods: We performed WGS of 30 comprehensively phenotyped DEE patient trios that were undiagnosed after first-tier testing, including chromosomal microarray and either research ES (n = 15) or diagnostic MGP (n = 15).

Results: Eight diagnoses were made in the 15 individuals who received prior ES (53%): 3 individuals had complex structural variants; 5 had ES-detectable variants, which now had additional evidence for pathogenicity.

Endovascular clot retrieval for acute ischaemic stroke due to basilar artery occlusion in childhood.

Endovascular clot retrieval (ECR) is an emerging therapy for treatment of acute ischaemic stroke (AIS) in adults, including basilar artery occlusion (BAO). Its role in children is not well established. We report four consecutive children with AIS due to BAO treated with ECR in Sydney, Australia.

Management of status epilepticus in children prior to medical retrieval: Deviations from the guidelines.

Aim: To evaluate the influence of adherence to treatment guidelines on outcomes in children presenting with status epilepticus (SE) using the Newborn and Paediatric Emergency Transport Service, New South Wales prospective registry.

Methods: We reviewed the treatment of children with SE, transported by the Newborn And Paediatric Emergency Transport Service to a tertiary paediatric hospital, over 1 year. We evaluated variation in management from the New South Wales clinical practice guideline.

Cannabidiol for treating drug-resistant epilepsy in children: the New South Wales experience.

Objective: To evaluate the tolerability and safety of cannabidiol for treating drug-resistant epilepsy in children, and to describe adverse events associated with such treatment.

Study Design: Prospective, open label cohort study.

Setting: Three tertiary NSW referral centres with paediatric neurology services.

Myotonic dystrophy type 1: clinical manifestations in children and adolescents.

Objective: Myotonic dystrophy type 1 (DM1) is an autosomal-dominant neuromuscular disease with variable severity affecting all ages; however, current care guidelines are adult-focused. The objective of the present study was to profile DM1 in childhood and propose a framework to guide paediatric-focused management.

Design, Setting And Patients: 40 children with DM1 (mean age 12.

Cost implications of PSA screening differ by age.

Background: Multiple guidelines seek to alter rates of prostate-specific antigen (PSA)-based prostate cancer screening. The costs borne by payers associated with PSA-based screening for men of different age groups-including the costs of screening and subsequent diagnosis, treatment, and adverse events-remain uncertain. We sought to develop a model of PSA costs that could be used by payers and health care systems to inform cost considerations under a range of different scenarios.

Outcomes of deviation from treatment guidelines in status epilepticus: A systematic review.

Objective: Due to a gap between published clinical guidelines on status epilepticus SE and clinician management of SE, a systematic review was performed to investigate treatment adherence to SE guidelines and its impact on patient outcomes.

Methods: Medline and Embase searches were conducted for studies appraising adherence to SE guidelines (from 1970 and 1st April 2018). The quality of eligible studies was assessed by QUADAS- 2 criteria.

A Mild PUM1 Mutation Is Associated with Adult-Onset Ataxia, whereas Haploinsufficiency Causes Developmental Delay and Seizures.

Certain mutations can cause proteins to accumulate in neurons, leading to neurodegeneration. We recently showed, however, that upregulation of a wild-type protein, Ataxin1, caused by haploinsufficiency of its repressor, the RNA-binding protein Pumilio1 (PUM1), also causes neurodegeneration in mice. We therefore searched for human patients with PUM1 mutations.

Cannabis for paediatric epilepsy: challenges and conundrums.

Research is expanding for the use of cannabidiol as an anticonvulsant drug. The mechanism of cannabidiol in paediatric epilepsy is unclear but is thought to play a role in modulation of synaptic transmission. Evidence for its efficacy in treating epilepsy is limited but growing, with a single pharmaceutical company-funded randomised double-blind controlled trial in children with Dravet syndrome.

Integrating exome sequencing into a diagnostic pathway for epileptic encephalopathy: Evidence of clinical utility and cost effectiveness.

Background: Epileptic encephalopathies are a devastating group of neurological conditions in which etiological diagnosis can alter management and clinical outcome. Exome sequencing and gene panel testing can improve diagnostic yield but there is no cost-effectiveness analysis of their use or consensus on how to best integrate these tests into clinical diagnostic pathways.

Methods: We conducted a retrospective cost-effectiveness study comparing trio exome sequencing with a standard diagnostic approach, for a well-phenotyped cohort of 32 patients with epileptic encephalopathy, who remained undiagnosed after "first-tier" testing.

Risk Factors for Peri-Procedural Arterial Ischaemic Stroke in Children with Cardiac Disease.

Improved survival of children with congenital heart disease has led to increasing focus on neurodevelopmental outcome, as close to half of the infants undergoing cardiac surgery are affected by neurodevelopmental disability. Stroke is particularly important as it frequently results in permanent neurologic sequelae. The aim of this study was to investigate risk factors for peri-procedural arterial ischaemic stroke (AIS) in children with cardiac disease.

Quality of life and excessive daytime sleepiness in children and adolescents with myotonic dystrophy type 1.

Objectives: Myotonic dystrophy type 1 (DM1) is an autosomal dominant neuromuscular disease with variable severity that affects all ages. Sleepiness is an important co-morbidity affecting a large proportion of paediatric DM1 patients. The current study examined the relationship between sleepiness and quality of life in a paediatric DM1 cohort.

Impact of a New Palliative Care Program on Health System Finances: An Analysis of the Palliative Care Program Inpatient Unit and Consultations at Johns Hopkins Medical Institutions.

Purpose: Palliative care inpatient units (PCUs) can improve symptoms, family perception of care, and lower per-diem costs compared with usual care. In March 2013, Johns Hopkins Medical Institutions (JHMI) added a PCU to the palliative care (PC) program. We studied the financial impact of the PC program on JHMI from March 2013 to March 2014.