Genomic answers for children: Dynamic analyses of >1000 pediatric rare disease genomes.

PURPOSE: This study aimed to provide comprehensive diagnostic and candidate analyses in a pediatric rare disease cohort through the Genomic Answers for Kids program. METHODS: Extensive analyses of 960 families with suspected genetic disorders included short-read exome sequencing and short-read genome sequencing (srGS); PacBio HiFi long-read genome sequencing (HiFi-GS); variant calling for single nucleotide variants (SNV), structural variant (SV), and repeat variants; and machine-learning variant prioritization. Structured phenotypes, prioritized variants, and pedigrees were stored in PhenoTips database, with data sharing through controlled access the database of Genotypes and Phenotypes. RESULTS: Diagnostic rates ranged from 11% in patients with prior negative genetic testing to 34.5% in naive patients. Incorporating SVs from genome sequencing added up to 13% of new diagnoses in previously unsolved cases. HiFi-GS yielded increased discovery rate with >4-fold more rare coding SVs compared with srGS. Variants and genes of unknown significance remain the most common finding (58% of nondiagnostic cases). CONCLUSION: Computational prioritization is efficient for diagnostic SNVs. Thorough identification of non-SNVs remains challenging and is partly mitigated using HiFi-GS sequencing. Importantly, community research is supported by sharing real-time data to accelerate gene validation and by providing HiFi variant (SNV/SV) resources from >1000 human alleles to facilitate implementation of new sequencing platforms for rare disease diagnoses.

Posters of the 2020 American Association of Neuroscience Nurses Annual Meeting: The Year There Was No Wall on Which to Hang Them.

The 2020 annual meeting of the American Association of Neuroscience Nurses was canceled because of the COVID-19 pandemic. This is a summary of 27 abstracts presented in poster format that were accepted to that meeting.

The Efficacy and Safety of Rapid Cycling Vagus Nerve Stimulation in Children With Intractable Epilepsy.

PURPOSE: Vagus nerve stimulation (VNS) is an effective adjunctive therapy for drug-resistant epilepsy. Nevertheless, information is lacking regarding optimization of stimulation parameters to improve efficacy. Our study examines the safety and efficacy of rapid duty cycle VNS (OFF time ≤1.1 minute keeping duty cycle less than 50%) in pediatric cohort with intractable epilepsy. METHODS: Retrospective chart review of 50 patients (one to 17 years) with drug-resistant epilepsy treated with VNS between 2010 and 2015 at a single pediatric epilepsy center. Safety and tolerability data were aggregated across all patient visits to determine frequency of adverse events between differing duty cycles. We also compared seizure reduction rates for each patient at (1) last regular duty cycle visit, (2) first rapid duty cycle visit, and (3) last recorded rapid duty cycle visit. RESULTS: Rapid duty cycle was well tolerated, with no adverse events reported in 96.6% patient encounters. At the last visit before switching to rapid duty cycle 45.5% patients were showing response to VNS (seizure reduction rates ≥50%). This rate increased to 77.3% after switching to rapid duty cycle and remained at 77.4% at the last rapid duty cycle visit. Fifteen patients (34.1%) became responders to VNS after switching to rapid cycling; another 19 (43.2%) maintained their response with mostly improved seizure reduction rates. In only a few instances, responders became nonresponders after switching to rapid duty cycle. CONCLUSIONS: Rapid duty cycle VNS is probably safe and well tolerated; it may also be more efficacious than regular cycling VNS in some patients. This study highlights the necessity of prospective, long-term, double-blinded studies for understanding the advantages of this VNS modality.

Standardized Screening for Depression in Pediatric Epilepsy.

INTRODUCTION: Depression is a common comorbidity of epilepsy that is under-recognized and under-diagnosed. To improve recognition, a brief screening tool, the Neurological Disorders Depression Inventory-Epilepsy-Youth (NDDI-E-Y) was implemented in a level-IV pediatric epilepsy clinic. METHOD: This quality improvement is a pre-post design measuring the impact of standardized depression screening, via the NDDI-E-Y tool, in youth 12-17 years with epilepsy. Those with positive screens, scores > 32, received social work evaluation and mental health resources. Education was provided to all patients in standard discharge paperwork. RESULTS: Of N = 176 patients evaluated, n = 112 met criteria to complete the NDDI-E-Y. Fifteen percent (n = 17) of patients had positive screens, suggesting that they are at risk for depression. DISCUSSION: Depression is a challenge when managing patients with epilepsy and may impact their quality of life and seizure control. Routine depression screening is recommended and feasible in the outpatient setting with a standardized work process.

Reflections on 50 Years of Pediatric Neuroscience Nursing.

Throughout the past 50 years, the role of the neuroscience nurse has become more specialized as we continue to keep pace with new innovations and improvement in care for our patients. This is evident when reviewing the hundreds of articles that have been published in the Journal of Neuroscience Nursing over the last half-century. These authors have had a tremendous influence over neuroscience nursing through dissemination of their expert knowledge. This article will review the areas of pediatric hydrocephalus, brain tumors, and epilepsy and the role neuroscience nurses have played in the advancement of these specialties.

Use of the ketogenic diet in the neonatal intensive care unit-Safety and tolerability.

Drug-resistant epilepsy poses a challenge in neonatal patients, especially those in the neonatal intensive care unit (NICU), who have various secondary comorbidities. We present results of four children with a history of drug-resistant epilepsy for whom a ketogenic diet was initiated and used in the NICU. A nonfasting induction into ketosis over 1-2 weeks was utilized, with gradual increases in the ketogenic ratio every 2-3 days. Data were collected retrospectively from a database, which included medical history, daily progress notes, relevant laboratory data, and imaging and diagnostic information. The ketogenic diet was well tolerated in all cases. The most common side effects observed were constipation, hypoglycemia, and weight loss. Serum ß-hydroxybutyrate levels demonstrated improved reliability as a marker of ketosis when compared to urine ketones in this population. Perceived benefits to the infants included improved seizure control, increased alertness, and decreased need for invasive respiratory support. These cases demonstrate that the use of the ketogenic diet for treatment of neonatal encephalopathy and refractory epilepsy can be undertaken safely in the NICU and is well tolerated by carefully screened neonates and infants.