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Abstract Background The COVID-19 pandemic forced healthcare institutions and many clinical research programs to adopt telehealth modalities in order to mitigate viral spread. With the expanded use of telehealth, there is the potential to increase access to genomic medicine to medically underserved populations, yet little is known about how best to communicate genomic results via telehealth while also ensuring equitable access. NYCKidSeq, a multi-institutional clinical genomics research program in New York City, launched the TeleKidSeq pilot study to assess alternative forms of genomic communication and telehealth service delivery models with families from medically underserved populations. Methods We aim to enroll 496 participants between 0 and 21 years old to receive clinical genome sequencing. These individuals have a neurologic, cardiovascular, and/or immunologic disease. Participants will be English- or Spanish-speaking and predominantly from underrepresented groups who receive care in the New York metropolitan area. Prior to enrollment, participants will be randomized to either genetic counseling via videoconferencing with screen-sharing or genetic counseling via videoconferencing without screen-sharing. Using surveys administered at baseline, results disclosure, and 6-months post-results disclosure, we will evaluate the impact of the use of screen-sharing on participant understanding, satisfaction, and uptake of medical recommendations, as well as the psychological and socioeconomic implications of obtaining genome sequencing. Clinical utility, cost, and diagnostic yield of genome sequencing will also be assessed. Discussion The TeleKidSeq pilot study will contribute to innovations in communicating genomic test results to diverse populations through telehealth technology. In conjunction with NYCKidSeq, this work will inform best practices for the implementation of genomic medicine in diverse, English- and Spanish-speaking populations.

Abstract Objective Antiseizure medications (ASMs) remain the mainstay of epilepsy treatment. These ASMs have mainly been tested in trials in adults with epilepsy, which subsequently led to market authorization (MA). For treatment of – especially young – children with epilepsy, several ASMs do not have a MA and guidelines are lacking, subsequently leading to “off‐label” use of ASMs. Even though “off‐label” ASM prescriptions for children could lead to more adverse events, it can be clinically appropriate and rational if the benefits outweigh the risks. This could be the case if “on‐label” ASM, in mono‐ or polytherapy, fails to achieve adequate seizure control. Methods The Medical Therapies Task Force of the International League Against Epilepsy (ILAE) Commission for Pediatrics performed a survey to study the current treatment practices in six classic, early life epilepsy scenarios. Our aim was not only to study first‐ and second‐line treatment preferences but also to illustrate the use of “off‐label” drugs in childhood epilepsies. Results Our results reveal that several ASMs (e.g. topiramate, oxcarbazepine, benzodiazepines) are prescribed “off‐label” in distinct scenarios of young children with epilepsy. In addition, recent scientific guidelines were not always adopted by several survey respondents, suggesting a potential knowledge gap. Significance We report the relatively common use of “off‐label” prescriptions that underlines the need for targeted and appropriately designed clinical trials, including younger patients, which will also result in the ability to generate evidence‐based guidelines.

Abstract Genetics is rapidly evolving and is actively playing a role in how we diagnose and manage epilepsy. The definition of an epilepsy syndrome has changed throughout the years. The International League Against Epilepsy (ILAE) has developed a classification of the epilepsies and has recently described specific epilepsy syndromes taking into account emerging genetic information which is rapidly evolving as well as etiology-specific syndromes. Understanding genetics can help clarify the syndrome and its treatment. This review provides a history of the definition of a syndrome, and the evolving contribution of genetic information that is part of the syndromic classification. We provide few examples of several phenotypes/genotypes of epilepsy syndromes in infancy and childhood and treatment issues that may arise from the available genetic information. Epilepsy syndromes and their genetics have been rapidly changing as new gene technologies are being developed. Understanding genetics can help clarify the syndrome, its treatment, and will help change the field of epilepsy to improve patients qualify of life by creating new means of preventing, controlling, and curing epilepsy.

An amendment to this paper has been published and can be accessed via the original article.

Abstract Background Increasingly, genomics is informing clinical practice, but challenges remain for medical professionals lacking genetics expertise, and in access to and clinical utility of genomic testing for minority and underrepresented populations. The latter is a particularly pernicious problem due to the historical lack of inclusion of racially and ethnically diverse populations in genomic research and genomic medicine. A further challenge is the rapidly changing landscape of genetic tests and considerations of cost, interpretation, and diagnostic yield for emerging modalities like whole-genome sequencing. Methods The NYCKidSeq project is a randomized controlled trial recruiting 1130 children and young adults predominantly from Harlem and the Bronx with suspected genetic disorders in three disease categories: neurologic, cardiovascular, and immunologic. Two clinical genetic tests will be performed for each participant, either proband, duo, or trio whole-genome sequencing (depending on sample availability) and proband targeted gene panels. Clinical utility, cost, and diagnostic yield of both testing modalities will be assessed. This study will evaluate the use of a novel, digital platform (GUÍA) to digitize the return of genomic results experience and improve participant understanding for English- and Spanish-speaking families. Surveys will collect data at three study visits: baseline (0 months), result disclosure visit (ROR1, + 3 months), and follow-up visit (ROR2, + 9 months). Outcomes will assess parental understanding of and attitudes toward receiving genomic results for their child and behavioral, psychological, and social impact of results. We will also conduct a pilot study to assess a digital tool called GenomeDiver designed to enhance communication between clinicians and genetic testing labs. We will evaluate GenomeDiver’s ability to increase the diagnostic yield compared to standard practices, improve clinician’s ability to perform targeted reverse phenotyping, and increase the efficiency of genetic testing lab personnel. Discussion The NYCKidSeq project will contribute to the innovations and best practices in communicating genomic test results to diverse populations. This work will inform strategies for implementing genomic medicine in health systems serving diverse populations using methods that are clinically useful, technologically savvy, culturally sensitive, and ethically sound. Trial registration ClinicalTrials.gov NCT03738098 . Registered on November 13, 2018 Trial Sponsor: Icahn School of Medicine at Mount Sinai Contact Name: Eimear Kenny, PhD (Principal Investigator) Address: Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Pl., Box 1003, New York, NY 10029 Email: eimear.kenny@mssm.edu

Abstract Objective Acute encephalopathy may occur in COVID‐19‐infected patients. We investigated whether medically indicated EEGs performed in acutely ill patients under investigation (PUIs) for COVID‐19 report epileptiform abnormalities and whether these are more prevalent in COVID‐19 positive than negative patients. Methods In this retrospective case series, adult COVID‐19 inpatient PUIs underwent EEGs for acute encephalopathy and/or seizure‐like events. PUIs had 8‐channel headband EEGs (Ceribell; 20 COVID‐19 positive, 6 COVID‐19 negative); 2 more COVID‐19 patients had routine EEGs. Overall, 26 Ceribell EEGs, 4 routine and 7 continuous EEG studies were reviewed. EEGs were interpreted by board‐certified clinical neurophysiologists (n = 16). EEG findings were correlated with demographic data, clinical presentation and history, and medication usage. Fisher's exact test was used. Results We included 28 COVID‐19 PUIs (30‐83 years old), of whom 22 tested positive (63.6% males) and 6 tested negative (33.3% male). The most common indications for EEG, among COVID‐19‐positive vs COVID‐19‐negative patients, respectively, were new onset encephalopathy (68.2% vs 33.3%) and seizure‐like events (14/22, 63.6%; 2/6, 33.3%), even among patients without prior history of seizures (11/17, 64.7%; 2/6, 33.3%). Sporadic epileptiform discharges (EDs) were present in 40.9% of COVID‐19‐positive and 16.7% of COVID‐19‐negative patients; frontal sharp waves were reported in 8/9 (88.9%) of COVID‐19‐positive patients with EDs and in 1/1 of COVID‐19‐negative patient with EDs. No electrographic seizures were captured, but 19/22 COVID‐19‐positive and 6/6 COVID‐19‐negative patients were given antiseizure medications and/or sedatives before the EEG. Significance This is the first preliminary report of EDs in the EEG of acutely ill COVID‐19‐positive patients with encephalopathy or suspected clinical seizures. EDs are relatively common in this cohort and typically appear as frontal sharp waves. Further studies are needed to confirm these findings and evaluate the potential direct or indirect effects of COVID‐19 on activating epileptic activity.