Summary Purpose:  Epilepsies have a highly heterogeneous background with a strong genetic contribution. The variety of unspecific and overlapping syndromic and nonsyndromic phenotypes often hampers a clear clinical diagnosis and prevents straightforward genetic testing. Knowing the genetic basis of a patient’s epilepsy can be valuable not only for diagnosis but also for guiding treatment and estimating recurrence risks. Methods:  To overcome these diagnostic restrictions, we composed a panel of genes for Next Generation Sequencing containing the most relevant epilepsy genes and covering the most relevant epilepsy phenotypes known so far. With this method, 265 genes were analyzed per patient in a single step. We evaluated this panel on a pilot cohort of 33 index patients with concise epilepsy phenotypes or with a severe but unspecific seizure disorder covering both sporadic and familial cases. Key Findings:  We identified presumed disease‐causing mutations in 16 of 33 patients comprising sequence alterations in frequently as well as in less commonly affected genes. The detected aberrations encompassed known and unknown point mutations (SCN1A p.R222X, p. E289V, p.379R, p.R393H; SCN2A p.V208E; STXBP1 p.R122X; KCNJ10 p.L68P, p.I129V; KCTD7 p.L108M; KCNQ3 p.P574S; ARHGEF9 p.R290H; SMS p.F58L; TPP1 p.Q278R, p.Q422H; MFSD8 p.T294K), a putative splice site mutation (SCN1A c.693A> p.T/P231P) and small deletions (SCN1A p.F1330Lfs3X [1 bp]; MFSD8 p.A138Dfs10X [7 bp]). All mutations have been confirmed by conventional Sanger sequencing and, where possible, validated by parental testing and segregation analysis. In three patients with either Dravet syndrome or myoclonic epilepsy, we detected SCN1A mutations (p.R222X, p.P231P, p.R393H), even though other laboratories had previously excluded aberrations of this gene by Sanger sequencing or high‐resolution melting analysis. Significance:  We have developed a fast and cost‐efficient diagnostic screening method to analyze the genetic basis of epilepsies. We were able to detect mutations in patients with clear and with unspecific epilepsy phenotypes, to uncover the genetic basis of many so far unresolved cases with epilepsy including mutation detection in cases in which previous conventional methods yielded falsely negative results. Our approach thus proved to be a powerful diagnostic tool that may contribute to collecting information on both common and unknown epileptic disorders and in delineating associated phenotypes of less frequently mutated genes.

Although stroke etiology and risk factors in children and young adults are different, stroke severity and clinical outcome were similar in both groups.

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The field of mechanical circulatory support has made great strides in the preceding 2 decades. Although pediatric mechanical circulatory support has lagged behind that of adults, the gap between them is expected to close soon. The only device currently approved by the US Food and Drug Administration for use in children is the Berlin Heart EXCOR ventricular assist device (VAD). The prospective Berlin Heart Investigational Device Exemption Trial demonstrated good outcomes, such as bridge to transplantation or recovery, in ~90% of children supported with this device. However, a high incidence of hemorrhagic and thrombotic complications was also noted. As a result, pediatric centers have just started implanting adult intracorporeal continuous-flow devices in children. This paradigm shift has opened a new era in pediatric mechanical circulatory support. Whereas children on VAD were previously managed exclusively in hospital, therapeutic options such as outpatient management and even destination therapy have been becoming a reality. With continued miniaturization and technological refinements, devices currently in development will broaden the range of options available to children. The HeartMate 3 and HeartWare MVAD are two such compact VADs, which are anticipated to have great potential for pediatric use. Additionally, a pediatric-specific continuous-flow VAD, the newly redesigned Jarvik Infant 2015, is currently undergoing preclinical testing and is expected to undergo a randomized clinical trial in the near future. This review aims to discuss the challenges posed by the use of intracorporeal adult continuous-flow devices in children, as well as to provide our perspective on the future prospects of the field of pediatric VADs.

This study has demonstrated that the Infant Jarvik 2015 VAD is capable of maintaining its functionality for an extended period of time with minimal hemolysis.

Summary Objective Pathogenic variants in SCN8A have been associated with a wide spectrum of epilepsy phenotypes, ranging from benign familial infantile seizures (BFIS) to epileptic encephalopathies with variable severity. Furthermore, a few patients with intellectual disability (ID) or movement disorders without epilepsy have been reported. The vast majority of the published SCN8A patients suffer from severe developmental and epileptic encephalopathy (DEE). In this study, we aimed to provide further insight on the spectrum of milder SCN8A‐related epilepsies. Methods A cohort of 1095 patients were screened using a next generation sequencing panel. Further patients were ascertained from a network of epilepsy genetics clinics. Patients with severe DEE and BFIS were excluded from the study. Results We found 36 probands who presented with an SCN8A‐related epilepsy and normal intellect (33%) or mild (61%) to moderate ID (6%). All patients presented with epilepsy between age 1.5 months and 7 years (mean = 13.6 months), and 58% of these became seizure‐free, two‐thirds on monotherapy. Neurological disturbances included ataxia (28%) and hypotonia (19%) as the most prominent features. Interictal electroencephalogram was normal in 41%. Several recurrent variants were observed, including Ile763Val, Val891Met, Gly1475Arg, Gly1483Lys, Phe1588Leu, Arg1617Gln, Ala1650Val/Thr, Arg1872Gln, and Asn1877Ser. Significance With this study, we explore the electroclinical features of an intermediate SCN8A‐related epilepsy with mild cognitive impairment, which is for the majority a treatable epilepsy.

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