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Large international consortia examining the genomic architecture of the epilepsies focus on large diagnostic subgroupings such as "all focal epilepsy" and "all genetic generalized epilepsy". In addition, phenotypic data are generally entered into these large discovery databases in a unidirectional manner at one point in time only. However, there are many smaller phenotypic subgroupings in epilepsy, many of which may have unique genomic risk factors. Such a subgrouping or "microphenotype" may be defined as an uncommon or rare phenotype that is well recognized by epileptologists and the epilepsy community, and which may or may not be formally recognized within the International League Against Epilepsy classification system. Here we examine the genetic structure of a number of such microphenotypes and report in particular on two interesting clinical phenotypes, Jeavons syndrome and pediatric status epilepticus. Although no single gene reached exome‐wide statistical significance to be associated with any of the diagnostic categories, we observe enrichment of rare damaging variants in established epilepsy genes among Landau–Kleffner patients (GRIN2A) and pediatric status epilepticus patients (MECP2, SCN1A, SCN2A, SCN8A). [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to evaluate benzodiazepine (BZD) administration patterns before transitioning to non‐BZD antiseizure medication (ASM) in pediatric patients with refractory convulsive status epilepticus (rSE). Methods: This retrospective multicenter study in the United States and Canada used prospectively collected observational data from children admitted with rSE between 2011 and 2020. Outcome variables were the number of BZDs given before the first non‐BZD ASM, and the number of BZDs administered after 30 and 45 min from seizure onset and before escalating to non‐BZD ASM. Results: We included 293 patients with a median (interquartile range) age of 3.8 (1.3–9.3) years. Thirty‐six percent received more than two BZDs before escalating, and the later the treatment initiation was after seizure onset, the less likely patients were to receive multiple BZD doses before transitioning (incidence rate ratio [IRR] =.998, 95% confidence interval [CI] =.997–.999 per minute, p =.01). Patients received BZDs beyond 30 and 45 min in 57.3% and 44.0% of cases, respectively. Patients with out‐of‐hospital seizure onset were more likely to receive more doses of BZDs beyond 30 min (IRR = 2.43, 95% CI = 1.73–3.46, p <.0001) and beyond 45 min (IRR = 3.75, 95% CI = 2.40–6.03, p <.0001) compared to patients with in‐hospital seizure onset. Intermittent SE was a risk factor for more BZDs administered beyond 45 min compared to continuous SE (IRR = 1.44, 95% CI = 1.01–2.06, p =.04). Forty‐seven percent of patients (n = 94) with out‐of‐hospital onset did not receive treatment before hospital arrival. Among patients with out‐of‐hospital onset who received at least two BZDs before hospital arrival (n = 54), 48.1% received additional BZDs at hospital arrival. Significance: Failure to escalate from BZDs to non‐BZD ASMs occurs mainly in out‐of‐hospital rSE onset. Delays in the implementation of medical guidelines may be reduced by initiating treatment before hospital arrival and facilitating a transition to non‐BZD ASMs after two BZD doses during handoffs between prehospital and in‐hospital settings. [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to describe long‐term clinical and developmental outcomes in pediatric refractory status epilepticus (RSE) and identify factors associated with new neurological deficits after RSE. Methods: We performed retrospective analyses of prospectively collected observational data from June 2011 to March 2020 on pediatric patients with RSE. We analyzed clinical outcomes from at least 30 days after RSE and, in a subanalysis, we assessed developmental outcomes and evaluated risk factors in previously normally developed patients. Results: Follow‐up data on outcomes were available in 276 patients (56.5% males). The median (interquartile range [IQR]) follow‐up duration was 1.6 (.9–2.7) years. The in‐hospital mortality rate was 4% (16/403 patients), and 15 (5.4%) patients had died after hospital discharge. One hundred sixty‐six (62.9%) patients had subsequent unprovoked seizures, and 44 (16.9%) patients had a repeated RSE episode. Among 116 patients with normal development before RSE, 42 of 107 (39.3%) patients with available data had new neurological deficits (cognitive, behavioral, or motor). Patients with new deficits had longer median (IQR) electroclinical RSE duration than patients without new deficits (10.3 [2.1–134.5] h vs. 4 [1.6–16] h, p =.011, adjusted odds ratio = 1.003, 95% confidence interval = 1.0008–1.0069, p =.027). The proportion of patients with an unfavorable functional outcome (Glasgow Outcome Scale‐Extended score ≥ 4) was 22 of 90 (24.4%), and they were more likely to have received a continuous infusion. Significance: About one third of patients without prior epilepsy developed recurrent unprovoked seizures after the RSE episode. In previously normally developing patients, 39% presented with new deficits during follow‐up, with longer electroclinical RSE duration as a predictor. [ABSTRACT FROM AUTHOR]

Objective: We aimed to characterize the clinical profile and outcomes of new onset refractory status epilepticus (NORSE) in children, and investigated the relationship between fever onset and status epilepticus (SE). Methods: Patients with refractory SE (RSE) between June 1, 2011 and October 1, 2016 were prospectively enrolled in the pSERG (Pediatric Status Epilepticus Research Group) cohort. Cases meeting the definition of NORSE were classified as "NORSE of known etiology" or "NORSE of unknown etiology." Subgroup analysis of NORSE of unknown etiology was completed based on the presence and time of fever occurrence relative to RSE onset: fever at onset (≤24 h), previous fever (2 weeks–24 h), and without fever. Results: Of 279 patients with RSE, 46 patients met the criteria for NORSE. The median age was 2.4 years, and 25 (54%) were female. Forty (87%) patients had NORSE of unknown etiology. Nineteen (48%) presented with fever at SE onset, 16 (40%) had a previous fever, and five (12%) had no fever. The patients with preceding fever had more prolonged SE and worse outcomes, and 25% recovered baseline neurological function. The patients with fever at onset were younger and had shorter SE episodes, and 89% recovered baseline function. Significance: Among pediatric patients with RSE, 16% met diagnostic criteria for NORSE, including the subcategory of febrile infection‐related epilepsy syndrome (FIRES). Pediatric NORSE cases may also overlap with refractory febrile SE (FSE). FIRES occurs more frequently in older children, the course is usually prolonged, and outcomes are worse, as compared to refractory FSE. Fever occurring more than 24 h before the onset of seizures differentiates a subgroup of NORSE patients with distinctive clinical characteristics and worse outcomes. [ABSTRACT FROM AUTHOR]

Objective: To develop and test a deep learning algorithm to automatically detect cortical tubers in magnetic resonance imaging (MRI), to explore the utility of deep learning in rare disorders with limited data, and to generate an open-access deep learning standalone application. Methods: T2 and FLAIR axial images with and without tubers were extracted from MRIs of patients with tuberous sclerosis complex (TSC) and controls, respectively. We trained three different convolutional neural network (CNN) architectures on a training dataset and selected the one with the lowest binary cross-entropy loss in the validation dataset, which was evaluated on the testing dataset. We visualized image regions most relevant for classification with gradient-weighted class activation maps (Grad-CAM) and saliency maps. Results: 114 patients with TSC and 114 controls were divided into a training set, a validation set, and a testing set. The InceptionV3 CNN architecture performed best in the validation set and was evaluated in the testing set with the following results: sensitivity: 0.95, specificity: 0.95, positive predictive value: 0.94, negative predictive value: 0.95, F1-score: 0.95, accuracy: 0.95, and area under the curve: 0.99. Grad-CAM and saliency maps showed that tubers resided in regions most relevant for image classification within each image. A stand-alone trained deep learning App was able to classify images using local computers with various operating systems. Conclusion: This study shows that deep learning algorithms are able to detect tubers in selected MRI images, and deep learning can be prudently applied clinically to manually selected data in a rare neurological disorder. [ABSTRACT FROM AUTHOR]

Objective: To determine whether publication of evidence on delays in time to treatment shortens time to treatment in pediatric refractory convulsive status epilepticus (rSE), we compared time to treatment before (2011-2014) and after (2015-2019) publication of evidence of delays in treatment of rSE in the Pediatric Status Epilepticus Research Group (pSERG) as assessed by patient interviews and record review., Methods: We performed a retrospective analysis of a prospectively collected dataset from June 2011 to September 2019 on pediatric patients (1 month-21 years of age) with rSE., Results: We studied 328 patients (56% male) with median (25th-75th percentile [p 25 -p 75 ]) age of 3.8 (1.3-9.4) years. There were no differences in the median (p 25 -p 75 ) time to first benzodiazepine (BZD) (20 [5-52.5] vs 15 [5-38] minutes, p = 0.3919), time to first non-BZD antiseizure medication (68 [34.5-163.5] vs 65 [33-142] minutes, p = 0.7328), and time to first continuous infusion (186 [124.2-571] vs 160 [89.5-495] minutes, p = 0.2236). Among 157 patients with out-of-hospital onset whose time to hospital arrival was available, the proportion who received at least 1 BZD before hospital arrival increased after publication of evidence of delays (41 of 81 [50.6%] vs 57 of 76 [75%], p = 0.0018), and the odds ratio (OR) was also increased in multivariable logistic regression (OR 4.35 [95% confidence interval 1.96-10.3], p = 0.0005)., Conclusion: Publication of evidence on delays in time to treatment was not associated with improvements in time to treatment of rSE, although it was associated with an increase in the proportion of patients who received at least 1 BZD before hospital arrival., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Aim: To determine whether attention deficit hyperactivity disorder (ADHD) is associated with other prevalent medical pathologies of the paediatric age., Development: Several paediatric pathologies were selected with the aim of reviewing their association with ADHD: in paediatric pulmonology, asthma and other allergic processes; in paediatric neurology, headache and febrile seizures; in paediatric gastroenterology, diarrhoea, constipation, abdominal pain, gastroesophageal reflux and infection by Helicobacter pylori; in paediatric nephrology, enuresis; in paediatric cardiology, bruits and congenital heart disease; in paediatric endocrinology, thyroid disorders and obesity; and in paediatric ophthalmology, ametropia and strabismus., Conclusions: Several studies were found that related ADHD with allergic processes, overweight/obesity, peripheral resistance to thyroid hormone, enuresis, febrile seizures, headache, congenital heart disease, ophthalmic disorders and tooth decay, with some controversial issues and details still to be defined. It can be concluded that further interdisciplinary studies are needed to clarify the associations and underlying mechanisms involved, so as to be able to gain a deeper understanding of the complex entity of ADHD and to suggest preventive, diagnostic and therapeutic interventions with regard to its comorbidities.