The past 25 years have seen a strong increase in the number of publications related to criticality in different areas of neuroscience. The potential of criticality to explain various brain properties, including optimal information processing, has made it an increasingly exciting area of investigation for neuroscientists. Recent reviews on this topic, sometimes termed brain criticality, make brief mention of clinical applications of these findings to several neurological disorders such as epilepsy, neurodegenerative disease, and neonatal hypoxia. Other clinicallyrelevant domains-including anesthesia, sleep medicine, developmental-behavioral pediatrics, and psychiatry-are seldom discussed in review papers of brain criticality. Thorough assessments of these application areas and their relevance for clinicians have also yet to be published. In this scoping review, studies of brain criticality involving human data of all ages are evaluated for their current and future clinical relevance. To make the results of these studies understandable to a more clinical audience, a review of the key concepts behind criticality (e.g., phase transitions, long-range temporal correlation, self-organized criticality, power laws, branching processes) precedes the discussion of human clinical studies. Open questions and forthcoming areas of investigation are also considered.

This paper deals with a Cox proportional hazards regression model, where some covariates of interest are randomly right-censored. While methods for censored outcomes have become ubiquitous in the literature, methods for censored covariates have thus far received little attention and, for the most part, dealt with the issue of limit-of-detection. For randomly censored covariates, an often-used method is the inefficient complete-case analysis (CCA) which consists in deleting censored observations in the data analysis. When censoring is not completely independent, the CCA leads to biased and spurious results. Methods for missing covariate data, including type I and type II covariate censoring as well as limit-of-detection do not readily apply due to the fundamentally different nature of randomly censored covariates. We develop a novel method for censored covariates using a conditional mean imputation based on either Kaplan–Meier estimates or a Cox proportional hazards model to estimate the effects of these covariates on a time-to-event outcome. We evaluate the performance of the proposed method through simulation studies and show that it provides good bias reduction and statistical efficiency. Finally, we illustrate the method using data from the Framingham Heart Study to assess the relationship between offspring and parental age of onset of cardiovascular events.

Mutations that disrupt the TBC1D24 presynaptic protein have been implicated in various neurological disorders including epilepsy, chronic encephalopathy, DOORS (deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures) syndrome, nonsyndromic hearing loss, and myoclonus. We present the case of a 22-month-old male with infantile-onset paroxysmal episodes of facial and limb myoclonus. The episodes were linked to biallelic variants in exon 2 of the TBC1D24 gene that lead to amino acid changes (c.304C >T/p.Pro102Ser and c.410T > C/p.Val137Ala), each variant being inherited from a parent. Follow-up imaging in adolescence revealed widened right cerebellar sulci. We discuss the evolving landscape of TBC1D24 associated phenotypes; this case adds to a growing body of evidence linking this gene to movement disorders in children.

Genetic sequencing technologies have led to an increase in the identification and characterization of monogenic epilepsy syndromes. This increase has, in turn, generated strong interest in developing “precision therapies” based on the unique molecular genetics of a given monogenic epilepsy syndrome. These therapies include diets, vitamins, cell-signaling regulators, ion channel modulators, repurposed medications, molecular chaperones, and gene therapies. In this review, we evaluate these therapies from the perspective of their clinical validity and discuss the future of these therapies for individual syndromes.

Summary: For various reasons, status epilepticus in children is different than in adults. Pediatric specificities include status epilepticus epidemiology, underlying etiologies, pathophysiological mechanisms, and treatment options. Relevant data from the literature are presented for each of them, and questions remaining open for future studies on status epilepticus in childhood are listed.