Maximum downward slope of sleep slow waves as a potential marker of attention-deficit/hyperactivity disorder clinical phenotypes.

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is a highly heterogeneous diagnostic category, encompassing several endophenotypes and comorbidities, including sleep problems. However, no predictor of clinical long-term trajectories or comorbidity has yet been established. Sleep EEG has been proposed as a potential tool for evaluating the synaptic strength during development, as well as the cortical thickness, which is presumed to be altered in ADHD.

The evolution of humoral immune responses to past and novel influenza virus strains gives evidence for antigenic seniority.

The high genetic and antigenic variability of influenza virus and the repeated exposures of individuals to the virus over time account for the human immune responses toward this pathogen to continuously evolve during the lifespan of an individual. Influenza-specific immune memory to past strains has been shown to affect the immune responses to subsequent influenza strains and in turn to be changed itself through the new virus encounter. However, exactly how and to what extent this happens remains unclear.

Trehalose Treatment in Zebrafish Model of Lafora Disease.

Mutations in the gene encoding laforin cause Lafora disease (LD), a progressive myoclonic epilepsy characterized by drug-resistant seizures and progressive neurological impairment. To date, rodents are the only available models for studying LD; however, their use for drug screening is limited by regulatory restrictions and high breeding costs. To investigate the role of laforin loss of function in early neurodevelopment, and to screen for possible new compounds for treating the disorder, we developed a zebrafish model of LD.

Kir4.1 Dysfunction in the Pathophysiology of Depression: A Systematic Review.

A serotonergic dysfunction has been largely postulated as the main cause of depression, mainly due to its effective response to drugs that increase the serotonergic tone, still currently the first therapeutic line in this mood disorder. However, other dysfunctional pathomechanisms are likely involved in the disorder, and this may in part explain why some individuals with depression are resistant to serotonergic therapies. Among these, emerging evidence suggests a role for the astrocytic inward rectifier potassium channel 4.

The Diagnostic Approach to Mitochondrial Disorders in Children in the Era of Next-Generation Sequencing: A 4-Year Cohort Study.

Mitochondrial diseases (MDs) are a large group of genetically determined multisystem disorders, characterized by extreme phenotypic heterogeneity, attributable in part to the dual genomic control (nuclear and mitochondrial DNA) of the mitochondrial proteome. Advances in next-generation sequencing technologies over the past two decades have presented clinicians with a challenge: to select the candidate disease-causing variants among the huge number of data provided. Unfortunately, the clinical tools available to support genetic interpretations still lack specificity and sensitivity.

Epilepsy in LAMA2-related muscular dystrophy: A systematic review of the literature.

Epilepsy is a common, often severe, feature of LAMA2-related muscular dystrophy (LAMA2-RD) and could represent its onset and main manifestation, even in the absence of overt muscle involvement. To date, there is no systematic characterization of epilepsy in LAMA2-RD, and its impact on neurodevelopment and on the clinical course remains poorly established. In view of this knowledge gap, we conducted a systematic review of the literature and, as an illustrative example, reported the clinical case of a boy with late-onset LAMA2-related limb-girdle muscular dystrophy presenting with severe epilepsy.

Sleep EEG microstructure in children and adolescents with attention deficit hyperactivity disorder: a systematic review and meta-analysis.

Attention deficit hyperactivity disorder (ADHD) is commonly associated with sleep problems, possibly due to shared pathophysiology. Microstructural sleep electroencephalographic (EEG) alterations may likely represent markers of disordered cortical maturation in ADHD, although literature data are still conflicting, deserving further assessment. After having systematically reviewed the literature, we included 11 studies from 598 abstracts, and assessed 23 parameters of cyclic alternating pattern (CAP), four parameters of sleep EEG power and one parameter of sleep graphoelements through 29 meta-analyses and, when possible, univariate meta-regressions.

Psychopathological features in referred adolescents with psychogenic nonepileptic seizures with or without epilepsy.

Psychogenic nonepileptic seizures (PNES) are episodic manifestations that mimic epileptic seizures (ES) although not associated with electroencephalogram (EEG) abnormalities. Psychogenic nonepileptic seizures and ES, however, can often cooccur. Emotional distress in adolescents can trigger PNES, but the psychopathological and personality features are still unknown.

Safe and sound: Meta-analyzing the Mozart effect on epilepsy.

Objective: The use of music-based neuro-stimulation for treating seizures and interictal epileptiform discharges (IED) (the so-called "Mozart effect") remains a controversial issue. We have conducted an updated meta-analysis in order to systematically review literature evidence and provide further insights about the role of the Mozart effect in epilepsy.

Methods: Following the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) guidelines, we searched three bibliographic databases from their date of inception to January 2020.

Evolution of Epileptiform Activity in Zebrafish by Statistical-Based Integration of Electrophysiology and 2-Photon Ca Imaging.

The study of sources and spatiotemporal evolution of ictal bursts is critical for the mechanistic understanding of epilepsy and for the validation of anti-epileptic drugs. Zebrafish is a powerful vertebrate model representing an excellent compromise between system complexity and experimental accessibility. We performed the quantitative evaluation of the spatial recruitment of neuronal populations during physiological and pathological activity by combining local field potential (LFP) recordings with simultaneous 2-photon Ca imaging.

Expanding the clinical and genetic heterogeneity of SPAX5.

Mutations in the ATPase family 3-like gene (AFG3L2) have been linked to autosomal-dominant spinocerebellar ataxia type 28 and autosomal recessive spastic ataxia-neuropathy syndrome. Here, we describe the case of a child carrying bi-allelic mutations in AFG3L2 and presenting with ictal paroxysmal episodes associated with neuroimaging suggestive of basal ganglia involvement. Studies in skin fibroblasts showed a significant reduction of AFG3L2 expression.

Loss of ap4s1 in zebrafish leads to neurodevelopmental defects resembling spastic paraplegia 52.

Autosomal recessive spastic paraplegia 52 is caused by biallelic mutations in AP4S1 which encodes a subunit of the adaptor protein complex 4 (AP-4). Using next-generation sequencing, we identified three novel unrelated SPG52 patients from a cohort of patients with cerebral palsy. The discovered variants in AP4S1 lead to reduced AP-4 complex formation in patient-derived fibroblasts.

Comparison of influenza-specific neutralizing antibody titers determined using different assay readouts and hemagglutination inhibition titers: good correlation but poor agreement.

Determination of influenza-specific antibody titers is commonly done using the hemagglutination inhibition assay (HAI) and the viral microneutralization assay (MN). Both assays are characterized by high intra- and inter-laboratory variability. The HAI assay offers little opportunity for standardization.

Customized multigene panels in epilepsy: the best things come in small packages.

Over the past 10 years, the increasingly important role played by next-generation sequencing panels in the genetic diagnosis of epilepsy has led to a growing list of gene variants and a plethora of new scientific data. To date, however, there is still no consensus on what constitutes the "ideal panel design," or on the most rational criteria for selecting the best candidates for gene-panel analysis, even though both might optimize the cost-benefit ratio and the diagnostic efficiency of customized gene panels. Even though more and more laboratories are adopting whole-exome sequencing as a first-tier diagnostic approach, interpreting, "in silico," a set of epilepsy-related genes remains difficult.

Electrophysiological features of sleep in children with Kir4.1 channel mutations and Autism-Epilepsy phenotype: a preliminary study.

Study Objectives: Recently, a role for gain-of-function (GoF) mutations of the astrocytic potassium channel Kir4.1 (KCNJ10 gene) has been proposed in subjects with Autism-Epilepsy phenotype (AEP). Epilepsy and autism spectrum disorder (ASD) are common and complexly related to sleep disorders.

Clinical and electroencephalographic correlates of psychiatric features in children with frontal lobe epilepsy.

Background And Objective: Frontal lobe epilepsy (FLE) is often associated with psychiatric features, although the factors predisposing to the concurrence of these conditions have yet to be determined, especially in younger children. We aimed at defining possible clinical and electroencephalography (EEG) features that may enhance the psychiatric risk in pediatric FLE.

Method: We performed a structured psychiatric assessment of 59 children with FLE, using both categorical and dimensional approaches, correlated psychopathology with epilepsy data, and cognitive development.

Transient Cognitive Impairment in Epilepsy.

Impairments of the dialog between excitation and inhibition (E/I) is commonly associated to neuropsychiatric disorders like autism, bipolar disorders and epilepsy. Moderate levels of hyperexcitability can lead to mild alterations of the EEG and are often associated with cognitive deficits even in the absence of overt seizures. Indeed, various testing paradigms have shown degraded performances in presence of acute or chronic non-ictal epileptiform activity.

encephalopathy: A distinctive generalized developmental and epileptic encephalopathy.

Objective: To delineate the epileptology, a key part of the phenotypic spectrum, in a large patient cohort.

Methods: Patients were recruited via investigators' practices or social media. We included patients with (likely) pathogenic variants or chromosome 6p21.

Defining the electroclinical phenotype and outcome of PCDH19-related epilepsy: A multicenter study.

Objective: PCDH19-related epilepsy is an epileptic syndrome with infantile onset, characterized by clustered and fever-induced seizures, often associated with intellectual disability (ID) and autistic features. The aim of this study was to analyze a large cohort of patients with PCDH19-related epilepsy and better define the epileptic phenotype, genotype-phenotype correlations, and related outcome-predicting factors.

Methods: We retrospectively collected genetic, clinical, and electroencephalogram (EEG) data of 61 patients with PCDH19-related epilepsy followed at 15 epilepsy centers.

Cross-Protective Immune Responses Induced by Sequential Influenza Virus Infection and by Sequential Vaccination With Inactivated Influenza Vaccines.

Sequential infection with antigenically distinct influenza viruses induces cross-protective immune responses against heterologous virus strains in animal models. Here we investigated whether sequential immunization with antigenically distinct influenza vaccines can also provide cross-protection. To this end, we compared immune responses and protective potential against challenge with A(H1N1)pdm09 in mice infected sequentially with seasonal A(H1N1) virus followed by A(H3N2) virus or immunized sequentially with whole inactivated virus (WIV) or subunit (SU) vaccine derived from these viruses.

Effector mechanisms of influenza-specific antibodies: neutralization and beyond.

Introduction: Antibodies directed against influenza virus execute their protective function by exploiting a variety of effector mechanisms. Neutralizing antibodies have been thoroughly studied because of their pivotal role in preventing influenza virus infection and their presence in host serum is correlated with protection. Influenza antibodies can also exploit non-neutralizing effector mechanisms, which until recently have been largely overlooked.

Understanding Spreading Depression from Headache to Sudden Unexpected Death.

Spreading depression (SD) is a neurophysiological phenomenon characterized by abrupt changes in intracellular ion gradients and sustained depolarization of neurons. It leads to loss of electrical activity, changes in the synaptic architecture, and an altered vascular response. Although SD is often described as a unique phenomenon with homogeneous characteristics, it may be strongly affected by the particular triggering event and by genetic background.

Internalizing and externalizing symptoms in preschool and school-aged children with epilepsy: Focus on clinical and EEG features.

Introduction: Psychiatric and behavioral problems are frequent comorbidities of epilepsy, although their clinical and electroencephalographic (EEG) correlates remain uncertain. In this study, we have assessed the frequency of psychopathological problems in a cohort of children with epilepsy, and established their main clinical and EEG-associated features.

Methods: One hundred fifty-nine young patients with epilepsy were recruited and assessed through the Child Behavior Checklist for preschool-aged children (CBCL 1 1/2-5) or for school-aged children (CBCL 6-18).

An integrated EEG and eye-tracking approach for the study of responding and initiating joint attention in Autism Spectrum Disorders.

Autism Spectrum Disorders (ASD) are characterised by impairment in joint attention (JA), which has two components: the response to JA and the initiation of JA. Literature suggests a correlation between JA and neural circuitries, although this link is still largely unexplored in ASD. In this pilot study, we aimed at investigating the neural correlates of responding and initiating JA in high-functioning children with ASD and evaluating the changes in brain function and visual pattern after six months of rehabilitative treatment using an integrated EEG/eye-tracking system.