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Background: Neuroinflammation is a key component in the etiopathogenesis of neurological diseases and brain aging. This process involves the brain immune system that modulates synaptic functions and protects neurons from infection or damage. Hence, the knowledge of neuroinflammation related-pathways and modulation by drugs or natural compounds is functional to the development of therapeutic strategies aimed at preserving, maintaining and restoring brain health. Objective: This review article summarizes the basics in neuroinflammation and related signaling pathways, the success of dietary intervention in clinical practice and the possible development of RNA-based strategies for the treatment of neurological diseases. Methods: Pubmed search (2012-2022); keywords: neuroinflammation and molecular mechanisms in combination with diet, miRNA and non-coding RNA. Results: Glial cells play a crucial role in neuroinflammation, but several pathways can be activated in response to different inflammatory stimuli, inducing cell death by apoptosis, pyroptosis or necroptosis. Dietary intervention has immunomodulatory effects and could limit the inflammatory process induced by microglia and astrocytes. Thus by ihibiting neuroinflammation and improving the symptoms of a variety of neurological diseases, diet exerts pleiotropic neuroprotective effects independently from the spectrum of pathophysiological mechanisms underlying the specific disorder. Furthermore, data from animal models revealed that altered expression of specific non-coding RNAs, in particular microRNAs, contributes to neuroinflammatory diseases; consequently, RNA-based strategies may be promising to alleviate the consequences of neuroinflammation. Conclusion: Further studies are needed to identify the molecular pathways and the new pharmacological targets in neuroinflammation to lay the basis for more effective and selective therapies to be applied, in parallel to dietary intervention, in the treatment of neuroinflammation-based diseases.

Objective: Despite of the large prevalence of obstructive sleep apnea syndrome (OSAS) in pediatric age, numerous aspects of its impact on day life and on parental quality are still poor studied and considered in the clinical management. The study evaluated the stress levels and copying styles in a large sample of mother of children with OSAS. Method: 374 mothers of children affected by OSAS (mOSAS) were compared with a group of mothers of 421 neurotypical healthy children (mTDC) for stress perceived stress levels and for coping strategies. Subjects were recruited from Italian Regions in Sicily, Campania, Calabria and Umbria. Results: Among both groups mOSAS and mTDC no differences were reported for children age (p=0.340), children gender (p=0.956), similarly for age of mothers (p=0.188). Discussion: The perceived stress assessment in mOSAS showed higher rate of all parental stress scores of PSI-SF: Parental Distress domain (p

Objectives: Deficits in facial emotion recognition and Theory of Mind are frequent in patients with epilepsy. Although this evidence, studies on pediatric age are few and the relation between these abilities and other cognitive domain remains to be better elucidated. The purpose of our study is to evaluate facial emotion recognition and Theory of Mind in children and adolescents with focal epilepsy, and correlate them with intelligence and executive functions. Materials and methods: Our work is a cross-sectional observational study. Sixty-two children and adolescents aged between 7-16 years diagnosed by focal epilepsy and 32 sex/age-matched controls were recruited. All participants were administered a standardized battery tests to assess social cognition (NEPSY-II), executive functions (EpiTrack Junior) and cognitive non-verbal level (Raven Progressive Matrices). Results: Emotion recognition mean score was significantly lower in the epilepsy group than in the controls to Student's t-test (p

The objective of our study was to evaluate the impact of the COVID-19 pandemic on the emotional and behavioral symptoms in minors with neuropsychiatric disorders and on parental stress through a standardized neuropsychological assessment, comparing the data collected before the pandemic with those collected during the lock-down. Another goal of our study was to analyze the relationship between parental stress and behavioral/emotional symptoms in children. Our study was conducted on 383 families of patients who had already been referred at the Child Neuropsychiatry Unit of the University Hospital of Salerno for different neuropsychiatric conditions. All the parents completed two neuropsychological standardized questionnaires for the assessment of parental stress (PSI—Parenting Stress Index-Short Form) and the emotional/behavioral problems of their children (Child Behaviour CheckList). The data collected during the pandemic were compared with those collected from questionnaires administered during the six months preceding the pandemic, as is our usual clinical practice. The comparison between the mean scores of PSI and CBCL before and after the pandemic showed a statistically significant increase in all subscales analyzed in the total sample. The correlation analysis showed significant positive relationship between the subscale Total Stress of PSI and the subscales Total Problems and Internalizing Problems of CBCL. Our study suggested that the COVID-19 pandemic and the corresponding measures adopted led to an increase in internalizing and externalizing symptoms in children and adolescents with neuropsychiatric disorder. Similarly, parental stress increased during COVID-19 and ahigher level of stress in parents can be related to the internalizing symptoms of their children.

Introduction: Benign epilepsy with centrotemporal spikes (BECTS) is a common epileptic syndrome in childhood, characterized by brief and infrequent partial motor seizures, with or without generalization and mostly recurring during sleep. Because of its favorable efficacy, tolerability, and safety profile, levetiracetam (LEV) monotherapy is often administered in these patients. Long-term effects of LEV therapy and its influence on cognitive functions remain controversial.Purpose: This evaluated the changes in the cognitive profile of children with BECTS treated with LEV monotherapy for 2 years, compared with a control group of children with specific learning disabilities.Method: Our patient cohort included 20 children aged 8-14 years diagnosed as having BECTS and administered LEV monotherapy and 10 age/sex-matched controls with specific learning disabilities. All participants underwent a standardized test for assessing cognitive profile (Wechsler Intelligence Scale for Children - Fourth Edition [WISC-IV]) before drug therapy and after 2 years of treatment. Average LEV blood level and electroencephalo-graphic (EEG) recordings were periodically monitored. Several factors such as age, sex, response to therapy, and EEG pattern changes were considered. Statistical analysis was performed using Student's t-test for paired and independent samples. p < 0.05 was considered statistically significant.Results: Children administered LEV for 24 months showed a mild but statistically significant improvement in overall cognitive abilities. Verbal skills, visual-perceptual reasoning, working memory, and processing speed showed slight but significant improvement. In the control group, cognitive profile remained substantially unchanged at 2-year follow-up.Conclusions: Not only do our data suggest a nonworsening of the cognitive profile in BECTS with LEV but, on the contrary, cognitive scores also improved over time, unlike the control group. (C) 2019 Elsevier Inc. All rights reserved.

Background: The aim of our study was to trace a specific neuropsychological profile, to investigate emotional-behavioral problems and parental stress in children with Autism Spectrum Disorder Level 1/High functioning (ASD-HF), Specific Learning Disorders (SLD) and Attention Deficit/Hyperactivity Disorder (ADHD) disorders and to highlight similarities and differences among the three groups. Methods: We retrospectively collected the data from a total of 62 subjects with ASD-HF (n = 19) ADHD (n = 21), SLD (n = 22) and 20 typical development. All the participants underwent neuropsychological standardized test for the evaluation of cognitive profile (Wechsler Intelligence Scale for Children Fourth Edition—WISC-IV), behavioral and emotional problems (Child Behavior CheckList CBCL), and parental stress (Parental Stress Index Short Form—PSI-SF). The scores of the ASD-HF, ADHD, and SLD groups were compared using non-parametric statistic methods (Kruskall–Wallis H test and U Mann–Whitney for post-hoc analysis). Results: The ASD-HF group were significantly higher in all areas of the WISC-IV than the other two clinical groups. The SLD group performed significantly lower than ASD-HF in Working Memory Index. The SLD group showed lower scores on the somatic problems subscale than the other two groups. In the Difficult Child subscale of the PSI-SF, parents of ADHD children scored lower than the mothers of SLD subjects and higher than the fathers of SLD subjects. In all three groups there are specific deficiencies compared to the control group in the cognitive profile, behavioral and emotional problems, and parental stress. Conclusions: Our comparative analysis highlighted similarities and differences in three groups of children with different neurodevelopmental disorders, helping to better define cognitive, behavioral, and emotional characteristics of these children and parental stress of their parents.

A large body of literature reports the higher prevalence of epilepsy in subjects with Autism Spectrum Disorder (ASD) compared to the general population. Similarly, several studies report an increased rate of Subclinical Electroencephalographic Abnormalities (SEAs) in seizure-free patients with ASD rather than healthy controls, although with varying percentages. SEAs include both several epileptiform discharges and different non-epileptiform electroencephalographic abnormalities. They are more frequently associated with lower intellectual functioning, more serious dysfunctional behaviors, and they are often sign of severer forms of autism. However, SEAs clinical implications remain controversial, and they could represent an epiphenomenon of the neurochemical alterations of autism etiology. This paper provides an overview of the major research findings with two main purposes: to better delineate the state-of-the-art about EEG abnormalities in ASD and to find evidence for or against appropriateness of SEAs pharmacological treatment in ASD.

Functional non-retentive fecal incontinence (FNRFI) is a common problem in pediatric age. FNRFI is defined as unintended loss of stool in a 4-year-old or older child after organic causes have been excluded. FNRFI tends to affects up to 3% of children older than 4 years, with males being affected more frequently than females. Clinically, children affected by FNRFI have normal intestinal movements and stool consistency. Literature data show that children with fecal incontinence have increased levels of separation anxiety, specific phobias, general anxiety, attention-deficit/hyperactivity disorder (ADHD), and oppositional defiant disorder. In terms of possible relationship between incontinence and sleep, disorders of sleep organization have been observed in the pathogenesis of enuresis so generating the hypothesis that the orexinergic system may have a crucial role not only for the sleep organization per se but also for the sphincterial control in general. This study aimed to focus on specific neurophysiological aspects to investigate on the possible relationship between sleep organizational abnormalities and FNRFI. Specifically, we aimed to measure orexin serum levels in children with FNRFI and assess their polysomnographic sleep macrostructure patterns. Two study groups were considered: FNFRI (n = 45) and typically developed (TD) (n = 45) group. In both groups, sleep patterns and respiratory events were assessed by polysomnographic recordings (PSG) during a period of two nights at least, and plasma levels of Orexin-A were measured in each participant. The findings of this initial investigation seem to support a major role of Orexin-A in sleep organization alterations in children with FNFRI. Also, our data suggest that sleep habits evaluation should be considered as screening and complementary tool for the diagnosis of fecal incontinence in children.

Objectives Perampanel (PER) is a noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor antagonist recently approved for focal and generalized epilepsies as an add-on therapy. It is well tolerated and effective as treatment of various pediatric epilepsy syndromes; PER does not seem to negatively affect the cognitive profile of children and adolescents, but its influence on executive functions is still to be assessed. Methods Our sample included 37 children aged 12–18 years, with focal pharmacoresistant epilepsy already in therapy with 2 or 3 antiepileptic drug (AED); PER was added with 1 mg/week increments up to a dose of 2–4 mg/day. Changes in executive functions were assessed by the EpiTrack Junior test. Emotional and behavioral aspects were evaluated through the interview for parents Child Behavior Checklist (CBCL). Both tests were performed before taking PER and after 6 and 12 months of treatment. Results After 12 months of PER in 22/30 patients, global score of the EpiTrack Junior test remained almost unchanged; in 7/30 patients, this score improved. The CBCL did not show significant changes in emotional or behavioral problems. Conclusions Adjunctive treatment with PER did not negatively affect executive functions that could also be improved. No emotional/behavioral negative effects have been reported, and this suggests a good tolerability in the middle/long term.

(1) Background: Some recent studies suggest that children and adolescents with different neurodevelopmental disorders perform worse in emotions recognition through facial expressions (ER) compared with typically developing peers. This impairment is also described in children with Specific Learning Disorders (SLD), compromising their scholastic achievement, social functioning, and quality of life. The purpose of our study is to evaluate ER skills in children and adolescents with SLD compared to a control group without learning disorders, and correlate them with intelligence and executive functions. (2) Materials and Methods: Our work is a cross-sectional observational study. Sixty-three children and adolescents aged between 8 and 16 years, diagnosed with SLD, and 32 sex/age-matched controls without learning disorders were recruited. All participants were administered standardized neuropsychological tests, evaluating facial emotion recognition (NEPSY-II), executive functions (EpiTrack Junior), and intelligence profile (WISC-IV). (3) Results: Emotion recognition mean score was significantly lower in the SLD group than in the controls group on the Mann–Whitney U test for unpaired samples (p < 0.001). The SLD group performed significantly lower than the control group in their abilities to identify neutral expressions, happiness, sadness, anger, and fear compared to controls (p < 0.001). ER scores were positively correlated to the executive functions scores. There was no correlation with the Total Intelligence Quotient scores but there is a significant positive correlation with Working Memory Index and Processing Speed Index measured by WISC.IV. (4) Conclusions: Our study showed that children and adolescents with Specific Learning Disorders have facial emotion recognition impairment when compared with a group of peers without learning disorders. ER abilities were independent of their global intelligence but potentially related to executive functions.

Objectives Cognitive abilities and executive functions in children and adolescents are important indicators of quality of life as well as academic and social achievements. Cognitive and executive functioning are often impaired in patients with epilepsy and can be exacerbated by seizures and antiseizure drugs. The aim of our observational retrospective study was to assess executive functioning in patients with pediatric epilepsy, currently taking a single antiseizure medication. Materials and methods Records of 172 children and adolescents aged between 6 and 18 years (mean age = 12 ± 3.4 years) with newly diagnosed epilepsy who had not yet commenced an antiepileptic treatment were included in the study. Longitudinal changes in executive functioning were assessed using the EpiTrack Junior test at baseline, before the introduction of antiepileptic monotherapy, and at 3-month, 6-month, and 9-month follow-up visits. All patients commenced a single antiepileptic treatment (levetiracetam n = 54; valproic acid n = 52; ethosuximide n = 20; oxcarbazepine n = 22; carbamazepine n = 24). Age, sex, seizure types, and seizure baseline frequency were also recorded. Results Relative to baseline, Epitrack Junior mean scores deteriorated at the 9-month follow-up visit for patients taking valproic acid, ethosuximide, and carbamazepine, but this was only statistically significant for patients taking carbamazepine. In contrast, mean scores improved for subjects taking levetiracetam and oxcarbazepine at the 9-month follow-up visit relative to baseline, but this was only statistically significant for patients taking levetiracetam. Conclusions Levetiracetam was the only antiseizure medication that led to slight improvements in executive functioning; whereas carbamazepine led to deteriorations in cognitive functioning. Further research using double-blinded, placebo-controlled trials are needed to confirm these results.

Background. Obstructive sleep apnea syndrome (OSAS) affects up to 4% of a pediatric population, with many comorbidities in the medium-long term. Functional alterations in the prefrontal cortex (PFC) may explain why OSAS impacts aspects such as executive functions, memory, motor control, attention, visual-spatial skills, learning, and mood regulation. Emotional intelligence (EI) is a complex neuropsychological function that could be impaired in many clinical conditions. Purpose. The aim of the study is to evaluate the difference in emotional intelligence skills among children with OSAS and healthy subjects (nOSAS). Methods. 129 children (72 males; mean age 7.64±1.98 years) affected by OSAS were compared to 264 non-OSAS (nOSAS) children (138 males; mean age 7.98±2.13) similar for gender, age, and socioeconomic status. In order to assess the emotional quotient, the Bar-On Emotional Quotient Inventory: Youth Version (EQ-i:YV) was used. Results. The comparison for means and standard deviation between OSAS children and nOSAS children for EQ-i:YV scores showed significant differences for Interpersonal, Adaptability, and Stress Management scales and EQ Total score. Conclusions. Our findings highlighted the role of intermittent hypoxia in the genesis of the effects of sleep-related respiratory disorders, which involves also aspects different from physical impairments.