Oral Health and Quality of Life in People with Autism Spectrum Disorder.

This article delves into the intricate relationship between oral health, quality of life, and behavioral characteristics in individuals with autism spectrum disorder (ASD). Background/Objectives: Autism has been associated with various challenges, and this study seeks to elucidate the impact of ASD on oral health outcomes and overall well-being. The research focuses on assessing overall oral health by evaluating various parameters, such as the condition of lips, tongue, gums and tissues, natural teeth, dentures, oral hygiene, and dental pain in individuals with ASD. Additionally, the study explores the influence of age, sex, and certain variables, like basic daily living skills on oral health practices, aiming to identify potential correlations between these factors and oral health outcomes. Methods: We employed standardized instruments to quantitatively measure and analyze the impact of oral health status on the overall quality of life experienced by individuals with ASD. Results: The study found a statistically significant positive association between oral health, measured by the Oral Health Assessment Tool (OHAT), and quality of life, as indicated by EuroQol 5-Dimensions Youth version (EQ-5D-Y) total scores (ß = 0.13045, p = 0.00271). This suggests that better oral health is linked to higher quality of life. When adjusting for age and sex in a multiple linear regression model, the association remained significant but with a slightly reduced effect size (ß = 0.10536, p = 0.0167). Age also showed a marginally significant positive association with quality-of-life scores. ANOVA results indicated that participants with advanced oral health status reported significantly higher quality-of-life scores than those with poorer oral health (p = 0.00246). The study also found that intelligence quotient (IQ) does not substantially influence dental health status, while the "Autonomy" subscale of the EQ-5D-Y is positively related to the OHAT. Conclusions: Unhealthy oral conditions significantly impact the overall quality of life in individuals with ASD. Therefore, it is crucial to include regular dental assessments and treatments in therapeutic protocols for patients with ASD.

PLEKHG1: New Potential Candidate Gene for Periventricular White Matter Abnormalities.

Hypoxic-ischemic brain damage presents a significant neurological challenge, often manifesting during the perinatal period. Specifically, periventricular leukomalacia (PVL) is emerging as a notable contributor to cerebral palsy and intellectual disabilities. It compromises cerebral microcirculation, resulting in insufficient oxygen or blood flow to the periventricular region of the brain. As widely documented, these pathological conditions can be caused by several factors encompassing preterm birth (4-5% of the total cases), as well single cotwin abortion and genetic variants such as those associated with GTPase pathways. Whole exome sequencing (WES) analysis identified a de novo causative variant within the pleckstrin homology domain-containing family G member 1 (PLEKHG1) gene in a patient presenting with PVL. The PLEKHG1 gene is ubiquitously expressed, showing high expression patterns in brain tissues. PLEKHG1 is part of a family of Rho guanine nucleotide exchange factors, and the protein is essential for cell division control protein 42 (CDC42) activation in the GTPase pathway. CDC42 is a key small GTPase of the Rho-subfamily, regulating various cellular functions such as cell morphology, migration, endocytosis, and cell cycle progression. The molecular mechanism involving PLEKHG1 and CDC42 has an intriguing role in the reorientation of cells in the vascular endothelium, thus suggesting that disruption responses to mechanical stress in endothelial cells may be involved in the formation of white matter lesions. Significantly, CDC42 association with white matter abnormalities is underscored by its MIM phenotype number. In contrast, although PLEKHG1 has been recently associated with patients showing white matter hyperintensities, it currently lacks a MIM phenotype number. Additionally, in silico analyses classified the identified variant as pathogenic. Although the patient was born prematurely and subsequently to dichorionic gestation, during which its cotwin died, we suggest that the variant described can strongly contribute to PVL. The aim of the current study is to establish a plausible association between the PLEKHG1 gene and PVL.

Neurodevelopmental Disorders and Suicide: A Narrative Review.

Specific risk factors for self-harm and suicide in children and adolescents with neurodevelopmental disorders (NDD) may differ from those in the general population within this age range. In the present review paper, we conducted a narrative analysis of the literature, aiming to establish a connection between suicide and affective disorders in children and adolescents with NDD. Emotion dysregulation (ED) as an individual factor and adverse childhood experiences (ACE) as environmental factors are discussed as risk factors for suicidality in all individuals with NDD. We propose a theoretical model in which ED and ACE can directly lead to self-harm or suicide, directly or indirectly by interacting with depressive spectrum disorders. Additionally, we suggest that specific risk factors are more frequently associated with each of the neurodevelopmental disorders listed in the DSM-V. This review underlines the key points useful to improve the knowledge of the trajectory leading to suicide risk in NDDs with the purpose to facilitate the early identification of the suicide risk.

Whole Exome Sequencing as a First-Line Molecular Genetic Test in Developmental and Epileptic Encephalopathies.

Developmental and epileptic encephalopathies (DEE) are severe neurodevelopmental disorders characterized by recurrent, usually early-onset, epileptic seizures accompanied by developmental impairment often related to both underlying genetic etiology and abnormal epileptiform activity. Today, next-generation sequencing technologies (NGS) allow us to sequence large portions of DNA quickly and with low costs. The aim of this study is to evaluate the use of whole-exome sequencing (WES) as a first-line molecular genetic test in a sample of subjects with DEEs characterized by early-onset drug-resistant epilepsies, associated with global developmental delay and/or intellectual disability (ID). We performed 82 WESs, identifying 35 pathogenic variants with a detection rate of 43%. The identified variants were highlighted on 29 different genes including, 3 new candidate genes (KCNC2, STXBP6, DHRS9) for DEEs never identified before. In total, 23 out of 35 (66%) de novo variants were identified. The most frequently identified type of inheritance was autosomal dominant de novo (60%) followed by autosomal recessive in homozygosity (17%) and heterozygosity (11%), autosomal dominant inherited from parental mosaicism (6%) and X-linked dominant de novo (6%). The most frequent mutations identified were missense (75%) followed by frameshift deletions (16%), frameshift duplications (5%), and splicing mutations (3%). Considering the results obtained in the present study we support the use of WES as a form of first-line molecular genetic testing in DEEs.

STXBP6 Gene Mutation: A New Form of SNAREopathy Leads to Developmental Epileptic Encephalopathy.

Syntaxin-binding protein 6 (STXBP6), also known as amysin, is an essential component of the SNAP receptor (SNARE) complex and plays a crucial role in neuronal vesicle trafficking. Mutations in genes encoding SNARE proteins are often associated with a broad spectrum of neurological conditions defined as "SNAREopathies", including epilepsy, intellectual disability, and neurodevelopmental disorders such as autism spectrum disorders. The present whole exome sequencing (WES) study describes, for the first time, the occurrence of developmental epileptic encephalopathy and autism spectrum disorders as a result of a de novo deletion within the STXBP6 gene. The truncated protein in the STXBP6 gene leading to a premature stop codon could negatively modulate the synaptic vesicles' exocytosis. Our research aimed to elucidate a plausible, robust correlation between STXBP6 gene deletion and the manifestation of developmental epileptic encephalopathy.

Diet-Related Attitudes, Beliefs, and Well-Being in Adolescents with a Vegetarian Lifestyle.

Vegetarianism can meet healthy, ethical, or ecological values (such as equality and protection of animals or the environment). At the same time, it can represent a response to the need for self-determination in adolescence. Furthermore, some studies show vegetarians have greater depressive risk and a lower sense of body satisfaction. Considering the spread of non-meat diets in the Western world, researchers have investigated the benefits and risks to physical and psychological health. Despite this, few studies have been conducted on factors influencing adolescent's vegetarian diet-related attitudes. Through self-administered loosely structured interviews, this research investigated factors potentially associated with vegetarian choices in adolescence. It checked (a) gender differences in vegetarian choices; (b) religious, familial, ethical, or health factors implied in vegetarian choices; and (c) indicators of well-being among young vegetarians. The findings suggest that for our sample, non-vegetarians have lower scores on health-related questions than others, while for vegetarian adolescents, the benefits of vegetarianism mainly depend on their ethical stances, beliefs, and values. Conversely, it is unrelated to factors such as the desire to lose weight, dissatisfaction about one's body shape, or depressive feelings.

Use and Abuse of Digital Devices: Influencing Factors of Child and Adolescent Neuropsychology.

The impact of technology on human life is significant, touching various aspects such as communication, economy, education, medicine, industry, and even ecosystems [...].

Specific Learning Disorders: Variation Analysis of 15 Candidate Genes in 9 Multiplex Families.

Background and Objectives: Specific Learning Disorder (SLD) is a complex neurobiological disorder characterized by a persistent difficult in reading (dyslexia), written expression (dysgraphia), and mathematics (dyscalculia). The hereditary and genetic component is one of the underlying causes of SLD, but the relationship between genes and the environment should be considered. Several genetic studies were performed in different populations to identify causative genes. Materials and Methods: Here, we show the analysis of 9 multiplex families with at least 2 individuals diagnosed with SLD per family, with a total of 37 persons, 21 of whom are young subjects with SLD, by means of Next-Generation Sequencing (NGS) to identify possible causative mutations in a panel of 15 candidate genes: CCPG1, CYP19A1, DCDC2, DGKI, DIP2A, DYM, GCFC2, KIAA0319, MC5R, MRPL19, NEDD4L, PCNT, PRMT2, ROBO1, and S100B. Results: We detected, in eight families out nine, SNP variants in the DGKI, DIP2A, KIAA0319, and PCNT genes, even if in silico analysis did not show any causative effect on this behavioral condition. In all cases, the mutation was transmitted by one of the two parents, thus excluding the case of de novo mutation. Moreover, the parent carrying the allelic variant transmitted to the children, in six out of seven families, reports language difficulties. Conclusions: Although the present results cannot be considered conclusive due to the limited sample size, the identification of genetic variants in the above genes can provide input for further research on the same, as well as on other genes/mutations, to better understand the genetic basis of this disorder, and from this perspective, to better understand also the neuropsychological and social aspects connected to this disorder, which affects an increasing number of young people.

Effectiveness of an Educational Filmmaking Project in Promoting the Psychological Well-Being of Adolescents with Emotive/Behavioural Problems.

Evidence suggests that adolescents respond positively to simple, early interventions, including psychosocial support and educational interventions, even when offered in non-clinical settings. Cinematherapy can help manage life challenges, develop new skills, increase awareness, and offer new ways of thinking about specific problems. This pilot trial was conducted in Italy, aiming to investigate the effects of a six-week filmmaking course on the psychological well-being of adolescents (N = 52) with emotional/behavioural problems and neurodevelopmental disorders. At the end of the project, most participants showed improvements mostly in social skills, such as social cognition (p = 0.049), communication (p = 0.009), and motivation (p = 0.03), detected using the SRS Social Responsiveness Scale. In addition, social awareness (p = 0.001) increased in all patients. Statistically significant differences resulted in four sub-scales of Youth Self-Report Scale: withdrawn/depressed (p = 0.007), social problems (p = 0.003), thought problems (p < 0.001), and rule-breaking behaviour (p = 0.03); these results showed a decrease in emotional and behavioural problems. This study is an innovative therapeutic and educational approach based on the filmmaking art. This research can offer an empirical basis for the effectiveness of alternative therapeutic tools in child and adolescent psychiatric disorders. At the same time, it can be replicated in broader contexts (e.g., school and communities) to promote children's psychological well-being.

The Complex Association between Sleep Quality, Psychological Wellbeing, and Neurodevelopmental Disorders in Childhood.

During child development, the psychophysiological state is influenced by factors such as family routine, school experiences, stressful life events, or, in general, the environmental context in which the child grows up [...].

Evolution of Pediatric Migraine Patients Admitted at an Emergency Department after a 10-Year Follow-Up.

BACKGROUND: Despite its high prevalence, the clinical course of pediatric migraine has not been fully understood, and previous studies present conflicting results. We present here the findings of a 10-year follow-up study involving children with severe migraine pain admitted to our emergency department. Furthermore, all studies were carried out on selected outpatient clinical case studies. Our aim was to evaluate a population of migraine children admitted to an emergency department because of increased severity or frequency of pain or even because of very anxious parents concerning their child's headache in order to describe their long-term outcomes, whether it differed from that of outpatient populations and to identify possible predictors of prognosis. METHODS: We recruited 80 subjects with migraine headaches (mean age 8 years with a range of 4-14 years, 50% females), attending the baseline examination of a population admitted for a headache to the Emergency Department in the first half year of 2012. Of the 80 subjects, 48 (60%) were eligible for follow-up in 2022. We included in our study only patients diagnosed with migraine, according to the diagnostic criteria of the International Classification of Headache Disorders. All were contacted by telephone, and a semi-structured questionnaire was provided to them by email. The association between several possible prognostic factors (gender, familiar neurologic disorders, prenatal and perinatal disorders, social activities, sleep disorders, etc.) and the long-term persistence of migraine headaches were explored using logistic regression analysis. RESULTS: Of 48 subjects with migraine headaches at baseline, 31 (65%) had persistent migraine, and 17 (35%) experienced remission. The preliminary results showed that the presence of neurologic disorders in parents (p < 0.01-odds ratio 9.34 (2.53-41.64) and sleep disorders (p < 0.01-odds ratio 13.18 (2.25-252.74) significantly predicted the 10-year persistence of migraine headaches, while the other considered predictors were found not to influence prognosis. CONCLUSIONS: To our knowledge, this was the first study conducted on a selected pediatric population upon admission to the emergency room. Our study suggests that a population of pediatric migraine selected for admission to the emergency department also shows a favorable long-term prognosis, like the studies conducted in the outpatient sample. Familial neurological comorbidity and sleep disorders were unfavorable factors for predicting good outcomes.

On the Waves of the COVID-19 Pandemic.

The COVID-19 pandemic has been a tsunami that has deeply changed the lives of the people all over the planet [...].

Epilepsy: A Multifaced Spectrum Disorder.

Epilepsy is one of the most widespread chronic conditions, affecting about 50 million people worldwide [...].

Poor School Academic Performance and Benign Epilepsy with Centro-Temporal Spikes.

BACKGROUND: Poor academic performance of students with epilepsy seems to be a multifactorial problem related to difficulties in reading, writing, math, and logic skills. Poor school and academic performances refer to learning problems in a specific academic area due to learning disorders and learning difficulties not excluding the ability to learn in a different manner during school and academic life. Sometimes, school, academic difficulties, and Rolandic epilepsy can coexist together, and there may be comorbidities. Consequently, the risk of impaired academic performance in people with epilepsy is high. METHODS: This review analyzed the relationship between Benign Epilepsy with Centro-Temporal Spikes (BECTS) and poor school and academic performance (PSAP) in children and adolescents (aged 6 to 19), and in adults (aged 20 to no age limit). The PRISMA guideline was used to guide our review strategy. RESULTS: This research shows that Benign Epilepsy with Centro-Temporal Spikes (BECTS) and poor school and academic performances are strongly correlated. An early onset age, as well as a long persistence of seizures, correlate more closely with PSAP. On the other hand, it appears that good pharmacological control of seizures and remission from the acute phase of the pathology support better school performance. CONCLUSIONS: This review highlights how neuropsychological aspects are also involved in patients with BECTS and PSAP, both in the greater predisposition to the establishment of other neuropsychiatric conditions and in the possibility that stigma conditions and poor academic results may have repercussions on the adaptation and functioning of these subjects. Global management of the subject with BECTS and PSAP is essential, which also pays attention to the aspects of social and scholastic inclusion, both to achieve age-appropriate educational and behavioral objectives, to give the necessary tools for the growth of the individual, and to allow a serene transition to adulthood, favoring autonomous learning and better outcomes.

1H-NMR-Based Metabolomics in Autism Spectrum Disorder and Pediatric Acute-Onset Neuropsychiatric Syndrome.

We recently described a unique plasma metabolite profile in subjects with pediatric acute-onset neuropsychiatric syndrome (PANS), suggesting pathogenic models involving specific patterns of neurotransmission, neuroinflammation, and oxidative stress. Here, we extend the analysis to a group of patients with autism spectrum disorder (ASD), as a consensus has recently emerged around its immune-mediated pathophysiology with a widespread involvement of brain networks. This observational case-control study enrolled patients referred for PANS and ASD from June 2019 to May 2020, as well as neurotypical age and gender-matched control subjects. Thirty-four PANS outpatients, fifteen ASD outpatients, and twenty-five neurotypical subjects underwent physical and neuropsychiatric evaluations, alongside serum metabolomic analysis with 1H-NMR. In supervised models, the metabolomic profile of ASD was significantly different from controls (p = 0.0001), with skewed concentrations of asparagine, aspartate, betaine, glycine, lactate, glucose, and pyruvate. Metabolomic separation was also observed between PANS and ASD subjects (p = 0.02), with differences in the concentrations of arginine, aspartate, betaine, choline, creatine phosphate, glycine, pyruvate, and tryptophan. We confirmed a unique serum metabolomic profile of PANS compared with both ASD and neurotypical subjects, distinguishing PANS as a pathophysiological entity per se. Tryptophan and glycine appear as neuroinflammatory fingerprints of PANS and ASD, respectively. In particular, a reduction in glycine would primarily affect NMDA-R excitatory tone, overall impairing downstream glutamatergic, dopaminergic, and GABAergic transmissions. Nonetheless, we found metabolomic similarities between PANS and ASD that suggest a putative role of N-methyl-D-aspartate receptor (NMDA-R) dysfunction in both disorders. Metabolomics-based approaches could contribute to the identification of novel ASD and PANS biomarkers.

Psychopathological Risk Assessment in Children with Hyperphenylalaninemia.

BACKGROUND: Phenylketonuria (PKU) is a rare congenital disorder caused by decreased metabolism of phenylalanine determining cerebral impairments. If untreated, PKU might lead to intellectual disability, seizures and behavioral disorders. The aim of this study is to provide a characterization of the psychopathological profile of a pediatric population diagnosed with PKU at newborn screening. METHODS: an accurate neuropsychological evaluation of 23 patients (aged 8-18 years) with hyperphenylalaninemia (defined as experimental group, EG) and in 23 age-matched healthy controls (defined as control group, CG) was performed using the Child and Adolescent Behavior Inventory (CABI) and Self-Administrated Psychiatric Scales for Children and Adolescents (SAFA) questionnaires. RESULTS: the CABI test showed significant differences for the sub-scales related to "Irritable mood", "Oppositional-provocative symptoms" and "ADHD" in the EG compared to CG (p = 0.014, p = 0.032, and p = 0.032, respectively). Patients with hyperphenylalaninemia also presented with significant differences both for anxiety disorder scale and depression scale of SAFA test than controls (p = 0.018 and p = 0.009, respectively). CONCLUSIONS: children and adolescents with early diagnosis of PKU showed a psychopathological risk profile characterized by an increased risk of experiencing symptoms such as mood deflection, anxiety, attention deficit, oppositional defiant behavior, and obsessive traits than healthy peers. Our findings highlighted the need of the inclusion of a neuropsychiatric evaluation in the management of these patients to improve their overall quality of life.

Impact of Three Kinds of Early Interventions on Developmental Profile in Toddlers with Autism Spectrum Disorder.

Autism spectrum disorder is a neurodevelopmental disorder with a rising prevalence disorder. This high-cost/high-burden condition needs evidence-based behavioral treatments that are able to reduce the impact of symptoms on children's functioning. This retrospective chart review study compared the impact of different types of early interventions on toddlers diagnosed with an autism spectrum disorder developmental profile. Analyses were conducted on 90 subjects (mean = 27.76 months, range 18−44 months; M:F = 4.29:1), of which 36 children underwent the usual treatment, 13 children underwent an intervention based on early intensive behavioral intervention (EIBI) and 41 children received the Early Start Denver Model, for one year, with the same weekly frequency of about 6 h a week. A significant decrease in the severity of autism symptoms was observed for all children when looking at the Ados-2 severity score (average difference = 3.05, SD = 0.71, p = < 0.001) and the Ados-2 social subscale (average difference = 2.87, SD = 0.59, p < 0.001). Otherwise, for most of the Griffiths subscales, we found a significant improvement only for those children who underwent the Early Start Denver Model intervention (General Quotient average difference = 14.47, SD = 3.22, corrected p < 0.001). Analyzing the influence of age on the investigated scores, we found a significant association with the Eye−hand Coordination Quotient (p = 0.003), Performance Quotient (p = 0.042) and General Quotient (p = 0.006). In all these domains, a mild negative correlation with age was observed, as measured by the Pearson's correlation coefficient (r = −0.32, p = 0.002; r = −0.21, p = 0.044; r = −0.25, p = 0.019, respectively), suggesting less severe developmental skills at the start of treatment for older children. Our results are consistent with the literature that underlines the importance of early intervention, since prompt diagnosis can reduce the severity of autism symptoms; nevertheless, in toddlers, our study demonstrated that an intervention model based on naturalistic developmental behavioral principles such as the Early Start Denver Model is more effective on children's developmental profile. Further studies are required to assess the extent of effectiveness of different early intervention models in community settings.

Prosocial priming and bystander effect in an online context.

The present study tested the effect of priming the concept of prosociality on the bystander effect in an online environment. Participants were sent an e-mail requesting a plea for help and randomly assigned to one of four conditions in a 2 (Bystander: 0 vs. 14) × 2 (Priming: present vs. absent) design. The results demonstrated support for the study hypothesis. As expected, the virtual presence of many others significantly reduced e-mail responsiveness except when the request for help is preceded by prosocial priming. Implications of these findings for the literature on the bystander effect and priming are discussed.

Perampanel and childhood absence epilepsy: A real life experience.

Objectives: The aim of our study was to evaluate the effectiveness and tolerability of perampanel (PER) as first add-on and as second line monotherapy in subjects with childhood absence epilepsy. Methods: Our sample consisted of 20 patients with childhood absence epilepsy, aged between 8 and 10, already in therapy with a first antiseizure medication with incomplete seizure control. PER was added as first add-on in a dose ranging from 3 to 8 mg/die with 1- 2 mg/week increments. The patients that were seizure-free were shifted to a PER monotherapy. All patients underwent a standardized neuropsychological evaluation in order to assess non-verbal intelligence and executive functions before adding PER and after 6 months of drug therapy. All parents completed two questionnaires, in order to assess the emotional-behavioral problems and parental stress. Results: 15/20 patients responded to add-on PER and were seizure-free, in 3/20 patients we observed a reduction of seizure frequency <50%, and in the 2 remaining patients the add-on therapy with PER did not lead to a reduction in seizures frequency from baseline. The patients who were seizure-free were switched to PER monotherapy. 9/15 patients remained seizure-free in monotherapy with PER. In the first month of therapy with PER 2/20 patients (10%) reported mild, transient side effects of irritability, headache and dizziness, which did not lead to discontinuation of therapy. Adjunctive treatment with PER did not negatively affect non-verbal intelligence, executive functions, emotional/behavioral symptoms of children and parental stress levels. Significance: Our clinical experience in real life showed that PER appears to be effective in the control of absence seizures in childhood absence epilepsy, with a favorable tolerability profile. PER would seem effective on absence seizures even in monotherapy. Further studies with larger samples, longer follow-up and controlled vs. placebo (or other first choice antiseizure medications) are needed to confirm our data.

Exome sequencing in a child with neurodevelopmental disorder and epilepsy: Variant analysis of the AHNAK2 gene.

BACKGROUND: The AHNAK2 gene encodes a large nucleoprotein expressed in several tissues, including brain, squamous epithelia, smooth muscle, and neuropil. Its role in calcium signaling has been suggested and to date, clear evidence about its involvement in the pathogenesis of clinical disorders is still lacking. METHODS: Here, we report a female 24-year-old patient diagnosed with a cardio-facio-cutaneous-like phenotype (CFC-like), characterized by epilepsy, psychomotor development delay, atopic dermatitis, congenital heart disease, hypotonia, and facial dysmorphism, who is compound heterozygote for two missense mutations in the AHNAK2 gene detected by exome sequencing. RESULTS: This patient had no detectable variant in any of the genes known to be associated with the cardio-facio-cutaneous syndrome. Moreover, the mode of inheritance does not appear to be autosomal dominant, as it is in typical CFC syndrome. We have performed in silico assessment of mutation severity separately for each missense mutation, but this analysis excludes a severe effect on protein function. Protein structure predictions indicate the mutations are located in flexible regions possibly involved in molecular interactions. CONCLUSION: We discuss an alternative interpretation on the potential involvement of the two missense mutations in the AHNAK2 gene on the expression of CFC-like phenotype in this patient based on inter-allelic complementation.