Onasemnogene abeparvovec gene replacement therapy for the treatment of spinal muscular atrophy: a real-world observational study.

Spinal muscular atrophy (SMA) is a genetically inherited recessive neuromuscular disease that causes muscular atrophy and weakness. Onasemnogene abeparvovec (formerly AVXS-101, Zolgensma®, Novartis) is a targeted therapy approved to treat patients with SMA in >40 countries worldwide. This study describes the clinical efficacy and tolerability of gene replacement therapy with onasemnogene abeparvovec over a 3-month period in 9 SMA type 1 patients aged 1.7-48 months, with 7 patients on stable nusinersen (i.e., had received all four nusinersen loading doses before inclusion in this study). Liver function (alanine aminotransferase, aspartate aminotransferase, total bilirubin), troponin I, platelet counts, creatinine levels, and motor function (CHOP-INTEND) were monitored. For the seven patients on stable nusinersen, the median baseline CHOP-INTEND score increased significantly during nusinersen treatment (Wilcoxon signed-rank test p = 0.018) and at 3 months after switching to onasemnogene abeparvovec (Wilcoxon signed-rank test p = 0.0467). We also identified two patients who responded poorly to nusinersen but showed the largest increase in baseline CHOP-INTEND scores at 1 and 3 months after switching, which could suggest that poor responders to nusinersen may respond favorably to onasemnogene abeparvovec. No unknown adverse events occurred. One patient developed moderate/severe thrombocytopenia 1 week after onasemnogene abeparvovec administration that resolved after treatment. Our study suggests the possibility of a change in the dynamic of CHOP-INTEND for patients who respond poorly to nusinersen after switching therapy to onasemnogene abeparvovec. Alternatively, patient age at treatment initiation may impact the response to onasemnogene abeparvovec. Testing in larger patient populations must be undertaken to assess the plausibility of these hypotheses.

Childhood Obesity and Maternal Personality Traits: A New Point of View on Obesity Behavioural Aspects.

The epidemic spread of childhood obesity in Western society has interested many researchers, who agree in defining it as a multifactorial disease in which not only eating habits and sedentary lifestyle play a role, but also genetic predisposition. The aim of this study was to analyze the personality profile of a group of mothers of children with obesity and to compare this profile to that of a group of mothers of children without obesity. A total of 258 mothers participated in the study (126 mothers of children with obesity and 132 mothers of children without obesity). Weight and height were measured and the body mass index was calculated. The Minnesota Multiphasic Personality Inventory second edition (MMPI-2), evaluating personality and psychological disorders, was used to evaluate the personality profile. The results suggested that mothers of children with obesity score higher than the mothers of children without obesity in all MMPI-2 subscales. In most of these subscales, the differences between the two groups of mothers were statistically significant and with a medium to high effect size. These data suggest a new perspective on childhood obesity, identifying it as a multifactorial pathology that requires a multimodal and multidisciplinary approach that also takes care of caregivers to ensure optimal therapeutic efficacy.

Association between anorexia nervosa and other specified eating or feeding disorders and paranoia in adolescents: what factors are involved?

INTRODUCTION: In eating disorders, the association with other psychiatric symptoms is of particular interest. The association between anorexia nervosa and psychotic symptoms is less studied than that with affective disorders (anxiety/depression). The aim of this study is to describe a psychotic symptom (paranoia) in adolescents with anorexia nervosa looking at several potential explicative associated factors: eating disorder symptoms, body image concerns, depression and social anxiety. Our hypothesis is that paranoia in anorexia nervosa patients is better explained by the concomitant depression and social anxiety symptoms than the core symptoms of the disease (eating disorder symptoms or body image concerns). METHODS: This is a retrospective study. Consecutive, help-seeking adolescents, admitted to the Eating Disorder Service of the Integrated Pediatric Care Department, Luigi Vanvitelli University Hospital, constituted the sample. Data was obtained through retrospective collection of clinical interviews and self-report questionnaires, used for the routine assessment of these patients, administered by trained and expert child and adolescent psychiatrists, they were the Eating Attitude Test-26 (EAT-26), the Body Uneasiness Test-A (BUT-A), the Children Depression Inventory (CDI), the Liebowitz Social Anxiety Scale-Children and Adolescents (LSAS-CA) and the paranoia subscale of the Specific Psychotic Experiences Questionnaire (SPEQ). RESULTS: We obtained data from 92 adolescents with anorexia nervosa and other specified feeding or eating disorder (OSFED). Our regression model explained that paranoia (SPEQ-paranoia subscale) in this population was better explained by depression (CDI) (coefficient= 0.415 SD: 0.210, p=0.052) and social anxiety symptoms (LSAS-CA) (coefficient= 0.253 SD: 0.060; p<0.001) than eating disorder symptoms (EAT-26) (coefficient= 0.092 SD: 0.107; p=0.398) and body image concerns (BUT-A) (coefficient= 1.916 SD: 2.079; p=0.359). CONCLUSIONS: This study has some theoretical, clinical and treatment implications. It is important to carrying out screening for the presence of psychotic symptoms in patients with eating or feeding disorders. These symptoms and associated factors (depression and social anxiety) may complicate the clinical picture of the disease with the need, in certain cases, of psychopharmacological drugs and, among these, anti-psychotics. Finally in the psychotherapy context, paranoid ideas may be subject of treatment for patient with anorexia nervosa.

Neurodevelopmental Disorders: Effect of High-Fat Diet on Synaptic Plasticity and Mitochondrial Functions.

Neurodevelopmental disorders (NDDs) include diverse neuropathologies characterized by abnormal brain development leading to impaired cognition, communication and social skills. A common feature of NDDs is defective synaptic plasticity, but the underlying molecular mechanisms are only partially known. Several studies have indicated that people's lifestyles such as diet pattern and physical exercise have significant influence on synaptic plasticity of the brain. Indeed, it has been reported that a high-fat diet (HFD, with 30-50% fat content), which leads to systemic low-grade inflammation, has also a detrimental effect on synaptic efficiency. Interestingly, metabolic alterations associated with obesity in pregnant woman may represent a risk factor for NDDs in the offspring. In this review, we have discussed the potential molecular mechanisms linking the HFD-induced metabolic dysfunctions to altered synaptic plasticity underlying NDDs, with a special emphasis on the roles played by synaptic protein synthesis and mitochondrial functions.

Emotional-Behavioral Disorders in Healthy Siblings of Children with Neurodevelopmental Disorders.

Background and Objectives: Siblings of disabled children are more at risk of developing mental illnesses. More than 50 international studies show that about 8% of children and adolescents suffer from a mental disorder, which is almost always a source of difficulties both at the interpersonal level (in the family and with peers) and at school. Healthy siblings of children with disabilities are one of the groups most at risk for consequences in psychological health and well-being. As some authors suggest, siblings build their idea of "being people", in terms of character and personality, by continuously and daily confronting themselves with the theme of disability and a family context subjected to continuous stress. The following contribution aims to compare emotional-behavioral disorders in healthy siblings of children with autism spectrum disorder, in healthy siblings of children with Down's syndrome and in healthy siblings of children with typical development. Materials and Methods: The results involve 153 children from the region of Campania and their caregivers through the administration of the Strength and Difficulties Questionnaire. Results: From the data, it emerged that siblings of children with autism spectrum disorder and siblings of children with Down's syndrome have a greater emotional fragility, especially among male subjects. Conclusions: Our results require us to reflect on the clinical and policy measures needed to ensure the well-being of siblings of disabled children, mainly through appropriate sibling coping training.

Electroencephalographic Abnormalities in Autism Spectrum Disorder: Characteristics and Therapeutic Implications.

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.

Neuropeptides' Hypothalamic Regulation of Sleep Control in Children Affected by Functional Non-Retentive Fecal Incontinence.

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.

Parental Stress and Parental Ratings of Behavioral Problems of Enuretic Children.

Background: Primary monosymptomatic nocturnal enuresis (PMNE) may have a stressful impact on the everyday life of children and parents, and it may represent a cumulative stress factor increasing feelings of "learned helplessness." Methods: The current study investigated parental stress in a group of parents (n = 330) of children affected by PMNE, compared to a group of parents (n = 330) of typical developing children (TDC). In addition, the study evaluated whether parents of PMNE children experience more emotional, social, and behavioral problems in their children, compared to parents of TDC. Finally, the study correlated frequency of enuresis with stress values and Child Behavior Checklist (CBCL) subscales and total stress with CBCL. Both groups were given The Parental Stress Inventory-Short Form (PSI-SF) and the Child Behavior Checklist (CBCL). Results: Parents of PMNE children showed significantly higher stress level than parents of TDC. Nocturnal enuresis, as a demanding clinical condition difficult to control, represents a relevant stress factor. Mothers appeared as more vulnerable to stress than fathers. Parents of PMNE children reported higher behavioral and emotional problems, compared to reports of parents of TDC. PMNE children appeared to their parents as having lower competency in social activities, school performance, and social relationships than TDC. Moreover, they were rated as more withdrawn, anxious-depressed, more aggressive, inattentive, and with more somatic complaints than healthy children. It was always the mother who rated a significantly higher number of emotional, social, and behavioral problems compared to fathers. Correlational analysis showed that the higher the frequency of enuresis, the greater the parental stress level, the lower the social activities, school performance and relational competencies and the higher the emotional, social and behavioral problems in children, according to the parents' evaluations. The greater the parental stress level, the lower the competencies rated and the higher the behavioral problems detected by parents. Conclusion: The physicians who deal with PMNE children have taken into account the stressful role and emotional dimensions of this clinical condition, both for children and mothers, in order to improve clinical management. Psychological support is needed for parents, and mothers especially, for a more functional stress management related to the PMNE.

Sleep Macrostructure and NREM Sleep Instability Analysis in Pediatric Developmental Coordination Disorder.

Developmental Coordination Disorder (DCD) is considered to be abnormal motor skills learning, identified by clumsiness, slowness, and/or motor inaccuracy impairing the daily-life activities in all ages of life, in the absence of sensory, cognitive, or neurological deficits impairment. The present research focuses on studying DCD sleep structure and Cyclic Alternating Pattern (CAP) parameters with a full overnight polysomnography and to study the putative correlations between sleep architecture and CAP parameters with motor coordination skills. The study was a cross-sectional design involving 42 children (26M/16F; mean age 10.12 ± 1.98) selected as a DCD group compared with 79 children (49M/30F; mean age 9.94 ± 2.84) identified as typical (no-DCD) for motor ability and sleep macrostructural parameters according to the MABC-2 and polysomnographic (PSG) evaluations. The two groups (DCD and non-DCD) were similar for age (p = 0.715) and gender (p = 0.854). More significant differences in sleep architecture and CAP parameters were found between two groups and significant correlations were identified between sleep parameters and motor coordination skills in the study population. In conclusion, our data show relevant abnormalities in sleep structure of DCD children and suggest a role for rapid components of A phases on motor coordination development.

Emotional Intelligence in Children with Severe Sleep-Related Breathing Disorders.

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.

Maternal Stress and Coping Strategies in Developmental Dyslexia: An Italian Multicenter Study.

BACKGROUND: Studies about the impact of developmental dyslexia (DD) on parenting are scarce. Our investigation aimed to assess maternal stress levels and mothers' copying styles in a population of dyslexic children. METHODS: A total of 874 children (500 boys, 374 girls; mean age 8.32 ± 2.33 years) affected by DD was included in the study. A total of 1,421 typically developing children (789 boys, 632 girls; mean age 8.25 ± 3.19 years) were recruited from local schools of participating Italian Regions (Abruzzo, Calabria, Campania, Puglia, Umbria, Sicily) and used as control-children group. All mothers (of both DD and typically developing children) filled out an evaluation for parental stress (Parenting Stress Index-Short Form) and coping strategies [Coping Inventory for Stressful Situations (CISS)]. RESULTS: No statistical differences for mean age (p = 0.456) and gender (p = 0.577) were found between DD and control children. Mothers of children affected by DD showed an higher rate of all parental stress indexes (Parental Distress domain p < 0.001, Difficult Child p < 0.001, Parent-Child Dysfunctional Interaction p < 0.001, and Total Stress subscale score p < 0.001) than controls mothers. According to the CISS evaluation, mothers of DD children reported a significantly higher rate of emotion-oriented (p < 0.001) and avoidance-oriented (p < 0.001) coping styles than mothers of typical developing children. On the other hand, a lower representation of task-oriented coping style was found in mothers of DD children (p < 0.001) in comparison to mothers of control-children. CONCLUSION: Our study shows the clinical relevance of the burden carried by the mothers of children affected by DD and suggests the importance to assess parents, particularly mothers, to improve family compliance and clinical management of this disorder.

Update on the safety of second generation antipsychotics in youths: a call for collaboration among paediatricians and child psychiatrists.

During the past decade, a substantial increase in the use of second generation antipsychotics (SGAs) has occurred for a number of juvenile psychiatric disorders, often as off-label prescriptions. Although they were thought to be safer than older, first generation antipsychotics, mainly due to a lower risk of neurological adverse reactions, recent studies have raised significant concerns regarding their safety regarding metabolic, endocrinological and cardiovascular side effects. Aim of this paper is to update with a narrative review, the latest findings on safety of SGAs in youths. Results suggest that different SGAs may present different safety profiles. Metabolic adverse events are the most frequent and troublesome, with increasing evidences of heightened risk for type II diabetes mellitus. Results are discussed with specific emphasis on possible strategies of an active monitoring, which could enable both paediatricians and child psychiatrists to a possible prevention, early detection, and a timely management of such effects.