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Background: Chromosome 14q11-q22 deletion syndrome (OMIM 613457) is a rare contiguous gene syndrome. Two regions of overlap (RO) of the 14q12q21.1 deletion have been identified: a proximal region (RO1), including FOXG1(*164874), NKX2-1(*600635), and PAX9(*167416) and a distal region (RO2), including NKX2-1 and PAX9. We report a 6-year-old boy with mild dysmorphic facial features, global developmental delay, and hypoplasia of the corpus callosum., Methods and Results: Array-CGH analysis revealed a 14q12q13.2 microdeletion. We compared the phenotype of our patient with previously published cases in order to establish a genotype-phenotype correlation., Conclusion: The study hypothesizes the presence of a new RO, not including the previously reported candidate genes, and attempt to define the associated molecular and psychomotor/neurobehavioral phenotype. This region encompasses the distal breakpoint of RO1 and the proximal breakpoint of RO2, and seems to be associated with intellectual disability (ID), hypotonia, epilepsy, and corpus callosum abnormalities. Although more cases are needed, we speculated on SNX6(*606098) and BAZ1A(*605680) as potential candidate genes associated with the corpus callosum abnormalities., (© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Background: The questionnaires completed by the parents give a first general information on the behavioral problems of the child-adolescent, as a useful orientation to the clinical evaluation. The Child and Adolescent Behavior Inventory (CABI) is a 75-item parent questionnaire, which explores a large number of problem areas. The study of its predictive validity for the clinical diagnosis, in comparison with the Diagnostic and Statistical Manual of Mental Disorders ( DSM )-oriented scales of the Child Behavior Checklist (CBCL), can assess whether its use may be advantageous., Material and Methods: Parents/caregivers of 462 children and adolescents responded to both CABI and CBCL as a preliminary routine investigation. The results were compared with those of diagnoses obtained after the completion of the usual clinical procedure., Results: Accuracy values (probability of correct classification) resulted high for both instruments and significantly better for CABI anxiety and attention-deficit hyperactivity disorder (ADHD) scales, and for CBCL oppositional defiant disorder (ODD) and conduct disorder (CD) scales; no significant difference was found for depression scales. All the areas under the curve (AUC) of the receiver operating characteristic analysis reached excellent values, suggesting a very good predictive ability of the five scales of the two instruments. The comparison of AUC showed the CABI's anxiety and ADHD scales to give significantly higher values than those of CBCL, indicating that these two scales have a better predictive ability., Conclusion: The study indicates a very good comparative (vs CBCL) and predictive validity of the CABI, suggesting an advantage in the use of this shorter questionnaire, available for free use both for clinical practice and supposedly for screening and epidemiological evaluations.

Objective: The objective of the study was to describe the electroclinical features, seizure semiology, and the long-term evolution of gelastic seizures (GS) not associated with hypothalamic hamartoma (HH)., Methods: We reviewed video-electroencephalogram (video-EEG) recordings from pediatric patients with GS without HH admitted to 14 Italian epilepsy centers from 1994 to 2013. We collected information about age at onset, seizures semiology, EEG and magnetic resonance imaging (MRI) findings, treatment, and clinical outcome in terms of seizure control after a long-term follow-up., Results: A total of 30 pediatric patients were stratified into two groups according to neuroimaging findings: group 1 including 19 children (63.3%) with unremarkable neuroimaging and group 2 including 11 children with structural brain abnormalities (36.7%). At the follow-up, patients of group 1 showed better clinical outcome both in terms of seizure control and use of AED polytherapy. Our patients showed remarkable clinical heterogeneity, including seizure semiology and epilepsy severity. Electroencephalogram recordings showed abnormalities mainly in the frontal, temporal, and frontotemporal regions without relevant differences between the two groups. Overall, carbamazepine showed good efficacy to control GS., Conclusions: Patients with nonlesional GS have a more favorable outcome with better drug response, less need of polytherapy, and good long-term prognosis, both in terms of seizure control and EEG findings., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Psychogenic nonepileptic seizures (PNES) are observable abrupt paroxysmal changes in behavior or consciousness that resemble epileptic seizures, but without concurrent electroencephalographic abnormalities., Methods: In this manuscript, we reviewed literature concerning pediatric PNES and focused on those articles published in the last 10 years, in order to try to understand what the state of the art is at the moment, particularly as regards relationship and differential diagnosis with epilepsy., Results: Psychogenic nonepileptic seizures have been extensively described in literature mainly in adults and less frequently in children. Despite the potential negative impact of a misdiagnosis (unnecessary investigations and antiepileptic drugs, structured pathological behavioral patterns), in literature there is little information regarding the real prevalence, clinical features, treatment, and outcome of PNES in children and adolescents., Conclusion: Psychogenic nonepileptic seizures are common but frequently missed entity in pediatric population. Diagnosis could be difficult, especially in those children who have both epileptic and nonepileptic seizures; video EEG and home video can help clinicians in diagnosis. More studies are needed to better classify PNES in children and facilitate diagnosis and treatment., (© 2019 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

Attention Deficit Hyperactivity Disorder (ADHD) is a childhood-onset neurodevelopmental disorder, whose etiology and pathogenesis are still largely unknown. In order to uncover novel regulatory networks and molecular pathways possibly related to ADHD, we performed an integrated miRNA and mRNA expression profiling analysis in peripheral blood samples of children with ADHD and age-matched typically developing (TD) children. The expression levels of 13 miRNAs were evaluated with microfluidic qPCR, and differentially expressed (DE) mRNAs were detected on an Illumina HiSeq 2500 genome analyzer. The miRNA targetome was identified using an integrated approach of validated and predicted interaction data extracted from seven different bioinformatic tools. Gene Ontology (GO) and pathway enrichment analyses were carried out. Results showed that six miRNAs (miR-652-3p, miR-942-5p, let-7b-5p, miR-181a-5p, miR-320a, and miR-148b-3p) and 560 genes were significantly DE in children with ADHD compared to TD subjects. After correction for multiple testing, only three miRNAs (miR-652-3p, miR-148b-3p, and miR-942-5p) remained significant. Genes known to be associated with ADHD (e.g., B4GALT2, SLC6A9 TLE1, ANK3, TRIO, TAF1, and SYNE1 ) were confirmed to be significantly DE in our study. Integrated miRNA and mRNA expression data identified critical key hubs involved in ADHD. Finally, the GO and pathway enrichment analyses of all DE genes showed their deep involvement in immune functions, reinforcing the hypothesis that an immune imbalance might contribute to the ADHD etiology. Despite the relatively small sample size, in this study we were able to build a complex miRNA-target interaction network in children with ADHD that might help in deciphering the disease pathogenesis. Validation in larger samples should be performed in order to possibly suggest novel therapeutic strategies for treating this complex disease.

The aim of this study was to evaluate whether empathizing and systemizing are part of the parental broad autism phenotype (BAP). Parents (N = 76) of preschool children with a diagnosis of ASD and parents (N = 48) of typically developing (TD) children completed the Empathy Quotient (EQ) and Systemizing Quotient-Revised (SQ-R) questionnaires. The E-S discrepancy (D score) was used to test for sex differences in five "brain types". Our results suggest that the E-S theory do not seem to be part of the BAP. However, a stronger drive to systemize than empathize (Type S brain) could be a highly inheritable cognitive endophenotype of mothers of children with ASD. This study should be repeated with a larger sample size.

Background: Recurrent painful ophthalmoplegic neuropathy (RPON), previously known as ophthalmoplegic migraine (OM), is an uncommon disorder with repeated episodes of ocular cranial nerve neuropathy associated with ipsilateral headache. The age of presentation is most often during childhood or adolescence. MRI has a central role in the assessment of the RPON, especially to distinguish orbital, parasellar, or posterior fossa lesions that mimic symptoms of RPON. Actually, oculomotor nerve tumors may be masquerade as RPON so that MRI follow-ups are required to detect the possibility of tumor etiology., Case Presentation: We report a 16-year-old boy with a 7-year follow-up and multiple brain MRI data, previously diagnosed as OM. The last brain MRI, performed during an acute phase of oculomotor paresis with ipsilateral headache, showed a nodular lesion described as schwannoma of III cranial nerve. Then, we reviewed the literature on OM and RPON in pediatric age with a focus on brain MRI findings., Conclusions: This review highlights the important role of serial brain MRIs in the long-term follow-up of RPON, especially in the cases with childhood onset, in order to not delay the diagnosis of a possible oculomotor nerve schwannoma., Competing Interests: The authors declare they have no conflicts of interest., (Copyright © 2019 Maria Giuseppina Petruzzelli et al.)

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 electroencephalographic (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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The prevalence of chronic pain is about 30% in children and adolescents which suffer from severe emotional distress. The aim of this observational study is to investigate cognitive, emotional and behavioral consequences of benign chronic pain in children and adolescents suffering of reumathologic diseases., Materials and Methods: A total of 49 participants, chronic pain participants (CPPs) and controls (CGPs), affected by rheumatic diseases, were enrolled. Assessment included collection of sociodemographic data, pain characteristics, and administration of Visual Analog Scale (VAS), Depression Inventory for Children and Adolescents (CDI), Conners' Parent Rating Scales-Revised (CPRS-R), Child Behavior Checklist (CBCL), and Screen for Child Anxiety-Related Disorders (SCARED). For the statistical analysis, Student's t -test for independent samples and Pearson's correlation were used. The significance value was set at p less than .05., Results: A significant difference of mean scores of CBCL items and of CPRS items between the two groups was found. In CPPs, a significant correlation between VAS and mean scores of several CBCL items and between VAS and mean scores of several CPRS items was found., Conclusion: Chronic pain is a real syndrome in which an interdisciplinary treatment should be applied, considering the psychopathological risk, especially in developmental age.

Background: Inflammatory bowel disease and schizophrenia spectrum disorders are complex and multifactorial conditions characterized by great variability of age at onset, clinical presentation, and longitudinal course. Several lines of evidence suggested different connections among immunological dysregulation, gastrointestinal inflammation, and psychosis, but to date many controversial issues still exist in this field., Case Presentation: We present the case of a 14-year-old Caucasian boy with refractory ulcerative colitis, admitted to the Child Neuropsychiatry Unit of the Polyclinic Hospital of Bari in the course of his first-episode psychosis. He showed an acute onset of psychotic symptomatology during treatment with thalidomide, an immunomodulatory drug used in the experimental therapy of refractory inflammatory bowel disease. Thalidomide was discontinued and orally administered mesalazine was restarted. In addition, treatment with antipsychotics and mood stabilizers was introduced with gradual improvement of psychotic symptoms. According to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria, a diagnosis of partial remission of a first episode of schizoaffective disorder was formulated after a 6-month follow-up. Throughout this period, both psychopharmacological and mesalazine-based gastrointestinal treatments were maintained with partial remission of psychiatric and gastrointestinal symptoms., Conclusions: We propose that refractory ulcerative colitis and psychosis might represent different manifestations of a common pathological pathway. However, it is also conceivable that thalidomide may have played a role in promoting the manifestation of psychotic symptoms in an individual with a specific vulnerability to schizoaffective disorders. Further investigations are needed to improve our knowledge regarding the complexity of brain-gut interactions, thus improving the management of co-existing inflammatory bowel and schizophrenia spectrum disorders.

Juvenile fibromyalgia (JFM) is a chronic pain syndrome with onset in developmental age, characterized by widespread musculoskeletal pain associated with other neurological or nonneurological symptoms. Headache is one of the most frequent comorbid conditions with JFM, but this association is still poorly studied in the juvenile population. The literature review was conducted searching through PubMed, Scopus, and Web of Science with a combination of the following free-text terms: "fibromyalgia," "juvenile fibromyalgia," "headache," "primary headache," "migraine," "children," "adolescents," and "comorbidity." The research resulted only in two specific studies regarding comorbidity JFM + Juvenile Headache (JH). From each study, we extracted data about sample features, clinical characteristics of both JFM and PH, and assessment tools. The clinical approach to JFM and JH should include a complete examination of the main causes of comorbid diseases, thus improving the therapeutic approach to the patient in developmental age.

Objective: To describe (a) the observed cognitive, emotional, and behavioral phenotype in a cohort of male children with 47,XYY syndrome and (b) stress levels in their parents., Methods: We conducted a cross-sectional observational study of 11 boys diagnosed with 47,XYY syndrome and compared them with 11 age-matched boys with normal karyotype (46,XY). The participants performed standardized assessments of cognitive function, emotional state, and behavioral features; the parents completed a questionnaire evaluating parental stress. All data were analyzed using parametric and nonparametric statistical methods., Results: All of the boys exhibited a normal cognitive profile. However, emotional-behavioral profiling revealed that internalizing and externalizing problems were more prevalent in the 47,XYY group. In addition, the stress levels of the parents of the 47,XYY group were reportedly higher than those of the parents of the 46,XY group. We also found that the time of the diagnosis had an effect on the mothers' stress levels; that is, postnatal fetal 47,XYY diagnosis was associated with higher maternal stress, whereas prenatal fetal 47,XYY diagnosis was not., Conclusions: Generally, 47,XYY syndrome is associated with certain cognitive, emotional, and behavioral features. High stress levels have been reported by the mothers of 47,XYY boys who had been diagnosed postnatally because of unexpected developmental delay and/or learning difficulties. The present study highlights the need to better define the neuropsychiatric phenotype of 47,XYY children; namely, the effect of the chromosomal abnormality on their cognitive function and emotional-behavioral (internalizing and externalizing) features. This study could improve prenatal counseling and pediatric surveillance.

Objective: The objective of the study was to explore stress levels in the parents of children with idiopathic epilepsy at different time points of the disease, specifically, at the time of diagnosis, during follow-up, and 1 and 2 years after discontinuation of antiepileptic drugs., Methods: Our study included 50 patients between 5 and 14 years of age, who were diagnosed with childhood absence epilepsy or idiopathic focal epilepsy with Rolandic paroxysms. Parents of the participants independently completed the Parenting Stress Index-Short Form at the time of initial diagnosis, and when the children started antiepileptic drugs (Time 0), and at 1 year (Time 1) and 2 years (Time 2) after discontinuation of therapy., Results: At Time 0, parental stress levels were increased, both in mothers and fathers, with average scores in the "clinical range" of the parental distress (PD), dysfunctional parent-child interaction (P-CDI), and total stress (TS) scales. At Time 1, the scores on these scales remained high. At Time 2, a mild reduction in the stress scores was observed in both parents, despite values remaining in the "clinical range" for all the scales., Conclusions: Results suggested that parents of children with epilepsy were not reassured about the child's condition, even after clinical improvement. Parental stress levels remained higher than expected, even 2 years after the discontinuation of therapy and freedom from seizures. This was probably due to concerns with the reappearance of new seizures or a more severe type of epilepsy with the discontinuation of drug(s), and feelings of inadequacy with their parental role(s)., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Over the last few years, new studies focused their attention on the gender-related features in high-functioning autism spectrum disorder (HFA), often leading to controversial results. Another interesting aspect of these subtype of patients is linked to the complexity of clinical presentation, where besides core symptoms, other co-occurrence disorders may complicate the diagnostic evaluation. Therefore, we retrospectively studied 159 HFA patients, male and female, investigating their comorbidities and to find any gender difference. For each patient, were evaluated the presence/absence, type and gender distribution of psychopathological comorbidities, according to DSM-5 diagnostic criteria. The total sample was divided in 100 male and 59 female patients, age and intelligence quotient matched. In our sample, the psychiatric comorbidities observed were Attention Deficit Hyperactivity Disorder, Anxiety Disorders, Depressive Disorders, Bipolar Disorder, Obsessive-Compulsive Disorder, and Anorexia Nervosa. No statistical significant differences were found between male and female HFA patients comorbidities except for Anorexia Nervosa. In both male and female patients, attention deficit and hyperactivity disorder and anxiety disorders were found in high percentage. In conclusion, our investigation showed that a statistical significant difference of comorbidity between male and female HFA patients was found only for AN diagnosis. However, the question about the distinction between female and male HFA patients remains quite interesting and an open area of research for future studies.

Cognitive deficit has been identified in one third of patients affected by Duchenne Muscular Dystrophy, primarily attributed to loss of the short Dp71 dystrophin, the major brain dystrophin isoform. In this study, we investigated for the first time the Dp71 and Dp71-associated proteins cellular localization and expression in human neurons obtained by differentiation from induced pluripotent stem cell line of a patient affected by cognitive impairment. We found structural and molecular alterations in both pluripotent stem cell and derived neurons, reduced Dp71 expression, and a Ca 2+ cytoplasmic overload in neurons coupled with increased expression of the SERCA2 pump in the dystrophic neurons. These results suggest that the reduction of Dp71 protein in the Duchenne muscular dystrophy neurons leads to alterations in SERCA2 and to elevated cytosolic Ca 2+ concentration with consequent potential disruption of the dystrophin proteins and Dp71-associated proteins.

Since Hans Asperger's first description (Arch Psych Nervenkrankh 117:76-136, 1944), through Lorna Wing's translation and definition (Psychol Med 11:115-129, 1981), to its introduction in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM, 1994), Asperger Syndrome has always aroused huge interest and debate, until vanishing in the DSM fifth edition (2013). The debate regarded its diagnostic validity and its differentiation from high functioning autism (HFA). The present study aimed to examine whether AS differed from HFA in clinical profiles and to analyze the impact of DSM-5's innovation. Differences in cognitive, language, school functioning and comorbidities, were revealed when 80 AS and 70 HFA patients (3-18 years) were compared. Results suggested that an AS empirical distinction within autism spectrum disorder should be clinically useful.

Objectivies: Monosomy 1p36 syndrome is a recognized syndrome with multiple congenital anomalies; medical problems of this syndrome include developmental delay, facial dysmorphisms, hearing loss, short stature, brain anomalies, congenital heart defects. Epilepsy can be another feature but there are few data about the types of seizures and long term prognosis. The aim of this work was to analyse the electroclinical phenotype and the long-term outcome in patients with monosomy 1p36 syndrome and epilepsy., Materials and Methods: Data of 22 patients with monosomy 1p36 syndrome and epilepsy were reconstructed by reviewing medical records. For each patient we analysed age at time of diagnosis, first signs of the syndrome, age at seizure onset, seizure type and its frequency, EEG and neuroimaging findings, the response to antiepileptic drugs treatment and clinical outcome up to the last follow-up assessment., Results: Infantile Spasm (IS) represents the most frequent type at epilepsy onset, which occurs in 36.4% of children, and a half of these were associated with hypsarrhythmic electroencephalogram. All patients with IS had persistence of seizures, unlike other patients with different seizures onset. Children with abnormal brain neuroimaging have a greater chance to develop pharmacoresistant epilepsy., Conclusion: This syndrome represents a significant cause of IS: these patients, who develop IS, can suffer from pharmacoresistent epilepsy, that is more frequent in children with brain abnormalities., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: This multicentric survey investigates the prevalence and characteristics of Airplane Headache in children affected by primary headaches., Methods: Patients with symptoms of Airplane Headache were recruited from nine Italian Pediatric Headache Centres. Each patient was handed a structured questionnaire which met the ICHD-III criteria., Results: Among 320 children suffering from primary headaches who had flights during their lifetime, 15 (4.7%) had Airplane Headache, with mean age of 12.4 years. Most of the patients were females (80%). The headache was predominantly bilateral (80%) and localized to the frontal area (60%); it was mainly pulsating, and lasted less than 30 min in all cases. Accompanying symptoms were tearing, photophobia, phonophobia in most of the cases (73.3%). More than 30% of patients used medications to treat the attacks, with good results., Conclusion: Our study shows that Airplane Headache is not a rare disorder in children affected by primary headaches and highlights that its features in children are peculiar and differ from those described in adults. In children Airplane Headache prevails in females, is more often bilateral, has frequently accompanying symptoms and occurs at any time during the flight. Further studies are needed to confirm the actual frequency of Airplane Headache in the general pediatric population not selected from specialized Headache Centres, with and without other concomitant headache condition, and to better clarify the clinical characteristics, pathophysiology and potential therapies.

Background: Over the last decade, several studies investigated the outcomes in children born very preterm. Only recently there has been an increasing interest in the late preterm infants (born between 34 + 0 and 36 + 6 weeks). This population is at high risk of morbidity and mortality in the first years of life. Other studies reported that they are also at risk of long-term developmental problem. Therefore, the aim of this study is to describe the neurodevelopmental and emotional-behavioral outcome in a sample of late preterm patients., Methods: The study included late preterm children and adolescents who had neuropsychiatric and/or neurological symptoms. They underwent a general, neurocognitive and an emotional-behavioral assessment. Exclusion criteria included: patients affected by Central Nervous System congenital abnormalities, neurodegenerative diseases, genetic disorders, epilepsy, or in pharmacological treatment, or adopted children. A descriptive statistics analysis was performed to describe the sociodemographic and clinical characteristics of patients. Risk factors related to late preterm birth, prevalence of neurodevelopmental disorders, and cognitive functioning were recorded and analyzed., Results: The sample included 68 LPI (45 males and 23 females) aged from 2 to 16.3 years (mean age 7,5 years), who were affected by one or more neurodevelopmental disorder, including Language Disorder, Attention Deficit Hyperactivity Disorder, Specific Learning Disorder, Developmental Coordination Disorder, Intellectual Disability and Autism Spectrum Disorder. Moreover, in 30.8% of patients, internalizing problems (affective and social skills problem) were detected., Conclusions: Our results support the importance of a long-term surveillance of late preterm and the great need for more longitudinal large population studies in order to collect data on the neurodevelopmental outcomes of this population.

Purpose: Recently, neuroimaging studies were performed using 1 H-magnetic resonance spectroscopy ( 1 H-MRS), revealing a quantitative alteration of neurochemicals (such as neurotransmitters and metabolites) in several brain regions of patients with autism spectrum disorder (ASD). The involvement of the frontal lobe in the neurobiology of ASD has long been documented in the literature. Therefore, the aim of this study was to analyze the alterations of N -acetylaspartate/creatine (NAA/Cr) and choline/Cr (Cho/Cr) ratios in the frontal lobe subcortical white matter (WM) in ASD patients, in order to reveal any alteration of metabolites that might be the expression of specific clinical features of the disorder., Patients and Methods: An 1 H-MRS study of the frontal lobe subcortical WM was performed in 75 children with ASD and in 50 age-matched controls to evaluate the functional activity of this brain region., Results: NAA/Cr and Cho/Cr ratios were significantly altered in ASD, compared to control subjects. Moreover, in the ASD group, NAA/Cr was significantly lower in patients with a cognitive impairment., Conclusion: Results from this study confirm the existence of brain metabolites' alterations in frontal lobe WM in children with ASD, supporting the relevance of this brain region in the clinical expressions of this disorder, including its role in the cognitive impairment. Further 1 H-MRS investigations will allow to comprehensively explain the relationship between metabolic alteration in a specific brain region and specific clinical features of ASD., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Introduction: The present work presents data on research into adolescents who committed sex offenses, carried out in the Apulia Region of southern Italy and focused in particular on the perpetrators' perception of the peculiar profile of the criminal act committed., Materials and Methods: Three University sections of the School of Medicine, Bari University, took part in this research: Criminology and Forensic Psychopathology, Psychiatry and Juvenile Neuropsichiatry, working in collaboration with the Department for Juvenile Justice and the Community, and the Center for Juvenile Justice in Apulia. In total, 31 subjects were included in the study, all Juvenile Sex Offenders. A detailed questionnaire was employed to obtain all the relevant information of criminological concern., Discussion: Among most of the minors considered, a very poor awareness emerged of the peculiar type of offense committed, and of its consequences on the victims and the social context., Results: This finding highlights an evident contradiction and confusion between legislative provisions in the area of sex offenses and rape, and the perspectives of juveniles and adolescents., Conslusions: There is an evident need for legislative norms to adopt registers that are more accessible to the complex juvenile world, that cannot be assimilated to the adult world.

Background: The treatment of cognitive deficits is challenging in pediatric onset multiple sclerosis (POMS) and in patients with attention deficit hyperactivity disorder (ADHD). We performed a pilot double-blind RCT to evaluate the efficacy of a home-based computerized-program for retraining attention in two cohorts of POMS and ADHD patients., Methods: POMS and ADHD patients failing in at least 2/4 attention tests on a neuropsychological battery were randomized to specific or nonspecific computerized training (ST, nST), performed in one-hour sessions, twice/week for 3 months. The primary outcome was the effect of the training on global neuropsychological performances measured by the cognitive impairment index (CII). The efficacy of the intervention was evaluated in each disease group by using repeated measures ANOVA., Results: Sixteen POMS (9 females, age 15.75 ± 1.74 years) and 20 ADHD (2 females, age 11.19 ± 2.49 years) patients were enrolled. In POMS patients the ST exposure was associated to a significantly more pronounced improvement of the CII (p < 0.0001) and on cognitive test exploring attention, concentration, planning strategies and visuo-spatial memory performances in comparison to nST exposure. In ADHD patients the difference between the ST and nST on the CII was not statistical significant (p = 0.06), but a greater effect of the ST was found only on cognitive test exploring attention and delayed recall of visuo-spatial memory performances., Conclusions: Our data suggest that a cognitive rehabilitation program that targets attention is a suitable tool for improving global cognitive functioning in POMS patients, whereas it has a less pronounced transfer effect in ADHD patients., Trial Registration: ClinicalTrials.gov; NCT03190902 ; registration date: June 15, 2017; retrospectively registered.

Headache is one of the most common neurological disorders in developmental age. Several studies investigated the relationship between headache and emotional/behavioral problems. We studied non-verbal cognitive abilities, including non-verbal memory and attention skills, in order to evaluate the impact of primary headache on these domains. The latest version of the cognitive battery Leiter International Performance Scale - Third Edition (Leiter-3), a non-verbal test, was administered to 35 children and adolescents affected by migraine or tension-type headache and to 23 healthy subjects. We found that frequency of attacks and headache disability (evaluated with the Pediatric Migraine Disability Assessment Score Questionnaire) significantly correlate with non-verbal memory and sustained attention skills. However, we found that headache disability has a significant impact on specific cognitive domains related to sustained attention and non-verbal memory skills. The relationship between headache and memory/attention deficits may have an explanation based on a possible common physiopathology ground, including noradrenergic and dopaminergic pathways.

Despite the growing interest in a dimensional approach to the assessment of symptoms and clinically relevant phenomena in schizophrenia spectrum disorders, very few studies, to date, have examined the dimensional structure of symptoms in early onset first episode psychosis. In the present study, we assessed a sample of 60 children and adolescents of both sexes with first episode schizophrenia spectrum psychosis. A principal component analysis (PCA) of the Positive and Negative Syndrome Scale (PANSS) was performed and the factors obtained were used to carry out a cluster analysis. Sex, age of onset before or after 13, markers of early neurodevelopmental impairment and intellectual disabilities were considered as variables to characterized potential clinical subtypes, applying a one-way analysis of variance. Four factors were extracted ("negative symptoms", "delusions", "conceptual disorganization" and "paranoid/hostility"), each of them identifying a discrete clinical subtype of patients. No difference was found among the groups about sex and age of onset; delayed speech/language development was significantly associated with the "delusions" subtype and both "conceptual disorganization" and "delusions" subtypes showed a lower intelligence quotient (IQ). The four factors model we presented highlights "negative symptoms" as the most consistent factor; among positive symptoms, unusual thought content and conceptual disorganization resulted more distinctive of psychosis, at this age range, than perceptual abnormalities. Evolutionary trajectories of the four clinical subtypes we obtained seem to be influenced by cognitive and neurodevelopmental impairment rather than sex and age of onset.

Purpose: "Single Nucleotide Polymorphisms (SNPs)" could be an important explanation of drug resistance in epilepsy. The aim of this study was to investigate if genetic polymorphisms (SNPs) of the SCN1A gene could influence the response to anti - epileptic drugs (AED) and if they could predispose to a drug resistant epilepsy in pediatric patients., Methods: We investigated SNPs in exon and intronic regions of the SCN1A gene in a sample of 120 pediatric patients, in both drug-resistant and drug-responsive patients. Association between polymorphisms and refractory epilepsy were investigated by comparing SNPs in exon and intronic regions between the two groups. The genotypes of each intronic polymorphism in the drug-resistant group was analyzed. Odds ratios and confidence intervals were calculated., Results: None of the SNPs identified in exons of the SCN1A gene were associated with drug-resistance. In the intronic regions, a statistically significant difference was found in the prevalence of three polymorphisms was found between the two patient groups (rs6730344A/C, rs6732655A/T, rs10167228A/T). The analysis of the genotypes of each intronic polymorphism in the drug-resistant group revealed that the AA and AT genotypes for the rs1962842 polymorphism are associated with an increased risk of developing drug resistance compared to TT genotype., Conclusion: The intronic rs6730344, rs6732655 and rs10167228 polymorphisms of the SCN1A gene are a potential risk factors for drug resistance. AA e AT genotype of the rs1962842 intronic polymorphism also emerged as a risk factor in the drug resistant group. Therefore, polymorphisms of the SCN1A gene could play a role in the response to AED in patients with drug-resistant epilepsy, with important implications for clinical practice., (Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Introduction: We studied children and adolescents with epilepsy (CAWE) and their families to evaluate symptoms of anxiety and depression, quality of life (QoL), and their correlations with epilepsy characteristics., Material and Methods: The study included 326 (52.5% females) 8 to 18years old CAWE. Anxiety and depression were assessed with the "Self-administered psychiatric scales for children and adolescents" (SAFA), and family's QoL with the parents' report "Impact of Epilepsy on QoL" (IEQoL)., Results: The CAWE exhibiting abnormal (T≥70) scores were 8.0% in the anxiety scale, 9.2% in the depression scale, and 4.6% in both scales. Social anxiety was the predominant anxiety symptom, while irritable mood and desperation were the most frequent symptoms of depression. Depressive symptoms were associated with parents' complaint of higher worries about the child's condition and future and lower well-being of the family. Severity and duration of the epilepsy and polypharmacy were independent from abnormal scores of anxiety and depression, but were associated with parents' worries about the child's condition and family's well-being., Conclusions: Anxiety and depression in CAWE are independent from the characteristics of the disease but are correlated to the lower well-being of the family. A search of these emotional problems is recommended for better care of the patients and their families., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Primary headache is a frequent and disabling disorder, common among children and adolescents, and it is a painful syndrome often accompanied by functional impairment and associated with emotional and behavior problems. The aim of this study was to investigate parenting stress and emotional/behavioral problems in adolescents affected by primary headache compared with healthy adolescents. The study population consisted of 35 adolescents and a control group of 23 healthy subjects. The assessment included the administration of clinical standardized scales such as Parent Stress Index-Short Form, Pediatric Migraine Disability Assessment Score Questionnaire, and Child Behavior Checklist (CBCL). Headache group and control group did not differ in terms of parenting stress ( p  = 0.29). On the contrary, headache group showed more internalizing problems ( p  = 0.023), affective problems ( p  = 0.01), anxious ( p  = 0.001), and somatic complaints ( p  < 0.001) compared with control group. In addition, we found a significant correlation between PSI domains and specific CBCL subscales in the headache group. The findings emphasize the need for expanded intervention in the clinical treatment of pediatric headache, a treatment that may also include the family members. Further research is needed.

Multiple sclerosis (MS) is a complex disease of the CNS that usually affects young adults, although 3-5% of cases are diagnosed in childhood and adolescence (hence called pediatric MS, PedMS). Genetic predisposition, among other factors, seems to contribute to the risk of the onset, in pediatric as in adult ages, but few studies have investigated the genetic 'environmentally naïve' load of PedMS. The main goal of this study was to identify circulating markers (miRNAs), target genes (mRNAs) and functional pathways associated with PedMS; we also verified the impact of miRNAs on clinical features, i.e. disability and cognitive performances. The investigation was performed in 19 PedMS and 20 pediatric controls (PCs) using a High-Throughput Next-generation Sequencing (HT-NGS) approach followed by an integrated bioinformatics/biostatistics analysis. Twelve miRNAs were significantly upregulated (let-7a-5p, let-7b-5p, miR-25-3p, miR-125a-5p, miR-942-5p, miR-221-3p, miR-652-3p, miR-182-5p, miR-185-5p, miR-181a-5p, miR-320a, miR-99b-5p) and 1 miRNA was downregulated (miR-148b-3p) in PedMS compared with PCs. The interactions between the significant miRNAs and their targets uncovered predicted genes (i.e. TNFSF13B, TLR2, BACH2, KLF4) related to immunological functions, as well as genes involved in autophagy-related processes (i.e. ATG16L1, SORT1, LAMP2) and ATPase activity (i.e. ABCA1, GPX3). No significant molecular profiles were associated with any PedMS demographic/clinical features. Both miRNAs and mRNA expressions predicted the phenotypes (PedMS-PC) with an accuracy of 92% and 91%, respectively. In our view, this original strategy of contemporary miRNA/mRNA analysis may help to shed light in the genetic background of the disease, suggesting further molecular investigations in novel pathogenic mechanisms., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by persistent deficits in social communication and interaction and restricted, repetitive patterns of behavior, interests, and activities. Various factors are involved in the etiopathogenesis of ASD, including genetic factors, environmental toxins and stressors, impaired immune responses, mitochondrial dysfunction, and neuroinflammation. The heterogeneity in the phenotype among ASD patients and the complex etiology of the condition have long impeded the advancement of the development of pharmacological therapies. In the recent years, the integration of findings from mouse models to human genetics resulted in considerable progress toward the understanding of ASD pathophysiology. Currently, strategies to treat core symptoms of ASD are directed to correct synaptic dysfunctions, abnormalities in central oxytocin, vasopressin, and serotonin neurotransmission, and neuroinflammation. Here, we present a survey of the studies that have suggested molecular targets for drug development for ASD and the state-of-the-art of medicinal chemistry efforts in related areas.

Purpose/background: Although second-generation antipsychotics are used to treat and manage symptoms for several psychiatric disorders, data about their adverse effects in developmental age are limited. The aim of this prospective observational study was to verify the cardiovascular and metabolic risk in a sample of antipsychotic-naive children/adolescent patients starting risperidone therapy., Methods: Twenty-two patients, younger than 18 years, were recruited. The assessment included anthropometric data, cardiovascular parameters, blood tests, and ultrasonographic abdominal study., Results: After an average follow-up period of 7.6 months, statistically significant increases in mean values of waist circumference, body mass index (BMI), BMI percentile, BMI z score, total cholesterol, and prolactin were found. Other cardiometabolic parameters showed an upward trend in time. Subjects in pubertal/postpubertal stage and female patients were more susceptible to developing cardiometabolic changes. Moreover, significant correlations between changes in anthropometric and several metabolic parameters were found. A tendency to change in constitution of the liver parenchyma and distribution of the abdominal fat mass with ultrasonographic abdominal study was also evident., Conclusions: In our sample, several metabolic parameters showed a sensitivity to risperidone treatment. Because most of these parameters are age dependent, metabolic syndrome criteria used for adults were inappropriate in children and adolescents. Periodic clinical and instrumental evaluations and guidelines for monitoring of any metabolic, laboratory, and instrumental complications are necessary in the perspective of even long-time second-generation antipsychotics treatment in children and adolescents.

Background/aim: Autism spectrum disorders (ASD) are neurodevelopmental disorders without a definitive etiology in most cases. Environmental factors, such as viral infections, have been linked with anomalies in brain growth, neuronal development, and functional connectivity. Congenital cytomegalovirus (CMV) infection has been associated with the onset of ASD in several case reports. The aim of this study was to evaluate the prevalence of congenital CMV infection in children with ASD and in healthy controls., Patients and Methods: The CMV genome was tested by polymerase chain reaction (PCR) on dried blood spots collected at birth from 82 children (38 with ASD and 44 controls)., Results: The prevalence of congenital CMV infection was 5.3% (2/38) in cases and 0% (0/44) in controls (p=0.212)., Conclusion: The infection rate was about 10-fold higher in patients with ASD than in the general Italian population at birth. For this reason, detection of CMV-DNA on dried blood spots could be considered in the work-up that is usually performed at ASD diagnosis to rule-out a secondary form. Given the potential prevention and treatment of CMV infection, this study could have intriguing consequences, at least for a group of patients with ASD., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: To assess prognostic factors for a second clinical attack and a first disability-worsening event in pediatric clinically isolated syndrome (pCIS) suggestive of multiple sclerosis (MS) patients., Methods: A cohort of 770 pCIS patients was followed up for at least 10 years. Cox proportional hazard models and Recursive Partitioning and Amalgamation (RECPAM) tree-regression were used to analyze data., Results: In pCIS, female sex and a multifocal onset were risk factors for a second clinical attack (hazard ratio [HR], 95% confidence interval [CI] = 1.28, 1.06-1.55; 1.42, 1.10-1.84, respectively), whereas disease-modifying drug (DMD) exposure reduced this risk (HR, 95% CI = 0.75, 0.60-0.95). After pediatric onset MS (POMS) diagnosis, age at onset younger than 15 years and DMD exposure decreased the risk of a first Expanded Disability Status Scale (EDSS)-worsening event (HR, 95% CI = 0.59, 0.42-0.83; 0.75, 0.71-0.80, respectively), whereas the occurrence of relapse increased this risk (HR, 95% CI = 5.08, 3.46-7.46). An exploratory RECPAM analysis highlighted a significantly higher incidence of a first EDSS-worsening event in patients with multifocal or isolated spinal cord or optic neuritis involvement at onset in comparison to those with an isolated supratentorial or brainstem syndrome. A Cox regression model including RECPAM classes confirmed DMD exposure as the most protective factor against EDSS-worsening events and relapses as the most important risk factor for attaining EDSS worsening., Interpretation: This work represents a step forward in identifying predictors of unfavorable course in pCIS and POMS and supports a protective effect of early DMD treatment in preventing MS development and disability accumulation in this population. Ann Neurol 2017;81:729-739., (© 2017 American Neurological Association.)

The need for performing clinical trials to develop well-studied and appropriate medicines for inherited neurometabolic disease patients faces ethical concerns mainly raising from four aspects: the diseases are rare; include young and very young patients; the neurological impairment may compromise the capability to provide 'consent'; and the genetic nature of the disease leads to further ethical implications. This work is intended to identify the ethical provisions applicable to clinical research involving these patients and to evaluate if these cover the ethical issues. Three searches have been performed on the European regulatory/legal framework, the literature and European Union-funded projects. The European legal framework offers a number of ethical provisions ruling the clinical research on paediatric, rare, inherited diseases with neurological symptoms. In the literature, relevant publications deal with informed consent, newborn genetic screenings, gene therapy and rights/interests of research participants. Additional information raised from European projects on sharing patients' data from different countries, the need to fill the gap of the regulatory framework and to improve information to stakeholders and patients/families., Conclusion: Several recommendations and guidelines on ethical aspects are applicable to the inherited neurometabolic disease research in Europe, even though they suffer from the lack of a common ethical approach. What is Known: • When planning and conducting clinical trials, sponsors and researchers know that clinical trials are to be performed according to well-established ethical rules, and patients should be aware about their rights. • In the cases of paediatric patients, vulnerable patients unable to provide consent, genetic diseases' further rules apply. What is New: • This work discusses which ethical rules apply to ensure protection of patient's rights if all the above-mentioned features coexist. • This work shows available data and information on how these rules have been applied.

Background: The assessment of the intelligence quotient (IQ) in children with autism spectrum disorder (ASD) is important to plan a detailed therapeutic-educative programme. The aim of the study was to evaluate the usefulness of the Psychoeducational Profile-third edition (PEP-3) to estimate the general cognitive development of children with ASD., Method: We recruited 30 children with ASD assessed with the Leiter International Performance Scale-Revised (Leiter-R) and the PEP-3. We compared the IQ of the Leiter-R with the developmental level (DL) of PEP-3., Results: The findings showed a significant positive correlation between IQ with DL of the cognitive verbal/pre-verbal (P = 0.0005), DL of the area of expressive language (P = 0.0004), DL of the area of receptive language (P = 0.0001), DL of fine motor (P = 0.0066), DL of gross motor (P = 0.0217), DL of visuo-motor imitation (P = 0.02), DL of communication (P = 0.0001) and DL of motor (P = 0.0063)., Conclusions: These findings show that the DLs could be considered as indicators of cognitive functioning in ASD., (© 2015 John Wiley & Sons Ltd.)

Corpus callosum abnormality (CCA) outcomes are quite unpredictable and variable, from asymptomatic forms to mild or severe neurodevelopment disorders. The aim of this study was to examine clinical outcomes in CCA patients. The study included 61 children and adolescents in whom brain magnetic resonance imaging (MRI) scans showed CCA, isolated or associated to other central nervous system lesions. All patients underwent anamnesis, physical and neurological examination, routine laboratory tests, electroencephalogram (EEG), and MRI scans. In all participants, the intelligence quotient (IQ) was determined. We divided the participants into two subgroups: the first subgroup included patients with an isolated CCA, and the second subgroup included patients with CCA associated with extra-callosal brain lesions (complex CCA). We found that CCA were associated with elevated frequency to intellectual disability (ID), other neurodevelopment disorders, epilepsy, and isolated EEG anomalies. Mild ID (p = 0.003) was more frequent in the isolated subgroup, while epilepsy (p = 0.036) and pre-perinatal risk factors (p = 0.023) were more frequent in the complex CCA subgroup. Although the role of the CC in the interhemispheric communication is known, neurological and neurodevelopment outcomes of CCA are extremely variable and unpredictable. The presence of extra-callosal brain anomalies is one of the major prognostic factor, and probably, they have an important impact on the clinical outcome.

In recent years, studies have shown that parents of children with Neurodevelopmental Disorders (NDDs) experience more parenting stress than parents of typically developing children, but the relation between the type of disorders and parenting stress is far from clear. The purpose of this study was to compare the parenting stress experienced by parents of 239 children with Specific Learning Disorders (SpLD), Language Disorders (LD), Autism Spectrum Disorder (ASD), Attention Deficit Hyperactivity Disorder (ADHD), and typical development (TD). Parents of children with NDDs experience more parenting stress than those of children who have TD. Although, parents of children with ASD or ADHD report the most high scores of parenting stress, also the parents of children with SpLD or LD report higher parental stress compared with parent of children without NDDs. Another interesting finding was that IQ level or emotional and behavioral problems are associated with the higher levels of parenting stress. This study suggest that parent, both mothers and fathers, of children with different type of NDDs should be provided with interventions and resources to empower them with the knowledge and skills to reduce their stress and to enhance their quality of life., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: The aim of our study was to identify possible risk factors related to carrying out of illegal conducts by minors on their first offense, and any individual variables, family, economic and socio-cultural related to phenomenon also investigated., Materials and Methods: The longitudinal study involved the acquisition of a series of biographical information, family, school, behavioral and clinical characteristics of children on their first crime recruited over a year in Puglia Region. For its purpose the study involved the use two standardized clinical scales (Youth Self-Report and Conners Adolescent Self Report Scale). For over a year we proceeded to follow-up., Results: The survey revealed some variables family, social and school related to antisocial behavior of children in their first contact with the judicial authorities., Conclusions: The results confirm the need for primary and secondary prevention of children at risk through mutidisciplinary, early, selective interventions.

Objective: An association between streptococcal infections, ABGA positivity, and no comorbidity ADHD (nc-ADHD) has been little investigated. The aim of this study was to evaluate the streptococcal infection frequency, defined entitled serum antistreptolysin O (ASO), and frequency of serum ABGA positivity in a sample of patients with nc-ADHD., Method: In all 40 participants were investigated the ASO titer and ABGA., Results: The results showed that ABGA positivity was statistically significantly higher in patients affected by ADHD than in patients of a control group, and pathological values of ASO were statistically more frequent in the ADHD group than the control group., Conclusion: These data suggest that streptococcal infections and autoimmune reactions against the basal ganglia are more frequent in ADHD patients than patients in a control group., (© The Author(s) 2012.)

In recent years, there has been an increasing interest in juvenile sex offenders showing that this population is highly heterogeneous. The aim of the present study was to identify possible different profiles that could help understand the motivation behind offending, comparing 31 Juvenile Sexual Offenders (JSOs), 31 Juvenile Sexual Non Offenders (JSNOs) and 31 Juvenile Non Offenders (Control Group). A data collection form, the Minnesota Multiphasic Personality Inventory-Adolescent (MMPI-A) or Minnesota Multiphasic Personality Inventory-2 (MMPI-2), the Coping Inventory for Stressful Situations (CISS) and the Parental Bonding Inventory (PBI) were administered to all participants. The results show that JSOs differs from JNSOs in some domains, such as living in single-parent homes, while maintain some common aspects such as academic failure and previous sexual intercourse. Moreover, JNSOs showed more abnormal personality traits, such as Authority Problems, MacAndrew Alcoholism, Acknowledgement and Alcohol-Drug Problem Proneness compared to JSOs and the Control Group, while JSOs and JNSOs use a coping strategy more oriented to Avoidance and Distraction compared to the Control group. Finally, JSOs described the relationships with fathers characterized by higher care and protection than JNSOs. These findings provide additional evidence with respect the prevention and treatment of criminal sexual behavior in adolescent., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Recent studies support several overlapping traits between autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD), assuming the existence of a combined phenotype. The aim of our study was to evaluate the common or distinctive clinical features between ASD and ADHD in order to identify possible different phenotypes that could have a clinical value. We enrolled 181 subjects divided into four diagnostic groups: ADHD group, ASD group, ASD+ADHD group (that met diagnostic criteria for both ASD and ADHD), and control group. Intelligent quotient (IQ), emotional and behavior problems, ADHD symptoms, ASD symptoms, and adaptive behaviors were investigated through the following test: Wechsler Intelligence Scale for Children, Wechsler Preschool and Primary Scale of Intelligence or Leiter International Performances Scale Revised, Child Behavior Checklist, Conners' Rating Scales-Revised, SNAP-IV Rating Scale, the Social Communication Questionnaire, Vineland Adaptive Behavior Scales. The ASD+ADHD group differs from ADHD or ASD in some domains such as lower IQ mean level and a higher autistic symptoms severity. However, the ASD+ADHD group shares inattention and hyperactivity deficit and some emotional and behavior problems with the ADHD group, while it shares adaptive behavior impairment with ASD group. These findings provide a new understanding of clinical manifestation of ASD+ADHD phenotype, they may also inform a novel treatment target., (© 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.)

The aim of this prospective observational study was to investigate the variations of serum prolactin hormone (PRL) in a sample of 34 drug-naive patients (mean age 13 years) who started risperidone therapy assuming that several factors may favor the increase in serum PRL. Serum PRL and hyperprolactinemia clinical signs were examined at baseline (T0) and after almost 3 months of treatment (T1). We considered sex, pubertal status, risperidone dosage, psychiatric diagnosis, and any personal/family history of autoimmune diseases. The mean serum PRL value increased between T0 and T1 (P=0.004). The mean serum PRL was higher in females in the pubertal/postpubertal stage and for risperidone dosage up 1 mg/day. Hyperprolactinemia was found in 20% of patients at T0 and in 38% of patients at T1 (P=0.03). The mean serum PRL increase was greater in early-onset schizophrenia spectrum psychosis patients compared with no-early-onset schizophrenia spectrum psychosis patients (P=0.04). The increase in PRL was higher in patients with a personal and a family history of autoimmune diseases. This study suggests that the increase in serum PRL in patients treated with risperidone may be linked not only to the drug and its dosage but also to several risk factors such as sex, pubertal stage, psychiatric disease, and autoimmune disorders.

Objective: The aim of this study was to assess the type and frequency of adverse events (AEs) in children with attention-deficit/hyperactivity disorder (ADHD) treated with methylphenidate or atomoxetine over a 5-year period in a large naturalistic study., Methods: We draw on data from the Italian ADHD Registry, a national database for postmarketing phase IV pharmacovigilance of ADHD medications across 90 centers. AEs were defined as severe or mild as per the classification of the Italian Medicines Agency. AE frequency in the two treatment groups was compared using incidence rates per 100 person-years (IR100PY) and incidence rate ratios (IRRs). Mantel-Haenszel adjusted IRRs were calculated to control for psychiatric comorbidity., Results: A total of 1350 and 753 participants (aged 6-18 years, mean age 10.7 ± 2.8) were treated with methylphenidate and atomoxetine, respectively, from 2007 to 2012. Ninety participants (7 %) were switched from methylphenidate to atomoxetine, and 138 (18 %) from atomoxetine to methylphenidate. Thirty-seven children treated with atomoxetine and 12 with methylphenidate had their medication withdrawn. Overall, 645 patients (26.8 %) experienced at least one mild AE (including decreased appetite and irritability, for both drugs) and 95 patients (3.9 %) experienced at least one severe AE (including severe gastrointestinal events). IR100PY were significantly higher in the atomoxetine-treated group compared with the methylphenidate-treated group for a number of mild and severe AEs and for any severe or mild AEs. After controlling for comorbidities, IRR was still significantly higher in the atomoxetine group compared with the methylphenidate group for a number of mild (decreased appetite, weight loss, abdominal pain, dyspepsia, stomach ache, irritability, mood disorder and dizziness) and severe (gastrointestinal, neuropsychiatric, and cardiovascular) AEs., Conclusions: In this naturalistic study, methylphenidate had a better safety profile than atomoxetine.

Background: Microphthalmia with linear skin defects (MLS) syndrome is a rare X-linked dominant male-lethal developmental disorder characterized by unilateral or bilateral microphthalmia and linear skin defects of the face and neck. Additional features affecting the eyes, heart, brain or genitourinary system can occur, corroborating the intra- and interfamilial phenotypic variability. The majority of patients display monosomy of the Xp22.2 region, where the holocytochrome c-type synthase (HCCS) gene is located., Case Presentation: We describe a 15-year-old-female affected by MLS syndrome and autism spectrum disorder (ASD). ASD has not previously been reported as a component of MLS. Our patient shows a large deletion of 12.9 Mb, involving Xp22.32-p22.2, which encompasses both the HCCS gene and autism X-linked genes., Conclusion: Thus, patients with a large deletion at Xp22 might display MLS with ASD, due to the deletion of contiguous genes, although the highly variable phenotype of these patients could be influenced by several genetic mechanisms, including different tissue-specific X-inactivation and somatic mosaicism.

Unlabelled: Abnormalities of the sex chromosomes (47, XXY, 47 XYY, 45,X/46,XY mosaicism) are frequently associated with Autism Spectrum Disorders (ASD), but the male predisposition to these disorders has not been clearly explained. Previously, the role of the X chromosome was considered important in the ASD mainly because autistic symptoms were detected in genetic syndromes involving X chromosome (fragile X syndrome, Rett syndrome, Klinefelter syndrome). Instead, few studies have analyzed the possible role of the Y chromosome in the ASD. This study explores the role of the Y chromosome in ASD through a systematic literature review about the association between ASD and XYY syndrome and a description of two new cases with this association. The literature review considered studies published in peer-reviewed journals, included in the MEDLINE and PubMed databases, that examined the association between ASD and XYY syndrome. Few studies reported the occurrence of ASD in children with XYY karyotype and the majority of them did not reported a well-defined autism diagnostic category associated with an extra Y chromosome, but several clinical conditions that are generically described as language and social impairment., Conclusion: This study underlines the underestimated role of the Y chromosome in ASD, and we postulate that all the ASD associated with the XYY karyotype may presumably fall within mild degree of ASD as in our cases.

Background: Learning Disorders (LD) are complex diseases that affect about 2-10% of the school-age population. We performed neuropsychological and psychopathological evaluation, in order to investigate comorbidity in children with LD., Methods: Our sample consisted of 448 patients from 7 to 16 years of age with a diagnosis of LD, divided in two subgroups: Specific Learning Disorders (SLD), including reading, writing, mathematics disorders, and Learning Disorders Not Otherwise Specified (LD NOS)., Results: Comorbidity with neuropsychopathologies was found in 62.2% of the total sample. In the LSD subgroup, ADHD was present in 33%, Anxiety Disorder in 28.8%, Developmental Coordination Disorder in 17.8%, Language Disorder in 11% and Mood Disorder in 9.4% of patients. In LD NOS subgroup, Language Disorder was present in 28.6%, Developmental Coordination Disorder in 27.5%, ADHD in 25.4%, Anxiety Disorder in 16.4%, Mood Disorder in 2.1% of patients. A statistically significant presence was respectively found for Language and Developmental Coordination Disorder comorbidity in LD NOS and for ADHD, mood and anxiety disorder comorbidity in SLD subgroup., Conclusions: The different findings emerging in this study suggested to promote further investigations to better define the difference between SLD and LD NOS, in order to improve specific interventions to reduce the long range consequences.

Background: Recurrent headache is common in childhood, but there is not a great amount of data on the associations between headaches and psychopathology in children., Objective: The aim of this study is to examine the relationships between primary headaches and psychopathology in children, using both the categorical and dimensional assessment., Methods: The sample consisted of 70 patients with primary headache compared to a matched sample of 50 healthy children. Psychiatric comorbidity was defined according to the diagnostic criteria of the Diagnostic and Statistical Manual of Disorders. Child psychopathology outcomes were assessed using child- and parent-reported standardized instruments., Results: Internalizing and externalizing problems were significantly represented among children with headaches compared to the control group, respectively 63% and 27%, without significant differences between migraine and tension-type headache children. Moreover, a total of 26% of the children with a headache reported psychiatric comorbidity such as anxiety and mood disorders., Conclusion: The dimensional approach improves accuracy in the recognition of emotional and behavioral problems compared to the categorical approach; however, the use of both of these approaches could be useful for clinical practice, treatment and research.

Incontinentia pigmenti (IP) is an X-linked dominant genodermatosis confined to females. It is usually lethal in males. However, the survival of some males has been reported in literature. We describe a long follow-up case of a 12-year-old male with IP and a normal karyotype but a genomic deletion of the NEMO gene in the Xq28 position in the form of somatic mosaicism. The patient showed severe ophthalmic abnormalities and neurological manifestations characterised by very mild cerebellar ataxia and a history of epilepsy that was severe at the beginning with West syndrome, become moderate overtime and is now resolved. Despite these neurological manifestations, probably related to the presence of at least some mutated cells in his brain, the long-term follow-up in this patient demonstrated good neurological and cognitive outcome.

The aim of this prospective observational study was to verify the tolerability and safety profile of risperidone in a sample of antipsychotic-naive children/adolescent patients having a different psychiatric diagnosis. Twenty-two (mean age of 12±3.2) antipsychotic-naive patients who started therapy with risperidone were recruited. The assessment involved anthropometric data (weight, height, BMI, BMI z-score and BMI percentile), cardiovascular parameters (blood pressure and QTc interval) and blood tests (levels of glucose, triglycerides, total cholesterol, glutamic oxaloacetic and pyruvic transaminases, γ-glutamyl transferase, prolactin, free triiodothyronine, free thyroxine, thyroid-stimulating hormone, thyroglobulin, antithyroid peroxidase and antithyroglobulin). After an average follow-up of 6 months of risperidone therapy, a statistically significant increase in weight and body composition was observed. Furthermore, an increase in serum levels of prolactin was observed in 50% of patients. No other significant changes in metabolic and cardiovascular parameters were found. Although an increase in these parameters was detected, it remained in the normal range. This study suggests the use of specific protocols for monitoring children/adolescents treated with second-generation antipsychotics to manage the metabolic long-term complications and progression to more severe disease states.

The association between cerebral venous thrombosis (CVT) and multiple sclerosis (MS) has already been reported in several adult patients with clinically definite MS, in a suspected relation to i.v. corticosteroids or previously performed lumbar puncture (LP). We are reporting a case, which is, to our knowledge, the first one concerning a child patient with a MS, who developed multiple CVT after LP and during high-dose i.v. corticosteroid. Our conclusions are that the sequence LP followed by high dose corticosteroids may be a contributory factor for the development of CVT when associated with other risk factors., (Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)