The developmental trajectories of the behavioral phenotype and neuropsychiatric functioning in Cornelia de Lange and Rubinstein Taybi syndromes: A longitudinal study.

Several changes in the behavioral phenotype arise with the growth of children affected by Cornelia de Lange Syndrome (CdLS) and Rubinstein-Taybi Syndrome (RSTS). However, previous research relied on a cross-sectional study design turning into age-related comparisons of different syndromic cohorts to explore age-dependent changes. We aim to outline the variating pathways of the neuropsychiatric functioning across the lifespan in CdLS and RSTS, through the setting up of a longitudinal study design. The sample included 14 patients with CdLS and 15 with RSTS. The assessments were carried out in two different timepoints. Our findings highlight that the cognitive profile of CdLS is subjected to a worsening trend with decreasing Intellectual Quotient (IQ) scores from T0 to T1, whereas RSTS shows a stable IQ over time. Patients affected by RSTS show greater improvements compared to CdLS in communication, daily living skills, social abilities, and motor skills across the lifespan. Both syndromes report an upward trend in behavioral and emotional difficulties even if CdLS exhibit a significant and major deterioration compared to individuals with RSTS. Being aware of the early dysfunctional patterns which might pave the way for later neuropsychiatric impairments is the first step for planning preventive interventions.

The Life Project of People with Autism and Intellectual Disability: Investigating Personal Preferences and Values to Enhance Self-Determination.

People with autism and intellectual disabilities, much like individuals with typical development, share a fundamental right and aspiration to realise their own life projects. However, this natural pursuit is uniquely challenging for individuals with autism and intellectual disabilities due to their communication and adaptive hurdles. This growing need has prompted the development of a specific procedure for crafting life projects geared toward enhancing their quality of life. In the present work, we will describe the six key steps and the corresponding assessment, support, and verification tools essential for establishing and actualising the life project for individuals with disabilities, as conceptualised by the Italian Society of Neurodevelopmental Disorders (SIDIN). We will start by delineating diverse preference and value assessment procedures, showcasing an array of tools tailored to accommodate the distinct characteristics of adaptive and communicative functioning in individuals with disabilities. Following this, we will provide a succinct overview of support needs assessment tools. Subsequently, we will introduce the Ecological Life Balance, which serves as an integrative tool for harmonising various assessment systems. We will propose methods for defining existential goals that prioritise quality of life and suggest strategies for implementing support plans. Lastly, we will delve into the methodologies for monitoring and verifying outcomes in the final section.

Cognitive outcome after epilepsy surgery in children: A controlled longitudinal study.

OBJECTIVE: To analyze the determinants of cognitive outcome two years after surgery for drug-resistant epilepsy in a cohort of 31 children when compared to a control group of 14 surgical candidates who had yet to undergo surgery two years after the first neuropsychological assessment. METHODS: Controlled longitudinal study including three evaluations of IQ (Intelligence Quotient) scores or GDQ (General Developmental Quotient) for each group depending on the patient's age: prior to surgery (T0), one year (T1) and two years (T2) after surgery for the surgical group; baseline (T0) and one year (T1) and 2years (T2) after the first evaluation for the control-group. At follow-up, 25 children (80%) of the surgical group were seizure free, while seizure outcome was unsatisfactory in the remaining six (20%). To analyze language, visuomotor skills, memory, reading, visual attention, and behavior, we selected 11 school age children in the surgical group and nine controls. We reported performance prior to (T0) and one year after surgery (T1). RESULTS: There was a significant correlation between earlier age at seizure onset and lower IQ/GDQ at T0 (r=0.39; p=0.03) in the overall cohort. IQ/GDQ scores did not significantly differ between the surgical and control groups when analyzed at T0 and T2. However, they evolved differently with an improved developmental trajectory becoming identifiable only in the surgical group (F1,31=5.33 p=0.028; η2=0.15). There was also a significant increase of forward digit span (Z=2.33; p=0.02) and Rey recall scores (Z=1.97; p=0.049) in the surgical school age subgroup at T1 versus T0. SIGNIFICANCE: We identified significantly different developmental trajectories in operated versus non- operated children with improved IQ/GDQ scores in operated children only. We also observed a significant increase of digit span scores and Rey recall scores a year after surgery. Further studies including larger samples with longer follow-ups are needed to confirm these preliminary findings.

Unaccompanied foreign minors and mental health: Implementation and evaluation of the RHS-15 screening procedure for unaccompanied foreign minors.

Background and objective: The recent notable increase in refugees' flows, with refugee children and adolescents relocating worldwide, posed severe challenges to the different national healthcare systems. Social groups such as refugees fleeing from their countries because of persecution, wars and violence are considered at high risk of developing mental health-related problems. Despite international and national policies legally regulating the reception process and protecting health-related rights, including the mental well-being of refugee migrants, there is a theoretical and applied need for evidence-based instruments and procedures to support mental health within this population. Recent evidence refers to the Refugee Health Screener-15 (RHS-15) as a reliable and valid instrument for the early detection of trauma-related mental health problems. In this scenario, this study aimed to test the RHS screening process within a multidisciplinary first intervention reception context for unaccompanied refugee minors. Design: The RHS-15 was administered with the support of cultural-linguistic mediators to 81 unaccompanied minor residents in a first intervention facility in Milan, Italy. This study aimed to assess psychometric characteristics, such as reliability, sensitivity and specificity feasibility and its implementation within a first intervention reception process. Results: The analysis resulted in the validation of the RHS in its 13-item format. The results highlighted and confirmed an efficient delivery, excellent reliability and a positive predictive and convergent validity of the 13-item version. Further analysis showed an excellent ability to avoid false negatives, although there was a clear tendency to identify false positives. Conclusions: The early identification of vulnerabilities among refugee minors is recommended to promote their long-term overall well-being. Integrating the screening results with additional observational elements and more specific diagnostic tools is recommended to gain a comprehensive perspective of the minors' well-being.

Age-related hallmarks of psychopathology in Cornelia de Lange and Rubinstein-Taybi syndromes.

BACKGROUND AND AIM: There is mounting evidence highlighting that Cornelia de Lange Syndrome (CdLS) and Rubinstein-Taybi Syndrome's (RSTS) behavioral phenotypes are not stable over individual developmental trajectories and that several psychiatric disorders might arise with age. Our study aims to examine the specific hallmarks of psychopathology and behavioral phenotypes in four different age ranges: infancy and toddlerhood, early childhood, middle childhood, and adolescence, in both genetic syndromes. METHOD: The sample included 44 patients with CdLS (48% boys, age = 6.67 ± 4.36) and 31 with RSTS (48% boys, age = 6.89 ± 4.58) recruited through follow-ups. Cognitive, behavioral, and autism assessments were carried out with Griffith's scales or the Leiter-R, the Child Behavior Checklist, and the Child Autism Rating Scales 2. Multiple ANOVA 2 × 4 were run to outline behavioral phenotypic age-related syndromic markers and ANCOVA to value the weight of IQ and ASD-related traits on the psychopathological outcome. RESULTS: Findings showed that anxiety is a crucial phenotypic hallmark, independent of IQ but associated with autistic traits, that increases from infancy to adolescence in both CdLS and RSTS. CONCLUSION AND IMPLICATIONS: Being aware of the developmental challenges that growing children are called to face is essential for drawing up proper standards of assessment turning into target age-related interventions, ensuring these patients personalized healthcare and improvement in life quality.

Behavioral markers of social anxiety in Cornelia de Lange Syndrome: A brief systematic review.

BACKGROUND: There is evidence that social impairments in Cornelia de Lange Syndrome (CdLS) differ from those observed in idiopathic autism as they are characterized mainly by social anxiety. However, the knowledge of the fundamental features of social anxiety symptoms in this target population is limited. This brief systematic review aims to investigate the relationship between social anxiety and CdLS through multiple cross-sectional comparisons. METHODS: PRISMA-P guidelines were followed, and the literature research was conducted in Pubmed, EBSCOhost, Google Scholar, and ScienceDirect using "Cornelia de Lange Syndrome" or "CdLS" and "social anxiety" as search terms. RESULTS: Six articles met the eligibility criteria. Results show that heightened levels of social anxiety in CdLS individuals occur before and after the social engagement and are mediated by both the nature of the social demand and the familiarity of the examiner they interact with. LIMITATIONS: The interpretation of results is limited by the wide heterogeneity of patients' age and sample size across the reviewed studies, and by the absence of a unique observational procedure to detect behaviors indicative of social anxiety in syndromic individuals. CONCLUSIONS: These findings have considerable clinical implications for intervention planning which might be generalized to all people with intellectual disability linked to a genetic syndrome.

Neuropsychiatric Functioning in CDLS: A Detailed Phenotype and Genotype Correlation.

Behavioural phenotype and autism-related traits of 38 patients affected by Cornelia de Lange syndrome (CdLS) were assessed using a specific neuropsychiatric protocol. Subsequently,we search for possible genotype-phenotype correlations comparing individuals with NIPBL variants and patients with negative molecular results. Firstly results showed a higher percentage of subjects with normal intellectual quotient (IQ) and borderline IQ; adaptive skills were lower than expected for age in all participants. 39.5% of the sample presented with autism spectrum disorder (ASD), NIPBL mutated individuals demonstrated a worse trend in comparison with the clinical diagnosis group. non-truncating individuals displayed no ASD and better communication abilities than truncating individuals. Findings increase our awareness of the strengths and weaknesses points in CdLS individuals.

The Relationship Between Resilience and Sleep Quality During the Second Wave of the COVID-19 Pandemic: A Longitudinal Study.

PURPOSE: Previous studies showed poor sleep quality during the first Italian lockdown consequent to the quick spread of the virus. Poor sleep quality remained stable during the so-called "second wave", which started in Autumn 2020. This study aimed to compare sleep quality between the two waves of contagions and to examine the effect of resilience, together with sociodemographic and COVID-related variables, on sleep quality during the second wave. PATIENTS AND METHODS: A total of 648 participated in this longitudinal study through an online survey during the first lockdown consequent to the COVID-19 and during the second wave. The Medical Outcomes Study-Sleep Scale (MOS-SS) and the Resilience Scale (RS) were administered. Sociodemographic and COVID-related information were also collected. RESULTS: The results showed sleep quality slightly increased in the second wave, even though with a small effect size. Correlational analysis showed that resilience is inversely correlated with sleep quality measured in the two waves. Sleep quality during the second wave was positively correlated with sleep quality in the first lockdown. Likewise, the results of multiple regression revealed that the sleep quality in the first lockdown and resilience were significant predictors of sleep quality during the second wave. CONCLUSION: These findings highlighted that the prevalence of poor sleepers remained high during the second wave. Together with the sleep quality in the first lockdown, resilience represents an important factor related to sleep quality during the second wave. Interventions to improve sleep quality among the general population should take into account these findings.

Italian Children's Well-Being after Lockdown: Predictors of Psychopathological Symptoms in Times of COVID-19.

The first Italian lockdown imposed to fight the spread of COVID-19 caused important disruptions in families' everyday lives. The main aim of this research was to investigate the predictors of psychopathology in children aged 5-10 years, immediately after the national 2-month lockdown. A total of 158 Italian parents (148 mothers, 10 fathers, mean age = 41 years) were recruited and asked to complete an online research concerning their 158 children (76 boys, mean age = 7.4 years). Parents completed questionnaires on parent-child conflict, resilience, temperament, behavior, and previous adverse childhood experiences. Hierarchical regressions showed that children's psychopathology was predicted by low child resilience, high novelty seeking and harm avoidance, adverse experiences, and high flooding levels. Moreover, girls exposed to adverse experiences appeared more vulnerable to psychopathology. The recruitment of a convenience sample, the small sample size, and the cross-sectional design of our study limit the generalizability and interpretation of the present findings. Nonetheless, this research extends our knowledge of children's functioning in such an exceptional period. Shedding light on predictors of children's psychopathology following prolonged quarantine can indeed guide effective psychological interventions now and in future similar situations.

Stress and wellbeing among professionals working with people with neurodevelopmental disorders. Review and intervention perspectives.

Supporting individuals with NDD is extremely demanding, with significant exposure to critical contexts and events, and painful ongoing experiences. Stress and burnout condition is a main concern with growing interest in research, despite the lack of consensus on theoretical explanatory models and modification standards.The paper provides an up-to-date review of risk factors and involved processes, and presents evidence-based procedures and protocols to implement effective preventive actions addressing both organizational and individual factors. The aim is to offer a global understanding of the subject and offer examples of practical plans to increase the impact on the quality of life of clients and staff members.

Neurodevelopmental disorders and development of project of lifein a lifespan perspective: between habilitation and quality of life.

For some years, the term "project of life" has become widely used in the field of neurodevelopmental disorders, and, at the same time, it has begun to make its way in many social and health planning documents. However, beyond its relatively widespread use, this term does not yet possess an adequate and shared frame of the main underlying decision-making processes. In particular, there is a need to identify the crucial questions for orienting the choice of goals within the adolescent transition, which represents the complex hinge between childhood and adulthood. Moreover, adulthood, which is often completely devoid of culturally and socially shared references, is still critical precisely because of the lack of future direction prompts usually represented by the stages of development. In this case, the themes of quality of life functioning as a guiding compass appear pertinent and much more relevant. The present contribution is, therefore, an attempt to present, in a unitary manner, the decision-making processes and questions at the basis of a construct of "project of life" shared within the scientific and associative communities.

The Role of Free and Cued Selective Reminding Test in Predicting [18F]Florbetaben PET Results in Mild Cognitive Impairment and Mild Dementia.

BACKGROUND: Free and Cued Selective Reminding Test (FCSRT) is a reliable cognitive marker for Alzheimer's disease (AD), and the identification of neuropsychological tests sensitive to the early signs of AD pathology is crucial both in research and clinical practice. OBJECTIVE: The study aimed to ascertain the ability of FCSRT in predicting the amyloid load as determined from amyloid PET imaging (Amy-PET) in patients with cognitive disorders. METHODS: For our purpose, 79 patients (71 MCI, 8 mild dementia) underwent a complete workup for dementia, including the FCSRT assessment and a [18F]florbetaben PET scan. FCSRT subitem scores were used as predictors in different binomial regression models. RESULTS: Immediate free recall and delayed free recall were the best predictors overall in the whole sample; whereas in patients <76 years, all models further improved with immediate total recall (ITR) and Index of Sensitivity of Cueing (ISC) resulting the most accurate in anticipating Amy-PET results, with a likelihood of being Amy-PET positive greater than 85% for ITR and ISC scores of less than 25 and 0.5, respectively. CONCLUSION: FCSRT proved itself to be a valid tool in dementia diagnosis, also being able to correlate with amyloid pathology. The possibility to predict Amy-PET results through a simple and reliable neuropsychological test might be helpful for clinicians in the dementia field, adding value to a paper and pencil tool compared to most costly biomarkers.

CSF biomarkers and amyloid PET: concordance and diagnostic accuracy in a MCI cohort.

Brain amyloid deposition is one of the main hallmarks of Alzheimer's disease (AD) and two approaches are available for assessing amyloid pathology in vivo: cerebrospinal fluid (CSF) biomarkers levels and amyloid load visualized by amyloid beta positron emission tomography imaging (Amy-PET) probes. We aimed to investigate the concordance between CSF biomarkers and Amy-PET in a memory clinic cohort. Moreover, using a proper clinical follow-up, we wanted to assess the diagnostic accuracy of CSF and PET biomarkers in predicting the progression of patients with mild cognitive impairment (MCI) to AD dementia. We included 31 MCI patients who underwent [18F]florbetaben PET and CSF sampling (Aß1-42, t-Tau, p-Tau). A semiquantitative visual scan assessment was used to quantify amyloid deposition in 5 brain regions, rating from 1 (negative), to 2 and 3 (positive). CSF biomarkers were considered abnormal if: Aß1-42 < 600 pg/ml, p-Tau/Aß1-42 > 0.08 and t-Tau/Aß1-42 > 0.52. We also applied less lenient cutoffs of 550 pg/ml and 450 pg/ml for Aß1-42. The concordance rate was 77% between Amy-PET and CSF Aß1-42 levels, and 89% between Amy-PET and p-Tau/Aß1-42 and t-Tau/Aß1-42. According to the clinical follow-up, Amy-PET (sensitivity [SE] 93.7%, specificity [SP] 80%) exhibited the best diagnostic accuracy in discriminating AD from non-AD, followed by p-Tau/Aß1-42 ratio and t-Tau/Aß1-42 ratio (SE 93.7%, SP 66.6%), and Aß1-42 levels (SE 81%, SP 60%). The regional uptake of [18F]florbetaben PET in the precuneus and the striatum showed the best SP (86.6%). In discordant cases, the clinical diagnosis was most often in agreement with PET results. In general, concordance between CSF biomarkers and Amy-PET was good, especially when the ratios between CSF amyloid and Tau biomarkers were used. However, Amy-PET proved to be superior to CSF Aß1-42 in terms of diagnostic accuracy for AD, with the possibility to further increase its specificity by focusing the analysis in specific areas such as the precuneus/posterior cingulate cortex and the striatum.

The Incremental Diagnostic Value of [18F]Florbetaben PET and the Pivotal Role of the Neuropsychological Assessment in Clinical Practice.

BACKGROUND: Amyloid pathology is a key feature of Alzheimer's disease (AD) and can be assessed in vivo with amyloid positron emission tomography (PET) imaging. OBJECTIVE: The objective of this study was to evaluate the incremental value of a PET scan with [18F]florbetaben, in terms of changes of diagnosis, diagnostic confidence, and treatment plan when added to a standardized diagnostic workup for cognitive disorders, with particular focus on the role of the neuropsychological assessment, including the Free and Cued Selective Reminding Test (FCSRT). METHODS: A total of 104 patients (69 mild cognitive impairment, 35 dementia), with diagnostic uncertainty after diagnostic workup, were recruited from our memory clinic. [18F]florbetaben PET scans were interpreted as amyloid negative or positive on the basis of a semi-quantitative visual rating. Clinical diagnosis and diagnostic confidence for AD or non-AD dementia were rated before and after PET result disclosure, as was the impact of PET on the patient management plan. RESULTS: There were 69/104 (66%) [18F]florbetaben positive scans, 51/62 (82%) patients were suspected as having AD before the PET scan and 18/42 (43%) were not. Overall, the data obtained at PET changed 18/104 diagnoses (17%) and increased diagnostic confidence from 69.1±8.1% to 83.5±9.1 (p < 0.001), with the greatest impact on diagnosis and confidence in PET negative patients with an initial diagnosis of AD (p < 0.01) and in early-onset patients (p = 0.01). CONCLUSION: Amyloid PET represents a source of added value in dementia diagnosis, with a significant effect on diagnosis and diagnostic confidence. However, the use of a complete neuropsychological assessment has an add-on value on limiting the amyloid PET influence on change of diagnosis, and the real impact of amyloid PET should always be weighed up together with an accurate standardized diagnostic workup.

Behavioral and Neurophysiological Effects of Transcranial Direct Current Stimulation (tDCS) in Fronto-Temporal Dementia.

Fronto-temporal dementia (FTD) is the clinical-diagnostic term that is now preferred to describe patients with a range of progressive dementia syndromes associated with focal atrophy of the frontal and anterior temporal cerebral regions. Currently available FTD medications have been used to control behavioral symptoms, even though they are ineffective in some patients, expensive and may induce adverse effects. Alternative therapeutic approaches are worth pursuing, such as non-invasive brain stimulation with transcranial direct current (tDCS). tDCS has been demonstrated to influence neuronal excitability and reported to enhance cognitive performance in dementia. The aim of this study was to investigate whether applying Anodal tDCS (2 mA intensity, 20 min) over the fronto-temporal cortex bilaterally in five consecutive daily sessions would improve cognitive performance and behavior symptoms in FTD patients, also considering the neuromodulatory effect of stimulation on cortical electrical activity measured through EEG. We recruited 13 patients with FTD and we tested the effect of Anodal and Sham (i.e., placebo) tDCS in two separate experimental sessions. In each session, at baseline (T0), after 5 consecutive days (T1), after 1 week (T2), and after 4 weeks (T3) from the end of the treatment, cognitive and behavioral functions were tested. EEG (21 electrodes, 10-20 international system) was recorded for 5 min with eyes closed at the same time points in nine patients. The present findings showed that Anodal tDCS applied bilaterally over the fronto-temporal cortex significantly improves (1) neuropsychiatric symptoms (as measured by the neuropsychiatric inventory, NPI) in FTD patients immediately after tDCS treatment, and (2) simple visual reaction times (sVRTs) up to 1 month after tDCS treatment. These cognitive improvements significantly correlate with the time course of the slow EEG oscillations (delta and theta bands) measured at the same time points. Even though further studies on larger samples are needed, these findings support the effectiveness of Anodal tDCS over the fronto-temporal regions in FTD on attentional processes that might be correlated to a normalized EEG low-frequency pattern.