Neuroradiologic, clinic and genetic characterization of cerebellar heterotopia: a pediatric multicentric study.

Background and purpose:Cerebellar heterotopia (CH) is a neuroradiological abnormality poorly reported and investigated in the literature. It can be observed as an isolated finding, but it has been mainly reported in the context of cerebellar dysgenesis and in syndromic conditions. The aim of this study is to provide a comprehensive neuroradiological, clinical, and genetic characterization of a cohort of pediatric patients with cerebellar heterotopia.Materials and methods:Patients with a diagnosis of CH were systematically selected from the neuroimaging databases of the four Italian Centers participating in this retrospective study. For each patient, information regarding demographic, clinical, genetic and neuroradiological data were collected.Results:Thirty-two pediatric patients were recruited and subdivided into two groups: patients with isolated CH and/or cerebellar malformations (n= 18) and patients with CH associated with cerebral malformations (n=14). Isolated CH consistently showed a peripheral subcortical localization in the inferior portion of cerebellar hemispheres, with either unilateral or bilateral distribution. Ten patients belonging to the second group had a diagnosis of CHARGE syndrome, and their nodules of CH were mainly but not exclusively bilateral, symmetric, located in the peripheral subcortical zone and in the inferior portion of the cerebellar hemispheres; the remaining 4 patients of the second group, showed either bilateral or unilateral CH, located in both peripheral cortex and deep white matter and in the superior and inferior portions of cerebellum. Patients with isolated CH showed high prevalence of language development delay; neurodevelopmental disorders were the most represented clinical diagnoses. Recurring features were behavioral problems and motor difficulties. A conclusive genetic diagnosis was found in 18/32 patients.Conclusions:We found distinctive neuroradiological patterns of CH. Genetic results raise the possibility of a correlation between cerebellar morphological and functional developmental disruption, underscoring the importance of CH detection and reporting to orient the diagnostic path.Abbreviations CH Cerebellar heterotopia; MRI Magnetic resonance imaging; CC Corpus callosum; ASD autism spectrum disorder; IVH inferior vermian hypoplasia.

Bridging early life trauma to difficult-to-treat depression: scoping review.

AIMS AND METHOD: Accumulating evidence suggests that early life trauma (ELT) initiates and perpetuates a cycle of depression, leading to challenges in management and achieving remission. This scoping review aimed to examine the intricate relationship between ELT and difficult-to-treat depression (DTD). An extensive literature search from 1 January 2013 to 21 October 2023 was conducted using the Cochrane Library, PubMed, Scopus, PsycINFO and OpenGrey. RESULTS: Our review identified scientific literature illustrating the multifaceted link between ELT and DTD, highlighting the dual impact of ELT on therapeutic resistance and clinical complexity. CLINICAL IMPLICATIONS: This complexity hampers management of patients with DTD, who are characterised by limited pharmacological responsiveness and heightened relapse risk. While exploring the ELT-DTD nexus, the review revealed a paucity of literature on the impact of ELT within DTD. Findings underscore the profound link between ELT and DTD, which is essential for comprehensive understanding and effective management. Tailoring treatments to address ELT could enhance therapeutic outcomes for patients with DTD. Future studies should use larger samples and well-defined diagnostic criteria and explore varied therapeutic approaches.

Pathogenic cryptic variants detectable through exome data reanalysis significantly increase the diagnostic yield in Joubert syndrome.

Joubert syndrome (JS) is a genetically heterogeneous neurodevelopmental ciliopathy. Despite exome sequencing (ES), several patients remain undiagnosed. This study aims to increase the diagnostic yield by uncovering cryptic variants through targeted ES reanalysis. We first focused on 26 patients in whom ES only disclosed heterozygous pathogenic coding variants in a JS gene. We reanalyzed raw ES data searching for copy number variants (CNVs) and intronic variants affecting splicing. We validated CNVs through real-time PCR or chromosomal microarray, and splicing variants through RT-PCR or minigenes. Cryptic variants were then searched in additional 44 ES-negative JS individuals. We identified cryptic "second hits" in 14 of 26 children (54%) and biallelic cryptic variants in 3 of 44 (7%), reaching a definite diagnosis in 17 of 70 (overall diagnostic gain 24%). We show that CNVs and intronic splicing variants are a common mutational mechanism in JS; more importantly, we demonstrate that a significant proportion of such variants can be disclosed simply through a focused reanalysis of available ES data, with a significantly increase of the diagnostic yield especially among patients previously found to carry heterozygous coding variants in the KIAA0586, CC2D2A and CPLANE1 genes.

Inflammatory biomarkers in depression: scoping review.

BACKGROUND: Inflammation is increasingly recognised as a fundamental component of the pathophysiology of major depressive disorder (MDD), with a variety of inflammatory biomarkers playing pivotal roles. These markers are closely linked to both the severity of symptoms and the responsiveness to treatments in MDD. AIMS: This scoping review aims to explore the scientific literature investigating the complex relationships between inflammatory biomarkers and depression, by identifying new studies and critical issues in current research. METHOD: Following the PRISMA Extension for Scoping Reviews guidelines, we systematically searched databases including PubMed, Scopus, PsycINFO, Open Grey and Cochrane Library. Our search focused on articles published from 1 January 2020 to 1 May 2024. We included studies evaluating inflammatory biomarkers in adult patients with MDD, utilising observational and randomised controlled trial designs, and review studies. RESULTS: Our analysis examined 44 studies on the complex interplay between inflammation and its multiple effects on MDD. Significant associations between specific inflammatory biomarkers and depression severity were found, requiring cautious interpretation. We also highlight several methodological limitations in the current studies, which warrant caution in directly applying these findings to clinical practice. However, identified methodologies show potential for using these biomarkers as diagnostic tools or therapeutic targets, including anti-inflammatory interventions. CONCLUSIONS: The findings emphasise the need for sophisticated, integrative research to understand inflammation's role in MDD. Future studies should identify specific biomarker panels for diagnosing depression and bridging peripheral biomarker measurements with central neuroinflammatory processes, leading to better diagnostic and treatment strategies.

Novel molecular, structural and clinical findings in an Italian cohort of congenital cataract.

The current genetic diagnostic workup of congenital cataract (CC) is mainly based on NGS panels, whereas exome sequencing (ES) has occasionally been employed. In this multicentre study, we investigated by ES the detection yield, mutational spectrum and genotype-phenotype correlations in a CC cohort recruited between 2020 and mid-2022. The cohort consisted of 67 affected individuals from 51 unrelated families and included both non-syndromic (75%) and syndromic (25%) phenotypes, with extra-CC ocular/visual features present in both groups (48% and 76%, respectively). The functional effect of variants was predicted by 3D modelling and hydropathy properties changes. Variant clustering was used for the in-depth assessment of genotype-phenotype correlations. A diagnostic (pathogenic or likely pathogenic) variant was identified in 19 out of 51 probands/families (~37%). In a further 14 probands/families a candidate variant was identified: in 12 families a VUS was detected, of which 9 were considered plausibly pathogenic (i.e., 4 or 5 points according to ACMG criteria), while in 2 probands ES identified a single variant in an autosomal recessive gene associated with CC. Eighteen probands/families, manifesting primarily non-syndromic CC (15/18, 83%), remained unsolved. The identified variants (8 P, 12 LP, 10 VUS-PP, and 5 VUS), half of which were unreported in the literature, affected five functional categories of genes involved in transcription/splicing, lens formation/homeostasis (i.e., crystallin genes), membrane signalling, cell-cell interaction, and immune response. A phenotype-specific variant clustering was observed in four genes (KIF1A, MAF, PAX6, SPTAN1), whereas variable expressivity and potential phenotypic expansion in two (BCOR, NHS) and five genes (CWC27, KIF1A, IFIH1, PAX6, SPTAN1), respectively. Finally, ES allowed to detect variants in six genes not commonly included in commercial CC panels. These findings broaden the genotype-phenotype correlations in one of the largest CC cohorts tested by ES, providing novel insights into the underlying pathogenetic mechanisms and emphasising the power of ES as first-tier test.

Gaze Orienting in the Social World: An Exploration of the Role Played by Caregiving Vocal and Tactile Behaviors in Infants with Visual Impairment and in Sighted Controls.

Infant attention is a cognitive function that underlines sensory-motor integration processes at the interface between the baby and the surrounding physical and socio-relational environment, mainly with the caregivers. The investigation of the role of non-visual inputs (i.e., vocal and tactile) provided by the caregivers in shaping infants' attention in the context of visual impairment is relevant from both a theoretical and clinical point of view. This study investigated the social attention (i.e., gaze orientation) skills in a group of visually impaired (VI) and age-matched sighted controls (SCs) between 9 and 12 months of age. Moreover, the role of VI severity and maternal vocalizations and touch in shaping the social attention were investigated. Overall, 45 infants and their mothers participated in a video-recorded 4 min interaction procedure, including a play and a still-face episode. The infants' gaze orientation (i.e., mother-directed, object-directed, or unfocused) and the types of maternal vocalizations and touch (i.e., socio-cognitive, affective) were micro-analytically coded. Maternal vocalizations and touch were found to influence gaze orientation differently in VI infants compared SCs. Moreover, the group comparisons during the play episode showed that controls were predominantly oriented to the mothers, while VI infants were less socially oriented. Visual impairment severity did not emerge as linked with social attention. These findings contribute to our understanding of socio-cognitive developmental trajectories in VI infants and highlight the need for tailored interventions to promote optimal outcomes for VI populations.

LZTFL1, a rare cause of Bardet-Biedl syndrome: A new patient with severe short stature and moderate intellectual disability, more than casual associations?

Bardet-Biedl syndrome (BBS) is an inherited ciliopathy affecting multiple organs and systems with wide clinical and genetic heterogeneity. To date, biallelic variants of the LZTFL1 gene have been reported only in six patients with BBS. We identified a homozygous LZTFL1 nonsense variant in a boy presenting with classical BBS features. In addition, he showed a more pronounced cognitive impairment than previously reported subjects and severe short stature, matching the phenotype displayed by some other patients with LZTFL1 variants and lztfl1 knock-out mice. This case report contributes to a better understanding of the clinical spectrum associated with LZTFL1 pathogenic variants, and highlights possible genotype-phenotype correlations.

Sensorimotor Oscillations in Human Infants during an Innate Rhythmic Movement.

The relationship between cerebral rhythms and early sensorimotor development is not clear. In recent decades, evidence revealed a rhythmic modulation involving sensorimotor processing. A widely corroborated functional role of oscillatory activity is to coordinate the information flow across sensorimotor networks. Their activity is coordinated by event-related synchronisation and desynchronisation in different sensorimotor rhythms, which indicate parallel processes may be occurring in the neuronal network during movement. To date, the dynamics of these brain oscillations and early sensorimotor development are unexplored. Our study investigates the relationship between the cerebral rhythms using EEG and a typical rhythmic movement of infants, the non-nutritive sucking (NNS) behaviour. NNS is an endogenous behaviour that originates from the suck central pattern generator in the brainstem. We find, in 17 infants, that sucking frequency correlates with beta synchronisation within the sensorimotor area in two phases: one strongly anticipating (~3 s) and the other encompassing the start of the motion. These findings suggest that a beta synchronisation of the sensorimotor cortex may influence the sensorimotor dynamics of NNS activity. Our results reveal the importance of rapid brain oscillations in infants and the role of beta synchronisation and their possible role in the communication between cortical and deep generators.

Blindness affects the developmental trajectory of the sleeping brain.

Sleep plays a crucial role in brain development, sensory information processing, and consolidation. Sleep spindles are markers of these mechanisms as they mirror the activity of the thalamocortical circuits. Spindles can be subdivided into two groups, slow (10-13 Hz) and fast (13-16 Hz), which are each associated with different functions. Specifically, fast spindles oscillate in the high-sigma band and are associated with sensorimotor processing, which is affected by visual deprivation. However, how blindness influences spindle development has not yet been investigated. We recorded nap video-EEG of 50 blind/severely visually impaired (BSI) and 64 sighted children aged 5 months to 6 years old. We considered aspects of both macro- and micro-structural spindles. The BSI children lacked the evolution of developmental spindles within the central area. Specifically, young BSI children presented low central high-sigma and high-beta (25-30 Hz) event-related spectral perturbation and showed no signs of maturational decrease. High-sigma and high-beta activity in the BSI group correlated with clinical indices predicting perceptual and motor disorders. Our findings suggest that fast spindles are pivotal biomarkers for identifying an early developmental deviation in BSI children. These findings are critical for initial therapeutic intervention.

Visual function in children with Joubert syndrome.

AIM: To describe visual function in children with Joubert syndrome and to investigate its possible association with diagnostic and developmental aspects. METHOD: This retrospective cross-sectional work included 59 patients (33 male; mean age 9 years 2 months, standard deviation 6 years 3 months, range 4 months to 23 years) diagnosed with Joubert syndrome from January 2002 to December 2020. Data about clinical (neurological, neuro-ophthalmological, developmental/cognitive) and diagnostic (e.g. genetic testing, neuroimaging, systemic involvement) evaluations were collected in a data set during a review of medical records. Clinical and diagnostic variables were described in terms of raw counts and percentages. A χ2 test was conducted to investigate their association with neuropsychological skills. RESULTS: Ocular motor apraxia was highly represented in our cohort (75%), with a high prevalence of refractive defects and retinal abnormalities. Developmental delay/intellectual disability was frequent (in 69.5% of the sample), associated with retinal dystrophy (p = 0.047) and reduced visual acuity both for near (p = 0.014) and for far distances (p = 0.017). INTERPRETATION: On the basis of the relevance of oculomotor and perceptual alterations and their impact on overall and cognitive impairment, we encourage early and multidisciplinary assessment and follow-up of visual function in children with Joubert syndrome. This would help in planning a personalized rehabilitation to sustain functional vision. Further studies will be important to explore the link between biological aspects and global functioning in children with Joubert syndrome. WHAT THIS PAPER ADDS: Perceptual deficits and oculomotor impairments frequently coexist in Joubert syndrome. Retinal dysfunction may be present despite the absence of funduscopic abnormalities. Both perceptual and oculomotor impairments negatively affect cognitive development in Joubert syndrome.

[Appreciation index of multifamily psychoanalysis within a territorial Mental Health Service.] / Indice di gradimento della psicoanalisi multifamiliare all'interno di un servizio di salute mentale territoriale.

AIM: The aim of the present research is to assess the satisfaction levels of participants in a multifamily psychoanalysis group conducted within a territorial mental health service, following the model developed by Argentine psychoanalyst Jorge García Badaracco. METHODS: To evaluate participant satisfaction in the therapeutic group, an anonymous satisfaction questionnaire was adopted and administered during each multifamily therapy session between 2016 and 2019. The sample consisted of designated patients and their family members participating in the groups. RESULTS: The results obtained from measuring participant satisfaction during the specified time period indicate a consistent and increasing level of satisfaction with the group activities conducted by all participants. DISCUSSION AND CONCLUSIONS: The obtained results indicate that the experience of multifamily psychoanalysis seems to be well-received and positively perceived by both users and family members, thereby contributing to an overall increase in satisfaction with the mental health service. The measurement of subjective satisfaction ratings in scientific literature is explored in relation to satisfaction, adherence, compliance, and treatment persistence, and can also be included as part of a broader set of variables aimed at identifying objective indicators of intervention outcomes in multifamily psychotherapies.

Visual Function and Neuropsychological Profiling of Idiopathic Infantile Nystagmus.

Though considered a benign condition, idiopathic infantile nystagmus (IIN) may be associated with decreased visual acuity and oculo-motor abnormalities, resulting in developmental delays and poor academic performance. Nevertheless, the specific visual function profile of IIN and its possible impact on neuropsychological development have been poorly investigated. To fill this gap, we retrospectively collected the clinical data of 60 children presenting with IIN over a 10-year period (43 male; mean age of 7 years, range of 2 months-17 years, 9 months). The majority of the subjects in our cohort presented with reduced visual acuity for far distances and normal visual acuity for near distances, associated with oculo-motor abnormalities. The overall scores of cognitive and visual-cognitive tests were in the normal range, but revealed peculiar cognitive and visual-cognitive profiles, defined by specific frailties in processing speed and visual-motor integration. The same neuropsychological profiles characterize many neurodevelopmental disorders and may express a transnosographic vulnerability of the dorsal stream. As the first study to explore the neuropsychologic competencies in children with IIN, our study unveils the presence of subclinical frailties that need to be addressed to sustain academic and social inclusion.

Difficult-To-Treat Depression. Scoping Review.

Objective: Recently, several academics have recommended that the concept of difficult-to-treat depression (DTD) should be considered in some of the cases where achieving or maintaining remission of depressive symptoms is not possible. In 2020, a consensus statement, not based on a formal process and systematic review defined difficult-to-treat depression as "depression that continues to cause significant burden despite normal treatment efforts". In addition to addressing symptom control, interventions for DTD should also target other factors, including the management of psychiatric and medical comorbidities, psychosocial functioning, self-esteem, and self-management strategies. The purpose of this scoping review is to explore the scientific literature, which is still unclear and vague, regarding the pathophysiology and treatment of difficult-to-treat depression, providing a summary of its current conceptualization. This represents a cultural and scientific shift that offers clinicians and researchers valid and up-to-date study criteria, thus expanding upon the model of treatment-resistant depression (TRD). Consequently contributions, concepts, theories and gaps of the state of the art in the description of difficult-to-treat depression have been summarized here. Method: A research study was conducted using PubMed, Scopus, PsycINFO, Cochrane Library, and Open Grey databases to identify and examine articles reporting key features related to the recent concept of difficult-to-treat depression. The research covered a period of time between January 1, 2013, and March 1, 2023. Based on a formal checklist, two researchers independently assessed the eligibility criteria to determine which studies to include or exclude in this search. Further data evaluations were conducted for the articles that were deemed to have the most comprehensive descriptions. Results: The results of the research yielded a body of literature that provides a clear definition of difficult-to-treat depression and insights into its clinical application and research perspective. Conclusions: DTD represents a cultural and scientific shift that provides clinicians and researchers with valid and up-to-date study criteria that allow the extension of the treatment-resistant depression (TRD) model. The main difference lies in the operational process of assessment and intervention in the depressive syndrome in relation to the search for a therapeutic response. The results of this review show that DTD is a theoretically and clinically useful conceptualization for depressive syndromes that are not just simply resistant to treatment. This clinical condition entails a novel clinical therapeutic approach for specific patients and may be used throughout the world to help recognize this clinical condition while optimizing overall care for these patients. However, as we have highlighted, in the absence of RCTs and further observational studies, it is desirable that DTD be further investigated and defined..

A multidisciplinary approach to inherited retinal dystrophies from diagnosis to initial care: a narrative review with inputs from clinical practice.

BACKGROUND: Non-syndromic inherited retinal dystrophies (IRDs) such as retinitis pigmentosa or Leber congenital amaurosis generally manifest between early childhood and late adolescence, imposing profound long-term impacts as a result of vision impairment or blindness. IRDs are highly heterogeneous, with often overlapping symptoms among different IRDs, and achieving a definite diagnosis is challenging. This narrative review provides a clinical overview of the non-syndromic generalized photoreceptor dystrophies, particularly retinitis pigmentosa and Leber congenital amaurosis. The clinical investigations and genetic testing needed to establish a diagnosis are outlined, and current management approaches are discussed, focusing on the importance of the involvement of an interdisciplinary team from diagnosis and initial care to long-term follow-up and support. RESULTS: The effective management of IRDs requires a multidisciplinary, and ideally interdisciplinary, team of experts knowledgeable about IRDs, with experienced professionals from fields as diverse as ophthalmology, neuropsychiatry, psychology, neurology, genetics, orthoptics, developmental therapy, typhlology, occupational therapy, otolaryngology, and orientation and mobility specialties. Accurate clinical diagnosis encompasses a range of objective and subjective assessments as a prerequisite for the genetic testing essential in establishing an accurate diagnosis necessary for the effective management of IRDs, particularly in the era of gene therapies. Improvements in genome sequencing techniques, such as next-generation sequencing, have greatly facilitated the complex process of determining IRD-causing gene variants and establishing a molecular diagnosis. Genetic counseling is essential to help the individual and their family understand the condition, the potential risk for offspring, and the implications of a diagnosis on visual prognosis and treatment options. Psychological support for patients and caregivers is important at all stages of diagnosis, care, and rehabilitation and is an essential part of the multidisciplinary approach to managing IRDs. Effective communication throughout is essential, and the patient and caregivers' needs and expectations must be acknowledged and discussed. CONCLUSION: As IRDs can present at an early age, clinicians need to be aware of the clinical signs suggesting visual impairment and follow up with multidisciplinary support for timely diagnoses to facilitate appropriate therapeutic or rehabilitation intervention to minimize vision loss.

Clinical assessment of the TechArm system on visually impaired and blind children during uni- and multi-sensory perception tasks.

We developed the TechArm system as a novel technological tool intended for visual rehabilitation settings. The system is designed to provide a quantitative assessment of the stage of development of perceptual and functional skills that are normally vision-dependent, and to be integrated in customized training protocols. Indeed, the system can provide uni- and multisensory stimulation, allowing visually impaired people to train their capability of correctly interpreting non-visual cues from the environment. Importantly, the TechArm is suitable to be used by very young children, when the rehabilitative potential is maximal. In the present work, we validated the TechArm system on a pediatric population of low-vision, blind, and sighted children. In particular, four TechArm units were used to deliver uni- (audio or tactile) or multi-sensory stimulation (audio-tactile) on the participant's arm, and subject was asked to evaluate the number of active units. Results showed no significant difference among groups (normal or impaired vision). Overall, we observed the best performance in tactile condition, while auditory accuracy was around chance level. Also, we found that the audio-tactile condition is better than the audio condition alone, suggesting that multisensory stimulation is beneficial when perceptual accuracy and precision are low. Interestingly, we observed that for low-vision children the accuracy in audio condition improved proportionally to the severity of the visual impairment. Our findings confirmed the TechArm system's effectiveness in assessing perceptual competencies in sighted and visually impaired children, and its potential to be used to develop personalized rehabilitation programs for people with visual and sensory impairments.

Recurrent, founder and hypomorphic variants contribute to the genetic landscape of Joubert syndrome.

BACKGROUND: Joubert syndrome (JS) is a neurodevelopmental ciliopathy characterised by a distinctive mid-hindbrain malformation, the 'molar tooth sign'. Over 40 JS-associated genes are known, accounting for two-thirds of cases. METHODS: While most variants are novel or extremely rare, we report on 11 recurring variants in seven genes, including three known 'founder variants' in the Ashkenazi Jewish, Hutterite and Finnish populations. We evaluated variant frequencies in ~550 European patients with JS and compared them with controls (>15 000 Italian plus gnomAD), and with an independent cohort of ~600 JS probands from the USA. RESULTS: All variants were markedly enriched in the European JS cohort compared with controls. When comparing allele frequencies in the two JS cohorts, the Ashkenazim founder variant (TMEM216 c.218G>T) was significantly enriched in American compared with European patients with JS, while MKS1 c.1476T>G was about 10 times more frequent among European JS. Frequencies of other variants were comparable in the two cohorts. Genotyping of several markers identified four novel European founder haplotypes.Two recurrent variants (MKS1 c.1476T>G and KIAA0586 c.428delG), have been detected in homozygosity in unaffected individuals, suggesting they could act as hypomorphic variants. However, while fibroblasts from a MKS1 c.1476T>G healthy homozygote showed impaired ability to form primary cilia and mildly reduced ciliary length, ciliary parameters were normal in cells from a KIAA0586 c.428delG healthy homozygote. CONCLUSION: This study contributes to understand the complex genetic landscape of JS, explain its variable prevalence in distinct geographical areas and characterise two recurrent hypomorphic variants.

[Treatment-resistant depression. From classification to new therapies.] / Depressione resistente a trattamento. Dalla classificazione alle nuove terapie.

AIMS: This paper aims to investigate the advances in recent years in the recognition and therapy of treatment-resistant depression starting from the concepts of: depressive disorder, resistance and pseudoresistance to drug treatment in depression, and appropriate treatments of treatment-resistant depression. METHODS: An extensive research was carried out on scientific databases such as: PubMed, PsychInfo and Cochrane Library, until May 2022, using the keywords "major depression", "treatment-resistant depression", "staging", "instrumental therapies for resistant depression", "esketamine" and "psilocybin". RESULTS: Subjects who do not respond to antidepressants show a form of treatment resistance that requires an approach with additional pharmacological and/or instrumental therapies. Recently, esketamine and psilocybin are of particular interest among clinicians, and instrumental treatments such as: vagus nerve stimulation, deep brain stimulation, repetitive transcranial magnetic stimulation, transcranial direct current stimulation, epidural cortical stimulation, and electro convulsive therapy, are being added to them. DISCUSSION AND CONCLUSIONS: Treatment-resistant depression has increasingly become a public health problem due to the significant number of relapses, hospitalizations and mortality it entails, with increased demand for the use of more drugs, therapeutic resources by health services, and loss of quality of life for patients. Treatment-resistant depression needs to be addressed through the creation of dedicated study protocols. Future research should focus on the need to establish operational, valid and appropriate criteria, both on the psychopathological, clinical governance and therapeutic levels, focusing on the latest therapies in order to provide reliable data on the benefits, risks and costs associated with their use.

Case report: Dancing in the dark: A critical single case study engaging a blind father in the rehabilitation journey of his visually impaired child.

Background: Face-to-face visual contact is a key component of the early parent-child interaction, therefore a visual impairment condition of the parent or the child represents a risk factor for dyadic patterns' development. Aims: The study presents a critical single case of a blind father and a 18-month-old visually impaired child. The study aims to explore changes in the relational functioning of this dyad during an early family-centered intervention. Methods and procedures: Ten parent-child sessions were videotaped and micro-analytically coded. Data were analyzed through a State Space Grid crossing child's social cues and types of father verbalizations. Outcomes and results: Findings showed a stable increase in the amount of child social cues over time. Moreover, the dyad exhibited progressive changes in dyadic regulation, stability, and organization. The return time to the "active interaction" region of interest decreased progressively. A reduction was observed also for the time spent by the dyad in the region "no vocal contact." Conclusions and implications: This critical single case highlighted the benefits of parental engagement in early interventions for the dyadic regulation in parent-child interaction.

Patient- and parent-reported outcome measures of developmental adaptive abilities in visually impaired children: The Visual Impairment Developmental Autonomy (VIDA) scale.

In the pediatric context, parents' and patients' engagement in the care process is strongly recommended and could be pursued using patient-reported outcome measures (PROMs), which therefore become useful for planning and monitoring treatments. Nevertheless, few data are available from families of children with neurodevelopmental disorders such as visual impairment (VI). The Visual Impairment Developmental Autonomy (VIDA) project aims to develop and validate a patient- and parent-reported tool to measure the most relevant aspects concerning everyday adaptive abilities in children and adolescents with visual impairment: the VIDA scale. The present paper illustrates the Delphi process of item generation engaging parents and patients and presents a protocol for the validation of this new co-designed tool in an Italian visually impaired pediatric population. Twenty-three families and five adolescents provided a list of 192 items and assessed their relevance. Items were categorized in 5 areas of adaptive abilities (i.e., table manners, clothing, personal hygiene, orientation and mobility, and socio-affectivity) and into three age ranges based on the patient's age. The final 102-item Vida Scale will be administered to a minimum of 300 visually impaired children together with measures of quality of life and child adjustment to investigate its psychometric properties.

Visual Function and Neuropsychological Profile in Children with Cerebral Visual Impairment.

Cerebral Visual Impairment (CVI) has become the leading cause of children's visual impairment in developed countries. Since CVI may negatively affect neuropsychomotor development, an early diagnosis and characterization become fundamental to define effective habilitation approaches. To date, there is a lack of standardized diagnostic methods to assess CVI in children, and the role of visual functions in children's neuropsychological profiles has been poorly investigated. In the present paper, we aim to describe the clinical and neuropsychological profiles and to investigate the possible effects of visual functions on neuropsychological performance of a cohort of children diagnosed with CVI. Fifty-one children with CVI were included in our retrospective analysis (inclusion criteria: verbal IQ > 70 in Wechsler scales; absence of significant ocular involvement). For each participant, we collected data on neuropsychological assessment (i.e., cognitive, cognitive visual, and learning abilities), basic visual functions (e.g., Best Corrected Visual Acuity­BCVA, contrast sensitivity, and ocular motor abilities) and global development features (e.g., neurological signs and motor development delay) based on standardized tests, according to patients' ages. The results showed that oculomotor dysfunction involving saccades and smooth pursuit may be a core symptom of CVI and might have a significant impact on cognitive visual and other neuropsychological abilities. Furthermore, visual acuity and contrast sensitivity may influence cognitive, cognitive visual, and academic performances. Our findings suggest the importance of a comprehensive assessment of both visual and neuropsychological functions in children when CVI is suspected, which is needed to provide a more comprehensive functional profile and define the best habilitation strategy to sustain functional vision.