Investigating Visual Perception Impairments through Serious Games and Eye Tracking to Anticipate Handwriting Difficulties.

Dysgraphia is a learning disability that causes handwritten production below expectations. Its diagnosis is delayed until the completion of handwriting development. To allow a preventive training program, abilities not directly related to handwriting should be evaluated, and one of them is visual perception. To investigate the role of visual perception in handwriting skills, we gamified standard clinical visual perception tests to be played while wearing an eye tracker at three difficulty levels. Then, we identified children at risk of dysgraphia through the means of a handwriting speed test. Five machine learning models were constructed to predict if the child was at risk, using the CatBoost algorithm with Nested Cross-Validation, with combinations of game performance, eye-tracking, and drawing data as predictors. A total of 53 children participated in the study. The machine learning models obtained good results, particularly with game performances as predictors (F1 score: 0.77 train, 0.71 test). SHAP explainer was used to identify the most impactful features. The game reached an excellent usability score (89.4 ± 9.6). These results are promising to suggest a new tool for dysgraphia early screening based on visual perception skills.

Investigating the effects of COVID-19 lockdown on Italian children and adolescents with and without neurodevelopmental disorders: a cross-sectional study.

We conducted a cross-sectional study to compare the impact of social distancing and lifestyle changes that occurred during Corona Virus Disease 2019 (COVID-19) lockdown on children and adolescents with and without Neurodevelopmental Disorders (NDDs). An online questionnaire was administered in order to investigate the effects of NDD condition, socio-demographic status, familiar/home environment and COVID-19 exposure on their lives during a two months period of social isolation. We used logistic regression, focusing on five endpoints (remote learning, lifestyle, stress/anxiety, sociality, scolding) to define the extent of these effects. Most questions were paired up to parents and children, to verify the occurrence of agreement. 8305 questionnaires were analyzed, 1362 of which completed by NDDs and 6943 by controls. Results showed that the presence of a NDD, compared to controls, had a significant impact on: Remote Learning (i.e. subjects with NDDs experienced more difficulties in attending online classes and studying), Sociality (i.e. subjects with NDDs missed their schoolmates less), Scolding (i.e. subjects with NDDs were scolded more often) and Anxiety (i.e. subjects with NDDs were perceived by their parents as more anxious). Substantial agreement between parents and children arose from questions concerning Remote learning, Lifestyle and Scolding. The current study actually points out that having a NDD gives account for a stronger influence on school performance and on behavioral and psychological aspects, during a two months lockdown. Such results may provide useful information to governments and school authorities on how carrying through supportive strategies for youth affected by NDDs. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-021-02321-2.

Self-reported impact of the COVID-19 pandemic and lockdown on young patients with tic disorders: findings from a case-control study.

BACKGROUND: Little is known about the perceived impact of the COVID-19 pandemic and subsequent lockdown measures on young patients with tic disorders. Previous studies focused on clinician and parent ratings of tic severity, whereas the only international self-report data are available for adult populations. We present the first findings from a case-control study on children and adolescents with tics during lockdown in Italy. METHODS: We surveyed 49 patients aged 6-18 years and 245 matched controls with a newly developed questionnaire covering socio-demographic and clinical data, as well as lockdown-related changes to daily life activities. RESULTS: About half (53.2%) of the Italian school-age patients who took part in our survey experienced changes in tic severity during lockdown. Perceived increases in tic severity (29.8%) were reported more often than decreases (23.4%). Analogous trends were reported for perceived restlessness and, more significantly, irritability, whereas changes in pain symptoms were less common and were similar in both directions. The presence of tics was associated with increased difficulties with remote learning (p = 0.01), but decreased feelings of missing out on social interactions with schoolmates (p = 0.03). CONCLUSIONS: Self-reported data on the impact of COVID-19 lockdown in school-age patients with tic disorders indicate perceived changes in tic severity, as well as restlessness and irritability, in about half of the cases. These findings could guide both clinicians and teachers in the implementation of targeted adjustments in the delivery of care and educational strategies, respectively.

European clinical guidelines for Tourette syndrome and other tic disorders-version 2.0. Part III: pharmacological treatment.

In 2011, the European Society for the Study of Tourette Syndrome (ESSTS) published the first European guidelines for Tourette Syndrome (TS). We now present an update of the part on pharmacological treatment, based on a review of new literature with special attention to other evidence-based guidelines, meta-analyses, and randomized double-blinded studies. Moreover, our revision took into consideration results of a recent survey on treatment preferences conducted among ESSTS experts. The first preference should be given to psychoeducation and to behavioral approaches, as it strengthens the patients' self-regulatory control and thus his/her autonomy. Because behavioral approaches are not effective, available, or feasible in all patients, in a substantial number of patients pharmacological treatment is indicated, alone or in combination with behavioral therapy. The largest amount of evidence supports the use of dopamine blocking agents, preferably aripiprazole because of a more favorable profile of adverse events than first- and second-generation antipsychotics. Other agents that can be considered include tiapride, risperidone, and especially in case of co-existing attention deficit hyperactivity disorder (ADHD), clonidine and guanfacine. This view is supported by the results of our survey on medication preference among members of ESSTS, in which aripiprazole was indicated as the drug of first choice both in children and adults. In treatment resistant cases, treatment with agents with either a limited evidence base or risk of extrapyramidal adverse effects might be considered, including pimozide, haloperidol, topiramate, cannabis-based agents, and botulinum toxin injections. Overall, treatment of TS should be individualized, and decisions based on the patient's needs and preferences, presence of co-existing conditions, latest scientific findings as well as on the physician's preferences, experience, and local regulatory requirements.

Possible tics diagnosed as stereotypies in patients with severe autism spectrum disorder: a video-based evaluation.

BACKGROUND: The association of stereotypies and tics is not rare in children with severe autism spectrum disorder (ASD). The differential diagnosis between stereotypies and tics in this patient population can be difficult; however, it could be clinically relevant because of treatment implications. METHODS: A total of 108 video recordings of repetitive behaviors in young patients with stereotypies in the context of ASD were reviewed by a movement disorders expert and a trainee, in order to assess the prevalence of possible co-morbid tics. The Modified Rush Videotape Rating Scale (MRVS) was used to rate tic frequency and severity. RESULTS: Out of 27 patients with stereotypies (24 males; mean age 14 years), 18 (67%) reported possible tics. The most frequently observed tics were eye blinking, shoulder shrugging, neck bending, staring, and throat clearing. The mean MRVS score was 5, indicating mild tic severity. The only significant difference between patients with tics and patients without tics was the total number of stereotypies, which was higher in the subgroup of patients without tics (p = 0.01). CONCLUSIONS: Expert review of video-recordings of repetitive behaviors in young patients with ASD and stereotypies suggests the possibility of a relatively high rate of co-morbid tics. These findings need to be integrated with a comprehensive clinical assessment focusing on the diagnostic re-evaluation of heterogeneous motor manifestations.

I stay at home with headache. A survey to investigate how the lockdown for COVID-19 impacted on headache in Italian children.

OBJECTIVE: The present Italian multicenter study aimed at investigating whether the course of primary headache disorders in children and adolescents was changed during the lockdown necessary to contain the COVID-19 emergency in Italy. METHODS: During the lockdown, we submitted an online questionnaire to patients already diagnosed with primary headache disorders. Questions explored the course of headache, daily habits, psychological factors related to COVID-19, general mood and school stress. Answers were transformed into data for statistical analysis. Through a bivariate analysis, the main variables affecting the subjective trend of headache, and intensity and frequency of the attacks were selected. The significant variables were then used for the multivariate analysis. RESULTS: We collected the answers of 707 patients. In the multivariate analysis, we found that reduction of school effort and anxiety was the main factor explaining the improvement in the subjective trend of headache and the intensity and frequency of the attacks (p < 0.001). The greater the severity of headache, the larger was the clinical improvement (p < 0.001). Disease duration was negatively associated with the improvement (p < 0.001). It is noteworthy that clinical improvement was independent of prophylaxis (p > 0.05), presence of chronic headache disorders (p > 0.05) and geographical area (p > 0.05). CONCLUSIONS: Our study showed that lifestyle modification represents the main factor impacting the course of primary headache disorders in children and adolescents. In particular, reduction in school-related stress during the lockdown was the main factor explaining the general headache improvement in our population.

Comorbidity prevalence and treatment outcome in children and adolescents with ADHD.

Although ADHD comorbidity has been widely studied, some issues remain unsolved. This multicenter observational study aims to examine comorbid psychiatric disorders in a clinical sample of newly diagnosed, treatment naïve children and adolescents with and without ADHD and, to compare treatment efficacy based on the type of comorbidity. We performed an analysis of the medical records of patients identified from the Regional ADHD Registry database, enrolled in 18 ADHD centers in the 2011-2016 period. 1919 of 2861 subjects evaluated (67%) met the diagnostic criteria for ADHD: 650 (34%) had only ADHD, while 1269 (66%) had at least one comorbid psychiatric disorder (learning disorders, 56%; sleep disorders, 23%; oppositional defiant disorder, 20%; anxiety disorders, 12%). Patients with ADHD of combined type and with severe impairment (CGI-S ≥5) were more likely to present comorbidity. 382 of 724 (53%) followed up patients improved after 1 year of treatment. ADHD with comorbidity showed greater improvement when treated with combined interventions or methylphenidate alone. Specifically, combined treatment showed significant superiority for ADHD with learning disorders (ES 0.66) and ODD (ES 0.98), lower for ADHD with sleep or anxiety disorders. Training intervention alone showed only medium efficacy (ES 0.50) for ADHD and learning disorders. This study was the first describing comorbidity patterns of ADHD in Italy, confirming, in a multicenter clinical setting, that ADHD is more often a complex disorder. Findings highlight important diagnostic, therapeutic, and service organization aspects that should be broadly extended to ensure an appropriate and homogenous ADHD management.

Headache and psychological disorders in children and adolescents: a cross-generational study.

BACKGROUND: Headache and psychopathology (especially anxiety and mood disorders) are comorbid across the life span. The present study is a clinical contribution in the direction of studying the familial recurrence of headache, and the interplay of headache and psychopathology in children. METHODS: The clinical sample is composed by 130 headache patients (53 boys and 77 girls, age range 8-18), while the control group is composed by 87 healthy subjects from the general population (39 boys and 48 girls, age range 8-18). A structured interview according to International Classification for Headache Disorders-II criteria has been administered to the clinical group; the Child Behavior Checklist (CBCL) and the Self Administrated Psychiatric Scales for Children and Adolescents (SAFA) have been used in order to assess psychopathology in both groups. RESULTS: The recurrence of headache in family members is confirmed by the present study, albeit limited to paternal side, χ2 (4, N.=130)=10.47, P=0.033. Results also showed that scores obtained by the clinical sample in CBCL and SAFA are generally higher than scores obtained by the control group, but without differences between headache sub-types. Finally, internalizing symptoms (anxiety and depression) in children correlate with mothers' point of view, r≥0.23, P<0.05, outlining a specific attunement between headache patients and their mothers. CONCLUSIONS: Headache runs in families, with high level of psychological disorders. Mothers are particularly attuned with the psychological needs of their headache children.

Psychological Therapy in Adolescents with Chronic Daily Headache.

Chronic daily headache is a serious disease, causing significant problems in terms of reduced quality of life and disability, with pain localized to the head (headache) occurring 15 or more days per month for more than 3 months (>180 days per year). Drugs, both used as preventive medications or as pain-killers, are insufficient for the management of these patients; a more global approach has been advocated. This paper reviews existing data concerning different psychological approaches, with a focus on adolescence. This leads to evidence still unanswered questions but also the importance to include psychological treatments in the management of this potentially disabling condition.

Molecular mechanisms generating and stabilizing terminal 22q13 deletions in 44 subjects with Phelan/McDermid syndrome.

In this study, we used deletions at 22q13, which represent a substantial source of human pathology (Phelan/McDermid syndrome), as a model for investigating the molecular mechanisms of terminal deletions that are currently poorly understood. We characterized at the molecular level the genomic rearrangement in 44 unrelated patients with 22q13 monosomy resulting from simple terminal deletions (72%), ring chromosomes (14%), and unbalanced translocations (7%). We also discovered interstitial deletions between 17-74 kb in 9% of the patients. Haploinsufficiency of the SHANK3 gene, confirmed in all rearrangements, is very likely the cause of the major neurological features associated with PMS. SHANK3 mutations can also result in language and/or social interaction disabilities. We determined the breakpoint junctions in 29 cases, providing a realistic snapshot of the variety of mechanisms driving non-recurrent deletion and repair at chromosome ends. De novo telomere synthesis and telomere capture are used to repair terminal deletions; non-homologous end-joining or microhomology-mediated break-induced replication is probably involved in ring 22 formation and translocations; non-homologous end-joining and fork stalling and template switching prevail in cases with interstitial 22q13.3. For the first time, we also demonstrated that distinct stabilizing events of the same terminal deletion can occur in different early embryonic cells, proving that terminal deletions can be repaired by multistep healing events and supporting the recent hypothesis that rare pathogenic germline rearrangements may have mitotic origin. Finally, the progressive clinical deterioration observed throughout the longitudinal medical history of three subjects over forty years supports the hypothesis of a role for SHANK3 haploinsufficiency in neurological deterioration, in addition to its involvement in the neurobehavioral phenotype of PMS.

Psychopathological symptoms in child and adolescent migraine and tension-type headache: a meta-analysis.

INTRODUCTION: After decades of research, the importance of psychological factors in child and adolescent headache is no longer in doubt. However, it is not clearly understood whether different types of headache are comorbid with specific kinds of psychopathology. To address this issue, we set out to establish whether young patients with migraine do or do not show significant levels of psychopathological symptoms compared with age-matched healthy controls and patients with tension-type headache (TTH). METHODS: Ten studies were selected on the basis of a widely used psychodiagnostic tool (the Child Behavior Checklist (CBCL)) and by applying rigorous criteria: The studies were compared in a meta-analysis in order to evaluate the presence of Internalizing (mainly anxiety and depression) and Externalizing (mainly behavioral problems) symptoms in different types of headache (and versus healthy controls). FINDINGS: Patients with migraine showed more psychopathological symptoms than healthy controls. TTH patients also had more psychopathology than controls, although the difference was more marked in the area of Internalizing disorders. Finally, no differences emerged between migraine and TTH. DISCUSSION AND CONCLUSION: Psychopathological symptoms affect children with migraine, but also children with TTH. Biological, pathophysiological and clinical links need to be established. Effective treatment of affected children and adolescents is imperative in order to prevent chronic evolution. In this context, the CBCL may be a good screening instrument with a view to developing a tailored clinical approach.

Headache and comorbidity in children and adolescents.

Headache is one of the most common neurological symptom reported in childhood and adolescence, leading to high levels of school absences and being associated with several comorbid conditions, particularly in neurological, psychiatric and cardiovascular systems. Neurological and psychiatric disorders, that are associated with migraine, are mainly depression, anxiety disorders, epilepsy and sleep disorders, ADHD and Tourette syndrome. It also has been shown an association with atopic disease and cardiovascular disease, especially ischemic stroke and patent foramen ovale (PFO).

A Neuropsychological Profile of Developmental Dyscalculia: The Role of Comorbidity.

Developmental dyscalculia (DD) has long been thought to be determined by multiple components. Dyscalculia has high comorbidity with other learning and developmental disabilities, including reading and writing disorders, attention deficits, and problems in visual/spatial skills, short memory, and working memory. This study aims to assess prevalence rates for isolated as well as comorbid DD in a sample of Italian-speaking children. In addition, we studied the neuropsychological profile of children with isolated or combined dyscalculia. We tested 380 children (176 males and 204 females) between the ages of 8.17 and 9.33 years using an extensive battery to determine the neuropsychological profile. The assessment included an arithmetic battery and nonverbal intelligence, short-term memory, reading, and writing tests. The results indicated that children with DD more frequently have a reading disorder and writing disorder. They also have a lower nonverbal intelligence quotient (IQ) and obtain significantly lower scores in short-term memory tests and on a visuospatial skills questionnaire. They also had significantly higher scores (indicative of greater attentional difficulties) on the Conners subscale for attentional problems. Children with DD present different cognitive and neuropsychological profiles.

Autism in Preschool-Aged Children: The Effects of COVID-19 Lockdown.

The COVID-19 lockdown affected children, especially those with autism spectrum disorder, due to the disruption in rehabilitation and educational activities. We conducted a cross-sectional study of 315 preschool-aged children, 35 of which had autism, to investigate this impact. A questionnaire was administered to explore socio-demographic status, familiar/home environment, and COVID-19 exposure. The clinical features of autistic subjects were also examined. Seven variables were considered to describe the effect of pandemic: Remote learning, Behavior changes, Home activities, Sleep habits, Night awakenings, Physical activity, Information about the virus. The lockdown had a significant impact on Remote learning, Behavior changes, and Information about the virus in participants with autism. Moreover, we found a worsening in repetitive movements, echolalia, restricted interests, and aggressive behaviors.

Cognitive Profile Discrepancies among Typical University Students and Those with Dyslexia and Mixed-Type Learning Disorder.

BACKGROUND: Previous studies have identified areas of cognitive weakness in children diagnosed with Specific Learning Disorder (SLD), in the areas of working memory and processing speed in particular. In adulthood, this literature is still scant, and no studies have compared the cognitive profile of university students with dyslexia (DD) with that of students with Mixed-type SLD. METHOD: Thus, in this study, the WAIS-IV was used to examine the cognitive functioning of three groups of university students: students with DD, with Mixed-type SLD, and typical students. Statistical analyses were performed to examine differences in WAIS-IV FSIQ, main, and additional indexes and subtests. RESULTS: The results showed strengths in perceptual reasoning and good verbal comprehension abilities in both the DD and Mixed-type SLD group, with weaknesses in working memory and processing speed, leading to a pattern of a better General Ability Index (GAI) than Cognitive Proficiency Index (CPI) in both clinical groups. Thus, discrepancies between GAI and CPI, well documented in children with SLD, still manifest in adulthood in university students. Our findings also revealed worse cognitive performance in university students with mixed learning disorder relative to students with only a reading deficit. CONCLUSIONS: The cognitive features and distinctive subtest profiles that emerged should guide the assessment and the definitions of intervention programs, special educational needs, and strategies of compensation.

Osmophobia as an early marker of migraine: a follow-up study in juvenile patients.

BACKGROUND: Osmophobia is frequent in children with migraine (20-35%) but can also occur in up to 14% of cases with tension-type headache (TTH). So far, the prognostic role of this symptom in children with primary headaches has never been evaluated. METHODS: A longitudinal prospective study was conducted on 90 young patients with TTH (37 with osmophobia, 53 without osmophobia). We evaluated whether osmophobia could predict the diagnosis transformation from TTH to migraine after a 3-year follow-up. RESULTS AND DISCUSSION: In our cases the rate of diagnosis change was significantly greater in cases with osmophobia (62%) than in those without (23%). Osmophobia persisted at a 3-year follow-up in the majority of our cases (85%) and it was found to be one of the major predictors for the development of migraine; other predictors of evolution to migraine were phonophobia, a probable rather than certain diagnosis of TTH and olfactory triggers (p < 0.05). CONCLUSION: Our data confirm that osmophobia has an important diagnostic and prognostic role in children with primary headaches and should be systematically investigated at diagnosis and during follow-up.

Chorea mollis: long-term follow-up of an infantile case.

We describe the long-term follow-up of a patient affected by chorea mollis, a rare variant of Sydenham's chorea of which there are very few reports in the literature. Our patient, a previously healthy 8-year-old boy developed progressive clumsiness, gait disturbance, generalised hypotonia and muscle weakness, choreic movements of the limbs and behavioural disturbances. Following the diagnosis of chorea mollis, the patient received prophylaxis (monthly injections of benzathine benzyl penicillin). Within a few weeks, his clinical conditions worsened and he became bedridden and incapable of standing and walking without assistance. The choreic movements were successfully treated with sodium valproate. Independent walking was achieved 14 months after the onset of the disease. At a 4-year follow-up, the patient showed a full neurological and psychiatric recovery. The clinical course observed in our patient shows that chorea mollis may not only have a dramatic course, but also have a good long-term prognosis.

Tourette syndrome.

Tourette syndrome (TS) is a neurodevelopmental disorder consisting of multiple motor and one or more vocal/phonic tics. TS is increasingly recognized as a common neuropsychiatric disorder usually diagnosed in early childhood and comorbid neuropsychiatric disorders occur in approximately 90% of patients, with attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) being the most common ones. Moreover, a high prevalence of depression and personality disorders has been reported. Although the mainstream of tic management is represented by pharmacotherapy, different kinds of psychotherapy, along with neurosurgical interventions (especially deep brain stimulation, DBS) play a major role in the treatment of TS. The current diagnostic systems have dictated that TS is a unitary condition. However, recent studies have demonstrated that there may be more than one TS phenotype. In conclusion, it appears that TS probably should no longer be considered merely a motor disorder and, most importantly, that TS is no longer a unitary condition, as it was previously thought.

Identification and characterization of learning weakness from drawing analysis at the pre-literacy stage.

Handwriting learning delays should be addressed early to prevent their exacerbation and long-lasting consequences on whole children's lives. Ideally, proper training should start even before learning how to write. This work presents a novel method to disclose potential handwriting problems, from a pre-literacy stage, based on drawings instead of words production analysis. Two hundred forty-one kindergartners drew on a tablet, and we computed features known to be distinctive of poor handwriting from symbols drawings. We verified that abnormal features patterns reflected abnormal drawings, and found correspondence in experts' evaluation of the potential risk of developing a learning delay in the graphical sphere. A machine learning model was able to discriminate with 0.75 sensitivity and 0.76 specificity children at risk. Finally, we explained why children were considered at risk by the algorithms to inform teachers on the specific weaknesses that need training. Thanks to this system, early intervention to train specific learning delays will be finally possible.

Visuo-spatial attention deficit in children with reading difficulties.

Although developmental reading disorders (developmental dyslexia) have been mainly associated with auditory-phonological deficits, recent longitudinal and training studies have shown a possible causal role of visuo-attentional skills in reading acquisition. Indeed, visuo-attentional mechanisms could be involved in the orthographic processing of the letter string and the graphemic parsing that precede the grapheme-to-phoneme mapping. Here, we used a simple paper-and-pencil task composed of three labyrinths to measure visuo-spatial attention in a large sample of primary school children (n = 398). In comparison to visual search tasks requiring visual working memory, our labyrinth task mainly measures distributed and focused visuo-spatial attention, also controlling for sensorimotor learning. Compared to typical readers (n = 340), children with reading difficulties (n = 58) showed clear visuo-spatial attention impairments that appear not linked to motor coordination and procedural learning skills implicated in this paper and pencil task. Since visual attention is dysfunctional in about 40% of the children with reading difficulties, an efficient reading remediation program should integrate both auditory-phonological and visuo-attentional interventions.