An individual-supported program to enhance placement in a sheltered work environment of autistic individuals mostly with intellectual disability: a prospective observational case series in an Italian community service.

Introduction: Autism spectrum disorder is a lifelong neurodevelopmental disorder. The profile of functioning in autistic people is very heterogeneous, and it is necessary to take into account individual characteristics to better support integration in the workplace. However, unemployment rates are higher for autistic people than for other types of disabilities. We present a prospective case series to explore the feasibility and efficacy of an individual-supported program to enhance placement in a sheltered work environment delivered by an Italian community day care center. Methods: Autistic subjects, aged from 12 to 31 years, participated in an individual-supported program regarding employment in sheltered art workshops, integrated into the regular activity of a semi-residential center three times a week for 1 year. Their feasibility retention rate and time worked per session were registered; moreover, working methods efficacy and self-organization improvement were tracked by the Likert-based rating system. Secondary outcome measures span functional levels, challenge behaviors, and sensory problems. Results: All the individuals presented a good adaptation to the environment, with a significant increase in time worked per session. After 1 year, the intervention allowed an increase in tasks completed in an assigned complex job and an improvement in self-organization within the work schedule in a group of subjects consisting mainly of severe-to-moderate levels of autism severity (86.6%). Finally, we observed a significant increase in independent functioning areas of the TEACCH transitional assessment profile. Challenge behaviors and sensory problems were also recorded. Conclusion: This case series supports the idea that individual-supported programs for placement in sheltered job environments delivered by community day care centers could be feasible and effective for ASD with higher levels of severity and co-occurring intellectual disability. Further targeted studies based on community models and accessible methods need to be planned to define the effectiveness of the intervention and promote improved practice at the community level with a better social impact.

Feasibility and Effectiveness of Speech Intervention Implemented with a Virtual Reality System in Children with Developmental Language Disorders: A Pilot Randomized Control Trial.

Language disorders are characterized by impairments in verbal expression/understanding, including difficulties with one or more language components. The Virtual Reality Rehabilitation System (VRRS) is a bioelectromedical device equipped with exercise sections aimed at improving cognitive and language deficits. It also increases patient motivation and engagement. The aim of our study was to test the feasibility and efficacy of VRRS intervention to improve speech therapy treatment for children with speech disorders. Thirty-two patients were enrolled in this study and randomly assigned to the experimental (EG) or control group (CG). The CG underwent conventional speech therapy, while EG underwent VRRS-implemented speech therapy. Both groups were evaluated before (T0) and after (T1) the intervention using the Language Assessment Test. The results showed improvements in both groups. However, the EG group showed greater improvement in various areas, including comprehension of total words, repetition, naming of body parts, naming of everyday objects, total naming, morphosyntactic accuracy, sentence construction, average length of utterance, and spontaneous word production. This study demonstrated that VRRS can be a valuable tool for implementing effective speech rehabilitation. Further studies are needed, as the use of VRRS is still in its early stages, requiring larger samples sizes and long-term follow-up.

Virtual Reality Technology to Enhance Conventional Rehabilitation Program: Results of a Single-Blind, Randomized, Controlled Pilot Study in Patients with Global Developmental Delay.

Global developmental delay (GDD) is a complex disorder that requires multimodal treatment involving different developmental skills. The objective of this single-blind, randomized, controlled pilot study is to evaluate the feasibility and effectiveness of conventional rehabilitation programs integrated with the BTs-Nirvana virtual reality system. Patients with GDD aged 12 to 66 months were enrolled and treated for a 48-session cycle. Patients were randomized into two groups, (1) conventional treatment and (2) conventional treatment supplemented with the use of BTs-Nirvana, in a 1:1 ratio. Before and after treatments, areas of global development were tested with the Griffiths-III Mental Developmental Scale and the clinical indicator of global improvement were measured with the Clinical Global Impressions-Improvement (CGI-I). Feasibility was confirmed by the high retention rate. The experimental group presented a significantly improvement in General Quotient (GQ) after treatment (GQ, p = 0.02), and the effect of the two treatments was significantly different in both the GQ (t =2.44; p = 0.02) and the Foundations of Learning subscale (t =3.66; p < 0.01). The overall improvement was also confirmed by the CGI-I (p = 0.03). According to these preliminary data, virtual reality can be considered a useful complementary tool to boost the effectiveness of conventional therapy in children with GDD.

Early and Innovative Rehabilitation in Warkany Syndrome 2 Associated with Agenesis of the Corpus Callosum: A Case Report.

Trisomy 8 mosaicism syndrome (T8MS) or "Warkany's syndrome 2" is a rare chromosomal disorder characterized by three copies of chromosome 8 in some cells of the body. T8MS incidence in the world population is about 1/25,000-50,000 live births with a 5:1 ratio between males and females. Since chromosomal mosaicism is often present in this syndrome, affected subjects present a phenotype varying from mild dysmorphism to severe structural anomalies. Malformations, including corpus callosum agenesis and renal abnormalities, have been described by many studies. We present a case in a girl 36 months in age, born to assisted fertilization (FIVET) and prenatal diagnosis by amniocentesis. In a fetus in the 22 week of gestation, she presented trisomy 8 mosaicism with ventriculomegaly, agenesis of the corpus callosum and a sequence of polymalformations. Through the early identification of symptoms that gradually occurred during development, the girl was submitted, early, to innovative complex instrumental using virtual reality (VR) rehabilitation. This study involves continuous monitoring and early management of symptoms, with the aim of improving the neurobehavioral outcomes of children with this rare disease by inducing structural neuroplastic responses and significantly reducing the impact that this disorder has on the development of children born without corpus callosum.

One-Year Follow-Up Diagnostic Stability of Autism Spectrum Disorder Diagnosis in a Clinical Sample of Children and Toddlers.

Some studies show that the diagnosis of Autism Spectrum Disorder could be considered reliable and stable in children aged 18 to 24 months. Nevertheless, the diagnostic stability of early ASD diagnosis has not yet been fully demonstrated. This observational study examines the one-year diagnostic stability of autism spectrum disorder diagnosis in a clinical sample of 147 children diagnosed between 18 and 48 months of age. The ADOS-2 scores were used in order to stratify children in three levels of symptom severity: Autism (AD; comparison score 5-7), Autism Spectrum Disorder (ASD; comparison score 3-4), and Sub-Threshold Symptoms; (STS; comparison score 1-2). Results: Overall, the largest part of children and toddlers diagnosed with autism spectrum disorder between 18 and 48 months continued to show autistic symptoms at one-year follow-up evaluation. Nevertheless, a significant percentage of children with higher ADOS severity scores exhibited a reduction of symptom severity and, therefore, moved towards a milder severity class one year later. Conversely, the number of subjects of the STS group meaningfully increased. Therefore, at one-year follow-up a statistically significant (χ2(2) = 181.46, p < 0.0001) percentage of subjects (25.2% of the total) who had received a categorical diagnosis of Autistic Disorder or Autism Spectrum Disorder in baseline no longer met the criteria for a categorical diagnosis. Furthermore, children who no longer met the criteria for autism spectrum disorder continue to show delays in one or more neurodevelopmental areas, possibly related to the emergence of other neurodevelopmental/neuropsychiatric disorders. Overall, the comprehensive results of the study account for a high sensibility but a moderate stability of ASD early diagnosis.

Recurrent rearrangements in synaptic and neurodevelopmental genes and shared biologic pathways in schizophrenia, autism, and mental retardation.

CONTEXT: Results of comparative genomic hybridization studies have suggested that rare copy number variations (CNVs) at numerous loci are involved in the cause of mental retardation, autism spectrum disorders, and schizophrenia. OBJECTIVES: To provide an estimate of the collective frequency of a set of recurrent or overlapping CNVs in 3 different groups of cases compared with healthy control subjects and to assess whether each CNV is present in more than 1 clinical category. DESIGN: Case-control study. SETTING: Academic research. PARTICIPANTS: We investigated 28 candidate loci previously identified by comparative genomic hybridization studies for gene dosage alteration in 247 cases with mental retardation, in 260 cases with autism spectrum disorders, in 236 cases with schizophrenia or schizoaffective disorder, and in 236 controls. MAIN OUTCOME MEASURES: Collective and individual frequencies of the analyzed CNVs in cases compared with controls. RESULTS: Recurrent or overlapping CNVs were found in cases at 39.3% of the selected loci. The collective frequency of CNVs at these loci is significantly increased in cases with autism, in cases with schizophrenia, and in cases with mental retardation compared with controls (P < .001, P = .01, and P = .001, respectively, Fisher exact test). Individual significance (P = .02 without correction for multiple testing) was reached for the association between autism and a 350-kilobase deletion located at 22q11 and spanning the PRODH and DGCR6 genes. CONCLUSIONS: Weakly to moderately recurrent CNVs (transmitted or occurring de novo) seem to be causative or contributory factors for these diseases. Most of these CNVs (which contain genes involved in neurotransmission or in synapse formation and maintenance) are present in the 3 pathologic conditions (schizophrenia, autism, and mental retardation), supporting the existence of shared biologic pathways in these neurodevelopmental disorders.

Risperidone treatment of children with autistic disorder: effectiveness, tolerability, and pharmacokinetic implications.

BACKGROUND: Recent evidence indicates that atypical antipsychotics represent a promising option for the treatment of autistic disorder. In particular, risperidone appears to be effective in treating aggressiveness, hyperactivity, irritability, stereotypies, social withdrawal, and lack of interests. OBJECTIVE: The aim of the present study was to evaluate the effectiveness and tolerability of risperidone in children with autistic disorder and to examine the correlation between plasma levels of risperidone and its active metabolite 9-hydroxyrisperidone (9-OH-risperidone) and the clinical response. METHODS: The effect of treatment with risperidone (0.75-2 mg/day; mean +/- SD dose = 1.26 +/- 0.42 mg/day) was studied for 24 weeks in 20 children (14 boys, 6 girls) ages 3 to 10 years (mean age 6.0 +/- 2.4 years), diagnosed with autistic disorder. Fourteen items selected from the Children's Psychiatric Rating Scale (CPRS-14) and Clinical Global Impression (CGI) were used for behavioral evaluation. Patients were classified as responders if they showed a 25% or greater decrease on CPRS-14 total score at final evaluation compared with baseline and a final CGI rating of 1 or 2. Patients were rated for extrapyramidal side effects on the Abnormal Involuntary Movement Scale (AIMS). Other side effects, including the expected side effects of atypical antipsychotics drugs, were assessed by a checklist. Blood samples for determination of risperidone and its active metabolite 9-OH-risperidone were obtained after 12 weeks, and serum prolactin levels were measured on admission and at weeks 12 and 24. RESULTS: The psychopathological state, as assessed by CPRS, improved significantly over the duration of treatment. The mean CPRS-14 scores decreased significantly from 63.7 +/- 10.0 at baseline to 52.9 +/- 14.3 at week 12 (p < 0.01). At the end of 12 weeks of treatment, 8 patients were considered responders, and 10 patients reached a minimal improvement. No further improvement was observed in the following 12 weeks. In all children, serum prolactin levels increased significantly (p < 0.001) from 166 +/- 88 UI/mL at baseline to 504 +/- 207 UI/mL at week 12 of risperidone treatment. Weight gain and increased appetite were the most common unwanted effects. A mean increase of 3.7 +/- 1.7 kg in body weight was observed at final evaluation as compared with baseline. There was no significant correlation between percent improvement in total CPRS score and the plasma level of risperidone's active fractions (the sum of the risperidone and 9-OH-risperidone plasma concentration). CONCLUSIONS: This study provides further evidence of the beneficial effects of risperidone in children diagnosed with autistic disorder. However, the potential advantages of risperidone should be weighed against the risk of unwanted effects, such as an increase in serum prolactin levels and weight gain. No relation was observed between total plasma risperidone and 9-OH-risperidone concentrations and clinical response.