Contributi a congressi internazionali

Notes:

1 - Villa Santa Maria Foundation, Tavernerio, Italy
2 - University of Milano Bicocca, Milano, Italy
3 - Politecnico di Milano, Italy
4 - IRCCS Eugenio Medea, Bosisio Parini (Lecco), Italy
5 - University of Connecticut, Storrs, USA

Notes:

1 - Villa Santa Maria Foundation, Tavernerio (Como)
2 - IRCCS San Gerardo dei Tintori, Monza
3 - University of Padua

Background:
Tip-toe behavior (TTB) is showed by about 20% of individuals with ASD and is poorly quantified with structured methods. In a previous study, we proposed a standardized method to quantify TTB during static and dynamic tasks using a video-recording approach in an ecological setting. This testing approach is very time-consuming and operator dependent requiring an operator to review the videos and computing the parameters. To overcome these limitations, an instrumental approach using wearable sensors (WS) and an automated calculation system was developed and applied. Moreover, WS approach would also permit monitoring gait for a longer time during the day.

Objectives:
This study aims at implementing a WS-based protocol for the quantitative assessment of TTB and its validation by the comparison with the reference video-recording approach.

Methods:
Individuals with ASD diagnosed according to DSM-5 criteria and a diagnosis confirmation using the Autism Diagnostic Observation Schedule (ADOS) were involved in the study. TTB was quantified during structured static and dynamic tasks using a video-recording approach, previously described. All the tests were performed without shoes albeit with "Sensoria® Smart Socks". The dynamic test consists in transporting 1 object (e.g. puzzle piece, Lego®) from the therapist to the playing table situated 2 meters away and back again 15 times. The static test consists in playing while standing in front of a table for 3 minutes. Both assessments were repeated on three different days for each individual (9 assessments).
"Sensoria® Smart Socks" (SSS) are the validated WS used during the video-recorded tests. In this way, we were able to collect data obtained from video-recording and WS approaches at the same time. The result of the video-recording and WS approaches were analyzed. The intraclass correlation coefficient (IC) was used to assess the reliability between the video-recording and WS approaches in quantifying the mean percentage of toe steps and the mean percentage of the time spent in ???.

Results:
We assessed 3 individuals with ASD and TTB. The age was 10.9yrs, 12.8yrs and 13yrs (3/3 males) and their ADOS calibrated severity score was 9, 10 and 8, respectively. The normal distribution of data was confirmed (Shapiro-Wilk test p>
0.05). The ICC values of the mean percentage of toe steps and the mean percentage of the time spent in TB were 0.778 (excellent) and 0.731 (good), respectively.

Conclusions:
The "Sensoria® Smart Socks" used for the quantitative assessment of TB in individuals with ASD showed good-to-excellent reliability in comparison with the reference video-recording approach both during a static and dynamic tests.
Further research is required to confirm the results of this preliminary study.

Notes:

1 - Villa Santa Maria Foundation Autism Research Unit, Tavernerio (Como), Italy
2 - Politecnico di Milano, Italy

Background: 
Toe walking is a clinical motor sign present in 20% of individuals with autism spectrum disorder (ASD). Because this behavior is also found during standing or running, the term tip-toe behavior (TTB) seems to be more appropriate. A systematic review found a lacking of studies that quantify TB in individuals with ASD. The most used and reliable instrumental tool to quantify motor deficit during standing and walking is the gait analysis, but this approach requests the positioning of a large number of markers on the skin of the patient, a long time to prepare the patient for the execution of the test and is conducted in a non-ecological setting. For all these reasons gait analysis could be difficult to use with individuals with severe ASD because of their clinical condition. Thus, a simpler instrumental approach that uses wearable sensors usable in an ecological setting could be a useful resource to quantify TTB in individuals with severe ASD. 

Objectives: 
The aims of this pilot study are: 1) to verify the feasibility and acceptability of wearable sensors in individuals with severe ASD; 2) to quantify TB using wearable sensors during structured standing and walking tasks. 

Methods: 
Subjects with ASD diagnosed according to DSM-5 criteria and confirmed using the Autism Diagnostic Observation Schedule were admitted to the study. TB was quantified using "Sensoria® Smart Socks" (SSS), a commercially available wireless gait monitoring technology (Figure 1). SSS was found a valid measure instrument in a previous study. To assess the TTB quantity during standing and walking we used a static and dynamic test following the methodology proposed in a previous study. The static test consisted in playing while standing in front of a table for 3 minutes. The dynamic test consisted in transporting 1 object (puzzle, Lego®, ...) from the therapist to the playing table situated 2 meters away and back again 15 times. The test is conducted without shoes albeit with SSS. The same person was tested three times on three different days (9 acquisitions). The data acquired from the SSS were elaborated from a dedicated algorithm. The result of the dynamic test is presented as the mean percentage number of toe steps and the result of the static test is reported as the mean percentage of seconds in TB. 

Results: 
Three individuals with severe ASD and TTB were assessed. Their age was 10.9yrs, 12.8yrs and 13yrs (3/3 males) and their ADOS CSS was 9, 10 and 8, respectively. We found the SSS was feasible and acceptable in the three individuals with severe ASD and TTB in all three trials. We were also able to quantify TTB during both the static and the dynamic tests using the SSS tool in 9/9 of the acquisition (100%) (example in Figure 2). 

Conclusions: 
"Sensoria® Smart Socks" seems to be a feasible and acceptable wearable sensors approach for quantifying TTB in individuals with severe ASD and TTB. Further research is required to confirm these preliminary results.

Notes:

1 - Villa Santa Maria Foundation Autism Research Unit, Tavernerio (Como), Italy

2 - Politecnico di Milano, Italy

Background: 
There has been recent interest in the relationship between socioeconomic status,urbanicity level and the diagnosis of autism in children. Studies in the United Stateshave found lower rates of autism diagnosis associated with lower socioeconomicstatus, while studies in other countries report no association, or the opposite. In alarge Danish register-based cohort the urbanicity level was critical, with an earlierage of ASD diagnosis in urban areas. No specific studies on the socioeconomicfactors and urban context associated with the age at ASD diagnosis have beenconducted in Italy. Since a diagnostic delay may depend on a heterogeneousfunctioning of the local health care systems in term of waiting times, a more specificconnection for our targets of interest is the age at first medical contact fordiagnostic suspicion rather than age at diagnosis. 

Objectives: 
The focus of this pilot study is the association between age at first medical contactfor diagnostic suspicion and socioeconomic status and urbanicity level in LombardyRegion, the most populous and rich Region in Italy. 

Methods: 
Twenty ASD cases referred to our Institute for rehabilitation from 2020 to 2021coming from 16 municipalities were entered in the study. The age at first medicalcontact for parental concern was determined from parents reports. Familysocioeconomic status was calculated from four factor index of social status (motherand father education achievement level and occupation level). Age and place of birthof parents (North, Centre, South Italy) and city size where the family lived, and childgender were other variables used for input data. 

Results: 
The study group was composed by 12 males and 8 females (mean age 7.19 yrs;range 2-11 yrs) diagnosed with autism according to DSM V criteria. The age at firstmedical contact for parental concern ranged between 13 and 79 months (mean=32.8 months) while the age at diagnosis ranged between 23 and 91 months (mean=43 months). The delta time between these two ages was in mean 10 months with apeak of 42 months. Family socioeconomic status index ranged from 4 to 15 (mean=10.25). Correlations between age at first access and study variables are shown intable 1. Mother education years, family SES and father education years being thevariables with the highest inverse correlation(R= -45; - 0.43; -0.41 respectively)resulted the most important factors for an early diagnostic suspicion. 

Conclusions: 
Higher mother and father education years and higher family socioeconomic status,play a substantial role in influencing positively the decision to seek medical help forASD suspicion and consequently the age at diagnosis, while city size has a minorrole.

Notes:

1 - Villa Santa Maria Foundation Autism Research Unit, Tavernerio (Como), Italy

Background: 
Autism spectrum disorder (ASD) is a genetically heterogeneous disorder and may becaused by both inherited and de novo gene variants. Increasing evidence points to acontribution of environmental and epigenetic factors in ASD, but their connectionsare still largely unexplored. 

Objectives: 
Aim of the present pilot study was to apply the Auto Contractive Map algorithm(Auto CM), a special kind of Artificial Neural Networks to link various ASD maternalrisk factors to the DNA methylation levels of selected genes, sex, and symptomsseverity (ADOS 2 score) of their children diagnosed with an ASD. 

Methods: 
A total of 58 ASD children aged less than 8 years (mean age 4.35 ± 1.79 years) wererecruited, including 23 males and 35 females. Blood DNA methylation levels of MECP2, BDNF, OXTR, RELN, BCL 2, EN 2, and HTR 1 A, were measured by means of MSHRM technique. Mothers filled in a detailed questionnaire on various environmentalfactors during pregnancy. We also investigated the methylation levels of miRNAencoding genes ( miR-30e, miR-23/27a, miR 28 miR 92 a 1 miR 92 a 2 miR 21) in DNAextracted from saliva of 11 idiopathic ASD and 13 typically developing preschoolaged girls. To graphically show the most important connections among variables weused a four generation artificial neural network called Auto-CM, that developsweights that are proportional to the strength of the associations of all variables eachother. The weights are then transformed in physical distances so that couples ofvariables whose connection weights are higher become nearer and vice versa. Afterthe training phase, the weights matrix of the Auto-CM represents the warpedlandscape of the dataset. Subsequently, a minimum spanning tree filter was appliedto the weights matrix of the Auto-CM system to obtain a map of the mainconnections between the variables of the dataset and the basic semantic of theirsimilarities, defined connectivity map (figure 1). 

Results: 
Sex differences were observed in blood DNA methylation levels of the studiedgenes, and ANNs revealed sex-specific connections among maternal risk factors andgene methylation. Furthermore, ANNs selected a set of variables allowingdiscriminating between high and low-moderate ADOS-2 scores with 86.8% overallaccuracy. Particularly, high gestational weight gain, lack of folic acid supplements,advanced maternal age, pre-term birth, low birthweight, and living in rural contextwere the best predictors of high ADOS-2 score. Moreover, the analysis of saliva DNAsamples revealed that Mir-28 methylation levels could represent a biomarker ofdisease severity in ASD children. 

Conclusions: 
ANNs revealed links among ASD maternal risk factors, symptoms severity and genemethylation levels, as well as sex differences in gene methylation levels that warrantfurther investigation in ASD.

Notes:

1 - University of Pisa, Italy

2 - IRCCS Fondazione Stella Maris, Calambrone (Pisa), Italy

3 - Villa Santa Maria Foundation Autism Research Unit, Tavernerio (Como), Italy

BACKGROUND:

Toe walking is a clinical sign present in 20% of individuals with autism spectrum disorder (ASD). Because this behavior is also found during standing or running, the term tip-toe behavior (TTB) seems to be more appropriate. TTB is poorly quantified with structured methods. Previously, we proposed a standardized method to quantify TTB during static and dynamic tasks using a video-recording approach (VRA) in an ecological setting. The most used and reliable instrumental tool to quantify motor deficit during standing and walking is the gait analysis, but this approach requests the positioning of a large number of markers on the skin of the patient, a long time to prepare the patient for the execution of the test and is conducted in a non-ecological setting. Thus, gait analysis could be difficult to use with individuals with severe ASD because of their clinical condition. To overcome these limitations, a simpler instrumental approach that uses wearable sensors (WS) usable in an ecological setting could be a useful resource. 

OBJECTIVES:

The aims of this pilot study are: 1) to verify the feasibility and acceptability of WS in individuals with severe ASD; 2) to quantify TTB using VRA and WS during structured standing and walking tasks; 3) comparing the quantitative assessment of TTB using a WS-based protocol with the VRA. 

METHODS:

Subjects with ASD diagnosed according to DSM-5 criteria and confirmed using the Autism Diagnostic Observation Schedule (ADOS) were involved to the pilot study. TTB was quantified using a VRA and WS approach during a structured static and dynamic tasks, previously described. All the tests were performed without shoes albeit with “Sensoria® Smart Socks” (SSS), a validated commercially available wireless gait monitoring technology (Figure 1). The static test consisted in playing while standing in front of a table for 3 minutes. The dynamic test consisted in transporting 1 object (puzzle, Lego®, …) from the therapist to the playing table situated 2 meters away and back again 15 times. The same person was tested three times on three different days (9 acquisitions). In this way, we were able to collect data obtained from video-recording and WS approaches at the same time. The result of the video-recording and WS approaches were analyzed. The intraclass correlation coefficient (ICC) was used to assess the reliability between the video-recording and WS approaches in quantifying the mean percentage of toe steps and the mean percentage of the time spent in TTB.  

RESULTS:

We assessed 3 individuals with ASD and TTB. The age was 10.9yrs, 12.8yrs and 13yrs (3/3 males) and their ADOS CSS was 9, 10 and 8, respectively. SSS was feasible and acceptable in the three individuals with severe ASD and TTB in all three trials. We were also able to quantify TTB during both the static and the dynamic tests using the SSS tool in 9/9 of the acquisition (100%) (Figure 2). The normal distribution of data was confirmed (Shapiro-Wilk test p > 0.05). The ICC values of the mean percentage of toe steps and the mean percentage of the time spent in TTB were 0.778 (excellent) and 0.731 (good), respectively. 

CONCLUSION:

SSS seems to be a feasible and acceptable WS approach for quantifying TTB in individuals with severe ASD and TTB. SSS used for the quantitative assessment of TTB in individuals with ASD showed good-to-excellent reliability in comparison with the VRA both during a static and dynamic tests. Further research is required to confirm the results of this preliminary study. 
Notes: 1) Villa Santa Maria Foundation Autism Research Unit, Tavernerio (Como), Italy 2) University of Milano Bicocca School of Medicine and Surgery, Milano, Italy 3) Politecnico di Milano Department of Design, Milano, Italy 4) Scientific Institute IRCCS “E. Medea” Bioengineering Laboratory, Bosisio Parini (Lecco), Italy

Notes:

1) Villa Santa Maria Foundation Autism Research Unit, Tavernerio (Como), Italy
2) University of Milano Bicocca School of Medicine and Surgery, Milano, Italy
3) Politecnico di Milano Department of Design, Milano, Italy
4) Scientific Institute IRCCS “E. Medea” Bioengineering Laboratory, Bosisio Parini (Lecco), Italy

Background:

There has been recent interest in the relationship between socioeconomic status, urbanicity level and the diagnosis of autism in children. Studies in the United States have found lower rates of autism diagnosis associated with lower socioeconomic status, while studies in other countries report no association, or the opposite. In a large Danish register-based cohort the urbanicity level was critical, with an earlier age of ASD diagnosis in urban areas. No specific studies on the socioeconomic factors and urban context associated with the age at ASD diagnosis have been conducted in Italy. Since a diagnostic delay may depend on a heterogeneous functioning of the local health care systems in term of waiting times, a more specific connection for our targets of interest is the age at first medical contact for diagnostic suspicion rather than age at diagnosis. 

Aim:

The focus of this pilot study is the association between age at first medical contact for diagnostic suspicion and socioeconomic status and urbanicity level in Lombardy Region, the most populous and rich Region in Italy.  

Methods:

Twenty ASD cases referred to our Institute for rehabilitation from 2020 to 2021 coming from 16 municipalities were entered in the study. The age at first medical contact for parental concern was determined from parents’ reports. Family socioeconomic status was calculated from four factor index of social status (mother and father education achievement level and occupation level). Age and place of birth of parents (North, Centre, South Italy), city size where the family lived, and child gender were other variables used for input data. Machine learning systems were employed to predict different classes of age at first medical contact (<30 months vs >30 months). 

Results:

The study group was composed by 12 males and 8 females (mean age 7.19 yrs.; range 2-11 yrs.) diagnosed with autism according to DSM V criteria. The age at first medical contact for parental concern ranged between 13 and 79 months (mean= 32.8 months) while the age at diagnosis ranged between 23 and 91 months (mean= 43 months). The delta time between these two ages was in mean 10 months with a peak of 42 months. Family socioeconomic status index ranged from 4 to 15 (mean= 10.25). Mother education years, family SES and father education years were the variables with the highest inverse correlation (R= -45; - 0.43; -0.41 respectively; p= 0.046; 0.058; 0.072 respectively) with age at first medical contact for parental concern. A machine learning model selected years of mother education, city size and parents geographical origin to build up a model predicting age at first contact higher or lower than 30 months with an overall accuracy of 88.69% (85.72 %sensitivity and 91.67% specificity). 

Conclusion:

This pilot study suggests that socioeconomic status and urban-rural environment play an important role in influencing positively the decision to seek medical help for ASD suspicion and consequently the age at diagnosis. A machine learning model built on selected study variables can predict class of age at first contact with a high accuracy. 

Notes:

1 - Villa Santa Maria Foundation, Tavernerio (Como), Italy

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Mounting evidence show that persons with ASD may present sensorimotor deficits. Tiptoe behavior (TTB) is a possible finding during standing and/or walking and/or running assessment of individuals with ASD [1]. TTB persistence may lead to Gastrocnemius (GM) and Soleus (SM) muscles length shortening [1]. Their assessment can be done measuring ankle dorsiflexion range of movement (ROM) with knee extended (GM) and knee 90° flexed (SM)[1]. Traditionally, ROM has been assessed using visual estimation or long-arm goniometer technique. Recently, photography-based goniometry has been validated as instrument to measure joint ROM [2,3]. This non-invasive tool could be useful when measuring GM and SM length in individuals with ASD, where tactile hypersensitivity can be often found.

Objectives: The aim of this study was to investigate the feasibility of measure GM and SM lengths in subjects with ASD through use a photography-based goniometry (“Dr. Goniometer” app).
Methods: We assessed SM and GM length values in a sample of ten subject with ASD (5 with TTB and 5 without TTB), diagnosed following the DSM-5 criteria. Moreover, the ASD severity was assessed using the Autism Diagnostic Observation Schedule (ver. 2) calibrated severity score.
To assess TTB presence or absence we applied a standardized qualitative assessment previously described [1]. Photography-based goniometry measurement was conducted following the methodology previously described from Wang et al. [4] (see Fig.1).

Results: The mean age of the study sample was 14.48 yrs (SD 3.4) (age range: 8.9-20.3 yrs; 10 males). The participants presented moderate to high ASD severity (mean ADOS CSS: 7.89 - SD 1.36; range: 6-10). We were able to assess measure of GM and SM lengths using “Dr.Goniometer” tool in 9/10 subjects (90%). Details about demographic characteristic of study sample and GM and SM length values are summarized in table 1.

Conclusion: Photography-based goniometry seems to be a feasible tool for assessing GM and SM muscle lengths in ASD individuals both with and without TTB.

Notes:

1 Autism Research Unit, Villa Santa Maria Foundation, Tavernerio (CO), Italy
2 School of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy 3 Institution, City, Country

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder, resulting in an impairment of socio-communicative interaction, restricted interests, and repetitive behaviors [1]. Growing evidence suggests that individuals with ASD may show sensorimotor deficits. Toe walking (TW) is a possible finding during gait observation in about 20% of subjects with ASD [2]. TW persistence could lead to a secondary shortening of the Achilles tendon [3]. However, there is no consensus about TW management.

Objectives: The aim of this systematic review was to summarize the evidence for conservative, pharmacological, and surgical interventions for treating TW in children and adolescents with ASD.
Methods: The study followed the PRISMA recommendations. Articles were searched on PubMed, CINAHL, PsycINFO, The Cochrane Library, Google Scholar, and OpenGrey from inceptions until May 2022. Two review authors independently screened titles and abstracts for eligibility; then independently screened full-text of potentially eligible studies. Hand-searching of the reference list of included studies was also performed by the reviewers to identify additional primary studies. Methodological quality was assessed using the Mayo Evidence-Based Practice Centre tool.

Results: The records identified through database searching were 658. After duplicate removal, 432 records were screened for relevance, and 423 records were excluded. Nine articles were included in qualitative synthesis. All studies were case reports, with a total 17 participants (16 males; age range: 4-15yrs). The methodological quality was heterogeneous (Table 1). All the studies applied a conservative treatment. Five studies assessed the effectiveness of behavioral interventions using acoustical feedback or tactile stimulus in addition to positive reinforcement; one study evaluated the efficacy of a lymphatic drainage technique, and one work used cognitive-motor dual-tasking and primitive reflex integration exercises; the remaining two studies administrated serial casting. All studies reported a reduction of TW frequency, but the follow-up was lacking in 7/9 studies. No studies assessed the effectiveness of pharmacological and surgical interventions in TW subjects with ASD.

Conclusion: There is a lack of high-quality studies with a sufficiently large and well-characterized sample to assess the effectiveness of treatments for TW in children and adolescents with ASD. The present findings strongly support the need for future studies on this area for providing higher level of evidence.

Notes:

1 School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
2 Autism research unit, Villa Santa Maria Foundation, Tavernerio (CO), Italy
3 Department of Physical Therapy, Waldron College of Health and Human Services, Radford
University, Roanoke, Virginia, USA

Background: Toe-walking is a possible finding during gait assessment of autism spectrum disorder (ASD) subjects, and it can be also manifested during standing and running [1]. Three mutually exclusive clinical functional classes of tiptoe behavior (TTB) of increasing severity have been described: TTB during running (TTB1), during walking and running (TTB2), and during standing, walking and running (TTB3) [1]. Moreover, a positive relationship between the presence and severity of TTB and the Achilles tendon shortening (assessed as Soleus (SM) and Gastrocnemius (GM) muscle lengths) was reported [2]. To our knowledge, no studies describe SM and GM length values of ASD subjects without and with TTB at different age classes.
Objectives: This cross-sectional study aimed: 1) to describe the prevalence of TTB in a sample of individuals with ASD and at different age classes; 2) to describe SM and GM length values of ASD subjects with and without TTB in the general sample and at different age classes; 3) to compare SM and GM length values of ASD subjects without TTB (NO-TTB subgroup) versus ASD subjects with moderate-severe TTB (i.e., TTB2+TTB3 subgroup) in the sample and for each age class subgroups.

Methods: 106 subjects (mean age: 11.27±4.95yrs; range: 3.66–24.83yrs; 83 males) diagnosed with ASD according to DSM-5 or ICD-10 criteria were included.
The presence of TTB was evaluated by a physiotherapist through direct observation and a structured interview of the main caregiver [1]. The SM and GM length were assessed using a manual goniometer [2]. The sample was divided according four age classes: 0-6 yrs, 7-12 yrs, 13-18 yrs, and 19-24 yrs. Subjects belonging to TTB2 and TTB3 were considered as moderate-high TTB severity subjects. Thus, a comparison of GM and SM length values between NO-TTB and TTB2+TTB3 subgroups was performed.

Results: The prevalence of TTB subjects was 28.3% (n=30). Table 1 describes the TTB prevalence in the four age classes. Table 1 provides a detailed description of SM and GM length values of ASD subjects with and without TTB. Performing a Mann-Whitney tests we found that ASD subjects with moderate-severe TTB manifest statistically significant lower SM and GM length values than ASD subjects without TTB in the general sample and in age class subgroups (p<0.05) (Table 2).
TABLES here

Conclusion: ASD subjects who present moderate-high TTB severity manifest a significant decrease in Achilles’ tendon length values. Further research is required to confirm the results.

Notes:

1 Villa Santa Maria Foundation, Tavernerio (CO), Italy
2 School of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy
3 School of Physical & Occupational Therapy, McGill University, Montreal, Canada
4 Istituto “La Casa del Sole”, Mantova, Italy
5 CTR di Fondazione Renato Piatti Onlus, Milano, Italy

Background/Objectives:
Increasing evidence points to a contribution of environmental and epigenetic factors in autism spectrum disorder (ASD), but their connections are still largely unexplored [1-3]. In the present study we used machine learning tools to unravel connections among ASD-related gene methylation levels, maternal ASD risk factors and ASD severity.

Methods:
The methylation levels of MECP2, OXTR, RELN, BDNF, EN2, BCL2 and HTR1A genes have been assessed in blood DNA samples of 58 ASD children (23 males and 35 females). We then used machine learning approaches (Auto-CM) to connect gene methylation levels with maternal ASD risk factors and with disease severity (ADOS-2 score).

Results:
Sex differences were observed in DNA methylation levels of the studied genes, with MECP2, HTR1A, and OXTR methylation connected to females, and EN2, BCL2, and RELN methylation connected to males. BDNF methylation was not linked to sex, but rather to maternal risk factors. Maternal prepregnancy BMI, gestational weight gain and living context were among factors linked to disease severity.

Conclusion:
The present study highlights the power of artificial intelligence tools to unravel connections among different variables in complex disorders, revealing links among maternal risk factors and disease severity or gene methylation levels, as well as sex differences in gene methylation levels that warrant further investigation in ASD.

Background:
Many different mathematical approaches have been tested in the last few years to disentangle the EEG data complexity and determine if it is possible to distinguish children with ASD from typically developing children or children with other neuropsychiatric disorders. Each method has advantages and disadvantages, like for example, the large computational time required to achieve the final task.

Objectives:
We present an alternative pre-processing approach of EEG data based on a novel algorithm applied to raw data to detect topological EEG features. Our assumption is that brain connection abnormalities can be detected through a specific mathematical topological approach, which is able to compare the minimal structure of functional networks beneath scalp electrodes.

Methods:
This new pre-processing approach of EEG data to detect topological EEG features has been applied to a continuous segment of artifact-free EEG data lasting 10 minutes in ASCII format derived from 50 ASD children and 50 children with other Neuropsychiatric disorders matched for age and male/female ratios whose data were obtained from a clinical archive. Both groups had the same age range (4-10 years) and the same gender distribution (m=39, f=11). None of the subjects were affected by genetic conditions, cerebral malformations, or epilepsy. In the control group, the range of primary diagnoses were ADHD (n=41), mood disorders (n=4),anxiety disorders (n=16), sleep disorders (n=12), ODD (n=6), and TBI (n=5).
Each EEG was manipulated using “Cin-Cin” algorithm, based on an input vector characterized by a linear composition of city-block matrix distances among 19 electrodes. From the resulting triangular matrix of 171 numbers expressing all of the one-by-one distances among the 19electrodes a minimum spanning tree (MST) is calculated. Electrode identification serial codes sorted according to the decreasing number of links in MST, and the number of links in MST are taken as input vectors for machine learning systems. With this method all the content of an EEG is transformed in 38 numbers which represent the input vectors for machine learning systems classifiers. The advantage is the simplicity and the small computational time required.

Results:
The robust set of 38 features related to MST were used as input for Machine Learning classifiers. KNN algorithm was used to develop a predictive model to distinguish subjects belonging to the two diagnostic classes (autism vs other disorders). Models' performances were tested with training/testing cross-validation procedures.
The best machine learning system (KNN algorithm) obtained a global accuracy of 93.2% (92.37% sensitivity and 94.03 % specificity) in differentiating ASD subjects from NPD subjects (table1).

Conclusions:
In conclusion the results obtained in this study suggest that the new preprocessing methods introduced, in particular the MST algorithm, have great potential to allow a machine learning system to discriminate EEGs obtained from subjects with autism from EEGs obtained from subjects affected by other psychiatric disorders.

Background:
COVID-19 pandemic has forced almost all activities as businesses, schools and entire countries to move completely online. For children and adolescents requiring special education like those affected by neuropsychiatric disorders (NPD), a particular effort was needed to ensure good results. A special program called “Smart School” has been developed between April and June 2020 involving 97 subjects with NPD whowere unable to access the school in our Institute, providing materials for specialized didactic, educational and rehabilitative activities.

Objectives:
The aim of this study is to compare the acceptance and compliance to Smart School programs between subjects with autism vs subjects with other NPD.

Methods:
The study group was composed by 28 subjects with autism (DSM-5 diagnosis), age 5-16 years ( mean 11);26 males and by 69 subjects with other NPD, age 4 – 17 years(mean 11); 32 males. The Smart School Project has foreseen the involvement of 20 Primary SchoolTeachers and 5 specialized operators, 1 Chief of Professional Education that coordinates the whole project in all the different steps, 1 DevelopmentalPsychologist 4 Professional Educators (EP) and 1 Neuro-Psychomotor Therapist ofDevelopmental Age
The overall scheme of Smart School program is the following: The teachers (bothPrimary and Secondary classes) prepare weekly teaching materials for their studentsand using the Google-Drive platform they insert them in the link generated for each student.
The specialized operators automatically access the links of Google Drive and check weekly the material sent by teachers to compare and integrate it with the educational project. Through We Transfer, the specialized operators send all the material to the families. After sending the material, the families are contacted by the specialized operators assigned to help and support them both in carrying out the activities and in managing their child and any behavioral problems manifested.
After two weeks from the beginning of the online education (April 2020) the index of appreciation and satisfaction expressed by the children was detected through the principal caregiver (mother in 93%) through a 4-point Lickert scale from1=unsatisfied to 4= very satisfied

Results:
The percentages of satisfactory + highly satisfactory judgment expressed by childrenand adolescents were 64.49% in group with autism and 25.8% in the group with other NPD ( p< 0.01).The corresponding percentages expressed by the caregiver were 60.8% and 55.3% ( p = NS) respectively .

Conclusions:
Subjects with autism showed a significantly higher appreciation of smart school online program at variance with subjects with other NPD. Caregivers judgments in the two groups were comparable. Lockdown for pandemic as expected seems to affect less the online education acceptance in students with autism despite their known resistance to the change routine context environment, probably because they suffer less from sociality lacking and because their environment at home seems to them more under control.

Background:
Toe-walking is a phenomenon present in 20-30% of ASD subjects. Using a qualitative structured assessment, we previously described three mutually exclusive clinical functional classes of tip toe behavior (TTB) of increasing severity: during running(TTB1); during walking and running (TTB2); during standing, walking and running(TTB3). In another study, we found a positive relationship between the presence and severity of TTB and the Achilles’ tendon shortening. It is not clear if ASD subjects who present TTB manifest the Achilles’ tendon shortening at a young age and if this deficit is related to the age of onset.

Objectives:
This cross-sectional study aimed to evaluate: 1) if ASD subjects who present moderate-high TTB severity manifest a deficit in gastrocnemius and soleus muscles(GM and SM) length values (the two muscles that coalesce into Achilles’ tendon) at a young age (i.e., before 8 years); 2) if the SM and GM length values decrease with agein moderate-high TTB severity subgroup.

Methods:
The study group consisted in 106 subjects (mean age: 11.27 years – 4.95 SD; 83males) with autism diagnosed according DSM-5 or ICD-10 criteria. A therapist assessed the presence of TTB during standing, walking, and running using direct observation and an interview of the main caregiver living with the children. Two therapists assessed both the SM and GM length values using a manual goniometer following the methodology previously described. We considered moderate-highseverity TTB subjects those belonging to TTB2 and TTB3 subgroups. Therefore, to assess the presence of muscle length deficit at a young age (0-8 years), we compared the GM and SM length values between NON-TTB (n=28) and TTB2+TTB3 (n=9)subgroups using a Mann-Whitney test. To assess if the SM and GM length values decrease with age in moderate-high TTB severity subgroup we performed aSpearman correlation test between age and GM and SM length values in theTTB2+TTB3 subgroup (n=25).

Results: At age of 0-8 years, the mean length value of the left GM of NON-TTB subgroup (n = 28) was 18.61° (6.37°SD) vs a value of 9.22° (4.09°SD) TTB2+TTB3subgroup (n = 9) (p<0.001). The mean length value of the right GM of NON-TTB subgroup was 18.32° (4.97°SD) vs a value of 11.33°(4.36°SD) TTB2+TTB3 subgroup(p<0.001). The mean length value of the left SM of NON-TTB subgroup was 27.39°(7.57°SD) vs a value of 15.56° (4.5° SD) TTB2+TTB3 subgroup (p<0.001). The mean length value of the right SM of NON-TTB subgroup was 26.39° (5.83°SD) vs a value of 18° (2.97° SD) TTB2+TTB3 subgroup (p<0.001). Moreover, we found a significative inverse correlation between age and left GM (r=-0.702; p<0.001), right GM (r=-0.623;p=0.001), and right SM (r=-0.412; p=0.04) of the TTB2+TTB3 subgroup. We found a not significative correlation between age and left SM (r=-0.253; p=0.221).

Conclusions: ASD subjects who present moderate-high TTB severity manifest a significant decrease of Achilles’ tendon length values at a young age (i.e., before 8years). We also found the existence of a significative inverse relationship between age and the Achilles’ tendon length values.

Vagus Nerve Stimulation (VNS) is a proven and safe technology to treat drugs resistant epilepsy (DRE) in children. The reduction ≥50% in baseline seizure frequency range among 43,8% at 24 months (percentage of seizures freedom in 8.2%) (1), 60.1% at 24 months (2) and 54% % at the 5th year (3).
The prediction of the efficacy of VNS is still difficult and only the duration of active epilepsy before the implantation seems to correlate with better outcomes: short time before the implant (4) or age < 5 years (5) are highlighted as the the only variable significantly predicting favorable outcome.
In UE rare diseases are considered those having a prevalence < 5/10000 inhabitants and epilepsy or drug resistant epilepsy is often one of the main features in the phenotype.

Abstract: Background: 
Toe walking is a possible finding in individuals with ASD. In a previous study, we documented the presence of this behavior also during the maintenance of standing position from which the term “tip-toe behavior” (TTB). In a further study, using the Short Sensory Pro le (SSP) tool we found different patterns of sensory pro le in TTB ASD individuals with two opposite forms: “Under responsive/Seeks sensation” or “tactile hypersensitivity” Since in a pilot study we found a TTB decreasing during standing on a mattress when compared on a hard surface, we have developed a device to be worn within shoes consisting in a special insole for subjects with tactile hypersensitivity. 

Objectives: 
The study aim is to offer a proof of concept behind a rational approach to TTB treatment based on individual sensory profile. 

Methods: 
The ASD diagnosis followed the DSM-5 criteria, and a diagnosis confirmation was performed using ADOS-2. Two subjects (subject A: male, 15 years; subject B: male, age: 10,5 years) were selected among a sample of 14 TTB ASD subjects to whom the SSP tool was administered. Subject A expressing a “de nite difference” in “Under responsive/seeks sensation” section and a typical performance in “Tactile Sensitivity” section, while subject B expressing a “de nite difference” in “Tactile Sensitivity” section and a typical performance in “Under responsive/seeks sensation” section. We developed an insole made of soft material such as cellular rubber to be inserted inside each shoe. This insole has a constant thickness between 2.0 and 12.0 millimeters which is adapted to individual needs and a density between 0.10 and 0.20 g/cm³. 
Both subjects wore the device for 48 weeks, 6 hours a day,  ve days a week. At baseline (T0) and every four months (T1, T2, T3) TTB intensity during standing position was assessed using video recordings taken during a static task (playing in front of a playing table for 90 seconds) without shoes and with socks, using a standardized methodology previously described. The test was repeated in three different days. An independent therapist not involved in test operation analyzed the videos of the static task trials by calculating the cumulative time in seconds spent along ninety seconds on full feet support versus one foot on toes versus both feet on toes. The mean time of the three trials was then calculated for the three conditions. In this study, we considered as outcome measure the mean percentage of cumulative time spent with a foot on the tips plus both feet on the tips. 

Results: 
In subject A no changes in TTB intensity was found (T0 value = 71%; T1-T3 average value = 79%), while in subject B a marked reduction in TTB intensity was found (T0 value = 72%; T1-T3 average value = 36,3%). 

Conclusions: 
The results obtained in these case reports constitute a proof of concept for the development of special devices to treat TTB according to sensory pro le expressed. In particular in presence of “tactile hypersensitivity”, an intervention with special rubber insole seems rationale.

Notes: 

1 - University of Milano-Bicocca, School of Medicine and Surgery
2 - Villa Santa Maria Foundation

Abstract: Background: 
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Despite motor impairment is not currently included in the diagnostic criteria or evaluation of ASD, there is increasing evidence that subjects with ASD also have motor impairments, including gait alterations. Toe walking (TW) is a possible finding during gait observation in about 20% of subjects with ASD. TW persistence can contribute to a secondary shortening of the Achilles’ tendon. 

Objectives: 
This systematic review aims to summarize the evidence about TW interventions in individuals with ASD. 

Methods: 
The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations and was prospectively registered in the International Prospective Register of Systematic Reviews (registration no.CRD42020176335). The literature search was performed up to July, 24 2020 on Medline (via PubMed), CINAHL, PsycINFO, The Cochrane Library, Google Scholar and Opengrey, from the inception of these databases. No restrictions regarding language, year of publication, and age of population were applied. Two reviewers independently screened titles and abstracts for eligibility; then independently screened full-text of potentially eligible studies. A hand searching of the reference 
list of included studies was also performed (Figure 1). Assessment of the studies’ completeness has been conducted using the CARE checklist. 

Results: 
After the selection process, a total of 7 articles were included. They were all case reports, considering a total sample of 11 subjects (11 males; age range of 4-9 years). Five studies assessed the effectiveness of behavioural interventions using acoustical feedback or tactile stimulus in addition to positive reinforcement. One study proposed serial casting, and the one evaluated the efficacy of a lymphatic drainage technique. In all 7 studies, a reduction of TW frequency has been reported. A follow-up assessment was conducted only in 2/7 studies. 

Conclusions: 
There is a lack of high-quality studies with a sufficiently large and wellcharacterized sample to assess the effectiveness of treatments for TW in individuals.

Notes:

1 - University of Milano-Bicocca
2 - Villa Santa Maria Foundation

Abstract: Background: 
Although abnormal pain sensitivity has become one of the diagnostic criteria for Autism Spectrum Disorder (ASD), this area is still under-investigated. Speci cally, a very few studies focused on the anticipatory components characterizing pain experience related to self and others in ASD. 

Objectives: 
The present study was aimed at investigating psychophysiological responses in adults with High Functioning Autism (HFA) when observing a painful stimulus approaching (pain anticipation) their own skin (self-condition), another participant skin (other social agent condition) or a robotic hand (other non-social agent condition). 

Methods: 
Skin Conductance Responses (SCR) were measured in a group of adult participants with ASD diagnosis and a control group of participants without any psychiatric or neurological diagnosis. The experimental sessions consisted of a naturalistic paradigm where the participants observed a painful (sterilized needle) or a neutral (cotton bad) stimulus that could approach their own skin, the skin of another person or the hand of a robot (Figure 1). Data were analysed by implementing a new Machine Learning approach combining predictive modelling (i.e. Arti cial Neural Networks) and Auto-Contractive Maps, that is an emerging data mining approach able to detect connectivity associations among variables through an arti cial adaptive system. 

Results: 
The predictive model was 91% accurate and able to differentiate ASD participants from control group participants. Two distinct patterns were found for each group. Specifically, ASD individuals exhibited a lower physiological activation than controls when the noxious stimulus (needle) approached their skin after repeated stimulations. Interestingly, ASD participants showed a higher response when the robotic hand was approached by the painful stimulus, whereas no differences related to the human social agent between the two groups emerged. 

Conclusions: 
These results can contribute to clarifying the psychophysiological mechanisms underlying pain experience in ASD individuals. Implications for the study of the self-injury phenomenon, often observed in ASD, will be discussed.

Notes:

1 - University of Milano - Bicocca, Italy
2 - Villa Santa Maria Foundation

Abstract: Background 

Complex neurodevelopmental disorders like ASD may be characterized by subtle brain function signatures which can be measured using advanced machine learning tools. 
Sound postural control system requires the interaction of sensory, motor and integration 
systems. There is evidence that individuals with Autism Spectrum Disorder (ASD) present postural 
control deficits but is not known if the complexity of sensorimotor contribution can play a role. 
Objective 
The aim of the study is to compare the degree of complexity of sensory and motor functions in a group of subjects with autism with a matched group of Typically developing children and adolescents. 
Methods 
The study sample included 18 children and adolescents with ASD and 18 age-matched typically-developing (TD) individuals, (age range 6-18 years; 16 males for both groups). 
Participants completed a Physiological Profile Assessment, which includes 17 tests : Visual acuity with high- and low-contrast, Edge contrast sensitivity, Depth perception, Touch sensitivity, Tactile lower limb Proprioception, Simple reaction time of hand and foot, Isometric knee extensor and flexor muscle strength, Ankle isometric dorsiflexion strength, Postural sway with eyes open and closed, first on a firm surface, then on a medium density foam rubber mattress, Maximum balance range and Coordinated stability. 
The complexity of interaction among these physiological functions has been explored with Maximally Regular Graph (MRG) theory applied to the Semantic Connectivity map produced by a fourth generation artificial neural network (Auto-CM system; Semeion, Rome, Italy). 
MRG is the graph whose hubness function attains the highest value among all the graphs generated by adding back to the original Minimum Spanning Tree (MST), one by one, the connections previously skipped during the computation of the MST itself. In other words, starting from the MST, the MRG, presenting the highest number of regular microstructures, highlight the most important connections of the dataset. The resulting “diamond” expresses the complexity core of the system and in our specific case, the core of the physiological system. 
Results 
The map relative to TD group showed a coordinating role of Maximal Balance Range with respect to physiological functions on study. The MRG was generated by the addition of twelve links to MST involving eight Nodes (figure 1). At variance, the map relative to ASD group showed a coordinating role of touch sensitivity. The MRG was characterized by only six additional links involving five nodes ( figure 2). 
Conclusion 
This proof-of-principle study suggests that ASD postural physiology is characterized by a loss of complexity in its component interaction which in the future might become a useful biomarker for early detection of risk for ASD. 

Notes: 

(1)Autism Research Unit, Villa Santa Maria Foundation, Tavernerio, Italy
(2)School of Medicine and Surgery, University of Milan-Bicocca, Milano, Italy

In 2 previous studies we have shown the ability of a special machine learning system applied to digital standard (19 channels) EEG data in distinguishing ASD from non ASD children with an overall accuracy rate of 100% and of 98.4% respectively. Since the equipment routinely available in neonatology units employ often few channels, we were curious to check if just two channels were enough to allow a good performance in the same cases of the above-mentioned studies. A continuous segment of artifact-free EEG data lasting 1 minute in ASCCI format from C3 and C4 EEG channels present in 2 previous studies, the first carried out in Italy on 25 subjects (15 ASD and 10 typicals) and the second carried out in US on 40 subjects (20 ASD and 20 with other NPI disord.) was used for features extraction and for subsequent analyses with advanced machine learning systems. A features extraction software package (Python tsfresh) applied on time-series raw data derived 1588 quantitative features. A special hybrid system called TWIST, coupling an evolutionary algorithm named Gen-D and a back propagation neural network was used to subdivide the dataset into training and testing sets as well as to select features yielding the maximum amount of information. After this intelligent preprocessing, 14 features were extracted from C3-C4 timeseries of study 1 and 31 C3-C4 timeseries of study 2 representing the EEG signature. Acting on these features the overall accuracy predictive capability of the best artificial neural network acting as classifier in deciphering autistic cases from typicals (study 1) and from other NP disorders (study 2) resulted 100 % for study 1 and 93.3 % for study 2. The results of this study suggest that also a minor part of EEG contain a precious information useful to detect autism if treated with advanced computational algorithms. This could allow in the future to use standard EEG from newborn to check if ASD signature is already present at birth.

* Autism Research Unit, Villa Santa Maria Foundation, Tavernerio, Italy
**Ephoran Multi Imaging Solutions, Milano, Italy

Abstract: Background 
In previous studies we have shown the ability of a novel method of machine learning system named MS-ROM/IFAST to extract interesting features in digital EEG with standard 19 electrodes montage that allow very good distinction of ASD children from those who are developing typically and from those affected by other neuro-psychiatric disorders. If this signature is already present already at birth, then a screening program could be afforded in general hospitals registering EEG signals in the newborn. Since the equipment routinely available in neonatology units employ often few channels (2-8 electrodes), we were curious to check if features extracted from just two channels were enough to allow a good diagnostic performance in the same cases of the above-mentioned studies. 
Aim 
The aim of this study is to evaluate the information load present in just two EEG channels to distinguish autistic subjects from typically developing ones and from those affected by other neuro-psychiatric disorders. 
Methods 
C3 and C4 time-series were isolated from EEG data sets used in two previous studies, the first carried out in Italy on 25 subjects (15 ASD and 10 typicals) and the second carried out in US on 40 subjects (20 ASD and 20 with other neuropsychiatric disorders). 
A continuous segment of artifact-free EEG data lasting 10 minutes in ASCCI format was used to compute multi-scale entropy values and for subsequent analyses. 
A Multi-scale ranked organizing map (MS-ROM), based on the self-organizing map (SOM) neural network, coupled with the TWIST system (an evolutionary system able to select predictive features) created an invariant features vector input of EEG on which supervised machine learning systems acted as blind classifiers. 
Results 
After MS-ROM/I-FAST preprocessing, ninety features were extracted from C3-C4 timeseries of study 1 and of study 2 representing the EEG signature. Acting on these features the overall predictive capability of different machine learning systems in deciphering autistic cases from typicals (study 1) and from other NP disorders (study 2) ranged between 93% and 94. % (study 1) and from 80 and 88% (study 2) These results were obtained at different times in separate experiments performed on the same training and testing subsets. 
Conclusion 
The results of this study suggest that also a minor part of EEG contain a precious information useful to detect autism if treated with advanced computational algorithms. This could allow in the future to use standard EEG from newborn to check if ASD signature is already present at birth.

Notes: 

(1) Autism Research Unit, Villa Santa Maria Foundation, Tavernerio, Italy
(2) Semeion Research Centre, Roma, Italy
(3) Tarnow Center for Self-Management, Huston, TX

Abstract: Background 
Effective sensorimotor postural control to maintain an upright stance is a crucial component for daily functional activity. A sound postural control system underlines a spatiotemporal integration of sensory and motor and systems. Evidence suggests that Autism Spectrum Disorder (ASD) population present postural control disruption. 
Aim 
A cross-sectional study was carried out aimed at investigating sensorimotor contributions to postural control and behavior in children and adolescents with ASD compared to typically developing (TP) peers through the Physiological Profile Assessment – long form (PPA). 
Methods 
ASD and TD age-matched TD subjects were consecutively recruited in a northern metropolitan city in Italy. Participants were assessed with the PPA by residents in physical medicine and rehabilitation clinician. PPA includes 17 tests: Visual acuity with high- and low-contrast, Edge contrast sensitivity, Depth perception, Touch sensitivity, Tactile lower limb Proprioception, Simple reaction time of hand and foot, Isometric knee extensor and flexor muscle strength, Ankle isometric dorsiflexion strength, Postural sway with eyes open and closed, first on a firm surface, then on a medium density foam rubber mattress, Maximum balance range and Coordinated stability. 
Percentiles of each PPA subset were computed from the TD peers. PPA performances of ASD participants were compared to the TD percentiles. 
Results 
Eighteen ASD individuals’ (16/2 male/female), mean age (SD) 12.4 (3.7) years, were included. Their intellectual disability ranged from mild (n=5), moderate (n=11) to severe (n=2). In the TD age-matched group, 135 subjects (100/35 male/female) were enrolled of the following ages: 6 years (n=11), 8 years (n=16), 11 years (n=21), 12 years (n=12), 13 years (n=14), 14 years (n=24), 16 years (n=18) and 18 years (n=19). ASD individuals’ scores were above the 90th percentile, i.e., poor performance, in most motor, sensory, and balance subtests. In particular: half of our sample of children and adolescents with ASD performed poorly in the tests of visual acuity, particularly when the lighting conditions were poor (low contrast). Tactile sensitivity was inferior in our ASD population, with three-quarters of participants scoring above the 90th percentile and one performing below the 10th percentile. One-quarter of ASD participants performed poorly in the test of proprioception. More than half of our participants performed above the 90th percentile in the tests of simple reaction time at the finger and the foot. Over a quarter of the children and adolescents with ASD presented muscle weakness in at least one of the three lower limb muscle groups we investigated. Performance in the majority of PPA significantly improved with older age in the TD group but not in the ASD group. 
Conclusions 
These findings suggest how poor balance performance may be due to sensorimotor deficiencies integration in ASD children and adolescents. The investigation of the mechanisms underlying impaired age-related maturation of sensorimotor systems should drive the research agenda of the scientific community. 

Notes:

(1) School of Medicine and Surgery, University of Milan-Bicocca, Milano, Italy 
(2) Autism Research Unit, Villa Santa Maria Foundation, Tavernerio, Italy
(3) Ospedale "G. Salvini" - Garbagnate MIlanese, ASST Rhodense, Garbagnate MIlanese, Italy
(4) School of Medicine and Surgery, University of Milan-Bicocca, MIlano, Italy
(5) School of Physical and Occupational Therapy, McGill University, Montreal, QC, Canada
(6) School of Medicine and Surgery, University of Milan–Bicocca, Milano, Italy
(7) Neuroscience Research Australia and School of Public Health and Community Medicine, University of New South Wales, Sydney, NSW, Australia

Abstract: Background 
Recent studies have shown that subjects with autism are able to perceive aesthetic stimuli of artistic beauty. Therefore, by making art accessible to the, potential benefits such as greater self-esteem, mental stimulation and greater social interaction may potentially ensue. 
Aim 
The aim of this pilot experience is to explore the impact on wellbeing of a special museum and performing arts experience in adolescents with autism. 
Methods 
Twelve adolescents with autism (age 10-17) took part to this study. The ASD subjects were diagnosed with autism according to the DSM V criteria, confirmed through ADOS-2 and under observation at our Institute. Their mean ADOS severity score was 7.8 (range 4-10).  
The experience consisted in a guided visit to the Teatro Alla Scala Museum by a cultural mediator with experience in the field of inclusion for people with cognitive disabilities. At the end of the visit, the guests were made to sit in the Exedra hall, which houses the famous Steinway piano that belonged to Franz Liszt. Here a team from the Conservatory "Giuseppe Verdi" in Como presented a special reduction of “The Magic Flute” by Mozart, illustrating the history and individual characters with drawings and objects such as the music box, and singing the famous arias accompanied by piano and flute along with stage movements and dances. The performance lasted about half an hour. 
The measurement of the impact of this experience on psychological well-being was done by using a special continuous chromatic analogue scale presented as a 10 cm rule. The ruler has a sliding cursor that the subject is invited to position at the level corresponding to his current perceived psychological well-being. 
Before visiting the museum, well-being measurements were taken for five consecutive days, to establish a basic level of reference by asking subjects to use the ruler to determine the level of their momentary psychological well-being at a given time of day, between 10 a.m. and 11 a.m. 
On the day dedicated to the theatre experience, the same type of evaluation was carried out at 11 a.m., immediately before the experience, at 12.30 p.m., immediately after the experience, and at 2.30 p.m. on return to the Institute. 
Results 
Measuring well-being immediately after the aesthetic experience highlighted a strong emotional impact with a 47% increase in the momentary psychological well-being (from 64 mm to 94 mm). 
The increase resulted similar to that obtained in a control group of twelve adolescent with other forms of neuropsychiatric disorders. 
Conclusion 
This pilot study confirms that adolescents with autism are keen to receiving enjoyment when exposed to beauty, art and music and that the measurement of their momentary well-being is feasible despite the presence of an important cognitive deficit. 

Notes:

(1) Autism Research Unit, Villa Santa Maria Foundation, Tavernerio, Italy
(2) International Council of Museums Italy, MIlano, Italy

Abstract: Background 
Toe-walking is a phenomenon present in 20-30% of ASD subjects. Persistent tip-toe behavior (TTB) can produce a shortening of the Achilles’s tendon (made up by the soleus muscle – SM, and gastrocnemius muscle - GM) in ASD subjects. It is currently unclear why some ASD subjects develop this tendon shortening while others do not. One possible contributing factor could be the amount of time subjects spend in TTB during the day. In a previous study, we described three mutually exclusive clinical functional TTB classes of increasing severity: TTB present only in running (TTBclass1), in walking and running (TTBclass2), in standing, walking and running (TTBclass3). We also found the existence of a positive correlation between the severity of TTB presence and the Achilles’s tendon shortening using a qualitative testing approach. 
Objectives 
The aim of this cross-sectional study is to evaluate the relationship between the quantity of TTB expressed during both static and dynamic tests and the Achilles tendon shortening in a cohort of TTB and NON-TTB ASD subjects. 
Material and methods 
The cross-sectional study included 51 consecutive ASD subjects (44 males, 7 females, mean age = 13.9 years – 3.67 SD) diagnosed according to the DSM V criteria and under observation at our Institute. The ASD severity was established through ADOS (2nd version). A therapist assessed the amount of TTB during both standardized static and dynamic tests previously described. The intensity of TTB expression during the static and dynamic tests was quantified as percentage of time spent on the tip-toes and as the percentage of toe steps, respectively. Two therapists, blind to the TTB quantitative testing, assessed both the soleus and gastrocnemius muscle lengths using a manual goniometer.  
Results 
The overall ADOS calibrated severity score (CSS) of all the subjects was 7.61 (1.65 SD). Overall 21/51 subjects presented TTB. Two subjects were in TTBclass1, 10 in TTBclass2 and 9 in TTBclass3.The mean percentage of time spent in TTB during the static test was 5.96% (15.68 SD) (range: 0%-96%). The mean percentage of toe steps during the dynamic test was 15.39% (26.51 SD) (range: 0%-100%). The mean length of the left and right GM of the sample were 6.84° (6.2 SD) and 7.9° (6.07 SD) respectively. The mean length of the left and right SM of the sample were 16.1° (6.89 SD) and 15.96° (6.36 SD) respectively. Using a Pearson’s correlation test we found a significant inverse correlation between the percentage of time spent on the tip-toes and both the GM and SM lengths (left GM: r=-0.703, p<0.001; right GM: r=-0.678, p<0.001; left SM: r=-0.541, p<0.001; right SM: r=-0.518, p<0.001 respectively). We also found an inverse correlation between the percentage toe steps and both the GM and SM lengths (left GM: r=-0.484, p<0.001; right GM: r=-0.425, p=0.002; left SM: r=-0.386, p=0.005; right SM: r=-0.363, p=0.009 respectively). 
Conclusions 
The quantitative data show the existence of an inverse relationship between TTB intensity during both the static and the dynamic tests and the Achilles’s tendon shortening in ASD subjects. Further research is required to confirm the results. 

Notes:

(1) Autism Research Unit, Villa Santa Maria Foundation, Tavernerio, Italy,
(2) School of Medicine and Surgery, University of Milan-Bicocca, Milano, Italy

Abstract: Neurodevelopmental disorders, neuropsychiatric and neurodegenerative diseases are the most significant chapters of the epidemiological transition of the XX-XXI century, characterized by the progressive reduction of the incidence of the infective diseases and by an equal rapid increment of the prevalence of chronic-degenerative, inflammatory and neoplastic pathologies, with a concerning anticipation of the age of onset [1]. This phenomenon makes a common pathogenetic paradigm and requires the adoption of a systemic perspective, able to rebuild the picture provided by super-specialized research and assistance. 
The autism spectrum disorder (ASD) can be assumed as an emblematic condition to think about the necessity of a perspective change and about the urgency of effective strategies (1 case out of 59 in the US; 1 out of 77 in Italy, ISS 2019) [2]. 
The recent rapid increase of the prevalence and the complex clinical picture of the people with ASD require understanding the perturbation of the construction of the neuronal network inside a complex paradigm. The epigenetic modifications of the embryo-fetal period provide the most plausible explanation, precondition of the pathogenetic model proposed by the DOHaD Theory (Developmental Origins of Health and Disease) [3, 4]. According to this theory, the origin of several pathologies – neuropsychiatric and neurodevelopmental disorders – could be due to a lacking or imperfect correspondence between epigenetic programming in the uterus and the postnatal reality, often with effects not only on the nervous system. Several environmental factors that reach the fetus through the mother can induce reactive-adaptive and predictive epigenetic changes (fetal programming), in the tissues and cellular differentiation processes, with a long-term impact not only on the individual but on the next generations as well [5]. The neuroplasticity in the First One Thousand Days (embryo-fetal period and first two years of age) makes the vulnerability maximum (thus the opportunities as well) in this temporal window. 
The interpretation of the ASD according to the pathogenetic key of DOHaD is the precondition for the building of GLIA (Gruppo di Lavoro Interdisciplinary per l’Autismo, meaning "the interdisciplinary workgroup for autism") in the SIPO. Among the main objectives, there is the beginning of effective strategies of primary prevention and the individuation of biomarkers for early diagnosis.

Notes:

1 Fondazione Istituto Sacra Famiglia, Varese, Italy

2 ECERI, European Cancer and Environment Research Institute – Bruxelles, Belgium

3 Neonatal Intensive Care Unit, AOU and University of Cagliari, Cagliari, Italy

4 Complex Operative Unit of Pediatrics of the Presidio Ospedaliero Moscati, Aversa, Italy

5 Fondazione Villa Santa Maria, Tavernerio, Como, Italy

Abstract: Introduction: The World Health Organization states that Post Partum Hemorrhage (PPH) is the leadingcause of mortality and severe maternal morbidity worldwide. Therefore, it becomes essential to study risk factors in order to identify women at risk to improve their clinical management. The aim of this studywas to identify the risk factors associated with primary post-partum hemorrhage and to determine the accuracy of artificial neural networks as a statistical method to identify mayor risk factors. The hypothesis is that artificial neural networks can be a valid forecasting tool for hemorrhage risk at the time of delivery.Methods: We conducted a retrospective study on 305 women with PPH and 305 controls matched by age, analyzing the role of variables that have been identified as possible risk factors. Other ante and intra-partum variables were also taken into consideration in order to identify other risk factors previouslyundetected. Traditional statistical methods and artificial neural networks (ANN) were used to analyze the data. Auto Contractive Maps were used as a neural network system. These have been shown to be capable of identifying hidden, non-linear associations and the strength that these associations have with the different parameters taken into account.Results: The results obtained by the two statistical methods were similar and ANN identified PPH with an overall accuracy of 70%. Variables that were significantly related to PPH overlapped and were mainly related to labor and delivery. Furthermore, neural networks allowed us to identify the impact of each variable. 
Conclusion: Artificial neural networks have proved to be capable of reaching a good sensitivity, specificity, and global accuracy in the identification of more relevant hemorrhage risk factors. The innovative potential of this method is represented by the possibility of identifying a priori women with an increased hemorrhagic risk. This will allow tailoring the management of these women minimizing the consequences that a delivery complicated by hemorrhage involves. These results represent the starting point for the expansion of the retrospective case series and the creation of an antepartum risk score, in addition to a subsequent prospective validation.

Notes:

1University of Milano, Milano, Italy

2Villa Santa Maria Foundation, Tavernerio, Italy

Background 

Recent studies with neuroimaging methods like diffusion tensor imaging, functional connectivity, and graph theoretic methods have showed atypical development of neural connectivity in ASD, with excessive local connectivity within neural assemblies and deficits in long-range connectivity between functional brain regions. In this paper we present a new pre-processing approach of EEG data based on a novel algorithm applied to raw data and to quantitative EEG features able to pick-up abnormal connections.

Objectives

The aim of this study is to focus brain connections abnormalities in ASD using novel algorithms applied to EEG data. Methods: Twenty children diagnosed with ASD (DSM-V criteria) and 20 children diagnosed with NPD (ADHD –N.16, mood disorders –N.2, anxiety disorders –N. 2) matched identically for age and male/female ratio, were entered into the study. A continuous segment of artifact-free EEG data lasting 10 minutes in ASCCI format were entered in Cin-Cin algorithm, a new preprocessing method to treat multichannel time series related to brain activity. The algorithm is based on an input vector characterized by a linear composition of city-block matrix distances between 19 electrodes. In this way, each EEG is transformed in a vector of 171 numbers expressing all the one by one distances among the 19 electrodes. Each distance value is assumed to express the connection among the two brain areas below corresponding electrodes. An evolutionary algorithm (a TWIST system based on KNN algorithm) was used to subdivide the dataset into training and testing set and select connections yielding the maximal amount of information. After this pre-processing different machine learning systems were used to develop a predictive model based on a training testing crossover procedure applied to selected connections distances.

Results

The connections subset involving 11 electrodes with nine connections (T4_F3, O2_F4, P3_T3, P3_C3, O1_C4, P3_T5, P4_T5, O1_T5, O1_P3) allowed the maximum degree of predictive performance by Machine Learning Systems used as classificators. Four of these connections are long range (three inter hemispherical and one intrahemispherical) and five short range. Long-range mean distances values resulted higher in ASD group while the opposite was true for short-range distances. The best machine learning system (three-layer feed- forward neural network with 8 hidden nodes) obtained a global accuracy of 96.2% (96.4 % sensitivity and 96.0 % specificity) in differentiating ASD subjects from NPD subjects.

Conclusions 

The results of this study indicate the existence of brain connections abnormalities in ASD detected with evolutionary algorithms and Electroencephalography Analysis applied on a linear composition of city-block matrix distances between 19 electrodes. In addition, the model could distinguish the autistic children from the control children with an accuracy rate of 96.2%.

Autism Research Unit, Villa Santa Maria Foundation, Tavernerio, Italy

Background 

Recent open studies have shown some promising results of probiotic supplementation in ASD on gastrointestinal (GI) symptoms, reporting also significant changes in behavioural symptoms. To date only one study was carried out as a randomized placebo controlled trial but it was affected by a high drop-out rate and other methodological limitations. Therefore, efficacy of probiotics in patients with ASD remains undefined. 

Objectives 

The main aim of this study is to determine the effects of a 6 months supplementation with a probiotic preparation in preschoolers with ASD on behavioral and GI symptoms. 

Methods 

Eighty-five children with ASD (age-range: 2.18-6.11 years; mean ± DS: 4.15 ± 1.08 years) diagnosed according to DSM-5 criteria, were included in this randomized double-blind randomized controlled trial (funded by the Italian Ministry of Health, grant GR-2011-02348280). Methodology was reported in Santocchi et al. 2016 (DOI 10.1186/s12888-016-0887-5) and in ClinicalTrials.gov (NCT02708901). 

At baseline each subject was classified as belonging to the Gastro-Intestinal (GI) group or to the Non-GI (NGI) group on the basis of the presence of significant GI symptoms measured through the Gastrointestinal Severity Index (GI Severity Index) (cut-off = 4.0). 

ASD participants belonging to the two groups (30 subjects for GI group and 55 for NGI group) were blindly randomized 1:1 to regular diet with probiotics or with placebo for 6 months-treatment. The probiotic preparation selected for this study is Vivomixx®, a multicomponent product containing 450 billions of lyophilized bacterial cells belonging to eight probiotic strains: one strain of Streptococcus thermophilus, three strains of Bifidobacterium and four strains of Lactobacillus. Vivomixx® is a patented and marketed product and it has been approved for the use in children. The primary end point of the trial was the reduction in ADOS total composite score (TCS). 

Results 

Sixty-three subjects (74%; 17 subjects for GI group and 46 for NGI group) completed the treatment follow-up; no significant difference between the dropout rates was observed in the two treatment groups. The placebo and probiotic groups resulted to be homogeneous at baseline with regard to all prognostic variables. 

The two treatments showed a very good tolerability profile, with negligible and similar adverse event rates. The mean difference between ADOS at baseline and post treatment TCS values resulted to be +0.03 in placebo group and -0.65 in probiotic group (p= 0.91 vs P= 0.02 respectively). The ADOS mean change in the probiotic group was not affected by the presence of GI symptoms. In fact, this value resulted -0.81 in subgroup without GI symptoms in comparison with -0.22 in subgroup with GI symptoms. The mean improvement in GI Severity Index in probiotic group (-0.83) was significant (p= 0.04) at variance with the same in placebo group (mean improvement = -0.08; P= 0.90). 

Conclusions 

Six-month treatment with probiotics at variance with placebo is significantly effective in reducing the severity of ASD. The response is not related to the presence of GI symptoms, which, incidentally, improve significantly in the probiotic group. 

Notes:

1) IRCCS Stella Maris Foundation, Calambrone, Pisa, Italy

2) National Research Council, Institute of Clinical Physiology, Pisa, Italy

3) Department of Clinical and Experimental Medicine, University of Pisa, Italy

4) Department of Autism Research, Villa Santa Maria Institute, Tavernerio, Como, Italy

Background 

About 20-30% of ASD individuals display toe-walking to some degree. Previously, using a qualitative structured assessment, we described three mutually exclusive clinical functional classes: tip-toe behavior (TTB) during running (TTB1), TTB during walking and running (TTB2) and TTB during standing, walking and running (TTB3). In another study, we also found a positive relationship between the presence and severity of TTB and the Achilles’s tendon shortening in ASD subjects. To our knowledge, no prospective quantitative TTB study is currently available.

Objectives

The aim of this prospective cohort study is to describe the natural history of TTB and NO-TTB ASD subjects at shortmedium term using a quantitative standardized method. Methods: We included 37 consecutive subjects (32 males; mean age: 12.32 years – SD 4.36) with ASD diagnosed according to the DSM V criteria, and then confirmed with ADOS–2. According to the qualitative assessment, 21 ASD subjects resulted NOTTB, 2 resulted in TTB1 subgroup, 7 in TTB2 subgroup and 7 in TTB3 subgroup. The intensity of TTB expression during static and dynamic tests was quantified as a percentage of time spent on the tip toes and as a percentage of toe steps, respectively, through a standardized method previously described. The second assessment was repeated 11 to 38 months (mean: 21.41 months – SD 6.82; median: 23 months) after the first observation.

Results

The overall ADOS CCS was 6,67 (1,43 SD) in NO-TTB, 10 (SD 0) in TTB1, 7,57 (2.07 SD) in TTB2 and 8,29 (1,25 SD) in TTB3 (p = 0.014 between groups). The mean percentage time spent on the tip-toes (TSTT) during the static quantitative test in NO-TTB group, TTB1 TTB2, TTB3 was 0.1% (0.3 SD) , 0.5% (0.71 SD), 4.86% (6.36 SD), 29% (25.15 SD) respectively. The values of TSTT registered in No-TTB group and in TTB1 group remained substantially unchanged at follow up. Five subjects of TTB2 group decreased and two increased their TSTT respectively. The same happened in TTB3 group. The mean percentage of toe steps (PTS) during the dynamic quantitative test in NO-TTB group, TTB1 TTB2, TTB3 was 0.91% (2.36 SD), 3.5% (4.95 SD), 18.71% (6.36 SD), 48.71% (33.74 SD) respectively. The PTS registered in No-TTB group and in TTB1 group remained substantially unchanged at follow up. Five subjects of TTB2 group decreased and two increased their PTS respectively while four subjects of TTB3 group decreased and three subjects increased their PTS in TTB3 group.

Conclusions

This is the first study that used a quantitative structured assessment to describe change over time in TTB of ASD subjects. NO-TTB and TTB1 subgroups substantially maintained their condition at follow up. TTB2 and TTB3 subgroups showed a more variable behavior: some subjects decreasing TTB over time as commonly known, but some increasing TTB. This finding underlies the importance of a TTB sub-classification and a close monitoring with quantitative standardized protocols of TTB phenomenon.

Notes:

(1) School of Medicine and Surgery, University of Milan-Bicocca, Milano, Italy

(2) Autism Research Unit, Villa Santa Maria Foundation, Tavernerio, Italy

Background

In a previous study we have validated the use of the Short Sensory Profile (SSP) scale in Italy confirming the existence of sensory impairments in ASD subjects that is related to ASD severity, particularly expressed as under-responsiveness or seeking stimuli and an increased or decreased response to auditory stimuli. Since tip toe behavior (TTB) is likely to be related to sensorial disorders, it is interesting to assess how the sensorial pattern is different in ASD subjects with and without TTB, for which we developed a standardized protocol of the assessment.

Objectives

The aim of this study is to explore the sensory pattern of Severe ASD Subjects with or without TTB through a validated cross-cultural Italian adaptation of the SSP. Methods: We administered the Short Sensory Profile in a sample of 50 Italian ASD children (7 females; 43 males; mean age 13.9 years). We chose capable special education teachers who carefully and thoroughly reported the children’s behaviors. The ASD diagnosis was done using the DSM V criteria and was confirmed using the ADOS 2. The presence of Tip-Toe Behavior (TTB) was assessed using both direct observation as well as a structured checklist completed during the day by the main caregiver living with the subject through a standardized protocol.

Results

The SSP mean total score of the sample was 149.22 (range 119-182) evidencing the presence of sensory function impairment in our study group (the expected value ranges between 155 and 190). We also found a negative correlation values between ADOS CSS score and total SSP score (r= -0.38). The SSP mean total score of the TTB subgroup was 144.06 (median 142) while the SSP mean total score of the NON-TTB subgroup was 151.65 (median 152): both the TTB and NON-TTB subgroups mean total score ranged in the “probable difference” score. The mean total score values of the two subgroups were not significantly different according to the Mann-Whitney test.Comparing the mean score of SSP subscales between TTB and NONTTB subgroups using a Mann-Whitney test we found a significant lower score of TTB subgroup only in the “Underresponsive/Seeks sensation” section (p=0.027). Instead the “tactile sensitivity” section was in the “probable difference” score for both TTB and NON-TTB without significant subgroups difference . We also evidenced a significant inverse relationship between toe walking severity and “Under-responsive/Seeks sensation” score ( r= -0.31).

Conclusions

We confirm the existence of sensory impairment in ASD subjects related to ASD severity. TTB ASD subjects show a sensory function impairment when compared with normative values and a more severe sensory impairment in the “Underresponsive/Seeks sensation” section when compared with NON-TTB ASD subjects. This finding seems suggest that TTB subjects show this behavior as an high need of sensations instead of a tactile oversensitivity.

Notes:

(1) School of Medicine and Surgery, University of Milan-Bicocca, Milano, Italy

(2) Autism Research Unit, Villa Santa Maria Foundation, Tavernerio, Italy

Background

The function of the vertebral column is to support humans in upright positions, mechanically balance the stress of gravity, permit locomotion and assist in purposeful movements. The term “spinal deformity” includes conditions such as posttraumatic deformities, iper-kyphosis, iper-lordosis and idiopathic adolescent scoliosis. Severe spinal curvatures may be associated with adverse long-term health outcomes (e.g. pulmonary disorders, disability, back pain, psychological effects, and reduced quality of life). Early identification and effective treatment of mild scoliosis could slow or stop curvature progression before skeletal maturity, thereby improving long-term outcomes in adulthood. There is scientific evidence to support the value of spinal deformity screening in general population. This is true also for children with Autism Spectrum Disorder (ASD) for which untreated spinal deformity can interplay with impairments in fine and gross motor skills, motor planning, motor coordination and praxis.

Objectives

The aim of this systematic review is to critically describe the current knowledge on spinal deformities in ASD subjects in terms of prevalence, assessment methods and treatment.

Methods

The systematic review protocol was previously registered on the PROSPERO database (registration number CRD 42018100894). We conducted an extensive literature search in PubMed, CINAHL, PsycINFO, The Cochrane Library, and Scopus databases. We also considered grey literature sources such as: Opengray, Penn Libraries and International Society for Autism Research (INSAR) Congress archives. There were no restrictions on the types of study design eligible for inclusion, publication date or language. The main keywords used were: ASD, Autism, Autistic Disorder, Spinal deformities, Scoliosis and Spine.

Results

Following the PRISMA statement study selection process, we screened 2640 records after removing duplicates for eligibility. We found 11 eligible studies (figure 1). All of them were excluded because the main object was not pertinent to our aim. The main topics found were genetics, spinal surgery or surgery outcomes, since ASD is also used in the literature as the acronym for Adult Spine Deformity.

Conclusions

Spinal deformities appear to be an understudied topic within autism research. At present, in all the literature screened, there is no evidence on prevalence, assessment methodology and treatment of spinal deformities in ASD subjects. Since adolescent idiopathic scoliotic curves typically progress most rapidly during adolescent growth and clinical settings reveal it is possible to find developing ASD subjects presenting spinal deformities, it becomes relevant and important to conduct studies that verify the applicability of screening protocols in developing ASD subjects.

Notes:

(1) Autism Research Unit, Villa Santa Maria Foundation, Tavernerio, Italy

(2) School of Medicine and Surgery, University of Milan-Bicocca, Milano, Italy

Background

The term “spinal deformity” includes conditions such as post-traumatic deformities, iper-kyphosis, iper-lordosis and idiopathic adolescence scoliosis. Early identification and effective treatment of mild scoliosis could slow or stop curvature progression before skeletal maturity, thereby improving long-term outcomes in adulthood (US task force JAMA 2018). In a systematic review (PROSPERO registration number CRD 42018100894), we found that spinal deformities appear to be understudied within autism research and that no studies on spinal deformities assessment in ASD subjects exist. Since severe spinal deformities may be associated with adverse long-term health outcomes (e.g. pulmonary disorders, disability, back pain, psychological effects, and reduced quality of life), the value of spinal deformities screening becomes increasingly relevant.

Objectives

Our study aims to assess the applicability of a spinal deformities screening protocol in ASD subjects. 

Methods

The screening protocol included two tests: the “Adam Test”, measured with the Bunnell method for assessing the trunk asymmetry on the frontal plane, and the “Sagittal Index” as suggested by Zaina that gives a measure of spinal deformities on a sagittal plane. The Literature indicates that subjects who present “Adam Test” or “Sagittal Index” values above cut-off limits are in need of second level clinical assessment. We also considered the three ASD severity grades and the four intellectual disability (ID) categories (mild, moderate, severe and profound) as suggested by DSM-V.

Results

Sixty-one subjects (mean age 14.03 – SD 4.26; 55 males) were included in the study. Seven out of 61 subjects (11,5%) presented grade 1, 26 (42,6%) grade 2, and 28 (45,9%) grade 3 ASD severity. Three subjects (4,9%) exhibited mild ID, 22 (36,1%) moderate ID, 34 (55,7%) severe ID, and 2 (3,3%) profound ID. Despite the relatively high autism severity of our sample, we found the screening test applicable to 92% of our population. Five subjects were non-testable because of their behavioral difficulties; all of them had high ASD severity grades and moderate to severe ID. Using this protocol screening, we found 11 ASD subjects (18%) presenting abnormal values: three subjects (4,9%) with Adam’s test values over cut-off (>5°), and eight subjects (13,1%) with “Sagittal Index” values over the cut-off (>9,5 cm). Using a chi-square test, we found that subjects over the cut-off limits had higher ASD severity (p=0.039), and ID severity (p=0.002).

Conclusions

The screening protocol for spinal deformity is generally applicable in ASD, also in subjects with high ASD severity and severe ID. About 20% of ASD subjects present spinal deformities, a value in line to what described in the general population (15%-20% over cut off) therefore deserving special attention for eventual adverse long-term health outcomes. 

Notes:

(1) Autism Research Unit, Villa Santa Maria Foundation, Tavernerio, Italy

(2) Department of Health Sciences (DISSAL), Section of Biostatistics, University of Genoa, Genoa, Italy

(3) School of Medicine and Surgery, University of Milan-Bicocca, Milano, Italy

Background

The speed with which an individual is able to make a simple motor response to a perceived stimulus may fairly be regarded as a significant index to his basic level of perceptual-motor integration. Developmental studies on reaction time in subjects with a neurotypical (NT) development report a decrease in simple reaction time (SRT) with increasing age and a strong correlation between upper and lower limb simple reaction time tasks. No studies are available in this regard in Autism Spectrum Disorder (ASD) subjects.

Objectives

The aims of this study are: 1) to assess developmental changes in the speed of a simple reaction at the lower and upper limb in ASD children as they age; 2) to assess the correlation between upper and lower limbs SRT in ASD children; 3) to assess the correlation between lower limb SRT and ankle dorsiflexors muscles strength in ASD children; 4) to compare the results with the same data obtained in a sample of 243 NT subjects. 

Methods

The study sample included 12 ASD subjects (10 males; age range 5 -18 years). The ASD subjects were diagnosed with autism according to the DSM V criteria, confirmed through ADOS-2 and under observation at our Institute. SRT was measured in milliseconds using a hand-held electronic timer and a light as the stimulus and finger or foot lever to trigger responses. The testing of ankle dorsiflexion force was done using a footplate attached to a spring gauge. All the tests employed have been validated for the study of sensorimotor components of balance into the Fall Screen Assessment System.

Results

At variance with NT group we found no significant correlation between both upper and lower SRT and age in ASD study group (upper limb: R Pearson=-0.056, p=0.863; lower limb: R Pearson=-0.065, p=0.841) and no correlation between lower limb SRT and ankle dorsiflexors muscles strength. Instead, similarly to NT group a significant positive correlation between upper and lower limb reaction time tasks was found (ASD: R Pearson=0.819, p=0.001; NT: R Pearson=0.666; p=0.000).

Conclusions

This is the first study that analyses upper and lower limbs SRT developmental variability and its correlation with ankle strength performance in ASD subjects. The absence of a developmental improvement in SRT and the impairment in lower limb SRT tasks found in ASD subjects point out a disorder of sensorimotor integration in ASD subjects potentially responsible for postural control imbalance.

Notes:

(1) School of Medicine and Surgery, University of Milan-Bicocca, Milano, Italy

(2) Autism Research Unit, Villa Santa Maria Foundation, Tavernerio, Italy

Background

Reaction Time (RT) has been used as biomarker of cognitive performance and of trans-diagnostic phenotype in Autism Spectrum Disorders (ASD). It is also well known that RT is an important component of effective postural control and balance. In this regard few studies have examined the relationship between static and dynamic balance and Simple Reaction Time (SRT) in neurotypical (NT) children and adolescents. No studies are available in this regard in ASD subjects.

Objectives

The three aims of this study are: 1) to assess SRT in a ASD sample 2) then measure the correlation between lower limb SRT and sway tests (ST), maximal balance range test (MBRT) and coordinated stability test (CST) in ASD children; 3) to compare the results with the same data obtained in a sample of 243 NT subjects.

Methods

The study sample included 12 ASD subjects (10 males). The ASD subjects were diagnosed with autism according to the DSM V criteria, confirmed through ADOS-2 and under observation at our Institute. SRT was measured in milliseconds using a hand-held electronic timer and a light as the stimulus and the activation of a foot lever for responses. We conducted all the postural control tests using a sway meter that measures displacements of the body at waist level. ST is the evaluation of anterioposterior and mediolateral sway as the subject attempts to stand as still as possible for 30 seconds; ST was performed in four different conditions: on the floor with open- eyes, on floor with their eyes closed, on a foam rubber mat with open-eyes and on a foam rubber mat with their eyes closed. MBRT measures the maximum distance traveled from the total forward and backward excursion. CST is the evaluation of errors made by the subject in moving the pen of the sway meter on a predefined track. All the tests employed have been validated for the study of sensorimotor components of balance into the Fall Screen Assessment System.

Results

The mean age of ASD subjects was 11.67y (SD 4.08y; range 5-18y). Seven out of 12 ASD subjects (58,3%) showed SRT values above the Reference Intervals age related of NT children; four ASD subjects (33,3%) were in and those of 1 subject (8,3%) was lower. We found no significant correlations between SRT and ST values in all the four conditions and between SRT and both MBRT and CST values, while in the NT reference group there was a significant correlation between SRT and ST in 3 of 4 conditions. In the same group SRT performance significantly correlated also with MBRT (R Pearson=-0.245; p=0.000) and with CST (R Pearson=0.644; p=0.000).

Conclusions

This is the first study that analyses correlation between lower limb SRT and postural control performance in ASD subjects. In contrast with results obtained in NT subjects, lower limb SRT are not correlated with sway tests, MBRT and CST values. These findings confirm the presence of deficits of sensorimotor integration and therefore impairment in postural control in ASD children.

Notes:

(1) School of Medicine and Surgery, University of Milan-Bicocca, Milano, Italy

(2) Autism Research Unit, Villa Santa Maria Foundation, Tavernerio, Italy

Background

Stereotypies, despite their high frequency and strong diagnostic significance within autism, have not yet been fully elucidated due to their broad spectrum of presentation and pattern complexity. The VICTORY project (A Video Catalogue from Observational Retrospective Study on Stereotypies) a cross-sectional cohort study assessing presentation patterns, clinical Severity, and extinction modalities of stereotypies in autism, offers a new possibility to relate the complexity of stereotypies presentation to autism severity.

Objectives

The aim of this study is to assess the feasibility of predicting ASD severity in individual subjects from stereotypies patterns using innovative machine learning systems. This possibility would also enable further understanding as to which factors are significantly involved.

Methods

Twenty expert caregivers wearing a body cam recorded specific stereotypic behavior in a natural context during the everyday activities of 67 autistic subjects for 3 months of close follow-up. After a few minutes of recording, the possibility to interrupt their behavior by intervening physically to divert attention was recorded. A team consisting of one senior child neuropsychiatrist together with a senior psychologist reviewed all the video recordings (1868) selecting 780 of them as the most meaningful to summarize the whole spectrum in each individual within the given time window. Each video was classified according to components (motor, sensorial, vocal, intellective), complexity (2 classes, simple and complex), body parts involved, sensory channels involved (hearing, sight, proprioception, taste, pain, smell), extinction modality and basic demographic features. Ninetytwo variables were used to represent the input for preprocessing. The existence of a poor linear correlation among features of stereotypies patterns and ADOS score prompted us to use a machine learning system approach. An evolutionary algorithm (a TWIST system based on the KNN algorithm) was used to subdivide the dataset into training and testing sets as well as to select features yielding the maximum amount of information. After this pre-processing, 19 input variables were selected and different machine learning systems were used to develop a predictive model based on a training testing crossover procedure able to distinguish subject with an ADOS total score ranging from 8 to 20 from those with an ADOS total score ranging from 22 to 28.

Results

Acting on these inputs, the best supervised machine learning system(MLS) obtained a global accuracy of 84.96% (85.12% - sensitivity and 84.79 % -specificity) in predicting the ADOS score class. Most of the stereotypies features selected by the algorithm were complex, with 2 or 3 different components in the same pattern among motor, sensorial, intellectual and vocal. A semantic connectivity map based on fourth generation unsupervised MLS depicted the association among high severity ADOS class with stereotypies made-up of 3 different components.

Conclusions

Machine-learning systems show a promising potential in highlighting the complex relationship between stereotypies patterns and ASD severity.

Autism Research Unit, Villa Santa Maria Foundation, Tavernerio, Italy

Background

Aggressive behavior (AB) refers to directed acts of aggression that can potentially harm, or already have harmed others, themselves or destroyed property. Parents frequently report that aggression in their child is more distressing than poor adaptive skills. Most studies on this topic rely on the use of specific scales like the Children’s Scale for Hostility and Aggression.

Objectives

The aim of the study is to quantify the expression of AB in a cohort of subjects with ASD admitted to a Rehabilitation Institute by means of direct careful observation of their behavior for 28 consecutive days. To our knowledge, this is the first study to explore directly observed AB and to correlate its intensity with autism severity.

Methods

Twenty consecutive children and adolescents (mean age 15.15 yrs; range: 5-19; 19 males) with autism, admitted to our Institute took part to this observational study. The ASD subjects were diagnosed according to the DSM V criteria, then confirmed through ADOS 2. Ten expert female educators continuously monitored the subjects for 28 consecutive days recording the occurrence of the following AB: aggression of peers or educators by punching, kicking, boosts, biting, spitting, scratching; or selfinflicted injury with bites, scratches, punches to body or to head. The total sum of aggression and self-inflicted injury acts during the four weeks were taken as biomarkers of AB in the specific subject. These values were correlated with the ADOS total score and with the number of stereotypies patterns, derived from a video catalogue developed for a parallel specific study.

Results

Five out of 20 subjects (mean age 14.8 ) showed zero aggression acts during the study period. Their mean ADOS score was 21.2. Fifteen subjects showed from 2 to 31 acts of aggression (mean= 7.46 ) during the study period. Their mean ADOS score was 19.06. Eleven out of twenty subjects showed zero self-injury acts during the study period. Their mean ADOS score was 18.09. Nine subjects showed from 1 to 37 acts of self-injury (mean = 13.22) during the study period. Their mean ADOS score was 21.44.The Pearson correlation index between the four-week number of aggression acts and ADOS scores and between four-week number of self-injury acts and ADOS scores resulted in 0.06 (NS) and 0.80 ( p =0.009) respectively. In the same subgroups, the Pearson correlation index between the total number of aggression acts and the number of stereotypies patterns, and between the total number of self-injury acts and number of stereotypies patterns resulted in -0.24 ( NS ) and 0.74 ( P = 0.001) respectively.

Conclusions

Our pilot study suggest that while self-injury behavior is highly correlated to Autism severity and stereotypies intensity, aggression per se is not at all correlated to both autism severity and stereotypies intensity. Future studies with direct observation on larger samples are needed to explain the nature of this difference.

Autism Research Unit, Villa Santa Maria Foundation, Tavernerio, Italy

Notes:

1 Villa Santa Maria Foundation, Tavernerio (CO), Italy

2 School of Medicine and Surgery, University of Milano Bicocca, Milan, Italy 

Abstract: BACKGROUND 

Twenty-thirty percent of individuals with autism stand, and/or walk, and/or run on their tiptoes. To our knowledge, studies about quantitative assessment of Tip-toe behavior (TTB) are scarce relating to walking and running and absent relating to standing. In a previous cohort study, using a qualitative assessment we described three mutually exclusive clinical functional classes of TTB of increasing severity: TTB only during running (TTB1), TTB only during walking and running (TTB2) and TTB during standing, walking and running (TTB3). 

OBJECTIVES 

The aims of this cross-sectional cohort study are: 1) to quantify TTB during both a static and a dynamic test in our ASD sample; 2) to compare the intensity of TTB in the three TTB clinical functional classes and in the NO-TTB group. 

METHODS 

Our study sample included 45 ASD subjects (mean age: 13,15 years – 4,63 SD; 40 males) diagnosed according to the DSM V criteria and under observation at our Institute. The confirmation and the severity of autism was established through ADOS-2. A therapist assessed the presence/absence of TTB during standing, walking and running using direct observation and a structured interview of the main caregiver living with the child. According to this assessment, 25 ASD subjects resulted not TTB, 3 resulted in TTB class 1, 10 in TTB class 2 and 7 in TTB class 3. The intensity of TTB expression during static and dynamic tests was quantified as percentage of time spent on the tip toes and as the percentage of toe steps, respectively. Both tests were conducted using standardized video recordings reviewed independently by two expert therapists. 

RESULTS 

The overall ADOS calibrated severity score (CSS) of all the subjects was 7.56 (1.71 SD). The overall ADOS CCS was 6,92 (1,55 SD) in NO-TTB, 8,15 (1,73 SD) in TTB1+2 and 8,71 (1,38 SD) in TTB3 (p = 0.02). The TTB time percentage values of the NO-TTB group during the static quantitative test was 0.25% (0.37 SD), while the time percentage values of the TTB1+2 was 1,82% (2,82 SD) vs 32,34% (31,82 SD) in TTB3 (table 1). We found a significant difference between each of the 3 groups (p < 0,02). In the NO-TTB group, during the dynamic quantitative test, the mean percentage of the TTB steps was 0.66% (1.48 SD), while it was 7,91% (5,71 SD) in TTB1+2 vs 60,93% (28,29 SD) in TTB3 (table 1). We found a significant difference between each of the 3 groups (p= 0.000) (fig. 1). Moreover, we found a significant correlation (r = 0.702) between the quantity of TTB in the static and the dynamic test. Finally, we also found a significant correlation between the severity of TTB during both the static and the dynamic tests and the ADOS-2 CSS (r = 0.305 and r = 0.406 respectively). 

CONCLUSIONS 

We quantified TTB using a new structured static and dynamic assessment test in our ASD sample. We found significant difference between NO-TTB and the 2 TTB subgroups. The TTB quantity in the static test is correlated with TTB quantity in the dynamic test.

Notes: * Autism Research Unit, Villa Santa Maria, Tavernerio (Como), Italy ** University of Genoa

Abstract: BACKGROUND 

Evaluating treatments outcome in children with low-functioning autistic disorder requires the utilization of specific but manageable instruments, both for patients and for their environment (parents, educators, doctors). Few studies so far have focused how use multidimensional data for outcome assessment in residential health settings. 

OBJECTIVE 

The aim of this study is to highlight the possible outcome prediction of personalized plans of intervention for low-functioning ASD subjects using innovative machine learning systems enabling also to understand which treatment factors are significantly involved. 

METHODS 

In this pilot observational study, twelve consecutive new patients with low-functioning autism (range of age 3-13 years) have been enrolled between November 2015 and October 2016. Four complementary assessment instruments (Vineland Adaptive Behavior Scales, a 540-item questionnaire which evaluate personal and social autonomy, communication and motoric competences; SDQ-Strenghts and Difficulties Questionnaire-, a 25-item questionnaire useful to screen emotional, behavioral and social problems in children aged 4-16 years; The HoNOSCA-Health of Nation Outcome Scale for Children and Adolescents-, a 15-item clinical assessment scale used as part of the routine outcome monitoring in mental health services, which measures global functioning in patients aged 3-18 years through 4 different areas: behavioral, impairment, symptoms, social functioning; DC-GAS -Disability Child Global Assessment Scale-, a dimensional scale used by the clinician to evaluate global functioning in disabled children and adolescents, have been used at the patients first access in the neuropsychiatric clinic and after 6 months of intensive personalized treatment. Vineland Scales and SDQ questionnaire have been completed by educators and parents; HoNOSCA and DC-GAS have been completed by the clinician. 

The most important outcome measure has been individuated in the DC-GAS total score, in particular considering differences between baseline evaluation (T1) and the assessment after 6 months (T2). Ninety four variables related to demographic, familiar, therapeutic, pharmacological, medical and checkup information have been used to represent the input for preprocessing. An evolutionary algorithm (a TWIST system based on KNN algorithm) has been used to subdivide the dataset into training and testing set and select features yielding the maximal amount of information. After this pre-processing, 21 input variables were selected and different machine learning systems have been used to develop a predictive model based on a training testing crossover procedure. 

RESULTS 

Eight out of twelve subjects have shown an improved global functioning at the end of the follow-up. The best machine learning system (three-layers feed- forward neural network with 8 hidden nodes) obtained a global accuracy of 83.3% ( 91.7 % sensitivity and 75% specificity ) with a ROC of 0.89. The variables selected for the predictive model included previous pharmacological and non-pharmacological treatments, actual treatment plan, and baseline scores of different subscales of Vineland, SDQ, HoNOSCA and DC-GAS. 

CONCLUSION 

Machine learning systems shows a promising potential in predicting the outcome of personalized multidimensional interventions in low-functioning ASD subjects. Accurate data collection, considering multidimensional aspects, and the use of a complex and complete statistical analysis, as the machine learning systems, could be useful in order to highlight predictable positive treatment factors. 

Abstract: BACKGROUND 

According to the literature, about one fourth of individuals with ASD present with toe walking. In a previous study, we found that this behavior is present not only during walking but also while standing and running, and described three mutually exclusive clinical functional classes with a different degree of severity: TTB during running (TTB1), TTB during walking and running (TTB2) and TTB during standing, walking and running (TTB3). In another study we also found a positive relationship between the presence and severity of TTB and the Achilles’s tendon shortening in ASD subjects. In this perspective, assessing and monitoring TTB in ASD subjects could become critical to identify ASD subjects at risk of developing muscle shortening. Moreover, to our knowledge in the literature systematic observations of the natural history of Tip-toe Behavior (TTB) in ASD children using standardized assessment are lacking. 

OBJECTIVES 

The aim of this prospective cohort study is to describe the natural history of TTB and NO-TTB ASD subjects at short-medium term. 

METHODS 

The prospective study included 72 consecutive subjects (62 males; mean age: 15,68 years – SD 3,85) present in our Institute. The inclusion criteria were: an ASD diagnosis according to the DSM V criteria, a diagnosis confirmation based on the ADOS–2. The exclusion criteria were: presence of co-morbid diagnoses that would have an impact on gait. The assessment of presence/absence of TTB during standing, walking and running was done through direct observation and a structured interview of the main caregiver living with the child. We repeated the same evaluation 12 to 44 During months (mean: 29,88 months – SD 8,86; median: 34,5 months) after the first observation. 

RESULTS 

During the first TTB assessment 49 subjects resulted Non-TTB (68,1%) and 23 resulted TTB. In TTB group, 4 subjects were TTB1, 9 subjects were TTB2 and 10 subjects were TTB3. At follow up 7 out of 23 TTB subjects (30%) changed the severity class, 5 decreasing and 2 increasing severity (table 1). No one shifted to NO-TTB group. In NO-TTB group 8 subjects (16%) shifted to TTB group (5 in TTB 1 class, 2 in TTB 2 class and 1 in TTB class 3. The ADOS calibrated severity score of the converters was not different from non-converters (7,5 – 1,4 SD versus 7,56 – 1,74 SD). 

CONCLUSION 

TTB behavior can change over time in ASD subjects. In an average time of two years about one third of TTB subjects change their severity class and 16% of Non-TTB subjects become TTB. This finding underlies the importance of close monitoring of TTB with standardized protocols. 

Abstract: BACKGROUND 

In addition to the core symptoms, both fine and gross motor delays/disorders have been reported in children with Autism Spectrum Disorders (ASD). However, it is still unclear whether motor impairments are uniformly distributed across the entire ASD spectrum and whether they are related to DSM-5 specifiers (i.e. intelligence, language, comorbidity and associated conditions). In the light of the high heterogeneity in ASD it could be possible that “a single symptom approach analysis” do not provide comprehensive information. The strong inherent non-linearity of the relationships between clinical variables may account for the inability to grasp the core problem by the traditional analysis. Artificial neural networks (ANNs) are computational adaptive systems particularly adapting to solving non-linear problems. The goal of this data mining model is to discover hidden trends and associations among variables. Recently this approach has been successfully applied to the ASD field. 

OBJECTIVES 

To investigate associations between motor skills and clinical/developmental features in preschoolers with ASD. We hypothesized that ANNs will be able to find hidden trends among the variables revealing the clinical profiles related to motor functioning in ASD. 

METHODS 

This study was carried out according to the standards for good ethical practice of the IRCCS Stella Maris Foundation and in accordance with the guidelines of the Declaration of Helsinki. 

32 male with ASD (age range: 30-60 months; nonverbal IQ ≥ 70) were recruited at the IRCCS Stella Maris Foundation, a tertiary care university hospital. Multidisciplinary comprehensive diagnostic evaluation was associated with a standardized assessment battery for motor skills, the Peabody Developmental Motor Scale- Second Edition (PDMS-2). The PDMS-2 consists of six motor subscales (Reflexes, Stationary, Locomotion, Object Manipulation, Grasping and Visual-Motor Integration) and three motor quotients (MQ) (Gross MQ, Fine MQ, Total MQ). According to PDMS-2, motor skills were classified into 7 categories: very superior, superior, above average, average, below average, poor and very poor. 

Analyses were performed through the Auto Contractive Map system which is a fourth-generation unsupervised ANNs. Auto Contractive Map system ‘spatializes’ the correlation among variables (‘closeness’) providing a graph that identifies the relevant associations and organizes them into a coherent picture. 

RESULTS 

Preliminary linear correlation analysis revealed that motor impairment was associated with both cognitive skills and repetitive behaviors in children with ASD (Table 1). The ANNs analysis (Figure 1) shows that motor disorders appeared to be strongly related to low level of expressive language and high level of repetitive behaviors in preschoolers with ASD. In addition, the ANNs approach consider the entire spectrum of relationship among clinical variables, revealing hidden trends among motor, cognitive and social skills. 

CONCLUSIONS 

The ANNs approach revealed motor skills as moderators of ASD core symptoms. This appears to be consistent with the growing literature suggesting that the systematic observation of motor development in ASD may improve the knowledge about clinical and neurobiological involvement as well as guide development of treatments. 

ACKNOWLEDGMENTS 

This work has been partially supported by the European Community's Horizon 2020 Program under grant agreement n. 642996 (BRAINVIEW) and by the Italian Minister of Health Network Project 'Italian Autism Spectrum Disorders Network: filling the gaps in the National Health System Care' (NET 2013-02355263) 

Notes: * IRCCS Stella Maris Foundation, Viale del Tirreno 331, Pisa, 56018, Calambrone, Italy ** Autism Research Unit, Villa Santa Maria Institute, Italy, Via IV novembre 22038 Tavernerio (Co), Italy *** Department of Clinical and Experimental Medicine, University of Pisa, Pisa, 56100, Italy

Abstract: BACKGROUND 

In a previous study the authors have shown the ability of a novel kind of Machine Learning System(MLS) named MS-ROM/I-FAST developed by The Semeion Research Institute in Rome to extract interesting features in computerized EEG that allow an almost perfectly distinction of ASD children from typically developing ones. The proof of concept study, published in 2017 in Computer Method and Programs in Biomedicine showed accuracy values near to 100% using training-testing protocol and to 84% - 92.8% using Leave One Out protocol. The similarities among the MLS weight matrixes measured with apposite algorithms were not affected by the age of the subjects suggesting that the MLS do not read age-related EEG patterns, but rather invariant features related to the brain’s underlying abnormalities. 

AIM OF THE STUDY 

The aim of the study is to assess how effectively this methodology distinguishes ADS subjects from children affected with other neuro-psychiatric disorders . 

METHODS 

Twenty definite ASD subjects and twenty subjects with neuropsychiatric disorders matched for age and gender distribution observed at Tarnow Center for Self-Management, Huston (US) were included in the study. The two groups had the same age range ( 4-14 yrs) and male/female ratio (14/6). ASD patients received independent Autism diagnoses according to DSM-V criteria, subsequently confirmed by a qualified psychiatrist using the ADOS scale. No autistic child was affected by genetic conditions and/or cerebral malformations documented by neuroimaging and epilepsy. In the comparison group the range of primary diagnoses was the following: Attention-Deficit Disorder ( N= 13), Disorder of social functioning( N=3), Anxiety disorders( N= 2), Major depressive disorder(N= 1), Specific developmental disorders of scholastic skills(N=1) 

A continuous segment of artefact-free EEG data lasting 10 minutes in ASCCI format was used to compute multi-scale entropy values and for subsequent analyses. 

A Multi-scale ranked organizing map (MS-ROM), based on the self-organizing map (SOM) neural network, coupled with the TWIST system (an evolutionary system able to select predictive features) created an invariant features vector input of EEG on which supervised machine learning systems acted as blind classifiers. 

RESULTS 

After MS-ROM/I-FAST preprocessing, twelve features were extracted representing the EEG signature. Acting on these features the overall predictive capability of different machine learning systems in deciphering autistic cases from other NP disorders ranged between 93% and 97.5% (Table 1). These results were obtained at different times in separate experiments performed on the same training and testing subsets. The similarities among the ANN weight matrixes measured with apposite algorithms were not affected by the age of the subjects. 

CONCLUSION 

This study demonstrates the value of EEG processing with advanced MLS in the differential diagnosis between ASD and other NP disorders confirming therefore the existence of a specific EEG signature in ASD. 

Notes: * Villa Santa Maria Institute, Neuropsychiatric Rehabilitation Center, Autism Unit, Tavernerio (Como), Italy ** Semeion Research Centre of Sciences of Communication Via Sersale 117, Rome, 00128, Italy *** Tarnow Center for Self-Management, 1001 West Loop South, Suite 215, Houston, TX 77027, USA

Abstract: BACKGROUND 

Stereotypies, despite their high frequency and strong diagnostic significance within autism, have not yet been fully elucidated due to their broad spectrum of presentation and pattern complexity. Standardized video-recordings can help to depict the complex pattern of stereotypies commonly observed in autism, thus allowing for a better definition of major phenotypes. 

AIM 

The aim of this study is to analyze stereotypies patterns observed in a sample of children and adolescents residing at our Institute and subsequently classify them by means of video-recordings. 

METHODS 

20 expert caregiver wearing a body cam recorded specific stereotypic behavior in a natural context during the everyday activities of 67 autistic subjects for 3 months of close follow-up. After a few minutes of recording, the possibility to interrupt their behavior by intervening physically to divert attention was registered. 

A team consisting of a senior child neuro-psychiatrist and a senior psychologist reviewed all the video recordings (1868) selecting 780 of them as the most meaningful to summarize the whole spectrum in each individual in the given time window. Each video was classified according to components (motor, sensorial, vocal, intellective), complexity (2 classes, simple and complex), body parts involved (n=18) and sensory channels involved (hearing, sight, proprioception, taste, pain, smell). 

RESULTS 

The vast majority ( 87%) of the780 patterns occurred several times generally (73%) in a state of tranquility. 

In more than half of cases (53.4%), the interruption required intervening physically, but a poor correlation was found between the pattern type and possibility to interrupt the behavior by way of verbal or physical intervention ( r= -0.08/+0.08). 

The individual stereotypies spectrum ranged from 1 to 33 different patterns (average= 11.6; S.D= 6.82). The most frequent pattern was represented by the combination of simple motor and sensorial components ( accounting for 23% of the total number) followed by simple motor and simple sensorial (9% and 8% respectively). The other 47 patterns with combinations from 1 to 4 components accounted for the remaining 60%. 

In the 569 patterns containing motor components, whole body and arms movements constituted the most frequent body parts involved (41% e 38% respectively) followed by mouth and hands (10% and 9.8% respectively). 

In the 531 patterns containing sensorial components, the most frequent channel involved was tactile (50%) followed by proprioceptive( 34%) and acoustic (19.5%). 

Most of the 127 stereotypies with vocal components were constituted by simple vocalizations, 85.8% and only 14.2% by phonemes or words. 

CONCLUSIONS 

This study represents a first attempt to systematically document the patterns of expression of stereotyped behavior in a cohort of autistic subjects closely followed by professional educators. 

Open access to this video bank and to the clinical data will be allowed to interested researchers , with the aim of improving the comprehension of this complex phenomenon and its correlation with clinical and demographic features.

Abstract: BACKGROUND 

Kindergarten is a privileged opportunity to observe children’s behavior in a natural context. This possibility allows for detecting signs of derangement in motor and neuropsychological development not otherwise previously observed. 

Our group has developed a standardized protocol with a checklist containing over 284 items for carefully detecting delay in the acquisition of a given capacity according to age related international developmental nomograms. 

OBJECTIVES 

The aim of this study is to assess the feasibility and effectiveness in the screening of ASD by simply observing child behavior while at Kindergarten. 

METHODS 

The protocol included two different tests: 

- The Denver Developmental Screening Test (Denver test)is a 41 item test for screening development of infants and preschool-aged children; items cover four general functions: personal social (e.g. smiling), fine motor adaptive (e.g. grasping and drawing), language (e.g. combining words), and gross motor (e.g. walking). Test age range 0-6. 

- The Adaptive Behavior Assessment System – Second edition (ABAS – II) containing 216 items is a global and normative assessment scale of behavior that measures daily life skills. The project protocol provides for teacher/caregivers questionnaires regarding subjects aged 2-5. It investigates 10 adaptive areas: Communication, Preschool/School skills, self-Control, Playing/leisure, Socializing, Self-Care, Home Care/School, Environmental Use, Health and Safety, Work. 

Expert psychomotor and education therapists with the supervision of a senior neuro-pediatrician (MN), observed and interacted with 62 children, aged 36 - 65 months, attending the “Istituto Comprensivo Don Milani” in Tavernerio (Como, Italy) during two sessions and after obtaining written informed consent. 

Seven out of 62 children were found to be affected by neuro-psychiatric disorders (ASD; Down syndrome; delay of psychomotor development; Cerebral Palsy; developmental disorder; hyperactivity) 

Our staff was pleasantly accepted in the classroom and was able to collect all the information required. The school teachers learned basic skills to heighten their observation capabilities in child behavior as a result of interacting with our professional staff. 

RESULTS 

In the 55 children without previous diagnoses of neuro-psychiatric disorders, the application of the Denver test and ABAS scales pointed out the presence of 7 and 12 cases respectively with at least one (range 1 - 6) item not corresponding to chronological age. The integration of this information with the experience and skills of our staff resulted in the recognition of possible undetected developmental disorders and the subsequent invitation to parents to bring the children in question to a neurodevelopmental diagnostic unit. 

In one of these cases, an Autism Spectrum Disorder (ASD) diagnosis was made. 

In one of two other cases, parents did not continue with the diagnosis, in the other, a pediatric psychiatrist did not confirm the presence of language developmental delay (table 1). 

CONCLUSIONS 

This experience shows that structured external observation in a kindergarten is a feasible and promising approach for the screening and the early detection of neurodevelopmental disorders. ABAS II seems to provide increased sensitivity in detecting suspicious cases.