Attività scientifica

Contributi a congressi internazionali

Titolo: Spinal deformities and autism spectrum disorders: a systematic review (2019)

Autore: Luca Trentin1, Giulio Valagussa1,2 Enzo Grossi1

Info: Submitted at WCPT (World Confederation of Physical Therapy) Congress 2019, Geneva, Switzerland, 10-13 May

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abstract

Notes:

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

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

Titolo: Postural function related to body sway test in ASD subjects: comparison with normative age-matched values (2019)

Autore: Giulio Valagussa 1,2, Valentina Gariboldi 2, Luca Trentin 1, Cesare Cerri 2, Miriam Mazzucchelli 2, Cecilia Perin 2, Enzo Grossi 1

Info: Submitted at WCPT (World Confederation of Physical Therapy) Congress 2019, Geneva, Switzerland, 10-13 May

url

abstract

Notes:

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

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

Titolo: Quantitative Assessment of Tip-toe Behavior in Autism Spectrum Disorder Subjects: a Cross-Sectional Cohort Study (2018)

Autore: Giulio Valagussa, Valeria Balatti, Luca Trentin, Alessio Signori, Enzo Grossi

Info: Accepted at INSAR 2018

abstract

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

 

Titolo: Outcome Evaluation of Personalized Multidimensional Interventions on Children with Low-Functioning ASD through an Innovative Machine Learning System: a Proof of Concept Study (2018)

Autore: Katiusha Hall, Enzo Grossi - Autism Research Unit, Villa Santa Maria Institute, Tavernerio (Como), Italy

Info: Accepted at INSAR 2018

abstract

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. 

Titolo: Tip-Toe Behavior in Autism Spectrum Disorder: a Prospective Cohort Study (2018)

Autore: Giulio Valagussa, Valeria Balatti, Luca Trentin, Enzo Grossi - Autism Research Unit, Villa Santa Maria, Tavernerio (Como), Italy

Info: Accepted at INSAR 2018

abstract

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. 

Titolo: Motor Skills as Moderators of ASD Core Symptoms: Insights from the Artificial Networks Approach (2018)

Autore: Francesca Fulceri*, Enzo Grossi**, Annarita Contaldo*, Antonio Narzisi*, Sara Calderoni*, ***, Fabio Apicella*, Ilaria Parrini*, Raffaella Tancredi*, Filippo Muratori*. ***

Info: Accepted at INSAR 2018

abstract

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

 

Titolo: EEG Data Processed by Advanced Machine Learning Systems Allow an Accurate Differential Diagnosis Between ASD Children and Children with Other Neuro-Psychiatric Disorders (2018)

Autore: Enzo Grossi*, Massimo Buscema**, Ronald J. Swatzyna***

Info: Accepted at INSAR 2018

abstract

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

Titolo: Stereotypies in Autism: the Construction of a Large Video Catalogue from a Cohort Study (2018)

Autore: Elisa Caminada, Franco Vanzulli, Beatrice Vescovo, Emanuela Alfiedi, Enzo Grossi - Autism Research Unit, Villa Santa Maria, Tavernerio (Como), Italy

Info: Accepted at INSAR 2018

abstract

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.

 

Titolo: Detection of Ignored Autism Spectrum Disorder by Simple External Observation in Kindergarten: a Proof of Concept Study (2018)

Autore: Eleonora Castagna, Rita Pirovano, Antonia Castelnuovo, Emanuela Alfiedi, Giulia Lanzi, Francesca Bernasconi, Marina Norsi, Enzo Grossi

Info: Accepted at INSAR 2018

abstract

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.

Titolo: Pregnancy Risk Factors in Autism: a Sibling Matched Case-Control Study in Italy (2017)

Autore: Lucia Migliore, Angela Lopomo, Antonio Narzisi, Filippo Muratori, Fabio Coppedè, Enzo Grossi

Info: Accepted at 10th DOHaD - Developmental Origin of Health and Disease - World Congress, Rotterdam, 15-18 October

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abstract

Background Autism Spectrum Disorder (ASD) is a multi-factorial disease, where a single risk factor unlikely can provide comprehensive information. Recent epidemiological studies have pointed out a number of pregnancy and peri-post natal factors which, contributing to focal brain inflammation, predispose to ASD development. In a previous study we have shown a significantly higher prevalence of six potential risk factors in autistic group in comparison with external control group. Objective The aim of this study was to assess the frequency of 12 potential environmental risk factors derived from a careful interview about pregnancy and peri/post history of mothers having had both one child with autism and one or two typically developing siblings observed in two Institutions in Italy adopting the same protocol. Methods The clinical sample included a cases group of 35 autistic children and adolescents (mean age 8.22, S.D. 6.35) compared to an internal control group formed by 42 siblings (mean age 8.98 years, S.D. 6.66). It is important to note that the latter group represented all the siblings available. Mothers of autistic children who met the inclusion criteria were invited to an individual structured interview about early risk factors in separate sessions (two or three) each dedicated to a specific pregnancy after having signed an informed consent. The first interview was always dedicated to the child with the disorder. Twelve risk factors were taken into account: solvents/paints exposure during pregnancy; living in apartments with PCV flooring; drinking tap water during pregnancy; pregnancy complications; dystocic delivery; cesarean delivery; perinatal complications; low gestational age at delivery; no breast feeding; child early antibiotic therapy; number of life stressful events during pregnancy; use of pharmaceutical drugs during pregnancy Results A higher prevalence of environmental risk factors was observed in 11 out of 12 risk factors in autistic group in comparison with siblings control group (sign test: p< 0.003). For seven of them the odds ratio was higher than 1.5 ( table 1): Solvents-paints exposure/pregnancy (OR 2.56); drinking tap water (OR 2.19); pregnancy complications (OR 1.81); cesarean delivery ( 2.75) perinatal complications (OR 1.94); low gestational age (OR 1.96) and early antibiotic treatment after delivery(OR 2.03). Conclusions Pregnancies related to autism development show a different pattern of pregnancy risk factors in the same mother, with an higher prevalence in 11 out of 12 of them. This suggest that environmental and incidental phenomena can influence pregnancy outcome in predisposed subjects.

Titolo: Assessing social, behavioral and emotional functioning in children: a feasibility pilot study (2017)

Autore: Katiusha Hall, Enzo Grossi, Laura Reale, Maurizio Bonati

Info: Accepted at IMFAR 2017

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abstract

Background The clinical assessment of global functioning in children with autism is essential in order to identify needs and to arrange therapeutic and educational interventions. Appropriateness of using rapid and cost-effective instruments, as the Strengths and Difficulties Questionnaire (SDQ) and the Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA), needs further evaluation and definition, in particular in children with low-functioning autism. Objective Through a pilot observational study to describe the trend in different areas (behavior, socialization, emotions) using SDQ and HoNOSCA, and to explore correlation pathways between the two instruments, thus to plan an adequate and wide collaborative study. Methods Ten consecutive new patients with low-functioning autism (age 5-14 years) were enrolled between November 2015 and October 2016. The SDQ is a 25-item questionnaire useful to screen emotional, behavioral and social problems in children aged 4-16 years. Scores for the 5 subscales (emotional symptoms, conduct problems, hyperactivity/inattention, peer problems and prosocial behavior) are classified in “normal”, “borderline” and “abnormal” ranges, according to the original cut-offs. The HoNOSCA is a 15-item clinical assessment scale used as part of the routine outcome monitoring in mental health services, especially in Netherlands, UK, Australia and New Zealand, which measures global functioning in patients aged 3-18 years through 4 different areas: behavioral, impairment, symptoms, social functioning. The SDQ completed by the educators was compared to the results of the global functioning evaluation of the clinician, who has used the HoNOSCA scale. A single psychologist of the children completed the HoNOSCA questionnaire. Associations have been assessed with Pearson linear correlation index and minimum spanning tree algorithm. Results The SDQ subscales with abnormal mean scores were “peer relations” (mean: 5.8, SD: 1.03) and “pro-sociality” (mean: 1.4, SD: 1.4), while in the HoNOSCA the social functioning domain resulted as the most problematic area. Linear correlation matrix between the items of the two instruments showed interesting values of r- index between behavioral score of HoNOSCA and both emotional difficulties (r = 0.71, p 0.02) and peer relationships of SDQ (r = 0.55, p = 0.09), and between social functioning score of HoNOSCA and behavioral problems of SDQ (r = 0.52, p = 0.12). These association were also confirmed by a map projection using the minimum spanning tree method. Conclusions The correlation between SDQ and HoNOSCA can be a simple and efficient way to screen for emotional disorders and behavioral problems in child and adolescents with low-functioning autism. It could help to recognize co-occurring disorders and reduce with appropriate interventions their impact on social functioning and peer relationship domains. However, further more systematic attempts at validation are warranted.

Titolo: Italian cross-cultural adaptation of the Short Sensory Profile (2017)

Autore: Alessandra Nale, Rita Pirovano, Giulio Valagussa, Enzo Grossi - Autism Research Unit, Villa Santa Maria, Tavernerio (Como), Italy

Info: Accepted at IMFAR 2017

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abstract

Background Autism is a neurodevelopmental disorder characterized by widespread abnormalities of reciprocal social interactions and communication, as well as severely restricted interests and highly repetitive behavior. Sensory processing problems are reported in children with autism spectrum disorders and are included in the diagnosis of autism in the latest Diagnostic and Statistical Manual of Mental Disorders (DSM-5). One of the most useful tools to assess sensory characteristics in ASD individuals is the Short Sensory Profile (SSP), but no Italian version of this instrument is currently available. Objectives The aim of this study is to validate an Italian cross-cultural adaptation of the Short Sensory Profile. Methods Following the guidelines for the process of cross-cultural adaptation of self-report measures (Beaton et al., 2000) we did a translation of the process (two independent translators) followed by a back-up translation (two independent translators) and a final review in which full agreement was reached by the study team. We also did a pilot study to apply the SSP in a sample of 46 Italian ASD individuals (7 females; 39 males; mean age 163.5 months – SD 34.3 months, range: 87 – 226 months). The ASD diagnosis was done using the DSM V criteria, and it was confirmed using the ADOS 2. We chose capable special education teachers who carefully and fully reported their behaviors. Results The SSP mean total score of the sample was 147.65 (range 119-176) pointing out the presence of sensory function impairment (the expected value ranges between 155 and 190). Thirty-two percent (N = 15) of the participants obtained a typical performance total score (range 155-190), 30.4% (N = 14) obtained a probable difference score (range 142-154), and 37% (N = 17) obtained a definite difference score (range 38-141). The sensory function impairment resulted particularly severe in two of the Scale sections (table 1): “Underresponsive/Seeks Sensation” (8.7% belonging to typical performance score, 26.1% belonging to probable difference score, 65.2% belonging to definite difference score) and “Auditory Filtering” (17.4% belonging to typical performance score, 39.1% belonging to probable difference score, 43.5% belonging to definite difference score). The section “Low energy / Weak” has a total mean score in the range of probable difference (58.7% belonging to typical performance score, 2.2% belonging to probable difference score, 39.1% belonging to definite difference score). The others sections (“Tactile sensitivity”, “Taste/Smell Sensitivity”, “Movement Sensitivity”, and “Visual Auditory Sensitivity”) have a mean score in the range of typical performance (table 1). Conclusion The Short Sensory Profile scale is now validated for use in Italy. The performance of the scales are in line with findings observed in the SSP literature. We confirm the existence of sensory impairments in ASD, particularly expressed as under-responsiveness or seeking stimuli and an increased or decreased response to auditory stimuli.

Titolo: Postural Control assessment in ASD individuals using the Pediatric Balance Scale and the Fall Screen Assessment System: Results from a pilot study (2017)

Autore: Giulio Valagussa, Erica Terragni, Luca Trentin, Davide Mauri, Valentina Gariboldi, Cecilia Perin, Cesare Cerri, Enzo Grossi

Info: Accepted at IMFAR 2017

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Background: Individuals with ASD have impairments in fine and gross motor skills, motor planning, motor coordination and praxis. A key sensorimotor control process affected by ASD is the management of upright standing. The maintenance of balance depends on the interaction of multiple sensory, motor and integrative systems (i.e. vestibular function, vision, peripheral sensation, muscle force and reaction time). A marked deficit in any one of these factors or a combination of mild impairments in multiple physiological domains may increase the risk of falling. Few studies on this topic are available in the literature and most of them have used just force platform instrumental approaches, neglecting the assessment of different balance components. Objectives The aims of this pilot study are: 1) to assess balance in a group of ASD subjects using the Pediatric Balance Scale (PBS), comparing the results with normative values; 2) to assess balance in the same sample, using the Fall Screen Assessment System (FSAS), comparing the results with a control group of normally developing children. Methods The study sample included nine ASD individuals and sixteen healthy age matched subjects. The ASD subjects were diagnosed with Autism according to the DSM V criteria, confirmed through ADOS 2 and under observation at our Institute. We employed: a) FSAS, a multi-item scale internationally validated in adult subjects, exploring sensorial and motor performances; b) PBS, a multi-item functional assessment tool exploring functional balance in the context of everyday tasks, commonly used in children and adolescents. Results: The two groups resulted homogeneous as regards age distribution (ASD group mean age 12.2 years - 4.29 SD vs control group mean age 12.8 years - 3.8 SD). We found that five (56%) ASD subjects showed a balance deficit as detected by the PBS (scores below the normality cut-off ) and were also positive for the FSAS. Two more subjects were found at risk of falling only by FSAS. FSAS was easily applicable to children and adolescents and showed a statistically significant difference (p = <0.05) between the two groups in the following tests: visual contrast sensitivity, touch sensitivity, ankle dorsiflexion force, knee extension and flexion force, reaction time for hand, and all postural sway tests (table 1), thus evidencing an overall postural control impairment in ASD. Conclusion: This study confirms that ASD individuals are at major risk of falling in everyday life. This is attributable to an altered integration and elaboration of sensory and motor information. FSAS integrates the information derived from standard clinical assessment, and can be suggested as a complementary tool in the management of ASD. Moreover, by directly assessing an individual’s physiological abilities, intervention strategies can be implemented to target areas of deficit. Further studies are necessary to confirm the results of this pilot study.

Titolo: Natural history of Tiptoe behavior in ASD subjects (2017)

Autore: Giulio Valagussa, Valeria Balatti, Luca Trentin, Enzo Grossi - Autism Research Unit, Villa Santa Maria, Tavernerio (Como), Italy

Info: Accepted at IMFAR 2017

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Background The literature confirms that 20-30% of individuals with autism walk on their tiptoes. In a previous study, we found that this behavior transpires not only during walking but also while standing and running, and described three mutually exclusive clinical functional classes. To our knowledge, systematic observations about the natural history of Tiptoe Behavior (TTB) in ASD children in the literature are scarce. Specifically, it is not known if TTB parallels the acquisition of standing, walking and running milestones or appears later on and if these milestones (using the criteria suggested by Dosman and Dedrick) are delayed compared to normally developing peers. Objectives The aims of this retrospective study are: 1) to observe if TTB was exhibited simultaneously or subsequently to the acquisition of standing, walking and running milestones; 2) to describe, in those diagnosed subsequently, when TTB ASD subjects started to stand, walk and run compared to both normal population and non-TTB ASD subjects. Methods Our study sample included 36 ASD subjects (34 males; mean age: 14.3 years) diagnosed with Autism according to the DSM V criteria, confirmed through ADOS 2 and under observation at our Institute. We asked all the subjects’ parents to answer a structured interview. We collected information about standing, walking and running milestones. We also asked if and when TTB was observed and when it eventually stopped. Another therapist confirmed the presence of TTB using a standardized method we described in a previous study. Results We found that 18 subjects (50%) never showed TTB, 13 TTB subjects (36%) present TTB at least in one of three previous described situations, while 5 subjects (14%) had TTB in the past but it later stopped. The mean age of standing acquisition of the ASD sample resulted in line with the normative values, without significant differences between TTB and non-TTB subjects (table 1). The mean age of walking acquisition of the ASD sample resulted higher compared to the normative value (16.4 months (9-30 range) vs 12 months (9-18 range) respectively) without significant differences between TTB and non-TTB subjects. The mean age of running acquisition in the ASD sample resulted higher compared to the normative value (26.55 months ( 12-72 range) vs 15 months (13-20 range)) without significant differences between TTB and non-TTB subjects (absolute difference in favor of non-TTB). We observed that Tip-toe behavior in TTB subjects started significantly later than the acquisition of standing and walking milestone (table 2). Conversely, there was no significant difference between running acquisition and the start of TTB while running. Conclusions: TTB subjects exhibit this behavior significantly later to the acquisition of standing and walking milestones while there is no significant difference between running acquisition and the start of TTB while running. No significant difference in the age of acquisition of standing, walking and running milestones between TTB and non-TTB ASD subjects was found. The ASD sample showed a delay in walking and running acquisition compared to the normative values. This finding, if confirmed in other studies, could be included in the clinical abnormalities constellation of autism.

Titolo: Development of a standardized protocol for food preference assessment in ASD through direct observation (2017)

Autore: Enzo Grossi, Sara Melli, Marina Norsi - Autism Research Unit, Villa Santa Maria, Tavernerio (Como), Italy

Info: Accepted at IMFAR 2017

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Background Food selectivity is a particular feature of the restrictions and stereotypes of Autism. The majority of studies have investigated food preferences and the factors influencing selectivity using caregiver or parent reports such as CEBI (Children’s Eating Behavior Inventory), BAMBI (Brief Autism Mealtime Behavior Inventory), FPI (Food Preference Inventory) or YAQ (Youth/Adolescent Food Frequency Questionnaire, FFQ (Food Frequency Questionnaire) or others. All of these assessments document the presence of food selectivity in Autism subjects when comparing them to typically developing children. Thus far, no study in the literature proposes a standardized direct observation of feeding behavior protocol, which in principal should guarantee better accuracy; hence the purpose of our study. Objective In this pilot study, we assess the feasibility of a standardized protocol application to explore and monitor food selectivity by directly observing eating behavior in children and adolescents with autism residing at our Rehabilitation Institution. Methods The study sample consisted of ten children and adolescents affected by Autism. The assessment of autism symptom severity was performed through the ADOS scale. Only patients with primary autism (with no cerebral damage or genetic diseases) were included in the final sample (subjects with ADOS Calibrated Severity Scale > 6). Ten subjects affected by mild-moderate intellectual disability not related to autism but residing at the Institution formed the control group. The caregivers present at each participant meal in the dining halls complied food diaries every day for lunch and dinner, carefully notating which foods the subjects accepted and which ones were refused. The observation period lasted four weeks with 20 days monitored (Monday to Friday of each week). The institution’s general menu during this observation period consisted of 39 different serving selections at lunch and 37 at dinner. A comparison between the scores obtained from dietary choice patterns of the two groups and in particular the scores of refused foods was performed using a Mann-Whitney U test; the level of significance was set at p < 0.05. In autism group the Spearman non-parametric test was performed in order to explore correlations between the variables studied. Results Subjects with autism resulted significantly more selective than controls (lunch: p = 0.016, dinner: p = 0.042). Furthermore, children and adolescents with autism were more at risk of becoming underweight or overweight because of unbalanced dietary intake. We found a negative correlation between: food selectivity and duration of stay ( R = - 0.5848 ), as well as food selectivity and age (R = - 0.6437 ), but a positive correlation between food refusal and disease severity measured with ADOS II scale ( R = 0.4441 ). Conclusion Our data confirm the feasibility of a direct observation monitoring protocol for feeding behavior and the importance of food selectivity in subjects with autism. Younger children are more selective than older ones and the duration of institutional residency seems to positively impact this behavior.

Titolo: Support Intensity Scale profile in Autism: a proof of concept study (2017)

Autore: Enzo Grossi, Tiziano Gomiero, Luigi Croce

Info: Accepted at IMFAR 2017

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Background Tailoring supports for individual needs in disability requires tools that reliably and validly measure those needs. That is the function of the Supports Intensity Scale for children (SIS-C) developed from the American Association on Intellectual and Developmental Disabilities. SIS-C measures the individual’s support needs in personal, work-related and social activities in order to identify and describe the types and intensity of the support an individual requires. SIS has been designed to be part of person-centered planning processes that help all individuals identify their unique preferences, skills and life goals. Aim The aim of the study is to assess the SIS-C profile in Autism in comparison with Intellectual and Developmental Disability (IDD) not related to autism Methods We have applied the Italian Version of SIS, during the process of Italian psychometric validation, to a group of children and adolescents with different kinds of neuropsychiatric disorders in a multicenter study carried out in13 units throughout the Italian territory. This paper presents the data concerning two specifics subgroup of 127 individuals with autism (mean age 9.76; range 4-17 years) and 62 persons with IDD not related to autism (mean age 11.33; range 5 – 16 years). Seven support need dominions have been explored through independently structured interviews, whereby the two principal caregivers for each subject in this study responded to a total of 61 items covering: home living, community and neighborhood, scholastic participation and learning, health and safety as well as social and advocacy activities. Results are expressed as a percentage of maximum theoretic support need in each dominion. Results The score profiles obtained from the interview of two caregivers resulted highly correlated in all dominions of the scale (r values ranging from 0.85 to 0.95). Individuals with AUTISM, despite an average level of intellectual disability similar to that individuals without autism diagnosis showed degrees of support need that were significantly higher than subjects in the comparison group for all dominions (see figure 1), with absolute differences ranging from +33% to +61% (mean +42%). As expected, the difference was particularly evident for home living, social activity, and community and neighborhood dominions. Conclusions Traditionally, a person's level of developmental disability has been measured by the skills the individual lacks. SIS-C shifts the focus from shortfalls to needs. The scale evaluates practical support people with developmental disabilities need to lead independent lives. The key message emerging from our study is that, given a similar level of intellectual function, special needs in individuals with AUTISM are around 40% higher than those in subjects with IDD not associated to autism.

Titolo: Stereotypies in autism: an innovative mathematical approach to depict the natural association scheme of their co-occurrence (2017)

Autore: Enzo Grossi, Elisa Caminada - Autism Research Unit, Villa Santa Maria, Tavernerio (Como), Italy

Info: Accepted at IMFAR 2017

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Background In autism, stereotypies (stereotypic movement disorders) are frequent and disabling and represent one of the most complex clinical pictures due to a broad spectrum of anomalies. Following the new wave of biology-based research in autism, motor anomalies and other repetitive behaviors are increasingly receiving attention. Indeed, the co-occurrence of many different stereotypies in the same subject theoretically offers the possibility to derive associative patterns useful in developing interpretative models. 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. By using advanced machine learning systems, we are able to develop a semantic connectivity map of the variables under investigation. Methods To define the spectrum of expressions of stereotypies we studied 67 autistic individuals which, as a group, expressed 37 different types of stereotypies defined through standardized video-recording. All individuals but one presented a certain number of stereotypies: average = 11.5; range 0-27. The data were analyzed with a special kind of unsupervised artificial neural network ( Auto-CM). Auto-CM is able to a semantic connectivity map in which the matrix of connections, visualized through a minimum spanning tree filter, takes into account nonlinear associations among variables and captures connection schemes among clusters. In this way, the patient state can be viewed as an hyperpoint in a “multimorbidity space” in which each dimension corresponds to a quantitative phenotype. Results The semantic connectivity map showed a meaningful scheme of connections among stereotypies. As far as motor abnormalities are concerned, mouth-trunk-arms movements constitute a central axis of the system from which all other type of movements involving head, legs, shoulder and feet take place. Toe walking is directly linked to other walking abnormalities. Licking, biting, smelling, rubbing and touching body parts form a unique cluster associated to medium ID severity and separate from licking, biting and smelling objects, which is associated to mild ID severity. Severe ID is associated to simple voicing and facial grimacing. Conclusion Machine learning algorithms are able to depict the complex pattern of stereotypies commonly observed in autism, thus allowing for a better definition of major phenotypes that are amenable for future large epidemiological surveys.

Titolo: Assessment of presentation patterns, clinical severity and sensorial mechanism of tip-toe behavior in severe ASD subjects with intellectual disability: a cohort observational study (2016)

Autore: Marina Norsi, Giulio Valagussa, Enzo Grossi

Info: The 21st congress of the Society for Children development and rehabilitation, Jerusalem, 8-10 November 2016

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We assessed paradigmatic characteristics and presentation features of Toe walking (TW) behavior in a group of 69 subjects affected by Autism Spectrum Disorder in two studies carried out in Villa Santa Maria, an Italian Institute which hosts many disabled children and adolescents. A therapist assessed the presence of TW during standing, walking and running using direct observation and an interview of the main caregiver living with the children has been carried out. As a consequence of this systematic observation it was possible to determine the presence of TW in 32% of the examined ASD subjects. We found three clinical presentation modalities of TW: 1) present while standing, walking and running (45.5%), 2) present when walking and running (18.4%) or 3) present only when running (36.4%). For this reason we prefer to call this phenomenon as Tip-Toe behavior rather than Toe Walking. We also note that TTB subjects were more frequently non-verbal than subjects without TTB. On the other hand, no significant difference in ASD severity according to the ADOS scale was found between TTB and non-TTB subjects. In a second study, carried out in a subgroup of 14 ASD subjects (7 TTB and 7 non-TTB), we show that acting upon a soft floor surface (foam mats) made a substantial difference in reducing the phenomenon, as the sensorial modulation could-be involved in this behavior. Further evaluation is needed to clarify the potential pathophysiological implications of this phenomenon.

Titolo: Unexpected improvement in core Autism Spectrum Disorders (ASD) Symptoms after long-term treatment with a Probiotic compound (2016)

Autore: Delia Dunca, Enzo Grossi, Vittorio Terruzzi, Sara Melli

Info: Submitted to IMFAR 2016

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Background Many studies report the existence of so-called gut-brain axis: a physiological framework in which the gut microbiota communicates with the CNS and vice-versa through neural, endocrine and immune pathways. If this is true, then it is plausible to expect that the modulation gut microbiota may be a tractable strategy in developing novel therapeutics for complex CNS disorders. Autism is definitely one of these disorders. Objectives To report the case of a 12 year old boy with ASD and severe cognitive disability in which an unexpected improvement of autistic core symptoms was observed after four months of probiotic treatment. Method The case study refers to a 12 year old boy with ASD, severe cognitive disability and gastrointestinal disturbances attending the Villa Santa Maria Institute in resident care since 2009. The boy was first diagnosed with Pervasive Developmental Disorder (PDD) at the age of two. Later on ASD Diagnosis was made according to DSM-V criteria and was confirmed by the ADOS-2 assessment (Autism Diagnostic Observation Schedule). In February 2014, a probiotic treatment was prescribed to control gastrointestinal symptoms (VSL#3, a product with lyophilized Bifidobacteria, Lactobacilli and Streptococci), which lasted four months. The diet was consistently followed throughout the entire period and treatment compliance was ensured by a careful supervision. No other dietary supplements containing probiotics or prebiotics or antibiotics was administered during the treatment and follow-up period. The rehabilitation program already in place, based on behavior, communication, psychomotor therapy, individualized Education Plan/School Services and parents involvement, was regularly maintained. Improvement in ASD symptoms already became apparent and clinically evident from the few weeks after starting the probiotic treatment. The ADOS-2 assessment was repeated six times over the October 2013-March 2015 period (twice before starting the treatment, twice during (after month 1 and month 4) and twice after treatment interruption. Results The probiotic treatment reduced the severity of abdominal symptoms as expected. While the Restricted Repetitive Behaviors domain scores did not change, an unexpected improvement of the Autistic core symptoms did occur. The Social Affect Domain Score of ADOS improved, going from 20 to 18 after two months of treatment, with a further 1 point reduction during the following two months. The severity level 17 remained stable during the follow up period. Conclusions The appropriate use of probiotics merits further research, which hopefully will open new avenues in the fight against ASD.

Titolo: EEG findings processed by Next Generation Artificial Adaptive Systems can perfectly distinguish ASD children from typically developing children: a proof of concept pilot study (2016)

Autore: Enzo Grossi, Massimo Buscema, Chiara Olivieri

Info: Accepted as poster at IMFAR 2016

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Background To our knowledge, this is the first study that applies an artificial adaptive system to extract interesting features in computerized EEG that distinguishes ASD children from typically developing ones. The new system, named MS-ROM/I-FAST, belongs to the family of systems developed by The Semeion Research Institute in Rome. MS-ROM/I-FAST is a new, complex algorithm used for blind classification of the original EEG tracing of each subject. This is accomplished by recording and analyzing a few minutes of their EEG without any preliminary pre-processing. A proof of concept study published in The Artificial Intelligence Journal in 2015 showed accuracy values ranging from 94%-98% in discerning subjects with Mild Cognitive Impairment and/or Alzheimer’s Disease from healthy elderly people. Even if the neuropathology related to autism is markedly different from that of Alzheimer disease, simple reasoning would support the idea that the atypical organization of the cerebral cortex present in autism should result in an EEG signature open to detection through potent analytical systems like ANNs. Aim of the study The aim of the study is to assess how effective this methodology distinguishes ADS subjects from typically developing ones. Methods Fifteen definite ASD subjects ( age range 8 -22) and ten typically developing subjects ( age range 7-12 ) were included in the study. Patients received independent Autism diagnoses according to DSM-V criteria, then subsequently confirmed by a qualified psychiatrist at Villa Santa Maria, where the patients reside, using the ADOS scale (overall severity score had a range from a minimum of 4 to a maximum of 10 points, average = 7.9). No autistic child was affected by genetic conditions and/or cerebral malformations documented by neuroimaging and epilepsy. A continuous segment of artefact-free EEG data lasting 60 s 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, the overall predictive capability of different machine learning systems in deciphering autistic cases from normal ones consistently amounted to 100% (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. This suggests that the ANNs do not read age-related EEG patterns, but rather invariant features related to the brain’s underlying disconnection signature. Conclusion This pilot study seems to open up new avenues for the development of non-invasive diagnostic testing for the early detection of ASD.

Titolo: Oral health and dental needs in adolescents with ASD: an Italian study (2016)

Autore: Enzo Grossi, Martina Gangale, Chiara Sciessere, Delia Dunca & Luca Levrini

Info: Accepted as poster at IMFAR 2016

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Background There are few studies that investigate oral health and dental needs of children with autism. Many ASD subjects experience great difficulties in performing oral hygiene due to their limited manual dexterity, sensory and intellectual disabilities and thus are prone to poor oral health. Different studies conducted on caries prevalence and oral inflammation in ASDs have shown contradictory results. Some studies report lower caries prevalence in autistic children, however this finding seems somewhat surprising. Children with ASD very often prefer soft and sweet foods that they tend to poach inside the mouth instead of swallowing them. This is due to poor tongue coordination that increases the susceptibility to caries. To date, there are no studies addressing this phenomenon in Italy. Aim The aim of this study is to determine the prevalence of caries and overall oral hygiene in ASD adolescents and compare them to adolescents belonging to the general population in Italy. Methods Thirty one (26 male-5 female) adolescents with ASD with a mean age of 15. 35 years diagnosed according to DSM V and ADOS-2 criteria and treated at our Institute as permanent residents were selected for the study. Exclusion criteria included subjects that had dental prophylaxes over the past 6 months, and/or those suffering from other diseases known to influence dental caries or the severity of periodontal disease such as Down’s syndrome and diabetes. All subjects were checked by one examiner for oral hygiene status and dental caries while seated in a standard dental chair. The examiner used a standard dental mirror, an explorer and periodontal probe with William’s markings. The examination of the soft and hard tissues was done under both a flash light and regular room light. The DMFT index was used, with codes and criteria established by the WHO. The gingival status, evaluated according to the gingival index of Loe and Silness, was then recorded as generalized or localized gingival inflammation, depending on the amount of gingival redness and bleeding during the examination. Results Both teeth-brushing time and technique were incorrect in 31/31 and in 28/31 cases respectively. Gingival status was assessable in 30/31 cases and the DMFT index in 23/31 cases due to insufficient cooperation. Mean age and mean ADOS total score of cooperative and un-cooperative subjects was not statistically different (8.36 vs 8.28; 14.95 vs 16.5). In this subset, the overall prevalence of dental caries was 34.7% and the mean DMFT index was 1.43. The corresponding values in the general population control group (made up of 805 adolescents from the surrounding area) was 54.5% and 2.04 respectively. The difference in the carious prevalence and DFMT index was significant (p<0.05) between the two groups. The prevalence of moderate/severe gingivitis was 78.2%, with the corresponding value in the control group being 60%. In this case the difference was also statistically significant (p>0.05). However, there was no significant correlation between the ADOS severity total score and gingivitis degree ( r = 0.10; NS) Conclusions The oral hygiene status in autistic adolescents observed in this study is indeed poor, but does not appear to be directly correlated to autism severity. The prevalence of caries is in fact lower in ASD adolescents than in the general population. Further investigation is required to explain this rather counterintuitive finding.

Titolo: Stressful life events during pregnancies related to children with ASD, their siblings and typically developing children (2016)

Autore: Enzo Grossi, Federica Veggo, Antonio Narzisi, Filippo Muratori, Ilaria Rolla, Lucia Migliore

Info: Accepted as poster at IMFAR 2016

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Background: The role of stressful events in contributing to increased autism risk deserves special attention since very few studies have attempted to collect this kind of information. Adverse experiences during the prenatal period (a time of rapid growth and of heightened brain plasticity) have been demonstrated to induce significant effects on neurobiology, metabolism, and physiology that can persist across the lifespan. Generally, the more variable the stressor and the earlier the stressors occur in the pregnancy, the more profound the effect on offspring development. A number of basic science studies indicate that a family history of stress may program central and peripheral pathways regulating gestational length and newborn health outcomes in the maternal lineage. Epigenomic programming related to hypothalamic-pituitary-adrenal (HPA) axis responses to chronic stress may be an important mechanism involved in autism development. Objectives: The aim of this study was to assess the frequency and impact of different stressful life events. Data was collected from careful interviewing during pregnancies of the following three groups: mothers of children with ASD, of their typically developing siblings (internal controls) and of only typically developing children ( external controls) in two Italian provinces, Como and Pisa. Methods: The clinical sample included a cases group of 73 ASD children and adolescents – group 1 (mean age 8.2; S.D. 6.35) compared to an internal control group formed by 45 healthy siblings – group 2 (mean age 8.9 years; S.D. 6.66) and to an external control group formed by 96 typically developing children – group 3 (mean age 7.8; S.D 5.67). It is important to note that the second group represented all the siblings available. Mothers of ASD children who met the inclusion criteria were invited to an individual structured interview about stressful life events after having signed an informed consent form. Stressful events considered in the survey were: death or severe disease of a relative, divorce, separation or conjugal conflict, loss of house or eviction or relocation, abuse or violence and job strain. Results: A statistically higher prevalence of the mean number of stressful events per pregnancy was recorded in the ASD group when compared to the internal and external control groups. The mean number stressful events (range) was = 0.45(0-5 ), 0.29(0-3) and 0.11(0-2 ) in the three groups respectively. Group 1 vs group 2: p< 0.05; Group 1 vs group 3: p <0.001; Group 2 vs group 3 p<0.01. Conclusions: Stressful life events during pregnancy are more frequent in mothers of children with autism than mothers of typically developing children. The rate observed in sibling pregnancies lies exactly in the middle, pointing out a possible threshold effect in women predisposed to suboptimal pregnancies.

Titolo: Tip-Toe Behavior (TTB) presentation pattern and Achilles’s tendon shortening: are they related in ASD children? (2016)

Autore: Giulio Valagussa , Valeria Balatti, Luca Trentin and Enzo Grossi

Info: Accepted as poster at IMFAR 2016

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Background: About twenty percent of individuals with ASD walk on their tiptoes. Persistent toe-walking in children with ASD may contribute to secondary motor deformities by producing a shortening of the Achilles’s tendon (made up by the soleus muscle SM and gastrocnemius muscle GM). It is not clearly understood why some ASD subjects develop this tendon shortening while others do not. A possible contributing factor could be the amount of time children spend in TTB during the day, i.e. if TTB is present only in running (class 3) or in walking and running (class 2) or in standing, walking and running (class1), three mutually exclusive patterns we described in a previous study. Objectives: The aim of this cross-sectional study is to evaluate the relationship between the three TTB presentation patterns described above and the Achilles’s tendon shortening. Material and methods: The study includes 69 consecutive children (57 males, 12 females, mean age = 14 years – 3.6 SD) diagnosed with ASD according to the DSM V criteria and under observation at our institute. The severity of ASD was established through ADOS (2nd version). A therapist assessed the presence of Tiptoe behavior (TTB) during standing, walking and running using direct observation and an interview of the main caregiver living with the children. Another therapist assessed both the soleus and gastrocnemius muscles length using a manual goniometer. Results: Overall 23/69 children presented TTB. Ten children exhibited it in standing, walking and running (class 1), 8 only during walking and running (class 2) and 5 children only during running (class 3). There were no significant differences in the mean overall ADOS score of the TTB children according to TTB classes: 20.13 (5.48 SD) no TTB class; 23.90 (5.36 SD) class1, vs 21.13 (4.29 SD) class 2 and vs 23.60 (5.13 SD) class3. The mean length of the left GM of non TTB children was 9.20° (5.18°SD) vs a value of -0.2°(10.16°SD) TTB class 1( p<0.01), vs 6° (2.73°SD) TTB class 2 (p NS) , vs 10.2° (9.92°SD) TTB class 3 ( p NS). The mean length of the right GM of non TTB children was 9.02° (5.39°SD) vs a value of 1.7°(10.91°SD) TTB class 1(p<0.01), vs 8.75° (4.58°SD) TTB class 2 ( p NS), vs 11.6° (4.39°SD) TTB class 3( p NS). The mean length of the left SM of non TTB children was 21.07° (7.67°SD) vs a value of 10° (9.65°SD) TTB class 1 ( p< 0.05), vs 18.63° (9.90°SD) TTB class 2( p NS), vs 22.80° (6.30°SD) TTB class 3( p NS). The mean length of the right SM of non TTB children was 19.33° (6.87°SD) vs a value of 9.7°(8.84°SD) TTB class 1( p <0.05), vs 19.25° (8.26°SD) TTB class 2( p NS), vs 21.8° (6.61°SD) TTB class 3 ( p NS). Conclusions: The data confirm the existence of a positive relationship between the presence and severity of TTB and the Achilles’s tendon shortening, with a significant difference between the NonTTB group and Class 1 TTB group.

Titolo: Artificial Neural networks in the study of intellectual disability: an introduction (2015)

Autore: Enzo Grossi

Info: Lecture at European Psychology Congress, Milano, 8th July2015

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Motivations to apply complex systems mathematics on intellectual disability: Mental health depends on complex networks of interacting elements (from genes to environment) . Disease status is the consequence of dynamic processes that regulate these networks Non linear critical thresholds regulate pathology expression and occurrence The predictions have to be applied at individual patient level. Huge amount of data per subject hamper statistical tests

Titolo: The emerging role of gut microbiota in autism pathogenesis: a new hope for effective prevention and treatment (2015)

Autore: Enzo Grossi, Vittorio Terruzzi

Info: Lecture at 8th Probiotics, Prebiotics & New Foods for microbiota and human health, Roma 13-15 September 2015

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Autism is a specific neurodevelopmental condition that typically displays qualitative socio-communicative impairment and restricted, stereotyped interests and activities (1). Although a large proportion of children with autism manifests abnormal development during the first year of life, 15-62% of them show a regression between eighteen and twenty-four months of age after a period of apparently typical development (2,3). Approximately 70% of individuals with autism present a variable degree of intellectual disability (4) and expressive/receptive language can be absent or very insufficient (5). Other problems, not exclusive of autism, are attention deficit and disturbed behaviors as etero-autolesivity. Thirty per cent of children manifest epileptic seizures by late childhood or adolescence and 10% of cases are associated with several genetic disorders as tuberous sclerosis, Angelman syndrome, phenylketonuria and fragile X syndrome (6). The etiopathogenesis of autism is not yet understood; the prevalence is undoubtedly rising and it is not clear if this increase is linked to the diagnostic improvement or to a greater susceptibility of the population to the disease. Many twins and family studies point out the importance of inherited predisposition to the disorder even though epidemiologic research suggest the strong contribution of prenatal and early postnatal environmental factors among which an abnormal intestinal flora. There is an increasing body of knowledge pointing out that gut flora influences a variety of social emotional, and anxiety-like behaviors, and contribute to brain development and function in animals( 7-8) and humans (9). In a recent study carried out by Hsiao et al. these authors demonstrated that a particular model of autistic mouse displays behavioral symptoms relevant to ASD and other neurodevelopmental disorders ( 10-11), while also exhibiting defective GI integrity, dysbiosis of the commensal microbiota, and alterations in serum metabolites. The administration of a particular commensal ( B. Fragilis ) is able to reverse autistic symptoms and metabolic derangement. These findings represent a major breakthrough in the microbiota hypothesis of ASD(12). In humans the possibility that autism is the consequence of an imperfect development of gut flora is supported by a number of observations. First, onset of the disease often follows antimicrobial therapy, for example, to treat ear infections that often are present in high frequency and persistency among young ASD patients. Second, GI symptoms are common at the onset of ASD and often persist. Finally, other antimicrobials may lead to a clear-cut response and relapse may occur when the antimicrobial is discontinued, which is demonstrated with, for example, the antimicrobials vancomycin and metronidazole. However, in higher doses, over a longer period of time (.6 d of treatment), vancomycin disrupts the anaerobic intestinal microflora and promotes colonisation by pathogens(13). The literature about the role played by intestinal dysbiosis in autism is increasing and in the last ten years a number of studies have been published (14). All these studies have targeted fecal microbiota but two( ileal and cecal biopsies) using a wide range of techniques. All the studies are case-control comparative studies with a small-medium sample size, ranging from 15 to 58 autistic children and from 10 to 53 typically developing children. The age of the children has a wide range: from 3 to 16 years. As expected there is a strong inhomogeneity as regards the microbiological assay method employed. One group has employed FISH analysis with specific 16SrRna oligonucleotide probes; other bacterial tag encoded FLX amplicon pyrosequencing. Other studies have been carried out using real-time PCR assays on CFX 384TM detection system and only one using bacterial and yeast culture using traditional techniques. Anyway only one study did not find any difference in microbiological pattern between autistic children and controls. In the others significant differences have been found in increase or decrease of specific bacterial population. Concluding from the findings listed above, it was hypothesised that: (1) relapse in autistic children after discontinuation of antibiotic treatment is due to the presence of Clostridium spores which then germinate to reproduce the disease; (2) the increased incidence of autism is related to the widespread exposure to Clostridium spores in the environment; and (3) the increase in families with multiple cases of autism is also due to contact with spores. However, the studies conducted so far are of low to moderate quality, predominantly due to small sample sizes and inadequate or absent explanation of sources of the sample, timing of the study and potential biases. In addition, the studies used a wide range of different assessment methods, which makes it impossible to make qualitative comparisons. A part from this, the suggestive role of abnormal gut microbiota and the frequent presence of abnormal gut permeability in children with ASD has promoted clinical studies on probiotics. In a double-blind, placebo-controlled study by Parracho et al.(15), Lactobacillus plantarum feeding of children with autism resulted in significant increased levels of the beneficial bacteria lactobacilli and enterococci, and a significant reduction of a cluster of Clostridium, compared with the placebo group. Through a 12-week study, the probiotic feeding resulted in reduced GI problems and, more importantly, in improved behaviour scores compared with baseline. In this respect, it is noteworthy that, during another double-blind, cross-over study, addressing the effects of the probiotic L. plantarum on autism failed during the changing of treatments in the cross-over period, because parents (who were blinded for the intervention) of children treated with the actual probiotics refused to make the switch, as they wanted their autistic children to continue their improvement(16). Noted improvements were decreased levels of clostridia bacteria in the stools and a positive effect on mood and general behaviour, as described by parents. Since this can only be considered as anecdotal evidence, further well-controlled studies are warranted. Another probiotic trial in autistic children was recently conducted by Kałuz˙ na-Czaplin´ska & Błaszczyk (17). Probiotic supplementation with L. acidophilus over 2 months led to a significant decrease in D-arabinitol and to a significant improvement in the ability to concentrate and carry out orders. D-Arabinitol is a metabolite of most pathogenic Candida species and its excretion in urine is elevated in autistic patients. Candida infections have been associated with autism previously. Unfortunately, these studies were not of sufficient methodological quality due to the absence of control groups, multiple treatments at once and/or small sample sizes. In conclusion the studies on intestinal microbiological profile in autism are nevertheless in their infancy. There are many methodological issues to be resolved, like the standardization of microbiological assay methods, of sampling protocols and mathematical analysis of the results.

Titolo: Data mining of quality of life construct in children with ID: a pilot study with Artificial Neural Networks (2015)

Autore: Tiziano Gomiero, Enzo Grossi, Elisa Caminada, Luisa Calliari

Info: Poster at 10th European Congress of Mental Health in Intellectual Disability. Firenze, 9-11 September 2015

abstract

Objectives: The construct of QOL has been widely applied in the field of ID and implies principles of emancipation and inclusion; our aim was to investigate the connection of multidimensional instruments that measure quality of life and support needs in children with ID. Methods: Analysis of opportunistic sample of 17 individuals (range from 6 to 17 years) with different levels of ID and adaptive behaviour. We have submitted at the same time different tools: Brown’s QoL, Support Intensity Scale CY and the Personal Outcome Scale CA, during the Italian validation study of the SIS CY. We used standard statistical index and an Artificial Neural Network (AutoCM). Results: These tools measure distinct constructs not strictly connected. In general we don’t find significant correlations between the instruments also on similar aspects (e.g. The scale of legal protection of the SIS CY with the POS’s subscale of Rights r=-0.014). The most interesting aspect of the analysis with AutoCM is that finds consistent patterns and/or systematic relationships and hidden trends and associations among variables, identifying which are the centrals hubs, the tools or subscale most significant and then drawing a very separate map of the different constructs. The SIS appears to be the most highly interconnected and it permits more associations with the level of DI and adaptive behavior. Conclusions: The QoL is a complex construct and difficult to assess in people with ID; it is necessary not only to have specific tools for data collection but also adequate instruments of analysis of the same and the use of AutoCM in this sector seems to be very promising

Titolo: Self-blame, self-forgiveness and well-being among parents of autistic children (2015)

Autore: Angelo Compare, F.Giorgia Paleari, Sara Melli, Cristina Zarbo, Enzo Grossi

Info: Oral communication at European Congress of Psychology, Milano 7-10 July 2015

abstract

Parents of autistic children tend to blame themselves for child’s disability. This dysfunctional explanation often leads to poorer resilience and health outcomes for parents. Recent research suggests that an effective way to mitigate the negative consequences of self-blaming is through self-forgiveness, the process whereby a person leaves self-resentment and self-criticism while admitting one’s own possible mistakes and omissions. Self-forgiveness has been proved to promote a better adjustment in people who blame themselves for life stressors like a medical illness. Given that no study has investigated the effects of self-forgiveness among parents of autistic children yet, the present study intended to overcome this limitation by examining whether self-forgiveness moderates the negative association between parents’ self-blame for their child disability and their well-being. Forty-one parents of autistic children receiving treatment at a day care center reported their degree of self-blame and self-forgiveness for their children’s autism as well as their level of personal well-being and parental distress across a number of dimensions. Results indicate that self-blame is significantly related to personal well-being and parental distress only for parents reporting lower levels of self-forgiveness. The present findings suggest that interventions promoting self-forgiveness may help parents with reducing negative outcomes that are associated with self-blame.

Titolo: Pregnancy Risk Factors in Autism: A Sibling Matched Case-Control Study in Italy and Israel (2015)

Autore: Enzo Grossi, Hanna Alonim, Federica Veggo, Irit Abramson Autism Unit, Villa Santa Maria Institute, Tavernerio ( Como ), Italy , The Mifne Center, Rosh Pina Bar Ilan University, Social Science School, Ramat Gan, Israel

Info: Accepted as poster at 6th Fred J. Epstein International Symposium on New Horizons in Pediatric Neurology,Neurosurgery and Neurofibromatosis Eilat, Israel, March 15-19, 2015

abstract

Introduction and Aim: Recent epidemiological studies have pointed out a number of pregnancy and peri-post natal factors which, contributing to focal brain inflammation, predispose to ASD development. The aim of this study was to assess the frequency of 24 potential risk factors derived from a careful interview about pregnancy and peri/post history of mothers of children with autism and of typically developing siblings in a "within subject design" enrolling cases (C ) and siblings( S) in Italy and Israel. Methods: The clinical sample included a cases group of 40 children with autism compared to an internal control group formed by 53 siblings representing all the siblings available ( 19 C + 24 S in Italy and 21 C+ 29 S in Israel ). Mothers were invited to a structured interview about early risk factors in separate sessions each dedicated to a specific pregnancy. Results: The frequency profile of factors in autism group pregnancies is clearly different in comparison with typical siblings group. Low gestational age has a prevalence of 17.5% vs 3.8% in the two groups respectively, with an odds ratio of 5.41, perinatal complications have a prevalence of 20% vs 9.4% , with an odds ratio of 2.4, pregnancy complications have a prevalence of 57.5% vs 39.6% , with an odds ratio of 2.06, and dystocic delivery has a prevalence of 7.5% vs 3.8% with an odds ratio of 2.05. TWIST system, an evolutionary algorithm capable to remove redundant and noisy information, selected 12 variables (father and mother_age>40) , smoking_pregnancy, divorce, separation or coniugal conflict, post_partum_depression, use_of_drugs_pregnancy, dystocic_delivery, perinatal_complications, low_gestational_age, no_breast_feeding, early_antibiotic_therapy) that allowed specialized Artificial Neural Networks( ANNs) to discriminate between cases and controls with 74.62% global accuracy ( sensitivity= 64.77%; specificity= 84.46%; AUC ROC= 0.77). Conclusions: Our data suggest that when the mix of potential risk factors overcome a certain threshold of frequency the suboptimal pregnancy predisposition of these mothers shifts toward autism in the newborn. ANNs can handle the quality of these risk factors building up a predictive model with good sensitivity and specificity which explain about at least two third of autism cases.

Titolo: The Early Signs of Autism in First Year of Life: Identification of Key Factors Using Artificial Neural Networks (2015)

Autore: Hanna Alonim, Enzo Grossi, Ido Liberman, Hillel Braude The Mifne Center and Social Science School, Bar Ilan University, Rosh Pina, Israel , Autism Unit, Villa Santa Maria Institute, Tavernerio ( Como ), Italy

Info: Accepted as poster at 6th Fred J. Epstein International Symposium on New Horizons in Pediatric Neurology,Neurosurgery and Neurofibromatosis Eilat, Israel, March 15-19, 2015

abstract

This study assesses the natural relationships among variables associated with autism onset using a special Artificial Neural Network (ANN) called Auto Contractive Map (Auto-CM). Auto-CM is a special kind of ANN successfully applied in many complex chronic degenerative diseases, able to find out consistent trends and associations among variables creating a semantic connectivity map. The matrix of connections, visualized through minimum spanning tree filter, takes into account nonlinear associations among variables and captures connection schemes among clusters. The authors of this study analyzed the results of 16 variables displayed in 110 infants who were diagnosed with autism at the age of 2-3 years, using retrospective analysis of video-recordings of the infants’ first year of life. The ESPASI variables investigated included: Excessive Passivity; Excessive activity; Lack of eye-contact; Lack of reaction to voice or presence; Resistance to eat; Aversion to touch; Delayed motor development; Accelerated growth of head circumference. The semantic connectivity map developed by Auto-Cm system showed a meaningful scheme of connections. Lack of eye contact and lack of reaction to voice or presence resulted the central nodes in the graph. Variables describing inhibition (Lack of eye contact; Lack of reaction to voice or presence; Excessive Passivity; Delayed motor development ); dishinibition (Excessive activity; Aggression; Excessive eating) and nutrition habits, (Resistance to eat; Refusal to eat vegetables/fruit; Refusal to eat solid food; Nutrition fixation )were naturally clustered together, parallelly diverging along the graph. Autism diagnosis resulted directly linked to nutrition fixation. Five variables composed an internal loop in the graph(Excessive Passivity; Lack of reaction to voice or presence; Lack of eye contact; Nutrition fixation and refusal to eat solid food)pointing out hypothetical core signature of the disease. Findings from this study indicate the presence of three major macro-classes as a three-leaf clover that aggregates in its “leaves” the more mutually connected variables. In this regard derangement in nutrition behavior play an important role in early diagnosis of autism possibly higher than well recognized manifestations like lack of eye contact and lack of reaction to voice or presence. The use of ANNs may be an important advance in autism research.

Titolo: Mental Stress in Parents of Autistic Children: A Pilot Study of the Related Psychological Dimensions (2015)

Autore: Sara Melli, Cristina Zarbo, Angelo Compare, Enzo Grossi - Autism Research Unit, Villa Santa Maria Institute, Tavernerio, Italy, Human and Social Science Department, Bergamo University, Bergamo, Italy

Info: Poster at IMFAR 2015

url

abstract

Background: Parental mental stress is clinically common in families of autistic children and adversely affects the care of the child. Moreover, parents of autistic children frequently experience feelings of guilt, maladaptive coping styles, lack of ability to forgive himself and the partner, and low mindfullness ability. However, is unclear which of these dimensions is predominant in these families and if it their associations are symmetrical in presence of high or low values. Objectives: The aims of this pilot study are: 1) to evaluate the most predominant dimensions in parents of autistic children and to establish the hierarchy of their relationship; 2) to evaluate if psychological dimensions works in different way when they are high or low; 3) to establish if psychological dimensions in parents of autistic children are related to the severity of the Autism Spectrum Disorder (ASD). Methods: Demographic and psychological information about mental stress, feelings of guilt, ability to forgive, mindfullness ability and coping styles were collected through clinical interviews and self-report questionnaires in 28 parents (mean age 43.5 yrs; 22 mothers; 6 fathers) of autistic children (mean age: 12.2 yrs; 3 females; 25 males). Severity of the ASD was assessed through Autism Diagnostic Observation Schedule (ADOS). Artificial Neural Networks (Auto-CM system) were applied to highlight the associations among variables under study. Auto-CM is fourth generation Artificial Neural Network developed at Semeion Research Institute (Rome) and successfully applied in many complex chronic degenerative diseases, able to find out consistent trends and associations among variables creating a semantic connectivity map. The matrix of connections, visualized through minimum spanning tree filter, takes into account nonlinear associations among variables and captures connection schemes among clusters. Results: Predominant dimensions in parents of autistic children were low feelings of guilt for himself and the partner, high levels of forgiveness of himself and the partner, and low levels of maladaptive coping responses. These three main dimensions are strictly related among themselves. While high parental mental stress was strictly related to high parental distress subscales, high maladaptive coping styles, and low self-forgiveness ability, conversely, low mental stress appeared to be marginal in relation to the other psychological dimensions. This behavior is typical of complex nonlinear systems. The severity of the ASD was not related to parental psychological dimensions. The ADOS scores, both low and high, were in fact marginal in the connectivity map in relation to the other dimensions. Conclusions: The interplay of psychological factors related to parental stress is complex. Understanding these relationships is the starting point to activate and enhance parental resources essential to the wellbeing of both children and caregivers. Due to the complexity of these relationships and the lack of symmetry between associations of the same dimension when high or low, the approach with advanced neural networks is essential for the analysis of the patterns of relationships.

Titolo: The Hardness of Standing Support Surfaces Influences Tip-Toe Behavior of Autistic Children: Evidence from a Pilot Study (2015)

Autore: Giulio Valagussa, Valeria Balatti, Luca Trentin, Vittorio Terruzzi, Enzo Grossi - Autism Unit, Villa Santa Maria Institute, Tavernerio, Italy

Info: Poster at IMFAR 2015

url

abstract

Background: As demonstrated in a previous study, 32% of autistic children observed in our Institute walk on their tiptoes (tiptoe behavior-TTB). TTB may occur in three modalities: class 1(TTB in standing, walking and running); class 2 (TTB in walking and running) and class 3 (TTB only during running). Thus far, the literature has yet to publish a standardized clinical method of assessment to "quantify" TTB during standing or walking. Objectives: The aims of this pilot study are: 1) to propose a protocol to quantify TTB and 2) to assess whether the hardness of standing support surfaces influences motor behavior in children with ASD. Methods: Seven autistic children with TTB (6 males), age range from 7.1 to 16.4 years diagnosed according to the criteria of DSM V were admitted to this study. All subjects presented an ankle dorsiflexion range of motion wider than 90°. Video recordings were taken during a static task (playing in front of a playing table for 3 minutes) and during a dynamic task (transporting an object from the playing table to a therapist situated 2 meters away and back again for 15 times) over a hard floor surface. Each task was repeated on three different days. The three repeats were repeated again on a soft floor surface (foam mat). An independent therapist not involved in tests operation assessed the videos of the static task trials by calculating the time spent on full foot support versus on tiptoes. The videos of the dynamic task trials count the number of times the child was able to walk the full length with all steps on full foot support versus toe walking. Results: On the hard floor surface, during the static tests, the subjects stayed on tiptoes for an average of 45.5/180 sec. During the dynamic tests the children toe walked an average of 23.6/30 times of the measured lengths. On the soft floor surface, during the static trials, the children used tip toe posture for an average of 24.6/180 sec. Meanwhile, during the dynamic trials they tiptoed an average of 11.2/30 times of the measured lengths. The p value of the differences were 0.11 for static tests and 0.008 for dynamic tests. The repeat observation values were consistent and reproducible. Conclusions: The proposed evaluation protocol seems to be a useful tool to monitor TTB behavior. Footing on soft surfaces induces an increase in the time spent on non TTB during static and dynamic tasks. This finding suggests that TW is a reflection of a sensory integration dysfunction or of a vestibular derangement. Further evaluation is needed to clarify the potential pathophysiological implications of this phenomenon.

Titolo: Toe Walking and Autism: Cross-Sectional Study on Presentation Patterns and Correlation with Autism Severity (2015)

Autore: Giulio Valagussa, Valeria Balatti, Luca Trentin, Sara Melli, Marina Norsi, Enzo Grossi

Info: Poster at IMFAR 2015

url

abstract

Background: According to the literature, about twenty per cent of individuals with autism walk on their tiptoes. “Toe walking” (TW) may present different functional patterns but thus far, there is no standardized clinical method of examination or assessment. Some authors describe TW as intermittent or persistent , while others grade TW by history and observation (e. g. absent, present in the past, intermittently present, and persistent). Moreover, it seems that the persistence of toe walking can be related to language impairment even if systematic observations in the literature are scarce. Objectives: The aims of this cross-sectional study are: 1) to assess the prevalence of toe walking in an ASD cohort; 2) to describe the functional patterns of presentation of TW; 3) to evaluate the relationship between TW presentation patterns and the severity of autism with particular regard to language delay. Methods: The study includes sixty nine consecutive children (56 males; 13 females; mean age = 12,4 years) diagnosed with Autism according to the DSM V criteria and under observation at our institute. A therapist assessed the presence of Tiptoe behavior( TTB) during standing, walking and running using direct observation and interview of the main caregiver living with the children. The severity of autism was established through ADOS (2nd version) Results: Overall: 22 children (31,88%) presented TTB. Ten children (14,49%) exhibited it while standing, walking and running (class 1), four (5,79%) only during walking and running (class 2) and eight children (11,59%) only during running (class 3). The overall ADOS mean score of all the children was 21.14 (7.93 SD). The ADOS mean score of non TTB children was 20.09 (7.66) vs a value of 23.41 (8.5 SD) in TTB children. There were no significant differences in the mean overall ADOS score of the TTB children according to the three TTB classes 24.9 (9.0 SD), class1 vs 20.25 (7.5 SD), class 2 and vs 23.13 (8.38 SD), class3. We divided the children in four groups, depending on the level of the language, according to the ADOS system: fluent language, able to produce simple sentences, able to produce single words, absence of any language( nonverbal ). 44.6% per cent of non TTB children and 72.7% of TTB children were nonverbal ( p<0.05). However, language delay severity was not correlated to the severity of TTB. Conclusions: TTB frequently manifests itself in individuals with Autism. It may occur in three mutually exclusive modalities, which include what is commonly defined toe walking. The presence of TTB is not correlated to autism severity but rather to language delay.

Titolo: L’apporto dell’arte, della religione e della comunicazione nella “cura” delle persone con disturbi dello spettro autistico. (2014)

Autore: Marina Norsi

Info: XXIX Conferenza Internazionale del Pontificio Consiglio per gli Operatori Sanitari “La persona con disturbi dello spettro autistico: animare la speranza” Città del Vaticano, 20-22 novembre 2014

abstract

L'apporto della religione e dell'arte nella cura dei bambini autistici viene analizzata basandosi sui dati riportati nella letteratura e sull'esperienza degli ultimi 10 anni nelle strutture terapeutiche(nidi e asili) in Israele. L'influenza della religione nell'accettare la diagnosi ed affrontare la cura dell'autismo puo' essere positiva(accettazione della malattia come espressione della volonta' Divina) o negativa(malattia come punizione divina per i dubbi dei genitori nei confronti di Dio) . I dati riportati in letteratura confermano che il supporto delle organizzazioni religiose e dei ministri del culto sono di grande aiuto: diminuiscono lo stress e lo stato di ansia delle famiglie. L'arte terapia usata ormai in tutto il mondo come terapia complementare ha vantaggi rispetto alle terapie convenzionali:e' un mezzo di comunicazione non verbale, viene accettata dai bambini in modo positivo e non minaccioso,potenzia il contatto di sguardo, potenzia l'apprendimento di colori, forme geometriche, oggetti. Sono stati descritti in modo particolareggiato esempi concreti dell'uso dell'arte terapia e pratiche religiose nella stesura dei programmi cognitivi, educativi nelle strutture terapeutiche per bambini autistici.

Titolo: Treatment As Usual (TAU) for Preschoolers with Autism: Insight from the Artificial Neural Networks Analyses (2014)

Autore: Antonio Narzisi, Enzo Grossi, Filippo Muratori, University of Pisa - Stella Maris Scientific Institute, Pisa, Italy, Autism Research Unit, Villa Santa Maria Institute, Tavernerio (Como), Italy

Info: International Meeting for Autism Research. May 13th-17th; ATLANTA ( USA )

abstract

Background: In Italy TAU is composed of specific treatments performed by child neuropsychiatric services (CNS) and of school inclusion with individual support teacher. The Artificial Neural Networks have never been used in order to study the effects of treatment. Auto-CM is a special kind of Artificial Neural Network able to find out consistent trends and associations among variables creating a semantic connectivity map. The matrix of connections, visualized through minimum spanning tree filter takes into account non linear associations among variables and captures connection schemes among clusters. Objectives: The main aim is to use Auto-CM, a specific Artificial Neural Networks, in order to evaluate the natural relationships among outcome measure in a group preschoolers with autism engaged in a treatment as usual (TAU). Methods: 61 preschoolers with ASD aged between 24 and 48 months were recruited at different centers in Italy. They were evaluated by blind researchers at baseline and after six months using ADOS-G, Griffiths Mental Developmental scales, and Vineland Adaptive Behavior scales. Parents filled out MacArthur Inventory, Social Communication Questionnaire, and Child Behavior Check List. All children were referred to community providers for available interventions. Results: At endpoint, most of the children were still classified as having an ADOS-G classification of ASD. However, 21 (34.2%) passed from Autism to Autism Spectrum and 3 (4.2%) from Autism Spectrum to Non-Spectrum. Treatment effects were obtained for cognitive functioning, language, adaptive behavior, and child behavior, without differences between developmental-oriented and behavioral-oriented interventions. Parent involvement was a mediator for the best clinical outcome. Baseline low impairments of communication, language comprehension, and gesture were predictors of positive outcome. On the other hand Auto-CM system showed complex relationships between studied outcome variables. Conclusions: Treatment as usual, composed of individual therapy plus school supported inclusion, may be an effective intervention in ASD. Better initial levels of communication in the child and parent involvement during treatment have an important role on positive outcome.

Titolo: Artificial Neural Networks Show Complex Interplay Among Risk Factors Related to Pregnancy, and Peri and Post Natal Period That May Contribute to Autism: A Pilot Study (2014)

Autore: Enzo Grossi, Federica Veggo, Filippo Muratori, Antonio Narzisi - Autism Research Unit, Villa Santa Maria Institute, Tavernerio (Como), Italy, University of Pisa – Stella Maris Scientific Institute, Calambrone (Pisa), Italy,

Info: International Meeting for Autism Research. May 13th-17th; ATLANTA ( USA )

abstract

Background: Autism Spectrum Disorder (ASD) is a multi-factorial disease, where a single risk factor unlikely can provide comprehensive information. Moreover, due to the non-linearity of biomarkers, traditional statistic is often unsuitable and underpowered to dissect their relationship. Recent epidemiological studies have pointed out a number of pregnancy and peri-post natal factors which, contributing to focal brain inflammation, predispose to ASD development. Objectives: The aim of the study is to assess the prevalence and natural relationships among 23 potential risk factors in pregnancy history and peri and post natal events in a group of 45 autistic children in comparison with 54 Typicals. Methods: Traditional statistics (Principal Component Analysis-PCA) and Artificial Neural Networks (Auto-CM system) were applied to highlight the associations among variables under study. Auto-CM is a special kind of Artificial Neural Network developed at Semeion Research Institute( Rome) and successfully applied in many complex chronic degenerative diseases, able to find out consistent trends and associations among variables creating a semantic connectivity map. The matrix of connections, visualized through minimum spanning tree filter, takes into account nonlinear associations among variables and captures connection schemes among clusters. Results: An higher prevalence of potential risk factors was observed in 18 out of 23 risk factors in autistic group; for five of them the difference in prevalence was statistically significant (p<0.05) despite the relative small sample size: exposure to solvent or paints during pregnancy (25% autism vs. 3.8% Typicals), pregnancy complications( 50% autism vs 32% Typicals), perinatal complications ( 36.4 % autism vs 20.75% Typicals), stressful life events (mean number per woman: 0.49 autism vs. 0.06 Typicals), early antibiotic therapy after birth(25.04% autism vs 13.21% Typicals). Auto-CM system, at variance with PCA, was able to point out complex relationships among variable under study showing a convergence of branches of risk factors toward autistic outcome. Conclusions: The general prevalence of potential risk factors in pregnancy history and peri and post natal events is higher in autistic group in comparison with Typicals. According to univariate analysis exposure to solvent or paints during pregnancy, pregnancy complications, perinatal complications stressful life events and early antibiotic treatment appear as key players. Artificial neural networks help to highlight the underlying interaction scheme among different factors on study showing a complex matrix of connections among them.

Titolo: The Early Signs of Autism in First Year of Life: Identification of Key Factors Using Artificial Neural Networks (2014)

Autore: H. Alonim, E. Grossi, I. Liberman, G. Schayngesicht and D. Tayar. The Mifne Center and Social Science School, Bar Ilan University, Rosh Pina, Israel, Autism Research Unit, Villa Santa Maria Institute, Tavernerio( Como), Italy

Info: International Meeting for Autism Research. May 13th-17th; ATLANTA ( USA )

abstract

Background: In a previous study we have presented an innovative methodology to detect early manifestations of autism, using retrospective analysis of parents’ video-recordings of their children's first year of life, filmed before any suspicion concerning defective development arose. Traditional statistics did not allow to handle all the information available due to the high intrinsic non linearity and skewed distribution of symptom frequencies. Similar problems hampered the understanding of natural relationships among factors on study, taking into account simultaneously occurrence, their severity and their precocity in onset. Objectives: The aim of the study is to assess the natural relationships among variables associated with autism onset. Methods: This continued data set is composed on 8 variables displayed in 110 infants (76. % boys and 24% girls between the ages of 3-15 months) who were diagnosed with autism at the age of 2-3 years, using retrospective analysis of video-recordings of the infants' first year of life. In addition, interview questionnaires were distributed to the parents. Variables investigated were: Excessive Passivity; Excessive activity; Lack of reaction to voice or presence; Lack of eye contact; Aversion to touch; Delayed motor development; Accelerated growth of head circumference; Resistance to eating; All variables were objectively measured according to a validated evaluation form scoring. Artificial Neural Networks (Auto-CM system) were applied to highlight the associations among variables under study. Auto-CM is a special kind of Artificial Neural Network developed at Semeion Research Institute (Rome) and successfully applied in many complex chronic degenerative diseases, able to find out consistent trends and associations among variables creating a semantic connectivity map. The matrix of connections, visualized through minimum spanning tree filter, takes into account nonlinear associations among variables and captures connection schemes among clusters. Results: The Semantic Connectivity Map developed by Auto-Cm system showed a meaningful scheme of connections. Lack of eye contact resulted a major node in the graph directly linked with autism spectrum diagnosis and coordinating the other three variables (Lack of reaction to voice o presence; Accelerated growth of head circumference; excessive activity); the other major node resulted to be Lack of reaction to voice o presence, coordinating the other four variables in study. Conclusions: Findings from this study indicate the utility of a data mining approach based on artificial neural networks in depicting complexity of the variables related to early manifestation of autism.

Titolo: Data Mining of Clinical Variables and Biological Endophenotypes in Autistic Patients Using Fourth Generation Artificial Neural Networks (2014)

Autore: R. Sacco, S. Gabriele, E. Grossi, M. Buscema and A. M. Persico. Child and Adolescent Neuropsychiatry Unit, Univ. Campus Bio-Medico, Rome, Italy, Semeion Research Center, Rome, Italy, Autism Unit, Villa Santa Maria Institute, Tavernerio ( Como), Italy

Info: International Meeting for Autism Research. May 13th-17th; ATLANTA ( USA )

abstract

Background: Several studies have attempted to partition autistic individuals into subtypes ideally homogeneous in terms of clinical presentation and/or underlying pathogenesis. Clinical subtyping has been defined one of the major short-term challenges in child and adolescent psychiatry. This is especially true for autism research, since clinical heterogeneity represents one of the hallmarks of ASD. We have recently analyzed the autistic phenotype taking into account observable behaviors, patient- and family-history variables, and biological endophenotypes. Using principal component and cluster analysis on 245 patients, we previously described at least four principal components and four patient clusters (Sacco et al., Autism Res. 2010 and 2012). Objectives: To identify specific patterns linking biological endophenotypes, such as macrocephaly and elevated serotonin blood levels, to autism clinical profiles. Methods: Artificial Neural Network were applied to a complete data set of 110 ASD patients encompassing 25 variables spanning clinical features, family history, morphological and biochemical quantitative traits. We applied semantic connectivity maps (AutoCM), a fourth generation artificial neural network able to detect non-linear trends and associations among variables with significantly greater power as compared to the traditional parametric statistics employed in our previous study. The matrix of connections, visualized through the minimum spanning tree, maintains non-linear associations among variables and captures schemes among clusters of variables. The strength of association in semantic connectivity maps ranges from 0 to 1 (i.e., from no to full association). Results: [1] clinical variables tend to cluster around two configurations: (a) “lower functioning”, which has its central node in the presence of motor stereotypies, strongly connected with intellectual disability (0.99), verbal stereotypies (0.98), hyperactivity (0.98), reduced pain sensitivity (0.97), history of regression (0.94) and self-injurious behaviors (0.93); (b) “higher functioning”, which has its two central nodes in positive history of allergies or immune disease in the patient, or in first-degree relatives, tightly linked to each other (0.97) and with obstetric complications (0.97), delayed onset of social smile (0.97), presence of any infectious disease at autism onset (0.96), pre-term delivery (0.89), normal intellectual level (0.89), and a DSM-IV Asperger (0.88) or PDD-NOS (0.85) diagnosis. [2] Macrocephaly is associated with a positive history of allergy and immune disease in first-degree relatives (0.92) and to a lesser extent with muscle hypotonia (0.77). [3] Hyperserotoninemia may be connected with abnormal EEG pattern and/or history of seizures in males (0.80), whereas in females it appears linked to positive history of allergy/immune disease in first-degree relatives and muscle hypotonia, although sample size limitations for females do not yet allow reliable coefficient estimations. Conclusions: AutoCM algorithms show several complex patterns which replicate and largely extend previous findings obtained with parametric approaches. New insights, such as those possibly linking hyperserotoninemia with abnormal EEG patterns, if replicated may allow novel hypothesis generation and experimental designs. These results will be replicated in an independent sample, so as to better define the relationship between biological endophenotypes, biomarkers and clinical features involved in autism.

Titolo: Prediction of autism from Risk Factors Related to Pregnancy, and to Peri/Post Natal Period: A Pilot Study with Artificial Neural Networks. (2014)

Autore: Enzo Grossi, Federica Veggo, Filippo Muratori, Antonio Narzisi - Autism Research Unit, Villa Santa Maria Institute, Tavernerio (Como), Italy, University of Pisa – Stella Maris Scientific Institute, Calambrone (Pisa), Italy, University of Pisa - Stella Mar

Info: The Autism and Neurodevelopmental Disorders Research Hub at the Institute for Medical Research Israel-Canada and the Canadian Friends of the Hebrew University February 2014

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