[Further clinical evaluations elicited by functional biological investigations in childhood autism]. / Evaluations cliniques complémentaires suscitées par des explorations biologiques fonctionnelles dans l'autisme de l'enfant.

As childhood autism is usually considered as a developmental disorder, complete assessment of each patient requires non only clinical examination but various biological investigations: EEG and evoked potentials recordings, biochemical dosages and sometimes, cerebral blood flow measures, molecular biologic explorations.... These investigations help to understand neurophysiological dysfunctionings which underly different autistic syndromes. It therefore seems necessary to develop quantified clinical tools which could allow closer matching between clinical evaluations and biological numerical data. These complementary evaluations must be both simple and quick to perform in medical practice, as they are added to an already heavy clinical examination. The main tools used in our bioclinical Department are described here. For each child, psychiatric, pediatric and neurological examination was performed. Different scales were progressively elaborated and validated to complete and precise behavioral parameters. Attention and perception were evaluated by a Behavior Summarized Evaluation (BSE) scale, association and imitation by appropriate scales, language by the Pre-Verbal Behavior Summarized Evaluation (PV-BSE) scale, early symptoms by the Infant Behavior Summarized Evaluation (t-BSE) scale. The main neurophysiological dysfunctionings were grouped in a Behavioral Functional Inventory (BFI). Clinical genetic data were scored in a summarized assessment carrying both on the antecedents and on the somatic abnormalities. The completed clinical data were gathered in a Quantified Multidimensional Assessment (QMA), with four axes: socialization, communication, cognition and neurological observation. These clinical evaluations provide behavioral details that can be integrated into a bioclinical database and give an objective approach to the heterogeneity of autism. They invite both clinicians and biologists to deepen the description of individual profiles which allow better understanding of physiopathological mechanisms in autistic children.

Validation of the Revised Behavior Summarized Evaluation Scale.

The Behavioral Summarized Evaluation scale (BSE), previously published and validated, was developed for the evaluation for the autistic behavior in developmentally disorder children. A revised version of this scale, the Revised Behavior Summarized Evaluation Scale (BSE-R) completed the 20-item BSE scale with the most relevant items extracted from a similar evaluation carried out with very young children. Thus 9 items were added to the original scale concerning nonverbal communication, emotional, and perception areas. This paper reports the reliability and validity studies of this new scale. In addition to confirming the previously published findings concerning the first version of the BSE, new items were extracted from the BSE-R content validity study. They involve fundamental functions such as intention and imitation which open new perspectives for a physiopathological approach to developmental disorders. The BSE-R is a useful tool for progressive recording of the evolution of patients both treated over long periods and included in short-term controlled therapeutic studies.

Quantified multidimensional assessment of autism and other pervasive developmental disorders. Application for bioclinical research.

A large number of investigation techniques are used to establish the relationships between the clinical and biological data which are necessary for physiopathological analysis in the field of developmental disorders. It therefore seemed necessary to develop a quantified grouping system, based on developmental assessments, which could allow closer matching between clinical evaluations and biological numerical data. Two hundred and two subjects presenting developmental disorders (autistic disorder, pervasive developmental disorder not otherwise specified and mental retardation) were examined. For each child, a quantification of autistic behaviour, intellectual impairment, neurological signs and language and communication disorders was performed. A cluster analysis of these quantified data elicited four subgroups according to the scores obtained in these four different areas. We showed the value of this approach by applying it to one of the studies of monoamines routinely examined in childhood autism--dopamine and HVA, its main urinary derivative. Moreover, this method revealed a subgroup within the total population which was independent of nosographic classification and which had a particular clinical and biochemical profile. Other applications could follow, for example in the fields of neurophysiology, cerebral imaging, molecular biology and genetics.

Association study with two markers of a human homeogene in infantile autism.

Epidemiological data and family studies in autism show that there is a genetic susceptibility factor in the aetiology of this syndrome. We carried out an association study in infantile autism. Two markers of the homeogene EN2 involved in cerebellar development were tested in a population of 100 autistic children and in a population of 100 control children. With the MP4 probe showing a PvuII polymorphism, significant differences in the allele frequencies between the two populations were found (chi 2 = 7.99, df = 1, p < 0.01). With the MP5 probe showing an SstI polymorphism, no difference appeared (chi 2 = 1.17, not significant). Several clinical examinations allowed us to characterise the autistic children. Most of them had high scores for autistic behaviour and language disorders but low scores for neurological syndromes. Two children had a significant family history and six children had confirmed syndromes or diseases of genetic origin. Discriminant analysis between clinical and molecular data did not give significant results. These preliminary results must be supported by further analyses of this gene and by studies of its potential involvement in the pathophysiology of the autistic syndrome.

Catecholaminergic metabolism and autism.

The authors determined levels of dopamine (DA) and its derivatives homovanillic acid (HVA), 3-4 dihydroxyphenylacetic acid (DOPAC), 3 methoxytyramine and norepinephrine + epinephrine (NE + E) in the urine, and DA, E and NE in the whole blood of 50 autistic children aged between 1 year 11 months and 16 years. An association was tested for between markers coding for the enzymes and D3 dopaminergic receptor genes implicated in the monoaminergic pathway and autism, using restriction fragment-length polymorphism. There were significant modifications of catecholamine metabolites, but no difference for allele frequencies of the genes coding for tyrosine hydroxylase, dopamine beta hydroxylase and DRD3 in this population compared with a healthy school population matched for chronological age. However, some of the data encourage a more complete study of chromosome 11.

[Childhood autism: a relating deficiency due to a developmental disorder of the central nervous system]. / L'autisme de l'enfant: une déficience relationnelle liée à un trouble du développement du système nerveux central.

Childhood autism with its difficulties in relating to others has been for a long time imputed to conscious or unconscious educative errors of the mother. Clinical and biological data can be opposed to this conception. Familial movies analysis exhibits early disorders in attention, perception, intention, limitation and muscular tone. Later, recording of cerebral reactivity to auditory stimulations confirms deficiencies in attention, perception, association ... and shows a diminution of the responses in the left hemisphere. Abnormalities in the development of the cerebellum are also described. Modifications of main neurotransmitters as Dopamine and Serotonin and their derivatives are often present. A recent study of the genes which control enzymes regulating metabolism of these transmitters does not show evident modifications by polymorphism analysis. On the contrary a peculiarity in the Harvey-RAS gene allows to differentiate in a significant way an autistic and a normal group. This gene is involved in the regulation of growth factor and/or differentiation of neural cells. These observations support the hypothesis considering autism as a relating deficiency due to a developmental disorder of central nervous system.

[Nosography of autism. Critical discussion of current classifications]. / Nosographie de l'autisme. Discussion critique des classifications actuelles.

Child autism is a serious and early-forming developmental disorder and its nosography is evolving quickly. Classifications of autism have been produced since the works of Kanner in 1943 and especially in the last fifteen years, or so in order to respond to the needs of clinical practice and of research. Because of the presence of borderline or various uncommon clinical forms and, more generally, considering the heterogeneousness of clinical conditions concerning autism, it appears necessary to break up autism into better defined sub-groups. Moreover, the existing systems do not apply very well before the age of two or three, when the diagnosis and investigations nevertheless begin. Progress is achieved today by using simultaneously multidimensional and quantitative evaluations, an example of which is presented. In the future, a knowledge of etiological factors and/or the identification of biological markers will guide the classification of developmental disorders.

Blind ratings of early symptoms of autism based upon family home movies.

Ratings of family home movies of 12 infants (0 to 2 years old) who were later diagnosed as autistic and 12 normal infants were performed by two diagnosis-blind psychiatrists with Infant Behavior Summarized Evaluation scale. The objective was to identify early symptoms of autism and their intensity and frequency before and after 1 year of age. Several pathological types of behavior related to socialization, communication, motility, and attention were noted during the first year of infant life and differentiated autistic and normal groups. These same differentiating behaviors, observed again in the second year, were more intense and associated with other pathological types of behavior, in particular, gaze avoidance, hypoactivity, and absence of emotional expressions. Analysis of the evolution of behavioral pathology in autistic children as a group during the 2 first years of life confirms the persistence of and the increase in some types of abnormality related to socialization, communication, motility, and attention functions. The limitations and values of this study concerning the early identification of autistic symptoms and functional impairments from home movies for diagnosis and establishing individualized treatment program are discussed.

Autistic children and the object permanence task.

Many mentally retarded autistic children can understand the concept of object permanence, but, in comparison to developmental-age matched normal children, the behavioral strategies they employ in carrying out the Casati-Lezine Object Permanence Test are deficient and lead to failure. These deficiencies appear unrelated to interference of stereotypic or other bizarre behavior in task performance. Similar problem-solving deficiencies can be found in mentally retarded children who are not autistic, suggesting that the deficiencies themselves are less related to the social-communication deficits of autistic children, but more to the general problem-solving difficulties found in children with a lower developmental quotient. Nevertheless, the qualitative analysis of results shows a tendency in autistic children, despite their better developmental level, to use less coordinated and regular sequences to solve the task than normal or mentally retarded children.

Validity and reliability of the infant behavioral summarized evaluation (IBSE): a rating scale for the assessment of young children with autism and developmental disorders.

The Infant Behavioral Summarized Evaluation (IBSE) is a rating scale adapted from the Behavioral Summarized Evaluation (BSE) and specifically related to the assessment of behaviors of young children having autistic disorders. Content validity and reliability studies described in the paper were made from behavior ratings of videotapes for 89 children aged from 6 to 48 months. Results show a significant group of 19 items including some characteristic early autistic behaviors (communicative and social abnormalities) and some that are less commonly described in the syndrome (attentional, perceptive, and adaptive disorders). The value of the use of this scale for clinicians and professionals involved in behavioral evaluations and treatment of young children with developmental disorders and the necessity for further psychometric investigations are discussed.

Early symptoms in autism from family home movies. Evaluation and comparison between 1st and 2nd year of life using I.B.S.E. scale.

The analysis of 11 home movies taken by parents before the recognition of autistic or atypical disorders of their own child has confirmed the major value of this method for describing early pathological signs. Symptomatology analysis has revealed anomalies of eye contact, a deficiency and variability of emotional expression, a defect of attention and initiation of communication, as well as motor abnormalities. The comparison of the frequency of abnormal behaviour, assessed with a rating scale among three groups of children (autistic, pervasive developmental disorders and normal) revealed behavioural differences as a function of early age and diagnosis, which concern not only social and communicative behaviours, but those of emotion and attention as well. The limits and interest of this methodological approach are discussed and the possibilities of subsequently using these documents in a more complete method, such as blind examination and scoring by uninformed investigators, are suggested.

Autism and family home movies: preliminary findings.

Preliminary analyses of 12 home movies taken by parents before the recognition of autistic disorders of their own child confirm the major value of this method for describing early signs: anomalies of eye contact, deficient variability of emotional expression, defect of attention and initiation of communication, motor abnormalities, etc. The possibilities of subsequently using these documents in a research context are described: behavior assignment with a rating scale, comparative analysis with movies of normal children, blind examination, and scoring by investigators not informed of the diagnosis.

[Autism in infants and young children. The value of early diagnosis]. / Autisme du nourrisson et du jeune enfant. Intérêt du diagnostic précoce.

Clinical studies of early symptoms are among the most significant advances achieved during recent years in the field of autism. The first descriptions of early symptoms were retrospective and lacked precision. Autistic children are now being seen increasingly early and new insight is being gained into the initial manifestations and differences in clinical patterns. Similarly, differential diagnosis problems (borderline forms) are changing as clinicians evaluate children at younger ages. Although a definitive diagnosis is neither possible nor even desirable before the age of 18 to 24 months, detailed clinical data should be collected early. This data forms the basis for differential diagnosis and will be needed later for differentiating various clinical patterns of developmental disorders, establishing a prognosis, and monitoring therapeutic effects. In prospective longitudinal studies of autistic children, comparison of recent observations with detailed early data is essential. Early initial evaluation includes videotape recordings, assessment of cognitive functions and communication skills, and use of a scale for autistic symptoms. Using the results of evaluations of very young children, a specific semiology (communication disorders) can be developed. Several symptoms probably denote neurophysiologic and/or perceptive disorders. Primary symptoms are now being better distinguished from secondary anomalies (behavior disorders) that may be avoidable or treatable.

[A psychiatric consultation service at a pediatric hospital. Definitions, nomenclature, perspectives]. / Psychiatrie de consultation-liaison à l'hôpital pédiatrique. Définitions, nomenclature, perspectives.

A psychiatric consultation service has been implanted for the last 15 years at the Children's Hospital of Tours. It co-ordinates pediatric psychiatric activities on the various wards of this large pediatric center (200 beds). All pediatric psychiatry personnel belong to this autonomous unit which plans their work: clinical care and liaisons, teaching and research activities. This unit manages 1,000 cases a year: 20% of children are aged 0 to 2 years, 40% are under 5 years of age. This type of structure in a university pediatric hospital fosters considerably an early diagnosis and the prompt triaging of children to the services available in their home districts for appropriate care. Furthermore, it facilitates a comprehensive approach with appropriate integration of the somatic and of the psychodynamic dimensions of the child. This type of implantation constitutes a significant step forward in the field. However, its professional activities are handicapped because of the discrepancy between resources made available to psychiatry and pediatrics due to the failure to take into account the type of interventions required of the pediatric psychiatrist. In the hope of remedying these problems of evaluating the services distributed by psychiatry to young children hospitalized in clinical units, we present a specific nomenclature, elaborated after several years of experience. It classifies services in four large categories: Consultation and liaison in in-patient care units; chronic care carried out on a part time basis; admissions to the Pediatric Psychiatry Unit in beds belonging to various pediatric services; complete workups in day care beds.