Neonatal acute myeloid leukemia in an infant whose mother was exposed to diethylstilboestrol in utero.

We report on an acute myeloid leukemia in a neonate whose mother was exposed to diethylstilboestrol in utero. The newborn presented with leukemia cutis, hemorrhagic skin lesions, hyperleucocytosis and disseminated intravascular coagulation. A bone marrow examination confirmed the diagnosis of acute monocytic leukemia with a t(11;19) MLL-ELL fusion transcript. Chemotherapy was initiated but the child developed a bilateral pulmonary infection that led to fatal respiratory distress. This case shows acute myeloid leukemia and the third pediatric leukemia reported after maternal diethylstilboestrol exposure.

[Prevalence of pervasive developmental disorders. A review]. / Sur la prévalence de l'autisme et des troubles envahissants du développement (TED).

INTRODUCTION: Estimates of the prevalence of autism and pervasive developmental disorders (PDD) are discordant and are moving towards an apparent increase in rates. LITERATURE REVIEW: The studies carried out since 1966 illustrate the variability of the protocols used and explanatory hypotheses put forward. These investigations are difficult, sparse, but still growing at the same time that a debate develops on the possible increase in actual prevalence. Indeed, the rate initially admitted for classic autism was 5/10,000, then 1/1000 with an expanded definition to the forms, but the current figures are very different (almost 0.7% for all PDD), and this increase raises questions. The arguments in favour of an apparent increase are primarily methodological. Several biases are encountered when one compares the recent publications with those of previous years. First, autism is better known and recognized than 30 or 40 years ago. Then, the diagnostic criteria used over time are changing variables, and comparisons difficult. Recent studies using the criteria of a broader definition of autism, polyhandicap with severe retardation and autism signs of lighter forms. The fact that children with autism are diagnosed more frequently in the younger age could also occasionally lead to an artificial increase in the number of cases identified in new surveys in populations of young children. Other factors are cited to explain the current increase. There could be higher rates of autism (and mental retardation) among children of migrants from distant countries, with the aetiological hypothesis of maternal infections, more frequent due to immune deficiency against infectious agents depending on the environment, metabolic decompensations also related to changes in surroundings, or more births from unions among migrant mothers and men with Asperger syndrome (with increased risk of paternity of a child with autism). Other theories relate to pollution, vaccinations, a growing number of premature babies; all assumptions that appear, for the time being, insufficiently explored and documented. The issue is also one of the motivations underlying these steps, and setting a parallel prevalence actually increased with this or that factor has presently been scientifically validated. Finally, if a careful reading of recent publications indicates that autism has become more frequent; assumptions that describe an increase in "artificial", based on methodological arguments, seem to be more consistent. EFFECTS OF EXTENSION OF DIAGNOSTIC CRITERIA AND NOSOGRAPHY FOR PDD: Today, the recruitment of individuals with autism in a population far exceeds the initial criteria of Kanner in the 1970's. It includes clinical forms with associated pathologies, or lighter and probably more frequent clinical forms. Other assumptions arouse interest, but also controversy regarding their relevance. The enumeration of cases of PDD in a population is actually at its beginning. In the 1970's, "childhood psychoses" (the term then used) seemed rare. The identification of cases was probably the main reason. Long available figures remain scarce, and their rate increases gradually from the 1990s, but is, in fact, a problem of inflation. What is the part played in this flight of changing diagnostic criteria and substitutions, or other methodological effects? Or even opportunistic effects, if we speak of an epidemic to undermine a variety of factors. The evidence provided so far is the improved identification of cases, enlargement of the concept, and better shared diagnostic criteria. However, the validity and limitations of clinical forms are still vague and unresolved. DISCUSSION: How to study epidemiology in the future - to move forward, studies should be designed with partners' medical history and medicosocial studies, based on a better consensual methodology, epidemiology, statistics and diagnosis, with a definition of the thresholds for inclusion, and arbitration procedures. On this basis, a study must also be coordinated with those concerning mental retardation, learning disorders, etc, otherwise the same topics will be counted twice or even three times. As for the addition of syndromic forms of PDD (those with known aetiology), their number is still below a proportion sufficient to be an appeal. Moreover, another problem exists: the degree of membership of each of these syndromes, or individual cases, or autistic spectrum disorders (internal variability phenotypes). For the moment, we could design two studies included better: developmental disorders and associated pathologies. Regarding the "ethic" dimension, a more regular diagnosis of PDD (preferred to that of mental retardation or learning disorder) will lead to shared practices and set limits for greater recognition.

[Autism and associated pathologies. Clinical study of 295 cases involving development disorders]. / Autisme et pathologies associées. Etude clinique de 295 cas de troubles envahissants du développement.

OBJECTIVE: Known since the first descriptions in 1943, diseases related to autism and associated disorders have incited a growing body of work. Both theoretical interrogations (what is the pathogenic role of autism?) and practical measures (management, screening) are implied. Nevertheless the frequency of autism-related disease has varied from 10 to 37% depending on the series reported. We studied the frequency of these factors in a population of children with major development disorders cared for at the Tours university hospital over a 39-month period. PATIENTS AND METHODS: We reviewed retrospectively the medial features of 295 children examined in our psychiatry and neurophysiology unit for children at the Tours center for major development disorders (based on the DSM IV diagnostic criteria) between September 1995 and December 1998. We divided these factors into 4 categories: hereditary diseases, serious medical conditions, minimal physical disorders and ante- or perinatal antecedents. RESULTS: Among these 295 children, 26.5% had a proven or probable hereditary disease, 19% had a serious medical condition and 21.7% had minimal physical disorders. Among the children with a serious medical condition, 34.4% also had ante- or perinatal antecedents. Among the 33% without any medical factor, 77% also had ante- or perinatal antecedents. CONCLUSION: Our data point out the quantitative importance of medical factors associated with major development disorders. They imply a close multidisciplinary collaboration between child psychiatrists, pediatricians and geneticists in order to identify these disorders and develop an integrated management scheme. On a more theoretical level, it appears possible to identify subgroups of children among such a population based on associated diseases and neuropsychological patterns. This dimension would be useful for research into the pathogenic mechanisms involved.

[Neuropsychology and academic achievement of epileptic children: executive-functions tests]. / Fonctions neuropsychologiques et acquisitions scolaires des enfants épileptiques: quelques tests d'évaluat8on et réflexions méthodologiques.

Children with epilepsy are exposed to learning disabilities. In young children, still not taught reading, spelling or mathematics, the standardized psychometric evaluation provides a usefull assessment tool enabling identification of the structural disturbances that will affect the learning process. For school-age children, assessment can be made in regard to the DSM IV criteria of specific learning disabilities, and within a neuropsychological framework that pays a particular attention to the executive functions.

Comparative response to single or divided doses of parenteral iron for functional iron deficiency in hemodialysis patients receiving erythropoietin (EPO).

EPO treatment rapidly corrects anemia in patients with end-stage renal failure treated with hemodialysis, as long as sufficient iron is available. Absolute and relative (to demand) iron deficiency blunts the erythropoietic response and parenteral iron is frequently required during the course of therapy to restore EPO efficacy. Since the optimum time course of iron administration to restore EPO response in the short term is unknown, we compared three protocols of i.v. iron dextran administration in apparent functionally iron-deficient HD patients on oral iron therapy (hemoglobin < 10.0 g/dl plus ferritin < 100 micrograms/l and/or transferrin saturation < 20%). Intravenous iron (Imferon; Fisons Pty Ltd.) was given either as a single 600 mg dose (n = 15, Group I) or in divided doses of 100 mg administered on 6 successive dialyses (n = 14, Group II) or weekly for 6 weeks (n = 14, Group III). Response was monitored for 8 weeks. No adverse effects were observed. Collectively, mean hemoglobin increased (p < 0.01) by 0.4-0.5 g/dl plateauing at 4 weeks (between group comparison, p = 0.92). Mean ferritin concentrations changed with time (p < 0.01), peaking at 2 weeks in Groups I and II and at 4 weeks in Group III. Mean transferrin saturation levels also increased during the study (p < 0.001). The between group comparisons for the trends in iron indices were significant (p < 0.01 and 0.05 respectively). As there were no clinically significant differences in hemoglobin response at 4 weeks, single dose iron infusion would seem to be the most expedient in the short term, however frequent small doses are similarly effective.

[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.

[Rett syndrome and autism. Early comparative evaluation for signs of autism using family movies]. / Syndrome de Rett et autisme. Evaluation comparative précoce des signes d'autisme à l'aide de films familiaux.

Rett's syndrome progresses in 4 stages: the first signs of the disorder appear after a period of 6 to 7 months, during which development is considered to be normal. This asymptomatic period is apparently an essential criterion of the diagnosis, but some parents have reported some prodromes. In stage II of the disease (before 3 years), signs common with autism dominate the clinical picture and the diagnosis of the latter was often formulated. Our working hypothesis is that the pedopsychiatric analysis of home movies of young girls with Rett's syndrome, taken by the parents before the age of 2, may be able to show early clinical signs. The present study involved examining home movies of children subsequently diagnosed as having Rett's syndrome (n = 9) in comparison to those of autistic (n = 9) and normal (n = 9) children, using semiological evaluation tools (IBSE, BFE). The persons scoring were not advised of the diagnosis. The observations were thus situated before the disorders and/or at the time of their appearance. The study confirms the asymptomatic interval between birth and the first signs of the disease, it defines the mode of onset and shows the disturbance of certain functions such as intent and imitation, more pronounced in Rett's syndrome children between 12 and 18 months. At this age, it also enables Rett's and autistic children to be differentiated on the basis of the different involvement of the "cognition" function and unusual posture, more pronounced in these girls. It does not, however, differentiate Rett's from autism between 6 and 12 months and it is thus not surprising that at this stage the diagnosis of rett's syndrome or autism may be a source of confusion.

[Bourneville's tuberous sclerosis and autism]. / Sclérose tubéreuse de Bourneville et autisme.

Tuberous sclerosis is often associated with developmental and behavioural disorders including typical or partial autistic syndrome. However, it may be difficult to recognize tuberous sclerosis behind an infantile autism during the early stages of the disease. Therefore, tuberous sclerosis must be regularly looked for on the basis of its major and minor criteria in any cases of infantile autism. The child psychiatrist is preferentially involved in the management of the various aspects of this association, ie, behavioural or character disorders, difficulties in social relationships and communication, mental retardation, feeding disorders, and psychological consequences for the families. The support provided may be complemented by that offered by the Association for Bourneville's tuberous sclerosis.

[Natural history of infantile autism (nosography)]. / Histoire naturelle de l'autisme infantile (Nosographie).

Natural history of infantile autism goes from its first description to current classifications. Most authors agree upon the perfect character of Kanner's description in 1943. But its situation in the nosography has much developed. The parution of 4th edition of Diagnostic and Statistical Manual of mental disorders (DSM IV) bring us to analyse this evolution and the place of autistic disorders in the pervasive developmental disorders, with this of associated pathologies. The comparison of current classifications (DSM IV, ICD 10, CFTMEA) allows us to do correspondence between each diagnostic category in psychosis or developmental disorders of these classifications. It exists a real concordance between DSM IV and ICD 10. The french classification of child and adolescent mental disorders (CFTMEA) proposes original categories.

Identification of behaviour profiles with a population of autistic children using multivariate statistical methods.

The Revised Behaviour Summarized Evaluation Scale (BSE-R) was developed for the objective evaluation of autistic behaviours in order to facilitate the recording of the evolution of developmentally disabled children. Among its 29 items, 13 items that precisely describe the degree of autistic behaviours were extracted by Principal Component Analysis. We hypothesised that these relevant behaviours could differentiate autistic behaviour profiles in a population of children previously diagnosed as typically autistic. For this purpose, we used an original multivariate descriptive statistical approach, Correspondence Analysis, which can help in detecting structural relationships among variables. In a population of autistic children initially diagnosed using DSM-III-R criteria, this procedure proved effective in identifying new main dimensions of behaviours among the 13 previously defined core autistic symptoms. Cluster analysis, which followed factorial analysis, allowed the identification of three meaningful behaviour profiles separated principally on the basis of two main functions, perception and imitation, which have been always considered to be fundamentally involved in autistic syndrome. The individualisation of homogeneous subgroups of children on the basis of the behavioural evaluation provides a potentially useful starting point for further biological and therapeutic studies.

Autism and genetics: clinical approach and association study with two markers of HRAS gene.

Twin studies and familial aggregation studies indicate that genetic factors could play a role in infantile autism. In an earlier study, we identified a possible positive association between autism and a c-Harvey-ras (HRAS) oncogene marker at the 3' end of the coding region. In an attempt to confirm this finding, we studied a larger population, well-characterized clinically and genetically. We report a positive association between autism and two HRAS markers, the 3' marker used in the initial study and an additional marker in exon 1.

Disorders of regulation of cognitive activity in autistic children.

Infantile autism is a pervasive developmental disorder characterized by disturbances concerning not only the areas of socialization and communication ("aloneness") but also the ability to modify and change behavior ("need for sameness"). In most recent studies, various abnormal and deviant cognitive activities, such as the ability to regulate one's behavior, were considered as accounting for these signs. In this report, we examined the regulation of cognitive activity, from a developmental perspective in comparing autistic with mentally retarded children matched in a pairwise manner by global, verbal, and nonverbal developmental ages. All children were tested with tasks adapted from the Object Permanence Test which corresponds to Piaget's sensorimotor development Stages IV to VI. Results showed that autistic children had a pervasive difficulty in maintenance set, made more perseverative errors when the abstraction degree of task was higher, and were more variable in their behavioral strategies. Discussion is focused on the interests and limits of these tasks for the examination of regulation activity from diagnostic and developmental perspectives. Finally, interpretations about recent neuropsychological and neurophysiological works, and additional interdisciplinary studies are suggested.

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.

[Psychotic women and their children]. / Les femmes psychotiques et leurs enfants.

With desinstitutionalization, the social life of psychiatric patients and particularly that of psychotics has arisen in new terms over the past twenty years. In particular, relationships and sexuality of these patients are manifest realities to which few studies are devoted. 61 schizophrenic and 21 bipolar women (18-45 years of age, mean 34 in-or outpatients) were interviewed with a battery of instruments (PANSS, Carpenter's criteria of schizophrenia with deficit syndrome, axis V of DSM-III-R) and with a semi-structured questionnaire related to clinical data, sexuality, relationships, children and motherhood. Half of the schizophrenic women have an active sexual life, and children. The study provides information about the reproduction rate of schizophrenic women, the precocity of their pregnancies and the outcome of their children. The study also treats these women's ability to rear their children, their desire to have children and any hospitalizations during the perinatal period. These results, as well as those related to abortion and contraception, are discussed in the light of those of the bipolar control group.

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.