The necessity of level IIb dissection for clinically negative neck oral squamous cell carcinoma.

AIM: Selective neck dissection reduces the incidence of complications associated with radical neck dissection while achieving the same oncological results, especially in clinically node-negative (cN0) cases. The most common complications associated with selective neck dissection are spinal accessory nerve dysfunction and shoulder disability, which result from level IIb dissection. The aim of the present study was to evaluate the incidence of level IIb lymph node metastasis in cN0 oral squamous cell carcinoma (OSCC) patients to determine the necessity of selective neck surgery. METHODS: The medical records of 138 consecutive OSCC cN0 patients seen from June 2012 to June 2017 were retrospectively reviewed for age, gender, tumor localization, and TNM classification. RESULTS: The incidence of occult metastasis was 29.7%, but level IIb nodes were not involved in any case. DISCUSSION: The lack of involvement of level IIb nodes in occult metastasis, and high prevalence of shoulder dysfunction caused by injury to the spinal accessory nerve during surgery, challenge the necessity of surgical IIb node clearance in cNO OSCC; this is true for all stages and especially for early T1 stage cases, when the likelihood of occult lymph node metastasis is low (15.6%).

Immunoreactivity of sera to a peptide derived from the serotonin 5-HT1A receptor in a group of children with developmental disorders: possible role in non-autistic epilepsy.

The presence of autoantibodies against the serotoninergic 5-HT1A receptor has been reported in serum from an autistic child using radioligand binding studies. It is now well established that, in cardiovascular diseases with an autoimmune component, patients present in their sera autoantibodies directed against the second extracellular loop of some G-protein coupled membrane receptors. We thus investigated by an enzyme-immunoassay method the presence of anti-5-HT1A receptor antibodies in sera of children with developmental disorders using synthetic peptides corresponding to the first and the second extracellular loops of this receptor. The population of children with developmental disorders was divided in autistic children with or without EEG abnormalities, and in non-autistic children with or without EEG abnormalities. We found that 6 out of 10 sera of non-autistic children with an abnormal EEG recognized the second extracellular loop of the 5-HT1A receptor. This is significantly higher than the other groups of children with developmental disorders or a healthy control group. These observations support the existence of an autoimmune component in epilepsy.

[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.

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.

Bioclinical profiles of autism and other developmental disorders using a multivariate statistical approach.

To study the relationships between clinical and biological data that are necessary for physiopathological analysis in the field of developmental disorders, we developed a quantified grouping system, based on four developmental assessment parameters. Parallel with this clinical research, we developed electrophysiological procedures adapted to the pathology of autism. In this paper, we report the utilization of an original multivariate descriptive statistical approach (correspondence analysis followed by cluster analysis) that allowed us to identify different bioclinical profiles using these clinical and electrophysiological data conjointly. These profiles are believed to be evidence for different underlying cerebral dysfunctions. This procedure proved effective in identifying two main bioclinical dimensions in a population of 145 developmentally disordered children. These dimensions reflect the association of intellectual impairment and centroparietal electrophysiological reactivity on the one hand, and autistic behavior and temporal electrophysiological reactivity on the other. This study, performed on a large population of children using objective methods of data analysis, provides validation of numerous multidisciplinary studies of autism and other developmental disorders carried out on small samples of children.

Neuropathological study of a case of autistic syndrome with severe mental retardation.

Infantile autism is a syndrome of unknown aetiology and unknown neuro-anatomic substrate. The authors report a histological study of the brain of a well-documented 16-year-old female with autistic syndrome and severe mental retardation, using direct microscopic examination of the whole brain. The major findings are low brain weight, a thin corpus callosum and ventricular dilatation. No abnormalities were found in the hippocampus or cerebellum. Excessive axonal elimination during brain development is hypothesized. The relations of hypothetical developmental events with the clinical features of autistic syndrome are discussed.

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.

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.

Delayed maturation of the frontal cortex in childhood autism.

OBJECTIVE: The authors investigated the metabolic maturation of the frontal cortex in pre-school autistic children. METHOD: Regional cerebral blood flow (CBF) in five children with primary autism diagnosed according to the DSM-III-R criteria was studied longitudinally. Regional CBF in each of the autistic children was measured with single photon emission computed tomography twice during their development: at the age of 3-4 years and 3 years later. At each stage, the autistic children were compared to an age-matched comparison group of five nonautistic children with normal development. RESULTS: A transient frontal hypoperfusion was found in the autistic children at ages 3-4 years; this corresponded to the pattern of perfusion observed in much younger normal children. By the ages of 6-7, the autistic children's frontal perfusion had attained normal values. CONCLUSIONS: Since CBF patterns in children are related to maturational changes in brain function, these results indicate a delayed frontal maturation in childhood autism. Such a delayed brain maturational process is consistent with the clinical data and cognitive performance of autistic children.

Cognitive and social dysfunction in childhood autism: a neuropsychological and physiological approach.

A neurophysiological approach to developmental studies of childhood autism has revealed major cognitive and sensori-motor disturbances which are associated with impairment in social relationships. This new approach suggests the existence of underlying cerebral dysfunction, signs of which are revealed by functional exploration and cerebral imaging.

Dopaminergic D2 receptor SPECT imaging in Rett syndrome: increase of specific binding in striatum.

A dopamine deficiency has been implicated in Rett syndrome, a progressive encephalopathy in girls that involves movement, tonus and cognitive disorders. To test the hypothesis that striatal D2 receptors increase in number in early stages of the disease, we measured the binding potential of 123I-Iodolisuride, a specific D2 ligand, in eleven Rett children aged 4-15 yr (7.9 +/- 3.5 yr) (mean +/- s.d.) and eight control subjects aged 3.5-13 yr (8.1 +/- 3.8 yr) who exhibited other neurological disorders. Regional cerebral blood flow (rCBF) was also measured with SPECT using 133Xe. The binding potential for 123I-ILIS and D2 receptors was significantly higher in Rett (0.45) than in controls (0.23) (p < 0.01). An increase in 123I-ILIS binding due to increased rCBF in patients' striata was excluded. Our results are consistent with a higher density of D2 receptors in young patients suffering from Rett syndrome because of reduced dopaminergic neurotransmission.

Auditory stimulus intensity responses and frontal midline theta rhythm.

The influence of stimulus intensity on the N1 component of auditory evoked potentials recorded at fronto-central sites was investigated in respect to the spectral components of the EEG recorded at Cz, Fz and Oz. The study was performed on 14 healthy adult subjects. The only EEG frequency bandwidth that was strongly correlated with the N1 amplitude-intensity slope was the theta rhythm, particularly the 5-7 Hz frequencies recorded at Cz and Fz. This frequency bandwidth corresponds to the previously described frontal midline theta rhythm related to performance of tests that require continuous concentration of attention. Our results show that the steeper the slope, the greater the amount of Fm theta. This suggests that the interindividual differences in the N1 amplitude/intensity slope could be related to interindividual differences in attentional readiness toward the auditory stimuli, even when delivered in "passive" conditions.

Theoretical aspects of the study of benzodiazepine receptors in infantile autism.

This paper is part of a special section on 'psychopharmacotherapy in children' and focuses on benzodiazepine receptors in autism. Infantile autism in an early and pervasive developmental disorder described by Kanner in 1943. Anatomical, pathological and magnetic resonance imaging studies have indicated changes in the cerebellum and hippocampus of autistic subjects. Given the numerical importance and diffuse benzodiazepine receptors, their study by functional brain imaging methods in vivo could be value in cases of infantile autism as a gauge of neuronal potentiality. The main data concerning benzodiazepine complex are presented. The relations between these data and the neurophysiological hypotheses of autism are discussed.

The complexity of dopamine receptors and psychopharmacotherapy in children.

The efficacy of dopaminergic antagonists, which are neuroleptics, has been shown in children in varied clinical situations. Five dopaminergic receptors (D1, D2, D3, D4, D5) have thus far been cloned: their existence has thus been confirmed, but their functional significance remains to be determined. This publication reviews their main characteristics. The multiplicity of cerebral dopamine receptors is consistent with the future development of new, more selective and discriminating psychotropic drugs. The diversity of interactions of dopaminergic receptors, among themselves and with receptors for other neurotransmitters, however, explains the difficulty in understanding the mechanism of action of neuroleptics and defining their more rational use in children.

Blood flow response to auditory stimulations in normal, mentally retarded, and autistic children: a preliminary transcranial Doppler ultrasonographic study of the middle cerebral arteries.

Using the noninvasive transcranial ultrasonic Doppler method, flow dynamics of the middle cerebral arteries were investigated in relation to auditory stimulations in 12 children with autistic behavior compared with 12 normal controls and 10 mentally retarded children. In normal children, auditory stimulation evoked lateralized modifications: blood flow increased and resistance index decreased on the left side; such modifications were not recorded on the right side. This pattern should indicate vasodilatation mechanisms induced by changes in the metabolism of the brain areas supplied by the left middle cerebral arteries (MCA). Although less asymmetrical, this pattern was also found in the mentally retarded children. Autistic children significantly differed from these two groups. They displayed a symmetric pattern of responses with a blood flow decrease and resistance-index increase on both sides; this could suggest abnormal metabolic mechanisms induced by auditory stimulation in autistic children and could be related to the previous hypothesis of impairment in the development of cerebral lateralization in autism. These preliminary results show that transcranial Doppler ultrasonography may be a valuable and practicable tool for the noninvasive study of evoked blood flow responses in psychopathology.

Regional cerebral blood flow in childhood autism: a SPECT study.

OBJECTIVE: The authors investigated a possible cortical brain dysfunction associated with infantile autism. METHOD: They measured regional cerebral blood flow with single photon emission computed tomography (SPECT) and xenon-133 in 21 children with primary autism (according to DSM-III-R criteria). Five cortical brain areas including frontal, temporal, and sensory association cortices were examined in order to test the recent hypothesis of cerebral dysfunction in primary autism. Anatomical references for each subject were obtained with computerized tomography or magnetic resonance imaging and were used to delimit the regions of interest for SPECT analysis. RESULTS: When the results from the group with primary autism were compared with an age-matched group of nonautistic children with slight to moderate language disorders (N = 14), no cortical regional abnormalities were found. CONCLUSIONS: It appears that there is no regional cortical dysfunction in primary autism; however, in light of methodological limitations, one cannot exclude the possibility of more localized or subcortical brain dysfunctions in autism.

[Development in the metabolism of dopamine and its derivatives. Application to gross development disorders]. / Evolution du métabolisme de la dopamine et de ses dérivés au cours du développement. Application aux troubles globaux du développement.

Dopamine (DA) and its metabolites homovanillic acid (HVA) in total, free and conjugated forms, dihydroxyphenylacetic acid (DOPAC) in total, free and conjugated forms, and 3 methoxytyramine (3 MT) levels were determined in the urine of autistic children from 2 years 8 months to 12 years of age and compared to those in normal children of identical age. Very significant group and age effects were found for DA, HVA and 3 MT. In the discussion, results are related to the hypothesis of a disorder in the maturation of the dopaminergic systems in infantile autism.