[Chronobiological aspect of children autism diagnostics].

The author reviews the history and classification of autistic disorders and describes in details (by months and year periods) clinical symptoms of early children autism from the birth to 6-8 years of age in 41 children. Follow up data on the patient's state at the age 8-14 years, with account for the effects of treatment and correction, are presented as well. The results are discussed in the aspect of critical periods and phases of early ontogenesis, their deviations and pathology.

[Clinical and neurophysiological aspects of severe forms of autism in children].

The aim of the study was to elucidate fundamentals for the phenomenon of universality of childhood autism by comparison of clinical and neurophysiological features of its severest forms--children endogenous autism (CEA) and Rett's syndrome (RS). Each group included 20 patients. Both groups were similar by age-at-disease-onset, clinical appearances during the disease course and dynamics of psychopathological syndromes. The theta-rhythm is common for CEA and RS at the disease stage with marked signs of disease acuity, autism, regress and, therefore, may be regarded as a marker of severity and development delay. The universality of autism phenomenon in its severe forms was confirmed both at the clinical and neurophysiological levels.

[An effect of long-term cerebrolysin therapy in combination with neuroleptics on behavioral and cognitive disturbances in endogenous childhood autism].

An open prospective clinical study included 25 patients with childhood autism aged from 3 to 8 years (mean age 5 years 11 months). Patients received 2 therapeutic courses (15 intramuscular Cerebrolysin injections of 1.0 ml every other day per course) with 2 months interval and basic antipsychotic therapy using typical neuroleptics in age-adjusted dosages. The duration of the study was 180 days. Significant or very significant improvement was achieved after the 1st Cerebrolysin course in 38% patients, after the 2nd course in more than 50% and to the end of the follow-up (180th day) in 71% of patients. There were no cases of deterioration during the trial. The autism severity as measured by the CARS scale consistently decreased from the day 0 to the day 180--from 37.7 to 32.6 scores, respectively (p < 0.001) in all assessments as compared with the baseline. To the end of the study, the patients demonstrated a significant decrease in mental retardation by 0.2 years. A statistically significant improvement was achieved in cognitive activity, attention during task performing as well as in self-service (by 0.3 years), receptive and expressive speech, cognitive performance and perception (by 0.2 years), fine motor function (by 0.1 years). The combined therapy comprising neuroleptics and Cerebrolysin double course can be recommended for correction of behavioral disorders and cognitive dysfunction in patients with mild moderate and moderate/severe autism.

[Current approaches to understanding of autism in childhood].

The authors analyse the trends in the study of childhood autism in the XX century and state of the art in view of nosology, systematics, clinical phenomenology, etiology and pathogenesis of autistic disorders. Mental Health Research Center of Russian Academy of Medical Sciences proposes a new classification of autism in children basing on the study of 500 cases. Each form of autistic disorders is characterized in clinicopsychopathological and pathogenetic aspects. The phenomenon of autism in childhood psychopathology is universal, dependent on peculiarities of ontogenesis of the nervous system, individual development of a child, genetic and environmental factors.

[Use of cholinomimetics in the treatment of endogenous autism in children]. / Primenenie kholinomimetikov v lechenii éndogennogo detskogo autizma.

Twenty children with endogenous autism of mild and moderate severity (30-44.5 scores according to the CARS), aged 3-8 years, were treated with choline alfoscerate (CA), 400 mg/day, during 8 weeks in the presence of maintenance therapy with neuroleptics (17 cases). Positive therapeutic effect was observed in 89% of the patients: significant improvement--in 61% and minimal efficacy--in 28%. Statistically significant positive changes in the patient's state were observed in the general improvement of behavior (p<0.001), development of social and communicative skills, as well as self-service, reduction of marked speech disturbances (p<0.001) and motor sphere (p<0.001), enhancement of learning activity and productivity (p<0.05). Good tolerability to the therapy, without patient's state worsening was registered. Some patients exhibited strengthening of affective lability in the first weeks of the treatment which attenuated to the 4th week as the CA dosages decreased to 400 mg every other day. CA may be recommended for combined therapy with neuroleptics as an effective and safe medicine for the treatment of cognitive and behavioral disorders in patients with children's autism.

[The effect of cerebrolysin on cognitive functions in childhood autism and in Asperger syndrome]. / Vliianie tserebrolizina na kognitivnye funktsii pri detskom autizme i sindrome Aspergera.

Nineteen children with childhood autism and 8 with Asperger's syndrome aged 2-8 year, were treated with cerebrolysin (CL) in inpatient clinic. All the patients received 10 microinjections (intramuscularly and perinervously) of 0.1 ml CL daily during 5 days. Clinical study was combined with device estimation of cognitive functions and communicative skills. CL therapy resulted in improvement of cognitive functions (expressive and receptive speech, fine motoring, playing). Positive effects were revealed in all the patients with Asperger's syndrome and in 89% of the patients with childhood autism. Any negative effects were not found. With regard to cognitive functions development, therapeutic efficacy proved to be more pronounced in the patients with Asperger's syndrome as compared to childhood autistic group (p < 0.005).

Speech and motor disturbances in Rett syndrome.

Rett syndrome is a severe, genetically determined disease of early childhood which produces a defined clinical phenotype in girls. The main clinical manifestations include lesions affecting speech functions, involving both expressive and receptive speech, as well as motor functions, producing apraxia of the arms and profound abnormalities of gait in the form of ataxia-apraxia. Most investigators note that patients have variability in the severity of derangement to large motor acts and in the damage to fine hand movements and speech functions. The aims of the present work were to study disturbances of speech and motor functions over 2-5 years in 50 girls aged 12 months to 14 years with Rett syndrome and to analyze the correlations between these disturbances. The results of comparing clinical data and EEG traces supported the stepwise involvement of frontal and parietal-temporal cortical structures in the pathological process. The ability to organize speech and motor activity is affected first, with subsequent development of lesions to gnostic functions, which are in turn followed by derangement of subcortical structures and the cerebellum and later by damage to structures in the spinal cord. A clear correlation was found between the severity of lesions to motor and speech functions and neurophysiological data: the higher the level of preservation of elements of speech and motor functions, the smaller were the contributions of theta activity and the greater the contributions of alpha and beta activities to the EEG. The possible pathogenetic mechanisms underlying the motor and speech disturbances in Rett syndrome are discussed.

Clinical, neurophysiological and immunological correlations in classical Rett syndrome.

Rett syndrome (RTT) is neurodevelopmental disorder with the onset at critical period of postnatal ontogenesis and age dependent occurrence of clinical manifestations. The aim of the present study was to investigate possible correlations of the age of disease onset with clinical manifestations at the stage 3 of illness and neurobiological parameters. The study was carried out in 38 girls with classical RTT, aged from 3 to 7 years, and twenty and eighteen patients with the disease onset before and after the age of one year were divided into the groups 1 and 2 (Gr1 and Gr2), respectively. Quantitative EEG (QEEG) and measurement of the serum levels of autoantibodies (AAB) to nerve growth factor (NGF) were performed. Clinically, speech and motor functions were significantly more severely affected in the Gr1 than in the Gr2. In QEEG, spectral density of theta activity was significantly higher in Gr1 than in the Gr2. The titer of AAB to NGF was significantly increased in comparison with healthy controls, and the titer in Gr2 was higher than in Gr1. The data obtained suggests that patients with the classical RTT can be divided into subgroups according to the age of disease onset and genetic factors such as mosaicism of MeCP2 mutation may be associated with the heterogeneity of phenotype in RTT patients.

[Speech and motor disorders in Rett syndrome]. / Rechevye i motornye rasstroistva pri sindrome Retta.

Rett syndrome (RS) is a severe genetically conditioned disorder of an early childhood with an definite clinical phenotype in girls. Motor and speech disturbances are noted as the essential part of RS clinical picture. The variability of motor dysfunction and degree of speech deterioration were noted at different stages of the illness. The aim of the present investigation was to study dynamics of both speech and motor disturbances during 2-5 years of the course of the illness and to analyze a correlation of motor and speech functions' disorders. The study was performed in 50 girls with classical RS aged from 12 months to 14 years. The data obtained show a gradual involvement of different brain cortex structures in pathological process during the course of RS (especially of frontal and temporal-parietal regions) at the early stage of the illness and subsequent spread of the pathological process with successive involvement of subcortical structures, cerebellum, brain stem and eventually spinal cord. The neurophysiological investigation showed a strong correlation of speech and motor disturbances' degree with the EEG parameters. The level of theta-activity was significantly lower and the level of alpha- and beta-activity was significantly higher in EEGs of RS patients with more preserved speech and motor functions. In discussion mechanisms of motor and speech disturbances in RS were considered.

[Quantitative EEG correlates of the human frontal lobe dysfunction]. / Kolichestvennye EEG-korreliaty disfunktsii lobnykh dolei kory golovnogo mozga cheloveka.

Increased central-parietal EEG theta-2 activity (about 6.5 per sec) was found in children with cognitive disorders (in Rett's syndrome, fragile X-syndrome, infantile autism) and in elderly patients with Alzheimer-type dementia (with prevalence of neuropsychological "frontal" disorders) in the presence of suppressed alpha rhythm. This theta-activity was closely associated with cognitive deficits and possessed a specific functional topography, namely it focused in the parietal region and suppressed by both visual stimulation and motor tests. The similar EEG pattern was observed in some patients treated with neuroleptics and/or during hyperventilation. By taking into account the data available in the literature on motor, oculomotor, regional cerebral blood flow and the probability prediction in frontal lobar dysfunction, it is suggested that the theta-activity described appears in the visuomanual coordination system and is a physiological correlate of decreased functional status of frontal lobes.

[Current approaches to the problem of autism in childhood]. / Sovremennye podkhody k probleme autizma v detstve.

The paper provides clinical and catamnestic descriptions of 240 children with infantile autism; 160 with atypical autism (of them 100 had schizophrenic attacks, 60 presented with mental retardation concurrent with atypical autism (in phenylketonuria, tuberose sclerosis, Down syndrome, Martin-Bell syndrome), 20 with Asperger's syndrome, 60 with Rett's syndrome, 20 with psychogenic paraautism according the Nissen classification. The similarity of autism-like disorders and atypical autism was considered. Syndromal verifications in accordance with ICD-10 (1994) and ICD-10 (1999) in Russian versions and clinical nosological verifications adopted in Russia were studied in all the examinees. New approaches to treating patients with autistic disorders were developed.

[Nerve growth factor auto-antibodies in the sera of mothers of schizophrenic children and children from high risk group]. / Autoantitela r faktory rosta vervov v syvorotke krovi materei bol'nykh shizofreniiei detei and detei gruppy vysokogo riska.

A level of autoantibodies (aAB) to nerve growth factor (NGF) was measured in blood serum of children from 4 groups: 1) schizophrenic patients; 2) children from the families, in which one of the parents suffered with schizophrenia (high risk groups of schizophrenia); 3) children with residual-organic damages of CNS; 4) control group. This index was also determined in their mothers. Significant elevation of a titer of aAB to NGF was observed in blood of children from groups 1 and 2 as well as in their mothers, as compared with 3 and 4 groups. Among the mothers of the children from 1 and 2 groups there were met women with different endogenous mental disorders, with the disorders of personality as well as mentally healthy women. An increase of a level of aAB to NGF was found in all the women from groups 1 and 2, independently of their mental status including mentally healthy women. Such results allow to consider elevated level of aAB to NGF as a risk factor of mental pathology.

[Treatment of atypical autism in Martin-Bell syndrome]. / Lechenie atipichnogo autizma pri sindrome Martina-Bell.

The paper reports the case of sibs, brother and sister, with Martin-Bell's syndrome confirmed cytogenetically. Mental retardation and autism were the main phenomena in the clinical picture. Positive effect was achieved by means of Skvortsov--Osipenko method (metameric injection of cerebral hydrolysates' preparations, stimulation of visual, acoustic and proprioceptive analyzers). A decline of the signs of intellectual retardation and autism were observed in both children.

[An elevation in the level of autoantibodies to nerve-growth factor in the blood serum of schizophrenic children]. / Povyshenie urovnia autoantitel k faktoru rosta nervov v syvorotke krovi detei, bol'nykh shizofreniei.

The level of autoantibodies (AAB) to nerve growth factor (NGF) was examined in blood of mentally healthy children, children with early children schizophrenia as well as with Kanner's and Asperger's syndromes too. The elevated titer of AAB to NGF was determined in blood of children with acute, active state of disease; meanwhile the same titer wasn't changed in the state of stable remission or steady defective state as compared with control group. The correlation was found between the level of AAB to NGF and the degree of disease progression. The correlations which were revealed between AAB to NGF level and peculiarities of the clinical state of patients permitted to use this index as the objective marker of both the acuteness and the severity of the patient's state.

[The characteristics of the mental development of young orphan children]. / Osobennosti psikhicheskogo razvitiia detei-sirot rannego vozrasta.

The peculiarities of the development of 45 orphan children who were bringing up in one Moscow's "baby's home" in early age from birth till first 3.5 years had been analysed. The "orphan syndrome" which was characterized by both alteration in affective background of personality and para-autistic appearance of deprivation character had been described. The article emphasized that the conditions of ordinary bringing up which were formed on the basis of standard crèche and kindergarten programmes for normal children were insufficient for orphan children in "baby's home". Deprivation psychopathological manifestations in orphan children must to attract attention of psychiatrists as well as psychologists toward the necessity of correction and prophylaxis of these disturbances with their direction on the softening of maternal deprivation consequences.

[The clinical, neurophysiological and differential diagnostic aspects in a study of severe forms of early childhood autism]. / Klinicheskie, neirofiziologicheskie i differentsial'no-diagnosticheskie aspekty izucheniia tiazhelykh form rannego detskogo autizma.

Clinical, pathopsychological and neurophysiological studies have been carried out in 85 children with infantile autistic psychosis and in 38 girls with Rett's syndrome. New improved differential diagnostic criteria between these two forms of early childhood autism have been suggested. EEG spectral density values in alpha-1, alpha-2, beta and theta subbands are established to be their neurophysiological markers. Special attention was paid to close relationship between ontogenetic neuromorphogenesis of the brain cortical structures (e.g. physiological lysis of cortical cell populations at the age 8-30 months of the child's life) and the defect severity in the onset of illness at the same age range in patients with the studied forms of early childhood autism. The data obtained are discussed in terms of new approaches to understanding pathogenesis of different forms of early childhood autism.

[The possibilities for prevention and rehabilitation at different stages in treating mentally ill children and adolescents]. / Vozmozhnosti profilaktiki i reabilitatsii na raznykh étapakh lecheniia psikhicheski bol'nykh detei i podrostkov.

The results of rehabilitational and psychological correction of mentally ill children and adolescents in hospital, inpatient-outpatient and outpatient conditions and of the follow-up are presented. The problem of prevention and rehabilitation is reviewed in general. Some considerations on further perfection of the aid to mentally ill children are suggested.