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.
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.
Objective: Corpus callosum (CC) size and interhemispheric communication differences have been reported between patients with schizophrenia and normal controls. Childhood-onset schizophrenia (COS) is a severe form of the disorder that is continuous with later-onset disorder. Corpus callosal area was examined for COS at initial scan and prospectively through adolescence, and related to other developmental abnormalities for this group. Method: A total of 113 anatomic brain MRI scans were obtained from 55 COS (22 female) and 110 scans from 56 age- and gender-matched healthy volunteers (22 female), across ages 8–24. Baseline and prospective rescans were obtained at approximately 2-year intervals. The midsagittal areas for total corpus callosum and seven subregions were calculated using an automated system. Cross-sectional and longitudinal data were combined using mixed model regression analysis to compare developmental changes for the two groups. Results: No diagnostic differences were seen at time of initial scan. Longitudinally, and in contrast to healthy volunteers, patients with schizophrenia showed a significant difference in developmental trajectory for the area of the splenium, both before (p=0.012) and after (p=0.05) adjustment for total cerebral volume. The area of the splenium becomes significantly smaller in COS, starting at about age 22. Conclusion: Patients with schizophrenia showed a significant difference in developmental trajectory for the splenial area, which seems to decline for COS. If replicated, this may reflect anticipated late occipital and extrastriate changes in brain regions.
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.
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).
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 θ activity and the greater the contributions of α and β activities to the EEG. The possible pathogenetic mechanisms underlying the motor and speech disturbances in Rett syndrome are discussed.
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.
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.
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.
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.
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.
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.