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 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.

[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.

[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.

[Follow-up of patients with a history of early childhood schizophrenia (its unfavorable variant)]. / Katamnez bol'nykh rannei detskoi shizofreniei (ee neblagopriiatnogo varianta).

The article presents the results of a follow-up of 113 patients suffering from infantile schizophrenia with an unfavourable course. The mean duration of the follow-up in 84 patients was over 11-15 years. In the follow-up period 84% of the patients were characterized by productive predominantly catatonic disturbances with features of pseudooligophrenic dementia, autistic behaviour and apathic manifestations. In the remaining 16% of the patients the state could be assessed as residual with the predominant oligophrenic defect and apatho-autistic behaviour. The author discusses infantile schizophrenia running an unfavourable course at delayed stages of its development, the formation of the defect and also the therapy and care for such children.

[Course and prognosis of childhood schizophrenia in the light of follow-up information]. / Techenie i prognoz detskoi shizofrenii v svete katamnesticheskikh dannykh.

Altogether 222 patients with early childhood schizophrenia, including 102 patients with an attack-like slow progressive schizophrenia were followed up. A distinct stability of the singled out forms of schizophrenia with the onset in early childhood was demonstrated. Within the framework of each form of the disease development a variability of the progression inherent to each form is established. Its greatest variability was noted within the range of the attack-like, slow progressive schizophrenia. It is mostly influenced by the ontogenetic, somato- and psychogenic factors.

[Catamnesis of patients with Kanner's early infantile autism syndrome]. / Katamnez bol'nykh s sindromom rannego infantil'nogo autizma Kannera.

By means of a follow-up study the author studied 28 patients who at the age of 3-6 years were diagnosed as suffering from early infantile autism. In 6 cases the mental state of patients was characterized by traits of dissociated oligophrenic-like defect with preserved autistic forms of contacts, residual disorders of the syndrome of Kanners early autism, simbiotical dependency from the parents. In 15 cases there was a personality distortion, with traits of autism, emotional poorness, motor insufficiency, indifferent negativistic forms of contacts, mental retardation of the pseudooligophrenic type. In 7 cases there was a formation of a psychopathic state of a schizoid type.

[Depersonalization disorders in schizophrenic children]. / Osobennosti depersonalizatsionnykh rasstroistv u bol'nykh shizofreniei detei.

The paper is concerned with a study of age variants of depersonalizational disturbances in schizophrenia children of early preschool age and preschool age. Depersonalizational disorders proper were found in 25 cases, disturbance of the self-conscious and its deterioration in 59, retardation in the development of the self-conscious formation--in 32 cases. Depersonalizational disturbances appear in children over 3 years, i.e. following the first physiological age crises. The following types of depersonalizational disturbances were distinquished: 1) moderately expressed loss of the self-conscious with disorders in the differentiation of the "I" from the associates; 2) a deeper disorder of the "I" with a substitution of the personal "I", by another "I"; 3) phenomena of estrangement of the self-conscious with a state similar to the splitting of the self-conscious, up to the appearance of the phenomena of a twin; 4) a change of the self-conscious expressed in a pathological play transformation and a substitution of the "I" by another "I", or a splitting of the self-conscious into the syndrome of play transformation near to a delusional; 5) derealization; 6) loss of the conscious of personal sex; 7) estrangement of the conscious of personal actions; 8) disturbance of self-conscious of a physical whole; 9) disturbance of the self-conscious in a deep depression with a loss of "I-vitality" appearance near to "anaesthesia psychica dolorosa" and "nihilistic delusions"; 10) loss of "I" conscious and regress of speech, motor activity, behaviour; 11) retardation in the formation of "I" conscious.

[Features of the relation between preclinical dysontogeny, the Kanner syndrome of early infantile autism and early childhood schizophrenia (according to the results of catamnestic examinations)]. / K osobennostiam vzaimosviazi domanifestnogo dizontogeneza, sindroma rannego detskogo autizma Kannera i rannei detskoi shizofrenii (po dannym katamnesticheskogo obsledovaniia).

The article is devoted to the correlation between manifestations of congenital dysontogenesis, the syndrome of Kanner's early infantile autism and early infantile schizophrenia. The article is largely based on the materials of a follow-up study of a cohort of schizophrenics (n = 268) and patients with Kanner's early infantile autism (n = 32). The authors established developmental deviations in the form of a stigmatized, distorted, retarded type in the premanifest premorbid period in patients with early infantile schizophrenia (in 78% of cases). It has been shown that Kanner's early infantile autism is characterized by disorders in the hierarchy of the development of functional systems and their underdevelopment, which allows some authors to refer it to unprogressive dysontogenesis, while others may refer it to congenital apsychotic schizophrenia.

[Clinico-catamnestic study of patients with paroxysmal-progressive schizophrenia with a history of affective, anxiety-affective and affective-hallucinatory attacks in childhood/and full-blown hallucinatory-delusional attacks in adolescence]. / Kliniko-katamnesticheskoe izuchenie bol'nykh pristupoobrazno-progredientnoi shizofreniei, perenosivshikh v detstve affektivnye, trevozhno-affektivnve, affektivno-galliutsinatornye i v podrostkovom vozraste razvernutye galliutsinatorno-bredovye pristupy.

Clinical follow-up covered 40 patients with paroxysmal progressive schizophrenia with a history of 52 affective, anxiety-affective and affective-hallucinatory attacks at the age of 0-10 years and of 70 hallucinatory-delusional attacks at the age of 11-17 years and older. Over one-third of the examined patients were under the authors' personal observation in early childhood. The follow-up lasted for 5 to 22 years. The authors have established a definite stereotype of the development of anxiety-affective, affective-hallucinatory and hallucinatory-delusional attacks. Remissions in this group of patients are characterized by atypical affective disturbances and changes of the personality. The authors have specified clinical characteristics of so-called "premanifest" episodes, attacks, and "premorbid" pseudopsychopathic conditions with manifestations of retardation of personality development and atypical affective disorders.

[Classification of the course of childhood schizophrenia in the light of long-term follow-up]. / Sistematika form techenia detskoi shizofrenii v svete otdalennogo katamneza.

The work deals with the catamnestic substantiation of the systematics of schizophrenia in children. A group of 328 patients was selected in 1982-1987 from a cohort of schizophrenic patients studied in 1962-1972 in which the onset of the disease fell on their first 5 years. The stability of the course patterns was evidenced in the early childhood schizophrenia. A set of subspecies of disorders similar to schizoactive psychoses and peculiar affective schizoid states was differentiated out of the general pool of slow progredient and attack-like schizophrenia. This allowed to prove the notion of the whole continuum of endogenous psychoses in not only adults but also in children.

[Problem of adaptation of patients with the syndrome of early childhood autism]. / K probleme adaptatsii bol'nykh s sindromom rannego detskogo autizma.

Sixty-seven children with early childhood autism received therapeutic and corrective treatment in a day-time clinic. In 37 cases socialization of children proved possible, and following treatment, they were transferred to specialized, logopedic, and general kindergartens and schools. The authors advocate the advisability of setting up day-time clinics in the framework of childhood psychiatric hospitals and of organization of separate groups for children with early childhood autism in the framework of specialized kindergartens.

[Characteristics of early childhood schizophrenia proceeding with astheno-adynamic, adynamic and affective-catatonic attacks (a clinico-catamnestic study)]. / Osobennosti rannei detskoi shizofrenii, protekaiushchei s astenoadinamicheskimi, adinamicheskimi i affektivno-katatonicheskimi pristupami (kliniko-katamnesticheskoe issledovanie).

Clinico-catamnestic approach was applied to study 40 children with early schizophrenia with astheno-adynamic, adynamic and affective-catatonic attacks. Catamnesis duration was 15 to 20 years. The authors describe the psychopathologic disorders and their repercussion around astheno-adynamic, adynamic, affective-catatonic attacks within four age periods: under 1 year, 1 to 4 years, 5 to 10 years, 11 to 17 and older. The remission structure and quality was clarified, its stage-by-stage development and defect types characterized. The described version of early child paroxysmal schizophrenia had relatively favorable prognosis: clear regression in 45% of the cases relative regression with shift to symptom-depleted steady level in 55%.

[Kanner's syndrome and childhood schizophrenia]. / Sindrom Kannera i detskaia shizofreniia

The examination of 32 children with Kanner's syndrome of early infantile autism permits to assume that this syndrome in some of the cases is expressed only by inborn anomalies which correspond to constitutional psychopathy in adults. In most of the cases this syndrome forms the initial expression of child schizophrenia. In separate cases disorders very similar to Kanner's syndrome may be seen after the first olliterated attack during early childhood (up to 3 years). A comparative study of the same indices of development of 268 children with an early onset of schizophrenic process in spite of some differences confirms that Kanner's syndrome is very close to childhood schizophrenia. An analysis of genealogical data shows genetical relations of Kanner's syndrome with child schizophrenia.

[Problem of rehabilitative correction of mental defects in children with schizophrenia]. / K voprosu o vosstanovitel'noi korrektsii defektnykh sostoianii u bol'nykh shizofreniei detei.

Problems of rehabilitative correction of defect conditions associated with schizophrenia that had occurred in early childhood remain little studied. After the disease attacks the schizophrenic children usually develop severe defect conditions. With no rehabilitation provided to such children, the defect gravity increases due to super-addition of secondary retardation of mental development. The characteristic features of defect conditions were investigated on a material of the follow-up of 75 persons who had suffered schizophrenic attacks of varying structure at the age under 3 years. A complex of measures for their rehabilitation has been elaborated.

[Characteristics of speech disorders in patients with early infantile autism of endogenous etiology]. / Osobennosti rechevykh rasstroistv u bol'nykh s rannim detskim autizmom éndogennogo geneza.

The paper is concerned with a study into the characteristic features of language pathology in children with early infantile autism of the process genesis. 68 patients with early infantile autism were entered into the study. The language as the earliest function of the central nervous system may suffer first of all. Language disorders of varying pathogenetic levels consequent on retarded development, catatonic disorders, mental regression, and pathology of the associative process have been revealed. Measures aimed at language pathology rehabilitation have been elaborated.

[The effect of the earthquake in Armenia on the mental health of the pediatric population of the damaged regions]. / Vliianie zemletriaseniia v Armenii na psikhicheskoe zdorov'e detskogo naseleniia postradavshikh raionov.

The authors relate neuropsychic disorders in children and adolescents of Armenia in the acute period and 3 months after the earthquake. The pathological disorders were dependent on the individual reactivity of the child and environmental factors. 3 months after the earthquake 31% of the examines demonstrated marked mental disturbances. The prevalence of mental pathology among the population groups living in the regions damaged by the earthquake demands organization of specialized assistance for the population.

[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.