Cerebrolysin therapy in Rett syndrome: clinical and EEG mapping study.

Based on the suggestion that nerve growth factor plays a core role in the brain maturation process, which is altered in Rett syndrome, we investigate the influence of Cerebrolysin--the brain-derived peptidergic drug - on motor and higher cortical functions in Rett syndrome girls. The open pilot study was performed on nine Rett syndrome girls (aged from 2 years and 2 months to 7 years and 6 months) at stage 3 of the illness, and included both clinical and quantitative EEG evaluations before and after Cerebrolysin treatment. After Cerebrolysin treatment, increases in the behavioral activity, attention level, motor functions, and non-verbal social communication have been shown in Rett syndrome patients. EEG parameters after Cerebrolysin treatment also changed towards normal values, indicating an improvement of the brain functional state. EEG changes included: decrease of theta activity over all cortical regions, increase of beta activity in the frequency band 13-15 Hz, and some restoration of the occipital alpha rhythm (in the narrow 8-9 Hz band). The data obtained suggested possible perspectives of Cerebrolysin in complex therapy of Rett syndrome.

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.

Brain-directed autoantibodies levels in the serum of Rett syndrome patients.

Increased titer of brain-directed autoantibodies (AAB) may represent a risk for brain development in children with Rett syndrome (RTT). The aims of this work were to study the levels of brain-directed AAB, mainly nerve growth factor (NGF) and S-100 protein AAB, to analyze morphological features of brain labeling by AAB produced in RTT patients, and to correlate with clinical manifestation. The increased titer of anti-NGF AAB, but not of anti-S100 AAB has been determined in the blood of RTT patients. The blood from five RTT girls was investigated repeatedly (two to four times) within 0.5-3 years. In these RTT patients the level of anti-NGF AAB was stable, not depending on the stage of illness, so individual stability of anti-NGF AAB levels have been detected. However, the negative correlation between the level of these AAB and severity of disease has been found: girls with the milder course of illness (with relative preservation of speech and locomotor functions, later disease onset, and later development of regressive symptoms) were characterized by the higher levels of AAB. The study also revealed immunohistochemical labeling of neuronal population with serum from RTT patients. Serum AAB from RTT cases labeled the cytoplasm and apical dendrites of pyramidal neurons in the neocortex and hippocampus, neurons in basal ganglia and brain stem, but not in the cerebellum of rats. Our results show the presence of brain-directed AAB in blood serum of RTT patients, which suggests an autoimmune component in pathogenesis of RTT.

PHYSIOLAB: a cardiovascular laboratory.

PHYSIOLAB is a cardio-vascular laboratory designed by CNES in cooperation with IMBP, with double scientific and medical goals: -a better understanding of the basic mechanisms involved in blood pressure and heart rate regulation, in order to predict and control the phenomenon of cardio-vascular deconditionning. -a real-time monitoring of cosmonauts during functional tests. Launched to the MIR station in 1996, this laboratory was set up and used for the first time by Claudie Andre-Deshays during the French mission "Cassiopeia". The scientific program is performed pre, post and in-flight to study phenomena related to the transition to microgravity as well as the return to the earth conditions. Particular emphasis was placed on the development of the real-time telemetry to monitor LBNP test. This function was successful during the Cassiopeia mission, providing the medical team at TSOUP (MIR Control Center in Moscow) with efficient means to control the physiological state of the cosmonaut. Based on the results of this first mission, IMBP and CNES will go on using Physiolab with Russian crews. CNES will take advantage of the upcoming French missions on MIR to improve the system, and intends to develop a new laboratory for the International Space Station.

PHYSIOLAB: a new laboratory for the study of the cardio-vascular system.

On the basis of the experience gained during the previous french-russian missions on board MIR about the adaptation processes of the cardio-vascular system, a new laboratory has been designed. The objective of this "PHYSIOLAB" is to have a better understanding of the mechanisms underlying the changes in the cardio-vascular system, with a special emphasis on the phenomenon of cardio-vascular deconditioning after landing. Beyond these scientific objectives, it is also intended to use PHYSIOLAB to help in the medical monitoring on-board MIR, during functional tests such as LBNP. PHYSIOLAB will be set up in MIR by the French cosmonaut during the next french-russian CASSIOPEE mission in 1996. Its architecture is based on a central unit, which controls the experimental protocols, records the results and provides an interface for transmission to the ground via telemetry. Different specific modules are used for the acquisition of various physiological parameters. This PHYSIOLAB under development for the CASSIOPEE mission should evolve towards a more ambitious laboratory, whose definition would take into account the results obtained with the first version of PHYSIOLAB. This "second generation" laboratory should be developed in the frame of wide International cooperation.

Biomedical program of the ALTAIR french russian flight onboard the MIR station.

One year after the achievement of the 2 weeks ANTARES french-russian mission in the MIR station in July 1992, a 22 days ALTAIR mission with a french cosmonaut has been performed in July 1993, making use of the scientific payload remaining on board. Taking benefit of the analysis of the previous mission, the experimental protocols were adapted to refine scientific objectives and gave to the scientists the opportunity to enhance quantitatively and qualitatively their results. The french biomedical program, conducted in close scientific cooperation with IMBP and associated laboratories, was composed of 8 experiments out of which 2 were new with regards to the ANTARES program. In the field of cardio-vascular physiology and fluid regulation, the experiments: ORTHOSTATISME, DIURESE have been renewed and complemented by the TISSU experiment (proposed by a german scientist) and a real-time tele-assistance program using US echography technic and ground support from the french CADMOS support control center located in Toulouse. With respect to neurosciences objectives, to the experiments VIMINAL (cognitive processes) and ILLUSIONS (study of proprioceptives cues), was added the SYNERGIES experiment to analyse the postural adjustments during movement. The IMMUNOLOGIE experiment carried on and the radiobiological experiment BIODOSE ended. Adding the results of the 2 missions ANTARES and ALTAIR, and the data obtained in between onboard with russian cosmonauts, the scientists have received a wealth of physiological data and gained reproducibility and confidence in their results.