[The relationship between cognitive impairment and localization of white matter lesions in patients with multiple sclerosis]. / Sviaz' kognitivnykh narushenii s lokalizatsiei ochagov porazheniia belogo veshchestva golovnogo mozga u bol'nykh rasseiannym sklerozom.

Objective. To study a role of parenchymal white matter lesions and lesions of the white matter underlying the cortical grey matter in cognitive impairment in patients with multiple sclerosis (MS). Material and methods. We examined 33 patients with clinically definite RRMS in clinical remission. Cognitive performance was assessed with neuropsychological and psychometric tests. MRI (1.5 tesla) was used to assess volume and localization of focal demyelination in the cerebral cortex. Results. The volume of juxtacortical brain lesions in the white matter had a negative effect on the correct performance on neuropsychological tests. The volume of parenchymal white matter lesions had a negative effect on the speed of task performance. Conclusion. The results suggest that MS patients had multiple cognitive impairments.

[Cortical atrophy in multiple sclerosis]. / Atrofiia kory golovnogo mozga pri rasseiannom skleroze.

Objective. To identify clear patterns of the cerebral cortex atrophy in multiple sclerosis that may provide valuable information for the development of additional paraclinical methods of stages and variants of MS objectification and verification and used for assessing treatment efficacy. Material and methods. The results of morphometric data analysis of 117 patients with different variants of MS and 25 healthy volunteers are presented. The original algorithm for postprocessing MRI images was used. Age, disease duration, type of disease, FS and EDSS scores, morphometric results were the source parameters for the statistical analysis. Results. The correlation analysis showed that the total cortex volume was in inverse correlation with EDSS score, pyramidal and cerebellar dysfunction, but not with disease duration. An analysis of regional changes in 43 bilateral regions of interest (ROI) demonstrated similar results in 7 ROIs in the left (dominant) hemisphere and in 4 ROIs in the right hemisphere. ANOVA revealed atrophic changes in 20 ROIs bilaterally. Deficit of certain functional systems was accompanied by the atrophy of various functional cortex regions. ANOVA of the regional cortical atrophy in groups with varying disease severity showed the presence of significant changes in patients with moderate to severe disability. Duration and type of MS were not predictive for development of atrophy, with the exception of the precuneus bilaterally, the right paracentral lobule and right posterior cingulate gyrus. Conclusion. Regional cortical atrophy is detected in the earliest stages of the disease and increases as the disease progresses. Inconsistency of data across studies can be explained by the lack of generally accepted morphometric standards and pathogenetic heterogeneity of MS. Regional cortical atrophy may be considered as a sensitive neuroradiological biomarker for MS.

[Neuroimmunology: theoretical and clinical aspects].

The aspects of neuroimmune interactions (during cerebral ischemia and stroke--experimental and clinical data, demyelinating process in patients with multiple sclerosis,secondary immunodeficiency) are discussed in this article. Literature overview and authors' experience are presented as well.

[Teriflunomide is a new peroral disease-modifying drug for multiple sclerosis (a review)].

Teriflunomide is a once-daily, orally administered, disease-modifying drug. The review presents the data concerning the mechanism of action, pharmacokinetics as well as results of clinical studies. Teriflunomide has received the regulatory approval in the USA, Argentina, Australia, South Korea, Chile and EU. The submission of a regulatory dossier is performed in Russia.

[The role of brain glucose metabolism in the development of cognitive dysfunctions in patients with remitting and secondary-progressive multiple sclerosis].

To study mechanisms of development of cognitive dysfunctions in multiple sclerosis (MS), brain glucose metabolism has been investigated using PET method. We have studied 61 patients with different types of MS course. Correlations between cognitive dysfunctions and regional glucose metabolic rate were revealed. The authors suggest that metabolic dysfunctions of the grey matter play the important role in the pathogenesis of cognitive disturbances in MS.

[Symptoms of circadian desynchronization in patients with multiple sclerosis].

Circadian rhythm of sleep-wakefulness and evacuation function of intestines, symptoms of neuropsychic adaptation were investigated in 36 patients, aged 21-53 years, with multiple sclerosis (MS). Frequencies of circadian rhythm disturbances of brain activity (insomnia in 66% of patients) and circadian rhythm disturbances of intestine evacuation (constipation in 72% of patients) were revealed. Insomnia and irritability in MS patients with bradyenteria occur 1.5 times more frequent than in patients with normal regulative activity of the bowels. The risk of anxiety and depression in MS patients with bradyenteria was 2-3 times higher than in patients with euenteria. The suitability of normalization of circadian desynchronization of MS patients by the restoration of optimal acrophases of circadian rhythms of the brain and bowels is established.

[Ethical aspects of clinical trials in patients with multiple sclerosis].

The ethical aspects of clinical trials are reviewed. Clinical trials in the Russian Federation must be conducted in accordance with the Good Clinical Practice, guiding principles of the Helsinki Declaration and Russian laws. The article includes information concerning principles of patient's informed consent, regulatory requirements and guidelines for clinical trials in multiple sclerosis.

[Brain atrophy and neurological impairment in patients with multiple sclerosis].

An aim of the study was to investigate a relationship between global and local brain atrophy with neurological impairment (motor dysfunction) in multiple sclerosis (MS) patients with different levels of disease severity. Fifty five patients with definite MS (Mc Donald's criteria), aged 18-60 years, disease duration 1-30 years, and 25 healthy age-matched controls have been studied. Neurological assessment (Kurtzke and EDSS scales) was performed in the all patients. The patients were divided into 3 groups: EDSS<3.5 mild disability, EDSS 3.5-6.0 moderate disability, EDSS>6.0 severe disability. In MS patients, the global brain atrophy was accompanied by the local atrophy of subcortical structures (thalamus, basal ganglia) and cerebellum. The processes of cerebral grey matter total and local atrophy were not similar. The progression of MS, neurological impairment is accompanied by the cerebellum and lentiform nuclei atrophy. There was the decrease of brain parenchyma volume, nucleus caudate and cerebellar local atrophy in patients with moderate disability. The severe disability was correlated with the thalamic atrophy and marked basal ganglia and cerebellar atrophy. Thus, we can suppose that the thalamic atrophy is important for the development of severe motor dysfunctions in MS patients.

[Neuromyelitis optica: problems of heterogeneity and systematization].

Prospective-retrospective data on 10 cases of neuromyelitis optica (NO) have been analyzed. Demographic and clinical features of patients with primary NO as well as NO comorbid with other organospecific disorders are discussed. Magnetic-resonance imaging data of the brain and spinal cord are summarized and discussed in the context of its heterogeneity. Positron emission tomography with the functional imaging of the brain performed in 3 patients revealed changes in glucose metabolism in the brain regions corresponding to deficits in motor and sensory functional systems. The issues of additional laboratory analyses, including those of cerebrospinal fluid, are reviewed.

[Pathogenetic treatment of multiple sclerosis: the present and the future].

Treatment of multiple sclerosis (MS) remains one of the most serious problems of modern medicine though a significant progress in understanding of disease pathogenesis has been achieved over the last years. Currently there are the ways of modifying the disease course that improve the remote prognosis. In this review, we present results of studies of drugs modifying the MS course which have been approved for MS treatment and those that are in the stage of clinical trials and expected to enlarge possibilities of MS treatment.

[Positron-emission tomography in the diagnosis of middle cerebral artery lesions].

The regional brain glucose metabolism after the intravenous drop-by-drop infusion of saline and 50 mg of cavinton was measured with positron-emission tomography (PET) in the right middle brain artery in 5 patients with ischemic stroke. The increase of glucose metabolism was found in the region of post stroke cystic-focal and perifocal changes as well as in contralateral regions. The dose of cavinton (50 mg) was safe and well-tolerated by patients. The use of PET in evaluating of glucose metabolism changes in the brain helps in prognosis of the disease.

[The peculiarities of plantar pressure distribution during gait in different variants of functional system impairment in patients with multiple sclerosis].

Gait disturbance is a prominent disabling presentation of multiple sclerosis. The data on the distribution of plantar pressure during gait and its relation to the level of neurological deficit in various disturbances of pyramidal and cerebral functions in remitting type of multiple sclerosis are presented.

[Clinical and radiological (PET, MRI) correlations depending on disease progression in patients with multiple sclerosis].

The aim of the study was to investigate the structural-functional changes in the cerebral gray matter (cortical and subcortical areas) of patients with multiple sclerosis (MS) depending on the disease severity. One hundred and seven patients (107) with definite diagnosis of MS (Mc Donald's criteria), aged 16-60 years, illness duration 1-30 years, and 21 healthy age-matched controls have been studied. Neurological assessment including Kurtzke and EDSS scales (range 0-8) was performed in all the patients. The patients and controls underwent MRI with a 1,5 imager and PET using 18F-flurodeoxyglucose (FDG). A type of the disease course was determined as remitting in 63 patients, primarily-progressive in 8, remitting progressive in 6 and secondary-progressive in 30. To analyze pathogenesis of the disease progression, the patients were divided into 3 clinical groups: (1) remitting (RRMS, n=63); (2) progressive (PRMS) with EDSS < or =6 (n=34); 3) PRMS with EDSS >6 (n=11). Along with the progression of MS from RRMS to PRMS and increasing of EDSS, the rCMRglu reduction of the cerebral gray matter developed from the supplementary motor cortex of a dominant hemisphere to the marked global reduction of cerebral metabolic rate in the PRMS group (EDSS >6). In the PRMS group with EDSS56, there was functional reorganization of cortical and subcortical areas compensatorily developing with the disease progression. In the PRMS group with EDSS >6, the data obtained did not support the evidence for the regional compensatory increase of rCMRglu in the same brain areas. Decompensation of the functional cortical reorganization in the PRMS group with EDSS >6 correlated with diffuse brain atrophy as well as with atrophy of the gray matter of the regional basal ganglia, first of all of the thalamus.

[Changes of cerebral glucose metabolism in patients with multiple sclerosis and their role in formation of the clinical picture and progression of the disease]. / Izmeneniia metabolizma gliukozy golovnogo mozga u bol'nykh rasseiannym sklerozom i ikh rol' v formirovanii klinicheskoi kartiny i v progressirovanii zabolevaniia.

Multiple sclerosis is an autoimmune disease, which characterized by CNS myelin lesion. The pathological changes include distinct demyelination foci well identified by MRI. However, because their volume and localizations weakly correlate with clinical appearances and progression of the disease, functional changes may exert a greater influence on disablement indices than regular MRI data. Positron emission tomography (PET), using a labeled native glucose analogue [18F] fluorinedesoxyglucose (FDG-PET) enables to evaluate cerebral glucose metabolism and specify an association between brain metabolism and clinical appearances. FDG-PET has been administered to 87 patients: 57 with valid MS, remitted course (group 1) and 30 with primary-, remitted- and secondary-progressive course (group 2). Besides, a patient's state was evaluated with EDSS and FS scales. A regional to global activity ratio was calculated according to ICVRglu indices. In both groups, significant negative correlation between glucose metabolism in the majority of the brain regions and MS duration was found, being more distinct in group 2. Also, cerebellum metabolism reverse correlated with FS 2 scale scores. In group 2, ICVRglu index in subcortical structures positively correlated with FS 1 scores. Positive correlation between ICVRglu in somatosensor area and EDSS and FS scores was detected. The associations with PET demonstrated a relationship between clinical syndromes, MS duration and cerebral metabolism level, being mostly pronounced in the group with progressive course. Both hypo- and hyper metabolism may be clinically significant. In the patients with progressive MS, hyper metabolism in sensomotor area is likely to be of compensatory importance.

[Myelopid correction of immune deficiency in staffers exposed to lead materials at work]. / Korretktsiia mielopidom immunodefitsita u sotrudnikov promyshlennogo predpriiatiia, rabotaiushchikh so svinetssoderzhashchimi materialami.

Authors demonstrated that immune dysfunction of chronic lead intoxication is manifested in low number and changed subpopulations of immune cells, in alterations of spontaneous lymphocytes proliferation. "Myelopid" corrects the symptoms of immune dysfunction.