[A combined preparation stalevo in Parkinson's disease: a 5-year experience of continuous dopaminergic stimulation].

Levodopa remains a 'gold standard' for the treatment of patients with Parkinson's disease (PD), but its chronic use is accompanied by fluctuations of symptoms and dyskinesias related to unfavorable pharmacokinetics of levodopa and progressing loss of the nigrostriatal neurons. Prescribing inhibitors of catechol-O-methyl-transferase (enzyme of dopamine metabolism), entacapone or tolcapone, is a perspective approach to the correction of the above-mentioned complications. We followed up 402 patients with PD who received long-term therapy with a combined preparation Stalevo (levodopa/carbidopa/entacapone) for 2-5 years (2.9 ± 0.9 years). The high (92.8%) compliancy and good tolerance of the drug in patients with PD was shown. Stalevo leads to the stabilization of the response to levodopa, improvement of patients' functional capacities, increase in their everyday activity, and improvement of quality of life. Stalevo may be regarded as a preparation of choice in the treatment of motor complications in elderly patients, correction of night symptoms of PD and in a number of other clinical situations arising in hospital and outpatient practice.

[Mexidant increases the effectiveness of levadopa treatment of Parkinson's disease].

The efficiency of mexidant therapy in patients with Parkinson's disease (PD) has been evaluated. The study included 49 patients aged 58-65 with a trembling-rigid and trembling forms of PD at an disease duration of 6.5 +/- 3.8 years. All patients were treated with levadopa-containing drugs, dopamine receptor agonists and/or amantadine. In addition, 27 patients received mexidant at a dose of 200 mg/day (i.v.) for the first 10 days, followed by intramuscular injections of 100 mg (twice a day) for 10 days. The dynamics of symptoms in the group of patients receiving mexidat showed that the inclusion of this drug into the therapeutic regime significantly decreased the degree of levadopa therapy side effects. Mexidant reduced the oxidative damages of blood plasma lipoproteins by neutralizing the growth of lipid hydroperoxide and increased the endogenous antioxidant status. The presented data show that mexidant enhances the efficiency of PD therapy.

[Analysis of single nucleotide polymorphism rs415430 in the WNT3 gene in the Russian population with the Parkinson disease].

The Parkinson disease (PD) is the second most common progressive neurodegenerative disorder that arises due to degeneration of dopaminergic neurons. The causes of this disease are still unknown, but a number of genes involved in pathogenesis of familial and sporadic forms of PD has been identified. According to recent data of genome wide association studies (GWAS), single nucleotide polymorphisms (SNPs) in these genes (including MAPT locus) may play an important role in the development of PD. Therefore, we analyzed distribution of genotype frequencies of SNP rs415430 in the WNT3 gene in the Russian patients with sporadic PD and in the Russian population controls (OR = 0.84, Confidence Interval (95% CI) 0.58-1.23, p = 0.39). It was concluded that SNP rs415430 in the WNT3 gene was not associated with the risk of development of PD.

[Expression of GSK3B gene in peripheral blood in patient with Parkinson's disease].

Parkinson's disease (PD) is the second most common progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons. Detecting changes in gene expression in untreated de novo patients with PD is important for understanding disease pathogenesis and for identifying biomarkers for preclinical stage of PD. In this study we investigate expression of gene of Glycogen synthase kinase-3 beta (GSK3B) in the peripheral blood of different groups of patients with neurological diseases using reverse transcription reaction and real-time polymerase chain reaction (PCR). Our results suggest that the expression levels of GSK3B can't serve as a biomarker for early stages of PD.

[Transcranial sonography in Parkinson's disease].

An abnormal hyperechogenecity of substantia nigra is thought to be the most characteristic sonographic feature in Parkinson's disease (PD). However specificity and sensitivity of the ultrasound method should be refined. Using transcranial sonography, authors have examined 168 patients with different clinical signs of parkinsonism, including 99 patients with idiopathic PD, and 56 patients without extrapyramidal disorders. Hyperechogenecity of substantia nigra was found in 93% of patients and in 14% of controls. It has been shown that this biomarker can successfully discriminate PD from a number of similar disorders (essential tremor, atypical parkinsonian syndromes). Sonographic features of late, early and genetically determined parkinsonism specifying some pathogenetic aspects of these pathologies are described. Taking into account the data obtained, transcranial sonography can be considered as a highly informative method in the differential and early diagnosis of PD.

[Application of transcranial pulsed electrostimulation and an alternating electrostatic field to the treatment of "restless legs" syndrome in patients with Parkinson disease].

The objective of this work was to evaluate the possibility to use combined therapy including application of transcranial pulsed electrostimulation and an alternating electrostatic field to the treatment of "restless legs" syndrome (RLS) in patients with Parkinson disease. A total of 31 patients with this syndrome were available for observation. A single course of combined therapy resulted in a substantial (60.4%) alleviation of painful sensation in 20 patients. Depression and anxiety decreased by 53.56% and 52.38% respectively. Accordingly, the quality of life increased (6.48%). In the 11 patients of the control group, these changes were much less pronounced; that is, painful sensation, depression, and anxiety decreased by 8.15%, 5.17%, and 10.11% respectively. It is concluded that combined therapy including application of transcranial pulsed electrostimulation and an alternating electrostatic field produced highly beneficial effect in patients with Parkinson disease and restless legs syndrome.

[Composite phytoadaptogens in oncology and gerontology].

The article describes results of research devoted to Phytomix-40, a mixture of plant adaptogens. It focuses on immunobiological criteria for its formulation, chemical composition and manufacture procedures, biological standartization tests, in vitro and in vivo preclinical studies, clinical trials in patients with non-malignant tumours (benign prostatic hyperplasia), precancer (oral leukoplakia), advanced cancer (malignant gastric cancer), and age-related neurodegenerative disease (parkinsonism). Prospects for the development of other plant preparations for non-toxic prevention and treatment of cancer and prolongation of life span of the affected subjects are discussed.

[Analysis of the alpha-synuclein gene dosage variation associated with autosomal dominant form of ParkinsonTs disease].

Fifty-two patients that had ParkinsonTs disease with autosomal dominant type of inheritance were analyzed for the presence of duplications and triplications in exons 4--6 of alpha-synuclein gene using real-time PCR with Taq-Man probes. No mutations involving the examined exons dosage were revealed in alpha-synuclein gene. Thus, mutations modifying copy number of alpha-synuclein gene do not significantly affect the pathogenesis of the autosomal dominant form of ParkinsonTs disease in patients from Russia.

[The role of apolipoprotein E in patients with amyotrophic lateral sclerosis (a clinical and genetic study)].

The apolipoprotein E (apoE) gene plays an important role in forming predisposition and modulating the course of Alzheimer's disease, primary parkinsonism and some other human neurodegenerative disorders. In this study, for the first time in the Russian population, we performed the analysis of genetic association of apoE gene variants in 62 patients with a sporadic form of amyotrophic lateral sclerosis (ALS) aged from 20 to 75 years (49.5+/-14.2); age at disease onset was from 18 to 74 years (47.1+/-15.2). No statistically significant differences in the distribution of apoE genotypes between patients and controls were found. It was shown that the frequency of the apoE-e2 allele was significantly higher in the young group characterized by more benign course of ALS (spinal variant, slow rate of progression of ALS and longer survival) as well as in patients with a more "benign" spinal form of the disease. On the contrary, the chance of carrying the apoE-e4 allele is higher in the older age group in which a prognostically more severe bulbar form is also more prevalent. Therefore, the apoE-e2 allele may be regarded as a neuroprotective factor in the development of neurodegenerative process in patients with ALS.

[A PARK8 form of Parkinson's disease: a mutational analysis of the LRRK2 gene in Russian population].

A recently described form of Parkinson's disease - PARK8 - is caused by mutations in the novel LRRK2 gene on chromosome 12q12. The most common mutation in this gene is the substitution G2019S and we studied it for the first time in a large group of Russian Slavonic patients (311 patients) with Parkinson's disease including 295 sporadic and 16 familial cases. The mutation LRRK2-G2019S was identified in 1% of patients examined (3 cases) and was not found in a group of population control. The clinical picture of all patients with the LRRK2-G2019S mutation was typical for levodopa-responsive parkinsonism and age of disease onset varied widely (from 39 to 71 years). Two different PARK8-linked haplotypes were found in carriers of the mutation that suggested the independent origin of the G2019S mutation on different chromosomes. The identification of mutations in the LRRK2 gene in patients with "ordinary" sporadic Parkinson's disease has serious implications for medical genetic counseling and prognosis in respective families.

[7-year experience in usage of mirapex in patients with different forms of primary parkinsonism].

The results of mirapex (pramipexol) treatment of 402 patients with Parkinson's disease and juvenile parkinsonism during the period from 6 months to 7 years are summarized. Mirapex was used in monotherapy as well as in combination with levadopa and other antiparkinsonic drugs. The drug was well tolerated and effective in rest tremor, hypokinesia, muscle rigidity and depression, the more pronounced effect being seen at the early stage of the disease. The use of mirapex allows an effective control of motor fluctuations developing during long-term continuous levodopa therapy. The results obtained characterize mirapex as a drug of choice in the treatment of juvenile parkinsonism. In case of a break in mirapex treatment, the recommencement of treatment usually is not accompanied by reduced sensitivity to drug effect.

[Neurodegenerative alterations induced by MPTP neurotoxin in senescence accelerated mice essay].

Behavioral modifications and alterations in biochemical pathways induced by neurotoxin MPTP in Senescence Accelerated Mice (SAM) brains are discussed. MPTP injections lead to specific injuries of dophaminergic neurons and to reinforcement of oxidative stress conditions. The ability of neuropeptide carnosine to protect animals from oxidative injuries induced by MPTP injections is also described.

[Clinical and genetic analysis of juvenile parkinsonism in Russia]. / Kliniko-geneticheskii analiz iuvenil'nogo parkinsonizma v Rossii.

Clinical and genetic analysis of juvenile parkinsonism was performed in 26 sibs from 20 families. Heterogeneity of the disorder was observed. Mutations in the parkin gene (locus PARK2, chromosome 6q25.2-27), with the prevalence of deletions over point mutations, have been identified in 41%. The comparative clinical analyses of patients examined confirmed the phenotypical polymorphism of "parkinopathy". We also showed the absence of asymmetric manifestation--an important and underestimated so far sign of the disease. The results of the study may be considered as a valuable clue to the clinical diagnosis of parkin-related juvenile parkinsonism in Russian population and implemented for mutation screening and medico-genetic counseling of affected families.

[Molecular genetic analysis of hereditary neurodegenerative diseases]. / Molekuliarno-geneticheskii analiz nasledstvennykh neirodegenerativnykh zabolevanii.

The review summarizes the results of a decade of molecular genetic studies of several high-incidence hereditary neurodegenerative diseases, including primary parkinsonism, various forms of hereditary dystonia and ataxia, polyglutamine disorders, hepatolenticular degeneration, essential tremor, etc. Various relevant mutations were studied. The character and frequencies of particular mutations and the corresponding genetic disorders were established for the Russian population. Particular genotypes were associated with various clinical variants of the diseases. Genetic loci were identified for several unique hereditary diseases of the nervous system (X-linked cerebellar hypoplasia, an atypical form of autosomal recessive muscular dystrophy, etc.). Nosological positions of the relevant clinical forms were clarified on the basis of the molecular genetic data. Protocols were developed for direct or indirect DNA diagnostics of the diseases under study to improve medical genetic counseling and prevention of new disease cases in affected families.

[Cytochemical activity of mitochondrial enzymes in Parkinson's disease]. / Tsitokhimicheskaia aktivnost' mitokhondrial'nykh fermentov pri bolezni Parkinsona.

Using cytochemical computerized morphometric method, activity of the key enzymes of energetic metabolism (succinate dehydrogenase, alpha-glycerophosphate dehydrogenase, malate dehydrogenase, glutamate dehydrogenase and lactate dehydrogenase) was studied in blood lymphocytes of 75 patients with Parkinson's disease and 15 healthy controls. The signs of systemic mitochondrial insufficiency, which correlated with the disease duration and severity, were found in all the patients, including those with juvenile parkinsonism. These data may provide a basis for introducing cytochemical monitoring as well as for administration of modern "mitochondrial" drugs (yantavit, coenzyme Q10, L-carnitine, etc).

[Clinical and stabilometric analysis of postural instability in Parkinson's disease]. / Kliniko-stabilometricheskii analiz postural'nykh narushenii pri bolezni Parkinsona.

A disturbance of postural control is one of the most invalidating symptoms of Parkinson's disease (PD), and mechanisms underlying its development have not been so far elucidated. To specify the postural control features in different PD forms, clinico-neurophysiological analysis was conducted in 61 patients divided into 3 groups according to PD forms: tremor-rigid, rigid-tremor and akinetic-rigid. Dissociation between clinical expression of postural instability and its stabilometric reflection--the square of statokinesogram was found, indicating importance of differentiated approach in performance of stabilometric analysis in patients with different PD forms. The square of statokinesogram may be regarded as a neurophysiological marker of postural instability only in patients with rigid forms, in tremor parkinsonian phenotypes an increased square of stabilogram being mainly a stabilometric reflection of tremor. The importance of stabilometric test performance with cognitive loading, allowing switching out of voluntary posture control, is shown. Possible neuromediator mechanisms involved in postural instability in PD are discussed.

[Features of learning voluntary control of posture after pyramidal and nigrostriatal lesions]. / Osobennosti obucheniia proizvol'nomu kontroliu pozy pri porazheniiakh piramidnoi i nigro-striarnoi sistem.

The study was aimed at investigation of a deficit of learning the center-of-pressure voluntary control in patients with lesions of corticospinal and nigrostriatal systems. Thirty three patients with Parkinson's disease and 20 patients with hemiparesis after cerebrovascular accidents in the MCA participated in the investigation. The subjects stood on a force platform and in the form of a computer game were trained to match the projection of the center of pressure (a cursor) with a target on the screen under the visual feedback control. Two different postural tasks were presented. In the first task the direction of the center-of-pressure shift was not known before, so the subject learned the general strategy of the center-pressure control. In the other task a precise postural coordination should be formed. The voluntary control of the center-of-pressure position was found to be impaired in both groups of patients. In the task of moving the center of pressure in various directions (general strategy), no differences in the initial deficit of the task performance were found between the groups, but the learning was more efficient in the group of hemiparetic patients. However, in the task with precise postural coordination, despite the greater initial deficit in the parkinsonian patients, the learning in this group of patients was substantially more efficient than in hemiparetic patients. The results suggest both common and different features of the involvement of the corticospinal and nigrostriatal systems in learning voluntary control of posture.

[Regularities of fixation of brain serum antibodies from patients with lateral amyotrophic sclerosis in rabbit CNS]. / Osobennosti fiksatsii protivomozgovykh syvorotochnykh antitel bol'nykh bokovym amiotroficheskim sklerozom v TsNS krolika.

Kuhns' indirect immunofluorescent test was used to study fixation of serum brain antibodies (Ab) of patients with bulbar, cervicothoracic, lumbosacral lateral amyotropic sclerosis (LAS) on brain sections of rabbits. The disease is characterized by formation of brain Ab complementary to various structures of nervous and glial cells, myelin of fibers from different conducting systems, vessels which exhibit both common and individual antigenic properties. It was found that fixation of antineuronal, antimyelin brain Ab of patients with bulbar, cervicothoracic and lumbosacral LAS in different CNS structures varies.

[Molecular genetic analysis of essential tremor]. / Molekuliarno-geneticheskii analiz éssentsial'nogo tremora.

Essential tremor (ET) is the most common extrapyramidal disorder of the central nervous system with autosomal dominant transmission in the majority of cases and age-dependent penetrance of the mutant gene. In a number of cases, it shares some phenotypic features with autosomal dominant idiopathic torsion dystonia (locus DYT1 on chromosome 9q32-34) and is genetically heterogeneous: distinct variants of ET were mapped to chromosomes 3q13 (ETM1) and 2p22-25 (ETM2). We performed studies of candidate loci in a group of Slavonic (11 patients) and Tajik (19 patients) families with ET. Mutational analysis of the DYT gene in probands did not reveal the major deletion 946-948delGAG characteristic of idiopathic torsion dystonia, which allows one to genetically distinguish the studied hereditary forms of ET and torsion dystonia. Based on analysis of genetic linkage in informative Tajik pedigrees with ET, linkage to locus ETM1 on chromosome 3q13 was established in four families. Maximum pairwise Lod score was 2.46 at recombination fraction of theta = 0.00; maximum combined multipoint Lod score was 3.35 for marker D3S3720 and a common "mutant" haplotype for markers D3S3620, D3S3576, and D3S3720 allowed us to locate a mutant gene in a relatively narrow chromosome region spanning 2 cM. In one informative pedigree with ET, both candidate loci ETM1 and ETM2 were definitely excluded on the basis of negative Lod scores obtained by linkage estimations, which testifies to the existence of another distinct gene for autosomal dominant ET.