[Changes in corneal nerves fibers in the early stages of Parkinson's disease according to in vivo confocal microscopy (preliminary report)]. / Izmeneniya nervnykh volokon rogovitsy na rannikh stadiyakh bolezni Parkinsona po dannym lazernoi konfokal'noi mikroskopii (predvaritel'noe soobshchenie).

One of the research directions of the so-called non-motor manifestations of Parkinson's disease (PD) is associated with the assessment of structural and functional changes in the organ of vision. An assessment of the state of thin non-myelinated corneal nerve fibers (CNF) in Parkinson's disease seems to be promising considering the neurodegenerative nature of the disease, as well as the possibility of objective intravital assessment of both functional and structural changes in CNF. PURPOSE: To analyze the changes in the course and structure of corneal nerve fibers in the early stages of Parkinson's disease based on an objective algorithm of in vivo corneal confocal microscopy (CCM). MATERIAL AND METHODS: The study was conducted on a group of 16 patients aged 39 to 66 years with verified diagnosis of PD. In addition to standard neurological and ophthalmological examinations, all patients underwent IVCCM on a Heidelberg Retinal Tomograph device with special Rostock Cornea Module (HRT3 RCM), followed by processing of the obtained images using a uniquely designed analysis algorithm. RESULTS: A significant decrease in the directional anisotropy coefficient and an increase in the directional symmetry coefficient of the nerve fibers of the cornea were established (average values 3.15±1.08 and 0.92±0.04, respectively); in healthy individuals of the identical age range these indicators are 3.5±0.85 and 0.86±0.11, respectively. In addition, qualitative structural changes were noted, which consisted of an increase in the number of branches from the main nerve trunks, an increase in the tortuosity of CNF, multidirectionality, and "beaded" shape. In 9 cases, the presence of macrophages was revealed - dendritic Langerhans cells, which is an indirect sign of the inflammatory process. CONCLUSION: The preliminary nature of the results obtained in this study and the need for further research in this area are related, on the one hand, to a small sample of observations and, on the other hand, to the criterion used to assess the status of CNF based on a comparative analysis with conditionally normal indicators. In the future, in order to solve the problem of the uniqueness of changes in CNF and the possibility of using these changes as a marker for PD progression, longitudinal studies are required to reveal the presence or absence of a correlation between the stage of the disease, the results of known monitoring methods (e.g. electromyography) and quantitative indicators of the status of CNF.

[Application of brain electrical activity burst analysis method for detection of EEG characteristics in the early stage of Parkinson's disease]. / Primenenie metoda analiza vspleskoobraznoi élektricheskoi aktivnosti mozga dlia vyiavleniia osobennostei ÉÉG patsientov na rannei stadii bolezni Parkinsona.

AIM: To develop a mathematical method of analysis and visualization of EEG based on the ROC analysis of burst electrical activity in the cerebral cortex. MATERIAL AND METHODS: Using a new method of analysis of EEG burst activity, the frequency parameters of brain electrical activity have been investigated in patients in the first stage of Parkinson's disease (PD) defined by the Hoehn and Yahr scale. Patients were right-handed, with disease onset in either the right or the left side. The burst term is used in neurophysiology for the description of wave activity in EEG signals. Bursts are reflected in the local peaks of wavelet spectrograms, some of the parameters of which have been analyzed. Electrical activity of the left and right central cortex areas was investigated. The results were compared with those obtained from healthy volunteers. RESULTS: In PD patients, burst activity was changed in alpha- and beta bands. Compared to healthy volunteers, it was higher in alpha band 8-9 Hz and lower in upper alpha band 11-13 Hz and beta band 18-24 Hz. With regard to asymmetry of the brain in PD patients, there was the change in burst activity in both brain hemispheres. Diagrams of burst activity showed the difference between the patients with tremor onset in the left hand and tremor onset in the right hand. CONCLUSION: This suggests differences in brain electrical activity changes in patients with left-sided and right-sided disease onset. The initial results of the study demonstrate that the method of analysis and visualization based on the evaluation of certain parameters of EEG bursts is promising for the analysis of EEG features in PD patients.

[Are Interlimb Interactions Disturbed in Patients with Parkinson's Disease: a Study in Unloading Condition?]

During natural human locomotion neural connections characteristic for the control of quadrupedal walking are activated. The degree of interaction between the neural networks generating rhythmic movements of the upper and lower extremities, depends on the tonic state of each of these networks, adjustable by motor command in the brain. The distortion of such command in patients with Parkinson's disease (PD) may lead to disturbance of interlimb interactions. In conditions of arms and legs unloading in 17 patients with PD and 16 healthy subjects investigated the effect of limb movement of one girdle on the parameters of motor activity of the limbs of the other girdle in their combined cyclic movements. In patients the weakening of influences of active or passive arm movements, and active movements of the distal parts of the arms on voluntary leg movements was shown, while in healthy subjects the effect of arm movements on the parameters of voluntary movements was significant. The effect of arm movements on the possibility of involuntary activation of air- stepping by vibratory stimulation of the leg muscles in patients was absent, while in healthy subjects the motor activity of the arms increased the opportunity of involuntary rhythm activation. The differences in the influence of leg movements to the rhythmic movement of the upper extremities in patients and healthy subjects were revealed. The medication exhibited interlimb interaction, but it was insufficient for normalization of the state of neural networks in patients. It is concluded that in patients with PD, neural networks generating stepping rhythm are in a state of heightened tonic activity. This does not allow not only activating involuntary rhythmic movements, but also showing facilitation effect with arms to legs.

Lack of non-voluntary stepping responses in Parkinson's disease.

The majority of research and therapeutic actions in Parkinson's disease (PD) focus on the encephalic areas, however, the potential involvement of the spinal cord in its genesis has received little attention. Here we examined spinal locomotor circuitry activation in patients with PD using various types of central and peripheral tonic stimulation and compared results to those of age-matched controls. Subjects lay on their sides with both legs suspended, allowing low-friction horizontal rotation of the limb joints. Air-stepping can be used as a unique and important model for investigating human rhythmogenesis since its manifestation is largely facilitated by the absence of external resistance. In contrast to the frequent occurrence of non-voluntary stepping responses in healthy subjects, both peripheral (muscle vibration) and central (Jendrassik maneuver, mental task, Kohnstamm phenomenon) tonic influences had little if any effect on rhythmic leg responses in PD. On the other hand, a remarkable feature of voluntary air-stepping movements in patients was a significantly higher frequency of leg oscillations than in age-matched controls. A lack of non-voluntary stepping responses was also observed after dopaminergic treatment despite the presence of prominent shortening reactions (SRs) to passive movements. We argue that the state and the rhythmogenesis capacity of the spinal circuitry are impaired in patients with PD. In particular, the results suggest impaired central pattern generator (CPG) access by sensory and central activations.

[Possibilities of treatment of dystonic syndromes with akineton].

Treatment of dystonia is a complex problem of current neurology due to the etiological and neurochemical heterogeneity of this clinical syndrome. Central cholinolytics is a most effective group of drugs for patients with dystonia and dystonic tremor. The authors present the results of the successful treatment with biperiden (akineton), a centrally active anticholinergic drug with additional peripheral choline- and ganglion-blocking effect in cervical dystonia. The time of response to treatment and duration of clinical effect, its possible predictors are analyzed. Perspectives of using cholinolytics in treatment of different forms of dystonic hyperkineses are discussed.

[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.

[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.

[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.

[Kinematic characteristics of the voluntary cyclic trunk movements in patients at the early stage of Parkinson's disease].

Patients with the initial stage of Parkinson disease (PD) and matched controls performed repetitive bendings and turnings in standing position. Tasks included trunk movements in each of the anatomical planes: sagittal, frontal and axial. Electromagnetic system Flock of Birds was used for movement registration. Sensors were fixed at different segments of subject's body. Joint angles in the ankle, hip and torso as well as coordinates of the center of pressure served as output parameters. The amplitudes of joint angles were found to be lower in PD patients. Performance of the axial rotation revealed most pronounced differences. Thus, the amplitudes of joint angles of trunk movements in different anatomical planes reliably discriminate between PD patients and healthy subjects.

[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.

[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.

[Gilbert's syndrome: a clinicogenetic trial].

AIM: To improve diagnosis of Gilbert's syndrome (GS) basing on functional and genetic methods of examination. MATERIAL AND METHODS: GS was diagnosed in 88 patients aged 15-72 years using clinical and genetic tests. RESULTS: Genotyping has detected changes in promotor part of the gene coding uridindiphosphateglucuroniltransferase. In homozygous carriers GS was characterized by a higher baseline level of bilirubin, distinct response to functional tests, frequent combination with essential tremor. In heterozygous patients GS often ran latently. CONCLUSION: Four variants of GS course were established: dispepsic, asthenovegetative, jaundice, latent. Low-caloric diet followed by fenobarbital raised sensitivity and specificity of the test. A clinical classification of GS is proposed. The detected disorders of antipirin pharmacokinetics allow prognosis of the risk of unwanted reactions to the drugs metabolized by monooxigenases of the liver.

[A simple and rapid method for detection of the 106Gln mutation in Wilson-Konovalov disease]. / Prostoi i bystryi metod opredeleniia mutatsii 1069Gln pri bolezni Vil'sona-Konovalova.

A simple and rapid method for detecting the 1069Gln mutation in gene ATP7B based on a PCR specific for this allele has been developed. The 1069Gln mutation is the main cause of Wilson disease (WD) in Russia and accounts for approximately 40% of all mutant alleles of gene ATP7B. Therefore, the method proposed makes the postnatal and prenatal diagnosis of Wilson disease in Russia considerably more rapid and less expensive.

[Analysis of mutations in ATP7B gene and experience with direct DNA-diagnosis in hepato-lenticular degeneration]. / Analiz mutatsii v gene ATP7B i opyt priamoi DNK-diagnostiki pri gepatolentikuliarnoi degeneratsii.

Hepatolenticular degeneration (HLD) is a severe autosomal-recessive disorder of the copper metabolism. It is characterized by excessive accumulation of copper in the brain and in viscera and is conditioned by the damage in the gene of copper ATP-ase (ATP7B). The paper presents the results of screening of ATP7B gene mutation in 42 patients with HLD from Russian population. The regions of ATP7B gene that are the most frequently exposed to the mutation have been studied (the exzones 14, 15, 16, 18). It is demonstrated that A-->C mutation in the 14-th exzone that led to the change of histidine1069 amino acid for glutamine, was found in more than 60% of patients--Slavs from the European Russia. This mutation was observed in both homo- and heterozygous states. The deletion of (CCC-->CC) nucleotide in the 15-th exzone of the gene was observed in 2 cases. The detailed analysis of the clinical-genetic correlations was performed in patients with the determined damages of ATP7B gene. In Russia the experience of the direct DNA-diagnosis of HLD is described for the first time. It is significant for early evaluation of the patients in preclinical state and for prescription of the preventive copper-eliminating therapy.

[Hydrogen peroxide--a marker for respiratory tract inflammation in patients with bronchial asthma]. / Perekis' vodoroda kak marker vospaleniia dykhatel'nykh putei u bol'nykh bronkhial'noi astmoi.

AIM: To test H2O2 as a marker of respiratory tract inflammation in patients with bronchial asthma (BA). MATERIAL AND METHODS: The study entered 70 patients (20 males and 50 females) with atopic asthma (AA) aged 18 to 62 years (mean age 32.6 years). H2O2 concentration in the expired air (CEA) was determined spectrophotometrically (Gallati & Pracht, 1985), content of eosinophilic cationic protein (ECP) in blood--with radioimmunoassay kits (Pharmacia & Upjohn, Sweden). Forced expiratory volume per 1 second (FEV1) was used for assessment of severity of bronchial obstruction. Bronchial hyperreactivity was studied by means of the histamine bronchoprovocative test. RESULTS: H2O2 in CEA in BA patients was higher than in healthy subjects (0.127 +/- 0.010 microm/l vs 0.024 +/- 0.004 microm/l). H2O2 concentration significantly correlates with FEV1 (r = -0.449; p < 0.001), bronchial hyperreactivity to histamine (rs = -0.382; p < 0.05) and ECP in blood plasma(r = 0.625; p < 0.01). CONCLUSION: It was proved possible to use H2O2 in CEA for evaluation of respiratory inflammation in BA patients.