[A comparative assessment of microbiocenosis of saliva and oropharynx in patients with migraine]. / Sravnitel'naya otsenka mikrobiotsenoza slyuny i rotoglotki u patsientov s migren'yu.

OBJECTIVE: To identify changes in the microbiome of saliva and to compare it with the microbiome of the oropharynx of patients with migraine. MATERIAL AND METHODS: Sixty patients with migraine (21-56 years old), were examined using a headache diary, MIDAS and VAS. A microbiological examination of saliva and smear from the mucosa of the posterior wall of the oropharynx with evaluation by the method of mass spectrometry of microbial markers (MSMM) with the determination of 57 microorganisms was performed. All patients had comorbid chronic diseases of the gastrointestinal tract and upper respiratory tract (URT), according to anamnestic data and examination by specialists. RESULTS: A significant increase in the content of markers of resident (conditionally pathogenic) microorganisms characteristic of chronic diseases of URT (strepto- and staphylococci); markers of transient microorganisms characteristic of intestinal microflora (clostridia, gram-negative rods, anaerobes) that are normally absent; viral markers of cytomegaloviruses and herpes groups; a decrease in the content of fungi were identified in saliva. A comparative analysis of the microbiome of saliva and oropharynx showed: 1) a significant decrease in the concentration of coccal flora Enterococcus spp., Streptococcus mutans, Staphylococcus aureus, anaerobic bacteria Clostridium difficile and Clostridium perfringens in saliva; enterobacteria Helicobacter pylori; gram-negative rods Kingella spp., fungi and Epstein-Barr virus; 2) an increase in salivary concentrations of Staphylococcus epidermidis, anaerobic Clostridium ramosum and Fusobacterium spp./Haemophilus spp. and gram-negative bacilli Porphyromonas spp. CONCLUSION: A comparative assessment of the microbiota of a smear from the posterior wall of the oropharynx and saliva using MMSM showed the presence of dysbiosis both in the oropharynx and in the saliva of patients with migraine. However, there were fewer deviations from the norm in saliva, therefore, for diagnostic purposes, a smear from the posterior wall of the oropharynx is more significant as a biomarker for patients with migraine.

[Nocturia in Parkinson's disease]. / Nokturiya, svyazannaya s bolezn'yu Parkinsona.

OBJECTIVE: Evaluation of nocturia and its relationship with clinical characteristics of Parkinson's disease (PD) and dopaminergic therapy. MATERIAL AND METHODS: One hundred and thirteen patients with PD of I-III Hoehn and Yahr stage (H&Y) were examined using the following scales: IPSS, including nocturia domain, UPDRS, Sch&En, PDQ-39, MMSE, FAB, BDI, STAI-S and STAI-T, PFS-16, NMSQuest, GDSS, GSRS, and orthotest. RESULTS: Nocturia was detected in 93 patients. It depended on the age of the patients (rS=0.345; p<0.001) and was more spread among women (p=0.002). We obtained positive correlations of nocturia (p<0.05) with: PDQ-39 (rS=0.296), H&Y (rS=0.223), UPDRS (rS=0.265) and its items (speech, walking disorders, standing up from chair, posture and postural stability), NMSQ (rS=0.318), FAB (rS= -0.359), BDI, STAI-S and STAI-T, PFS-16, gastrointestinal parameters and blood pressure in the supine position. No significant effect of dopaminergic therapy on the severity of nocturia was found. According to regression analysis (stepwise method), predictors of nocturia are depression, higher lying blood pressure, constipation and postural instability (R2=0.474). CONCLUSIONS: Nocturia is the most common urological symptom in patients with PD and it significantly reduces the quality of life starting from the early stages of the disease. Nocturia increases as PD progresses, it is independent of dopaminergic medications, and it is directly associated with a number of parkinsonian symptoms (postural, frontal cognitive, affective and autonomic), which are partly dopamine-resistant. This indicates the common pathogenesis of nocturia and other symptoms of PD and the significant influence of polytransmitter imbalance.

[Lower gastrointestinal dysfunction in patients with Parkinson's disease]. / Disfunktsiya nizhnikh otdelov zheludochno-kishechnogo trakta u patsientov s bolezn'yu Parkinsona.

OBJECTIVE: To assess the lower gastrointestinal tract dysfunction in patients with Parkinson's disease (PD) and to reveal its relationships with motor and non-motor symptoms. MATERIAL AND METHODS: One hundred and eighteen patients with PD of I-III Hoehn and Yahr (H&Y) stages were studied using UPDRSI-IV, Sch&En, PDQ-39, MMSE, BDI, STAI-S and STAI-T, PFS-16, NMSQ, GSRS, BSFS, AUA. Body mass index and saliva amount and lacrimation (Schirmer's test) were assessed. RESULTS: Constipation from mild to moderate intensity was present in 71.2% of the patients; predominantly mild diarrhea occurred in 27.9%; alternations of diarrhea with the difficulty in intestine emptying were observed in 25.4%. We found significant correlations of constipation with the following parameters: Sch&En scales (rS=-0.291) and PDQ-39 (rS=0.478), patient's age (rS=0.275), H&Y stage (rS=0.2604), UPDRS (rS=0.254), axial motor symptoms of parkinsonism, and a number of affective and autonomic disorders, most of which were partly dopamine-resistant. Diarrhea did not affect the quality of patient's life, or depend on age, PD stage, main digital and non-motor symptoms, but directly correlated with the severity of constipation (rS=0.263) and other gastrointestinal disorders. There were no effects of dopaminergic therapy, including levodopa, dopamine-receptor-agonists, and amantadine, on the lower gastrointestinal tract dysfunction. CONCLUSION: Dysfunction of the lower gastrointestinal tract (predominantly from mild to moderate intensity) was detected in most PD patients of I-III stages. Our data indicate a complex pathogenesis of the PD impaired bowel emptying, involving degeneration of non-dopaminergic structures, and the predominant influence of concomitant diseases and inadequate laxative therapy on the formation of diarrhea syndrome in PD.

[The role of food allergy as a provoking factor of migraine]. / Rol' pishchevoi allergii kak provotsiruyushchego faktora migreni.

OBJECTIVE: To assess the effect of food allergies on the course of migraine. MATERIAL AND METHODS: Seventy patients with migraine, aged 21-56 years old, were examined using headache diary, MIDAS and VAS, studies of specific antibodies of the IgG4 class (delayed type food allergy) by immuno-enzyme analysis (ELISA), microbiological examination of a smear from the mucous membrane of the posterior wall of the oropharynx with mass spectrometry of microbial markers (MSMM) with the identification of 57 microorganisms. RESULTS: We found an increase in specific IgG4 for a number of food allergens in most patients with migraine, of which 48.5% had a pronounced increase in IgG4 (>150 kEd/l) for at least one allergen (cow's milk - 13% patients, wheat flour - 5%, egg white - 47% or yolk - 26%, quail egg - 15%, sweet pepper - 6%), in 29% of people to several food allergens at once (all of them had chicken egg protein as one of the allergens). There was the association of IgG4 titers to wheat allergen with the severity of headache according to VAS (r-S=0.7; p=0.0046) in patients with the most severe, chronic migraine (17 people) and with an imbalance of the oropharyngeal microbiota, namely, concentration of pathological viruses Herpes spp. (rs=0.29; p=0.02), Epstein-Barr (rs=0.46; p=0.0002) and microscopic fungi (rs=0.39; p=0.0016), detected in these patients. CONCLUSION: We show for the first time the relationship between delayed-type food allergy and redistribution in the microbiome of the oropharynx of patients with migraine and once again confirm the role of delayed-type food allergy as a clinically significant factor influencing the course of migraine (its intensity and chronicity).

[Motor and autonomic disorders influence on pain syndrome of patients with Parkinson's disease of the I-III H&Y stages]. / Vliyanie motornykh i vegetativnykh narushenii na vyrazhennost' bolevogo sindroma u patsientov s I­III stadiyami bolezni Parkinsona.

OBJECTIVE: To evaluate the influence of motor and autonomic disorders on the pain of patients with PD of the I-III H&Y stages and possibility of correcting the pain with dopamine receptor agonists (ADR). MATERIAL AND METHODS: 252 patients (128 women and 124 men, 42-80 years old) with PD of I-III Hoehn and Yahr stages (H&Y) were examined using the following scales: UPDRS, daily activity Sch&En, quality of life PDQ-39, MMSE, BDI, PFS-16, NMSQuest, GSRS, AUA; 53 patients were piribedil treated during 6 months. RESULTS: Our results indicated a wide prevalence of pain syndrome in PD patients (58.6%), starting from the early stages (50% for the Ist stage). The most stable pain associations were found with the PD stage, levodopa doses, severity of motor symptoms (postural disorders and hypokinesia manifestations) and motor complications («off-periods¼ and dyskinesias), as well as non-motor PD manifestations depression and autonomic dysfunctions (constipation, swallowing disorders, and frequent urination). The regression analysis showed, that the severity of motor complications and depression were the predictors of pain occurrence. The pain syndrome in patients with PD of I-III stages underwent significant regression (by 51% and 62%, after 1.5 and 6 months of therapy, respectively) after ADR (piribedil) addition to their therapy; it's probably due to improving the motor component and decreasing depressive disorders. CONCLUSIONS: The piribedil inclusion contributes to the reduction of pain syndrome, regardless is it used in monotherapy or in conjunction with levodopa preparations.

[The state of the oropharyngeal microbiome in patients with migraine]. / Sostoyanie mikrobioma rotoglotki u patsientov s migren'yu.

OBJECTIVE: To determine a role of changes in the oropharyngeal microbiome in the development and clinical manifestations of migraine. MATERIAL AND METHODS: Seventy patients with migraine, aged 21-56 years, and 15 healthy subjects matched for age and sex were examined using headache diary, MIDAS and VAS, the Gastrointestinal Symptom Rating Scale (GSRS), microbiological smear examination from the mucous membrane of the posterior wall of the oropharynx with evaluation by the method of mass spectrometry of microbial markers (MSMM) with determination of 57 microorganisms. RESULTS: The following changes in the oropharynx of individuals with migraine compared with the group of healthy individuals (control group) were found: a) a significant increase in the content of markers of resident (conditionally pathogenic) microorganisms characteristic of chronic diseases of the upper respiratory tract (strepto- and staphylococci); b) the appearance of markers of transient microorganisms normally absent, characteristic of the intestinal microflora (clostridia, gram-negative rods, enterobacteria, anaerobes); c) the appearance of viral markers of cytomegaloviruses, Herpes group, Epstein-Barr; d) a significant decrease in the content of bifidobacteria and lactobacilli). All people with migraine had a history or were found on examination to have chronic diseases of the upper respiratory tract (sinusitis in 48%, pharyngitis in 43%, tonsillitis in 25% of people), and gastrointestinal diseases. Dyspepsia was the most frequent and pronounced of the gastrointestinal syndromes on the GSRS in people with migraine (87%). This corresponds to the data on the extremely frequent occurrence of IBS (70% of patients) and other gastrointestinal pathology obtained from the patient history. CONCLUSION: In our work, the microbiota of the oropharynx in patients with migraine was studied for the first time using a new MSMM method. Disturbance of the oropharyngeal microbiome compared to the norm was detected in 100% of people with migraine. The changes characteristic of most patients included a significant decrease in the content of normal flora, an increase in the concentration of conditionally pathogenic microorganisms and the appearance of pathogenic microflora characteristic of chronic diseases of the upper respiratory tract and gastrointestinal tract, which may indicate their role in the pathogenesis of migraine.

[Upper gastrointestinal tract dysfunction and its correction by dopamine agonists for patients with Parkinson's disease of I-III stage]. / Disfunktsiya verkhnikh otdelov zheludochno-kishechnogo trakta u patsientov na I­III stadiyakh bolezni Parkinsona i ee korrektsiya agonistami dofaminovykh retseptorov.

OBJECTIVE: To evaluate the main symptoms of the upper gastrointestinal dysfunction (salivation and swallowing disorders) and to determine their impact on the quality of life for patients with PD of stages I-III, as well as the possibility of their correction by dopamine receptor agonists. MATERIAL AND METHODS: 252 patients (128 women and 124 men, 42-80 years old) with PD of stages I-III were examined using: UPDRS items «salivation¼, «swallowing¼ and «anorexia¼, scale of daily activity (Schwab and England ADL scale), questionnaire quality of life (PDQ-39), measurement of saliva amount, BMI, MMSE scale; 53 patients were treated with piribedil during 6 months. RESULTS: The upper gastrointestinal tract dysfunction of mild to moderate severity was detected in 51.2% of patients. The prevalence of sialorrhea was 38.9, 42.9 and 46.2%, and that of dysphagia was 22.2, 24.3 and 17.3% at stages I-III, respectively. According to the results of the correlation analysis dysphagia is associated with a long history of PD, low BMI, high doses of levodopa and low Sch & En score; and sialorrhea is also associated with low BMI and with old age. For the early stages of PD we can tell, that the quality of patients' life deteriorates, and this to a large extent is due to impaired salivation and swallowing, which manifest themselves in daily activity and communication difficulties. CONCLUSIONS: The inclusion of piribedil (150-250 mg/day) in the 6-months therapy reduces the dysfunction of the upper gastrointestinal tract (by 61 and 74% of the initial level of dysphagia and sialorrhea, respectively) regardless the drug use in monotherapy or in complex therapy with levodopa.

[The influence of age and gender on the characteristics of cognitive impairment in patients with cardiovascular risks]. / Vliyanie vozrasta i gendera na kharakteristiki narusheniya kognitivnykh funktsii u patsientov s faktorami serdechno-sosudistogo riska.

OBJECTIVE: Assessment of the features of cognitive impairment in patients with vascular risk factors, depending on age and gender. MATERIAL AND METHODS: The observational cross-sectional study included data from 1.651 patients aged 45 to 84 years with vascular risk factors from various regions of the Russian Federation. The presence and nature of cognitive impairment (CI) were detected using the MOCA test, taking into account the total MOCA score and MOCA indexes evaluating violations of individual cognitive functions (memory, attention, speech, executive and visual-constructive functions, orientation). RESULTS: CI was detected in 89.2% of the surveyed (the total score of the MOCA <26). In middle-aged patients, 45-49 years old, executive functions and attention suffered more. The negative dynamics of CI significantly worsened in the age range of 70-75 years, statistically significantly increased every subsequent five years and was manifested by deterioration both in the mnestic sphere and in other cognitive domains. Statistically significant differences in the indicators of the total MOCA score in women and men were revealed at the age of 80-84 years (16.1 vs. 13.8 points, respectively, p=0.0279). By the age of 80-84, women had higher indicators of attention (p=0.025) and orientation (p=0.028) than men of the same age. CONCLUSION: The data obtained make it possible to identify patients, regardless of gender, under the age of 70 as an important target group for the treatment and more aggressive prevention of CI.

Gastrointestinal Dysfunction Impact on Life Quality in a Cohort of Russian Patients with Parkinson's Disease I-III H&Y Stage.

Background: There are still no clearly proven methods to slow down or stop the progression of Parkinson's disease (PD). Thus, improving the quality of life (QoL) of patients with PD becomes of primary importance. Autonomic dysfunction and its symptoms are known to worsen the quality of life in PD, but the degree of this influence is underinvestigated. Particularly, impacts of the separate significant gastrointestinal symptoms, such as dyspepsia, constipation, and abdominal pain, in PD should be more precisely evaluated with the help of specific scales. Objective: To assess the impacts of gastrointestinal dysfunction and its symptoms on PD patient's QoL using PDQ-39. Methods: 111 PD patients in the I-III Hoehn and Yahr (H&Y) stage were enrolled in the study. The following scales were applied: UPDRS III, PDQ-39, GSRS, GDSS, MMSE, BDI, STAI-S, and STAI-T. Results: The linear regression model showed that the PDQ-39 SI depended on summary assessments GSRS-SI (ß = 0.333, p < 0.001), BDI (ß = 0.463, p < 0.001), and UPDRS III (ß = 0.163, p < 0.05). The use of the stepwise method, adding GSRS-SI and UPDRS III scores to the BDI predictor, improved the model (R2 increased from 0.454 to 0.574). The investigation of GSRS domain's influence revealed that PDQ-39 SI had a significant correlation with almost all of them, but the regression analysis showed significant QoL impacts of only two factors: constipation and abdominal pain (ß = 0.288, p < 0.01 and ß = 0.243, p < 0.05 accordingly). Conclusions: Our results suggest a considerable negative influence of depression and gastrointestinal dysfunction (especially constipation and abdominal pain) on QoL of patients with PD. Their impact on QoL in patients with I-III H&Y stages of PD is more significant than that of motor symptoms. Therefore, the correction of depression and gastrointestinal dysfunction should be prioritized in PD therapy.

[Mild cognitive impairment: modern aspects of diagnostics and therapy]. / Umerennye kognitivnye rasstroistva: sovremennye aspekty diagnostiki i terapii.

The article provides a review of current literature on the diagnosis and treatment of mild cognitive impairment (MCI). MCI is not a common outcome of brain aging; it is an intermediate state between normal cognitive status and mild dementia. The MCI concept has been actively developing over the past few decades, a lot of knowledge and clinical experience has been accumulated, and numerous clinical trials are being conducted to develop effective methods of diagnosis and therapy. Treatment of pre-dementia cognitive disorders differs in many ways from therapy for dementia and has a better prognosis, therefore, it is recommended to diagnose and begin treating cognitive disorders as early as possible. The main possibilities of drug and non-drug therapy are described, with an emphasis on the use of the dopamine receptor agonist piribedil in the treatment of MCI and sensory deficit in elderly patients. The mechanisms of action of the drug are analyzed, data from the main clinical studies of the efficacy and safety of piribedil are presented: the positive effect of the drug on cognitive functions has been shown in more than 10 international clinical trials including about 7000 patients and in a number of post-marketing works performed on the Russian population of patients. Piribedil is successfully used for various types of cognitive disorders, both neurodegenerative and vascular, of mild to moderate severity.

[Chronic cerebral ischemia in obstructive pulmonary diseases]. / Khronicheskaia ishemiia mozga pri obstruktivnykh zabolevaniiakh legkikh.

Chronic obstructive pulmonary disease (COPD) is one of the main causes of disease and death incidences worldwide. Different organs and systems are involved in COPD activating tissue hypoxia. It affects especially tissue functioning with the high level of intensity of metabolic processes, and the nervous system suffers first. Neuroimaging studies show white and grey matter damage and cerebral atrophy, which may clinically manifest themselves in different neurological symptoms depended on vascular system lesions, and cognitive and affective impairments. Despite of its potential importance, encephalopathy in COPD remains a little-studied concomitant pathology. Application of cytoprotective drugs is pathogenetically justified in this case and must be included in COPD complex therapy. In particular, the inclusion of mexicor in the treatment of patients with chronic pulmonary heart increases the efficacy of treatment of the main and associated diseases (chronic cerebral ischemia, cardiac insufficiency and arrhythmia).

[The agonist of dopamine receptors piribedil in treatment of Parkinson's disease]. / Agonist dofaminovykh retseptorov piribedil v terapii bolezni Parkinsona.

In this paper, the authors review the current foreign and domestic literature on a role of the agonist of dopamine receptors piribedil in the treatment of Parkinson's disease. The results of the main studies of the efficacy and safety of piribedil, mechanisms of actions and a comparative characteristics with other dopamine receptors agonist are reviewed.

[An impact of pronoran on cognitive and affective disorders in Parkinson's disease].

Sixty patients with different types of Parkinson's disease (PD), the disease stage 2.3 +/- 0.08 according to Hoehn&Yahr scale, were treated with Pronoran. Impact of the drug on movement, cognitive and affective disorders assessed by corresponding scales and psychological tests has been studied. Pronoran exerted a positive effect on all the disorders. It improved cognitive function, i.e. reasoning, memory and attention. A more pronounced influence on cognitive function was detected in earlier stages of the disease and for less severity cases of rigid-tremor PD type. A moderate antidepressive effect of Pronoran was found, being more pronounced in the severe PD stages. Emotional disorders were better treated, when Pronoran was used in combination with madopar, and cognitive dysfunction--in case of monotherapy.