[Cognitive impairment in multiple system atrophy - exclusion criteria or an integral part of the clinical picture?] / Kognitivnye narusheniya pri mul'tisistemnoi atrofii ­ kriterii isklyucheniya ili neot"emlemaya chast' klinicheskoi kartiny?

Multiple system atrophy (MSA) is a severe, orphan disease characterized by a steady increase in symptoms of parkinsonism, cerebellar disorders, and autonomic failure. In addition to autonomic failure, which is considered the defining symptom of this type of atypical parkinsonism, there are a range of other non-motor clinical manifestations, such as sleep disorders, pain syndrome, anxiety-depressive disorders, cognitive impairment (CI). CI, especially severe CI, has long been considered as a distinctive feature of MCA. Recently, there have been many clinical studies with pathomorphological or neuroimaging confirmation, indicating a high prevalence of cognitive disorders in MCA. In this article, we discuss the pathogenetic mechanisms of the development of MCA and CI in MCA, as well as the range of clinical manifestations of cognitive dysfunction.

[Tremor-dominant form of Parkinson's disease]. / Tremor-dominantnaya forma bolezni Parkinsona.

The article is of a review nature and is devoted to tremor, one of the maladaptive and difficult-to-treat symptoms of Parkinson's disease (PD). Along with the classic rest tremor, patients with PD may experience tremor of other modalities: postural tremor, kinetic tremor, which reflects a multimodal mechanism of tremor formation involving multiple neurotransmitter systems. The unpredictable response to therapeutic options, the ambiguous response to levodopa, also reflects the role of multiple underlying pathophysiological processes. Among the drug methods of tremor correction, preference is given to dopamine receptor agonists - due to the spectrum of their pharmaceutical action, high efficiency in relation to all leading motor and a number of non-motor manifestations. The evidence for advanced neurosurgical, non-invasive modalities is mixed, and there are insufficient comparative studies to assess their efficacy in patients with tremor-dominant forms of PD.

[The complex effect of polyphenols on the gut microbiota and triggers of neurodegeneration in Parkinson's disease]. / Kompleksnoe vliyanie polifenolov na mikrobiom kishechnika i puskovye mekhanizmy neirodegeneratsii pri bolezni Parkinsona.

Intestinal dysfunction and microbiome changes are actively discussed in the modern literature as the most important link in the development of neurodegenerative changes in Parkinson's disease. The article discusses the pathogenetic chain «microbiome- intestine-brain¼, as well as factors that affect the development of intestinal dysbiosis. A promising direction for influencing microflora and inflammatory changes in the intestine is the use of polyphenols, primarily curcumin. The review of experimental, laboratory, clinical research proving the pleiotropic effect of curcumin, including its antioxidant, anti-inflammatory, neuroprotective effects, realized both through peripheral and central mechanisms is presented.

[Postural stability and walking in Parkinson's disease]. / Postural'naya ustoichivost' i khod'ba pri bolezni Parkinsona.

The article is of an overview nature and is devoted to movement disorders in Parkinson's disease. The article discusses the existing problems according to the latest literature data, a review on the treatment and rehabilitation of postural instability. Special attention in the article is paid to dopamine receptor agonists - namely, piribedil, prescribed for the correction of these disorders.

[Asthenia, mental fatigue and cognitive dysfunction]. / Asteniya, psikhicheskaya utomlyaemost' i kognitivnaya disfunktsiya.

Conditions associated with asthenia are usually characterized by increased fatigue, impaired activities of daily living and decreased productivity. In clinical practice it is important to distinguish between idiopathic chronic fatigue (primary or functional asthenia) and chronic fatigue syndrome (CFS). Fatigue can also be classified by neuromuscular and/or cognitive and mental fatigue. The article discusses the neuroanatomical basis and focuses on the neurocognitive theory of pathological fatigue. In addition the relationship between mental stress, fatigue and cognitive impairments such as subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) are also discussed. We discuss the rationale that for treatment of asthenic conditions accompanied by cognitive dysfunction it is justified to use combination therapy - fonturacetam and a preparation containing nicotinoyl-GABA and Ginkgo Biloba.

[Questionnaire of the Ryzhikh National Medical Research Centre for Coloproctology is a new tool for assessing chronic pelvic pain and pelvic organ dysfunction]. / Oprosnik NMITs koloproktologii imeni A.N. Ryzhikh ­ novyi instrument otsenki khronicheskoi tazovoi boli i narusheniya funktsii tazovykh organov.

The article presents the work of a multidisciplinary team of experts from various fields of medicine to optimize the «Questionnaire for assessing chronic pelvic pain and pelvic organ dysfunction (QCPPD) of the Ryzhikh National Medical Research Centre for Coloproctology¼ for use in clinical practice. The survey of respondents was conducted from June 28 to September 28, 2021. As a result of this survey, by repeatedly making edits and clarifications during communication with respondents, the final version was obtained, which allows assessing the patient's subjective sensations by the nature and localization of pelvic pain, sensitivity disorders and pelvic organ function. The main objective of this Questionnaire is to differentiate patients with neurogenic pain from a huge number of patients with chronic pelvic pain. This aspect will allow a more targeted approach to the diagnosis and pathogenetically justified treatment of patients, including after appropriate instrumental examinations. The work of a multidisciplinary team implies a higher degree of objectification and terminological accuracy of the Questionnaire under discussion. The presented version of the «Questionnaire for assessing chronic pelvic pain and pelvic organ dysfunction (QCPPD) of the Ryzhikh National Medical Research Centre for Coloproctology¼ will be primarily used in coloproctological patients with pelvic pain problems and anal incontinence and obstructive defecation. Further studies will be directed to the clinical evaluation of the results of the work carried out.

[First experience of thalamotomy by focused ultrasound under MR-guided navigation in the treatment of tremor. Neuroimaging follow-up. Case report and literature review]. / Pervyi opyt talamotomii fokusirovannym ul'trazvukom s MRT-navigatsiei pri lechenii tremora. Neirovizualizatsiya v dinamike. Klinicheskoe nablyudenie i obzor literatury.

The authors describe dynamic MRI and clinical data after non-invasive treatment of tremor in the upper extremity. Thalamotomy by high-intensity focused ultrasound under MR-guided navigation was performed. A 57-year-old patient with Parkinson's disease underwent treatment with focused ultrasound. MRI of the brain was performed 1 and 48 hours, 47 days, 3 and 6 months later. Features of natural course of focal brain changes after treatment, data of MR tractography necessary for correction of target zone are described. The authors conclude that MR changes are characterized by presence of a focus in the area of focused exposure. Peak severity is observed on the second day after procedure with subsequent regression. MR-based analysis of predictors is promising to forecast treatment outcomes.

[The problem of pharmacoresistant tremor in Parkinson's disease and essential tremor]. / Farmakorezistentnyi tremor pri bolezni Parkinsona i essentsial'nom tremore.

MR-guided focused ultrasound (MRg-FUS) is a new noninvasive method for the treatment of contralateral disabling and pharmacoresistant tremor. Clinical studies have confirmed the high efficacy and safety of using MRg-FUS in patients with essential tremor and Parkinson's disease, in short and long-term studies. Advantages of this method in comparison with currently used invasive and noninvasive technics, potential brain target areas, the possibility of bilateral intervention, indications and contraindications are discussed.

[Mechanisms of development of constipation in Parkinson's disease and therapeutic approaches]. / Mekhanizmy razvitiya i vozmozhnosti korrektsii konstipatsii pri bolezni Parkinsona.

Constipation is one of the most common non-motor symptoms of Parkinson's disease. The pathogenetic mechanisms of constipation, diagnostic criteria, approaches to investigations and treatment are discussed in the paper.

[Roadmap for ecosystem-based approach for patients with Alzheimer disease in Russia: current needs, barriers, and possible solutions (resolution of the scientific and practical experts meeting)]. / Dorozhnaya karta po okazaniyu pomoshchi patsientu s bolezn'yu Al'tsgeimera v Rossii v formate ekosistemy: tekushchie potrebnosti, bar'ery i vozmozhnye resheniya (rezolyutsiya nauchno-prakticheskoi vstrechi ekspertov).

The care of a patient with Alzheimer's disease (AD) is considered from the perspective of an ecosystem, that is, a systemic approach describing effective partnership, collaboration and research aimed at creating value, involving all participants in the AD patient journey. The effectiveness of this ecosystem is only possible with the involvement of all stakeholders in its development, including patients, healthcare professionals at all levels, government agencies, private companies, and patient organizations. The unmet health care and information needs of patients with AD are a consequence of barriers in the AD ecosystem. Key barriers for the patient include low awareness and stigmatization of the disease in society, lack of quality epidemiological data, difficulties in timely diagnosis, lack of prevention programs, unpreparedness of most physicians to conduct AD patient rehabilitation, and other factors. Based on the analysis of the ecosystem of AD and the patient pathway, 10 main directions (strategies) necessary for the formation of the ecosystem were identified: conducting research in the diagnosis and epidemiology of AD, creating and implementing a cognitive health program, forming a legal framework, raising public awareness, optimizing patient routing for timely diagnosis, organizing a network of memory clinics/laboratories, creating a register of patients with dementia, developing digital solutions and supporting social projects.

[A rare clinical case of comorbidity of early-onset Parkinson's disease and remitting multiple sclerosis]. / Redkii klinicheskii sluchai sochetaniya rannego nachala bolezni Parkinsona i remittiruyushchego rasseyannogo skleroza.

Comorbidities of extrapyramidal disorders and multiple sclerosis (MS) are rare. The chance of a combination of MS and Parkinson's disease (PD) is less than 1 in 12.5 million. In total, 42 cases of joint development of these disorders are described in the literature. All described patients had no initial changes in the basal ganglia on MRI, and the development of MS was diagnosed after 1-8 years. Possible common links in the pathogenesis of neurodegenerative disease and MS, as well as the cumulative effect of the two diseases on the severity of axonal degeneration and neuronal loss are discussed. A description of a clinical case of a combination of early onset PD and relapsing-remitting multiple sclerosis is presented.

[Amantadine in the treatment of Parkinson's disease. New opportunities in the context of COVID-19]. / Amantadiny v lechenii bolezni Parkinsona. Novye vozmozhnosti v usloviyakh COVID-19.

The article presents data from recent studies on the mechanisms of action and clinical efficacy of amantadines, and also describes a possible protective effect against COVID-19.

[Restless legs syndrome]. / Sindrom bespokoinykh nog.

Restless legs syndrome (RLS) is seen widely in clinical practice. RLS commonly occurs at night time and presents with unpleasant or uncomfortable sensations in the legs that causes an urge to move them. This article describes the epidemiology, risk factors and pathophysiology of RLS. There is a detailed description of clinical presentations, diagnostic criteria and also management of RLS.

[Development of early diagnosis of Parkinson's disease and comprehensive economic analysis of the effect of its implementation]. / Razrabotka rannei diagnostiki bolezni Parkinsona i kompleksnyi ekonomicheskii analiz effekta ot ee vnedreniya.

The paper summarizes the literature and author's data on the development of early (preclinical) diagnosis of Parkinson's disease (PD). Implementation of this diagnosis will promote the use of preventive therapy and change investments in diagnosis and treatment of patients. The paper declares that at present the only approach to early diagnosis of PD is positron-emission tomography of the nigrostriatal dopaminergic system, but it cannot be used for preventive examination due to its high cost. The authors consider that a less specific, but more promising approach to the development of early diagnosis of PD is the search for markers in body fluids, mainly in the blood, in patients at the prodromal stage of PD. Indeed, a number of markers as changes in the level of metabolites of monoamines, sphingolipids, urates, and indicators of oxidative stress were found in patients selected for the risk group of the prodromal stage of PD, according to characteristic premotor symptoms. In addition, it is assumed that the search for blood markers at an earlier - pre-prodromal stage is possible only in animal models of PD at the early preclinical stage. This approach can also be used to verify blood markers identified in patients at the clinical stage of PD. It is also evident that the complex socio-economic factors influencing the incidence of PD is different in developed versus developing countries. The societal and medical costs of Parkinson's are huge and efforts to improve early preclinical diagnosis of PD will lead to considerable economical and societal benefits. For instance this will allow efficient selection of patients for preclinical diagnostic tests. To assess the effectiveness of this strategy considering the uncertainty of socio-economic issues, a modification of the «cost-utility¼ analysis is proposed. For the first time, a Markov model of PD including preclinical diagnostic tests and possible neuroprotective therapy was developed and studied. Analytical outcomes of this process suggest that the idea of developing a new multimodal strategy is promising from a socio-economic point of view.

[Development of early diagnosis of Parkinson's disease based on the search for biomarkers such as premotor symptoms and changes in blood]. / Razrabotka rannei diagnostiki bolezni Parkinsona na osnove biomarkerov v vide premotornykh simptomov i izmenenii v krovi.

OBJECTIVE: To determine changes in the chemical composition of blood plasma in subjects at risk of Parkinson's disease (PD) at the prodromal stage compared with age control. MATERIAL AND METHODS: Subjects at risk were selected for the presence of characteristic premotor symptoms, including impairments of sleep, olfaction and constipation.The risk group included 12 people, the control group - 8 people. RESULTS: Among seven catecholamines and their metabolites detected in the blood, only the concentration of L-dioxiphenylalanine (L-DOPA) changed (decreased) in subjects at risk compared with the control. A decrease in the concentration of L-DOPA is considered as a manifestation (marker) of selective degeneration of central and peripheral catecholaminergic neurons in PD. In contrast to L-DOPA, the concentration of seven of the twelve detected sphingomyelins in the blood of the subjects at risk increased. Given that a change in the metabolism of sphingomyelins is associated with processes such as apoptosis, autophagy, and synucleinopathy, an increase in their concentration in the blood of patients at risk is considered as a manifestation of systemic general degeneration of central and peripheral neurons. Finally, in the blood of subjects at risk, we found a trend towards a decrease in the concentration of urates, which are endogenous neuroprotectors. CONCLUSION: The changes in the level of L-DOPA, sphingmyelins and urates in the blood of subjects at risk may serve as diagnostic markers of PD at the prodromal stage.

[Differential diagnosis of neurological conditions in cardiac patients on the first day after cardiac, ascending aortic and aortic arch surgery and repair of internal carotid arteries]. / Nevrologicheskii status u patsientov v pervye sutki posle serdechno-sosudistykh operatsii.

The review is devoted to analysis of current trends in interdisciplinary approach to the differential diagnosis of patients' conditions on the first day after cardiac, ascending aortic and aortic arch surgery and repair of internal carotid arteries (neurological disorders, delirium, cognitive dysfunction, psycho-emotional disorders, postoperative sedation). This approach is valuable to determine the prognosis and timely treatment. The basic concepts reflecting the discussion between neurologists, cardiovascular surgeons, anesthetists, radiation diagnostics specialists and rehabilitators are summarized. The authors concluded that timely and correct differential diagnosis of the states on the first postoperative day using current tests and interdisciplinary approach to the treatment of patients with postoperative impaired consciousness or neurological/psycho-emotional dysfunction can improve their quality of life and efficiency of medical care.

[Creativity in patients with Parkinson's disease]. / Tvorcheskie sposobnosti u patsientov s bolezn'iu Parkinsona.

In some cases, a variety of creative abilities appear in patients with Parkinson's disease receiving dopaminergic therapy. These are the creativity of thinking, unusual motivation and efficiency, which are not inherent to the patients before. The author considers a spectrum of these changes, as well as their possible pathobiochemical and pathophysiological basis. The connection between creativity in art and impulsive-compulsive disorders is discussed. Specific personality traits, type of temperament and emotional stability can play a significant role in the development of creative abilities. It is important to recognize and control the severity of the creative potential of patients with Parkinson's disease, improving the quality of life, and to increase self-esteem, psychological attitude and social adaptation among these patients preventing the excesses of this process.

[Approaches to early diagnosis of Parkinson's disease]. / Podkhody k rannei diagnostike bolezni Parkinsona.

Parkinson's disease (PD) is characterized by a long period of 'latent' course of the neurodegenerative process. Non-motor symptoms, including behavioral dysfunction in the REM sleep phase, hyposmia, constipation, depression, may be detected in patients before the development of movement disorders. The combination of these manifestations can be used to identify the risk group for the subsequent development of PD. These patients can be further investigated using biomarkers. Dopamine receptor agonists are the first-choice drugs at the onset of disease, providing correction of not only motor, but also non-motor symptoms.

[A clinical and genetic study of impulsive-compulsive disorders in patients with Parkinson's disease]. / Kliniko-geneticheskoe issledovanie impul'sivno-kompul'sivnykh rasstroistv u bol'nykh bolezn'iu Parkinsona.

AIM: To evaluate the frequency and spectrum of impulsive-compulsive disorders (ICDs) in patients with Parkinson's disease (PD) without dopaminergic medication and among patients receiving dopaminergic replacement therapy, depending on personality type, genetic factors, and to determine the influence of ICDs on the development of other non-motor manifestations of the disease. MATERIAL AND METHODS: Three hundred and eighty-six consecutive patients with idiopathic PD, including untreated patients with PD (de novo) and patients receiving dopaminergic replacement therapy during one year, were examined. ICDs were evaluated with QUIP and diagnostic criteria. Personality type and temperament features were assessed by the Eysenck personality inventory. Genotyping for the single nucleotide polymorphism rs141116007 in the DBH gene involved in the pathogenesis of PD and ICDs was performed. RESULTS AND CONCLUSION: ICDs were identified in 20.2% patients with PD and in 4% patients of the de novo group. The most common (10.36%) behavioral disorder was a binge eating. The frequency of ICDs among patients with PD before the onset of dopamine replacement therapy increased by 1.03 times after one year treatment. Smoking and young age were risk factors for ICDs (p<0.05). The results of the study allowed the determination of social and neuropsychological risk factors for ICDs in patients with PD. The account of these features, as well as early detection of ICDs using screening questionnaires may help to personalize treatment of patients with PD and to prevent the risk of developing comorbid non-motor manifestations of the disease.

[Comorbid states in Parkinson's disease: an effect of MAO-B inhibitors].

The comorbidity in Parkinson's disease (PD), which is closely related to the tolerability of antiparkinsonian drugs, is-'analyzed. The authors present the results of the studies that have confirmed the greater safety of rasagiline compared to dopamine receptor agonists in elderly patients. The effects of rasagiline, including combinations of this drug with antidepressants, on-depression in PD and the low risk,of the serotonin -syndrome caused by these combinations are considered. The studies demonstrated the effect of rasagiline on fatigue and cognitive functions in PD patients are described. Single cases of the development of impulsive compulsive disorders:in patients treated with- rasagiline are presented.