Value of determining the cerebrospinal fluid protein markers of amyloidosis and neurodegeneration in the diagnosis of vascular and neurodegenerative cognitive impairments

The article presents data on different forms of moderate cognitive impairments (MCI) and the specific features of their transformation to dementia. Cerebrospinal fluid (CSF) was investigated in 60 patients with the amnestic and neurodynamic types of MCI, in 15 patients with vascular dementia (VD), 50 patients with Alzheimer’s disease (AD), and 23 patients with mixed vascular and neurodegenerative dementia (MVND). The specific features of β-amyloid and τ-protein concentrations were established in the preclinical stages of dementia, which reflects the main components of the pathogenesis of neurodegeneration. In the amnestic form of MCI and AD, there was drastically decreased Aβ-42 and increased τ-protein levels in SCF. As cognitive impairments progressed, there was a rise in the concentration of τ-protein; its level correlated with the severity of dementia. In MND, the level of Aβ-42 was significantly reduced while the concentration of τ-protein was much increased; moreover, to a greater extent than in AD and VD. Cerebrovascular damage and neurodegeneration were related to each other and mutually worsened clinical and pathogenic effects

Opportunities in multimodal neuroimaging for optimizing thrombolytic therapy for ischemic stroke

The main purpose of examination of patients before thrombolytic therapy for ischemic stroke (IS) is to timely identify contraindications to the use of recombinant tissue plasminogen activator.Objective: to estimate opportunities and benefits in applying multimodal magnetic resonance imaging (MRI) to improve clinical outcomes in acute stroke, among other processes, by enhancing the efficiency and safety of thrombolytic therapy.Patients and methods. The clinical experience of the S.M. Kirov Military Medical Academy in using multimodal MRI of the brain since 2004 was analyzed in patients with stroke.Results. Comprehensive assessment of the results of perfusion-weighted MRI of the brain and those of transcranial Doppler ultrasound identified five clinically significant variants of perfusion changes in IS: normal perfusion; postischemic hyperemia; persistent hypoperfusion; acute pathological hyperperfusion, and unrecovered perfusion. With an irreversible tissue damage volume of >60 cm3 on day 1 of stroke, as evidenced by diffusion-weighted MRI, the odd ratio for cerebral edema in the acutest period of the disease is 39.4% (95% CI 2.57–2436; p<0.05). The risk of hemorrhagic transformation increases with a measured diffusion coefficient in the area of the nucleus of developing nonlacunar infarct <35×10-5 mm2/sec within the first 24 hours after disease onset (p<0.005).Conclusion. The data of local clinical practice and the results of international clinical trials show that multimodal MRI of the brain is a reliable tool for the detailed evaluation of the expected efficiency and safety of thrombolytic therapy for IS. When persistent hypoperfusion is detected, the determination of perfusion-diffusion mismatch is of no informative value in deciding on whether thrombolytic therapy can be performed. Estimating the volume of pathological changes on diffusion-weighted images and the measured diffusion coefficient in the area of the nucleus of developing nonlacunar infarct in the measured diffusion coefficient maps allows the risk of major intracranial complications due to IS to be identified

Signs and Symptoms of Central Nervous System Involvement and Their Pathogenesis in COVID-19 According to The Clinical Data (Review)

Detailed clinical assessment of the central nervous system involvement in SARS-CoV-2 infection is relevant due to the low specificity of neurological manifestations, the complexity of evaluation of patient complaints, reduced awareness of the existing spectrum of neurological manifestations of COVID-19, as well as low yield of the neurological imaging.The aim. To reveal the patterns of central nervous system involvement in COVID-19 and its pathogenesis based on clinical data.Among more than 200 primary literature sources from various databases (Scopus, Web of Science, RSCI, etc.), 80 sources were selected for evaluation, of them 72 were published in the recent years (2016-2020). The criteria for exclusion of sources were low relevance and outdated information.The clinical manifestations of central nervous system involvement in COVID-19 include smell (5-98% of cases) and taste disorders (6-89%), dysphonia (28%), dysphagia (19%), consciousness disorders (3-53%), headache (0-70%), dizziness (0-20%), and, in less than 3% of cases, visual impairment, hearing impairment, ataxia, seizures, stroke. Analysis of the literature data revealed the following significant mechanisms of the effects of highly contagious coronaviruses (including SARS-CoV-2) on the central nervous system: neurodegeneration (including cytokine- induced); cerebral thrombosis and thromboembolism; damage to the neurovascular unit; immune-mediated damage of nervous tissue, resulting in infection and allergy-induced demyelination.The neurological signs and symptoms seen in COVID-19 such as headache, dizziness, impaired smell and taste, altered level of consciousness, bulbar disorders (dysphagia, dysphonia) have been examined. Accordingly, we discussed the possible routes of SARS-CoV-2 entry into the central nervous system and the mechanisms of nervous tissue damage.Based on the literature analysis, a high frequency and variability of central nervous system manifestations of COVID-19 were revealed, and an important role of vascular brain damage and neurodegeneration in the pathogenesis of COVID-19 was highlighted

Особенности симптоматики и патогенеза повреждения центральной нервной системы при COVID-19 по данным клинических исследований (обзор)

Detailed clinical assessment of the central nervous system involvement in SARS-CoV-2 infection is relevant due to the low specificity of neurological manifestations, the complexity of evaluation of patient complaints, reduced awareness of the existing spectrum of neurological manifestations of COVID-19, as well as low yield of the neurological imaging.The aim. To reveal the patterns of central nervous system involvement in COVID-19 and its pathogenesis based on clinical data.Among more than 200 primary literature sources from various databases (Scopus, Web of Science, RSCI, etc.), 80 sources were selected for evaluation, of them 72 were published in the recent years (2016-2020). The criteria for exclusion of sources were low relevance and outdated information.The clinical manifestations of central nervous system involvement in COVID-19 include smell (5-98% of cases) and taste disorders (6-89%), dysphonia (28%), dysphagia (19%), consciousness disorders (3-53%), headache (0-70%), dizziness (0-20%), and, in less than 3% of cases, visual impairment, hearing impairment, ataxia, seizures, stroke. Analysis of the literature data revealed the following significant mechanisms of the effects of highly contagious coronaviruses (including SARS-CoV-2) on the central nervous system: neurodegeneration (including cytokine- induced); cerebral thrombosis and thromboembolism; damage to the neurovascular unit; immune-mediated damage of nervous tissue, resulting in infection and allergy-induced demyelination.The neurological signs and symptoms seen in COVID-19 such as headache, dizziness, impaired smell and taste, altered level of consciousness, bulbar disorders (dysphagia, dysphonia) have been examined. Accordingly, we discussed the possible routes of SARS-CoV-2 entry into the central nervous system and the mechanisms of nervous tissue damage.Based on the literature analysis, a high frequency and variability of central nervous system manifestations of COVID-19 were revealed, and an important role of vascular brain damage and neurodegeneration in the pathogenesis of COVID-19 was highlighted.Актуальность пристальной клинической оценки поражения центральной нервной системы вирусом SARS-CoV-2 определяется низкой специфичностью ряда неврологических симптомов, сложностью объективизации жалоб пациента, неоднородной осведомленностью и настороженностью по поводу имеющегося спектра неврологических симптомов COVID-19, низкой частотой патологических изменений по данным нейровизуализации.Цель обзора. Выявление особенностей симптоматики и патогенеза поражения центральной нервной системы при COVID-19 на основе анализа данных клинической практики.Из более 200 первично отобранных источников литературы различных баз данных (Scopus, Web of science, РИНЦ и др.) для анализа выбрали 80 источников, из них — 72 источника, опубликованных в течение последних лет (2016-2020 гг.). Критерием исключения источников служили малая информативность и устаревшие данные.Клиническая картина поражения центральной нервной системы при COVID-19 включает в себя: нарушение обоняния (5-98% случаев), нарушение вкусовой чувствительности (6-89%), дисфонию (28%), дисфагию (19%), количественные и качественные нарушения сознания (3-53%), головную боль (0-70%), головокружение (0-20%), менее 3% случаев — нарушение зрения, слуха, атаксию, судорожный приступ, инсульт. Анализ данных литературы позволил выделить следующие значимые механизмы воздействия высококонтагиозных коронавирусов (в том числе вируса SARS-CoV-2) на центральную нервную систему: нейродегенерация (в том числе цитокининдуцированная); церебральный тромбоз и церебральная тромбоэмболия; повреждение нейрососудистой единицы; иммуноопосредованное поражение нервной ткани, приводящее к развитию инфекционно-аллергического демие-линизирующего процесса.Рассмотрели симптомы поражения нервной системы при COVID-19, такие как головная боль, головокружение, нарушение обоняния и вкусовых ощущений, изменение уровня сознания, бульбарные нарушения (дисфагия, дисфония). Соответственно, проанализировали данные о возможных путях проникновения SARS-CoV-2 в центральную нервную систему и механизмы поражения нервной ткани.По результатам проведенного анализа отечественной и зарубежной литературы показали высокую частоту и полиморфность симптомов поражения центральной нервной системы, а также важную роль сосудистого поражения головного мозга и нейродегенерации в патогенезе COVID-19

Levodopa-carbidopa intestinal gel in the treatment of patients with parkinson disease: Results of a 12-month open study

© 2017, Media Sphera. All rights reserved.Objective: To evaluate the long-term safety and efficacy of intrajejunal levodopa-carbidopa intestinal gel (LCIG) infusion in the treatment of patients with severe stages of Parkinson disease (PD) who did not respond adequately to treatment with oral drugs. Material and methods: A large-scale international prospective open-label 54-week study of LCIG in patients with PD with severe motor fluctuations was carried out. A total of 48 patients were enrolled in Russia, 46 patients (95.8%) had PEG-J inserted, and 43 of them completed the study. The safety, including adverse events (AEs), infusion system and pump failures analysis, number of patients completely terminated the study, and efficacy (duration of “off” periods, “on” periods with or without troublesome dyskinesias, UPDRS scores, Clinical Global Impression, Quality of Life (PDQ-39, EQ-5D и EQ-VAS) dynamics, an analysis of patient’s diaries) were assessed throughout the whole study. Results: The majority of AEs were mild or moderate with most AEs connected with infusion system application (28.3% patients) including procedure pain. Serious AEs were registered in 8 patients (16.7%). 3 patients (6.3%) discontinued their participation in the study due to AEs. Mean duration of “off” periods by the end of the study decreased by 5.35±2.59 hours (p<0.001), duration of “on” periods without troublesome dyskinesia increased by 5.74±3.91 hours (p<0.001), reduction of “on” periods duration with troublesome dyskinesia became statistically significant by week 36 (p=0.020). The statistically significant improvement of UPDRS (generally and in respect to sub-scales), Clinical Global Impression, and Quality of Life scores was observed throughout the study. Levodopa dose remained stable throughout the 54 treatment weeks. Forty-three patients (93.5%) received LCIG monotherapy throughout the whole study. Conclusion: LCIG intrajejunal infusion during 54 weeks showed the favorable safety profile, high tolerability, and efficacy in PD motor symptoms correction

Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis

Supported by F. Hoffmann–La Roche

Abstract

This paper describes the design and implementation of virtual memory in the Rialto kernel. The Rialto VM system supports sparse virtual address spaces with mapping between address spaces, copy-on-write faults, and auto-commit (demand-allocation) faults. It does not currently support demand page-in, pageout, or external pagers. Novel aspects of the design include a VTLB architecture that bounds the memory consumed in machine-dependent mapping structures, real-time requirements for preemptibility and interruptibility, provision for efficient sharing between user address spaces and the kernel via a user/kernel address bias, and growable kernel-mode thread stacks. The Rialto kernel is a light-weight, “soft ” real-time kernel. It has been successfully deployed as part of Microsoft’s MiTV/OS for the set-top boxes in the Microsoft/NTT interactive TV trial in Yokosuka, Japan. 1

The Rialto Virtual Memory System

This paper describes the design and implementation of virtual memory in the Rialto kernel. The Rialto VM system supports sparse virtual address spaces with mapping between address spaces, copy-on-write faults, and auto-commit (demand-allocation) faults. It does not currently support demand page-in, pageout, or external pagers. Novel aspects of the design include a VTLB architecture that bounds the memory consumed in machine-dependent mapping structures, real-time requirements for preemptibility and interruptibility, provision for efficient sharing between user address spaces and the kernel via a user/kernel address bias, and growable kernel-mode thread stacks. The Rialto kernel is a light-weight, &quot;soft&quot; real-time kernel. It has been successfully deployed as part of Microsoft&apos;s MiTV/OS for the set-top boxes in the Microsoft/NTT interactive TV trial in Yokosuka, Japan. 1. Introduction Rialto is a light-weight, soft real-time kernel that supports virtual memory, designed primarily for u..

Capacities for the drug correction of functional disorders in posthypoxic encephalopathy

Отражены данные литературы о патогенезе постгипоксической энцефалопатии (ПЭ), каскаде патобиохимических реакций, развивающихся в головном мозге при ишемии/гипоксии. Особое внимание уделено возникновению синаптической дисфункции в условиях энергетического дефицита и дестабилизации мембран нервных клеток. Представлены сведения об основных клинических синдромах, алгоритме диагностики, принципах лечения ПЭ. Обсуждается применение актовегина в комплексной терапии ПЭ