Vol 12, No 4 (2018)

Introduction. Cerebral microangiopathy (CMA) is one of the leading causes of cognitive impairment (CI). Recently proposed international standards for MRI diagnosis of SVD in aging and neurodegeneration (STRIVE, 2013) are aimed at standardization of SVD research.

Objective: to clarify the severity and structure of CI and their relationships with vascular risk factors in SVD diagnosed with the STRIVE criteria.

Material and methods: Ninety-six patients with with SVD and cognitive complaints (31 men and 65 women, mean age 61.0 ± 6.6 years) were exmanied. The severity of CI was assessed with the MoCA scale: patients with MoCA<26 points who were independent in their daily life were graded as having mild CI (MCI), and those who was dependent were graded as having dementia; in patients with MoCA≥26, the assessment of separate cognitive functions (CF) was made. The type of CI was determined according to isolated or predominantly impaired CF, and in case of equal impairment of several CFs the type was cassifide as mixed. Impairment of CF was assessed by a deviation from the normal test parameters: >1.5σ, mild and >2,5σ, severe.

Results. The severity structure of CI was as follows: dementia, 15.5%, MCI, 66.7% and subjective CI, 17.7%. Neuropsychological profile of MCI included: isolated (21.3%) and predominantly (24.3%) executive dysfunction, predominantly amnestic dysfunction (28.3%), and mixed dysfunction (26.1%); in dementia we observed mixed dysfunction (80%), predominantly executive dysfunction (13.3%) and predominantly amnestic dysfunction (6.7%). A tendency to increase in the CI severity with age was revealed. Among the risk factors, only grade 3 arterial hypertension was significant for the development of dementia.

Conclusions: Dementia in SVD patients aged 46–69 is characterized by mainly mixed profile of CI and associated with grade 3 arterial hypertension. MCI is characterized by variability of the CI types and the lack of a clear link with vascular risk factors, which justifies the need for clarifying the causes and risk factors of SVD and mechanisms of the development of CI.

The paper presents preliminary results of a comparative study assessing the gut microbiota in patients with Parkinson's disease and the control group using the gas chromatography with mass spectrometric detection. Sixteen patients with stage 3 Parkinson's disease and 94 age-matched persons without Parkinson's disease were examined. It was revealed that the total number of microbial markers in parietal intestinal microbiota in patients with Parkinson's disease was increased by 43% compared with the control group. This increase is due to a 2-fold increase in the number of conditional-pathogenic flora, and at the same time there was a 2-fold decrease in the number of microbial markers of useful microflora. The obtained results may be regarded as preliminary and need to be assessed in a large cohort of patients with Parkinson’s disease. It is also necessary to assess the relationship between immune status and changes in microbiota, and to develop methods of correction of the revealed changes. Analysis of the efficiency of restoration of qualitative and quantitative composition of microbiota should be carried out using methods for the assessment of bioequivalence levodopa dose.

Introduction. Niemann–Pick type C disease (NPC) is a rare neurovisceral lysosomal storage disease with an autosomal recessie type of inheritance that develops as a result of abnormal intracellular transport of cholesterol and other lipids. The possibility of pathogenetic therapy makes it very important to screen the population and identify new cases of the disease.

Objective. Conducting biochemical and genetic screening in the group of adult patients with early-onset ataxia of unclear origin to detect new cases of NPC, with subsequent initiation of pathogenetic substrate reduction therapy and studies of clinical, genetic and biochemical characteristics the disease.

Materials and methods. Ninety-five persons (18–40 years of age), both males and females, from different regions of Russia suffering from primary ataxia of unknown origin, associated with other neurological symptoms and/or visceral and psychiatric disorders, were examined. Patients underwent neurological examination and neuropsychological testing. During biochemical screening, the concentrations of blood plasma oxysterols (cholestane-3β,5α,6β-triol and 7-ketocholesterol) and chitotriosidase were examined. The presence of pathogenic mutations in the NPC1 and NPC2 genes was detected by total sequencing of all exons of these genes.

Results. On biochemical screening, 3 patients were identified whose cholestane-3β,5α,6β-triol concentration and chitotriosidase activity were significantly higher than the reference norm, and 7-ketocholesterol concentration was either higher or at the level of the upper limit of the norm. On sequencing of the NPC1 gene, two unrelated patients (21-year-old woman and 37-year-old man) were found to carry 2 pathogenic compound heterozygous mutations each, and these findings confirm the diagnosis of NPC. The clinical picture was represented by a combination of neurological, psychiatric and visceral symptoms. In both patients, cerebellar ataxia was accompanied by dystonia and other extrapyramidal disorders, as well as vertical supranuclear gaze palsy, and bulbar and pseudobulbar symptoms. There were also affective disorders and progressive cognitive decline up to dementia of the frontal type. Both patients had ultrasound signs of isolated splenomegaly. The score for the NPC suspicion index was ≥200 points. Thus, in the studied group, NPC was detected in 2.1% of patients.

Conclusions. Biochemical screening of oxysterols and chitotriosidase of blood plasma is a quick and inexpensive method for biochemical diagnosis of NPC, the diagnostic value of which is unquestionable in the case of integrated assessment of the history of the disease, the clinical picture and the results of instrumental diagnostic exams. Adult patients with early-onset ataxia associated with visceral and psychiatric disorders are at risk group for having NPC. They should primarily be sent to screening biochemical studies, and, in case of positive results, to carry out mutation screening of NPC1 and NPC2 genes.

Introduction. Oxidative stress is an important pathogenic factor in cerebral ischemia, which occupies one of the leading places among various forms of cerebral pathology in mortality and disability of the working-age population and is recognized as an actual problem of experimental and clinical neurology. Naturally, modeling of neurodestructive processes and their correction under the action of oxidative stress in vitro contributes to the study of protective mechanisms that counteract ischemic damage of neurons.

Objective. To reveal the influence of chemical preconditioning induced by transient inhibition of Na⁺/K⁺-ATPase activity on tolerance of cultured cerebellar granule neurons to oxidative stress at different stages of their differentiation in vitro.

Materials and methods. The activity of Na⁺/K⁺-ATPase was inhibited with ouabain, which was added at 3–4 and 7–8 days in vitro to cerebellar cell cultures of 7-day rats at a concentration of 0.1 mM for 24 hours before induction of oxidative stress by hydrogen peroxide (0.05 and 0.075 mM, 4 hours) or paraquat (0.15 and 0.2 mM, 24 hours).

Results. Oxidative stress induced by paraquat causes the most pronounced death of cultured granular neurons in immature (3–4 days) cultures, in which survival was 44±2,5% of neurons, compared to mature (7–8 days) cultures, in which survival was 61±5,4%. Pretreatment of cultures with ouabain has a protective effect, the most significant in mature cultures. The exposure of mature cultures with hydrogen peroxide kills more than 90% of neurons, whereas pretreatment with ouabain increases the survival rate by 44%. At the same time in the immature cultures the damaging effects of H₂O₂ and the protective effect of ouabain is less pronounced.

Conclusion. The increased tolerance of cultured cerebellar granule cells to oxidative stress after transient inhibition of Na⁺/K⁺-ATPase activity by ouabain is shown. The direct dependence of the efficiency of the ouabain protection on the degree of neuronal morphochemical differentiation in vitro is revealed.

The review provides modern understanding of the pathogenesis of progressive multifocal leukoencephalopathy (PML), a severe and potentially fatal form of multiple-lesion disorder of the brain white matter. Information about the frequency of its development in patients with disease-modifying treatment of multiple sclerosis is analyzed. The algorithms of optimization of PML risks in this category of patients with multiple sclerosis are described in detail. Summarized are the data on most significant PML biomarkers, the search for which is currently under way in many centers across the world. The first case of PML in Russia is briefly described.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive disease characterized by relentless increase in weakness of limb and respiratory muscles. Whereas the etiology is still not clear, there have been a remarkable progress in understanding ALS pathogenesis and pathophysiology over the last years.  In 2017 the second drug that can alter ALS progression rate has been registered. Nevertheless, the prognosis remains very poor and the average life expectancy in ALS does not exceed 5 years. The most common causes of death in ALS are respiratory complications and respiratory failure. Consequently, monitoring of the respiratory system function in ALS patients by neurologists and pulmonologists is crucial for survival and prolongation of life in this condition. Currently the most available diagnostic tool for the assessment of the respiratory profile in ALS is spirometry. Other methods, such as measurement of sniff nasal pressure, overnight oximetry and polysomnography, are also important but, due to technical complexity, their use in routine practice is limited. The principal method of respiratory support used in ALS is noninvasive lung ventilation (NIV). It can increase the average life expectancy and improve the patients’ quality of life. Invasive lung ventilation with endotracheal tube is another technique that can increase life expectancy and improve quality of life. However, the number of patients accepting this type of mechanical ventilation is very low. Multidisciplinary approach involving different medical specialists including neurologists, pulmonologists and critical care physicians is the key to successive management of ALS patients with respiratory disorders.

Perivascular spaces (Virchov–Robin spaces, VRS) surround the walls of vessels along their route from the subarachnoid space through the brain parenchyma. Dilated VRS are often observed by MRI in healthy people. They can be a rare cause of neurological disorders. In the literature there are a small number of cases with VRS being a probable cause of the parkinsonian syndrome or affecting the course of Parkinson’s disease (PD). We report our observation of the PD patient with complications of antiparkinsonian therapy who underwent bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN). The localization of VRS in the STN projection probably changed the clinical course of the disease but didn`t influence the outcomes of stimutation of the “cribriform” STN.