Vol 13, No 3 (2019)

Original articles

Cluster analysis of immunological serum markers in patients with Parkinson’s disease

Klyushnik T.P., Simonov A.N., Androsova L.V., Ponomareva N.V., Illarioshkin S.N.


Introduction. The study of patients’ biological features, including their immune responses, in specific diseases, is an important step towards personalized diagnosis and treatment. Parkinson’s disease (PD) is thus of particular interest as one of the most common age-related neurodegenerative diseases.

Study aim – to determine the immunophenotypes of patients with PD using cluster analysis.

Materials and methods. Mathematical analysis was conducted on a database of 46 patients with PD. The levels of the following functionally related inflammatory markers were used as the classification characteristics: the enzymatic activity of leukocyte elastase (LE), the functional activity of α1-proteinase inhibitor (α1-PI), the auto-antibody levels to S-100b and myelin basic protein.

Results. Based on the immunological markers, the use of multiple algorithms in the cluster analysis of the PD database allowed to obtain two consistent clusters. The patients in cluster 1 were characterized by a high level of LE activity and a low level of functional α1-PI activity, which indicates insufficient serum antiproteolytic capacity and is an unfavourable prognostic indicator for further development of the inflammation-associated pathological process in the brain tissue. The patients in cluster 2 were characterized by increased functional α1-PI activity in the serum, increased S-100b antibody levels and a decreased LE activity as compared with cluster 1, which indicates dysregulation of the inflammatory response, associated with insufficient neutrophil degranulation, whereas elevated autoantibody levels to the neural antigen S100b characterize the most severe lesions in the nervous system.

Conclusion. The results of the cluster analysis enable the identification of two immunophenotypes in patients with PD, indicating that a phenotypically similar presentation can be due to a different spectrum of immune markers. The obtained data will serve as a basis for development of an immunological approach to personalized diagnosis and treatment.

Annals of Clinical and Experimental Neurology. 2019;13(3):5-10
pages 5-10 views

Gender features in cerebrovascular disorders in different age groups

Maksimova M.Y., Sazonova V.Y., Ayrapetova A.S.


Introduction. Numerous studies of ischaemic stroke pathogenesis allowed to develop the modern concept of the causes of ischaemic stroke. Risk factors are of primary importance in the development of cerebrovascular disorders (CVD).

Study aim – to examine the representation of risk factors for CVD and the causes of ischaemic stroke in the territory of the internal carotid artery, taking into account age and gender differences.

Materials and methods. We examined 331 (47.7%) men and 363 (52.3%) women aged 25–89 years with chronic CVD and ischaemic stroke in the territory of the internal carotid artery. Of the 279 patients with ischaemic stroke in the territory of the internal carotid artery, 57.7% were male and 42.3% were female. The majority of patients with ischaemic stroke were aged between 60 and 74 years, both among the men (72; 57.6%) and among the women (53; 42.4%).

Results. Men were more likely to have arterial hypertension (64.4% vs. 49.6%; p<0.001), a history of transient ischaemic attacks (16.6% vs. 8.6%; p=0.002) and ischaemic stroke (14.5% vs. 9.1%; p=0.033), coronary heart disease (post-infarction cardiosclerosis) (13.9% vs. 7.2%; p=0.004), and to smoke (42.3% vs. 20.2%; p<0.001) and to consume excess alcohol (14.8% vs. 2.5%; p<0.001) than women. Atherothrombotic stroke was more common in men than in women (38.1% versus 21.2%; p=0.003). Women were more likely than men to have a cardioembolic stroke (39.0% vs. 21.9%; p=0.002) and a stroke due to internal carotid artery dissection (6.8% vs. 1.3%; p=0.020). In the 60–74-year age group, men were more likely to have atherothrombotic stroke (49.3% vs. 22.6%; p=0.002), while women were more likely to have cardioembolic stroke (47.2% vs. 26.8%; p=0.019) or a lacunar infarct (17% vs. 4.2%; p=0.017).

Conclusion. Gender and age differences were found in the frequency of risk factors for CVD and in subtypes of ischaemic stroke. Men are more likely than women to have arterial hypertension, a history of transient ischemic attacks and stroke, coronary heart disease, and to smoke and to consume excess alcohol. Ischaemic stroke in the territory of the internal carotid artery occurs more often in older men and women. Among the ischaemic stroke subtypes in that age group, atherothrombotic stroke was more common in men, while cardioembolic and lacunar infarcts were more common in women.

Annals of Clinical and Experimental Neurology. 2019;13(3):11-19
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Analysis of factors affecting adherence to treatment in post-stroke patients

Bogolepova A.N., Kovalenko E.A.


Introduction. The effectiveness of secondary stroke prevention depends not only on the prescribed medications but also on patients’ compliance with doctors’ recommendations in general. Adherence to therapy among post-stroke patients remains insufficient. This is due to factors that negatively affect compliance with medical recommendations. Among those factors, post-stroke cognitive impairment deserves particular attention.

Study aim – to identify the main factors that determine adherence to long-term therapy in patients after stroke and to assess the impact of post-stroke cognitive impairment on compliance with medical recommendations.

Materials and methods. A total of 56 patients (mean age 64.67±10.19 years), who experienced a hemispheric ischaemic stroke 6 months ago, were examined. Cognitive function was evaluated using the Montreal Cognitive Assessment tool, the battery of tests to assess frontal dysfunction, drawing and clock copying tests, and tests of phonetic and semantic speech activity. Adherence to long-term therapy after stroke was determined using the Morisky–Green test. We also studied the role of sociodemographic and vascular risk factors, that determine treatment adherence.

Results. More than half (51.8%) of post-stroke patients did not comply with medical recommendations. The main barriers to optimal adherence were the male gender, engagement in physical labour throughout life, and the presence of left ventricular hypertrophy, chronic heart failure or bad health habits. The presence of post-stroke cognitive impairment had a negative impact on the adherence to medical recommendations (r=0.49; p<0.001). The results of the survey showed that regular visits to medical specialists were one of the main requirements for maintaining optimal adherence to treatment. Most patients (59.6%) thought that forgetfulness is a key factor affecting adherence to therapy.

Summary. Treatment adherence should be evaluated in all patients after stroke, especially in those with post-stroke cognitive impairment. The identification and correction of ‘modifiable’ risk factors is a way to increase adherence to treatment

Annals of Clinical and Experimental Neurology. 2019;13(3):20-27
pages 20-27 views

Experimental parkinsonism in modeling striatal astrocyte damage

Stavrovskaya A.V., Voronkov D.N., Ol’shansky A.S., Gushchina A.S., Yamshchikova N.G.


Introduction. Astrocyte dysfunction is typical for many CNS pathologies, yet few experimental models of selective astrocyte damage, which would enable a fuller understanding of the role of astrocytes in the pathogenesis of neurodegenerative disorders, exist.

Study aim — to characterize the morphological brain changes with the administration of α-aminoadipic acid (L-AA), a glial toxin, into the rat striatum and to assess the effect of astrocyte dysfunction on motor activity in animals.

Materials and methods. Astrocyte damage was achieved by administering L-AA (100 μg in 5 μl) into the rats’ right striatum; the same volume of phosphate-buffered saline was injected into the left hemisphere as a control. On the third day after L-AA administration, motor impairment was assessed with normal and reduced dopaminergic neurotransmission; the latter was achieved with administration of the α-methyl-p-tyrosine, a tyrosine hydroxylase inhibitor. The immunohistochemical studies included assays for glial fibrillary acidic protein (GFAP), neuronal nuclear antigen (NeuN), and tyrosine hydroxylase.

Results. When dopamine synthesis was inhibited, damage to the striatal astrocytes, which was confirmed by immunohistochemistry, caused a reduction in motor activity in the open field test and an increase in the number of errors in the beam walking test. When dopaminergic transmission was reduced through the inhibition of tyrosine hydroxylase by α-methyl-p-tyrosine, the motor disturbances caused by astrocyte damage sustained and worsened.

Conclusion. The obtained data indicate the regulatory role of astroglia in the nigrostriatal system and emphasize the possible contribution of glial dysfunction to the motor disturbances in Parkinson’s disease.

Annals of Clinical and Experimental Neurology. 2019;13(3):28-33
pages 28-33 views


The translational potential of experimental pharmacology for cerebrovascular disorders

Mirzoian R.S., Gan’shina T.S., Kim G.A., Kurza E.V., Maslennikov D.V., Kurdyumov I.N., Turilova A.I., Gorbunov A.A.


The efficacy of reperfusion therapy to restore cerebral blood supply in patients with ischaemic cerebrovascular disorders is well recognized. Medications with proven cerebrovascular activity, such as oxymethylethylpyridine succinate (Mexidol), nicotinoyl-gamma-aminobutyric acid (Picamilon), and nimodipine, are successfully used in neurological practice with the first two having antiplatelet activity. This review analyses the vascular and antiplatelet effects of those medications, their effect on cerebral blood circulation, blood pressure and the central nervous system, and their neuroprotective activity. Potential compounds are also reviewed: S-amlodipine nicotinate and succinic acid ester of 5-hydroxyadamantan-2-one, which have significant cerebrovascular anti-ischaemic activity but a diametrically opposite effect on blood pressure. S-amlodipine nicotinate lowers blood pressure, while the succinic acid ester of 5-hydroxyadamantan-2-one elevates it. A GABA-positive component is present in the mechanism of action of all the studied drugs except for nimodipine. Experimental data on the effect of substances on cerebral circulation, blood pressure and platelet aggregation, as well as the interaction with GABAA receptors, significantly increase the translational potential of cerebrovascular medications.

Annals of Clinical and Experimental Neurology. 2019;13(3):34-40
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The role of micro-RNA in cerebrovascular disease

Raskurazhev A.A., Tanashyan M.M.


The article touches upon micro-RNA as new, potentially significant diagnostic, prognostic and therapeutic biomarkers in cerebrovascular pathology. Synthesis processes and effector mechanisms of micro-RNA are described. The micro-RNA that play an important role in the pathogenesis of major risk factors for cerebrovascular pathology (atherosclerosis, arterial hypertension, atrial fibrillation, diabetes mellitus) and the micro-RNA in acute cerebrovascular disorders are reviewed in detail. The need for thorough replication studies to justify the choice of micro-RNA and methods for micro-RNA detection is substantiated.

Annals of Clinical and Experimental Neurology. 2019;13(3):41-46
pages 41-46 views


Full Outline of UnResponsiveness (FOUR) scale: translation and linguistic and cultural adaptation of the Russian language version

Piradov M.A., Suponeva N.A., Ryabinkina Y.V., Sergeev D.V., Legostayeva L.A., Yazeva E.G., Yusupova D.G., Luneva I.E., Domashenko M.A., Samorukov V.Y., Zaytsev A.B., Zimin A.A., Polekhina N.V., Bundhun P., Ramchandani N.M., Ilyina K.A.


Introduction. The assessment of the level of consciousness in patients with acute brain injury is a mandatory first step of neurological examination. There is a need for clinical scales which allow to assess the level of wakefulness and degree of patient non-responsiveness in 2–3 minutes. The Full Outline of UnResponsiveness (FOUR) scale is an optimal tool for such clinical assessment, which focuses on eye response, motor response, brainstem reflexes, and respiratory pattern. The absence of an officially translated and validated version impedes the use of FOUR scale in Russia, while the use of non-validated clinical scales carries a risk of erroneous diagnosis and reduces the quality and information value of research studies.

Study aim: to develop an official Russian language version of the FOUR scale, taking into account its linguistic and cultural characteristics as part of the validation study.

Materials and methods. The first stage of the validation process was completed, consisting of the linguistic and cultural adaptation of the FOUR scale. Medical professionals (Russian and English native speakers) performed forward and back translations of the original scale. The developed version then underwent review by the Expert Commission, which included a linguist, neurologists, anaesthesiologists and intensive care specialists. The next step was a pilot test of the scale.

Results. The main difficulties in the translated text of the scale were solved during the first meeting of the Expert Commission. Then, taking into account the inclusion and exclusion criteria, a pilot test was performed by assessing 15 patients with the developed version of the FOUR scale. The statistics of this cohort are presented. Investigators had no difficulties in understanding and interpreting the scale instructions during the pilot test. Based on the results, the final version of the scale was adopted. The Russian version of the scale text with instructions and illustrations is presented in this paper.

Conclusion. Translation, linguistic and cultural adaptation of the FOUR scale was conducted at the Research Centre of Neurology (Moscow, Russia). For the first time, the Russian version of the scale is officially presented and recommended for widespread use in clinical and research practice in Russia and other Russianspeaking countries based on the results of pilot testing. The next publication will present the results of the evaluation of psychometric properties (reliability, sensitivity, etc.) of this version of the scale

Annals of Clinical and Experimental Neurology. 2019;13(3):47-54
pages 47-54 views

Navigated TMS mapping using the grid-based algorithm to evaluate the reorganization of cortical muscle representation in amyotrophic lateral sclerosis

Bakulin I.S., Sinitsyn D.O., Poydasheva A.G., Chernyavskiy A.Y., Suponeva N.A., Zakharova M.N., Piradov M.A.


Introduction. Motor cortex mapping using navigated transcranial magnetic stimulation (TMS) is a promising method for assessing motor cortex reorganization in amyotrophic lateral sclerosis (ALS). The use of the grid-based algorithm allows the mapping protocol to be standardized and can help to reduce the variability of the assessed parameters.

Study aim — to analyse the reorganization features of the cortical representations of hand muscles in patients with classical ALS using navigated TMS mapping with a grid-based algorithm.

Materials and methods. The study included 14 patients with classical ALS and 9 healthy volunteers. Navigated TMS mapping of the cortical representations of the right abductor pollicis brevis (APB) muscle was performed using a predetermined grid (7×7 square cells) centred around a ‘hot spot’. Five stimuli with an intensity of 110% of the individual resting motor threshold (RMT) were randomly applied to each cell. The RMT and area of cortical representation of the APB muscle were analysed, amplitude or probability weighted.

Results. Patients with ALS showed a statistically significant decrease in the weighted amplitude of the area of cortical representations of the APB muscle compared with healthy volunteers. The RMT, area and weighted probability area of the cortical representations of the APB muscle did not differ significantly between the groups. A statistically significant correlation between RMT and severity of dysfunction and upper motor neuron damage was found in patients with ALS, based on the clinical data. There were no statistically significant correlations between cortical representation parameters and the clinical symptoms in patients with ALS.

Conclusion. Navigated TMS mapping of the motor cortex with a grid-based algorithm in patients with ALS revealed a decrease in the weighted amplitude of the cortical representation area of the APB muscle. It is important to clarify the role of navigated TMS mapping with the proposed algorithm in the diagnosis, prognosis and monitoring of ALS.

Annals of Clinical and Experimental Neurology. 2019;13(3):55-62
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Clinical analysis

Cognitive behavioural therapy in the treatment of chronic daily headache

Golovacheva V.A., Parfenov V.A.


There is a high prevalence of chronic daily headache (CDH) in Russia. CDH is most often represented by chronic migraine or chronic tension headache, with an interdisciplinary approach using cognitive behavioural therapy (CBT) being effective in its treatment. Two clinical cases of CDH are presented: a female patient 38 years old with chronic migraine and a female patient 53 years old with chronic tension headache. Interdisciplinary treatment, including CBT, allowed a relatively rapid (within 3 months) and persistent (for 5 years) improvement to be achieved for both the headache and the recovery of functional activity in patients. The practical aspects of using CBT are presented. The efficacy of CBT in clinical practice and the feasibility of the widespread introduction of CBT for CDH are discussed.

Annals of Clinical and Experimental Neurology. 2019;13(3):63-70
pages 63-70 views

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