Vol 16, No 3 (2022)

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Original articles

Risk factors for falls in different age groups of patients with chronic cerebral ischaemia

Geraskina L.A., Galaeva A.A., Sheikhova R.D., Fonyakin A.V., Maksimova M.Y.


Introduction. Cognitive impairment, gait and balance disorders are the most important risk factors for falls in older persons. These neurological impairments are the main clinical manifestations of chronic cerebral ischaemia (CCI), and can develop at a younger age.

Aim: to evaluate the risk factors for falls in patients with CCI in different age groups and to identify the most significant predictors of falls.

Materials and methods. We examined 104 patients with CCI. Patients were divided into three age groups: middle age (40–59 years old; n = 13), older age (60–74 years old; n = 62), and the elderly (75 years and older; n = 29). We assessed the frequency of falls and the presence of risk factors.

Results. Thirty-seven (36%) patients had a history of falls, with its incidence increasing from 8% in the middle-aged group to 37% in the older persons and 45% in the elderly. Some patients had multiple risk factors for falls, while the presence of 5 risk factors increased the risk of falling fourfold. The most common factors in middle age were pain due to degenerative spine conditions (85%), anxiety (54%), and visual impairment (31%); in older age – back pain (77%), cognitive impairment (45%), visual impairment (39%), and decreased walking speed (23%); in the elderly — visual impairment (76%), cognitive impairment (69%), back pain (69%), decreased walking speed (38%), and orthostatic hypotension (28%). Discriminant analysis revealed that the best predictors of falls in CCI were female sex, age over 69 years, depression, cognitive impairment, and a walking speed below 1 m/sec.

Conclusion. Falls were observed in all age groups of people with CCI. Not only the presence of a specific risk factor for falls, but the presence of multiple risk factors, has predictive value. The presence of five or more risk factors, as well as a walking speed below 1 m/sec, can indicate a high risk of falls.

Annals of Clinical and Experimental Neurology. 2022;16(3):5-14
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Inflammation and endothelial toxicity: pathogenetic aspects of central nervous system damage due to novel coronavirus disease

Prokhorova M.V., Yakovlev A.I., Voznyuk I.A., Morozova E.M., Gogoleva E.A., Pivovarova L.P.


Introduction. There are inconsistent data on the incidence of stroke in patients with COVID-19, including acute cerebrovascular accidents in younger people without obligate risk factors, as well as the risk of SARS-CoV-2 infection in patients with acute stroke.

The aim of the study was to evaluate the features of concomitant stroke and COVID-19, and the role of inflammation and endothelial toxicity in cerebral damage.

Materials and methods. The study included 1,524 patients admitted to vascular clinics across St. Petersburg in 2020–2021, including 1,068 people with confirmed COVID-19 infection and 551 death cases. The patients were divided into four groups depending on disease severity, for clinical and laboratory data analysis.

Results. There were marked changes in the laboratory markers of inflammation, haemostasis, fibrinolysis, cytolysis, iron metabolism, cerebral ischaemia, proteolysis, immunodeficiency (lymphocytopenia, monocytopenia, elevated white blood cell count, elevated levels of C-reactive protein, fibrinogen, D-dimer, creatine kinase, ferritin and neutrophil elastase), with statistically significant differences when compared with patients without COVID-19. Changes in inflammatory markers in the first 24–72 hours provided the most information. A multifold increase (escalation) in the marker values was always correlated with an imminent adverse outcome and was usually accompanied by subsequent laboratory confirmation of COVID-19 infection or specific signs of viral pneumonia.

Conclusion. COVID-19 should be considered an independent risk factor for acute stroke, while the virus-induced thrombosis, manifesting in an escalation in inflammatory factors and products of endothelial damage, should be considered a pathogenetic link leading to cerebral tissue damage.

Annals of Clinical and Experimental Neurology. 2022;16(3):15-24
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Differential diagnosis of stroke and vestibular neuritis in emergency neurology

Monak A.A., Kulesh A.A., Parfenov V.A., Astanin P.A.


Introduction. The differential diagnosis of vertebrobasilar stroke (VBS) and vestibular neuritis (VN) is important challenge for a neurologist when a patient presents to the emergency department with acute vertigo. Current approaches and algorithms of management need to be modified, taking into account clinical practice.

The aim of the study was to identify the clinical features of acute vestibular syndrome that are the most helpful in the differential diagnosis of VBS and VN.

Materials and methods. We examined 80 emergency admissions to the neurological ward with suspected stroke. A detailed otoneurological examination (including the STANDING and HINTS+ algorithms) and brain imaging (DWI MRI) were performed.

Results. Out of 80 patients, 26 were diagnosed with VBS, 30 with VN, 11 with vestibular migraine and 2 with Meniere's disease, while the cause of vertigo could not be determined in 11 patients. The most powerful indicator of VBS in the differential diagnosis was gaze-evoked nystagmus, which had a 15.9-fold association with VBS. An increased likelihood of VBS was also associated with unsteadiness (6.3 times), age over 58 years (4.1 times), dysmetria in the finger-to-nose test (3.7 times), adiadochokinesia (3.1 times), and trunk ataxia (3 times). An increased likelihood of VN was associated with a positive unilateral head impulse test (6 times), nystagmus that followed Alexander's law (3.7 times), and presence of nausea (2.5 times). A model was developed for the differential diagnosis of VBS and VNin patients presenting with acute vertigo. The model accuracy was 100% in the validation sample.

Conclusions. Clinical approach remains crucial when differentiating between VBS and VN. The most useful criteria for a differential diagnosis in emergency neurology were the patient's age, the type of nystagmus, head impulse test, and cerebellar dysfunction.

Annals of Clinical and Experimental Neurology. 2022;16(3):25-33
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Effects of tumor necrosis factor α on the structure of brain networks and cognitive functions in patients with chronic cerebral ischemia

Fokin V.F., Shabalina А.A., Ponomareva N.V., Konovalov R.N., Medvedev R.B., Lagoda O.V., Krotenkova M.V., Tanashyan M.M.


Introduction. The processes of cognitive decline, which are typical for elderly and senile people, as well as for patients with chronic cerebral circulation insufficiency, involve pro-inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin-6, etc.

The aim of this work was to study the association of TNF-α with brain network structure and cognitive functions in patients with chronic cerebral ischemia (CCI).

Materials and methods. We examined 101 patients with CCI (50–85 years old, men and women) who were assessed for the saliva levels of TNF-α during cognitive testing. The status of resting-state networks was analyzed in 55 patients using functional magnetic resonance therapy.

Results. After cognitive tasks, the saliva level of TNF-α increased by 17.6 ± 6.2 pg/mL. Half of the CCI patients older than 60 years showed a significant increase in the level of TNF-α. This cytokine correlated with delayed word recall and the ratio of delayed recall to their performance on the Luria Memory Words Test. The change in TNF-α saliva levels correlated with the status of the resting-state network, mainly with the salience network. An increase in TNF-α levels was associated with a higher frequency of negative correlations than at lower values of TNF-α (less than 80 pg/mL). TNF-α-sensitive connectivities correlated with cognitive tasks, not only memory tests, but also with the Montreal Cognitive Assessment Scale, verbal fluency test scores, etc.

Discussion. The study revealed two significant facts: an increase in the TNF-α saliva level during cognitive performance and a lower success rate of cognitive performance associated with an increase in the levels of this cytokine. The central mechanism for the implementation of this relationship includes the restructuring of the salience network, namely the additional increase of negative correlations within the connective structure of the salience neural network of the right hemisphere.

Conclusions. A change in the saliva level of TNF-α affects the connectivity of resting-state networks, mainly the salience network

Annals of Clinical and Experimental Neurology. 2022;16(3):34-40
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The myoprotective effect of non-quantal acetylcholine: in vitro model of the myopathy component of chronic inflammatory demyelinating polyneuropathy

Gavrichenko A.V., Pasatetckaia N.A., Sokolova M.G., Lopatina E.V.


Introduction. Chronic inflammatory demyelinating polyneuropathy (CIDP) is one of the most common primary polyneuropathies. A degenerative process is the underlying cause of muscular atrophy in CIDP, while muscle strength may not fully recover in patients after pathogenesis-based treatment, thus extending the period of disability. Information about factors affecting the trophic function of muscles can be used to treat neuromuscular disorders.

Study aim — to examine the trophotropic properties of the study participants' blood plasma and the myoprotective effect of acetylcholine concentration equivalent to non-quantal release, using an in vitro model of the myopathy component of CIDP.

Materials and methods. The study included 25 patients diagnosed with typical CIDP in accordance with the EFNS/PNS 2010 criteria. The control group consisted of 25 healthy individuals. Serum antibody levels to the nicotinic acetylcholine receptor were measured in all study participants. A method for organotypic cultivation of skeletal muscle tissue and an in vitro model of the myopathy component of CIPD were developed. The effect of the study participants' blood plasma on the growth of skeletal muscle explants in organotypic culture was assessed.

Results. Patients with CIPD were found to have symmetrical sensorimotor polyneuropathy of varying severity (100%); muscle atrophy (88%), and sensory ataxia (84%). The median INCAT Overall Disability Sum Score was 2 [1; 3] for the arms and 3 [2; 5] for the legs. The median Neurological Impairment Scale (NIS) score was 17 [10; 34]. The nicotinic acetylcholine receptor antibody levels were higher in patients with CIDP (0.47 [0.31; 0.54] nmol/l) than in the control group (0.02 [0.01; 0.03] nmol/l). For the first time, a myotoxic effect of the blood plasma from patients with CIDP was observed in organotypic skeletal muscle culture. Using 1:70 and 1:100 dilutions, patient blood plasma inhibited the growth of explants by 27% (n = 120; p < 0.001) and 21% (n = 120; p < 0.001), respectively. This myotoxic effect removed acetylcholine at a concentration equivalent to non-quantal release (10–8 М).

Conclusion. These results expand our understanding of skeletal muscle damage in CIPD and the role of non-quantal acetylcholine in regulating skeletal muscle growth.

Annals of Clinical and Experimental Neurology. 2022;16(3):41-46
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A method of inhibiting the ABCB1 protein in the blood-brain barrier in vivo

Chernykh I.V., Shchulkin A.V., Mylnikov P.Y., Kirichenko E.E., Gatsanoga M.V., Yakusheva E.N.


Introduction. Increased functional activity of the P-glycoprotein transporter (ABCB1) in the blood-brain barrier (BBB) is a possible reason why neuroprotective pharmacotherapy is ineffective after ischaemic stroke.

Study aim — to develop a way to inhibit the functional activity of ABCB1 at the BBB.

Materials and methods. The study was performed on 60 male Wistar rats weighing 200-280 g. The functional activity of ABCB1 at the BBB was assessed by measuring the plasma and cortical levels of the marker transporter substrate fexofenadine (intravenous administration of 10 mg/kg). Thirty minutes before the administration of fexofenadine, 1 ml/kg of intravenous saline (n = 30) or 17.6 mg/kg of omeprazole, the transporter's systemic inhibitor (n = 30), was administered to the rats. The total amount of fexofenadine in the systemic circulation and the cerebral cortex was assessed using high performance liquid chromatography, by calculating the area under the blood concentration–time curve (AUC0-t(plasma)) or the cerebral cortex concentration (AUC0-t(brain)). BBB permeability was calculated using the ratio AUC0-t(brain)/AUC0-t(plasma).

Results. The administration of omeprazole before fexofenadine did not affect the plasma level of the latter at any time point under analysis. Fexofenadine’s AUC0-t(plasma) also did not differ between the series. However, the administration of omeprazole increased the cortical level of fexofenadine by 2.96 times (p = 0.009), 5 minutes after administration of the latter, and increased the AUC0-t(brain) by 1.49 times (p = 0.012). AUC0-t(brain)/AUC0-t(plasma) increased by 1.71 times when omeprazole was used (p = 0.003). Therefore, omeprazole inhibits the functional activity of ABCB1 at the BBB.

Conclusions. We developed and tested a method for inhibiting ABCB1 activity at the BBB.

Annals of Clinical and Experimental Neurology. 2022;16(3):47-52
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High-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation in multiple sclerosis: approaches to risk management

Polushin A.Y., Zalyalov Y.R., Totolyan N.A., Kulagin A.D., Skoromets A.A.


Introduction. High-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation (HDIT/AHSCT) is a promising and effective method for treating immune disorders, including multiple sclerosis (MS). The frequency and severity of adverse effects from therapy have decreased significantly over the last 20 years due to a reduction in conditioning regimen intensity, changes in patient selection, and the accumulated experience of the transplantation centres.

Study aim: to analyse the published data on HDIT/AHSCT complications in MS and ways to reduce their risk.

Materials and methods. We analysed and summarized the research findings regarding conditioning regimen protocols for HDIT/AHSCT, early and late complications, and risk factors associated with treatment recipients.

Results. HDIT/AHSCT may have a wide range of serious complications. However, the shift to less intense conditioning regimens and stricter patient selection criteria have minimized adverse events. The latest moderate-intensity protocols may be less effective than high-intensity protocols, but their timely use may provide the maximum benefit to people with MS refractory to standard treatment. HDIT/AHSCT cannot be the method of choice for all categories of patients with MS, because expectations may not be met due to the significant risk of complications, in particular, in cases of long-term disease, significant neurological deficit, and no disease activity. The maximum effect should be expected in early or emergency HDIT/AHSCT.

Conclusion. This information can be used to justify further expansion of the medical assistance provided to patients with MS in the Russian Federation.

Annals of Clinical and Experimental Neurology. 2022;16(3):53-64
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The cerebrovascular, neuroprotective and antiarrhythmic properties of the anxiolytic fabomotizole

Mirzoyan R.S., Balasanyan M.G., Topchyan H.V., Hakobyan V.P., Gan'shina T.S., Khaylov N.A., Kurdyumov I.N., Turilova A.I., Antipova Т.A., Kraineva V.A., Seredenin S.B.


Aim. To examine the cerebrovascular, neuroprotective and antiarrhythmic properties of fabomotizole (brand name Afobazole).

Materials and methods. A comprehensive study of fabomotizole's effects on the blood supply, morphology and neuropsychology of the rat brain in various experimental disorders. We recorded cerebral blood flow and studied brain morphology in models of local permanent and global transient ischaemia, haemorrhagic brain damage, combined cerebrovascular and cardiovascular pathology, cardiac arrhythmias, and assessed the neuropsychological status. We measured the levels of GABA, glutamic acid, nerve growth factor, and heat shock protein (HSP70).

Results. Fabomotizole improves blood supply, limits the area of injury, normalizes pathological brain changes in localized cerebral ischaemia, and eliminates neuropsychological damage in models of ischaemic and haemorrhagic stroke. The drug increases cerebral blood flow in ischaemic and haemorrhagic stroke, myocardial infarction and, to a greater extent, in combined cerebrovascular and coronary disease. Fabomotizole acts through the cerebrovascular GABAAergic system, as well as having significant antiarrhythmic properties.

Conclusions. Fabomotizole should be considered not only as an anxiolytic, but also as a drug with potential clinical efficacy in cerebrovascular disease, with concomitant coronary disease and cardiac arrhythmias.

Annals of Clinical and Experimental Neurology. 2022;16(3):65-73
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Metaplasticity and non-invasive brain stimulation: the search for new biomarkers and directions for therapeutic neuromodulation

Bakulin I.S., Poydasheva A.G., Zabirova A.H., Suponeva N.A., Piradov M.A.


Metaplasticity (plasticity of synaptic plasticity) is defined as a change in the direction or degree of synaptic plasticity in response to preceding neuronal activity. Recent advances in brain stimulation methods have enabled us to non-invasively examine cortical metaplasticity, including research in a clinical setting. According to current knowledge, non-invasive neuromodulation affects synaptic plasticity by inducing cortical processes that are similar to long-term potentiation and depression. Two stimulation blocks are usually used to assess metaplasticity — priming and testing blocks. The technology of studying metaplasticity involves assessing the influence of priming on the testing protocol effect.

Several dozen studies have examined the effects of different stimulation protocols in healthy persons. They found that priming can both enhance and weaken, or even change the direction of the testing protocol effect. The interaction between priming and testing stimulation depends on many factors: the direction of their effect, duration of the stimulation blocks, and the interval between them.

Non-invasive brain stimulation can be used to assess aberrant metaplasticity in nervous system diseases, in order to develop new biomarkers. Metaplasticity disorders are found in focal hand dystonia, migraine with aura, multiple sclerosis, chronic disorders of consciousness, and age-related cognitive changes.

The development of new, metaplasticity-based, optimized, combined stimulation protocols appears to be highly promising for use in therapeutic neuromodulation in clinical practice.

Annals of Clinical and Experimental Neurology. 2022;16(3):74-82
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Clinical analysis

Rare co-occurrence of multiple sclerosis and Parkinson's disease: a case report

Ruina E.A., Aleksandrova E.A., Parshina E.V., Rodygin D.N., Yulin V.S.


A review of Russian and foreign medical literature, as well as the Web of Science, PubMed and Scopus databases, revealed 8 cases of multiple sclerosis and Parkinson's disease co-occurrence. Parkinson's disease is a chronic, progressive neurological disease caused by degeneration of dopaminergic neurons in the substantia nigra. Multiple sclerosis is a chronic demyelinating disease, in which a range of autoimmune-driven inflammatory and neurodegenerative processes lead to formation of numerous focal and diffuse lesions in the central nervous system, resulting in disability and a significant decrease in patient quality of life. The co-occurrence of these two neurodegenerative CNS disorders is rarely seen in clinical practice.

The authors describe a clinical case to demonstrate their approach to the diagnosis and management of this patient group.

Annals of Clinical and Experimental Neurology. 2022;16(3):83-91
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Clinical features of stroke in the artery of Percheron territory (case series)

Annushkin V.A., Nikonov A.A., Maksimova M.Y., Lagoda О.V., Tanashyan M.M.


The article describes two clinical cases of stroke in the artery of Percheron territory. The difficulty in recognizing the causes of ischaemic stroke in these patients was due to the polymorphism in the mental disorders and the rare "strategic infarct dementia", as well as impaired consciousness. We hereby present the clinical features of this condition, which can be used together with neuroimaging methods (including various MRI sequences) to ensure a timely and accurate diagnosis.

The authors describe a clinical case to demonstrate their approach to the diagnosis and management of this patient group.

Annals of Clinical and Experimental Neurology. 2022;16(3):92-98
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NEUROFORUM-2022: V National Congress on Parkinson's Disease and Movement Disorders

Annals of Clinical and Experimental Neurology. 2022;16(3):99-100
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