Vol 17, No 2 (2023)

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Full Issue

Original articles

Assessment of Biomarker Profile in Patients Post Carotid Angioplasty and Stenting

Tanashyan М.М., Annushkin V.A., Raskurazhev A.A., Lagoda O.V., Shabalina А.A., Medvedev R.B., Shchipakin V.L.


Introduction. Cardiovascular diseases are predominantly caused by atherosclerosis as a multifactorial chronic condition. Alterations in the hematological system and the blood vessel wall are considered as highly significant for onset and development of cerebrovascular disorders associated with atherosclerosis. Biomarkers as measurable indicators are to verify abnormal activity.

Objective: to assess atherogenesis biomarkers in patients after carotid angioplasty and stenting (CAS) as associated with development of cerebrovascular disease.

Materials and methods. We evaluated 50 individuals (50% men, 50% women; average age 65.4 ± 6.4 years) with established cerebrovascular disease associated with brain atherosclerosis. All of them had hemodynamically significant abnormalities in the internal carotid artery (ICA) with both symptomatic (stenosis 60% and more) and asymptomatic (stenosis 70% and more) stenoses confirmed by duplex scanning of the brachiocephalic arteries. All patients underwent CAS as indicated. Before and 1 year after the intervention, we performed clinical and neurological examinations, brain magnetic resonance imaging, and laboratory tests of atherogenesis biomarkers.

Results. At baseline, all the individuals demonstrated a pro-atherogenic shift in the assessed indicators, predominantly markers of extracellular matrix degradation, inflammation and atherogenesis (including osteoprotegerin and chromogranin А). Additionally, we established a direct correlation between osteoprotegerin levels and the characteristics of mostly hyperechoic atherosclerotic plaques (r = 0.29; p < 0.05). A year later, no signs of restenosis were shown in follow-up ultrasound assessment of stented arteries in any patient.

In 1 year post CAS, we found significant changes in the levels of osteoprotegerin (decrease to 1.765 pg/mL [1.592; 1.937]; p < 0.05) and chromogranin А (elevation to 31.3 μg/L [13.9; 90.7]; p < 0.05). Re-assessment demonstrated association between changes in the pattern of the nitrogen oxide system, which tends to improve (NO elevation to 38.23 μmol/L [32.95; 43.51]; p < 0.001), and atheroprotective shift in the morphology of atherosclerotic plaques and biomarker profile.

Conclusion. Prospective, 1-year long observation for patients who underwent CAS for symptomatic/asymptomatic hemodynamically significant ICA stenoses revealed favourable atheroprotective shift in both ultrasound and hematological atherogenesis biomarker ratio. This shift contributed to the absence of cerebral atherosclerosis progression during the follow-up. The process may be mediated by chromogranin А and osteoprotegerin, and their further research is needed from perspective of atherogenesis.

Annals of Clinical and Experimental Neurology. 2023;17(2):5-15
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Predictors of In-Hospital Mortality Among Patients with COVID-19 Related Stroke

Rakhmatullin A.R., Kutlubaev M.A., Khayrullin A.T.


Introduction. COVID-19-related stroke is associated with a significantly higher mortality than COVID-19 or stroke alone. Mechanisms underlying the increased mortality of patients with stroke and COVID-19 should be thoroughly studied.

Objective: to analyze predictors of hospital mortality associated with COVID-19-related stroke.

Materials and methods. We retrospectively analyzed 1,386 cases of COVID-19-related stroke reported by an infectious diseases inpatient clinic in 2020. We studied clinical, laboratory, and instrumental parameters in patients with different outcomes. Logistic regression was used to identify independent predictors of mortality.

Results. 539 (38.9%) patients died during their hospital stay, with 437 (38.0%) deaths from ischemic stroke and 102 (42.7%) deaths from hemorrhagic stroke (p = 0.0001). Independent predictors of mortality associated with COVID-19-related stroke included age, neurological deficit severity measured by NIHSS, COVID-19 severity, and laboratory parameters including white blood cell count, creatinine, glucose, and D-dimer blood levels.

Discussion. The results of logistic regression analysis were able to explain only 41% of the variability in hospital deaths among patients with stroke associated with COVID-19.

Conclusion. Hospital mortality in patients with COVID-19-related stroke is associated with severity of inflammatory response, impaired coagulation, age, neurological deficit severity, and somatic comorbidities.

Annals of Clinical and Experimental Neurology. 2023;17(2):16-21
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The Management of High-Frequency Episodic and Chronic Migraines with Calcitonin Gene-Related Peptide Monoclonal Antibody

Dobrynina L.A., Afanasev M.A., Belopasova A.V., Gubanova M.V., Baydina E.V.


Introduction. High prevalence of migraine and its impact on quality of life requires the development of original agents. In 2020, fremanezumab, a new calcitonin gene-related peptide monoclonal antibody was authorized in Russia.

Objective: to evaluate safety and effectiveness of fremanezumab in patients with high-frequency episodic migraine (HF EM) and chronic migraine (CM).

Materials and methods. We assessed 60 patients at the age of 35.5 ± 8.96 years (85%, females) with HFEM and CM with and without aura who were either receiving preventive treatment or not. Fremanezumab was administered subcutaneously at a single dose of 675 mg. The study participants were followed-up for efficacy in 3 months. The investigators assessed change in the number of days with headache per month as well as headache intensity, its impact on the daily activities, anxiety, and depression.

Results. By the end of month 3 post dosing, the number of days with headache decreased by >50% in 76.7% of participants where 77.8% of individuals suffered from HF EM and 72.7% of individuals had CM while headache intensity decreased in all the patients equally. No response (decrease in the number of days with headache by < 30%) was reported in 15% of participants including 14.8% of individuals with HF EM and 15.2% of individuals with CM. By the end of study month 3, 81% of participants demonstrated no anxiety symptoms and 79% of participants showed no depression with significant MIDAS and HIT-6 score decline in both groups. Only 3 (5%) patients noted adverse events (redness, itching at the administration site).

Conclusion. We documented higher fremanezumab safety and effectiveness in patients with EM and CM in real-world practice as compared to fremanezumab safety and efficacy in randomized clinical trials. A single dose of fremanezumab (675 mg) resulted in effective migraine prevention, decline in comorbid anxiety and depression, and improved quality of life during 3-month follow-up.

Annals of Clinical and Experimental Neurology. 2023;17(2):22-27
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Clinical Exome Sequencing in Patients with Undifferentiated General Developmental Delay and Intellectual Disabilities

I D.V., Ioksha V.A., Proskokova T.N.


Introduction. Each fifth neurodevelopmental disorder is diagnosed in massively parallel sequencing only.

Objective: to present the experience of exome sequencing in children with undifferentiated general developmental delay and intellectual disabilities.

Materials and methods. We assessed 33 patients (19 males and 14 females) at the age of 4.5 ± 2.4 years with general developmental delay and intellectual disabilities. We studied patients' medical and family histories and their neurological statuses as well as the findings of neuropsychological testing and clinical exome sequencing.

Results.The effectiveness of clinical exome sequencing in the sample was 39.4% (MECP2, WDR45, SYNJ1, ADAR, PMM2, SHANK3, KMT5B, UBE3A, PTPN11, CTNNB1, and MTOR mutations). The pathogenic variants were significantly more prevalent in the patients with motor development delay, 53.8% of patients (P < .05). Most incident conditions included insomnias (46.2%), autism spectrum disorders (38.5%), developmental regression (38.5%), and epilepsy (38.5%). Genetic disorders were more common in the female patients .

Conclusion. With the study results, we can suppose that ca. 40% of patients with undifferentiated general developmental delay and intellectual disabilities had genetic disorders and, therefore, needed further evaluation with molecular genetic testing.

Annals of Clinical and Experimental Neurology. 2023;17(2):28-35
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Role of Inflammatory Mediators, Growth Factors, and Osteodystrophy in Recurrent Lumbar Disk Herniation

Chekhonatskiy V.A., Dreval O.N., Kuznetsov A.V., Chekhonatskiy A.A., Zakharova N.B., Grishina E.A., Gorozhanin A.V., Volna V.V.


Introduction. Reintervention in patients with spinal disk herniation is shown to significantly decrease likelihood of favorable outcomes in the postoperative period. Thus, it is important to individually assess risk factors for and likelihood of spinal disk herniation recurrence for each patient, and choose a suitable surgical option.

Objective: to evaluate changes in the levels of immunoregulatory mediators in the blood serum and extracted spinal disc tissue of allegedly healthy individuals and patients with lumbar disk herniation relapses.

Materials and methods. We examined 60 patients. The control group included 19 patients with traumatic spinal cord injuries at the lumbar level. The main group included 41 patients with spinal disk herniation. Twenty-two individuals had primary herniation while 11 patients presented with single clinical and neurological relapses at the pre-operated lumbar level and 8 patients presented with recurrent relapses. Solid-phase enzyme immunoassay detected proinflammatory cytokines (interleukin-6, tumor necrosis factor-α), chemokines (interleukin-8, monocyte chemoattractant protein-1), growth factors (vascular endothelial growth factor, transforming growth factor-β1), and osteodestruction markers (osteoprogesterin, matrix metalloproteinase-8) in the blood serum and the extracted spinal disc tissue.

Results. We found that spinal disk destruction and chronic inflammation developed with both locally and generally elevating levels of proinflammatory cytokines/chemokines, growth factors, and matrix metalloproteinase 8.

Conclusion. The results emphasize the significance of local changes in the studied parameters to choose and plan personalized surgical treatment in patients with spinal disk herniation.

Annals of Clinical and Experimental Neurology. 2023;17(2):36-42
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Morphological Changes in Neural Progenitors Derived from Human Induced Pluripotent Stem Cells and Transplanted into the Striatum of a Parkinson's Disease Rat Model

Voronkov D.N., Stavrovskaya A.V., Lebedeva O.S., Li W., Olshansky A.S., Gushchina A.S., Kapkaeva M.R., Bogomazova A.N., Lagarkova M.A., Illarioshkin S.N.


Introduction. Development of cell therapy for Parkinson's disease (PD) requires protocols based on transplantation of neurons derived from human induced pluripotent stem cells (hiPSCs) into the damaged area of the brain.

Objective: to characterize neurons transplanted into a rat brain and evaluate neural transplantation efficacy using a PD animal model.

Materials and methods. Neurons derived from hiPSCs (IPSRG4S line) were transplanted into the striatum of rats after intranigral injection of 6-hydroxydopamine (6-OHDA). Immunostaining was performed to identify expression of glial and neuronal markers in the transplanted cells within 2–24 weeks posttransplant.

Results. 4 weeks posttransplant we observed increased expression of mature neuron markers, decreased expression of neural progenitor markers, and primary pro-inflammatory response of glial cells in the graft. Differentiation and maturation of neuronal cells in the graft lasted over 3 months. At 3 and 6 months we detected 2 graft zones: one mainly contained the transplanted neurons and the other — human astrocytes. We detected human neurites in the corpus callosum and surrounding striatal tissue and large human tyrosine hydroxylase-expressing neurons in the graft.

Conclusion. With graft's morphological characteristics identified at different periods we can better understand pathophysiology and temporal patterns of new dopaminergic neurons integration and striatal reinnervation in a rat PD model in the long-term postoperative period.

Annals of Clinical and Experimental Neurology. 2023;17(2):43-50
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COVID-19 Features in Patients with Multiple Sclerosis: Main Approaches to Their Management, Treatment, and Vaccination

Malko V.A., Bisaga G.N., Topuzova M.P., Ternovykh I.K., Alekseeva T.M.


The COVID-19 pandemic calls for correct and evidence-based decisions regarding management and treatment of patients with multiple sclerosis. Information on researches, clinical cases, and recommendations for treatment of such patients during the pandemic should be classified. We report COVID-19 features in patients with multiple sclerosis, risk factors for infection and development of severe disease. We also describe management strategies for multiple sclerosis: from relapse treatment to the selection of disease-modifying therapies focusing on patient’s safety. We analyze the latest observational and comparative studies, clinical cases of multiple sclerosis patients vaccination and demyelinating disease onset after COVID-19 or vaccination.

Annals of Clinical and Experimental Neurology. 2023;17(2):51-60
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Several Risk Factors for Aneurysmal Subarachnoid Hemorrhage

Shnyakin P.G., Kazadaeva I.A.


We reviewed current literature on the role of seasonal, meteorological, or circadian factors in ruptured cerebral aneurysms. We found that cerebral aneurysm rupture most frequently occurs in winter and spring, and less frequently — in summer. The highest number of ruptured cerebral aneurysms happens in the morning, between 8 am and 12 pm. The data regarding meteorological factors' effect on the risk of cerebral aneurysm rupture are conflicting. However, it should be noted that changes in barometric pressure and falling temperature are associated with the risk of aneurysmal subarachnoid hemorrhage.

Annals of Clinical and Experimental Neurology. 2023;17(2):61-64
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B Cell Depletion Therapy as a Cutting-Edge Treatment of Demyelinating Diseases of the Central Nervous System

Simaniv T.O., Belkina A.A., Zakharova M.N.


Demyelinating diseases of the central nervous system and multiple sclerosis in particular are a pressing issue for medical community and society as a whole. Deve- lopment and implementation of highly effective specific therapy significantly slow the disease progression and help maintain patients' quality of life and social participation. We analyzed pathogenic mechanisms of multiple sclerosis and other B cell-mediated diseases and reviewed therapeutic options for main disease stages.

Annals of Clinical and Experimental Neurology. 2023;17(2):65-74
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State-of-the-Art Technologies for Studying Cellular and Molecular Mechanisms Underlying Alzheimer's Disease

Mukhamedyarov M.A., Akhmadieva L.A., Nagiev K.K., Zefirov A.L.


Alzheimer's disease (AD) is the most common neurodegenerative disease and cause of dementia. It is associated with progressive cognitive decline due to the development of cortical and hippocampal atrophy.

We reviewed key factors in AD pathogenesis, such as synaptic dysfunction, accumulation and aggregation of amyloid beta (Aβ) peptide, tau phosphorylation causing neurofibrillary tangles, mitochondrial dysfunction, and neuroinflammation. We studied the dysbiosis role in AD development and demonstrated how much the bidirectional communication between the gut and brain sheds new light on some pathogenic processes underlying AD. We reviewed state-of-the-art biomedical technologies for studying AD: transgenic models, electrophysiological techniques, optogenetics, multi-omics approaches, neuroimaging, etc. New biomedical technologies significantly expanded our current knowledge of the AD pathogenesis and laid the groundwork for state-of-the-art treatment approaches.

Annals of Clinical and Experimental Neurology. 2023;17(2):75-83
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Clinical analysis

Single-Stage Extracranial and Intracranial Stenting of the Internal Carotid Artery in a Patient with Open Circle of Willis and Associated Renovascular Hypertension

Agarkov M.V., Safuanov A.A., Evreeva S.T., Gertsog O.B., Safuanova O.S., Popov V.V., Khilchuk A.A.


We describe a case of 72-year-old patient with recurrent transient ischemic attacks in the right internal carotid artery (ICA) territory associated with uncontrolled hypertension. Duplex ultrasonography und carotid angiography showed a < 60% stenosis with signs of a vulnerable plaque in the cervical segment, as well as a < 90% stenosis in the cavernous segment of the right ICA. After further examination the patient was diagnosed with an 80% renal artery stenosis. First, the patient had a single-stage stenting for extracranial and intracranial stenoses of the right ICA, then left renal artery stenting. No intraoperative and postoperative complications were observed. These results show that this surgical treatment is minimally invasive, safe, and effective in symptomatic patients and may be considered for the disease.

Annals of Clinical and Experimental Neurology. 2023;17(2):84-91
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