Vol 17, No 1 (2023)

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Full Issue

Original articles

Factors that pre-determine the main subtypes of ischemic stroke in middle-aged and senior women

Maximova M.Y., Sazonova V.Y.


Introduction. Brain health and active longevity are affected by a number of stroke risk factors. We should identify their relative impact on the main subtypes of ischemic stroke (IS) in middle-aged and senior women to consider prevention and management strategies.

Objective. To assess prevalence of isolated and combined factors that may contribute with a high probability to development of the various IS subtypes in women aged 45–74 years.

Materials and methods. The study included 348 female patients aged 45–74 years including 145 inpatients with carotid IS (main group) from Neurology Department 2, the Research Center of Neurology, and 203 women with cognitive disorders due to the chronic cerebral ischemia (controls). To assess the impact of various risk factors on the main IS subtypes, we generated multivariate predictive models using logistic regression and the Wald test.

Results. Predictive modeling of atherothrombotic IS demonstrated that type 2 diabetes mellitus increases IS risk by over 5 times (odds ratio [OR] = 5.961; 95% confidence interval [CI] 1.102–32.257; р = 0.038); internal carotid artery stenosis, by 7 times (OR = 7.187; 95% CI 1.827–28.273; р = 0.005); history of transient ischemic attacks (TIA), by 61 times (OR = 61.442; 95% CI 7.673–491.998; р < 0.001); excessive alcohol intake, by 49 times (OR = 49,382; 95% CI 4.557–535.121; р = 0.001); and HTN severity, by 4 times (OR = 4.445; 95% CI 2.331–8.476; р < 0.001). Predictive modeling of cardioembolic IS demonstrated that post-infarction cardiosclerosis increases IS risk by over 118 times (OR = 118.025; 95% CI 5.210–2673.796; р = 0.003), atrial fibrillation, by 108 times (OR = 108.493; 95% CI 24.312–484.159; р < 0.001), history of TIA, by over 71 times (OR = 71.558; 95% CI 7.945–644.535; р < 0.001); and HTN severity, by over 3 times (OR = 3.957; 95% CI 2.069–7.566; р < 0.001). Predictive modeling of lacunar IS demonstrated that type 2 diabetes mellitus increases IS risk by 8 times (OR = 8.324; 95% CI 1.923–36.041; р = 0.005), history of IS, by over 8 times (OR = 8.99; 95% CI 1.772–45.598; р = 0.008); and HTN severity, by 7 times (OR = 7.139; 95% CI 3.491–14.599; р < 0.001).

Conclusion. We identified a number of risk factors that may contribute to the development of the main IS subtypes in middle-aged and senior women.


Annals of Clinical and Experimental Neurology. 2023;17(1):5-13
pages 5-13 views

Examining the frequency of dysphagia and the predictive factors of dysphagia that require attention in patients with Parkinson's disease

Babajani Roshan T., Behzad C., Saadat P., Bijani A., Dehghan M., Ahmadi Ahangar A.


Introduction. Due to the prevalence of dysphagia in patients with Parkinson's disease (PD) and its complications such as aspiration pneumonia, which is the main cause of death in these patients, PD-related disability can be prevented by early diagnosis and treatment of dysphagia.

Objective. The present study was aimed at investigating the frequency of dysphagia in PD patients.

Materials and methods. This cross-sectional study included 150 PD patients visiting a Neurology Clinic. The severity of PD was determined based on the Unified Parkinson Disease Rating Scale (UPDRS) and modified Hoen and Yahr (HYS) Scale. The Munich Dysphagia Test-Parkinson's disease (MDT-PD) questionnaire was used to assess dysphagia. Comparisons were made using generalized Fisher exact, Chi-square, ANOVA, and Kruskal–Wallis tests. Predictive factors were analyzed using logistic regression. Statistical analyses were performed at significance level of 0.05.

Results. Out of all 150 patients referred to the Clinic, the prevalence of dysphagia requiring attention was 25.3% (n = 38). The patients of the three groups according to the MDT-PD (no noticeable dysphagia, noticeable oropharyngeal, and dysphagia with aspiration risk) had a significant difference only in terms of the PD duration (p < 0.001). In the predicting of dysphagia, the longer PD duration (p = 0.011) and homemaker occupation (p = 0.033) were protective factors, while female gender was a risk factor (p = 0.011).

Conclusion. The prevalence of dysphagia requiring attention in the studied patients was 25.3%. It decreased with the longer duration of the disease, and its prevalence was lower in homemaker patients, while the odds of dysphagia was 5.8 times higher in women than in men.

Annals of Clinical and Experimental Neurology. 2023;17(1):14-19
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Assessing trigeminal microstructure changes in patients with classical trigeminal neuralgia

Rozhnova E.N., Dashyan V.G., Tokarev A.S., Evdokimova O.L., Neznanova M.V., Sinkin M.V.


Introduction. The crucial role of neuro-vascular conflict (NVC) in trigeminal neuralgia (TN) is getting increasingly challenged. Microstructural changes can be assessed using fractional anisotropy (FA) in diffusion tensor images (DTI).

Objective. To evaluate usefulness of FA in brain MRI with DTI for TN lateralization assessment.

Materials and methods. The study included 51 patients with classical TN divided into two groups: neurosurgical intervention free, post radiofrequency ablation (RFA), and a control group (patients without facial pain). All the patients were tested for NVC with FIESTA (Fast Imaging Employing Steady State Acquisition) brain MRI at 3Т. Difference in thickness of trigeminal roots on the intact and symptomatic sides was assessed for each group. The findings were compared to those in the control group. The MRI protocol was supplemented with DTI. The FA difference in thickness of the intact and symptomatic roots (∆FA) was calculated for each study group to assess microstructural root changes. The results were compared to those in the control group.

Results. In trigeminal root DTIs, ∆FA over 0.075 [0.029; 0.146] is statistically significant to establish NVC-associated microstructural changes on the symptomatic side in patients without any past surgeries (p = 0,030). In patients with a history of trigeminal ganglion RFA, statistically significant (p = 0.026) thinned symptomatic trigeminal root (difference in thickness of trigeminal roots over 0.45 cm [0.4; 0.6]) was found as compared to that of the control patients.

Conclusion. ΔFA may be used as a quantitative demyelination biomarker in clinical TN. Trigeminal ganglion RFA leads to hypotrophy throughout the trigeminal nerve root.

Annals of Clinical and Experimental Neurology. 2023;17(1):20-26
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Cerebrovascular complications of hematopoetic stem cell transplantation in patients with hematologic malignancies

Polushin A.Y., Skiba I.B., Bakin E.A., Vladovskaya M.D., Yakovleva V.A., Moiseev I.S., Yanishevskiy S.N., Voznyuk I.A., Kulagin A.D.


Introduction. Modern transplantation and biological therapy methods are associated with a wide range of adverse events and complications. Incidence and variety of neurological complications mostly depend on myelo- and immunosuppression severity and duration as well as on donor's and recipient's characteristics. The most frequent complications involving the nervous system include neurotoxic reactions, infections, autoimmune and lymphoproliferative diseases, and dysmetabolic conditions as well as cerebrovascular complications that potentially affect transplantation outcomes.

Objective. To evaluate the impact of post-transplantation cerebrovascular events (CVEs) on transplantation outcomes in patients with hematologic malignancies.

Materials and methods. We analyzed 899 transplantations performed at the Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology, and Transplantation, Pavlov First Saint Petersburg State Medical University, from 2016 to 2018. We assessed transplantation parameters and donor's and recipient's characteristics by intergroup comparison, pseudo-randomization (propensity score matching), Kaplan–Meier survival analysis, and log-rank tests.

Results. Post-transplantatively, CVEs developed in 2.6% (n = 23) of cases: 13 (1.4%) ischemic strokes and 11 (1.2%) hemorrhagic strokes or intracranial hemorrhages were diagnosed. CVEs developed on days 99.5 ± 39.2 post hematopoetic stem cell transplantation (HSCT). There were more patients with non-malignant conditions in the CVE group as compared to the non-CVE group (21.7% vs 7.9%; p = 0.017). Patients with CVE had a significantly lower Karnofsky index (75.6 ± 21.3 vs 85.2 ± 14.9; p = 0.008). Statistically, we also note some non-significant trends: patients with CVE more often underwent allogenic HSCT (82.6% vs 64.0%; p = 0.077) while donors were more often partially (rather than totally) HLA compatible for recipients (39.1% vs 21.1%; p = 0.33). Patients with CVE more often had a history of venous thromboses (13.3% vs 4.2%; p = 0.077). Post-HSCT stroke decreased post-transplantation longevity by approximately 3 times (331.8 ± 81.6 vs 897.9 ± 25.4 post HSCT; p = 0.0001). In the CVE group, survival during first 180 days post HSCT (landmarks post-HSCT Day+60 and Day+180) was significantly lower as compared to that in the CVE-free group. If CVE developed during first 30 days and 100 days post HSCT, vascular catastrophe did not affect post-HSCT survival significantly.

Conclusion. Whereas ischemic stroke is a long-term HSCT complication (beyond D+100 post transplantation), hemorrhagic stroke is a short-term complication (D0–D+100 post HSCT). CVEs affect survival in patients with hematologic malignancies, especially those developed between D+60 and D+180 post HSCT. History of venous abnormalities, low Karnofsky index at HSCT initiation, and the type of allogenic HSCT, especially from half-matched donors, can be considered as negative outcome risk factors in post-HSCT CVE.

Annals of Clinical and Experimental Neurology. 2023;17(1):27-35
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Salivary gland immunohistochemistry vs substantia nigra sonography: comparative analysis of diagnostic significance

Khacheva K.K., Karabanov A.V., Bogdanov R.R., Voronkov D.N., Sobolev V.B., Chechetkin A.O., Danilova A.D., Sipkin A.M., Illarioshkin S.N.


Introduction. Parkinson's disease (PD) urges for new instrumental methods of diagnosis. Transcranial sonography of the substantia nigra (SN TCS) is an established method for early PD diagnosis but its application is limited. Recently, biopsies (primarily that of salivary gland) and test for abnormal α-synuclein are suggested to verify PD.

Materials and methods. We assessed 12 individuals with PD, Hoehn–Yahr 2.3 ± 0.4. The assessments included: UPDRS, NMSQ, NMSS, RBDSQ, PDQ-8, MoCA, and HADS scoring; SN TCS; and sublingual gland immunohistochemistry for phosphorylated α-synuclein (PS-129) with automated morphometric analysis.

Results. Substantia nigra hyperechogenicity was shown in 75% of patients whereas biopsy revealed PS-129 in 100% of patients. Echogenic area of the substantia nigra was 0.24 [0.21; 0.3] cm2. PS-129 inclusion area varied from 28.47 [27.55; 96.26] to 238.77 [234.13; 272.49] μm2, and PS-129 proportion varied from 13.4% to 93.4% of the nervous fiber area across the patients. We found relations between PS-129 and NMSQ (r = 0.8; p < 0.001), NMSS (r = 0.9; p < 0.001), PDQ-8 (r = 0.7; p = 0.003), UPDRS-I (r = 0.7; p = 0.009), UPDRS-II (r = 0.6; p = 0.03), and HADS (anxiety r = 0.8; p = 0.002; depression r = 0.6; p = 0.04) scores.

Conclusion. The results demonstrate a higher biopsy sensitivity as compared to SN TCS. Automated morphometric analysis has been newly applied to assess PS-129 occurrence. Immunohistochemistry results are directly related to non-motor symptom severity, which may indicate high probability of PS-129 presence and diagnosis confirmation in early disease.

Annals of Clinical and Experimental Neurology. 2023;17(1):36-42
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Molecular mechanisms of neuroprotective effects of thyroid hormones and their metabolites in acute brain ischemia

Filimonov D.A., Yevtushenko S.K., Fedorova A.A.


As endovascular reperfusion advances and multimodal neuroimagimg is implemented, neuroprotection in ischemic stroke progresses to the next level. In the recent years, the focus of neuroprotection research has been gradually shifting towards the research of endogenous substances and their synthetic analogs. According to the available evidence, thyroid hormones (THs) and their metabolites are potentially effective neuroprotectors in brain ischemia.

Objective. To identify and classify TH neuroprotective effects in acute brain ischemia by analyzing contemporary data.

We studied and analyzed publications indexed in РubMed, SciElo, ScienceDirect, Scopus, Biomedical Data Journal, and eLibrary.

The molecular basis of TH effects includes genomic and non-genomic mechanisms aimed at mitochondrial activity regulation, neuro- and angiogenesis, axonal transport, cytoskeleton maintenance, and impact on ion channels as well as activation and expression of specific proteins. TH effects on the central nervous system can be classified into following clusters: influence on neuronal and glial metabolism, apoptosis modulation, neuroplasticity and angiogenesis, impact on hemostasis, and local and systemic immune response.

Conclusion. THs are multimodal and selective regulators of cellular processes that affect neuroplasticity and neuro-reintegration both in the brain ischemic zone and beyond it. Therefore, a promising research can cover THs and and their metabolites as cerebral cytoprotectors to improve functional outcomes of ischemic strokes.

Annals of Clinical and Experimental Neurology. 2023;17(1):43-54
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Neuroinflammation as secondary damage in head injury

Karchevskaya A.E., Payushina O.V., Sharova E.V., Oknina L.B., Titov O.Y.


Head injury is one of the main disability causes among the working-age population. Stroke energy induces mechanical injury of tissues to launch secondary damage, i.e. neurotransmission, blood-brain barrier disruption, blood infiltration of brain tissues, cytokine and chemokine overexpression, and other processes. Activated by the injury, microglia plays a special part to initially 'protect' intact tissues from the products of necrosis and apoptosis. After the injury, microglia rapidly differentiates to phenotypes М1 and М2. Pro-inflammatory phenotype М1 produces neuronal cytotoxic cytokines including tumor necrosis factor-α, interleukins (IL)-6 and IL-1β, and NO that induce apoptosis while phenotype М2 secretes IL-4 and IL-13 that may supposedly reduce inflammation and improve recovery of brain tissues. М2 response lasts much less than М1 response, and increasing pro-inflammatory activation leads to further neuronal death, which affects cognitive and physical status of patients with head injury. The review covers main biochemical processes in the injured brain and possible ways of neuroinflammation modulation.

Annals of Clinical and Experimental Neurology. 2023;17(1):55-68
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MicroRNA detection in carotid atherosclerosis: prospects for clinical use

Tanashyan М.М., Rakurazhev A.A., Kuznetsova P.I., Mazur A.S., Shabalina А.A.


Carotid atherosclerosis is a significant cause of cerebrovascular disease. However, with many candidate markers, precise assessment of its development and progression risks is still limited. This paper reviews state-of-the-art concepts of microRNA as an atherogenesis biomarker throughout various stages including endothelial dysfunction, cholesterol/lipid metabolism, inflammation, oxidative stress, angiogenesis regulation, and proliferation and migration of vascular smooth muscle cells. Based on the available literature, we have described most significant microRNAs for each stage characterized in brief. We have visualized interactions between microRNAs and validated target genes with MIENTURNET and suggest and justify a set of microRNAs for further pilot studies of carotid atherosclerosis.

Annals of Clinical and Experimental Neurology. 2023;17(1):69-74
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Clinical analysis

A case series of cerebral toxoplasmosis in the practice of a neurological hospital

Shnyakin P.G., Botov A.V., Rudenko P.G., Khorzhevsky V.A., Usatova I.S.


Introduction. Central nervous system is one of the main targets in patients with HIV infection. Neurological complications in AIDS are primarily caused by opportunistic brain infections including toxoplasmosis as the most common one. Patients with cerebral toxoplasmosis are often hospitalized with diagnosed strokes, tumors, or encephalitis. At that, their HIV status may be unknown and their state severity often does not allow conducting the range of required examinations.

Materials and methods. We have described our experience in management of 6 patients admitted to the neurosurgery department with single toxoplasmosis foci and diagnosed brain tumors.

Results. HIV infection was initially known in 3 patients only. In 2 compensated patients, the diagnosis was confirmed via Toxoplasma IgG blood test. In 2 individuals, negative serological Toxoplasma reactions were followed by neuronavigationally controlled biopsies. A patient with an extensive perifocal edema and, as a result, dislocated midline structures underwent decompressive craniectomy and mass removal. One female patient, with an unclear diagnosis, was operated for a suspected brain tumor. After additional assessments (including 4 histologies to confirm cerebral toxoplasmosis), all the patients were transferred to the infectious disease hospital for specific treatment.

Annals of Clinical and Experimental Neurology. 2023;17(1):75-81
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Post-Covid disorders of nervous system: personal experience

Shchepankevitch L.A., Arkhipov I.E., Polyanskaya V.V., Veretelnikov I.A., Taneeva E.V., Rerikh K.V.


Introduction. In the COVID-19 pandemic, high lethality as well as long-term outcomes are getting more and more relevant. According to the accumulated study results, COVID-19 affects the nervous system both directly and indirectly.

Objective: to study the variants of post-COVID syndrome based on the data from the State Novosibirsk Regional Clinical Hospital from July 2020 to February 2022.

Materials and methods. We have performed post hoc analysis of the medical records of 1,500 patients with a past history of COVID-19 admitted following various neurological disorders manifested from July 2020 to February 2022.

Results. While temporary and pathogenetic association with past COVID-19 was revealed in 455 patients, primary involvement of the central nervous system was reported in 91.6% of cases, primary involvement of the peripheral nervous system — in 8.1% of cases, and musculoskeletal disorder (idiopathic myodystrophy) — in 0.3% of cases.

Conclusion. Prevalence of the neurological variants of post-COVID syndrome is still unknown. However, patients with severe COVID-19 are more susceptible to neurological complications during the following six months.

Annals of Clinical and Experimental Neurology. 2023;17(1):82-86
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