To assess the tolerability and safety of using high-tech software complexes with biofeedback (BF) via a brain-computer interface (BCI) in the recovery of patients after a stroke, based on an analysis of neuropsychological examination data.

The study included 100 stroke patients: 40 patients in the main group, 40 patients in the comparison group, and 20 patients in the control group. The Hospital Anxiety and Depression Scale (HADS), the Beck Depression Inventory (BDI), the Hamilton Anxiety Rating Scale (HARS), the Hamilton Depression Rating Scale (HDRS), the Montreal Cognitive Assessment (MoCA), and the Mini-Mental State Examination (MMSE) were used. In the main group, sessions were conducted using BCI-BF1 based on the P300 potential; in the comparison group, sessions were conducted using BCI-BF2 based on the mu-rhythm of electroencephalography (EEG); control group patients received standard of care.

Improvement of the symptoms was reported; no «aggravation/increase» of the existing symptoms or the occurrence of new symptoms was observed, which indicated good tolerance of using BCI-BF1 and BCI-BF2. The results of the assessment on the BDI, HARS, and HDRS scales showed a statistically significant improvement, indicating the regression of existing affective disorders corresponding to the level of minor disorders, namely «subclinical anxiety/depression» (p<0.001). When assessing the BDI and HDRS scales, a statistically significant decrease in the scores for the subscale of affective-cognitive disorders was found in the main group (p=0.002) and in the comparison group (p<0.001). MoCA score showed no decrease from the baseline score of 25 or more: in the main group, there was an increase in the median total score (p=0.014); in the comparison group, there was no change (p=0.683).

Treatment with BCI-BF1 based on P300 and BCI-BF2 based on the EEG mu-rhythm was safe in patients in the recovery period of stroke, showed good tolerance, did not cause the occurrence or increase of affective disorders, and did not reduce the MoCA score.

To assess the effectiveness of low-frequency repetitive transcranial magnetic stimulation (rTMS) in improving chronic motor aphasia after ischemic stroke (IS) compared with memantine.

A randomized, open-label, parallel-group study was conducted at the Urgench Rehabilitation Hospital in Urgench from February 2022 to May 2024. Patients with motor aphasia after IS were randomized into two groups.

Group 1 (n=30) received 10 sessions of a low-frequency (1 Hz) rTMS protocol. Group 2 (n=30) received memantine (initial dose 5 mg QD, increased to 20 mg QD) for eight weeks. The Western Aphasia Battery (WAB) was used for assessment before and after the intervention.

Intra-group comparison before and after treatment in each part of the WAB score showed a significant increase in patients' scores in both groups (p<0.001). Compared to the memantine group, the low-frequency rTMS group showed more significant improvements in word repetition and naming objects (p<0.001).

Both memantine and rTMS improved verbal function in patients with post-stroke motor aphasia. Compared to memantine, TMS treatment was associated with a more significant improvement in repetition and naming.

To discusses the practical healthcare implications of the MIR trial and its post-hoc analyses.

MIR was an international multicenter randomized double-blind placebo-controlled trial conducted in 17 centers In Russia, Kazakhstan, and Uzbekistan. 304 patients were randomized, and 279 patients were included in the per-protocol analysis (276 for clinical scales applicable to survivors only). Non-reperfused patients aged 40-75 years with first-ever hemispheric IS, presenting ≤48 hours from onset with CT/MRI signs of ischemia or no signs of intracerebral hemorrhage, were included. Additionally, at screening, the included patients had a National Institutes of Health Stroke Scale (NIHSS) score of 9-15 and a modified Rankin Scale score (mRS) of 3 or higher. In the treatment group, patients received sequential therapy as follows: 500 mg (10 mL) of intravenous Mexidol diluted in 100-200 ml of normal saline twice per day for 10 days, followed by 250 mg of Mexidol FORTE 250 orally thrice per day for 60 days. In the control group, patients received a placebo administered in a similar manner. The primary endpoint was a change in mRS score from baseline at days 69-73. The trial protocol was registered in the Registry of Permits for Conducting Clinical Trials (PHS-APIS-004-MEX-SOL-TAB) and the ClinicalTrials.gov registry (NCT06437626).

In the placebo group (n=138), the average change in the mRS score was -2.01 [95% CI -2.25- -1.87], while in the treatment group (n=141) it averaged -2.45 [95% CI -2.70- -2.32], which was indicative of a more favorable functional outcome in the treatment group (p=0.003). In addition, several post-hoc analyses showed that sequential multimodal antioxidant treatment was associated with a 2.2-fold increase in favorable functional outcome odds (mRS score of 0-1) and a 3.9-fold increase in complete neurological recovery odds (NIHSS score of 0) at day 69-73 compared to placebo.

The MIR randomized clinical trial showed that 70-day sequential therapy with Mexidol and Mexidol FORTE 250 was superior to placebo in non-reperfused patients with first-ever IS and a baseline NIHSS score of 9-15.

The study aimed to evaluate the efficacy and safety of Revelise (alteplase), a Russian medicinal product used as thrombolytic therapy (TLT) to treat ischemic stroke (IS) in real-world practice.

A total of 2202 patients with IS were included in the study. The mean age was 68 years, with 20% of patients aged 80 years or older. Of the patients, 53.6% were men and 46.4% were women; 233 (10.6%) patients with large vessel occlusion underwent staged reperfusion. The most common comorbidities were hypertension (96%), chronic heart failure (57.3%), coronary artery disease (56.9%), and cardiac arrhythmias (33.8%). Nearly one-third (28.9%) of patients received antiplatelet agents before TLT, whereas 4.7% received anticoagulants. The mean NIHSS score for the entire study population was 10, and 11.6% had disabling symptoms with a NIHSS score< 5. Symptomatic hemorrhagic transformation was determined using the ECASS 3 criteria.

A substantial reduction in neurological deficit was reported within one day, which differed significantly from the previous value (p< 0.001). Twenty-four hours after TLT, 42.8% of patients demonstrated a decrease in their NIHSS score by ≥4. The hospital mortality rate was 8.2%. Symptomatic hemorrhagic transformation developed in 2.5% of patients. Favorable outcomes (mRS 0-2) were reported in 49.9% of patients at discharge and 66.4% of patients 90 days after TLT.

The obtained results confirm the high efficacy and safety of Revelise in patients with IS. The wide practical use in various patient groups is justified by an up-to-date patient selection algorithm. This includes patients aged 80 years and older with minor stroke (NIHSS score< 5) who receive treatment with antiplatelet agents or anticoagulants, as well as staged reperfusion. The obtained results are consistent with those of previously published studies with a similar design.

To study the relationship between the parameters of the right heart and the thickness of the common carotid artery (CCA) intima-media complex (IMC) in patients with chronic cerebral ischemia (CCI).

A single-center cross-sectional study analyzed clinical and instrumental data from 263 patients (137 males and 126 females) diagnosed with CCI. Depending on the average thickness of CCA IMC, patients were divided into two groups: Group 1 (n=184) with CCA IMC ≤1.3 mm and Group 2 (n=79) with CCA IMC ≥1.31 mm.

Patients in Group 2 were significantly older (64.7±10.8 years vs. 60.7±8.5 years for males; p<0.05) and had a higher rates of hypertension (64.5% vs. 40.2%; p<0.05), obesity (51.8% vs. 32.6%; p<0.05), chronic kidney disease (39.2% vs. 19.0%; p<0.05), a stable form of coronary heart disease (56.9% vs. 27.7%; p<0.05), hypercholesterolemia (49.3% vs. 35.8%; p<0.05), elevated levels of C-reactive protein (37.9% vs. 19.5%; p<0.05), and blood glucose (8.11±5.70 mmol/L vs. 6.26±2.4 mmol/L; p<0.05) compared to Group 1 patients. Parameters of the right heart, including right ventricular size (2.335±0.483 cm vs. 2.221±0.373 cm; p<0.05), thickness of the right ventricle anterior wall (0.437±0.104 cm vs. 0.396±0.079 cm; p<0.05), TAPSE (2.445±0.445 cm vs. 2.567±0.316 cm; p<0.05), pulmonary artery diameter (2.507±0.407 cm vs. 2.339±0.328 cm; p<0.05), and pulmonary artery pressure (38.4±16.1 mm Hg vs. 32.6±10.3 mm Hg; p<0.05) were significantly higher in Group 2. There were significant correlations between the average thickness of the CCA IMC and the size of the right ventricle (r=0.19; p<0.05), the thickness of the right ventricle anterior wall (r=0.21; p<0.05), the diameter of the pulmonary artery (r=0.22; p<0.05), and the systolic pressure in the pulmonary artery (r=0.20; p<0.05).

In patients with CCI, an increase in CCA IMC thickness ≥1.3 mm was associated with a higher rate of cardiovascular and metabolic risk factors, including hypertension, obesity, chronic kidney disease, stable coronary artery disease, hypercholesterolemia, elevated levels of C-reactive protein, and venous blood glucose. A significant correlation was established between the structural changes in the carotid arteries and the parameters of the right heart, which may reflect systemic atherosclerotic and hemodynamic changes that contribute to the progression of cerebrovascular disorders.

To assess the serum levels of matrix metalloproteinases (MMP) MMP-2, MMP-9, and vascular endothelial growth factor (VEGF) during the acute period of ischemic stroke (IS) in the context of clinical and functional recovery of patients.

The study sample consisted of 114 patients with IS. Patient groups: Group 1 - mild stroke (n=57 patients), Group 2 - moderate stroke (n=25 patients), Group 3 - severe stroke (n=32 patients). Observation period: 14 days. Assessment timepoints: I - 48-72 hours from the onset of the disease; II - Day 14. Scores: Glasgow Coma Scale (GCS), National Institutes of Health Stroke Scale (NIHSS), Modified Rankin Scale (mRS). Serum MMP-2 and MMP-9 were measured using enzyme-linked immunosorbent assay (ELISA), and VEGF was measured on a multiplex analyzer. Statistical data processing was performed using the Statistica 13.0 software bundle.

Patients of Groups 1 and 2 showed significant improvement in the NIHSS and mRS scores (p<0.001), and patients of Group 3 demonstrated no change (p=0.157 and p=0.315, respectively). MMP-2 levels were significantly lower in Group 3 when compared with patients of Groups 1 and 2 at timepoints I and II (p_1-3=0.03 and p_1-3=0.014). A strong positive correlation was found between ΔGCS=0 [-3; 1] and MMP-2_II (r=0.927; p=0.024). ΔMMP-9 in Group 1 was 75 [-38; 302] ng/mL and positively correlated with mRs_II (r=0.613; p=0.034). Group 3 patients showed a significant increase in VEGF at timepoint II (p_I-II=0.021); ΔVEGF=68 [38; 105] pg/mL positively correlated with NIHSS_I (r=0.691; p=0.027). In patients of Group 2, the inverse relationship was observed, a negative correlation between ΔVEGF and ΔNIHSS (r=-0.653; p=0.041). Significant interbiomarker associations were found: positive between MMP-2_I and MMP-9_II in Group 2 (r=0.566, p=0.044), and negative between MMP-2_I and VEGF_II in Group 3 (r=-0.721, p=0.019).

The study demonstrated the association of biomarker profiles (VEGF, MMP-2, and MMP-9) with stroke severity. In mild to moderate disease, their modulation contributes to recovery, while in severe disease, it requires control. The obtained data support the development of personalized therapeutic strategies aimed at optimizing neuroplasticity by regulating the activity of the studied molecules.

Cardiovascular disease (CVD) is a leading global cause of mortality, and understanding its underlying mechanisms is crucial for developing effective interventions. The liver-derived protein PCSK9 (proprotein convertase subtilisin/kexin-type-9) plays a vital role in regulating lipoprotein metabolism by binding to the low-density lipoprotein receptor (LDLR) and promoting its lysosomal degradation, ultimately reducing low-density lipoprotein (LDL) clearance. Loss-of-function (LOF) variants in PCSK9 are associated with decreased LDL cholesterol (LDL-C) levels, suggesting that these variants may contribute to a lower risk of cardiovascular events. Our computational analysis of PCSK9 LOF variants revealed significant alterations in stability, flexibility, and free energy compared to the native protein. Protein-protein docking studies of both wildtype and mutant PCSK9 with LDLR demonstrated variations in binding energy and interacting residues. Notably, while the binding cavity remained the same as that of the wildtype, all variants exhibited distinct binding interactions. Molecular dynamics simulations further highlighted increased flexibility and solvent exposure in the mutant protein complexes. These findings indicate that LOF variants in PCSK9 induce substantial structural changes, leading to a decreased affinity for LDLR binding.

Post-stroke depression (PSD) is a common and clinically significant complication of stroke, associated with worse rehabilitation potential and increased mortality risk. The prevalence of PSD varies from 25% to 59%, depending on the duration of follow-up, peaking in the first years after the stroke event. The pathogenesis of PSD results from a complex interplay of biological and psychological factors, extending far beyond monoamine deficiency. Key roles are played by damage to monoaminergic pathways, neuroinflammation, dysfunction of the hypothalamic-pituitary-adrenal axis, reduced neuroplasticity (including BDNF deficit), and impaired integrity of neuronal networks. The clinical picture is characterized by a complex of affective (apathy, anhedonia), cognitive (executive dysfunction), and dyssomnic disorders. Although selective serotonin reuptake inhibitors remain the first-line treatment, the modern therapeutic approach to PSD requires targeting all components of its pathogenesis. A promising direction is the use of antidepressants with a multimodal mechanism of action, such as the original drug fluvoxamine, which combines serotonergic effects with anti-inflammatory and neuroprotective properties via sigma-1 (σ1) receptor agonism. Optimizing PSD treatment is achievable through the implementation of a personalized approach, including long-term screening and comprehensive management of the identified disorders.

Cerebral venous thrombosis is a condition that can lead to a cerebrovascular accident and is associated with thromboses in the cerebral sinuses. The clinical presentation is often similar to ischemic cerebral infarction and depends on the location of the thrombosis, but one of the most common symptoms is headache. Cerebral venous thrombosis in most cases is associated with risk factors for this condition, such as pregnancy, various types of coagulopathy, autoimmune diseases, infections, etc. The objective of this paper is to present a clinical case of a patient with thrombophilia who developed thrombosis of the left transverse sinus.

To study the features of cerebrovascular accidents (CVAs) in patients with primary vasculitis of the intracranial arteries (PVICA) and the change of contrast agent uptake by the vascular wall after treatment with corticosteroids.

The study included 34 patients (19 males, 56%; mean age 41.4±8.8 years) with CVA associated with PVICA. All patients underwent MR angiography (MRA) of the intracranial arteries and a high-resolution MRI scan of the vascular wall before and after the contrast agent (CA) injection. Twenty-seven patients were treated with corticosteroids, and 25 of them were followed up.

Of the 34 study patients, 76% had CVA in the form of ischemic stroke (IS), which recurred in 29% of patients. Repeated transient CVAs (tCVAs) were reported in 82%. In 91% of cases, IS and tCVA occurred in the internal carotid artery (ICA) system. The National Institutes of Health Stroke Scale (NIHSS) showed mild or moderate IS in 96% of patients. MRA of the intracranial arteries revealed stenoses (56%), occlusions (12%), or their combination (32%). The CA uptake by the vascular wall was detected in all patients. After treatment with corticosteroids, 80% of 25 patients followed up for 29.1±28.7 months showed a clinical improvement. Repeated MRI of the vascular wall, performed in 16 patients within 21.1±26.3 months after treatment, showed the absence or decreased CA uptake in 4 patients, increased uptake in 2 patients, and no change in the uptake in 10 patients.

CVAs in patients with PVICA usually occur as a minor stroke or repeated CVAs, and in 91% of cases, they involve the ICA system. Treatment with corticosteroids is effective in 80% of patients. The persistence of CA uptake by the vascular wall, as observed by MRI after treatment with clinical improvement, is likely due to post-inflammatory fibrosis.