[The relationship between the development of post-stroke cognitive impairment and changes in the coagulation component of hemostasis]. / Svyaz' postinsul'tnykh kognitivnykh narushenii i izmenenii koagulyatsionnogo zvena gemostaza.

OBJECTIVE: To evaluate the relationship between the severity of post-stroke cognitive impairment (PSCI) and coagulation parameters assessed using the dynamic thrombophotometry. MATERIAL AND METHODS: Thirty-five patients with hemispheric ischemic stroke (IS) with moderate neurological deficit at admission were included. All patients underwent a comprehensive clinical and instrumental assessment according to the current guidelines. On days 10-14, the cognitive status of patients was assessed using the Montreal Cognitive Assessment (MoCA). Coagulation parameters were assessed using the dynamic thrombophotometry at admission, on 6-8th days and 13-15th days from the onset of the disease. A database of laboratory studies of 30 apparently healthy volunteers was used as a comparison group. RESULTS: Data analysis revealed that a number of spatial and temporal parameters were within the reference values, and there were no significant changes over time. Nevertheless, though the optical density of the fibrin clot (D) was within the reference values, it showed a steady increase from the admission by the end of the 1st week of the disease (p=0.007) and by 13-15th days (p=0.009). Correlation and multivariate linear regression, including baseline stroke symptom severity, showed significant associations (p<0.01 in all tests) between the higher optical density of the fibrin clot (D) on days 6-8 and 13-15 and lower MoCA score, confirming the negative effect of altered hemostatic parameters on cognitive function in IS patients. CONCLUSION: The increase of optical density of the fibrin clot (D) by 6-8th and 13-15th days is a potential prognostic biomarker for the early development of PSCI.

[Efficacy and safety of the drug Cellex for the treatment of patients with cognitive impairment with chronic cerebral ischemia - results of a multicenter randomized double-blind placebo-controlled clinical trial]. / Effektivnost' i bezopasnost' primeneniya preparata Tselleks dlya lecheniya patsientov s kognitivnymi narusheniyami s khronicheskoi ishemiei golovnogo mozga ­ rezul'taty mnogotsentrovogo randomizirovannogo dvoinogo slepogo platsebo-kontroliruemogo klinicheskogo issledovaniya.

OBJECTIVE: To evaluate the efficacy and safety of using Cellex for the treatment of cognitive impairment as part of the complex therapy of patients with chronic cerebral ischemia (CCI) compared with placebo. MATERIAL AND METHODS: The study randomized 300 patients with a reliable diagnosis of CCI stage 1-2, all participants were divided into two groups, 150 participants in each - main and control. The study drug Cellex or placebo was administered as two 10-day treatment courses, 1 ml once a day. The duration of the study was 90±5 days for each participant. The primary end point for evaluating the effectiveness of the therapy was the degree of improvement in the state of cognitive functions relative to the initial state according to the Montreal Cognitive Dysfunction Scale (MoCA) on the 31st and 60th days from the start of therapy in the compared groups. Secondary endpoints were the assessment of the degree of improvement in the state of cognitive functions according to psychometric testing scales (MoCA, Correction Test, Frontal Dysfunction Test Battery) relative to the initial state on the 31st, 60th and 90th days from the start of therapy. Also, a dynamic assessment of the systemic concentration of markers of brain damage - S100ß, GFAP, MMP9 and neurotrophins - BDNF and GDNF was carried out. RESULTS: The primary endpoint of the study was achieved-the MoCA score in each group increased uniformly after baseline. However, in the main group, this indicator was significantly higher starting from visit 3 - 23.4±2.8 points in the main group, in the placebo group 22.7±2.3 (p<0.001), a statistically significant difference also remained at visit 5 (p<0.001). When analyzing the secondary endpoints according to the battery of frontal dysfunction tests and the correction test, a more pronounced positive trend was also noted in the main group. Changes in the emotional sphere in both groups remained within the normal range. The dynamics of the systemic concentration of markers of brain damage and neurotrophins was multidirectional, the assessment of which was possible only at the trend level. CONCLUSION: Based on the statistical analysis of the results of the study, Cellex was confirmed to be superior to Placebo in the degree of improvement in cognitive functions measured by the MoCA scale after the 1st and 2nd treatment courses.

Key design elements of successful acute ischemic stroke treatment trials.

PURPOSE: We review key design elements of positive randomized controlled trials (RCTs) in acute ischemic stroke (AIS) treatment and summarize their main characteristics. METHOD: We searched Medline, Pubmed and Cochrane databases for positive RCTs in AIS treatment. Trials were included if (1) they had a randomized controlled design, with (at least partial) blinding for endpoints, (2) they tested against placebo (or on top of standard therapy in a superiority design) or against approved therapy; (3) the protocol was registered and/or published before trial termination and unblinding (if required at study commencement); (4) the primary endpoint was positive in the intention to treat analysis; and (5) the study findings led to approval of the investigational product and/or high ranked recommendations. A topical approach was used, therefore the findings were summarized as a narrative review. FINDINGS: Seventeen positive RCTs met the inclusion criteria. The majority of trials included less than 1000 patients (n = 15), had highly selective inclusion criteria (n = 16), used the modified Rankin score as a primary endpoint (n = 15) and had a frequentist design (n = 16). Trials tended to be national (n = 12), investigator-initiated and performed with public funding (n = 11). DISCUSSION: Smaller but selective trials are useful to identify efficacy in a particular subgroup of stroke patients. It may also be of advantage to limit the number of participating countries and centers to avoid heterogeneity in stroke management and bureaucratic burden. CONCLUSION: The key characteristics of positive RCTs in AIS treatment described here may assist in the design of further trials investigating a single intervention with a potentially high effect size.

COVID-19-Associated Stroke.

The COVID-19 pandemic has had significant influences on the incidence of acute cerebrovascular accidents and the structure of mortality. SARS-CoV-2 increases the risks of developing both ischemic and hemorrhagic stroke. The key pathogenetic element underlying the development of cerebral stroke in COVID-19 consists of impairments to the operation of angiotensin 2 receptors, which are accompanied by accumulation of excess quantities of angiotensin 2, endothelial dysfunction, hypercoagulation, overproduction of proinflammatory cytokines, and an oxidative storm. In patients with stroke and COVID-19, lesion severity is associated with dual mechanisms of ischemia - systemic and cerebral. The possibilities of medication-based correction of both systemic impairments associated with coronavirus infection and local impairments due to ischemic or hemorrhagic brain damage, are limited. Substances with antioxidant activity may potentially be effective in patients with stroke and COVID-19. Data from a number of clinical rials indicate that Mexidol significantly improves functional outcomes in ischemic stroke. Use of Mexidol in patients with stroke and COVID-19 is advised.

[COVID-19 related stroke]. / Insul't, assotsiirovannyi s COVID-19.

The COVID-19 pandemic had a significant impact on both the incidence of acute cerebral circulatory disorders and the structure of mortality. SARS-CoV-2 increases the risk of both ischemic and hemorrhagic stroke. The key pathogenetic links underlying the development of cerebral stroke in COVID-19 are impaired functioning of angiotensin 2 receptors, accompanied by the accumulation of excess angiotensin 2, endothelial dysfunction, hypercoagulation, hyperproduction of proinflammatory cytokines and oxidative storm. In patients with stroke and COVID-19, the severity of the lesion is associated with a dual mechanism of ischemia - systemic and cerebral. The possibilities of medical correction of systemic disorders associated with coronavirus infection, as well as local ones caused by ischemic or hemorrhagic brain damage, are limited. Substances with antioxidant activity could potentially be effective in patients with stroke and COVID-1.

[Prognostic value of endothelial dysfunction and von Willebrand factor in acute and chronic hemispheric intracerebral hemorrhage]. / Prognosticheskoe znachenie disfunktsii éndoteliia i faktora fon Villebranda v ostrom i otdalennom periodakh gemorragicheskogo insul'ta polusharnoi lokalizatsii.

AIM: To study the changes in endothelial dysfunction and von Willebrand factor activity in acute and chronic stages of hemispheric intracerebral hemorrhage (ICH) and their influence on clinical severity and functional recovery. MATERIAL AND METHODS: Fifty patients with hemispheric ICH, aged 61.6±11.2 years, and 30 patients with AH, aged 59.6±6.2 years, (comparison group) were examined. Patients with ICH were examined on admission, 6-8th, 13-15th days, and 11.1±0.9 months after stroke onset. Patients with arterial hypertension (AH) were examined on admission. Changes in NIHSS, Glasgow coma scale, and modified Rankin scale were studied. Restocetin induced platelet aggregation (RIPA) was assessed by optical aggregometry (BIOLA LA230-2 AGGRWB) in modification by G. Born and Z. Gabbasov. von Willebrand factor (vWF) activity was examined as described by J. Olson. RESULTS: RIPA was significantly higher in acute ICH compared to chronic ICH, AH and reference values. RIPA values were negatively correlated with hematoma volume and midline shift (r≥ -0.308, p≤0.035). vWF activity was significantly higher in ICH patients than in AH and reference values. Patients with AH also had significantly higher vWF activity than reference values. In acute ICH, vWF activity steadily increased reaching maximal values by 13-15th day. In chronic ICH, vWF activity decreased compared to the acute phase, but still remained higher than in AH patients or reference values. In acute phase, 1% increment in vWF values resulted in 0.5% increase in the risk of death during the follow-up period (95% CI 1.001-1.008, p=0.007). CONCLUSION: Endothelial dysfunction assessed by vWF activity increases during the acute hemispheric ICH and remains elevated in the chronic stage. vWF activity may be used as a marker in assessing stroke outcome and prognosis.