[The trial of the efficacy and safety of sequential therapy with Mexidol forte 250 in acute and early recovery stages of hemispheric ischemic stroke]. / Issledovanie effektivnosti i bezopasnosti lekarstvennogo preparata Meksidol FORTE 250 v ramkakh posledovatel'noi terapii u patsientov s polusharnym ishemicheskim insul'tom v ostrom i rannem vosstanovitel'nom periodakh.

OBJECTIVE: To evaluate the efficacy and safety of sequential therapy with mexidol (solution for intravenous and intramuscular injections) and mexidol forte 250 (coated tablets) in acute and early recovery stages of hemispheric ischemic stroke. MATERIAL AND METHODS: The changes in scores on the modified Rankin Scale (mRs) (primary endpoint), the National Institute of Health Stroke Scale (NIHSS), the Bartel Index (BI), the Montreal Cognitive Assessment (MoCa), the Beck Depression Inventory (BDI), the EuroQol Quality of Lifes Scale ( EQ-5D) were assessed in the end of treatment (secondary endpoint). RESULTS AND CONCLUSION: Prolonged and sequential therapy with mexidol at the dose 500 mg daily during 14 days (saturation phase) and mexidol forte 250 at the dose of 250 mg three times a day during 60 days (maximum therapeutic effect) provides additional opportunities for a more complete recovery in acute and early recovery stages of hemispheric ischemic stroke (increases quality of life, improves movement and cognitive functions).

[Pharmacological neuroprotection in stroke in clinical practice: new perspectives]. / Farmakologicheskaia neiroprotektsiia pri ishemicheskom insul'te v real'nykh klinicheskikh usloviiakh.

Despite recent advances in acute stroke care, clinical armamentarium against stroke remains limited. Furthermore, highly effective approaches to stroke treatment, such as systemic reperfusion and mechanical thrombectomy, cannot be performed in the majority of patients. Neuroprotective strategies, i.e. prevention of irreversible cell damage due to the ischemia, may improve stroke outcomes. However, only few pharmacological agents demonstrated clinical efficacy. Citicoline is an endogenous mononucleotide with neuroprotective effect and established clinical safety and tolerability, which effectiveness in acute stroke was studied in several large, well-controlled trials. Recent meta-analysis confirmed benefit of citicoline treatment in terms of increase of chance for better recovery of functional independence compared to placebo. Maximal effect of citicoline is seen when it is administered as soon as possible after stroke onset in patients who are not eligible for reperfusion therapy.

[Stroke: the review of the problem (15 years after)].

The critical review of the key achievements in ischemic and hemorrhagic stroke of the past 15 years is presented in the article including stroke epidemiology and classification, experimental models, treatment of malignant edema after stroke, thrombolytic therapy, surgical treatment of intracranial hematomas, surgery on extracranial arteries, polyorganic insufficiency syndrome, secondary prevention of cardioembolic stroke, neuroprotection and early rehabilitation.

[Resistance to antiplatelet drugs in patients with cerebrovascular disorders].

This review concerns clinical and laboratory resistance to antiplatelet drugs (aspirin and clopidogrel) in patients with cerebrovascular disorders. Results of certain clinical trials showed that laboratory resistance to antiaggregants is associated with recurrent thromboembolic vascular events. The commonest causes of aspirin resistance are production of arachidonic acid metabolites via the lipoxygenase pathway, poor compliance with the treatment, polymorphism of the genes encoding for cyclooxygenase and glycoprotein (GP) IIb/IIIa, endothelial dysfunction. The causes of clopidogrel resistance include inadequate doses of the drug, its low absorption, poor compliance with the treatment, polymorphism of ADP receptors, GP IIb/IIIa and cytochrome P450 genes, acute coronary syndrome and stroke, metabolic syndrome. Therapeutic efficacy of antiaggregants can be improved by increasing their doses, using membranotropic agents, correcting endothelial dysfunction, etc. Because the apparent variability of antiplatelet drug resistance is currently due to the use of different test-systems by different authors, the evaluation of individual sensitivity to a given drug showing laboratory resistance and the choice of alternative therapy are thus far possible only in the framework of clinical studies. Large-scale prospective multicenter trials of antiplatelet drug resistance are needed along with research for better understanding mechanisms of individual platelet sensitivity and resistance to antiaggregants and developing efficacious methods for their correction.

[Changes of haemostatic parameters in patients with acute cardioembolic stroke].

Haemostatic parameters: platelet aggregation, hematocrit, fibrinogen, antithrombin III, fibrinolytic activity and euglobulin lysis time, plasminogen, plasminogen activator and anti-activator activity, thrombin- antithrombin and plasmin-antiplasmin complexes and serum von Willebrand factor were studied at the most acute stage of cardioembolic stroke (1-7 days after development of neurological symptoms). State of the vascular wall was assessed using the "cuff"-test. The activation of hemostasis in patients with cardioembolic stroke was characterized by the hypercoagulation and decrease of fibrinolysis and athrombogenic potential of vessel wall properties (antiaggregation, fibrinolytic and anticoagulative). In conclusion, haemostatic disbalance and decreasing of athrombotic potential of the vessel wall may be the indicator of embolism in patients with cardioembolic stroke.

[Hemorheology and hemostasis in patients suffering from ischemic cerebral stroke and metabolic syndrome].

A high level of mortality and disability makes study of various aspects of ischemic cerebral stroke (ICS) an extremely important problem. Presently, combination of various cardiovascular risk factors significantly increases the probability of such life-threatening conditions as ICS. Such risk factors as arterial hypertension, dyslipoproteinemia, excessive body weight, glucose intolerance or diabetes are often combined, which led to a suggestion to consider them together as one symptom complex, metabolic syndrome (MS). It is evident that MS affects the functioning of different organs and systems, including the systems of hemorheology and hemostasis. These are changes in hemorheological and hemostatic parameters that play a leading (in some cases decisive) role in the development of ICS. The present study found that the presence of MS in ICS patients hindered improvement in hemorheological and hemostatic parameters in the course of the disease. This was manifested by the absence of positive changes in thrombocyte aggregation, as well as fibrinogen level elevation in patients with MS in the course of treatment. Elevated blood level of D-dimers within the whole acute period in most MS patients also reflected more active thrombus formation. The development of ICS is very unfavorable to the condition of vascular wall athrombogenic activity in all patients. At the same time, worsening in all the chains of endothelial wall athrombogenic ability was more prominent in MS patients. Significant influence of MS on the forming of prothrombotic condition, which determines unfavorable clinical course of ICS, was demonstrated.