[Nonimmunogenic staphylokinase in the treatment of acute ischemic stroke (FRIDA trial results)]. / Neimmunogennaya stafilokinaza ­ novyi tromboliticheskii preparat v lechenii ishemicheskogo insul'ta (rezul'taty issledovaniya FRIDA).

AIM OF THE STUDY: To investigate the efficacy and safety of non-immunogenic staphylokinase (NS) compared with alteplase (A) in patients with acute ischemic stroke (AIS) within 4.5 h after symptom onset. MATERIAL AND METHODS: 336 patients with IS within 4.5 h after symptom onset were included in a randomized, open-label, multicenter, parallel-group, non-inferiority comparative trial of NS vs A (168 patients in each group). NS was administered as an intravenous bolus in a dose of 10 mg, regardless of body weight, over 10 s, A was administered as a bolus infusion in a dose of 0.9 mg/kg, maximum 90 mg over 1 hour. The primary efficacy endpoint was a favorable outcome, defined as a modified Rankin scale (mRS) score of 0-1 on day 90. Safety endpoints included all-cause mortality on day 90, symptomatic intracranial haemorrhage, and other serious adverse events (SAEs). RESULTS: At day 90, 84 (50%) patients reached the primary endpoint (mRS 0-1) in the NS group, 68 (41%) patients - in the A group (p=0.10, OR=1.47, 95% CI=0.93-2.32). The difference between groups NS and A was 9.5% (95% CI= -1.7-20.7) and the lower limit of the 95% CI did not cross the margin of non-inferiority (pnon-inferiority<0.0001). There were no significant differences in the frequency of deaths between the groups: on day 90, 17 (10%) patients in the NS group and 24 (14%) in the A group had died (p=0.32). There was a trend towards significant differences in the frequency of symptomatic intracranial haemorrhage: NS group - 5 (3%) patients, A group - 13 (8%) patients (p=0.087, OR=0.37, 95% CI=0.1-1.13). There were significant differences in the number of patients with SAEs: in the NS group - 22 (13%) patients, in the A group - 37 (22%) patients (p=0.044, OR=0.53, 95% CI=0.28-0.98). CONCLUSION: The presented results of the FRIDA trial are the first in the world to use a drug based on NS in patients with IS. It has been shown that a single bolus (within 10 s) administration of NS at a standard dose of 10 mg, regardless of body weight, allows to conduct fast, effective and safe thrombolytic therapy in patients with IS within 4.5 h after symptom onset. In further clinical tials of NS, it is planned to expand the therapeutic window beyond 4.5 h after symptom onset in patients with IS.

[Efficacy and safety of sampeginterferon ß-1a in the treatment of relapsing remitting multiple sclerosis: results of 52 weeks of therapy in a randomized, double-blind clinical trial]. / Effektivnost' i bezopasnost' sampeginterferona ß-1a dlya lecheniya remittiruyushchego rasseyannogo skleroza: rezul'taty 52-nedel'nogo randomizirovannogo dvoinogo slepogo klinicheskogo issledovaniya.

OBJECTIVE: To evaluate the efficacy and safety of samPEG-IFN-ß1a 180 µg and 240 µg administered once every 2 weeks for the treatment of relapsing remitting multiple sclerosis (RRMS) compared to placebo and low dose interferon beta-1a (LIB) 30 µg administered once weekly. The primary endpoint after 52 weeks of therapy was the time to first relapse, the hypotheses of non-inferiority and superiority to LIB were tested. MATERIAL AND METHODS: This international, multicenter, double blind, comparative, placebo-controlled clinical study enrolled 399 patients with the diagnosis of RRMS, randomized in 4 groups: samPEG-IFN-ß1a180 µg (n=114), samPEG-IFN-ß1a 240 µg (n=114), LIB (n=114) and placebo (n=57). Placebo group patients participated in the study for 20 weeks. After 52 weeks of therapy and 4 weeks of follow-up, LIB group patients completed their participation in the study, patients from PEG-IFN-ß1a groups continued to receive therapy until week 100 inclusive. The article presents the results of an analysis conducted after the end of 52 weeks of a double-blind, comparative, randomized, placebo-controlled clinical trial. RESULTS: Final analysis of the efficacy and safety was performed after 52 weeks of study. Main statistical hypothesis testing proved that both doses of samPEG-IFN-ß1a were equally effective when compared to LIB by the primary endpoint - «Time to first relapse¼. Due to detection of statistically significant differences in the primary endpoint between the study drug and the reference drug, indicating a greater efficacy of the study drug, an additional testing was carried out and the hypothesis of superiority of samPEG-IFN-ß1a at a dose of 240 µg over the reference LIB was proved. Evaluation of the dynamics of certain key parameters of magnetic resonance imaging (MRI) of the brain and clinical outcomes demonstrated a positive effect of samPEG-IFN-ß1a therapy in the form of decreased activity of the demyelinating process in the brain and reduce the number of relapses. The proportion of patients without new T2 lesions after 52 weeks was 87.6% and 90.4% in 180 µg and 240 µg samPEG-IFN-ß1a groups, versus 72.6% in the LIB group (p=0.0199 and p=0.0033). No progression of multiple sclerosis was shown based on EDSS scale evaluation. During the study, the most common adverse reactions were flu-like symptoms and injection site reactions. CONCLUSION: The new drug samPEG-IFN-ß1a is an effective and safe agent for relapsing remitting multiple sclerosis treatment, while having an advantage over other low-dose interferons in the form of reduced frequency of intramuscular injections.

The Novel Coronavirus Infection (COVID-19) and Nervous System Involvement: Mechanisms of Neurological Disorders, Clinical Manifestations, and the Organization of Neurological Care.

The new coronavirus SARS-CoV-2 and the disease it causes COVID-19 involves not only respiratory system damage, but can also lead to disorders of the central and peripheral nervous system, as well as the muscular system. This article presents published data and our own observations on the course of neurological disorders in COVID-19 patients. There is a relationship between the severity of COVID-19 and the severity and frequency of neurological manifestations. Severe neurological disorders are mostly seen in severe cases of COVID-19 and include acute cerebrovascular accidents (aCVA), acute necrotizing encephalopathy, and Guillain-Barré syndrome. Factors potentially complicating the course of COVID-19 and increasing the development of neurological complications include arterial hypertension, diabetes mellitus, and chronic cardiac and respiratory system diseases. Questions of the possible effects of human coronaviruses on the course of chronic progressive neurological diseases are addressed using multiple sclerosis (MS) as an example. We discuss the management of patients with aCVA and MS depending on the risk of developing coronavirus infection.

["Ictal" Bradyarrhythmias in Patients with Drug-Resistant Epilepsy: Results of Long-Term Heart Rhythm Monitoring].

Aim      To determine the type and incidence of ictal bradyarrhythmias in patients with drug-resistant types of epilepsy by long-term electrocardiogram (ECG) monitoring.Material and methods  Subcutaneous ECG monitors programed for recording pauses >3 sec and episodes of bradycardia ≤45 bpm were implanted in 193 patients with persistent epileptic seizures without organic pathology of the myocardium. Recording was activated by the patient/family at the onset of epileptic seizure. The follow-up period was 36 months with visits to the clinic every three months.Results For 36 months of monitoring, 6494 ECG fragments were recorded. Ictal bradycardia was observed in 6.7 % of patients, including ictal asystole in 2.6 % of patients. Episodes of bradycardia and asystole during epileptic seizures were transient and developed significantly more frequently in men, patients with long duration of the disease, bilateral tonic-clonic or focal seizures with disorder of consciousness, during sleep, on the background of treatment with several antiepileptic agents, mostly from the group of potassium channel blockers.Conclusion      Bradyarrhythmias accompanying epileptic seizures are transient and reproducible from seizure to seizure. They reflect functional changes in the myocardium and do not determine the life prediction for patients with epilepsy without organic pathology of the heart.

[Development of early diagnosis of Parkinson's disease and comprehensive economic analysis of the effect of its implementation]. / Razrabotka rannei diagnostiki bolezni Parkinsona i kompleksnyi ekonomicheskii analiz effekta ot ee vnedreniya.

The paper summarizes the literature and author's data on the development of early (preclinical) diagnosis of Parkinson's disease (PD). Implementation of this diagnosis will promote the use of preventive therapy and change investments in diagnosis and treatment of patients. The paper declares that at present the only approach to early diagnosis of PD is positron-emission tomography of the nigrostriatal dopaminergic system, but it cannot be used for preventive examination due to its high cost. The authors consider that a less specific, but more promising approach to the development of early diagnosis of PD is the search for markers in body fluids, mainly in the blood, in patients at the prodromal stage of PD. Indeed, a number of markers as changes in the level of metabolites of monoamines, sphingolipids, urates, and indicators of oxidative stress were found in patients selected for the risk group of the prodromal stage of PD, according to characteristic premotor symptoms. In addition, it is assumed that the search for blood markers at an earlier - pre-prodromal stage is possible only in animal models of PD at the early preclinical stage. This approach can also be used to verify blood markers identified in patients at the clinical stage of PD. It is also evident that the complex socio-economic factors influencing the incidence of PD is different in developed versus developing countries. The societal and medical costs of Parkinson's are huge and efforts to improve early preclinical diagnosis of PD will lead to considerable economical and societal benefits. For instance this will allow efficient selection of patients for preclinical diagnostic tests. To assess the effectiveness of this strategy considering the uncertainty of socio-economic issues, a modification of the «cost-utility¼ analysis is proposed. For the first time, a Markov model of PD including preclinical diagnostic tests and possible neuroprotective therapy was developed and studied. Analytical outcomes of this process suggest that the idea of developing a new multimodal strategy is promising from a socio-economic point of view.

[Pulmonary insufficiency in acute stroke: risk factors and mechanisms of development]. / Dykhatel'naya nedostatochnost' v ostrom periode tserebral'nogo insul'ta: faktory riska i mekhanizmy razvitiya.

Various degrees of pulmonary insufficiency (PI) (PaO2 ≤60 mm Hg, SaO2 ≤90%) are diagnosed in most of patients with severe acute stroke (AS). Frequency and severity of PI positively correlates with the severity of AS. PI worsens patient's condition, prolongs the hospitalization period, and increases the probability of fatal outcome. Early clinical signs of PI may be undiagnosed due to the severity of stroke and thus not treated. The initiating pathogenic mechanism of PI is stress-related activation of sympathetic nervous system (SNS) and systemic immunosuppression. In severe stroke with mass effect, the rapid and significant increase in intracranial pressure may additionally activate the SNS. Risk factors of PI include older age, previous pulmonary disease, prolonged supine position, respiratory muscle dysfunction, apnea, and concomitant somatic diseases. Decompensation of somatic diseases leads to multiple stage reactions with facilitation of functional and morphologic changes in the pulmonary system, hypoxemia and hypoxia, promotes infectious complications and multiple organ failure and worsens neurological outcome. Diagnosis and treatment of PI in AS decreases mortality and improves rehabilitation prognosis.

[Novel coronavirus infection (COVID-19) and nervous system involvement: pathogenesis, clinical manifestations, organization of neurological care]. / Novaya koronavirusnaya infektsiya (COVID-19) i porazhenie nervnoi sistemy: mekhanizmy nevrologicheskikh rasstroistv, klinicheskie proyavleniya, organizatsiya nevrologicheskoi pomoshchi.

Novel coronavirus SARS-CoV-2 and COVID-19, besides affecting the respiratory system, may lead to central and peripheral nervous system disorders and also cause muscular symptoms. The authors review the literature and own clinical case with respect to nervous system involvement in COVID-19 patients. There is a correlation between the severity of COVID-19 and the severity and frequency of neurologic complications. Severe neurologic symptoms are primarily observed in patients with severe COVID-19. Neurologic-associated symptoms may include stroke, acute necrotizing encephalopathy, and Guillen-Barre syndrome. Diseases that potentially aggravate COVID-19 and increase the risk of neurologic complications include arterial hypertension, diabetes, chronic diseases of the heart and respiratory system. The probable impact of human coronaviruses on chronic and progressive diseases of the nervous system with particular respect to multiple sclerosis is reviewed. A triage plan for stroke and MS patients during the COVID-19 pandemic, depending on the risk of coronavirus infection, is presented.

[Kinematic parameters of gait in patients with supra- or subtentorial focus location during the early rehabilitation period after ischemic stroke]. / Kinematicheskie parametry pokhodki pri supra- i subtentorial'noi lokalizatsii ochaga v rannem vosstanovitel'nom periode ishemicheskogo insul'ta.

OBJECTIVE: To study kinematic gait parameters during early rehabilitation period in patients with supra- or subtentorial ischemic stroke (IS). MATERIAL AND METHODS: We examined 24 patients (11 women, 13 men, age 61.3±8.2) 4-6 weeks after stroke onset. 15 patients had supratentorial IS (middle cerebral artery location), 9 patients had subtentorial IS (brainstem and cerebellum). NIHSS score was 6.4±0.6/6.1±0.8, modified Ashwort scale score - 0.5±0.6/0.4±0.7, hand paresis - 3.4±0.9/3.7±0.7, leg paresis - 4.1±0.7/4.0±0.8 points. Kinematic gait parameters were recorded on video analysis system Physiomed Smart (Physiomed, Germany, Davis protocol). RESULTS: Gait kinematic parameters in paretic and in unaffected leg were changed in both groups. Patients with supratentorial lesion had on paretic side exaggerated pelvic obliquity, an excessive internal rotation and amplitude of movements in the paretic hip joint, and an insufficient plantar extension on both sides. Patients with subtentorial stroke had exaggerated pelvic tilt forward, excessive flexion and insufficient extension of the hip joint, insufficient extension of the knee joint, excessive plantar flexion, and insufficient plantar extension on both sides. CONCLUSION: Patients with supra- or subtentorial IS with muscle weakness less than 3-4 points and slightly changed or normal muscle tone differed in kinematic parameters in pelvic motions and in joints of paretic and unaffected lower extremity. These results highlight the importance of differentiating rehabilitation techniques according to supra- or subtentorial focus location and cerebellar involvement.

[Development of early diagnosis of Parkinson's disease based on the search for biomarkers such as premotor symptoms and changes in blood]. / Razrabotka rannei diagnostiki bolezni Parkinsona na osnove biomarkerov v vide premotornykh simptomov i izmenenii v krovi.

OBJECTIVE: To determine changes in the chemical composition of blood plasma in subjects at risk of Parkinson's disease (PD) at the prodromal stage compared with age control. MATERIAL AND METHODS: Subjects at risk were selected for the presence of characteristic premotor symptoms, including impairments of sleep, olfaction and constipation.The risk group included 12 people, the control group - 8 people. RESULTS: Among seven catecholamines and their metabolites detected in the blood, only the concentration of L-dioxiphenylalanine (L-DOPA) changed (decreased) in subjects at risk compared with the control. A decrease in the concentration of L-DOPA is considered as a manifestation (marker) of selective degeneration of central and peripheral catecholaminergic neurons in PD. In contrast to L-DOPA, the concentration of seven of the twelve detected sphingomyelins in the blood of the subjects at risk increased. Given that a change in the metabolism of sphingomyelins is associated with processes such as apoptosis, autophagy, and synucleinopathy, an increase in their concentration in the blood of patients at risk is considered as a manifestation of systemic general degeneration of central and peripheral neurons. Finally, in the blood of subjects at risk, we found a trend towards a decrease in the concentration of urates, which are endogenous neuroprotectors. CONCLUSION: The changes in the level of L-DOPA, sphingmyelins and urates in the blood of subjects at risk may serve as diagnostic markers of PD at the prodromal stage.

[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.

[Immunological predictors of acute post-stroke period]. / Immunologicheskie prediktory techeniia ostrogo perioda insul'ta.

INTRODUCTION: At the present time, there is an increased interest in the search for biological predictors of the course and outcome of ischemic stroke (IS). Numerous studies have shown the relationship between neuroinflammation (in the brain) and systemic inflammatory response (in the blood). AIM: To study the relationship of inflammatory and autoimmune markers in blood serum of patients with acute ischemic stroke (on the 1st day) with the dynamics of the severity of neurological deficit (on the 1st and 10th day) and to assess the predictive ability of these indicators. MATERIAL AND METHODS: Twenty-two patients in the acute period of IS (mean age 60±15.5 years) were examined. The severity of neurological deficit was assessed by ESS and NIHSS. The enzymatic activity of leukocyte elastase (LE), α1-proteinase inhibitor (α1-PI), level of autoantibodies to S-100B and MBP in serum was determined. The control group consisted of 33 healthy subjects. Blood samples were carried out on the 1st day of the post-stroke period, the clinical examination was performed on the 1st and 10th day of observation. RESULTS: Depending on the dynamics of neurological symptoms by the 10th day of observation, two subgroups of patients were identified. The1st subgroup was characterized by the normalization of neurological deficit (n=10). In the 2nd group, the negative dynamics of neurological deficit/lack of any positive changes was observed (n=12). Both subgroups demonstrated the increase in the LE and α1-PI activity as compared to the control (p=0.0019, p=0.00079; p=0.038, p=0.00041, respectively). The highest LE activity was detected in the 1st subgroup (p=0.035). The high level of autoantibodies to MBP was also observed in the 1st subgroup as compared to the control and the 2nd group (p=0.047, p=0.03, respectively). The 2nd subgroup was characterized by a higher functional activity of acute phase protein α1-PI (p=0.04). Using regression analysis, a model for predicting the course of the early post-stroke period depending on the determined immunological parameters was developed. CONCLUSION: The results suggest that the studied inflammatory and autoimmune markers may be possible predictors of the course of the early post-stroke period.

[Hyperhomocysteinemia and endothelial dysfunction in patients with cerebral vascular and autoimmune diseases]. / Gipergomotsisteinemiia i éndotelial'naia disfunktsiia pri sosudistykh i autoimmunnykh zabolevaniiakh golovnogo mozga.

Endothelial dysfunction today is recognized as one of the leading factors in the pathogenesis of diseases of the central nervous system of various etiologies. Numerous studies have shown the role of hyperhomocysteinemia in the development of endothelial dysfunction and prothrombogenic state. The most important condition in the development of multiple sclerosis (MS) is dysregulation of the blood-brain barrier (BBB) and transendothelial leukocyte migration. It has been proven that homocysteine also contributes to the damage of neurons by the mechanism of excitotoxicity and induction of apoptosis of neurons. These processes can be one of the factors of neurodegenerative brain damage, which plays a leading role in the progression of MS. This review describes the pleiotropic effect of homocysteine on these processes and its role in the pathogenesis of MS.

[Possibilities of digital fluorography and other X-ray methods in the detection of carotid atherosclerosis]. / Vozmozhnosti tsifrovoi fliuorografii i drugikh luchevykh metodov v vyiavlenii ateroskleroza sonnykh arterii.

AIM: To evaluate possibilities of routine X-ray methods for the diagnosis of atherosclerosis of carotid arteries. MATERIAL AND METHODS: At the initial stage of the study, 468 X-ray radiograms of the cervical spine with the detailed description of soft tissues and projections of the neck vessels were studied. The next stage included evaluation of 'screening' abilities of digital fluorography of lungs (886 X-ray radiograms were analyzed). The last stage is a current pilot project aimed to introduce opportunistic screening of atherosclerosis of carotid arteries using X-ray and ultrasound examination of the thyroid gland taking into account disease history collected with help of a special questionnaire and clinical examination. RESULTS AND CONCLUSION: The study shows a high specificity of the shadows in the projections of the neck vessels as a sign of atherocalcinosis. During mass examinations these X-ray findings are useful to identify patients who need duplex scanning and other high-tech methods.

[The dynamics of markers of apoptosis in the acute period of ischemic stroke]. / Dinamika markerov apoptoza v ostrom periode ishemicheskogo insul'ta.

AIM: To study the dynamics of markers of apoptosis (Bcl-2, p53) in serum in the acute period of ischemic stroke (IS) in comparison to the severity of the neurological condition and the volume of infarct. MATERIAL AND METHODS: Fifty-one patients (mean age 60.5±2.2 years) with the first ever carotid IS were examined within the first 24 hours. The comparison group consisted of 20 patients (mean age 58.7±2.1 years) with chronic cerebral insufficiency. Clinical and neurological dynamic examinations with assessment of neurological deficit using (NIHSS), CT/MRI of the brain; ELISA immunoassay of p53 and Bcl-2 in blood serum were carried out. RESULTS AND CONCLUSION: Significantly higher levels of p53 and of Bcl-2 were shown on the 3rd and 10th days in patients with IS compared to the control group (p<0.05). An increase in the content of p53 was positively correlated with the severity of neurological deficit (NIHSS≥10) on the first and third days of acute IS and with larger amounts of damage to the brain parenchyma according to the MRI study from the first day of IS and all subsequent days. High levels of Bcl-2 were positively correlated with the large volume of brain damage only on the 10th day of IS (p<0.045). The results confirm the active involvement of pro- and antiapoptotic processes in the formation of delayed neuronal death in the brain, which are important components of damaged brain tissue in IS.

[The improvement of quality of life of patients with multiple sclerosis over 15-year period]. / Uluchshenie pokazatelei kachestva zhizni bol'nykh rasseiannym sklerozom za 15-letnii period.

In this article, the authors compared the results of the studies on quality of life (SF-36 questionnaire) of large groups of patients with multiple sclerosis conducted in 2000-2003 and 2012-2016 years.

[Issues of the current terminology in multiple sclerosis]. / Voprosy sovremennoi terminologii pri rasseiannom skleroze.

New terminology used by neurologists with multiple sclerosis (MS). The current use of terms 'definite' MS, 'MS signs', 'retrobulbar neuritis' and 'optic neuritis', 'relapse and exacerbation, types of MS course, criteria of effectiveness of MS therapy, NEDA, NEP, NEPAD; the classification therapy methods - 'escalation', 'induction' and therapy of immune reconstitution (TIR), therapy of maintenance/escalation (TME) and discussed.

[The efficacy of semax in the tretament of patients at different stages of ischemic stroke]. / Éffektivnost' semaksa pri lechenii bol'nykh na raznykh stadiiakh ishemicheskogo insul'ta.

AIM: To evaluate the efficacy of semax and timing of rehabilitation on the dynamics of plasma BDNF levels, motor performance, and Barthel index score in patients after ischemic stroke (IS). MATERIAL AND METHODS: One hundred and ten patients after IS (43 men, 67 women, mean age 58.0±9.7, Ме 63 years) were examined. All patients were divided into early (89±9 days) and late (214±22 days) rehabilitation groups. Each group was subdivided into semax+ and semax- subgroups. Standard regimen of semax included 2 courses (6000 mcg/day) for 10 days with 20 day interval. Plasma BDNF levels, motor performance on the British Medical Research Council scale and Barthel index were assessed in all groups. RESULTS: Administration of semax, regardless of the timing of rehabilitation, increased BDNF plasma levels which remained high during the whole study period. In semax- subgroups high BDNF plasma levels were positively correlated with early rehabilitation. Administration of semax and high BDNF levels accelerated the improvement and ameliorated the final outcome of Barthel score index. There was a positive correlation between BDNF plasma levels and Barthel score, as well as a correlation between early rehabilitation and motor performance improvement. The correlation between BDNF plasma levels and Barthel score was modified by the timing of rehabilitation. CONCLUSION: Early rehabilitation and administration of semax increase BDNF plasma level, speed functional recovery, and improve motor performance.

[Thrombolytic therapy of ischemic stroke]. / Tromboliticheskaia terapiia ishemicheskogo insul'ta.

Reperfusion therapy is one of the main treatment strategies of ischemic stroke. The first studies of the efficacy of thrombolytic medications started form the use of streptokinase and fibrinolysin in patients with ischemic stroke in late 50 - early 60 of the XX century in the United States, Soviet Union, and Western Europe. After the development of recombinant tissue plasminogen activator, thrombolysis became one of the main methods of reperfusion in patients with acute ischemic stroke, acute myocardial infarction, or other acute vascular thrombotic events. Later, modified variants of tissue plasminogen activator with prolonged clearance time, high fibrin-selectivity, and bolus delivery were introduced. Another group of thrombolytic agents includes derivatives of flora and fauna - external plasminogen activators, of which streptokinase, staphylokinase, and desmoteplase are most common drugs. These medications are not a structural part of the human organism, and overcoming of immunogenicity while preserving fibrinolytic activity and fibrin specificity is one of the main tasks in applying them in clinical practice.

[Current algorithms of diagnosis and treatment of multiple sclerosis based on the individual assessment of the patient]. / Sovremennye algoritmy diagnostiki i lecheniia rasseiannogo skleroza, osnovannye na individual'noi otsenke sostoianiia patsienta.

This review presents the current knowledge on diagnosis, therapy of relapses of multiple Sclerosis (MS) and disease-modifying therapy (DMT) in MS. Algorithms of diagnosis and therapy of MS are presented. Special attention is paid to the analysis of efficacy, tolerability and safety of DMT in MS.

[Pathogenetic aspects of the development of acute focal cerebral ischemia]. / Patogeneticheskie aspekty formirovaniia ostroi fokal'noi ishemii golovnogo mozga.

Current concepts on the main mechanisms of brain damage in ischemic stroke are considered. Chemical regulation of physiological and pathological processes of maintaining cellular pool is supported by a multistep system that included compounds of different structure and complexity. A complex assessment and comparison of the processes taking place during the development of acute local cerebral ischemia (necrosis, apoptosis, autoimmune inflammatory reaction, neuroplasticity) can help in the objectification and prognosis of individual characteristics of the course and outcome of ischemic stroke. Understanding of the cascade of events that occur during the acute ischemic damage is critical for determining current and future diagnostic and therapeutic approaches.