Volosovets A. Clinical and pathogenetic characteristics and risk factors of acute ischemic stroke depending on the time of occurrence: features of diagnosis, treatment and prognosis

Українська версія

Thesis for the degree of Doctor of Science (DSc)

State registration number

0518U002549

Applicant for

Specialization

  • 14.01.15 - Нервові хвороби

10-10-2018

Specialized Academic Board

Д 64.566.01

Essay

Brain stroke is a set of various injuries, neurological disorders, which are the result of acute cerebrovascular accident and are caused by various pathophysiological mechanisms. Significant role in the pathogenesis and peculiarities of the course of a cerebral stroke is the time of day, which involves the initiation of pathological symptoms of cerebral stroke. Despite the common pathophysiological mechanisms of the formation of damage to the nervous tissue, cerebral strokes that have arisen at different times of the day, show the differentiated character of the course of symptoms and have different predictors of the formation of the pathological focus. It is the study of these features and the identification of the most informative predictors of ischemic risk and is devoted to this work. The purpose of the work is to improve risk prediction and optimize treatment and secondary prevention of acute ischemic stroke based on a comprehensive analysis of the interconnection of polymorphous variants of genetic markers with features of the course and prognosis of ischemic stroke, depending on the time of occurrence. To optimize the analysis of the data obtained, all patients were divided into 3 groups according to the period of the day when an ischemic stroke occurred: 1 group, patients suffering from cerebral ischemia during the day (8:00-14:59); Group 2, among patients whose stroke was observed in the evening (15:00-21:59); Group 3, where patients had an ischemic stroke at night (22:00-7:59). All patients had a clinical neurological examination of patients using structured scales, computed tomography, magnetic resonance imaging and diffusion-weighted MRI of the brain, transcranial dopplerography, ultrasound dopplerography of the major vessels of the head in the extracranial department, molecular genetic methods for the study of polymorphic variants glands of the folate and thrombophilic systems of patients by polymerase chain reaction and polymorphism of the length of the restriction fragment, laboratory and statistical methods. On the basis of the obtained data in the dissertation work the theoretical substantiation of new ways of solving the actual scientific problem concerning the peculiarities of occurrence, course and clinic of ischemic strokes is presented, depending on the time of origin and pathogenetic factors, the role of genetic and exo- and endogenous shifts are revealed. Based on the obtained data, the criteria for diagnosis of acute ischemic stroke were developed based on the time of occurrence, optimized algorithm of treatment tactics and secondary prevention of stroke. For the first time, on the basis of the analysis of social risk information informativeness and probabilistic statistical analysis methodology, a specialized prognostic scale for assessing the risk of ischemic stroke in various periods of the day (Se = 97.9%; Sp = 77.2%) was developed and proposed for use in the examination of patients. allowed to determine the risk of recurrence of stroke and to introduce an individualized prophylaxis of the disease. The genetic analysis of the MTHFR C7661T gene polymorphism among patients with a "day" stroke was found to have a significant concentration of mutated homozygous TT form (20.5%), which makes it highly predisposed to thrombotic formation, whereas for patients with evening and night periods of stroke the lower frequency of TT mutation (3.5% and 4.3% respectively) was more characteristic, affecting homocysteine metabolism and posing a threat to the cardiovascular system (p < 0.05). The dependence of the features of the ischemic stroke clinic on the time of occurrence was first established. The difference in the rate of recovery between the main and control groups with the "evening" stroke was only 4.7%, but even in these patients, the risk of ineffective treatment decreased by 50.7% (NNT was 26.3) in the case of modification therapies. Recovery rate in the 3rd group was 23.4% higher than the control group. Patients in the 3rd group demonstrated a reduction in the risk of ineffectiveness of therapy by 58.9% (NNT = 5.6). The optimized prophylactic regimens for each group of patients showed significant efficacy compared with control groups in reducing the incidence of recurrent ischemic stroke during the monitoring period at 3.06 (group 1), 2.4 (group 2) and 2.09 times (group 3) comparatively with control groups.

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