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CNAA / Theses / 2022 / June /

Epidemiology, determinants and prediction of ischemic stroke in children


Author: Sprincean Mariana
Degree:doctor habilitat of medicine
Speciality: 14.00.13 - Neurology
Year:2022
Scientific consultants: Svetlana Hadjiu
doctor habilitat, professor
Ninel Revenco
doctor habilitat, professor, Nicolae Testemitanu State University of Medicine and Pharmacy of the Republic of Moldova
Larisa Spinei
doctor habilitat, professor, Nicolae Testemitanu State University of Medicine and Pharmacy of the Republic of Moldova
Institution: Nicolae Testemitanu State University of Medicine and Pharmacy of the Republic of Moldova

Status

The thesis was presented on the 29 June, 2022
Approved by NCAA on the 30 September, 2022

Abstract

Adobe PDF document – 0.93 Mb / in romanian

Thesis

CZU 616.831-005.4-053.2

Adobe PDF document 6.75 Mb / in romanian
359 pages

Keywords

central nervous system, ischemic stroke or ischemic cerebral vascular accident, neurotrophic factors, vascular endothelial growth factor, ciliary neurotrophic factor, S100B protein, endoglin (CD105), interleukin 6, antiphospholipid antibodies, neuroinflammation, angiogenesis

Summary

Structure of thesis: introductions, 5 chapters, synthesis of obtained results, general conclusions and practical recommendations, bibliography of 310 sources, 279 pages of basic text, 37 tables, 102 figures, and 5 annexes. Obtained results were published in 60 personal scientific works.

Studied area: neurology, pediatrics

The aim and objectives of the work. Research of epidemiology, determinants, pathogenetic and clinico-paraclinical aspects of ischemic stroke (IS) in children for the analysis of morbidity, mortality and disability of this disease in the Republic of Moldova and the proposal of some methods of prediction and prophylaxis.

Scientific novelty and originality. The conducted study represents a first attempt of complex, integral research of the epidemiology, determinants and methods of prediction of neonatal and pediatric IS at national level. Research of perinatal causes using medical genetic and postnatal counseling by complex multidisciplinary analysis that allows the systematization of IS risks in children and the reasoning of some measures of prophylaxis. For the first time, the markers of neuroinflammation, oxidative stress, and angiogenesis were studied, including: interleukin 6, S100B protein, vascular endothelial growth factor, endoglin, ciliary neurotrophic factor in patients/children with acute ischemic stroke, which will allow highlighting the role of the neuro-inflammatory/immune system in the pathogenetic mechanisms of the process in children. The results of this study can find the framework of a scientific approach to the development of diagnostic as well as predictive and treatment strategies in neonatal and pediatric IS based on the variability of the causes leading to IS in newborns and infants.

Fundamentally new scientific and practical results. The research of the IS structure in children of Republic of Moldova, i. e., incidence, prevalence, morbidity and mortality, allowed the recognition of this disease as an important cause of morbidity and infantile neurological disability. The analysis of the profile of the causes that determined the occurrence of IS in the pediatric population of the Republic of Moldova allowed the systematization of the IS etiologies according to the age category and the elucidation of the methods of prophylaxis of this condition. The supervision of pregnant women in the high-risk group for perinatal problems allowed to determine the implicit role of the medico-genetic counseling and to identify the prenatal factors involved in IS. The exploration of new methods of neuro-immunological research lead to the highlighting of some neuro-inflammatory/immune mechanisms involved in IS, which will contribute to the increase of the knowledge in the respective field and the optimization of effective therapeutic and prophylactic strategies and directions. The obtained results were useful in the development of a clinical etiological classification of IS in children, and of the algorithm of diagnosis and conducting of the pediatric patient with IS in the light of clinical-pathogenetic aspects, as well as in the development of educational programs for prophylaxis and treatment of children with IS, of the National Register of children with IS, of the National Clinical Protocol, of the surveillance programs of children suffered from IS, being a methodological support for physicians in the country, thus reducing the economic burden caused by neuromotor disability following neonatal and pediatric IS.

Theoretical significance based on the development of a complex methodological and conceptual framework which has a multidisciplinary and interdisciplinary character, in the analytical plan of scientific and practical exploration of the issue of prediction of neonatal and pediatric IS. The concept of IS in children keeping in mind of neuroinflammation allowed the understanding of some mechanisms involved and the need to approach the child according to the changes established in the conditions of neuronal tissue damage. The assessment of the role of neuroinflammatory factors in the lesions caused by cerebral ischemia completes the data on the pathogenesis of IS in children and the highlighting of some associations between the clinical form of the disease, the relative rate of modified serum values of immunoenzymatic markers and the relevant imaging changes. The analysis of the determinants responsible for IS allowed the development of an algorithm of conduct of pregnant women and of newborns and children at risk for this condition as well as the proposal of recommendations for the prevention of IS in children.

The applicative value of the theme. The analysis of the structure of IS in the Republic of Moldova in children of different ages allowed the assessment of the frequency of the disease in relation to the general population, obtaining the data regarding the incidence and prevalence of IS in children, i. e., morbidity, disability and mortality. The high rate of epidemiological indexes of IS in children imposed the need for a medical-genetic counseling of pregnant women in the high-risk group and a mandatory screening in all children predisposed to IS. The evaluation of the neuro-endocrine/immune mechanisms in children with IS allowed the assessment of importance of some biomarkers investigated in correlation with the dimensions of the ischemic focus of IS and with the age of the child. The new data obtained on the role of specific markers of neuroinflammation, oxidative stress, angiogenesis, i. e. interleukin 6, S100B protein, vascular endothelial growth factor, endoglin CD105, ciliary neurotrophic factor which are contribute to the prediction of the evolution of neurological manifestations in patients with IS and the implementation of modern diagnostic and treatment strategies by cerebral integrative adaptation in the conditions of neuronal cytoprotection and neuroplasticity of vascular processes. The systematization of IS risks in children allowed the optimization of diagnosis, treatment and prophylaxis, as well as the elaboration of a clinical diagnostic protocol of IS in children.

Implementation of scientific results. The results of the presented work and the application of the methods of IS prediction in the child were implemented in the Clinic Pediatrics and Pediatric Neurology of the SPMI Institute of Mother and Child, SPMI Municipal Clinical Hospital No. 1 and in the postgraduate teaching process for neurologists residents, neurologists pediatricians, pediatricians and other specialties, as well as in the process of continuous education of the Pediatric Neurology Clinic, Department of Pediatrics of the State University of Medicine and Pharmaceutics Nicolae Testemitanu, of the Department of Molecular Biology and Human Genetics of the State University of Medicine and Pharmaceutics Nicolae Testemitanu, of the neuropediatricians, pediatricians, and family doctors. There were registered 4 patents, 14 certificates of innovations and 12 acts of implementation of the results.