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CNAA / Theses / 2016 / July /

Diagnostic particularities and therapeutic perspectives for children with residual disorders of central nervous system

Author: Hadjiu Svetlana
Degree:doctor habilitat of medicine
Speciality: 14.00.13 - Neurology
Scientific consultants: Ion Iliciuc
doctor habilitat, professor, Nicolae Testemitanu State University of Medicine and Pharmacy of the Republic of Moldova
Ninel Revenco
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


The thesis was presented on the 15 July, 2016
Approved by NCAA on the 6 October, 2016


Adobe PDF document1.04 Mb / in romanian


CZU 616.831-053.2-07-08

Adobe PDF document 16.00 Mb / in romanian
322 pages


Central Nervous System (CNS), neonatal encephalopathy (NE), perinatal cerebral injuries (PCI), hypoxic-ischemia (HI), residual disorders (RD), neurotrophic factors (NF), brain derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF)


Structure of the thesis: introduction, 5 chapters, synthesis results, general conclusions and practical recommendations, bibliography containing 297 titles, 241 pages of main text, 34 tables, 86 figures and 23 annexes. The obtained results are published in 72 scientific works.

Study domain: neurology, pediatrics.

Objectives: explanation of different etiopathogenic aspects concerning neuroimmune processes and evolutive clinical and paraclinical particularities, in order to optimize the clinical diagnosis, the prognosis and the management of residual disorders of the CNS in children with cerebral injuries secondary to perinatal hypoxic-ischemic trauma (PHIT).

Novelty and scientific originality: we conducted a retrospective-prospective witness-case study on PCI secondary to HI perinatal trauma in order to provide an early detection and the assessment of RD of CNS in the light of continuous neurodevelopment in correlation with clinical, neurophysiological and neuroimaging manifestations. We elaborated the first classification of RD that allows to deepen and enlarge the concept of a continuum of neurodevelopmental periods of the child and the corresponding RD.

Results: we elaborated a new integral vision of cerebral perinatal hypoxic ischemic injuries related to anamnesis, the evolutive clinical outcomes, as well as the neurophysiological, neuroimaging and neuroimmune ones; the assessment of rates of risks involved in triggering NE HI and the mathematical individualized analysis according to the number of variables in order to estimate the probability of neurological sequelae. We provided the first complex diagnosis and the classification of RD of the CNS using the continuum of neurodevelopmental periods. We systemized the neurological syndromes and the evolutive diagnosis in nurslings and infants (up to 3-5 years old). We studied the pathogenetic aspects of cerebral injuries through the seric levels of NF (BDNF and CNTF), their concentrations being correlated to the severity of the injury, to the degree of motor and neuropsychic development, to the severity of neurological syndrome and chronological diagnosis. There were also different levels of NF depending on the nature of neurophysiological and neuroimaging changes, as well as the type of residual disorders. We implemented noninvasive methods of neuropsychic assessment and early diagnosis, thus we were able to determine the early clinical symptomatology and to found pathogenetic links important to the creation of new perspectives concerning the optimization of diagnosis, prognosis and therapeutic management of RD. And finally, we identified the predictive factors of the cerebral perinatal hypoxic ischemic injuries.

Theoretical significance consists in improving fundamental knowledge concerning correlative links and changes of neuroimmune, morphofunctional and neurophysiological status of children with cerebral injuries secondary to PHIT, as well as the predictive value of anamnesis, electrophysiological, imaging and NF (BDNF and CNTF) changes for early diagnosis and prognosis of RD of the CNS, thus representing a strong argument in favor of neuroprotective therapeutic strategies for the prevention of neuropsychomotor handicap.

Applicative value: We structured anamnesis, syndromological and evolutive diagnosis of CI secondary to PHIT, generating RD of the CNS in children. We developed a classification of RD concerning the continuum of the child’s neurodevelopment, that allows to optimize the diagnostic and therapeutic processes in order to enhance the neuroprotective effects. We developed questionnaires, behavioral algorithms and practical recommendations concerning etiopathogenic aspects and the optimization of evolutive diagnosis, management and effectiveness of neuroprotective therapies.

Scientific results were implemented in Neurologic Clinics of IMSP Institute of Mother and Son, in Municipal Clinic Hospital Nr.1 as well as during the postgraduate didactic process of medicine residents: neurologists, neuropediatricians, pediatricians and other specialties with allied cycles to the field of “Pediatric neurology”; the postgraduate training of neuropediatricians, pediatricians, general practitioners at Pediatrics Department of SUMP „Nicolae Testemiţanu”. Ten acts of implementation of our results were recorded.