## 2 Materials and Methods
A total of 510 children with acute IS were included in the study, of which 402 were examined retrospectively and 108 children prospectively. The gender characteristics of the children included in this study showed a predominance of boys--317 (62.2%; 95% CI [57; 58; 59; 60; 61; 62; 63; 64])--compared to girls--193 (37.8%; 95% CI [33; 64; 65; 66; 67; 68; 69; 70; 71; 72; 73; 74; 75; 76; 77; 78; 79; 80; 81; 82; 83; 84; 85; 86; 87; 88; 89; 90; 91; 92; 93; 94; 95; 96; 97; 98; 99; 100; 101; 102; 103; 104;  
children, 72 (66.7%; 95% CI [62.16-71.24]) were boys and 36 (33.3%; 95% CI [28.76-37.84]) were girls with neonatal or pediatric IS. Of the total of 510 cases of acute IS in children, according to the study results, 362 (71%, 95% CI [68.99-73.01]) occurred in the neonatal period and 148 (29%, 95% CI [26.99-31.01]) in early childhood and adolescence. Among the neonatal IS cases, 242 (66.9%; 95% CI [64.43-69.37]) were boys, and 120 (33.1%; 95% CI [30.63-35.57]) were girls. It was found that, in newborns, the anterior and middle circulation were predominantly affected--228 (63.0%; 95% CI [60.46-65.54])--as well as the left cerebral hemisphere--245 (67.7%; 95% CI [65.24-70.16]). Multifocal brain lesions were found in about one-third of the children--119 (32.9%; 95% CI [30.43-35.37]). For monitoring, children with IS were selected, and their perinatal history as well as the factors of high risk for IS development were evaluated. In the approach to acute IS in children, the following aspects were monitored: the degree of central nervous system (CNS) impairment at birth and later in children who had suffered acute IS, the evolution of neurological manifestations during the neonatal and childhood periods, and the development of clinical manifestations in the first months after IS (paroxysmal manifestations and motor, cognitive, and behavioral performance: communication, memory, intelligence, and social adaptability). Additionally, the following were evaluated: (1) immunoenzymatic changes in VEGF, CNTF, IL-6, endoglin, APAa, and the S100B protein, as well as the VEGF and S100B protein levels, assessed during the acute phase and six months after IS; (2) EEG patterns; and (3) CT and MRI brain imaging characteristics. Patients were examined in neurological departments, intensive care units, and neonatal neurology. The periodic observation of patients was conducted repeatedly, depending on the established diagnoses and the child's age. All data were included in the questionnaire (Annex 1), comprising interviews including data on risk factors, determinants, and clinical outcomes after the Amiel-Tison test (for neonates and children up to 3 months) and the PedNIHSS scale (after 3 months). To assess the functional and structural changes in the brain, additional exams such as CT, MRI, and EEG were used. Investigations were conducted in a stationary setting. EEG was performed based on existing indications. Imaging examinations were performed on 108 children with acute neonatal or pediatric IS in the prospective study group. The results of the additional investigations confirmed the diagnosis of acute IS in the children, assessed the dimensions of the cerebral ischemic focus, and evaluated the prognosis of the disease.