Valerii V. Gorev

Background. There are no standardised protocols for the treatment of ischaemic stroke in children to date. Objective. To evaluate outcomes in patients with a confirmed diagnosis of acute arterial ischaemic stroke who received antithrombotic therapy at the Centre for Cerebrovascular Diseases in Children and Adolescents (the Centre) based at the Morozovskaya Children's City Clinical Hospital of the Moscow City Health Department. Materials and methods. A single-centre retrospective study was conducted, including 145 patients with confirmed arterial ischaemic stroke between 2019 and 2023. All patients underwent a comprehensive examination, including assessment of neurological status using the PedNIHSS scale, neuroimaging (MRI with angiography), extensive laboratory testing of the haemostasis system, and cardiac and vascular evaluation. Aetiological classification was performed according to the CASCADE criteria. Four antithrombotic therapy regimens were used: anticoagulant therapy with unfractionated heparin with or without transition to low molecular weight heparin, or monotherapy with low molecular weight heparin – 21 patients (14.5%); monotherapy with acetylsalicylic acid – 25 patients (17.2%); combination therapy with transition from heparins to acetylsalicylic acid within 3-6 months – 99 patients (68.3%). Doses were adjusted based on anti-Xa activity monitoring. Systemic thrombolysis with alteplase was performed in 17 patients (11.7%). Long-term outcomes were assessed at a median of 41 months using the modified Rankin Scale and the PSOM scale. Statistical analysis was performed using non-parametric methods. Results. In this cohort the median age was 4 years 5 months; 64.8% were boys. Aetiology remained undetermined in 21.4% of cases; arteriopathies were identified in 18.6%, and multifactorial genesis in 15.9%. Thrombolytic therapy was administered to 17 patients (11.7%). No statistically significant differences in long-term outcomes were found between the different antithrombotic therapy regimens. Recurrent stroke was recorded in 8.3% of patients. Post-stroke epilepsy developed in 9.3% and was associated with more severe neurological deficit (p < 0.05). In patients with cardioembolic stroke in the perioperative period, a significant decrease in antithrombin III activity (p = 0.005) and protein C activity (p = 0.006) was observed. In the group of patients with post-stroke epilepsy, long-term outcomes were significantly worse than in patients without epilepsy, which likely indicates a negative impact of epileptogenesis on neuroplasticity processes. Thrombolytic therapy was not associated with severe bleeding or recurrences. However, its benefits require further study due to the lack of randomisation. Conclusion. Anticoagulants, antiplatelet agents, and thrombolysis are used in the treatment of acute arterial ischaemic stroke in children, but to date, no proven advantages of any specific treatment regimen for arterial ischaemic stroke in children have been established.

Atelectasis, characterized by partial or complete collapse of the lung or its lobe/segment, is a common and serious clinical problem in children. No proven treatments for atelectasis exist. Dornase alfa (recombinant human deoxyribonuclease) reduces the viscosity of purulent secretions in the bronchi and is effective in patients with cystic fibrosis. Data on the use of dornase alfa in other diseases are limited. This article presents clinical observations of two girls – a 2-month-old with lung hypoplasia due to diaphragmatic hernia and a 7-year-old with status asthmaticus and acute respiratory distress syndrome, hospitalized in intensive care units and requiring extracorporeal membrane oxygenation therapy, who showed positive dynamics in the form of atelectasis resolution during dornase alfa therapy. The presented clinical observations, as well as the analysis of cases described in the literature on the use of dornase alfa in children with atelectasis, demonstrate the efficacy and safety of the drug in children of different ages, including those on extracorporeal membrane oxygenation.

Surgical treatment of central nervous system (CNS) tumors in children presents a complex medical and social challenge, driven not only by the relatively low prevalence of this pathology in pediatric practice but also by the significant heterogeneity of the disease, owing to the variability of patient age, tumor location, and histopathological structure. Despite these challenges, recent decades have seen progress in improving overall survival in children with CNS tumors, driven by the introduction of a multidisciplinary, personalized approach into clinical practice, based on modern therapeutic protocols and integrating the efforts of specialists from various fields. The introduction of molecular genetic tumor profiling methods has become particularly important in improving neuro-oncological care. The introduction of histological and molecular characteristics has become an integral diagnostic standard, allowing not only to establish a diagnosis, prognosis, and treatment strategy, but also to identify targets for targeted therapy. We present an analysis of surgical interventions in children with CNS tumors at a multidisciplinary hospital in Moscow. Interdisciplinary collaboration among neurosurgeons, oncologists, neurologists, radiologists, pathologists, and other related specialists plays a key role in achieving optimal treatment outcomes and improving patients’ quality of life. The study included 417 children who underwent surgery for CNS tumors at the Morozov Children’s City Clinical Hospital of the Department of Health of Moscow. The analysis included tumor resection volumes according to the Gnekow classification, CSF shunt procedures, complications, tumor location, histomolecular variants, overall survival, and mortality in this cohort of patients.

Diffuse astrocytoma with MYB or MYBL1 alteration is a newly defined molecular subtype of pediatric-type low-grade diffuse gliomas. This tumor type was first included in the 2021 World Health Organization classification of tumors of the central nervous system. To date, only a limited number of cases with a similar histo-molecular profile have been reported in the literature. The tumor is characterized by a favorable clinical course and prognosis. This report presents a clinical case of a brain astrocytoma with MYB/MYBL1 alteration in a 2-year-old girl. A distinctive feature of this case is the absence of any specific antitumor treatment – the patient did not undergo chemotherapy or radiotherapy. Only stereotactic biopsy was performed, followed by histological and molecular verification of the diagnosis. Eight years after the initial diagnosis, the disease remains stable, with some reduction in tumor size observed over time. According to our data, the presented case of MYB/MYBL1-altered astrocytoma is unique within the Russian medical literature.

Background. Diffuse brainstem tumors account for 10—20% of all brain tumors in children. These neoplasms are the leading cause of death in pediatric neuro-oncology. There are no effective treatments for this disease. Overall survival rarely exceeds 1.5—2 years. Objective. Biopsy of diffuse brainstem tumors to determine their histological type and molecular genetic markers; to identify potential targets for targeted therapy. Material and methods. In 2021—2025, 26 patients with diffuse brainstem tumors underwent surgery at the Morozovskaya Children’s Clinical Hospital. Age of patients was 1.5—17 years, duration of disease — from 1 week to 13 months. There was primary tumor in 96% of cases. Preliminary diagnosis was based on clinical presentation and MRI. Stereotactic biopsy using BrainLab neuronavigator via transcerebellar approach was performed in 24 patients, open biopsy — in 2 cases. Results. The tumor was verified in 24 (92%) patients. Brain tissue was obtained from two patients. According to morphological data, 80% of patients had diffuse midline glioma. Ganglioglioma was detected in one case, high–grade glioma in one case, and low-grade glioma in one case. All patients underwent immunohistochemical examination of specimen, and 58% were examined using the NGS program. The H3K27M mutation was detected in 71% of cases, BRAF-V600E mutations in 2 patients, and FGFR2 gene mutation in 1 patient. Targeted therapy was based on information about mutations. The overall 2-year survival rate was 20%, event-free 2-year survival — 0%. Event–free survival of a patient with the BRAF-V600E mutation who received targeted therapy was 21 months. Conclusion. Stereotactic biopsy of diffuse brainstem tumors can be performed safely. Identification of targets for personalized therapy may be essential for management of these patients.

Objective. To assess the efficacy and safety of onasemnogene abeparvovec (OA) in children with spinal muscular atrophy (SMA) treated between 2021 and 2025 at a Moscow regional rare disease referral center (Morozov Children’s City Clinical Hospital). Material and methods. This study included 20 children with a confirmed diagnosis of 5q spinal muscular atrophy (SMA). Safety was evaluated in all 20 patients for up to 3.5 years following treatment, with adverse events graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v.5.0. Efficacy was analyzed in 16 patients at 8 to 37 months post-injection. Motor function was assessed using the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND), while general motor development was evaluated using the Hammersmith Infant Neurological Examination, Section 2 (HINE-2). Key motor milestones were compared to established World Health Organization (WHO) norms. Data was analyzed by stratifying patients into two groups: those identified through expanded newborn screening (Group 1) and those diagnosed via high-risk screening (Group 2). Results. In Group 1, the mean age at treatment initiation was 1.9 (1.4—2.8) months, with a mean weight of 4.8 (3.7—6.25) kg. In Group 2, the mean age at treatment was 14.8 (5.5—47) months, with a mean weight of 9 (6—13.7 )kg. Within one week post-OA administration, most patients (19/20) experienced clinical symptoms, including hyperthermia (Group 1: 8/9; Group 2: 10/11), increased regurgitation/vomiting (Group 1: 5/9; Group 2: 6/11), and decreased appetite/refusal to feed (Group 1: 3/9; Group 2: 9/11). These symptoms were more severe in Group 2, requiring intravenous and symptomatic therapy, nasogastric tube placement, and parenteral nutrition in some cases. Grade 1—2 thrombocytopenia (CTCAE v.5) was observed one week post-OA in three patients from Group 2. Elevated hepatic transaminases were observed in 16/20 children: Group 1 — 6/9 (66%), Group 2 — 10/11 (90%). In Group 1, all children experienced Grade 1 elevations (CTCAE v.5), while in Group 2, 6 children had Grade 1 elevations (54%), 2 had Grade 2 (18%), 1 had Grade 3 (9%), and 1 had Grade 4 (>20x ULN) (9%). Asymptomatic troponin I elevations were recorded in 6 children from Group 1 and 4 from Group 2. The median duration of prednisolone administration was 13 weeks (8—24) in Group 1 and 21 weeks (12—42) in Group 2. In Group 1, the mean CHOP INTEND score increased by 11.5 at 4 months, the HINE-2 score increased by 10.5 points at 4 months and 15.5 points at 6 months from baseline; all children achieved main motor milestones according to WHO norms. In Group 2, the mean CHOP INTEND score increased by 4 at 6 months and 7.2 points at 12 months from baseline; the HINE-2 score increased by 2.3 points at 6 months and 4.7 points at 12 months from baseline; five children improved their functional status, and 6/9 children acquired new motor skills. Conclusion. This study presents the findings of a long-term assessment of the efficacy and safety profile of drug OA in pediatric patients across various age groups and functional ability levels, including individuals identified through expanded newborn screening. Younger patients exhibited a significantly lower incidence of adverse events and demonstrated superior therapeutic efficacy. The majority of older children experienced either positive progression or stabilization of their condition, outcomes that were largely contingent upon their initial functional status and the duration of the pre-treatment waiting period.

Background. Congenital alveolar dysplasia (CAD) and alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) are rare, fatal, genetically determined interstitial lung diseases in infants, associated with pulmonary hypertension. Aim. Clinical, instrumental, and pathomorphological characteristics of patients with CAD and ACD/MPV. Materials and methods. Fifteen patients with CAD (9) and ACD/MPV (6) were included in a multicenter study. The following examination methods were used: echocardiography, chest X-ray, and chest computed tomography, angiopulmonography, catheterization of the right heart, whole-exome sequencing, and histological autopsy. Results. CAD and ACD/MPV were diagnosed in term infants (13/15) and manifested in the first 3 days of life with high pulmonary hypertension resistant to therapy. Deaths were recorded in the first 3 months. Conclusion. CAD and ACD/MPV have similar clinical presentations. Diagnosis can be verified through histological examination of the lungs and whole-exome sequencing.

BACKGROUND: Anaphylaxis is a severe, life-threatening systemic allergic reaction. Currently, the only biomarker of anaphylaxis recommended for use in Russian and international consensus documents is tryptase, with very limited data on the efficacy of its use in real clinical practice in children. AIM: To determine the frequency of measurement and diagnostic significance of tryptase level estimation in children with anaphylaxis within the recommended time frame in real clinical practice, as well as its relationship with the age of patients and the severity of symptoms. METHODS: The study included 128 patients aged 0 to 18 years who were hospitalized urgently in the State Budgetary Institution Morozov Children’s City Clinical Hospital due to an episode of anaphylaxis in the period from May 2022 to April 2025 and were included in the Pediatric Moscow Anaphylaxis Register. The diagnosis of anaphylaxis was verified by an expert allergist-immunologist based on clinical criteria for anaphylaxis. Serum tryptase levels were measured in patients admitted to the hospital within 3 hours of the onset of symptoms of acute allergic reaction. The patients’ clinical and laboratory parameters were entered into an online registry questionnaire and processed using a computer program, which is a system for data recording and analysis. RESULTS: Of the 128 children, 52 (40.6 %) had their tryptase levels measured within 3 hours of symptom onset. Among these, 15 (28.8 %) showed elevated tryptase levels. For the 76 children who were not assessed (due to delayed hospitalization), a higher frequency of mild anaphylaxis was observed compared to those assessed for tryptase levels (31.6 % vs 15.4 %; p = 0.037). No correlation was found between age and tryptase levels, though there was a trend toward older patients (median 12 years vs 10 years; p = 0.052) being within the timeframe for tryptase measurement. Severity of reaction did not affect tryptase concentrations. CONCLUSION: In clinical practice, tryptase levels can be measured within 3 hours of symptom onset in less than half of patients, with only one third showing elevated levels. Delayed hospital arrival in patients with mild anaphylaxis is likely to delay diagnosis and treatment.

Bronchiolitis obliterans is a rare severe complication of Stevens–Johnson syndrome and toxic epidermal necrolysis. The article presents an observation of a fatal histologically confirmed bronchiolitis obliterans in a 16-year-old patient developed as a delayed complication of Stevens–Johnson syndrome after the use of lamotrigine and nonsteroidal anti-inflammatory drugs. The diagnosis of bronchiolitis obliterans was established based on the development of severe bronchoobstructive syndrome, confirmed by a study of the external respiratory function, chronic respiratory failure 2 months after Stevens–Johnson syndrome, characteristic computed tomography signs (foci of mosaic perfusion, bronchiectasis). Bronchiolitis obliterans therapy, in addition to commonly used drugs, included the janus kinase inhibitor tofacitinib. To discuss clinical observation, a systematic review of the world literature over 45 years was conducted. 43 cases of post-Stevens–Johnson syndrome/toxic epidermal necrolysis were selected from 187 publications with an analysis of the etiology, timing of onset, spirometric and radiological signs, features of therapy and course. According to the analysis, the main triggers of Stevens–Johnson syndrome/toxic epidermal necrolysis were antibiotics (50 %) and nonsteroidal anti-inflammatory drugs (40 %), infection caused by Mycoplasma pneumoniae (12 %), and less often anticonvulsants. The average age of children with bronchiolitis obliterans was 7 years, and the average age of adults was 28 years. In 50 % of cases, the manifestation of bronchiolitis obliterans occurred 1–3 months after the start of Stevens–Johnson syndrome/toxic epidermal necrolysis. Most patients (35 %) had severe bronchoobstructive syndrome, and characteristic computed tomography signs included mosaic perfusion (75 %) and bronchiectasis (49 %). Systemic (77 %) and inhaled (35 %) glucocorticosteroids, bronchodilators (63 %), and macrolide antibiotics (26 %) formed the basis of bronchiolitis obliterans therapy. Mortality in the analyzed cases reached 30 %, complete recovery was observed in only 33 %, and 35 % of patients retained persistent bronchoobstructive syndrome.

Introduction. Pathogenic variants of the FLNA gene cause damage to various organs and systems formed in the embryonic period. The most frequently affected organs are the brain (epilepsy), cardiovascular system (congenital heart defects, pulmonary hypertension — PH), and lungs (emphysema). The aim of the study: genetic, clinical, laboratory, and instrumental characteristics of patients with a disease caused by pathogenic variants of the FLNA gene. Materials and methods. Six girls with identified pathogenic variants of the FLNA gene were observed. The methods used: genealogical, whole exome sequencing, Sanger sequencing, electroencephalography, brain MRI, echocardiography, right heart catheterization with determination of pressure and resistance in the pulmonary circulation and pulmonary capillary wedge pressure, CT of the chest organs. Results. The article presents the results of a molecular genetic study of the FLNA gene. All patients were diagnosed with periventricular nodular heterotopia and psychomotor retardation, 2 of them had epilepsy; 4 children had heart valve dysplasia; 3 had patent ductus arteriosus, 3 had septal defects, 2 had bicuspid aortic valve, 5 had pulmonary hypertension; 5 had pulmonary emphysema; 1 had congenital diaphragmatic hernia. Two patients died during the observation period. Conclusion. Diagnosis and observation of patients with pathogenic variants of the FLNA gene is a challenge for a multidisciplinary team of doctors at a multidisciplinary pediatric hospital. The presented cohort of 6 patients reflects the most typical manifestations of this pathology, the severity and rate of development of disease in infants.