Один из побочных эффектов метотрексата-подострая энцефалопатия, которая характеризуется рядом определенных неврологических симптомов, наличием лейкоэнцефалопатии, по данным магнитно-резонансной томографии (МРТ), и медленноволновой активностью на электроэнцефалограмме (ЭЭГ). Цель работы-определение клинико-электрофизиологических характеристик метотрексатовой энцефалопатии у детей с различными типами опухолей, а также сопоставление полученных данных с литературными. Данное исследование поддержано Независимым этическим комитетом и утверждено решением Ученого совета НМИЦ ДГОИ. Проведен ретроспективный анализ результатов лечения 31 пациента в взрасте от 1,5 до 17 лет с подострой метотрексатовой энцефалопатией. У большинства пациентов (n = 26) был диагностирован острый лимфобластный лейкоз. Согласно терапевтическим протоколам пациенты получали внутривенное, интратекальное и интравентрикулярное введение метотрексата. Степень тяжести метотрексатовой энцефалопатии опеределяли по шкале NCI-СTCAE, версия 4.0. ЭЭГ-исследования проводили всем; МРТ-26 пациентам. Метотрексатовая энцефалопатия развилась через 2-12 сут (в среднем 5,3 ± 3,2 сут) после введения метотрексата. Энцефалопатия 1-й степени тяжести имела место в 35,5% случаев; 2-й степенив 19,4%; 3-й и 4-й степеней-в 25,8 и 19,4% случаев соответственно. Повторные симптомы при продолжении терапии развились у 5 пациентов. Наиболее частые неврологические симптомы: патологическая сонливость (50,1%), нарушение сознания (32,3%), когнитивные нарушения (25,8%), эпилептические приступы (19,6%) и атаксия (19,6%). Регресс неврологических симптомов наблюдался у 26 пациентов через 1-10 сут (в среднем 3,3 ± 2,2 сут); у 5 пациентов сохранялся стойкий неврологический дефицит. ЭЭГ-паттерн был представлен диффузной тета-активностью (39%), тета-дельта активностью (42%), дельта-активностью (6,5%), бета-активностью (3,0%), снижением амплитуды альфа-ритма (6,5%) и не был изменен у 1 пациента. По данным МРТ, в 84,6% случаев выявлены признаки лейкоэнцефалопатии. Установлена завсимость между изменениями на ЭЭГ, сроками дебюта и разрешения энцефалопатии. При этом между тяжестью энцефалопатии, ЭЭГ-картиной, способом введения метотрексата, возрастом пациента, клиренсом метотрексата и сопутствующей неврологической патологией связи не отмечено. Полученные нами результаты в целом сходны с зарубежными данными о клинической картине и сроках дебюта метотрексатовой энцефалопатии. У пациентов с метотрексатовой энцефалопатией ЭЭГ не всегда была представлена диффузной медленноволновой активностью тета-диапазона. Для корректной оценки результатов электрофизиологического исследования при метотрексатовой энцефалопатии пациентам рекомендовано проведение инициального ЭЭГ-исследования. Требуется дальнейшее изучение факторов риска метотрексатовой энцефалопатии.

Neuroblastoma (NB) can manifest through neurological symptoms caused by tumor extension into the spinal canal and the resulting epidural compression (EC). Clinical symptoms and management in patients with epidural compression depend on its level and duration, the severity of spinal cord compression, the patient's age and other factors. One of the biggest challenges is the diagnosis and treatment of EC in infants in the first months of life. Our retrospective analysis included 13 patients with NB complicated by spinal cord EC who had been diagnosed at the age of 0–6 months and treated at the D. Rogachev NMRCPHOI over the period from 01.01.2012 to 01.12.2018 (82 months). The study was approved by the Independent Ethics Committee and the Scientific Council of the D. Rogachev NMRCPHOI of the Ministry of Healthcare of the Russian Federation. The diagnosis of NB was based on the international diagnostic criteria. The tumors were staged in accordance with the INSS classification. The patients were stratified into risk groups and treated according to the modified NB-2004 protocol of the German Oncology Group. All the patients underwent diagnostic testing for neurogenic tumors as well as contrast-enhanced magnetic resonance imaging of the spinal cord with the assessment of the level of tumor invasion and the degree of spinal cord compression. The children were evaluated by a neurologist at admission and at follow-up visits. The median age at diagnosis of NB was 3.9 (0.5–6) months. At disease onset, 53.8% of patients had neurological symptoms, with motor deficiencies being the most common ones. In this group of patients, the median time from first neurological symptoms to diagnosis of NB was 1.56 months. Neurological symptoms at disease onset were not present or diagnosed at local healthcare facilities in 46.2% of infants. Extra-organic retroperitoneal primary tumors were found in 61.6% of patients; 30.7% of primary tumors were located in the posterior mediastinum, and 7.7% of primary tumors – in the lesser pelvis. No patients had MYCN-amplified tumors; in 1 case the MYCN gene status was evaluated as Gain; neither 1p nor 11q deletions were detected. The distribution of patients by INSS stages was as follows: stage 2 – 15.3%, stage 3 – 46.1%, stage 4 – 23.3% and stage 4S – 15.3%. The majority of patients (77.7%) were stratified into an observation group, the remaining patients (23.3%) were allocated to a medium risk group in accordance with the NB-2004 protocol. The level of tumor invasion into the spinal cord canal varied. Tumor invasion at the level of the cervicothoracic spine was observed in 15.4% of patients, at the level of the thoracic spine – in 15.4%, at the level of the thoracolumbar spine – in 46.2%, at the level of the lumbar spine – in 15.4%, and at the level of the sacral spine – in 7.7%. Neurosurgical intervention (laminotomy) was performed in 4 cases (30.7%). In one patient, laminotomy was the only treatment option (chemotherapy was not given). In two patients, neurosurgery was performed because of the deterioration of neurological symptoms caused by the start of the first polychemotherapy (PCHT) cycle. Chemotherapy was carried out in 92.3% patients. The patients from the observation group received 1–3 PCHT cycles (the median number of cycles was 2). Only one patient from the observation group did not receive PCHT. This patient underwent 2 surgeries. Currently, 10/13 (77%) patients are alive, 3/13 (33%) patients are dead (2/3 patients died of therapy-related infectious complications, and 1/3 – of acute heart failure in the early postoperative period). The median follow-up was 37.3 months. According to the assessment of late effects, neurological disorders were found in all the analyzed patients (n = 9), and orthopedic disorders were found in 66.6% (6/9) patients. The results of our analysis illustrate both the difficulty of diagnosis and management of EC in patients with NB and the need¬ for uniform testing and treatment standards with established follow-up and rehabilitation strategies for this group of patients.

This article is devoted to the analysis of problems related to the state of the nervous system in patients who have survived malignant neoplasm in childhood. The main diseases and pathological conditions that can develop in this population are considered. The risks of the development of pathological changes in the nervous system, treatment and prevention are described. Separately analyzed issues of peripheral neuropathy, Raynaud’s syndrome, chronic pain.