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Background: Vincristine polyneuropathy is a major neurotoxic complication of treatment for acute lymphoblastic leukemia in children. A close relationship between genetic variants in candidate genes associated with the vincristine neurotoxicity in various ethnic groups has been proposed. Therefore, identification of the genetic risk factors underlying the predisposition to vincristine polyneuropathy could allow the development of effective tools for preventive diagnostics aimed at identifying a high-risk group among patients treated with vincristine for a personalized approach to their chemotherapy. Aim: To study an association between the rs924607 polymorphism of the CEP72 gene and vincristine polyneuropathy in children with acute lymphoblastic leukemia. Materials and methods: This single center cohort study enrolled 199 children aged 3 to 17 years with newly diagnosed acute lymphoblastic leukemia, who received ALL-MB 2015 chemotherapy regimen. All patients were genotyped for the single nucleotide variant rs924607 in the CEP72 gene by real-time polymerase chain reaction and subsequent allelic discrimination. A comparative analysis of the incidence and clinical signs of vincristine polyneuropathy depending on the carrier of the genetic polymorphism was performed. Results: The incidence of vincristine polyneuropathy in the study pediatric group was 81.0% (n = 161); mostly these were patients with NCI-STCAE grade 2 severity. The rs924607 single nucleotide variant in the CEP72 gene was significantly associated with the neurotoxic complication, with 19.1% (n = 38) of the patients were homozygous for the minor allele (rs924607 genotype TT) and 46.2% (n = 92) had the ST genotype. Among the carriers of at least one rs924607 risk allele (T), the odds ratio for vincristine polyneuropathy was 2.91 (95% confidence interval 1.415.99, p = 0.004). No significant association between the genetic variant assessed and clinical signs of vincristine-induced polyneuropathy was found. Conclusion: The single nucleotide rs924607 polymorphism of the CEP72 gen can be a putative pharmacogenetic marker for vincristine polyneuropathy.

The prevalence of cognitive impairment in patients with multiple sclerosis is 40 to 65%. Improvement of cognitive-oriented therapy and search for its new techniques is considered to be promising for slowing the progression or for recovery of cognitive functions. It is related to low efficacy of medical treatment, preserved neuroplasticity in most patients with multiple sclerosis, positive results of studies on selected cognitive rehabilitation techniques in other nervous system disorders. The spectrum of techniques for cognitive training varies from technically feasible methods using a sheet of paper and a pen to the most advanced ones, such as the use of immersive virtual reality. The effectiveness of cognitive rehabilitation in patients with multiple sclerosis with virtual reality technologies has not been studied in large-scale randomized placebo-controlled studies.

Background: Chemotherapy-induced peripheral polyneuropathy is a major neurotoxicity of treatment for acute lymphoblastic leukemia (ALL) in children. Pathophysiological mechanisms of the injury of peripheral neural system are not fully investigated; however, some studies have shown the involvement of vascular endothelial growth factors. Aim: To evaluate plasma levels of angiogenic growth factors in children with ALL and to identify their association with the development of vincristine-induced peripheral polyneuropathy. Materials and methods: This single center prospective study included 41 patients with ALL aged 3 to 17 years. All patients were given the ALL-MB 2015 chemotherapy regimen. Depending on the vincristine-induced peripheral polyneuropathy, the patients were divided into two groups: the main group (n = 22) comprised of the patients with neurological signs and symptoms of peripheral neuropathy and the control group (n = 19), those without clinical signs of the peripheral nervous system involvement. The levels of angiogenic growth factors (VEGF-A, VEGF-D, PlGF-1, and PDGF-BB) were measured in plasma by multiparameter immunofluorescent analysis. Results: During 3 months of the follow up the chemotherapy-induced signs of peripheral polyneuropathy developed in 53.6% (n = 22) of the children. In 72.7% (n = 16) of the patients the chemotherapy-induced peripheral polyneuropathy was characterized by a combination of neurologic abnormalities with prevailing motor symptoms. The comparative analysis of plasma angiogenic growth factors in children with ALL depending on the presence or absence of the vincristine-induced peripheral polyneuropathy showed that there was a significant decrease of the VEGF-A in those with chemotherapy-induced peripheral polyneuropathy, compared to those without (Me [Q1; Q3]: 178.20 [138.40; 228.45] and 558.50 [160.10; 650.0], respectively, p 0.017). This parameter had diagnostic sensitivity of 77.7% and specificity of 76.9%. Conclusion: We have shown a high clinical value of plasma vascular endothelial growth factor (VEGF-A) level, which makes it possible to consider it as a significant biological marker of neurotoxicity in vincristine-induced peripheral polyneuropathy.

The article provides the review of literature on the issue of neurotoxic complications of chemotherapy in children. The data search was carried out in the PubMed, CyberLeninka, RSCI databases and others. There are many works devoted to studying the distribution, structure, and clinical features of chemo-induced neurological disorders in modern literature. In general, analysis of literature has shown that the incidence of neurotoxic complications varies widely depending on the research methods and used chemo-ther-apeutic drugs. Manifestations of chemotherapy-induced neurological disorders are quite diverse and accompanied by the central and peripheral nervous system damage. However, it has been shown that the platinum-based drugs have effective ototoxic effect with the damage of the auditory nerve. The Vincristine often causes peripheral polyneuropathy. Methotrexate and Ifosfamide cause metabolic encephalopathy. Cytarabine’s neurotoxicity is the damage of the cerebellum. The addition of neurological symptoms leads to decrease in the quality of life of patients. Some studies present the results of study of the causes and pathogenetic manifestations of neurotoxic reactions, changes in the genome associated with the development of specific toxic effects are identified. Despite the fact that many pathogenetic mechanisms of chemotherapy-induced neurotoxic complications have been revealed, the significance of laboratory predictors for prognosing and early assessment of these complications has not been essentially established yet, thus, there is the need for further study of this topic.