Background. The efficacy and safety of onasemnogene abeparvovec have been demonstrated in patients with spinal muscular atrophy (SMA) in several clinical and observational studies. Gene replacement therapy results in Russian patients with SMA is not investigated yet.Objective. The aim of the study is to study the safety and efficacy of onasemnogene abeparvovec in children with SMA in real clinical practice.Methods. The study included patients with proximal 5q SMA administered with onasemnogene abeparvovec. Diagnosis was verified by biallelic deletion in the 7th exon of the SMN1 gene. Gene replacement therapy was administered according to the decision of neurologists consensus in case of the absence of antibodies to the adeno-associated serotype 9 virus. The therapy safety was estimated via clinical and laboratory data from the hospital (at least 7 days) and from outpatient departments (at least 60 days). Efficacy was estimated via CHOP INTEND scale and mastering new motor skills ≥ 6 months after therapy onset.Results. Treatment outcomes were studied in 10 SMA patients aged 19 months (15; 21). All patients developed at least one clinical manifestation (hyperthermia, vomiting, lethargy and/or loose stool) associated with drug administration during the first week of follow-up. Increased hepatic transaminases activity and monocytosis was recorded in all patients, thrombocytopenia — in 9, neutropenia — in 5, increased troponin I concentration — in 3. In three cases it was necessary to increase the oral prednisolone dose of to 2 mg/kg, in one case — the dexamethasone pulse therapy dose. The therapy efficacy was monitored ≥ 6 months after therapy onset via the CHOP INTEND scale in 2 patients (scores increased by 32 and 19 points, respectively), and via mastering new motor skills in 8 patients (positive dynamics was noted in 7 cases).Conclusion. The onasemnogene abeparvovec is relatively safe and quite effective for using in real clinical practice

No abstract

No abstract

Introduction. Predicting relapse in acute demyelinating episode (ADE) in children is an urgent problem, since progressive demyelinating diseases are associated with the risk of disability and cognitive impairment.Methods. Descriptive cohort study. The results of long-term follow-up of 75 children after the first episode of demyelination are presented. Based on the clinical and radiological parameters of the first demyelinating event, the prognostic factors for the relapse in children were determined using the logistic regression method.Results. When comparing the clinical and instrumental signs of the first demyelinating event, we identified those that were significantly associated with relapse. These included age ≥ 11 years (p <0.001), brain stem symptoms (p = 0.002), multiple demyelinating lesions on brain magnetic resonance imaging (p = 0.001) periventricular (p = 0.002), subcortical (p = 0.001), brainstem lesions (p = 0.006), well-defined lesions (p = 0.03) and perpendicular to the corpus callosum lesions (p = 0.002), cervical spinal cord lesions (p = 0, 02) and lateralized spinal cord lesions (p = 0.02). Regression analysis showed independent risk factors for relapse in children with demyelinating diseases: age ≥ 11 years (OR = 1.34, 95% CI (1.11: 1.61), p = 0.003), brain stem symptoms (OR = 7.00, 95% CI (0.73: 67.25, p = 0.09), multiple CNS lesions, corresponding to the criteria for dissemination by McDonald (2010) (OR = 8.60, 95% CI (2, 24: 33.07), p = 0.002).Discussion. Existing descriptions of pediatric populations with demyelinating diseases often have short follow-up and focus on outcomes in multiple sclerosis and neuromyelitis optica. The article presents data on previously unexplored risk factors for exacerbation after the first episode of demyelination. Conclusion. The identified predictors of relapse in ADE in children are a simple and generally available tool for predicting the course of demyelinating diseases.

No abstract