RESUMEN
SCN8A-developmental and epileptic encephalopathy is caused by pathogenic variants in the SCN8A gene encoding the Nav 1.6 sodium channel, and is characterized by intractable multivariate seizures and developmental regression. Fenfluramine is a repurposed drug with proven antiseizure efficacy in Dravet syndrome and Lennox-Gastaut syndrome. The effect of fenfluramine treatment was assessed in a retrospective series of three patients with intractable SCN8A epilepsy and severe neurodevelopmental comorbidity (n = 2 females; age 2.8-13 years; 8-16 prior failed antiseizure medications [ASM]; treatment duration: 0.75-4.2 years). In the 6 months prior to receiving fenfluramine, patients experienced multiple seizure types, including generalized tonic-clonic, focal and myoclonic seizures, and status epilepticus. Overall seizure reduction was 60%-90% in the last 3, 6, and 12 months of fenfluramine treatment. Clinically meaningful improvement was noted in ≥1 non-seizure comorbidity per patient after fenfluramine, as assessed by physician-ratings of ≥"Much Improved" on the Clinical Global Impression of Improvement scale. Improvements included ambulation in a previously non-ambulant patient and better attention, sleep, and language. One patient showed mild irritability which resolved; no other treatment-related adverse events were reported. There were no reports of valvular heart disease or pulmonary arterial hypertension. Fenfluramine may be a promising ASM for randomized clinical trials in SCN8A-related disorders.
Asunto(s)
Epilepsias Mioclónicas , Fenfluramina , Adolescente , Niño , Preescolar , Comorbilidad , Epilepsias Mioclónicas/tratamiento farmacológico , Epilepsias Mioclónicas/genética , Femenino , Fenfluramina/uso terapéutico , Humanos , Canal de Sodio Activado por Voltaje NAV1.6/genética , Estudios Retrospectivos , Convulsiones/genéticaRESUMEN
OBJECTIVES: To assess the efficacy of high-flow nasal cannula (HFNC) oxygen therapy and safety in children with asthma and moderate respiratory failure in the emergency department (ED). STUDY DESIGN: This was a prospective randomized pilot trial of children (aged 1-14 years) presenting to a tertiary academic pediatric ED with moderate-to-severe asthma exacerbations between September 2012 and December 2015. Patients with a pulmonary score (PS) ≥6 or oxygen saturation <94% with a face mask despite initial treatment (salbutamol/ipratropium bromide and corticosteroids) were randomized to HFNC or to conventional oxygen therapy. Pharmacologic treatment was at the discretion of attending physicians. The primary outcome was a decrease in PS ≥2 in the first 2 hours. Secondary outcomes included disposition, length of stay, and need for additional therapies. RESULTS: We randomly allocated 62 children to receive either HFNC (n = 30) or standard oxygen therapy (n = 32). Baseline patient characteristics were similar in the 2 groups. At 2 hours after the start of therapy, PS had decreased by ≥2 points in 16 patients in the HFNC group (53%) compared with 9 controls (28%) (P = .01). Between-group differences in disposition, length of stay, and need for additional therapies were not significant. No side effects were reported. CONCLUSION: HFNC appears to be superior to conventional oxygen therapy for reducing respiratory distress within the first 2 hours of treatment in children with moderate-to-severe asthma exacerbation refractory to first-line treatment. Further studies are needed to demonstrate its overall efficacy in the management of asthma and respiratory failure in the ED. TRIAL REGISTRATION: EudraCT: 2012-001771-36.