RESUMO
OBJECTIVE: To evaluate the effects of nusinersen on respiratory function of patients with type 1 spinal muscular atrophy. STUDY DESIGN: Observational, longitudinal cohort study. We collected respiratory data from 118 children with type 1 spinal muscular atrophy and differing pulmonary requirements and conducted a semistructured qualitative interview among a subsample of caregivers at baseline, 6 months, and 10 months after the first nusinersen treatment. Patients were stratified according to ventilation modalities and age at study entry. RESULTS: Most patients in our cohort remained stable (84/109 = 77%). More than 80% of the children treated before age 2 years survived, in contrast to the lower survival reported in natural history studies, and did so without tracheostomy or noninvasive ventilation (NIV) ≥16 hours. In those less than 2 years old, only 3 patients shifted from NIV ≤10 hours to NIV >10 hours, and the other 3 reduced the hours of NIV required. Most of the older patients remained stable; this included not only those on tracheostomy or NIV >10 hours but also 75% of those on NIV ≤10 hours. CONCLUSIONS: Our results suggest that nusinersen may produce some improvement in the progression of respiratory impairment, both in terms of survival and need for respiratory support ≥16 hours, especially before the age of 2 years.
Assuntos
Ventilação não Invasiva , Oligonucleotídeos/uso terapêutico , Respiração , Atrofias Musculares Espinais da Infância/fisiopatologia , Atrofias Musculares Espinais da Infância/terapia , Estudos de Coortes , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Atrofias Musculares Espinais da Infância/tratamento farmacológicoRESUMO
PURPOSE: To quantitatively describe passive lower extremity range of motion in participants with spinal muscular atrophy (SMA) types 2 and 3, and to establish preliminary thresholds to identify individuals at risk for performing poorly on disease-specific motor function outcome measures. METHODS: Eighty participants with SMA types 2 and 3, enrolled in an international multicenter natural history study, were evaluated with lower extremity range of motion testing and the Hammersmith Functional Motor Scale-Expanded. RESULTS: A hip extension joint angle of -7.5° or less for SMA type 2 and 0° or less for SMA type 3 identified diminished motor ability with good sensitivity. For knee extension, a joint angle of -9.0° or less for SMA type 2 or 0° or less for SMA type 3 was similarly sensitive. CONCLUSIONS: Minimal hip and knee joint contractures were associated with diminished motor ability. Clinical trial designs should consider the effect of contractures on motor function.