Respiratory characteristics in children with spinal muscular atrophy type 1 receiving nusinersen.

Background: Spinal muscular atrophy type 1 (SMA1) is a neuromuscular disorder with a natural history of chronic respiratory failure and death during infancy without ventilation. Recently, disease-modifying therapies such as nusinersen have improved disease trajectory. However, objective data on the trajectory of polysomnography outcomes, the relationship between motor scores and respiratory parameters, respiratory technology dependence and healthcare utilization in children with SMA1 remain to be elucidated.

Methods: This was a retrospective observational study of children with SMA1 receiving nusinersen between October 2016 and February 2021 at two tertiary care hospitals in Canada. Baseline polysomnography data, motor scores, respiratory technology, and unanticipated healthcare utilization were examined.

Results: Eleven children (five females, two SMN2 copies each) were included. Median (interquartile range [IQR]) age at diagnosis was 3.6 (2.8-5.0) months and age at diagnostic polysomnogram following nusinersen initiation was 9.4 (5.3-14.0) months. Nusinersen was initiated at a median (IQR) age of 5.4 (3.4-7.6) months and 8/11 children had respiratory symptoms at that time. Diagnostic polysomnography data showed a median (IQR) central apnea-hypopnea index (AHI) of 4.1 (1.8-10.0) and obstructive AHI of 2.2 (0-8.0) events/h. We observed an inverse relationship between motor scores and central apnea-hypopnea indices. All children required ventilatory support at the end of the study period.

Conclusion: This study showed abnormal polysomnography parameters and need for ventilation despite nusinersen suggesting ongoing need for regular monitoring with polysomnography. Understanding the respiratory disease trajectory of children undergoing treatment with nusinersen will inform decision-making regarding optimal timing of ventilatory support initiation.