Sleep architecture and Nusinersen therapy in children with Spinal Muscular Atrophy type 1

Background: Spinal muscular atrophy (SMA) is a severe neuromuscular disorder, the phenotype of the disease is caused by the mutation of the SMN1 (survival motor neuron 1) gene which encodes for the SMN protein. Innovative treatments for SMA have become available and the first molecule approved is Nusinersen, an anti-sense oligonucleotide that increases the production of SMN protein. Nusinersen has been shown to be associated with a significant motor improvement and an increase of the event-free survival. For these reasons the aim of the present study is to assess if Nusinersen is able modify sleep architecture and microstructure and to improve sleep structure in these patients.Methods: Sixteen patients affected by SMA1 were enrolled in the study (4 boys, 12 girls; median age 72.5 months, intelligence quotient range 24-84). All patients underwent complete nocturnal PSG before the start of the treatment trough intrathecal injections with Nusinersen (T0) and after the fifth infusion (day 180, T180). PSG recordings were visually scored and interpreted according to the indications of the American Academy of Sleep Medicine (AASM) and and microstructure by means of the Cyclic Alternating Pattern (CAP).Results: After 6 months therapy we found a significantly reduced sleep latency and a significantly increased sleep efficiency. Regarding sleep microstructure parameters (CAP), we did not find any significant change after therapy however, it is worth mentioning that a moderate effect size was observed for the increase in CAP A3 index.Conclusions: We observed short-term effects of Nusinersen on sleep with an improvement in sleep efficiency and reduction in sleep onset latency; regarding sleep microstructure, a moderate effect size was found for the number of CAP A3 subtypes that slightly increased, possibly indicating a slightly higher arousability. This finding points at a probably overall better sleep pattern organization associated with the treatment, but they need to be confirmed by larger studies with patients treated earlier in life and for a longer period.