Assessment of Bulbar Function in Adult Patients with 5q-SMA Type 2 and 3 under Treatment with Nusinersen

Abstract

The antisense oligonucleotide nusinersen has been shown to improve trunk and limb motor function in patients with spinal muscular atrophy (SMA). Bulbar dysfunction, which is regularly present in SMA, is not captured by standard motor scores, and validated measurement instruments to assess it have not yet been established. Data on whether and how bulbar function changes under gene-based therapies in adult SMA patients are also unavailable. Here, we present data on the course of bulbar dysfunction assessed prospectively before nusinersen treatment initiation and 6 and 14 months later in 23 adult SMA patients using the Sydney Swallow Questionnaire (SSQ) and the bulbar subscore of the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R). While no improvement in bulbar scores was observed under treatment with nusinersen, the absence of a decline still implies a therapeutic effect of nusinersen on bulbar dysfunction. The results of this study aim to contribute to a standardized assessment of bulbar function in adult SMA patients, which may show therapeutic effects of gene-based therapies that are not evident from standard motor scores.

Keywords: ALSFRS-R; ASO; SSQ; spinal muscular atrophy; swallowing.

Figure 1

Measures of central tendency and dispersion and the mean bulbar and extremity motor scores at T0, T1 and T2. The boxes are defined by the upper and lower quartiles. The median is marked as a continuous line in the box. The length of the whiskers is limited to a maximum of 1.5 times the interquartile range. Data points outside this range are marked as circles. Crosses represent the respective arithmetic means. Significant differences based on a significance level of α = 0.05 and calculated with the Wilcoxon signed rank test are indicated by an asterisk *.