Risdiplam improves subjective swallowing quality in non-ambulatory adult patients with 5q-spinal muscular atrophy despite advanced motor impairment

J Neurol. 2024 May;271(5):2649-2657. doi: 10.1007/s00415-024-12203-9. Epub 2024 Feb 15.

Abstract

Background: 5q-associated spinal muscular atrophy (SMA) is characterized by the progressive loss of motor neurons with consecutive weakness and atrophy of the limb, respiratory, and bulbar muscles. While trunk and limb motor function improve or stabilize in adults with SMA under nusinersen and risdiplam treatment, the efficacy on bulbar function in this age group of patients remains uncertain. However, it is important to assess bulbar dysfunction, which frequently occurs in the disease course and is associated with increased morbidity and mortality.

Methods: Bulbar function was evaluated prospectively in 25 non-ambulatory adults with type 2 and 3 SMA before and 4 and 12 months after risdiplam treatment initiation using the Sydney Swallow Questionnaire (SSQ) and the bulbar subscore of the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (b-ALSFRS-R). Extremity function was assessed using the Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM).

Results: Subjective swallowing quality, measured with the SSQ, improved after 12 months of therapy with risdiplam. For the b-ALSFRS-R, a non-significant trend towards improvement was observed. The RULM score improved after 12 months of risdiplam therapy, but not the HFMSE score. HFMSE and RULM scores did not correlate with the SSQ but the b-ALSFRS-R score at baseline.

Conclusions: The improvement in subjective swallowing quality under risdiplam treatment, despite an advanced disease stage with severe motor deficits, strengthens the importance of a standardized bulbar assessment in addition to established motor scores. This may reveal relevant treatment effects and help individualize treatment decisions in the future.

Keywords: ALSFRS-R; Risdiplam; SSQ; Spinal muscular atrophy; Swallowing.

MeSH terms

  • Adult
  • Aged
  • Azo Compounds*
  • Deglutition / drug effects
  • Deglutition / physiology
  • Deglutition Disorders* / drug therapy
  • Deglutition Disorders* / etiology
  • Deglutition Disorders* / physiopathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Muscular Atrophy, Spinal / drug therapy
  • Muscular Atrophy, Spinal / physiopathology
  • Prospective Studies
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use
  • Spinal Muscular Atrophies of Childhood / complications
  • Spinal Muscular Atrophies of Childhood / drug therapy
  • Spinal Muscular Atrophies of Childhood / physiopathology
  • Treatment Outcome
  • Young Adult

Substances

  • Risdiplam
  • Pyrimidines
  • Azo Compounds