Auditory-perceptual voice and speech evaluation in ATP1A3 positive patients

J Clin Neurosci. 2020 Nov:81:133-138. doi: 10.1016/j.jocn.2020.09.007. Epub 2020 Oct 5.


Introduction: Bulbar symptoms are frequent in patients with rapid-onset dystonia-parkinsonism (RDP). RDP is caused by ATP1A3 mutations, with onset typically within 30 days of stressor exposure. Most patients have impairments in speech (dysarthria) and voice (dysphonia). These have not been quantified. We aimed to formally characterize these in RDP subjects as compared to mutation negative family controls.

Methods: We analyzed recordings in 32 RDP subjects (male = 21, female = 11) and 29 mutation negative controls (male = 15, female = 14). Three raters, blinded to mutation status, rated speech and vocal quality. Dysarthria was classified by subtype. Dysphonia was rated via the GRBAS (Grade, Roughness, Breathiness, Asthenia, Strain) scale. We used general neurological exams and the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) to assess dysarthria, dystonia, and speech/swallowing dysfunction.

Results: The presence of dysarthria was more frequent in RDP subjects compared to controls (72% vs. 17%, p < 0.0001). GRBAS voice ratings were worse in the RDP cohort across nearly all categories. Dysarthria in RDP was associated with concordant cranial nerve 9-11 dysfunction (54%, p = 0.048), speech/swallowing dysfunction (96%, p = 0.0003); and oral dystonia (88%, p = 0.001).

Conclusions: Quantitative voice and speech analyses are important in assessing RDP. Subjects frequently experience dysarthria and dysphonia. Dystonia is not the exclusive voice abnormality present in this population. In our analysis, RDP subjects more frequently experienced bulbar symptoms than controls. GRBAS scores are useful in quantifying voice impairment, potentially allowing for better assessments of progression or treatment effects. Future directions include using task-specific diagnostic and perceptual voice evaluation tools to further assess laryngeal dystonia.

Keywords: ATP1A3; RDP; Rapid-onset dystonia-parkinsonism; Speech; Voice.

MeSH terms

  • Adult
  • Dysarthria / genetics*
  • Dysphonia / genetics*
  • Dystonic Disorders / genetics*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Sodium-Potassium-Exchanging ATPase / genetics*
  • Speech*


  • ATP1A3 protein, human
  • Sodium-Potassium-Exchanging ATPase

Supplementary concepts

  • Dystonia 12