title: Phonatory dysfunction as a preclinical symptom of Huntington disease.
abstract: OBJECTIVE
  Although dysphonia has been shown to be a common sign of Huntington disease (HD), the extent of phonatory dysfunction in gene positive premanifest HD individuals remains unknown. The aim of the current study was to explore the possible occurrence of phonatory abnormalities in prodromal HD.
  
  
  METHODS
  Sustained vowel phonations were acquired from 28 premanifest HD individuals and 28 healthy controls of comparable age. Data were analysed acoustically for measures of several phonatory dimensions including airflow insufficiency, aperiodicity, irregular vibration of vocal folds, signal perturbations, increased noise, vocal tremor and articulation deficiency. A predictive model was built to find the best combination of acoustic features and estimate sensitivity/specificity for differentiation between premanifest HD subjects and controls. The extent of voice deficits according to a specific phonatory dimension was determined using statistical decision making theory. The results were correlated to global motor function, cognitive score, disease burden score and estimated years to disease onset.
  
  
  RESULTS
  Measures of aperiodicity and increased noise were able to significantly differentiate between premanifest HD individuals and controls (p<0.01). The combination of these aspects of dysphonia led to a sensitivity of 91.5% and specificity of 79.2% to correctly distinguish speakers with premanifest HD from healthy individuals. Some form of disrupted phonatory function was revealed in 68% of our premanifest HD subjects, where 18% had one affected phonatory dimension and 50% showed impairment of two or more dimensions. A relationship between pitch control and cognitive score was also observed (r =  -0.50, p =  0.007).
  
  
  CONCLUSIONS
  Phonatory abnormalities are detectable even the in premotor stages of HD. Speech investigation may have the potential to provide functional biomarkers of HD and could be included in future clinical trials and therapeutic interventions.
authors.affiliation: Department of Circuit Theory, Faculty of Electrical Engineering, Czech Technical University in Prague, Prague, Czech Republic; Department of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Rusz
authors.affiliation: Department of Neurology, Huntington-Centre NRW, St. Josef Hospital, Ruhr-University of Bochum, Bochum, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Saft
authors.affiliation: Department of Neurology, Knappschaftskrankenhaus, Ruhr-University of Bochum, Bochum, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Schlegel
authors.affiliation: Department of Neurology, Huntington-Centre NRW, St. Josef Hospital, Ruhr-University of Bochum, Bochum, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Hoffman
authors.affiliation: Department of Neurology, Knappschaftskrankenhaus, Ruhr-University of Bochum, Bochum, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Skodda
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D055154:Dysphonia / Q000209:etiology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000150:complications* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D013061:Speech Acoustics; D014831:Voice / Q000502:physiology