Fiberoptic endoscopic evaluation of swallowing in early-to-advanced stage Huntington's disease

Abstract

Huntington's disease (HD) is a neurodegenerative disorder characterized by motor disturbances, cognitive decline, and behaviour changes. A well-recognized feature of advanced HD is dysphagia, which leads to malnutrition and aspiration pneumonia, the latter being the primary cause of death in HD. Previous studies have underscored the importance of dysphagia in HD patients with moderate-to-advanced stage disease, but it is unclear whether dysphagia affects patients already at an early stage of disease and whether genetic or clinical factors can predict its severity. We performed fiberoptic endoscopic evaluation of swallowing (FEES) in 61 patients with various stages of HD. Dysphagia was found in 35% of early-stage, 94% of moderate-stage, and 100% of advanced-stage HD. Silent aspiration was found in 7.7% of early-stage, 11.8% of moderate-stage, and 27.8% of advanced-stage HD. A strong correlation was observed between disease progression and dysphagia severity: worse dysphagia was associated with worsening of motor symptoms. Dysphagia severity as assessed by FEES correlated with Huntington's Disease Dysphagia Scale scores (a self-report questionnaire specific for evaluating swallowing in HD). The present findings add to our understanding of dysphagia onset and progression in HD. A better understanding of dysphagia onset and progression in HD may inform guidelines for standard clinical care in dysphagia, its recognition, and management.

Figure 1

Dysphagia parameters in controls (n = 31) and HD patients (n = 61): early (n = 26), moderate (n = 17), and advanced HD (n = 18). (a) Comparison of the Dysphagia Outcome and Severity Scale (DOSS) level in HD patients and controls. DOSS levels were lower in early-moderate-advanced HD patients compared to controls (mean ± SEM of DOSS: controls 6.52 ± 0.10, early-stage 5.54 ± 0.16, moderate-stage 4.53 ± 0.21, advanced-stage HD 3.83 ± 0.28, Kruskal–Wallis and Dunn's test, *p < 0.05; **p < 0.01, ***p < 0.001, ****p < 0.0001). (b) Distribution of dysphagia frequency. Dysphagia was present in 35% of early-stage, 94% of moderate-stage, and 100% of advanced-stage HD patients (p < 0.0001, df 3, Chi-square 64.58). (c) Comparison of Penetration-Aspiration Scale (PAS) scores. PAS scores were higher for HD patients than for controls (mean ± SEM of PAS scores: controls 1.26 ± 0.12, early-stage 2.58 ± 0.42, moderate-stage 4.24 ± 0.47, advanced-stage HD patients 5.44 ± 0.58. Kruskal–Wallis and Dunn's test, *p < 0.05; ***p < 0.001, ****p < 0.0001). (d) Pie chart showing the percentage of silent aspiration, aspiration and penetration in HD patients.

Figure 2

Correlations between dysphagia severity parameters and disease progression. (a) Correlation between DOSS levels and the total motor score in HD patients. A negative correlation was found between the two parameters. Spearman correlation coefficient r = − 0.6781, p < 0.0001. (b) Correlations between DOSS levels and UHDRS I subitem scores. All parameters but maximal chorea correlated negatively with DOSS level. c Receiver operating curve (ROC) of gain-of-function mutations and control mutations as a function of UHDRS I total motor score (TMS). Based on a cut-off TMS of 36.5 that maximizes sensitivity and specificity, TMS correctly classified 15 out of 18 HD patients as having normal swallowing (DOSS ≥ 6) and 35 out of 43 as having dysfunctional swallowing DOSS ≤ 5 (81% sensitivity and 83% specificity). The area under the curve is 0.86 (95% confidence interval = 0.77 to 0.95).