Amyotrophic lateral sclerosis (ALS) is a fatally progressive neurodegenerative disorder. Despite the prevalence and implications of bulbar involvement, there remains an absence of robust, objective, bulbar-specific biomarkers in ALS. Electrical impedance spectroscopy (EIS) of the tongue has been identified as a potential biomarker of bulbar function in ALS.
Multi-frequency tongue EIS phase data utilising 12 distinct electrode configurations were obtained from 32 ALS patients and 29 healthy volunteers, with longitudinal data collected for up to 6 months. Reliability was assessed using the intraclass correlation coefficient (ICC). Between group differences were examined using Mann-Whitney U tests. The Youden index was employed to summarise receiver operating characteristic (ROC) analysis of diagnostic classification performance. Spearman correlation coefficients were calculated to determine the relationship between EIS phase and the ALS Functional Rating Scale-Revised (ALSFRS-R) and tongue strength measurements. Related-samples tests were undertaken to investigate longitudinal EIS phase change.
EIS phase demonstrated excellent reliability (ICC: 0.774, 95% CI: 0.766-0.782). Highly significant differences between patients and volunteers in EIS phase were widely observed across all frequencies and electrode configurations (p < 0.001). Excellent area under the ROC curve (AUC) was displayed by a number of frequency/electrode configuration combinations, with sensitivity and specificity exceeding 80%. EIS phase correlated significantly with ALSFRS-R total score (p < 0.05) and bulbar subscore (p < 0.001), as well as with tongue strength measurements (p < 0.001). No discernible longitudinal change in EIS phase was observed; further investigation is, however, required.
Tongue EIS is a reliable marker, with the ability to distinguish ALS patients from healthy controls. The demonstrated relationship between EIS phase and established measures of disease severity, particularly the ALSFRS-R bulbar subscore and tongue strength measurements, suggest tongue EIS may be a suitable biomarker of bulbar function in ALS.