Multimodal speech biomarkers for remote monitoring of ALS disease progression.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that severely impacts affected persons' speech and motor functions, yet early detection and tracking of disease progression remain challenging. The current gold standard for monitoring ALS progression, the ALS functional rating scale - revised (ALSFRS-R), is based on subjective ratings of symptom severity, and may not capture subtle but clinically meaningful changes due to a lack of granularity. Multimodal speech measures which can be automatically collected from patients in a remote fashion allow us to bridge this gap because they are continuous-valued and therefore, potentially more granular at capturing disease progression. Here we investigate the responsiveness and sensitivity of multimodal speech measures in persons with ALS (pALS) collected via a remote patient monitoring platform in an effort to quantify how long it takes to detect a clinically-meaningful change associated with disease progression. We recorded audio and video from 278 participants and automatically extracted multimodal speech biomarkers (acoustic, orofacial, linguistic) from the data. We find that the timing alignment of pALS speech relative to a canonical elicitation of the same prompt and the number of words used to describe a picture are the most responsive measures at detecting such change in both pALS with bulbar (n = 36) and non-bulbar onset (n = 107). Interestingly, the responsiveness of these measures is stable even at small sample sizes. We further found that certain speech measures are sensitive enough to track bulbar decline even when there is no patient-reported clinical change, i.e. the ALSFRS-R speech score remains unchanged at 3 out of a total possible score of 4. The findings of this study have the potential to facilitate improved, accelerated and cost-effective clinical trials and care.