Longitudinal bulbar and respiratory declines in Amyotrophic Lateral Sclerosis (ALS) (4786)

Objective: The primary objective of this study was to estimate the effect of progressive respiratory decline on progressive bulbar decline. A secondary goal was to determine which other factors may predict advancement of bulbar disease. Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that results in progressive loss of motor function. Respiratory muscle weakness occurs in all patients, resulting in eventual respiratory failure and death. Bulbar (speech and swallowing) muscles are also affected in up to 85% of patients. Bulbar and respiratory impairments are related on the physiological level through the loss of motor neurons in the hypoglossal nucleus and functionally, as both speech and swallowing are tightly coupled to respiration. Because of this tight coupling, it is often difficult to delineate the extent to which bulbar disease progression is conflated with the rapid decline in respiratory function. Design/Methods: 471 patients were followed longitudinally (total number of session=1022). At each session patients completed ALS – Functional Rating Scale – Revised, functional vital capacity test (%FVC), as well as a detailed bulbar assessment protocol, which included a Sentence Intelligibility Test and passage reading. An ordered logistic random effects model with fixed effects and random intercept was used. The stage 0 of bulbar disease progression was operationalized as SIT speaking rate > 155 words per minute (WPM), and stage 1 (active) as SIT speaking rate Results: The preliminary results indicated that %FVC was highly predictive of advancing bulbar disease to its active stage; the odds of a patient moving to stage 1 of bulbar disease given that they were at stage 1 of their FVC decline were 3.9 fold. Ongoing work is focused on incorporating the fixed effects (e.g., patient demographics) into the model. Conclusions: NA Disclosure: Dr. Asidianya has nothing to disclose. Dr. Korngut has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion, Novartis, Mitsubishi Tanabe Pharma, Sarepta, Biogen, CSL Behring. Dr. Korngut has received compensation for serving on the Board of Directors of Dataffinity Health. Dr. Korngut holds stock and/or stock options in Dataffinity Health. Dr. Korngut has received research support from Biogen Idec, Sanofi Genzyme, Cytokinetics. Dr. Genge has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AB Sciences, AL-S Pharma, Avexis, Biogen, Cytokinetics, MTPA, and Roche. Dr. Genge has received research support from Sanofi-Genzyme. Dr. Abrahao has nothing to disclose. Dr. Kalra has nothing to disclose. Dr. Zinman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Mitsubishi Tanabe Pharma Canada.Dr. Yunusova has nothing to disclose.