P 76 MUNIX in combination with D50 disease progression model reflects disease accumulation independently of disease aggressiveness in Amyotrophic Lateral Sclerosis

Abstract

Introduction: Motor Unit Number Index (MUNIX) is a reliable and non-invasive neurophysiological technique to reflect functional loss of motor units in amyotrophic lateral sclerosis (ALS). MUNIX is even able to show loss of motor units in pre-symptomatic, non-wasted muscles [1,2]. So, it has been recognized as a promising biomarker in ALS. ALS, as a multisystemic neurodegenerative disease, shows a high heterogeneity in clinical presentation, including disease phenotypes, progression and survival. We urgently need reliable surrogate markers to describe the individual disease course, reduce diagnostic delay and monitor efficacy of therapeutic strategies in ALS [3]. Additionally to MUNIX, we use the D50 disease progression model to analyze disease aggressiveness and disease accumulation. Patients and Methods: 237 ALS patients, 45 healthy controls and 22 ALS-Mimics received MUNIX of abductor pollicis brevis (APB), abductor digiti minimi (ADM) and tibialis anterior (TA) in clinical routine by trained and certified electrophysiologists using a standardized protocol [4]. MUNIX was further analyzed by disease aggressiveness (D50) and disease accumulation (rD50 phase) in ALS using the D50 progression model. Results: MUNIX and CMAP were significantly lower in ALS patients and ALS-mimics compared to healthy controls (p < 0,05) in all investigated muscles. In ALS subgroup analysis, MUNIX in APB and TA showed significant decrease between rD50 Phase I and II (p < 0,001/p < 0,01), while significant differences in ADM just occurred in advanced disease stage between Phase II and III/IV (p < 0,05). Throughout the subgroups of aggressiveness, there were no significant differences. Conclusion: MUNIX in combination with D50 progression model demonstrates disease accumulation in ALS, especially in APB in early disease compared to ADM. This supports the clinical split-hand-phenomenon. Also, MUNIX seems to be independent of disease aggressiveness. Therefore, we apply MUNIX in combination with the D50 disease progression model to reflect the individual disease course in ALS, which might be useful in clinical trials to evaluate therapeutic strategies and agents in ALS independently of disease aggressiveness.