Early Axonal Dysfunction of the Peripheral Nervous System Influences Disease Progression of ALS: Evidences From Clinical Neuroelectrophysiology

Abstract

Background:Studies have indicated that more axonal dysfunction in early ALS predictive of more aggressive phenotypes. However, as an important electrophysiological index to detect motor axonal damage, the prognostic value of compound muscle action potential (CMAP) in ALS remains unclear. We aimed to determine if CMAP could be a prognostic indicator of disease progression in early ALS.Methods: Patients were stratified into 4 groups according to the decrement of the CMAP amplitude within 12 months of symptom onset (CMAP-12 amplitudes): normal (≥the lower limit of normal, LLN), mild (<LLN but ≥50% of LLN), moderate (<50% but ≥30% of LLN) and severe (<30% of LLN). All patients were followed up every 3 months. Survival was analyzed using the Kaplan-Meier method and Cox proportional hazards regression.Results: A total of 149 patients included in the analysis [90 male (60.4%); mean age at onset, 50.7 years]. The decrement of CMAP-12 amplitudes was normal in 24.2%, mildly in 22.1%, moderately in 15.4% and severely in 38.3%. Kaplan-Meier analysis showed there was a significant difference in the overall survival across the 4 groups (p<0.05). Further pairwise comparison found there were significant differences in survival between the normal vs. the moderately groups (p<0.05), and the normal vs. the severely groups (p<0.01). There was a significant inverse correlation between the CMAP-12 amplitude and overall survival. Compared to the normal group, survival in the moderately and severely decreased groups were significantly shorter (HR 3.394, 95%CI 1.292-8.917, p=0.013; and HR 4.732, 95%CI 2.032-11.017; p=0.000, respectively).Conclusions: Our results suggested that CMAP-12 amplitude could be a prognostic indicator of disease progression in ALS. More importantly, it provided clinical evidences to the viewpoint that early axonal dysfunction of peripheral nervous system accelerates disease progression of ALS.