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

Objective: To assess the prognostic value of the decrement in compound muscle action potential amplitude within 12 months of symptom onset (CMAP-12 amplitude) for the survival of patients with amyotrophic lateral sclerosis (ALS). Methods: Patients were stratified into 4 groups according to the decrement of the 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 were included in the analysis [90 males (60.4%); mean age at onset, 50.7 years]. The decrement of CMAP-12 amplitudes was normal in 24.2% of patients, mild in 22.1%, moderate in 15.4% and severe 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 comparisons identified significant differences in survival between the normal vs. the moderate group (p < 0.05) and the normal vs. the severe group (p < 0.01). There was a significant inverse correlation between the CMAP-12 amplitude and overall survival. Compared to that in the normal group, survival in the moderately and severely decreased groups was 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 suggest that CMAP-12 amplitude could be a prognostic indicator of disease progression in ALS. More importantly, our findings provide clinical evidence for the viewpoint that early axonal dysfunction of the peripheral nervous system accelerates disease progression of ALS.