Motor neuron axonal excitability changes in the clinical course of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by slowly progressive degeneration of upper motor neurons (UMNs) and lower motor neurons (LMNs). Although the pathogenesis of sporadic form of ALS has not been fully elucidated, the initial damage mostly leads to hyperexcitability of the central and peripheral motor neuron. The results of our study aimed to confirm the changes in the excitability of the peripheral motor axon and contribute to the emergence of these measurements as potential biomarkers for disease progression. A total of 56 ALS patients [24 women (43%), median age 62.5 (interquartile range: 53.75-70.25) years] were finally included in the study. Twenty-four healthy controls that were age- and sex-matched to the cases [12 women (50%), mean age 58.46 ± 8.84] were recruited. The first main finding of our study is the fact that abnormalities of the voltage gated K⁺ ion channels were constantly present in ALS patients than in the controls. The multivariate analysis revealed that Superexcitability 7ms lower than - 21.06%, related to shorter survival. Additionally using receiver operating characteristic (ROC) curves, the c-statistic showed Superexcitability 7ms moderate predictive ability. The clinical significance of our results is that Superexcitability 7ms can be used as a biomarker not only for survival but also for disease progression.