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Fasciculation is a characteristic feature of ALS. Nerve excitability studies have shown increased persistent sodium currents and reduced potassium currents in motor axons of ALS patients, both of which lead to axonal hyperexcitability and thereby generation of fasciculations. The present study was undertaken to investigate whether abnormal axonal excitability indices are correlated with survival in ALS patients. A total of 112 consecutive patients with sporadic ALS were followed-up until endpoint (death or tracheostomy). Univariate analyses revealed longer strength-duration time constant (SDTC) was associated with a shorter survival. In multivariate analyses using the Cox proportional hazard model, onset age&gt;60 years and longer SDTC were strong predictors of shorter survival. Assuming that SDTC depends on nodal persistent sodium conductances, our results showed that an increased persistent sodium current is strong and independent predictor for short survival of ALS patients. These findings support the hypothesis that membrane hyperexcitability would contribute to motor neuronal death in ALS.

Motor axonal excitability properties are strong predictors for survival in amyotrophic lateral sclerosis