SOD1 and amyotrophic lateral sclerosis: Importantly, longitudinal studies in pre-symptomatic SOD1 mutation carriers revealed that cortical hyperexcitability develops prior to clinical onset of ALS (Vucic et al., 2008), and characterizes also early sporadic patients (Mills and Nithi, 1997; Zanette et al., 2002; Vucic, 2006; Hardiman et al., 2017a).