To characterize clinical and electrophysiological hallmarks of C9ALS and determine if there are features that allow differentiation from C9ORF72 negative ALS (non-C9ALS).

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal, neurodegenerative disorder of the motor neurons. Although the majority of cases are sporadic, identification of familial forms, of which C9ORF72 (C9ALS) contributes to a significant majority, can have important implications for evaluation, prognosis and potentially therapeutics.

We retrospectively reviewed clinical and electrodiagnostic (EDX) data for all genetically confirmed C9ALS cases seen between 1/1/2012 to 10/1/2020 and compared them 1:1 with non-C9ALS patients in same time frame. 

99 C9ALS and 99 non-C9ALS were identified. Compared to non-C9ALS, C9ALS demonstrated higher prevalence of women (57.6%, P=0.002), lesser variability in racial makeup (97/99 Caucasian, P=0.005), expected strong family history of ALS (50.5%, P <0.001) and higher predominance of upper motor neuron signs (cervical hyperreflexia P=0.02, limb spasticity: P<0.001 - right upper limb, P=0.03 - right lower and left upper limb). EDX testing showed higher median antidromic sensory nerve action potential amplitudes (P=0.004) and lower fibular compound muscle action potential amplitudes (P=0.003) among C9ALS.

Although some individual nerve conduction parameters reached statistical significance in our study, it is unclear if this is sufficient to discriminate C9ALS from non-C9ALS on case-by-case basis. In contrast to prior studies, we were not able confirm that the prevalence of EDX sensory abnormalities were higher among C9ALS. Genetic testing is required to identify C9ALS patients.