O3-C-3. Electrophysiological study of familial amyotrophic lateral sclerosis with expansions in the C9ORF72

Abstract

A hexanucleotide repeat expansion in the chromosome 9 open reading frame 72 (C9ORF72) gene was recently discovered as a cause underlying familial amyotrophic lateral sclerosis (ALS), and considered as the most common genetic cause of sporadic ALS in Caucasian populations. We investigated electrophysiological features of an ALS patient with expansion in the C9OFR72.The patient was a 63-year-old female and had family history of ALS. She developed bulbar palsy and subsequent limb weakness for 9 months. On admission, muscle atrophy in the tongue and four limbs, and pyramidal signs in the cranial, cervical, and lumbar segments were seen. She showed neither dementia nor Parkinsonism. On electromyogram, fasciculations were detected in the tibialis anterior. Axonal excitability testing showed greater strength-duration time constant, greater changes in depolarizing threshold electrotonus, and greater supernormality in recovery cycle, which indicate increased sodium conductance and reduced potassium conductance. The above findings suggest increased axonal excitability in this case. Motor axonal hyperexcitability is considered as one of the major prognostic factors in sporadic ALS. This might enhance neuronal death also in FALS with the C9ORF72 repeat expansion.