Background There is little information on the earliest changes in motor unit (MU) physiology in amyotrophic lateral sclerosis (ALS) and the development of the classical neurophysiological features of ALS over time.

Objective We studied the earliest abnormalities in MU physiology in ALS and changes over time.

Design Observational, cross-sectional and longitudinal study.

Population and methods We studied the tibialis anterior (TA) muscle in three groups of subjects; 73 patients with ALS, 10 with benign fasciculation and 37 healthy control subjects. In the ALS group, 61 had normal strength in the TA muscle and 12 had TA muscle strength of 4 on the medical research council scale. In all subjects we evaluated the presence of fasciculation potentials (FPs) and fibrillation/sharp-waves (fibs-sw), and quantified MU potentials (MUPs) and jitter. Twenty-six ALS patients with TA muscle of normal strength were investigated in serial studies.

Results FPs were recorded in TA muscles (medical research council 5) of 21 ALS patients with normal MUPs. Longitudinal studies confirmed that the patients presenting with FPs as the only abnormality progressed to MUP instability before large MUPs associated with fibs-sw were detected. FPs from ALS patients with no other neurophysiological change were simpler than in patients in whom there were also fibs-sw and neurogenic MUPs. The complexity of FPs in patients with weak TA muscle was greater than in the latter group. FPs in patients with benign fasciculations were simpler than FPs in ALS patients with normal TA muscle strength.

Conclusions FPs are a very early marker of ALS and anticipate MUP instability or reinnervation, consistent with a very early phase of increased axonal excitability. Later, widespread neuronal dysfunction causes widespread fibs-sw and loss of MUPs with compensatory reinnervation. Our results confirm the importance of FP morphology analysis in the differential diagnosis of ALS and other disorders, and indicate that benign FPs represent a different phenomenon.