Fasciculation discharge frequency in amyotrophic lateral sclerosis and related disorders

In amyotrophic lateral sclerosis (ALS), fasciculations are believed to become less frequent during disease progression, associated with the loss of motor units. To address this issue, we studied the variation of fasciculation potential (FPs) frequency as evaluated by surface electromyography of the first dorsal interosseous muscle (1st DI) in patients with ALS and other related disorders, and to relate this change with the neurophysiological index (NI), a surrogate measure of functional motor units.

We measured the FP frequency and mean amplitude during a two minute recording of the relaxed right first dorsal interosseous muscle (1st DI) in 34 ALS patients, 9 subjects with benign fasciculations (BFS), 6 with primary lateral sclerosis (PLS) and 4 with spinal muscle atrophy (SMA). ALS patients were evaluated 2-5times at 4month intervals, people with BFS were evaluated 3-4 times at the same interval, those with SMA and PLS were evaluated at 6month intervals 2-4times. The NI was derived from the amplitude of the motor response and F-wave frequency after distal ulnar nerve stimulation.

The NI decreased significantly in ALS (p<0.001) but not in the other groups. At baseline, the median FP frequency was 0.29Hz in the ALS group and did not change significantly. During progression, in some ALS patients with very weak 1st DI the FP frequency increased. In subjects with BFS the mean FP frequency was 0.28Hz at entry and remained stable. In patients with PLS FPs were less frequent (median 0.038Hz) but more frequent in SMA patients (median 1.15Hz). In both groups their firing frequency did not change. During the study the mean amplitude of FPs was unchanged in all groups.

In ALS, the generators of FPs remain active even when the number of motor units is quite reduced, consistent with increased motoneuron excitability associated with unstable axonal sprouts during the process of continuous partial reinnervation. In BFS and other neuromuscular disorders, including SMA, the FP frequency is stable over time, suggesting mature motor axons that are not hyperexcitable and less prone to ectopic activity.

In ALS, the FP firing frequency does not decline significantly over several months, in spite of a marked reduction in the number of functional motor units.