Activity-dependent conduction block in multifocal motor neuropathy

Patients with multifocal motor neuropathy may complain of muscle fatigue, e ven though the degree of conduction block assessed at rest has improved wit h treatment. To explore the mechanism involved, we examined changes in musc le force during maximum voluntary contraction (MVC) and monitored conductio n block before and after MVC in five patients with multifocal motor neuropa thy, The results were compared with those for the contralateral unaffected homonymous muscles. For one patient, who had bilateral involvement, a norma l subject of a similar age and stature served as the control. Results of co nduction studies were also compared with those from six patients with amyot rophic lateral sclerosis (ALS) with similar compound muscle action potentia l (CMAP) amplitudes after proximal stimulation, During MVC for 60 s, the af fected muscles developed prominent fatigue; the force at the end of contrac tion compared with the initial force was significantly lower for the affect ed muscles [42 +/- 19% (mean +/- standard deviation) of the initial force] than for the control muscles (93 +/- 9%; P = 0.01). After MVC, the amplitud e ratio of CMAPs after proximal versus distal nerve stimulation transiently decreased to 19 +/- 14% of that before MVC in the affected muscles, but no t in the control muscles (94 +/- 3.8% of that before MVC) and in patients w ith ALS (95 +/- 6.7%). In one patient with a focal lesion in the forearm, n erve excitability was monitored at the lesion site before and after MVC for 120 s. There were significant increases in axonal threshold (similar to 48 %) and supernormality (similar to 135%) immediately after MVC, suggesting t hat the axonal membrane had undergone hyperpolarization and, by extrapolati on, that this had precipitated the conduction block. This study is the firs t to show that activity-dependent conduction block plays a role in human di sease by causing muscle fatigue.