Axonal function and activity-dependent excitability changes in myotonic dystrophy.

To investigate peripheral nerve function and its potential contribution to symptoms of weakness in myotonic dystrophy type 1 (MD), nerve excitability was assessed in 12 MD patients. Compound muscle action potentials (CMAPs) were recorded at rest from abductor pollicis brevis (APB) following stimulation of the median nerve. Stimulus-response behavior, threshold electrotonus, a current-threshold relationship, and recovery cycles were successfully recorded in each patient. Compared with controls, there was significant reduction in CMAP amplitude in MD patients. This was accompanied by reduction in depolarizing threshold electrotonus and an increase in refractoriness and in the duration of the relative refractory period. To determine whether alteration in axonal resting membrane potential was a factor underlying these changes, axonal excitability was assessed following maximal contraction of APB for 60 seconds. Following contraction, there was reduction in CMAP amplitude for a submaximal stimulus (by 51.5+/-11.8%) and an increase in super-excitability (of 22.2+/-12.0%), consistent with activity-dependent hyperpolarization, with a greater increase in threshold for MD patients compared to controls (MD group, 22.3+/-5.1%; controls, 11.7+/-2.1%; P<0.04) and prolonged recovery to baseline. The present study has established that greater activity-dependent changes in excitability may be induced in MD patients by maximal voluntary contraction when compared to controls. The excitability changes and prolonged recovery of threshold following contraction are likely to contribute to symptoms of fatigue and weakness in MD patients.