Levodopa normalizes exercise related cortico-motoneuron excitability abnormalities in Parkinsonʹs disease

Objectives: To measure exercise induced changes in cortico-motoneuron excitability in Parkinsonʹs disease (PD) before and after levodopa. Methods: Transcranial magnetic stimulation was delivered at 10% above resting motor threshold in 9 PD and 8 control subjects. Each subject performed repetitive isometric wrist extension at 50% of the baseline maximal voluntary contraction (MVC) for 30 s with 3 s rest between extensions until fatigued, defined as the inability to generate force at more than 25% of the baseline MVC. We recorded motor evoked potentials (MEPs) from the resting extensor carpi radialis muscle before (baseline), during, and after fatiguing exercise. Baseline electromyographic activity was closely monitored. We compared absolute MEP amplitudes between PD and controls, before and after levodopa, during baseline, exercise, and recovery periods. We correlated absolute MEP amplitudes with an objective measure of fatigability. Results: PD subjects in the “off” state had increased absolute MEP amplitudes compared with controls. The effect was present in all 3 exercise periods. These differences disappeared after levodopa. Post-exercise facilitation was clear for PD subjects before and after levodopa, but post-exercise depression was not significant. Absolute MEP amplitude showed negative correlation with objective fatigability for PD subjects before levodopa. Conclusions: Levodopa normalized the increased cortico-motoneuron excitability in PD patients before, during, and after fatiguing exercise. Significance: This study demonstrated the abnormal cortico-motoneuron excitability associated with motor fatigue in PD.