Differential effects of levodopa and subthalamic nucleus deep brain stimulation on bradykinesia in Parkinson's...

Cardinal symptoms of Parkinson's disease (PD) respond well to treatment with levodopa and deep brain stimulation (DBS) of the subthalamic nucleus (STN). However, it has remained unclear whether levodopa and STN-DBS have differential effects on bradykinesia. We investigated 8 PD-patients with STN-electrodes in four conditions: STN-DBS and levodopa (ON(MED)/ON(STIM)), STN-DBS only (OFF(MED)/ON(STIM)), levodopa only (ON(MED)/OFF(STIM)), without STN-DBS/levodopa (OFF(MED)/OFF(STIM)). Fourteen volunteers served as controls. Subjects performed fastest possible (1) pronation/supination of the forearm (diadochokinesia) and (2) flexion and extension of the index finger (finger movements). Movements were recorded using a 3D-ultrasound-system. Maximum frequency, amplitude, and smoothness of movements were determined. During OFF(MED)/OFF(STIM), all parameters were worser than in all other conditions. In proximal diadochokinesia, OFF(MED)/ON(STIM) significantly improved the amplitude and frequency, whereas ON(MED)/OFF(STIM) had no significant effect. In contrast, we found a stronger effect of levodopa (ON(MED)/OFF(STIM)) on amplitudes of distal finger movement than on amplitudes of diadochokinesia. Combination of treatments during ON(MED)/ON(STIM) further improved both movements. However, maximum frequency remained lower in PD-patients during ON(MED)/ON(STIM) compared with controls. This study demonstrates a better effect of levodopa on distal finger movements and STN-DBS on proximal diadochokinesia. Furthermore, a complementary effect of both therapies on brain areas involved in bradykinesia can be assumed.