Effect of bilateral subthalamic nucleus stimulation on levodopa-unresponsive axial symptoms in Parkinson's disease

The levodopa responsiveness of motor, particularly axial symptoms is a good predictor of the effectiveness of subthalamic nucleus (STN) stimulation in patients with Parkinson's disease (PD). However, many Japanese PD patients are intolerant of higher doses of antiparkinsonian drugs and some aspects of their axial symptoms may remain unresponsive to treatment. We retrospectively investigated the effects of bilateral STN stimulation on the axial signs unresponsive to levodopa in Japanese patients with PD.

We enrolled 29 consecutive patients into this study. Six independent axial symptoms, i.e. falling, freezing, gait, standing, posture, and postural instability, were scored on the Unified Parkinson's Disease Rating Scale (UPDRS), before and 3 months after bilateral STN stimulation and differences were statistically analysed.

Postoperatively, the mean levodopa dosage was decreased by 27%. The preoperative responsiveness to antiparkinsonian drugs with respect to freezing, gait, posture, and postural instability were positively correlated with postoperative off-medication improvement (p < 0.05). For each individual axial symptom, some patients showed an excellent response to STN stimulation, despite preoperative unresponsiveness to levodopa. These selected patients were not always treated with lower doses of antiparkinsonian drugs preoperatively, but they had milder preoperative scores on the UPDRS with respect to daily activities and overall axial function.

The axial symptoms of PD unresponsive to levodopa were ameliorated by bilateral STN stimulation in patients manifesting a milder degree of preoperative axial signs. Our findings suggest that STN stimulation exerted a definite but limited effect on levodopa-unresponsive axial features, pointing to the need to identify different target structures that control axial functions via non-dopaminergic systems.