Low-frequency subthalamic nucleus deep brain stimulation for axial symptoms in advanced Parkinson’s disease

Abstract

Axial symptoms such as freezing of gait and falls are common manifestations of advanced Parkinson's disease (PD) and are partially responsive to medical treatment. High-frequency (≥130 Hz) deep brain stimulation (DBS) of the subthalamic nucleus (STN) is highly efficacious in ameliorating appendicular symptoms in PD. However, it is typically less effective in improving axial symptomatology, especially in the long term. We have studied the effects of low-frequency stimulation (LFS) (≤80 Hz) for improving speech, gait and balance dysfunction in the largest patient population to date. PD patients with bilateral STN-DBS and resistant axial symptoms were switched from chronic 130 Hz stimulation to LFS and followed up to 4 years. Primary outcome measures were total motor UPDRS scores, and axial and gait subscores before and after LFS. Bivariate analyses and correlation coefficients were calculated for the different conditions. Potential predictors of therapeutic response were also investigated. Forty-five advanced PD patients who had high frequency stimulation (HFS) for 39.5 ± 27.8 consecutive months were switched to LFS. LFS was kept on for a median period of 111.5 days before the assessment. There was no significant improvement in any of the primary outcomes between HFS and LFS, although a minority of patients preferred to be maintained on LFS for longer periods of time. No predictive factors of response could be identified. There was overall no improvement from LFS in axial symptoms. This could be partly due to some study limitations. Larger prospective trials are warranted to better clarify the impact of stimulation frequency on axial signs.