Persistent adverse effects following different targets and periods after bilateral deep brain stimulation in patients with Parkinson's disease

Abstract

Background: Performed as one of the major treatments for advanced Parkinson's disease (PD), deep brain stimulation (DBS) surgery can induce adverse effects (AEs) on cognition, gait, mood, speech and swallowing, which are frequently reported and seriously affect the patient's daily life.

Objective: To comprehensively analysis the adverse effect rates (AERs) of cognition, mood, gait, speech and swallowing after bilateral DBS in patients with PD.

Method: We performed a systematic search in PubMed, EMBASE and the Cochrane Library to collect all the articles reporting AEs after DBS in sufferers of PD. The cited articles were also manually searched.

Results: A total of 31 articles were quantitatively analyzed. Random-effects models were used to calculate the AERs and 95% confidence intervals. Of all patients, the pooled AER of the five types of events was 24.0%. Specifically, the risks of cognition, mood and speech disturbance were higher after subthalamic nucleus (STN) -DBS than after globus pallidus interna (GPi) -DBS: 25.1% versus 14.6%, 26.3% versus 22.2% and 29.0% versus 19.6%, respectively. However, the AER of dysphagia was slightly lower after STN-DBS: 8.6% versus 10.1%. The risk of gait disorders was similar between two target groups in sub-analysis of random control trials (RCTs): 38.3% in STN group and 37.3% in GPi group. In three follow-up intervals, short-term follow-up (STF), mid-term follow-up (MTF) and long-term follow-up (LTF), gait (17.6%~19.9%~28.0%), speech (7.8%~26.9%~31.5%) and mood (7.4%~24.9%~30.7%) disorders worsened progressively. While cognitive disturbance (22.5%~27.1%~16.7%) reached its highest rate at MTF.

Conclusion: STN-DBS was 10% more likely to cause cognitive and speech disturbance than GPi-DBS, while STN-DBS had a lower risk of dysphagia. Two target groups had similar effects on gait. The pooled AER increased over time, while cognitive disturbance reached its highest rate at the 6- to 18-month follow-up. Additionally, speech and mood disturbance deteriorated rapidly from STF to MTF. Further investigation of the pathophysiology will help alleviate those AEs after DBS.

Keywords: Adverse effects; Deep brain stimulation; Globus pallidus internus; Parkinson's disease; Subthalamic nucleus.