Deep brain stimulation for monogenic Parkinson’s disease: a systematic review

Abstract

<p>Deep brain stimulation (DBS) is an effective treatment for Parkinson’s disease (PD) patients with motor fluctuations and dyskinesias. The key DBS efficacy studies were performed in PD patients with unknown genotypes; however, given the estimated monogenic mutation prevalence of approximately 5–10%, most commonly <em>LRRK2, PRKN, PINK1</em> and <em>SNCA</em>, and risk-increasing genetic factors such as <em>GBA</em>, proper characterization is becoming increasingly relevant. We performed a systematic review of 46 studies that reported DBS effects in 221 genetic PD patients. The results suggest that monogenic PD patients have variable DBS benefit depending on the mutated gene. Outcome appears excellent in patients with the most common <em>LRRK2</em> mutation, p.G2019S, and good in patients with <em>PRKN</em> mutations but poor in patients with the more rare <em>LRRK2</em> p.R1441G mutation. The overall benefit of DBS in <em>SNCA, GBA</em> and <em>LRRK2</em> p.T2031S mutations may be compromised due to rapid progression of cognitive and neuropsychiatric symptoms. In the presence of other mutations, the motor changes in DBS-treated monogenic PD patients appear comparable to those of the general PD population.<br /></p>