Deep brain stimulation for atypical parkinsonism: A systematic review on efficacy and safety

Background: Atypical Parkinsonisms (APs) -including progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB)- are neurodegenerative diseases lacking satisfying symptomatic therapies. Deep Brain Stimulation (DBS) is an established neurosurgical option for advanced Parkinson disease (PD). Although DBS effectiveness in PD fed expectations for the treatment of APs, DBS is still not recommended for APs on the basis of expert consensus and lack of clinical trials. Objective: In this systematic review, we sought to analyze current evidence on the safety and efficacy of DBS in APs, discussing clinical indications, anatomical targets, and ethical issues. Methods: Following the PRISMA guidelines, we systematically searched PubMed for studies reporting the outcome of patients with APs treated with DBS. Results: We identified 25 eligible studies for a total of 66 patients with APs treated with DBS: 31 PSP, 22 MSA, 12 DLB, 1 unspecified parkinsonism with tongue tremor. Targeted nuclei were subthalamic nucleus (STN), globus pallidus pars-interna (GPi), pedunculopontine nucleus (PPN), and nucleus basalis of Meynert (nbM). Only 3/25 studies were randomized controlled trials, and most studies showed a high risk of bias. Conclusion: Taking into account study biases and confounding factors, current evidence does not support the use of DBS in APs. However, some interesting insights arise from the literature, such as the high frequency of cognitive/neurobehavioral issues in MSA patients treated with STN-DBS, the low frequency of complications in trials of nbM-DBS for DLB, and the possible good response of dystonic symptoms in PSP with GPi DBS.