A Systematic Review of the Biological Processes Involved in Deep-Brain Stimulation for Parkinson's disease: A Focus on the Potential Disease-Modifying Effects
Authors:   Department of Human Neuroscience, ", Sciancalepore Francesco ,   Sapienza",   University of Rome, Rome, Italy,   National Center for Disease Prevention and Health Promotion, Italian National Institute of Health, Viale Regina Elena, 299, 00161 Rome, Italy, Remoli Giulia ,   National Center for Disease Prevention and Health Promotion, Italian National Institute of Health, Viale Regina Elena, 299, 00161 Rome, Italy, Tariciotti Leonardo ,   Unit of Neurosurgery, IRCSS Fondazione Cà Grande Ospedale Maggiore Policlinico, University of Milan, Via Francesco Sforza, 35, 20122 Milan, Italy,   Department of Oncology and Hemato-oncology, University of Milan, Via Festa del Perdono 7, 20122 Milan, Italy, Sarti Giulia ,   Department of Human Neuroscience, "Sapienza" University of Rome, Rome, Italy, Trentin Federica ,   Department of Oncological and Degenerative Spine Surgery, IRCCS, Rizzoli Orthopedic Institute, Via G.C. Pupilli, 1, 40136 Bologna, Italy, Riccardi Gabriele ,   Department of Sense Organ, Sapienza University of Rome, Viale del Policlinico, 155, 00161 Rome, Italy, Lacorte Eleonora ,   National Center for Disease Prevention and Health Promotion, Italian National Institute of Health, Viale Regina Elena, 299, 00161 Rome, Italy, Corbo Massimo ,   Department of Neurorehabilitation Sciences, Casa Cura Policlinico, Via Dezza 48, 20144 Milan, Italy, Canevelli Marco ,   Department of Human Neuroscience, "Sapienza" University of Rome, Rome, Italy,   National Center for Disease Prevention and Health Promotion, Italian National Institute of Health, Viale Regina Elena, 299, 00161 Rome, Italy, Vanacore Nicola ,   National Center for Disease Prevention and Health Promotion, Italian National Institute of Health, Viale Regina Elena, 299, 00161 Rome, Italy, Piscopo Paola ,   Department of Neuroscience, Italian National Institute of Health, Viale Regina Elena, 299, 00161 Rome, Italy
Published: May 2021

Deep-Brain Stimulation (DBS) is an important treatment option for the management of Parkinson’s disease (PD) and is a common symptomatic treatment. However, an increasing number of studies have examined the biological processes to assess if DBS can also modify the natural history of PD by acting on its pathophysiological mechanisms. Relevant literature published up to November 2020 was systematically searched on databases such as PubMed, ISI Web of Knowledge, Academic Search Index, and Science Citation Index. The following predefined inclusion criteria were applied to the full-text versions of the selected articles: i) recruiting and monitoring of PD subjects that were previously treated with DBS and ii) investigating the electrophysiological, biochemical, epigenetic, or neuroimaging effects of DBS. Studies focusing exclusively on motor and clinical changes were excluded. Reviews, case reports, studies on animal models, and computational studies were also not considered. Out of 2,960 records screened, 43 studies met the inclusion criteria. Only three studies described a potential disease-modifying effect of DBS. However, a wide heterogeneity was observed in the investigated biomarkers, and the design and methodological issues of several studies limited their ability to find potential disease-modifying features. Specifically, 60.4% of the trials followed-up subjects for no more than 1 year from the surgical intervention, and 67.4% observed patients with PD only once after DBS. Moreover, 64.2% of the studies enrolled late-stage PD patients. Most of the studies (88.4%) reported that DBS only had a symptomatic effect, with several of them showing some limitations in the study design and recruitment of patients. Further studies using shared biomarkers are encouraged to assess if and how DBS might affect the progression of PD. Based on the existing preclinical literature, prospective clinical trials examining the course of PD in early-stage patients are needed.