Association of Subthalamic Deep Brain Stimulation With Motor, Functional, and Pharmacologic Outcomes in Patients With Monogenic Parkinson Disease
Authors: Carlo Alberto Artusi, Alok K. Dwivedi, Alberto Romagnolo, Gian Pal, Marcelo Kauffman, Ignacio Mata, Dhiren Patel, Joaquin A. Vizcarra, Andrew Duker, Luca Marsili, Binith Cheeran, Daniel Woo, Maria Fiorella Contarino, Leonard Verhagen, Leonardo Lopiano, Alberto J. Espay, Alfonso Fasano, Aristide Merola
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Comparative outcomes among different monogenic forms of Parkinson disease after subthalamic nucleus deep brain stimulation (STN DBS) remain unclear. <h3>Objective</h3> To compare clinical outcomes in patients with the most common monogenic forms of Parkinson disease treated with STN DBS. <h3>Design, Setting, and Participants</h3> Systematic review and meta-analysis in which a PubMed search of interventional and noninterventional studies of Parkinson disease with<i> LRRK2, GBA,</i>or<i>PRKN</i>gene mutations published between January 1, 1990, and May 1, 2018, was conducted. Among the inclusion criteria were articles that reported the Motor subscale of the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) before and after STN DBS treatment, that involved human participants, and that were published in the English language. Studies that used aggregated data from patients with different genetic mutations were excluded, and so were studies with assumed but not confirmed genetic data or incomplete follow-up data. <h3>Main Outcomes and Measures</h3> Changes in UPDRS-III scores and levodopa equivalent daily dose (LEDD) were analyzed for each monogenic form of Parkinson disease. Additional end points included activities of daily living (UPDRS-II), motor complications (UPDRS-IV), and cognitive function. <h3>Results</h3> Of the 611 eligible studies, 17 (2.8%) met the full inclusion criteria; these 17 studies consisted of 8 cohort studies (47.1%), 3 case series (17.6%), and 6 case reports (35.3%), and they involved a total of 518 patients. The UPDRS-III score improved by 46% in<i>LRRK2</i>(mean change, 23.0 points; 95% CI, 15.2-30.8;<i>P</i> &lt; .001), 49% in<i>GBA</i>(20.0 points; 95% CI, 4.5-35.5;<i>P</i> = .01), 43% in<i>PRKN</i>(24.1 points; 95% CI, 12.4-35.9;<i>P</i> &lt; .001), and 53% in idiopathic Parkinson disease (25.2 points; 95% CI, 21.3-29.2;<i>P</i> &lt; .001). The LEDD was reduced by 61% in<i>LRRK2</i>(mean change, 711.9 mg/d; 95% CI, 491.8-932.0;<i>P</i> &lt; .001), 22% in<i>GBA</i>(269.2 mg/d; 95% CI, 226.8-311.5;<i>P</i> &lt; .001), 61% in<i>PRKN</i>(494.8 mg/d; 95% CI, –18.1 to –1007.8;<i>P</i> = .06), and 55% in idiopathic Parkinson disease (681.8 mg/d; 95% CI, 544.4-819.1;<i>P</i> &lt; .001). Carriers of the<i>PRKN</i>mutations showed sustained improvements in UPDRS-II and UPDRS-IV, whereas<i>LRRK2</i>mutation carriers sustained improvements only in UPDRS-IV. Carriers of the<i>GBA</i>mutation showed worse postsurgical cognitive and functional performance. <h3>Conclusions and Relevance</h3> Treatment with STN DBS for patients with Parkinson disease with<i> LRRK2, GBA,</i>or<i>PRKN</i>mutations appears to be associated with similar motor outcomes but different changes in dopaminergic dose, activities of daily living, motor complications, and cognitive functions.