OBJECTIVE: The objective of this study was to evaluate clinical features and response to deep brain stimulation (DBS) in G2019S LRRK2-Parkinson disease (LRRK2-PD) and idiopathic PD (IPD). METHODS: The authors conducted a clinic-based cohort study of PD patients recruited from the Mount Sinai Beth Israel Genetics database of PD studies. The cohort included 87 participants with LRRK2-PD (13 who underwent DBS) and 14 DBS participants with IPD enrolled between 2009 and 2017. The baseline clinical features, including motor ratings and levodopa-equivalent daily dose (LEDD), were compared among LRRK2-PD patients with and without DBS, between LRRK2-PD with DBS and IPD with DBS, and between LRRK2-PD with subthalamic nucleus (STN) and internal segment of the globus pallidus (GPi) DBS. Longitudinal motor scores (Unified Parkinson's Disease Rating Scale-part III) and medication usage were also assessed pre- and postoperatively. RESULTS: Compared to LRRK2-PD without DBS (n = 74), the LRRK2-PD with DBS cohort (n = 13) had a significantly younger age of onset, longer disease duration, were more likely to have dyskinesia, and were less likely to experience hand tremor at disease onset. LRRK2-PD participants were also more likely to be referred for surgery because of severe dyskinesia (11/13 [85%] vs 6/14 [43%], p = 0.04) and were less likely to be referred for medically refractory tremor (0/13 [0%] vs 6/14 [43%], p = 0.02) than were IPD patients. Among LRRK2-PD patients, both STN-DBS and GPi-DBS targets were effective, although the sample size was small for both groups. There were no revisions or adverse effects reported in the GPi-DBS group, while 2 of the LRRK2-PD participants who underwent STN-DBS required revisions and a third reported depression as a stimulation-related side effect. Medication reduction favored the STN group. CONCLUSIONS: The LRRK2-PD cohort referred for DBS had a slightly different profile, including earlier age of onset and dyskinesia. Both the STN and GPi DBS targets were effective in symptom suppression. Patients with G2019S LRRK2 PD were well-suited for DBS therapy and had favorable motor outcomes regardless of the DBS target. LRRK2-DBS patients had longer disease durations and tended to have more dyskinesia. Dyskinesia commonly served as the trigger for DBS surgical candidacy. Medication-refractory tremor was not a common indication for surgery in the LRRK2 cohort.
OBJECTIVE: The objective of this study was to evaluate clinical features and response to deep brain stimulation (DBS) in G2019S LRRK2-Parkinson disease (LRRK2-PD) and idiopathic PD (IPD). METHODS: The authors conducted a clinic-based cohort study of PD patients recruited from the Mount Sinai Beth Israel Genetics database of PD studies. The cohort included 87 participants with LRRK2-PD (13 who underwent DBS) and 14 DBS participants with IPD enrolled between 2009 and 2017. The baseline clinical features, including motor ratings and levodopa-equivalent daily dose (LEDD), were compared among LRRK2-PD patients with and without DBS, between LRRK2-PD with DBS and IPD with DBS, and between LRRK2-PD with subthalamic nucleus (STN) and internal segment of the globus pallidus (GPi) DBS. Longitudinal motor scores (Unified Parkinson's Disease Rating Scale-part III) and medication usage were also assessed pre- and postoperatively. RESULTS: Compared to LRRK2-PD without DBS (n = 74), the LRRK2-PD with DBS cohort (n = 13) had a significantly younger age of onset, longer disease duration, were more likely to have dyskinesia, and were less likely to experience hand tremor at disease onset. LRRK2-PD participants were also more likely to be referred for surgery because of severe dyskinesia (11/13 [85%] vs 6/14 [43%], p = 0.04) and were less likely to be referred for medically refractory tremor (0/13 [0%] vs 6/14 [43%], p = 0.02) than were IPD patients. Among LRRK2-PD patients, both STN-DBS and GPi-DBS targets were effective, although the sample size was small for both groups. There were no revisions or adverse effects reported in the GPi-DBS group, while 2 of the LRRK2-PD participants who underwent STN-DBS required revisions and a third reported depression as a stimulation-related side effect. Medication reduction favored the STN group. CONCLUSIONS: The LRRK2-PD cohort referred for DBS had a slightly different profile, including earlier age of onset and dyskinesia. Both the STN and GPi DBS targets were effective in symptom suppression. Patients with G2019S LRRK2 PD were well-suited for DBS therapy and had favorable motor outcomes regardless of the DBS target. LRRK2-DBS patients had longer disease durations and tended to have more dyskinesia. Dyskinesia commonly served as the trigger for DBS surgical candidacy. Medication-refractory tremor was not a common indication for surgery in the LRRK2 cohort.
Authors: Kenneth A Follett; Frances M Weaver; Matthew Stern; Kwan Hur; Crystal L Harris; Ping Luo; William J Marks; Johannes Rothlind; Oren Sagher; Claudia Moy; Rajesh Pahwa; Kim Burchiel; Penelope Hogarth; Eugene C Lai; John E Duda; Kathryn Holloway; Ali Samii; Stacy Horn; Jeff M Bronstein; Gatana Stoner; Philip A Starr; Richard Simpson; Gordon Baltuch; Antonio De Salles; Grant D Huang; Domenic J Reda Journal: N Engl J Med Date: 2010-06-03 Impact factor: 91.245
Authors: Roy N Alcalay; Helen Mejia-Santana; Ming Xin Tang; Llency Rosado; Miguel Verbitsky; Sergey Kisselev; Barbara M Ross; Elan D Louis; Cynthia L Comella; Amy Colcher; Danna Jennings; Martha A Nance; Susan Bressman; William K Scott; Caroline Tanner; Susan F Mickel; Howard F Andrews; Cheryl H Waters; Stanley Fahn; Lucien J Cote; Steven J Frucht; Blair Ford; Michael Rezak; Kevin Novak; Joseph H Friedman; Ronald Pfeiffer; Laura Marsh; Bradley Hiner; Andrew Siderowf; Elise Caccappolo; Ruth Ottman; Lorraine N Clark; Karen S Marder Journal: Arch Neurol Date: 2009-12
Authors: Frances M Weaver; Kenneth Follett; Matthew Stern; Kwan Hur; Crystal Harris; William J Marks; Johannes Rothlind; Oren Sagher; Domenic Reda; Claudia S Moy; Rajesh Pahwa; Kim Burchiel; Penelope Hogarth; Eugene C Lai; John E Duda; Kathryn Holloway; Ali Samii; Stacy Horn; Jeff Bronstein; Gatana Stoner; Jill Heemskerk; Grant D Huang Journal: JAMA Date: 2009-01-07 Impact factor: 56.272
Authors: Vincent J J Odekerken; Judith A Boel; Ben A Schmand; Rob J de Haan; M Figee; Pepijn van den Munckhof; P Richard Schuurman; Rob M A de Bie Journal: Neurology Date: 2016-01-27 Impact factor: 9.910
Authors: Alexander Zimprich; Saskia Biskup; Petra Leitner; Peter Lichtner; Matthew Farrer; Sarah Lincoln; Jennifer Kachergus; Mary Hulihan; Ryan J Uitti; Donald B Calne; A Jon Stoessl; Ronald F Pfeiffer; Nadja Patenge; Iria Carballo Carbajal; Peter Vieregge; Friedrich Asmus; Bertram Müller-Myhsok; Dennis W Dickson; Thomas Meitinger; Tim M Strom; Zbigniew K Wszolek; Thomas Gasser Journal: Neuron Date: 2004-11-18 Impact factor: 17.173