Efficacy and safety of deep brain stimulation in tourette syndrome the international tourette syndrome deep brain stimulation public database and registry

Daniel Martinez-Ramirez, Joohi Jimenez-Shahed, James Frederick Leckman, Mauro Porta, Domenico Servello, Fan Gang Meng, Jens Kuhn, Daniel Huys, Juan Carlos Baldermann, Thomas Foltynie, Marwan I. Hariz, Eileen M. Joyce, Ludvic Zrinzo, Zinovia Kefalopoulou, Peter Silburn, Terry Coyne, Alon Y. Mogilner, Michael H. Pourfar, Suketu M. Khandhar, Man AuyeungJill Louise Ostrem, Veerle Visser-Vandewalle, Marie Laure Welter, Luc Mallet, Carine Karachi, Jean Luc Houeto, Bryan Timothy Klassen, Linda Ackermans, Takanobu Kaido, Yasin Temel, Robert E. Gross, Harrison C. Walker, Andres M. Lozano, Benjamin L. Walter, Zoltan Mari, William S. Anderson, Barbara Kelly Changizi, Elena Moro, Sarah Elizabeth Zauber, Lauren E. Schrock, Jian Guo Zhang, Wei Hu, Kyle Rizer, Erin H. Monari, Kelly D. Foote, Irene A. Malaty, Wissam Deeb, Aysegul Gunduz, Michael S. Okun

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

IMPORTANCE Collective evidence has strongly suggested that deep brain stimulation (DBS) is a promising therapy for Tourette syndrome. OBJECTIVE To assess the efficacy and safety of DBS in a multinational cohort of patients with Tourette syndrome. DESIGN, SETTING, AND PARTICIPANTS The prospective International Deep Brain Stimulation Database and Registry included 185 patients with medically refractory Tourette syndrome who underwent DBS implantation from January 1, 2012, to December 31, 2016, at 31 institutions in 10 countries worldwide. EXPOSURES Patients with medically refractory symptoms received DBS implantation in the centromedian thalamic region (93 of 163 [57.1%]), the anterior globus pallidus internus (41 of 163 [25.2%]), the posterior globus pallidus internus (25 of 163 [15.3%]), and the anterior limb of the internal capsule (4 of 163 [2.5%]). MAINOUTCOMESANDMEASURES ScoresontheYale GlobalTicSeverity Scaleandadverseevents. RESULTS The International Deep Brain Stimulation Database and Registry enrolled 185 patients (of 171 with available data, 37 females and 134 males; mean [SD] age at surgery, 29.1 [10.8] years [range, 13-58 years]). Symptoms of obsessive-compulsive disorder were present in 97 of 151 patients (64.2%) and 32 of 148 (21.6%) had a history of self-injurious behavior. The mean (SD) total Yale Global Tic Severity Scale score improved from 75.01 (18.36) at baseline to 41.19 (20.00) at 1 year after DBS implantation (P < .001). The mean (SD) motor tic subscore improved from 21.00 (3.72) at baseline to 12.91 (5.78) after 1 year (P < .001), and the mean (SD) phonic tic subscore improved from 16.82 (6.56) at baseline to 9.63 (6.99) at 1 year (P < .001). The overall adverse event rate was 35.4%(56 of 158 patients), with intracranial hemorrhage occurring in 2 patients (1.3%), infection in 4 patients with 5 events (3.2%), and lead explantation in 1 patient (0.6%). The most common stimulation-induced adverse effects were dysarthria (10 [6.3%]) and paresthesia (13 [8.2%]). CONCLUSIONS AND RELEVANCE Deep brain stimulationwas associated with symptomatic improvement in patients with Tourette syndrome but also with important adverse events. A publicly available website on outcomes of DBS in patients with Tourette syndrome has been provided.

Original languageEnglish (US)
Pages (from-to)353-359
Number of pages7
JournalJAMA Neurology
Volume75
Issue number3
DOIs
StatePublished - Mar 2018

Bibliographical note

Funding Information:
reported serving as an advisor for the European Multicentre Tics in Children Studies (EMTICS) and Tasly Pharmaceuticals LLC; receiving support from the National Institutes of Health (for research projects), the Tourette Association of America, and Grifols LLC; and receiving royalties for books published by John Wiley and Sons, McGraw-Hill, and Oxford University Press. Dr Okun reported serving as a consultant for the National Parkinson Foundation; receiving research grants from the National Institutes of Health, the National Parkinson Foundation, the Michael J. Fox Foundation, the Parkinson Alliance, Smallwood Foundation, the Bachmann-Strauss Foundation, the Tourette Syndrome Association, and the University of Florida Foundation; receiving grants R01 NR014852 and R01NS096008 from the National Institutes of Health for DBS research; receiving royalties for publications with Demos, Manson, Amazon, Smashwords, Books4Patients, and Cambridge (movement disorders books); serving as an associate editor for New England Journal of Medicine Journal Watch Neurology; participating in continuing medical education and educational activities on movement disorders (in the last 36 months) sponsored by PeerView, Prime, QuantiaMD, WebMD, Medicus, MedNet, Henry Stewart, and Vanderbilt University; and participating as a site principal investigator and/or coinvestigator for several National Institutes of Health, foundation, and industry-sponsored trials over the years but has not received honoraria. The institution and not Dr Okun received grants from Medtronic, Abbvie, Allergan, and Abbott/St Jude, and Dr Okun has no financial interest in these grants. No other disclosures were reported.

Funding Information:
Additional Contributions: We would like to acknowledge the support of the Tourette Association of America (TAA), the TAA Center of Excellence at the University of Florida (UF), the UF Foundation, and the UF INFORM database at the University of Florida Center for Movement Disorders and Neurorestoration.

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