Daniel Martinez-Ramirez1, Joohi Jimenez-Shahed2, James Frederick Leckman3, Mauro Porta4, Domenico Servello5, Fan-Gang Meng6, Jens Kuhn7,8, Daniel Huys7, Juan Carlos Baldermann7, Thomas Foltynie9, Marwan I Hariz9,10, Eileen M Joyce9, Ludvic Zrinzo9, Zinovia Kefalopoulou9, Peter Silburn11, Terry Coyne11, Alon Y Mogilner12, Michael H Pourfar12, Suketu M Khandhar13, Man Auyeung14, Jill Louise Ostrem15, Veerle Visser-Vandewalle16, Marie-Laure Welter17, Luc Mallet18,19,20, Carine Karachi21, Jean Luc Houeto22,23, Bryan Timothy Klassen24, Linda Ackermans25, Takanobu Kaido26,27, Yasin Temel28, Robert E Gross29, Harrison C Walker30,31, Andres M Lozano32, Benjamin L Walter33,34,35, Zoltan Mari36, William S Anderson36, Barbara Kelly Changizi37, Elena Moro38,39, Sarah Elizabeth Zauber40, Lauren E Schrock41, Jian-Guo Zhang42, Wei Hu1, Kyle Rizer1, Erin H Monari1, Kelly D Foote43,44, Irene A Malaty1, Wissam Deeb1, Aysegul Gunduz45, Michael S Okun1,44. 1. Center for Movement Disorders and Neurorestoration, Department of Neurology, University of Florida, Gainesville. 2. Parkinson's Disease Center and Movement Disorders Clinic, Baylor College of Medicine, Houston, Texas. 3. Yale Child Study Center, Yale University School of Medicine, New Haven, Connecticut. 4. Tourette's Syndrome and Movement Disorders Center, Galeazzi Hospital, Milan, Italy. 5. Neurosurgical Department, Isituto Ortopedico Galeazzi, Milan, Italy. 6. Department of Functional Neurosurgery, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China. 7. Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany. 8. Department of Psychiatry, Psychotherapy, and Psychosomatic Medicine, Johanniter Hospital Oberhausen, Oberhausen, Germany. 9. Sobell Department of Motor Neuroscience, University College London Institute of Neurology, London, United Kingdom. 10. Department of Clinical Neuroscience, Umeå University, Umeå, Sweden. 11. Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia. 12. Department of Neurosurgery, Center for Neuromodulation, New York University Langone Medical Center, New York. 13. Department of Neurology, The Permanente Medical Group (Kaiser Permanente Northern California), Comprehensive Movement Disorders Program, Sacramento, California. 14. Department of Medicine, Pamela Youde Nethersole Eastern Hospital, Hong Kong, SAR China. 15. Department of Neurology, University of California, San Francisco. 16. Department of Stereotaxy and Functional Neurosurgery, University Hospital Cologne, Cologne, Germany. 17. The French National Institute of Health and Medical Research U 1127, The National Center for Scientific Research 7225, Sorbonne Universités, University of Pierre and Marie Curie University of Paris 06 UMR S 1127, Institut du Cerveau et de la Moëlle Epinière, The Brain and Spinal Cord Institute, Paris, France. 18. Assistance Publique-Hôpitaux de Paris, Personalised Neurology and Psychiatry University Department, Hôpitaux Universitaires Henri Mondor-Albert Chenevier, Université Paris-Est Créteil, Créteil, France. 19. Sorbonne Universités, University of Pierre and Marie Curie University of Paris 06, CNRS, INSERM, Institut du Cerveau et de la Moëlle épinière, Paris, France. 20. Department of Mental Health and Psychiatry, Global Health Institute, University of Geneva, Geneva, Switzerland. 21. Institut du Cerveau et de la Moëlle Epinière, The French National Institute of Health and Medical Research U 1127, The National Center for Scientific Research 7225, Sorbonne Universités, University of Paris 06, UMR S 1127 Paris, France; Department of Neurosurgery, Pitié-Salpêtrière Hospital, Paris, France. 22. Service de Neurologie, Centers for Clinical Investigation 1402, Centre Hospitalier Universitaire de Poitiers, Poitiers, France. 23. Université de Poitiers, Poitiers, France. 24. Department of Neurology, Mayo Clinic, Rochester, Minnesota. 25. Department of Neurosurgery, Maastricht University Medical Centre, Maastricht, the Netherlands. 26. Department of Neurosurgery, National Hospital Organization Nara Medical Center, Nara, Japan. 27. Anatomy and Physiology Laboratory, Department of Health and Nutrition, Osaka Shoin Women's University, Osaka, Japan. 28. Maastricht University Medical Center, Maastricht, the Netherlands; MHeNs, Experimental Neurosurgery, Maastricht University, Maastricht, the Netherlands. 29. Emory University, Atlanta, Georgia. 30. Division of Movement Disorders, Department of Neurology, University of Alabama at Birmingham. 31. Department of Biomedical Engineering, University of Alabama at Birmingham. 32. Toronto Western Hospital, Division of Neurosurgery, University of Toronto, Toronto, Ontario, Canada. 33. School of Medicine, Case Western Reserve University, Cleveland, Ohio. 34. US Department of Veterans Affairs, Louis Stokes Cleveland Veterans Affairs Medical Center, Functional Electrical Stimulation Center of Excellence, Rehabilitation R&D Service, Cleveland, Ohio. 35. Department of Neurology, University Hospitals Cleveland Medical Center, Cleveland, Ohio. 36. Department of Neurology and Neurosurgery, Johns Hopkins University, Baltimore, Maryland. 37. Department of Neurology, The Ohio State University Wexner Medical Center, Columbus. 38. Division of Neurology, Centre Hospitalier Universitaire de Grenoble, Grenoble, France. 39. Grenoble Alpes University, Grenoble, France. 40. Department of Neurology, Indiana University School of Medicine, Indianapolis. 41. Neuromodulation Research Center, Department of Neurology, University of Minnesota, Minneapolis. 42. Department of Functional Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. 43. Center for Movement Disorders and Neurorestoration, Department of Neurosurgery, University of Florida, Gainesville. 44. Fixel Center for Neurological Diseases, Gainesville, Florida. 45. Brain Map Lab, Center for Movement Disorders and Neurorestoration, Department of Neurology, University of Florida, Gainesville.
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%]). Main Outcomes and Measures: Scores on the Yale Global Tic Severity Scale and adverse events. 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 stimulation was 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.
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%]). Main Outcomes and Measures: Scores on the Yale Global Tic Severity Scale and adverse events. 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 stimulation was 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.
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