Prospective randomized double-blind trial of bilateral thalamic deep brain stimulation in adults with Tourette syndrome

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The severity of Tourette syndrome (TS) typically peaks just before adolescence and diminishes afterward. In some patients, however, TS progresses into adulthood, and proves to be medically refractory. The authors conducted a prospective double-blind crossover trial of bilateral thalamic deep brain stimulation (DBS) in five adults with TS.


Bilateral thalamic electrodes were implanted. An independent programmer established optimal stimulator settings in a single session. Subjective and objective results were assessed in a double-blind randomized manner for 4 weeks, with each week spent in one of four states of unilateral or bilateral stimulation. Results were similarly assessed 3 months after unblinded bilateral stimulator activation while repeated open programming sessions were permitted.


In the randomized phase of the trial, a statistically significant (p < 0.03, Friedman exact test) reduction in the modified Rush Video-Based Rating Scale score (primary outcome measure) was identified in the bilateral on state. Improvement was noted in motor and sonic tic counts as well as on the Yale Global Tic Severity Scale and TS Symptom List scores (secondary outcome measures). Benefit was persistent after 3 months of open stimulator programming. Quality of life indices were also improved. Three of five patients had marked improvement according to all primary and secondary outcome measures.


Bilateral thalamic DBS appears to reduce tic frequency and severity in some patients with TS who have exhausted other available means of treatment.

Abbreviations used in this paper:BDI-2 = Beck Depression Inventory; DBS = deep brain stimulation; FDA = Food and Drug Administration; GPI = globus pallidus internus; HAM-A = Hamilton Rating Scale for Anxiety; HAM-D = Hamilton Rating Scale for Depression; MR = magnetic resonance; mRVRS = modified Rush Video-Based Rating Scale; SD = standard deviation; SF-36 = 36-Item Short Form Health Survey; TS = Tourette syndrome; TSSL = TS Symptom List; VAS = visual analog scale; Y-BOCS = Yale-Brown Obsessive Compulsive Scale; YGTSS = Yale Global Tic Severity Scale.

Article Information

Address correspondence to: Robert J. Maciunas, M.D., M.P.H., Department of Neurosurgery, Neurological Institute, University Hospitals Case Medical Center, 11100 Euclid Avenue, Cleveland, Ohio 44106. email:

© AANS, except where prohibited by US copyright law.



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    Timeline representing steps in the pilot study. Video camera icons designate video recording sessions. Assessment of secondary outcome measures are indicated by N (neuropsychological battery), Q (quality of life), T (TSSL), and Y (YGTSS). Combins = combinations; f/u = follow-up.

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    Coronal and axial T1-weighted MR images featuring the target point in all five surgically treated patients. A, D, and E: Responders (Cases 1, 4, and 5). B and C: Nonresponders (Cases 2 and 3). The image labeled “Plan” (lower right) is in the oblique plane, along electrodes, of the planned thalamic target and electrode trajectory using the BrainLab software.

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    Plots depicting motor (A and C) and sonic (B and D) tic counts normalized so that the preoperative count equals 1. The cross-hairs indicate the 50th percentile; the upper and lower box limits, the 25th and 75th percentiles; and the vertical span, the 0 and 100th percentiles. L = left; pre-stim = prestimulation; R = right.

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    Plots revealing secondary outcome measures at the preoperative and 3-month follow-up assessments. A: Complete-scale YGTSS scores. B: The VAS scores. C: The SF-36 scores. The cross-hairs indicate the 50th percentile; the upper and lower box limits, the 25th and 75th percentiles; and the vertical span, the 0 and 100th percentiles. QoL = quality of life.



Ackermans LTemel YCath Dvan der Linden CBruggerman RKleijer M: Deep brain stimulation in Tourette's syndrome: two targets?. Mov Disord 21:7097132006


American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders ed 4Washington, DCAmerican Psychiatric Association1994


Beck ATSteer RABrown GK: BDI-II. Manual for the Beck Depression Inventory ed 2San Antonio, TXThe Psychological Corporation1996


Bloch MHPeterson BSScahill LOtka JKatsovich LZhang H: Adulthood outcome of tic and obsessive-compulsive symptom severity in children with Tourette syndrome. Arch Pediatr Adolesc Med 160:65692006


Channon SPratt PRobertson MM: Executive function, memory, and learning in Tourette's syndrome. Neuropsychology 17:2472542003


Cooper IS: Dystonia reversal by operation on basal ganglia. Arch Neurol 7:1321451962


Cooper IS: Involuntary Movement Disorders New YorkHoeber Medical Division1969. 274279


Corkum PVSiegel LS: Is the continuous performance task a valuable research tool for hyperactivity disorder?. J Child Psychol Psychiatry 34:121712391993


Deuschl GHerzog JKleiner-Fisman GKubu CLozano ALyons KE: Deep brain stimulation: postoperative issues. Mov Disord 21:14 SupplS219S2372006


Diederich NJKalteis KStamenkovic MPieri VAlesch F: Efficient internal pallidal stimulation in Gilles de la Tourette syndrome: a case report. Mov Disord 20:149614992005


Flaherty AWEskandar ENWilliams ZMCebula CCosgrove GR: Novel control of tics, mood, and creativity with internal capsule and nucleus accumbens stimulation. Neurology 62:5 SupplP02.1412004. (Abstract)


Georgiou NBradshaw JLPhillips JGBradshaw JAChiu E: The Simon effect and attention deficits in Gilles de la Tourette's syndrome and Huntington's disease. Brain 118:130513181995


Goetz CGKompoliti K: Rating scales and quantitative assessment of tics. Adv Neurol 85:31422001


Goetz CGPappert EJRaman RLeurgans S: Advantages of a modified version of an objective video-based rating scale for Gilles de la Tourette syndrome. Mov Disord 14:5025061999


Goetz CGTanner CMStebbins GTLeipzig GCarr WC: Adult tics in Gilles de la Tourette's syndrome: description and risk factors. Neurology 42:7847881992


Goetz CGTanner CMWilson RSShannon KM: A rating scale for Gilles de la Tourette's syndrome: description, reliability, and validity data. Neurology 37:154215441987


Goodman WKPrice LHRasmussen SAMazure CFleischmann RLHill CL: The Yale-Brown Obsessive Compulsive Scale: I. Development, use, and reliability. Arch Gen Psychiatry 46:100610111989


Hamilton M: The assessment of anxiety states by rating. Br J Med Psychol 32:52551959


Hamilton M: Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol 6:2782961967


Hassler RStereotaxic surgery for psychiatric disturbances. Schaltenbrand GWalker AE: Stereotaxy of the Human Brain ed 2New YorkThieme-Stratton1982. 570590


Hassler RDieckmann GRelief of obsessive-compulsive disorders, phobias, and tics by stereotactic coagulations of the rostral intralaminar and medial-thalamic nuclei. Laitinen LVLivingston K: Surgical Approaches in Psychiatry. Proceedings of the 3rd International Congress of PsychosurgeryCambridge, UKGarden City Press1973. 206212


Hathaway SRMcKinley JC: Minnesota Multiphasic Personality Inventory—2nd Edition (MMPI-2): Manual for Administration and Scoring MinneapolisUniversity of Minnesota Press1989


Hornse HBanerjee SZeitlin HRobertson M: The prevalence of Tourette syndrome in 13-14–year-olds in mainstream schools. J Child Psychol Psychiatry 42:103510392001


Houeto JLKarachi CMallet LPillon BYelnik JMesnage V: Tourette's syndrome and deep brain stimulation. J Neurol Neurosurg Psychiatry 76:9929952005


Jankovic J: Tourette syndrome. N Engl J Med 345:118411922001


Jin RZheng RYHuang WW: Epidemiological survey of Tourette syndrome in children and adolescents in Wenzhou of P.R. China. Eur J Epidemiol 20:9259272005


Khalifa Nvon Knorring AL: Tourette syndrome and other tic disorders in a total population of children: clinical assessment and background. Acta Paediatr 94:160816142005


Leckman JF: Tourette's syndrome. Lancet 360:157715862002


Leckman JFRiddle MAHardin MTOrt SISwartz JLStevenson J: The Yale Global Tic Severity Scale: initial testing of a clinician-rated scale of tic severity. J Am Acad Child Adolesc Psychiatry 28:5665731989


Leckman JFZhang HVitale ALahnin FLynch KBondi C: Course of tic severity in Tourette syndrome: the first two decades. Pediatrics 102:14191998


Maddux BNRiley DEWhitney CMMaciunas RJ: Clinical efficacy and video analysis of deep brain stimulation for medically intractable Tourette Syndrome. Mov Disord 19:11232004. (Abstract)


Mink JW: Basal ganglia dysfunction in Tourette's syndrome: a new hypothesis. Pediatr Neurol 25:1901982001


Ozonoff SJensen J: Brief report. Specific executive function profiles in three neurodevelopmental disorders. J Autism Dev Disord 29:1711771999


Pappert EJGoetz CGLouis EDBlasucci LLeurgans S: Objective assessments of longitudinal outcome in Gilles de la Tourette syndrome. Neurology 61:9369402003


Robertson MM: Diagnosing Tourette syndrome. Is it a common disorder?. J Psychosom Res 55:362003


Robertson MM: Tourette syndrome, associated conditions, and the complexities of treatment. Brain 123:4254622000


Shahed JPoysky JKenney CJankovic J: Bilateral GPi deep brain stimulation for Tourette Syndrome. Neurology 66:2 SupplA3662006. (Abstract)


Shucard DWBenedict RGBTekok-Kilie ALichter DG: Slowed reaction time during a continuous performance test in children with Tourette's syndrome. Neuropsychology 11:1471551997


Silverstein SMComo PGGPalumbo DRWest LLOsborn LM: Multiple sources of attentional dysfunction in adults with Tourette's syndrome. Neuropsychology 9:1571641995


Temel YVisser-Vandewalle V: Surgery in Tourette syndrome. Mov Disord 91:3142004


Torrance GWFeeny DFurlong W: Visual Analog Scales: do they have a role in the measurement of preferences for health states?. Med Decis Making 21:3293342001


Visser-Vandewalle VTemel YBoon PVreeling FColle Hvan der Linden C: Chronic bilateral thalamic stimulation: a new therapeutic approach in intractable Tourette syndrome. A report of three cases. J Neurosurg 99:109411002003


Ware JEKosinski MDewey JE: How to Score Version 2 of the SF-36 Health Survey Lincoln, RIQualityMetric Incorporated2000




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