Abstract
Tourette syndrome (TS) is a childhood onset neurologic disorder with manifestations including multiple motor and phonic tics, and in most cases a variety of behavioral comorbidities such as attention deficit hyperactivity disorder, obsessive compulsive disorder, and other impulse control disorders. Although it is considered a hereditary disorder, likely modified by environmental factors, genetic studies have yet to uncover relevant causative genes and there is no animal model that mimics the broad clinical phenomenology of TS. There has been a marked increase in the number of neurophysiological, neuroimaging, and other studies on TS. The findings from these studies, however, have been difficult to interpret because of small sample sizes, variability of symptoms across patients, and comorbidities. Although anti-dopaminergic drugs are the most widely used medications in the treatment of TS, there has been increasing interest in other drugs, behavioral therapies, and surgical approaches including deep brain stimulation. Herein, we review the current literature and discuss the complexities of TS and the challenges in understanding its pathophysiology and in selecting the most appropriate treatment. We also offer an expert’s view of where the field of TS may be headed.
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Trivet HA, Chien HF, Munhoz RP, Barbosa ER. Charcot’s contribution to the study of Tourette syndrome. Arq Neuropsiquiatr. 2008;66:918–21.
Gilles de la Tourette G. Étude sur une affection nerveuse caractérisée par de l’incoordination motrice accompagnée d’écholalie et de coprolalie [French]. Arch Neurol. 1885;9:158–200.
Itard JM. Mémoire sur quelques functions involontaires des appareils de la locomotion, de la préhension et de la voix [French]. Arch Gen Med. 1825;8:385–407.
Trousseau A. Clinique Médicale de l’Hôtel Dieu de Paris Paris: J.-B. Bailliere; 1868.
Hughlings JJ. Clinical lectures and reports to the London Hospital. 1868;1.
McNaught KS, Mink JW. Advances in understanding and treatment of Tourette syndrome. Nat Rev Neurol. 2011;7:667–76.
Kurlan R. Clinical practice. Tourette’s syndrome. N Engl J Med. 2010;363:2332–8.
Singer HS. Tourette’s syndrome: from behaviour to biology. Lancet Neurol. 2005;4:149–59.
Jankovic J. Phenomenology and classification of tics. Neurol Clin. 1997;15:267–75.
Ganos C, Ogrzal T, Schnitzler A, Münchau A. The pathophysiology of echopraxia/echolalia: relevance to Gilles De La Tourette syndrome. Mov Disord. 2012;27:1222–9.
Freeman RD, Zinner SH, Muller-Vahl KR, et al. Coprophenomena in Tourette syndrome. Dev Med Child Neurol. 2009;51:218–27.
Hanna PA, Jankovic J. Sleep and tic disorders. Woburn: Butterworth-Heinemann; 2003.
Demirkiran M, Jankovic J. Paroxysmal dyskinesias—clinical-features and classification. Ann Neurol. 1995;38:571–9.
Jankovic J. Tourette’s syndrome. N Engl J Med. 2001;345:1184–92.
Leckman J, Walker D, Cohen D. Premonitory urges in Tourette’s syndrome. Am J Psychiatry 1993;150.
Kwak C, Vuong KD, Jankovic J. Premonitory sensory phenomenon in Tourette’s syndrome. Mov Disord. 2003;18:1530–3.
Banaschewski T, Woerner W, Rothenberger A. Premonitory sensory phenomena and suppressibility of tics in Tourette syndrome: developmental aspects in children and adolescents. Dev Med Child Neurol. 2003;45:700–3.
Rajagopal S, Cavanna AE. Premonitory urges and repetitive behaviours in adult patients with Tourette syndrome. Neurol Sci. 2014;35:969–71.
Tallur K, Minns RA. Tourette’s syndrome. Paediatr Child Health. 2010;20:88–93.
Hirschtritt ME, Lee PC, Pauls DL, et al. Lifetime prevalence, age of risk, and genetic relationships of comorbid psychiatric disorders in Tourette syndrome. JAMA Psychiatry. 2015;72:325–33.
Canitano R, Vivanti G. Tics and Tourette syndrome in autism spectrum disorders. Autism. 2007;11:19–28.
Leckman JF. Tourette’s syndrome. Lancet. 2002;360:1577–86.
Leckman JF, Zhang HP, Vitale A, et al. Course of tic severity in Tourette Syndrome: the first two decades. Pediatrics. 1998;102:14–9.
Bloch MH, Peterson BS, Scahill L, et al. Adulthood outcome of tic and obsessive-compulsive symptom severity in children with Tourette syndrome. Arch Pediatr Adolesc Med. 2006;160:65–9.
Scharf JM, Miller LL, Gauvin CA, Alabiso J, Mathews CA, Ben-Shlomo Y. Population prevalence of Tourette syndrome: a systematic review and meta-analysis. Mov Disord. 2015;30(2):221–8. This study is a systematic review of published studies on TS prevalence. The authors performed random-effects meta-analysis weighted by sample size and meta-regressions to examine covariates that were potential sources of heterogeneity. This study refined the population prevalence estimate of TS in children to be 0.3 to 0.9 %.
Knight T, Steeves T, Day L, Lowerison M, Jette N, Pringsheim T. Prevalence of tic disorders: a systematic review and meta-analysis. Pediatr Neurol. 2012;47:77–90.
Bitsko RH, Holbrook JR, Visser SN, et al. A national profile of Tourette syndrome. J Dev Behav Pediatr. 2014;35:317–22.
Cheung MY, Shahed J, Jankovic J. Malignant Tourette syndrome. Mov Disord. 2007;22(12):1743–50.
Ganos C, Garrido A, Navalpotro-Gomez I, et al. Premonitory urge to tic in Tourette’s is associated with interoceptive awareness. Mov Disord 2015.
Grados MA, Mathews CA. Clinical phenomenology and phenotype variability in Tourette syndrome. J Psychosom Res. 2009;67:491–6.
American Psychiatric Association. Diagnostic and Statistal Manual of Mental Disorders (DSM-V). Washington: American Psychiatric Association Press; 2012.
Jankovic J, Mejia N. Tics associated with other disorders. Philadelphia: Lippincott Williams & Wilkins; 2006.
Khalifa N, von Knorring A-L. Tourette syndrome and other tic disorders in a total population of children: clinical assessment and background. Acta Paediatr. 2007;94:1608–14.
Hanna P, Janjua F, Contant C, Jankovic J. Bilineal transmission in Tourette syndrome. Neurology. 1999;53:813–8.
Pauls DL, Raymond CL, Stevenson JM, Leckman JF. A family study of Gilles de la Tourette syndrome. Am J Hum Genet 1991;48.
Hyde TM, Aaronson BA, Randolph C, Rickler KC, Weinberger DR. Relationship of birth weight to the phenotypic expression of Gilles de la Tourette’s syndrome in monozygotic twins. Neurology. 1992;42:652–8.
Price RA, Kidd KK, Cohen DJ, Pauls DL, Leckman JF. A twin study of Tourette syndrome. Arch Gen Psychiatry. 1985;42:815–20.
Davis LK, Yu D, Keenan CL, Gamazon ER, Konkashbaev AI, et al. Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture. PLoS Genet 2013;9.
Deng H, Gao K, Jankovic J. The genetics of Tourette syndrome. Nat Rev Neurol. 2012;8:203–13.
Genetics TTSAICf. A complete genome screen in sib pairs affected by Gilles de la Tourette syndrome. Am J Hum Genet. 1999;65:1428–36.
Genetics TTSAICf. Genome scan for Tourette disorder in affected-sibling-pair and multigenerational families. Am J Hum Genet. 2007;80:265–72.
Roessner V, Plessen KJ, Rothenberger A, et al. European clinical guidelines for Tourette syndrome and other tic disorders. Part II: pharmacological treatment. Eur Child Adolesc Psychiatry. 2011;20:173–96.
Dietrich A, Fernandez TV, King RA, et al. The Tourette International collaborative genetics (TIC Genetics) study, finding the genes causing Tourette syndrome: objectives and methods. Eur Child Adolesc Psychiatry 2014.
Selling L. The role of infection in the etiology of tics. Arch Neurol Psychiatry. 1929;22:1163–71.
Petek E, Windpassinger C, Vincent JB, et al. Disruption of a novel gene (IMMP2L) by a breakpoint in 7q31 associated with Tourette syndrome. Am J Hum Genet. 2001;68:848–58.
Patel C, Cooper-Charles L, McMullan DJ, Walker JM, Davison V, Morton J. Translocation breakpoint at 7q31 associated with tics: further evidence for IMMP2L as a candidate gene for Tourette syndrome. Eur J Hum Genet. 2011;19:634–9.
Bertelsen B, Melchior L, Jensen LR, et al. Intragenic deletions affecting two alternative transcripts of the IMMP2L gene in patients with Tourette syndrome. Eur J Hum Genet. 2014;22:1283–9.
Whatley SA, Curti D, Marchbanks RM. Mitochondrial involvement in schizophrenia and other functional psychoses. Neurochem Res. 1996;21:995–1004.
Lin H, Williams KA, Katsovich L, et al. Streptococcal upper respiratory tract infections and psychosocial stress predict future tic and obsessive-compulsive symptom severity in children and adolescents with Tourette syndrome and obsessive-compulsive disorder. Biol Psychiatry. 2010;67:684–91.
Swedo SE, Leonard HL, Garvey MA, Mittleman B, Allen JP, Perlmutter JS. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. Am J Psychiatry. 1998;155:264–71.
Mell LK, Davis RL, Owens D. Association between streptococcal infection and obsessive-compulsive disorder, Tourette’s syndrome, and tic disorder. Pediatrics. 2005;116:56–60.
Kaplan EL. PANDAS? or PAND? Or Both? Or Neither? Assessing a possible temporal or pathogenetic relationship with the group A “strep- tococcal diseases complex”. Contemp Pediatr. 2000;8:81–96.
Kurlan R. Tourette’s syndrome and ‘PANDAS’: will the relationship bear out? Neurology. 1998;50:1530–4.
Singer HS. PANDAS and immunomodulatory therapy: commentary. Lancet. 1999;354:1137–8.
Kurlan R, Kaplan EL. The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) etiology for tics and obsessive-compulsive symptoms: hypothesis or entity? Practical considerations for the clinician. Pediatrics. 2004;113:883–6.
Swedo SE, Leckman JF, Rose NR. From research subgroup to clinical syndrome: modifying the PANDAS criteria to describe PANS (Pediatric Acute-onset Neuropsychiatric Syndrome). Pediatrics & Therapeutics 2012;2.
Lerner A, Bagic A, Simmons JM, et al. Widespread abnormality of the γ-aminobutyric acid-ergic system in Tourette syndrome. Brain. 2012;135:1926–36.
van der Salm S, Tijssen M, Koelman J, van Rootselaar A. The bereitschaftspotential in jerky movement disorders. J Neurol Neurosurg Psychiatry. 2012;83:1162–7.
Patel N, Jankovic J, Hallett M. Sensory aspects of movement disorders. Lancet Neurol. 2014;13:100–12.
Albin RL, Young AB, Penney JB. The functional-anatomy of basal ganglia disorders. Trends Neurosci. 1989;12:366–75.
Mink JW. The basal ganglia and involuntary movements—impaired inhibition of competing motor patterns. Arch Neurol. 2003;60:1365–8.
Mink JW. Basal ganglia dysfunction in Tourette’s syndrome: a new hypothesis. Pediatr Neurol. 2001;25:190–8.
Albin RL, Mink JW. Recent advances in Tourette syndrome research. Trends Neurosci. 2006;29:175–82.
Marceglia S, Servello D, Foffani G, et al. Thalamic single-unit and local field potential activity in Tourette syndrome. Mov Disord. 2010;25:300–8.
Maling N, Hashemiyoon R, Foote KD, Okun MS, Sanchez JC. Increased thalamic gamma band activity correlates with symptom relief following deep brain stimulation in humans with Tourette’s syndrome. PLoS One. 2012;7, e44215. This study presents the first chronic electrophysiological data in humans with TS, which shows correlation between increased gamma band activity and clinical improvement.
Shute J, Maling N, Rossi PJ, et al. Neural correlates of Tourette syndrome within the centromedian thalamus, premotor and primary motor cortices. Neuroscience Annual Meeting 2014; Washington, DC.
Franzkowiak S, Pollok B, Biermann-Ruben K, et al. Altered pattern of motor cortical activation-inhibition during voluntary movements in Tourette syndrome. Mov Disord. 2010;25:1960–6.
Biermann-Ruben K, Miller A, Franzkowiak S, et al. Increased sensory feedback in Tourette syndrome. NeuroImage. 2012;63:119–25.
Peterson BS, Thomas P, Kane MJ, et al. Basal ganglia volumes in patients with Gilles de la Tourette syndrome. Arch Gen Psychiatry. 2003;60:415–24.
Bloch M, Leckman J, Zhu H, Peterson B. Caudate volumes in childhood predict symptom severity in adults with Tourette syndrome. Neurology. 2005;65:1253–8.
Makki MI, Munian Govindan R, Wilson BJ, Behen ME, Chugani HT. Altered Fronto-Striato-Thalamic connectivity in children with tourette syndrome assessed with diffusion tensor MRI and probabilistic fiber tracking. J Child Neurol. 2009;24:669–78.
Worbe Y, Gerardin E, Hartmann A, et al. Distinct structural changes underpin clinical phenotypes in patients with Gilles de la Tourette syndrome. Brain. 2010;133:3649–60.
Thomalla G, Siebner HR, Jonas M, et al. Structural changes in the somatosensory system correlate with tic severity in Gilles de la Tourette syndrome. Brain. 2009;132:765–77.
Cavanna AE, Stecco A, Rickards H, et al. Corpus callosum abnormalities in Tourette syndrome: an MRI-DTI study of monozygotic twins. J Neurol Neurosurg Psychiatry. 2010;81:533–5.
Jackson SR, Parkinson A, Jung J, et al. Compensatory neural reorganization in Tourette syndrome. Curr Biol. 2011;21:580–5.
Bäumer T, Thomalla G, Kroeger J, et al. Interhemispheric motor networks are abnormal in patients with Gilles de la Tourette syndrome. Mov Disord. 2010;25:2828–37.
Muellner J, Delmaire C, Valabrégue R, et al. Altered structure of cortical sulci in Gilles de la Tourette syndrome: further support for abnormal brain development. Mov Disord. 2015;30:655–61. This comprehensive study with 52 adult patients with TS (and 52 matched controls) shows abnormal structural patterns of cortical sulci, which correlated with severity of clinical symptoms.
Bohlhalter S. Neural correlates of tic generation in Tourette syndrome: an event-related functional MRI study. Brain. 2006;129:2029–37.
Debes N, Hansen A, Skov L, Larsson H. A functional magnetic resonance imaging study of a large clinical cohort of children with Tourette syndrome. J Child Neurol. 2011;26:560–9.
Mazzone L, Yu S, Blair C, et al. An FMRI study of frontostriatal circuits during the inhibition of eye blinking in persons with Tourette syndrome. Am J Psychiat. 2010; 341–9.
Worbe Y, Malherbe C, Hartmann A, et al. Functional immaturity of cortico-basal ganglia networks in Gilles de la Tourette syndrome. Brain. 2012;135:1937–46.
Singer HS, Gilbert DL, Wolf DS, Mink JW, Kurlan R. Moving from PANDAS to CANS. J Pediatr. 2012;160:725–31.
Roessner V, Schoenefeld K, Buse J, Bender S, Ehrlich S, Munchau A. Pharmacological treatment of tic disorders and Tourette syndrome. Neuropharmacology. 2013;68:143–9.
Saporta ASD, Chugani HT, Juhász C, et al. Multimodality neuroimaging in Tourette syndrome: alpha-[11C] methyl-L-tryptophan positron emission tomography and diffusion tensor imaging studies. J Child Neurol. 2010;25:336–42.
Wong DF, Brasic JR, Singer HS, et al. Mechanisms of dopaminergic and serotonergic neurotransmission in Tourette syndrome: clues from an in vivo neurochemistry study with PET. Neuropsychopharmacology. 2007;33(6):1239–51.
Singer HS. Neurochemical analysis of postmortem cortical and striatal brain tissue in patients with Tourette syndrome. Adv Neurol. 1992;58:135–44.
Swedo SE, Leonard HL, Kruesi MJP, et al. Cerebrospinal fluid neurochemistry in children and adolescents with obsessive-compulsive disorder. Arch Gen Psychiatry 1992;49.
Harris K, Singer HS. Tic disorders: neural circuits, neurochemistry, and neuroimmunology. J Child Neurol. 2006;21:678–89.
Cheon KA, Ryu YH, Namkoong K, Kim CH, Kim JJ, Lee JD. Dopamine transporter density of the basal ganglia assessed with [123I]IPT SPECT in drug-naive children with Tourette’s disorder. Psychiatry Res. 2004;130:85–95.
Serra-Mestres J, Ring H, Costa D. Dopamine transporter binding in Gilles de la Tourette syndrome: a [123I]FP-CIT/ SPECT study. Acta Psychiatr Scand. 2004;109:140–6.
Minzer K, Lee O, Hong JJ, Singer HS. Increased prefrontal D2 protein in Tourette syndrome: a postmortem analysis of frontal cortex and striatum. J Neurol Sci. 2004;219:55–61.
Wong DF, Singer HS, Brandt J, et al. D2-like dopamine receptor density in Tourette syndrome measured by PET. J Nucl Med. 1997;38:1243–7.
Albin RL, Koeppe RA, Wernette K, et al. Striatal [11C]dihydrotetrabenazine and [11C]methylphenidate binding in Tourette syndrome. Neurology. 2009;72:1390–6.
Müller-Vahl KR, Meyer GJ, Knapp WH, et al. Serotonin transporter binding in Tourette syndrome. Neurosci Lett. 2005;385:120–5.
Steeves TDL, Ko JH, Kideckel DM, et al. Extrastriatal dopaminergic dysfunction in Tourette syndrome. Ann Neurol. 2010;67:170–81.
Xu M, Kobets AJ, Du J-C, et al. Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome. Proc Natl Acad Sci PNAS. 2015;112:893–8. The authors developed a strategy for targeted ablation of cholinergic interneurons in the mice dorsolateral striatum, which demonstrated for the first time that these interneurons can cause behavioral changes that resemble aspects of TS.
Castellan Baldan L, Williams KA, Gallezot J-D, et al. Histidine decarboxylase deficiency causes tourette syndrome: parallel findings in humans and mice. Neuron. 2014;81:77–90.
Singer HS. Treatment of tics and tourette syndrome. Curr Treat Options Neurol. 2010;12:539–61.
Jankovic J. Treatment of hyperkinetic movement disorders. Lancet Neurol. 2009;8:844–56.
Conelea CA, Woods DW, Zinner SH, et al. Exploring the impact of chronic tic disorders on youth: results from the Tourette syndrome impact survey. Child Psychiatry Hum Dev. 2011;42:219–42.
Leckman JF, Riddle MA, Hardin MT, et al. The Yale Global Tic Severity Scale: initial testing of a clinician-rated scale of tic severity. J Am Acad Child Adolesc Psychiatry. 1989;28:566–73.
Goetz CG, Pappert EJ, Louis ED, Raman R, Leurgans S. Advantages of a modified scoring method for the Rush Video-Based Tic Rating Scale. Mov Disord. 1999;14:502–6.
Ackermans L, Duits A, van der Linden C, et al. Double-blind clinical trial of thalamic stimulation in patients with Tourette syndrome. Brain 2011; 832–44.
Maciunas RJ, Maddux BN, Riley DE, et al. Prospective randomized double-blind trial of bilateral thalamic deep brain stimulation in adults with Tourette syndrome. J Neurosurg. 2007;107:1004–14.
Wilhelm S, Deckersbach T, Coffey BJ, Bohne A, Peterson AL, Baer L. Habit reversal vs supportive psychotherapy for Tourette’s disorder: a randomized controlled trial. Am J Psychiatry. 2003;160:1175–6.
Deckersbach T, Rauch S, Buhlmann U, Wilhelm S. Habit reversal vs supportive psychotherapy in Tourette’s disorder: a randomized controlled trial and predictors of treatment response. Behav Res Ther. 2006;44:1079–90.
Piacentini J, Woods DW, Scahill L, et al. Behavior therapy for children with Tourette disorder a randomized controlled trial. JAMA J Am Med Assoc. 2010;303:1929–37.
Wilhelm S, Peterson AL, Piacentini J, et al. Randomized trial of behavior therapy for adults with Tourette syndrome. Arch Gen Psychiatry. 2012;69:795–803.
O’connor KP, Laverdure A, Taillon A, Stip E, Borgeat F, Lavoie M. Cognitive behavioral management of Tourette’s syndrome and chronic tic disorder in medicated and unmedicated samples. Behav Res Ther. 2009;47:1090–5.
Verdellen CWJ, Keijsers GPJ, Cath DC, Hoogduin CAL. Exposure with response prevention versus habit reversal in Tourettes’s syndrome: a controlled study. Behav Res Ther. 2004;42:501–11.
Wile DJ, Pringsheim TM. Behavior therapy for Tourette syndrome: a systematic review and meta-analysis. Curr Treat Options Neurol. 2013;15:385–95.
McGuire J, Piacentini J, Brennan E, et al. A meta-analysis of behavior therapy for Tourette syndrome. J Psychiatr Res. 2014;50:106–12.
Weisman H, Qureshi IA, Leckman JF, Scahill L, Bloch MH. Systematic review: pharmacological treatment of tic disorders—efficacy of antipsychotic and alpha-2 adrenergic agonist agents. Neurosci Biobehav Rev. 2013;37:1162–71.
Scahill L, Chappell PB, Kim YS, et al. A placebo-controlled study of guanfacine in the treatment of children with tic disorders and attention deficit hyperactivity disorder. Am J Psychiatry. 2001;158:1067–74.
Leckman JF, Cohen DJ, Detlor J, Young JG, Harcherik D, Shaywitz BA. Clonidine in the treatment of Tourette syndrome: a review of data. Adv Neurol. 1982;35:391–401.
Kushner HI. From Gilles de la Tourette’s disease to Tourette syndrome: a history. CNS Spectr. 1999;4:24–35.
Pena MS, Yaltho TC, Jankovic J. Tardive dyskinesia secondary to Aripiprazole. Ann Neurol. 2010;68:S21–S.
Wijemanne S, Wu L, Jankovic J. Long-term efficacy and safety of fluphenazine in patients with Tourette syndrome. Mov Disord. 2014;29:126–30.
Ondo WG, Jong D, Davis A. Comparison of weight gain in treatments for Tourette syndrome: tetrabenazine versus neuroleptic drugs. J Child Neurol. 2008;23:435–7.
Kenney C, Hunter C, Mejia N, Jankovic J. Tetrabenazine in the treatment of Tourette syndrome. J Pediatr Neurol. 2007;5:9–13.
Jimenez-Shahed J, Jankovic J. Tetrabenazine for treatment of chorea associated with Huntington’s disease. Expert Opin Orphan Drugs. 2013;1:423–36.
Jankovic J, Jimenez-Shahed J, Brown LW. A randomised, double-blind, placebo-controlled study of topiramate in the treatment of Tourette syndrome. J Neurol Neurosurg Psychiatry. 2010;81:70–3.
Marras C, Andrews D, Sime E, Lang A. Botulinum toxin for simple motor tics: a randomized, double-blind, controlled clinical trial. Neurology. 2001;56:605–10.
Viswanathan A, Jimenez-Shahed J, Baizabal Carvallo J, Jankovic J. Deep brain stimulation for Tourette syndrome: target selection. Stereotact Funct Neurosurg. 2012;90:213–24.
Hassler R, Dieckmann G. Traitement stéréotaxique des tics et cris inarticulés ou coprolaliques considérés comme phenomena d’obsession motrice au cours de la maladie de Gilles de la Tourette. Rev Neurol (Paris). 1970;123:89–100.
Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group. Tourette syndrome deep brain stimulation: a review and updated recommendations. Move Disord in press. This paper presents a review of all reported cases of TS DBS and provides updated recommendations for selection, assessment, and management of potential TS DBS cases based on the literature and implantation experience.
Shprecher DR, Schrock L, Himle M. Neurobehavioral aspects, pathophysiology, and management of Tourette syndrome. Curr Opin Neurol. 2014;27:484–92.
Okun MS, Fernandez HH, Foote KD, Murphy TK, Goodman WK. Avoiding deep brain stimulation failures in Tourette syndrome. J Neurol Neurosurg Psychiatry. 2008;79:111–2.
Le K, Liu L, Sun M, Hu L, Xiao N. Transcranial magnetic stimulation at 1 Hertz improves clinical symptoms in children with Tourette syndrome for at least 6 months. J Clin Neurosci. 2013;20:257–62.
Kwon HJ, Lim WS, Lim MH, et al. 1-Hz low frequency repetitive transcranial magnetic stimulation in children with Tourette’s syndrome. Neurosci Lett. 2011;492:1–4.
Ganos C, Roessner V, Münchau A. The functional anatomy of Gilles de la Tourette syndrome. Neurosci Biobehav Rev 2013; 1050–62.
Rossi PJ, Shute J, Gunduz A, Bowers D, Foote KD, Okun MS. Fewer than 2 hours of daily thalamic stimulation reduces tics in Tourette syndrome: two-year follow-up of scheduled deep brain stimulation. Brain 2014;submitted.
Almeida L, Martinez-Ramirez D, Rossi PJ, Peng Z, Gunduz A, Okun MS. Chasing tics in the Human brain: development of open, scheduled and closed loop responsive approaches to deep brain stimulation for Tourette syndrome. J Clin Neurol 2015;11.
Acknowledgments
We would like to acknowledge the support of the TSA Center of Excellence located at the University of Florida Center for Movement Disorders and Neurorestoration. We would also like to acknowledge the following grant support NIH R34MH080764 (Okun), NIH R211NS072897 (Okun), and UF CTSI NIH KL2 Scholarship (Gunduz). The authors would also like to sincerely thank Drs. Don Gilbert, Tamara Hershey, Joseph Jankovic, Carol Mathews, Jon Mink, and Doug Woods for their insightful comments on this manuscript.
Authors’ contributions
Aysegul Gunduz planned the outline of the manuscript, performed the literature search, drafted the text, designed the tables and figures, and approved the manuscript. Michael S. Okun planned the outline of the manuscript, contributed to and edited the text, contributed to the tables and figures, and approved the manuscript.
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Aysegul Gunduz has received research grants from the Michael J. Fox Foundation, UF Clinical and Translational Sciences Institute, and DARPA. The institution and not Dr. Gunduz receives grants from Medtronic, and Dr. Gunduz has financial interest in these grants.
Michael S. Okun serves as a consultant for the National Parkinson Foundation and has received research grants from NIH, NPF, the Michael J. Fox Foundation, the Parkinson Alliance, Smallwood Foundation, the Bachmann-Strauss Foundation, the Tourette Syndrome Association, and the UF Foundation. Dr. Okun has previously received honoraria, but in the past >60 months has received no support from industry. Dr. Okun has received royalties for publications with Demos, Manson, Amazon, Smashwords, Books4Patients, and Cambridge (movement disorders books). Dr. Okun is an associate editor for New England Journal of Medicine Journal Watch Neurology. Dr. Okun has participated in CME and educational activities on movement disorders (in the last 36 months) sponsored by PeerView, Prime, Quantia, Henry Stewart, and by Vanderbilt University. The institution and not Dr. Okun receives grants from Medtronic, Abbvie, and ANS/St. Jude, and the PI has no financial interest in these grants. Dr. Okun has participated as a site PI and/or co-I for several NIH, foundation, and industry-sponsored trials over the years but has not received honoraria.
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Gunduz, A., Okun, M.S. A Review and Update on Tourette Syndrome: Where Is the Field Headed?. Curr Neurol Neurosci Rep 16, 37 (2016). https://doi.org/10.1007/s11910-016-0633-x
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DOI: https://doi.org/10.1007/s11910-016-0633-x