Tourette's syndrome is a developmental neuropsychiatric disorder characterized by multiple motor, stereotypical but non-rhythmic movements and vocalizations/phonics called tics. It is one of several disorders that have tics as their cardinal feature. These tics manifest themselves in various ways, ranging from simple eye blinking to coprolalia (involuntary swearing).
Method
We conducted a thorough search for the literature using Medline and ScienceDirect. A literature review was then carried out to identify relevant information and improve the profession's understanding of the syndrome, including its pathophysiology.
Results
This disorder is much more common than once believed, and may interfere with patients’ social relationships and occupational functions. The development of new treatments is important to achieve more effective management with fewer side effects. Animal models of Tourette's syndrome would help foster understanding the pathophysiology and pharmacological treatment of tic symptoms.
Conclusions
Although significant advances have been made, research in the field is crucial to clarify further the physiological aspects of the syndrome.
SingerHS, MinkJW, GilbertDL, . Movement disorders in childhood.Philadelphia, PA: WB Saunders; 2010.
7.
SwainJE, ScahillL, LombrosoPJ, . Tourette syndrome and tic disorders: a decade of progress. J Am Acad Child Adolesc Psychiatry. 2007;46:947–968.
8.
LeckmanJF, BlochMH, ScahillL, . Tourette syndrome: the self under siege. J Child Neurol. 2006;21:642–649.
9.
ScahillL, OrtSI, HardinMT.Tourette's syndrome, part I: definition and diagnosis. Arch Psychiatr Nurs. 1993;7:203–208.
10.
RobertsonMM.The Gilles de la Tourette syndrome: an update. Psychiatry. 2004;3:3–7.
11.
GazeC, KepleyHO, WalkupJT.Co-ocurring psychiatric disorders in children and adolescents with Tourette syndrome. J Child Neurol. 2006;21:657–664.
12.
FreemanRD, FastDK, BurdL, . An international perspective on Tourette syndrome: selected findings from 3,500 individuals in 22 countries. Dev Med Child Neurol. 2000;42:436–447.
13.
AminoffMJ, DaroffRB.Encyclopedia of the neurological sciences. Amsterdam, The Netherlands: Academic Press, Elsevier; 2003.
14.
RickardsH, CavannaAE.Gilles de la Tourette: the man behind the syndrome. J Psychosom Res. 2009;67:469–474.
15.
MonacoF, ServoS, CavannaAE.Famous people with Gilles de la Tourette syndrome?J Psychosom Res.2009;67:485–490.
16.
SingerHS.Neurobiological issues in Tourette syndrome. Brain Dev. 1994;16:353–364.
17.
HoekstraPJ, AndersonGM, LimburgPC, . Neurobiology and neuroimmunology of Tourette's syndrome: an update. Cell Mol Life Sci. 2004;1:886–898.
18.
BerardelliA, CurraA, FabbriniG, . Pathophysiology of tics and Tourette syndrome. J Neurol. 2003;250:781–787.
19.
SingerHS, MinzerK.Neurobiology of Tourette's syndrome: concepts of neuroanatomic localization and neurochemical abnormalities. Brain Dev. 2003;25:70–84. 20.
20.
AlexanderGE, CrutcherMD.Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends Neurosci. 1990;13:266–271.
21.
GraybielAM, CanalesJJ, Capper-LoupC.Levodopa-induced dyskinesias and dopamine-dependent stereotypies: a new hypothesis. Trends Neurosci. 2000;23:71–77.
22.
SacksOW.Acquired Tourettism in adult life. Adv Neurol. 1982;35:89–92.
23.
RauchSL, BaerL, CosgroveGR, . Neurosurgical treatment of Tourette's syndrome: a critical review. Compr Psychiatry. 1995;36:141–156.
24.
DursunSM, BurkeJG, ReveleyMA.Antisaccade eye movement abnormalities in Tourette syndrome: evidence for cortico-stiriatal network dysfunction?J Psychopharmacol.2000;14:37–39.
25.
CummingsJL.Frontal-subcortical circuits and human behavior. Arch Neurol. 1993;50:873–880.
26.
SegawaM.Neurophysiology of Tourette's syndrome: pathophysiological considerations. Brain Dev. 2003;25:(suppl 1)S62–S69.
27.
ObesoJA, RothwellJC, MarsdenCD.The neurophysiology of Tourette syndrome. Adv Neurol. 1982;35:105–114.
28.
StevensA, GuntherW, LutzenbergerW, . Abnormal topography of EEG microstates in Gilles de la Tourette syndrome. Eur Arch Psychiatry Clin Neurosci. 1996;246:310–316.
29.
HydeTM, EmsellemHA, RandolphC, . Electroencephalographic abnormalities in monozygotic twins with Tourette's syndrome. Br J Psychiatry. 1994;164:811–817.
CastellanosFX, FineEJ, KaysenD, . Sensorimotor gating in boys with Tourette's syndrome and ADHD: preliminary results. Biol Psychiatry. 1996;39:33–41.
32.
WeateSJ, NewellSA, BongnerJE, . Contingent negative variation in Giles de la Tourette syndrome. Clinical Encephalography. 1993;24:188–191.
33.
WalterWG, CooperR, AldridgeVJ, . Contingent negative variation: an electric sign of sensorimotor association an expectancy in the human brain. Nature. 1964;203:380–384.
34.
SingerHS, DicksonJ, MartinieD, . Second messenger systems in Tourette's syndrome. J Neurosci. 1995;128:78–83.
35.
LeeO, LoiselleCR, BeckerKG, . Nemochemical markers and microarrays in postmortem Tourette syndrome putamen and brain area 9. Ann Neurol. 2002;(suppl 1):SlOl.
36.
JankovicJ, OrmanJ.Tetrabenazine therapy of dystonia, chorea, tics, and other dyskinesias. Neurology. 1988;38:391–394.
37.
JankovicJ, Rohaidy MotorH., behavioral and pharmacological findings in Tourette's patients. Can J Neurol Sci.1987;14:541–546.
HoukJ, DavisJ, BeiserD.Models of information processing in the basal ganglia. Cambridge, MA: MIT Press; 1995.
40.
MinkJW.Basal ganglia dysfunction in Tourette's syndrome: a new hypothesis. Pediatr Neurol. 2001;25:190–198.
41.
SingerHS, TuneLE, ButlerIJ, . Clinical symptomatology, CSF neurotransmitter metabolites, and serum haloperidol levels in Tourette syndrome. Adv Neurol. 1982;35:177–183.
42.
ButlerIJ, KoslowSH, SeifertWEJr, . Biogenic amine metabolism in Tourette syndrome. Ann Neurol. 1979;6:37–39.
43.
SingerHS, HahnIH, MoranTH.Abnormal dopamine uptake sites in postmortem striatum from patients with Tourette's syndrome. Ann Neurol. 1991;30:558–562.
44.
StamenkovicM, SchindlerSD, AsenbaumS, . No change in striatal dopamine re-uptake site density in psychotropic drug naive and in currently treated Tourette's disorder patients: a [(123)I]-ß-CIT SPECT-study. Eur Neuropsychopharmacol. 2001;11:69–74.
45.
Muller-VahlKR, BerdingG, BruckeT, . Dopamine transporter binding in Gilles de la Tourette syndrome. J Neurol. 2000;247:514–520.
MeyerP, BohnenNI, MinoshimaS, . Striatal presynaptic monoaminergic vesicles are not increased in Tourette's syndrome. Neurology. 1999;53:371–374.
49.
ErnstM, ZametkinAJ, JonsPH, . High pre-synaptic dopaminergic activity in children with Tourette's disorder. J Am Acad Child Adolesc Psychiatry. 1999;38:86–94.
50.
SingerHS, SzymanskiS, GiulianoJ, . Elevated intrasynaptic dopamine release in Tourette's syndrome measured by PET. Am J Psychiatry. 2002;159:1329–1336.
51.
KhoshboueiH, SenN, GuptaroyB, . N-Terminal phosphorylation of the dopamine transporter is required for amphetamine-induced efflux. PLo S Biol. 2004:2:e87.
52.
GraceAA.Cortical regulation of subcortical dopamine systems and its possible relevance to schizophrenia. J Neural Transm. 1993;91:111–134.
53.
NieuwenhuysR.The neocortex. An overview of its evolutionary development, structural organization and synaptology. Anat Embryol (Berl). 1994;190:307–337.
54.
AndersonGM, PollakES, ChatterjeeD, . Postmortem analysis of subcortical monoamines and amino acids in Tourette syndrome. Adv Neurol. 1992;58:123–133.
55.
CanalesJJ, Capper-LoupC, HuD, . Shifts in striatal responsivity evoked by chronic stimulation of dopamine and glutamate systems. Brain. 2002;125:2353–2363.
56.
WuY, PearlSM, ZigmondMJ, . Inhibitory glutamatergic regulation of evoked dopamine release in striatum. Neuroscience. 2000;96:65–72.
57.
ComingsDE.Blood serotonin and tryptophan in Tourette syndrome. Am J Med Genet. 1990;36:418–430.
58.
LeckmanJF, GoodmanWK, AndersonGM, . Cerebrospinal fluid biogenic amines in obsessive compulsive disorder, Tourette's syndrome, and healthy controls. Neuropsychopharmacology. 1995;12:73–86.
59.
Muller-VahlKR, MeyerGJ, KnappWH, . Serotonin transporter binding in Tourette syndrome. Neurosci Lett. 2005;385:120–125.
60.
SniderLA, SwedoSE.Post-streptococcal autoimmune disorders of the central nervous system. Curr Opin Neurol. 2003;16:359–365.
61.
SwedoSE, LeonardHL, GarveyM, . Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. Am J Psychiatry. 1998;155:264–271.
62.
KurlanR, JohnsonD, KaplanEL.Streptococcal infection and exacerbations of childhood tics and obsessive-compulsive symptoms: a prospective blinded cohort study. Pediatrics. 2008;121:1188–1197.
63.
MurphyTK, SniderLA, MutchPJ, . Relationship of movements and behaviors to group A streptococcus infections in elementary school children. Biol Psychiatry. 2007;61:279–284.
64.
MellLK, DavisRL, OwensD.Association between streptococcal infection and obsessive-compulsive disorder, Tourette's syndrome, and tic disorder. Pediatrics. 2005;116:56–60.
65.
MorrisCM, Pardo-VillamizarC, GauseCD, . Serum autoantibodies measured by immunofluorescence confirm a failure to differentiate PANDAS and Tourette syndrome from controls. J Neurol Sci. 2009;276:45–48.
66.
PavoneP, BianchiniR, ParanoE, . Anti-brain antibodies in PANDAS versus uncomplicated streptococcal infection. Pediatr Neurol. 2004;30:107–110.
67.
ArchelosJJ, HartungHP.Pathogenetic role of autoantibodies in neurological diseases. Trends Neurosci. 2000;23:317–327.
68.
HydeTM, AaronsonBA, RandolphC, . Relationship of birth weight to the phenotypic expression of Gilles de la Tourette's syndrome in monozygotic twins. Neurology. 1992;42:652–658.
69.
PriceRA, KiddKK, CohenDJ, . A twin study of Tourette syndrome. Arch Gen Psychiatry. 1985;42:815–820.
70.
MeretteC, BrassardA, PotvinA, . Significant linkage for Tourette syndrome in a large French Canadian family. Am J Hum Genet. 2000;67:1008–1013.
71.
Tourette Syndrome Association International Consortium on Genetics. A complete genome screen in sib pairs affected by Gilles de la Tourette syndrome. Am J Hum Genet. 1999;65:1428–1436.
72.
Díaz-AnzaldúaA, JooberR, RivièreJB, . Tourette syndrome and dopaminergic genes: a familybased association study in the French Canadian founder population. Mol Psychiatry. 2004;9:272–277.
73.
MathewsCA, WallerJ, GliddenD, . Self injurious behaviour in Tourette syndrome: correlates with impulsivity and impulse control. J Neurol Neurosurg Psychiatry. 2004;75:1149–1155.
74.
SimonicI, GerickeGS, OttJ, . Identification of genetic markers associated with Gilles de la Tourette's syndrome in an Afrikaner population. Am J Hum Genet. 1998;63:839–846.
75.
DuJC, ChiuTF, LeeKM, . Tourette syndrome in children: an updated review. Pediatr Neonatal. 2010;51:255–264.
76.
ComingsDE, ComingsBG.Alternative hypotheses on the inheritance of Tourette syndrome. Adv Neurol. 1992;58:189–199.
77.
SingerHS.Tourette's syndrome: from behavior to biology. Lancet Neurol. 2005;4:149–159.
MathewsCA, BimsonB, LoweTL, . Association between maternal smoking and increased symptom severity in Tourette's syndrome. Am J Psychiatry. 2006;163:1066–1073.
80.
KhalifaN, von KnorringAL.Tourette syndrome and other tic disorders in a total population of children: clinical assessment and background. Acta Paediatr. 2005;94:1608–1614.
81.
PetersonBS, ZhangH, AndersonGM, . A doubleblind, placebo-controlled, crossover trial of an antiandrogen in the treatment of Tourette's syndrome. J Clin Psychopharmacol. 1998;18:324–331.
82.
LinH, KatsovichL, GhebremichaelM, . Psychosocial stress predicts future symptom severities in children and adolescents with Tourette syndrome and/or obsessive-compulsive disorder. J Child Psychol Psychiatry. 2006;48:157–166.
83.
SniderLA, SwedoSE.PANDAS: current status and directions for research. Mol Psychiatry. 2004;9:900–907.
84.
PetersonBS, ThomasP, KaneMJ, . Basal Ganglia volumes in patients with Gilles de la Tourette syndrome. Arch Gen Psychiatry. 2003;60:415–424.
85.
SingerHS, ReissAL, BrownJE, . Volumetric MRI changes in basal ganglia of children with Tourette's syndrome. Neurology. 1993;43:950–956.
86.
FredericksenKA, CuttingLE, KatesWR, . Disproportionate increases of white matter in right frontal lobe in Tourette syndrome. Neurology. 2002;58:85–89.
87.
BlochMH, LeckmanJF, ZhuH, . Caudate volumes in childhood predict symptom severity in adults with Tourette syndrome. Neurology. 2005;65:1253–1258.
88.
MoriartyJ, VarmaAR, StevensJ, . A volumetric MRI study of Gilles de la Tourette's syndrome. Neurology. 1997;49:410–415.
89.
BaumgardnerTL, SingerHS, DencklaMB, . Corpus callosum morphology in children with Tourette syndrome and attention deficit hyperactivity disorder. Neurology. 1996;47:477–482.
90.
PetersonBS, LeckmanJF, DuncanJS, . Corpus callosum morphology from magnetic resonance images in Tourette's syndrome. Psychiatry Res. 1994;55:85–99.
91.
PetersonBS, SkudlarskiP, AndersonAW, . A functional magnetic resonance imaging study of tic suppression in Tourette syndrome. Arch Gen Psychiatry. 1998;55:326–333.
92.
BiswalBB, UlmerIL.Blind source separation of multiple signal sources of fMR1 data sets using independent component analysis. J Comput Assist Tomogr. 1999;23:265–271.
93.
StoetterB, BraunAR, RandolphC, . Functional neuroanatomy of Tourette syndrome. Limbic-motor interactions studied with FDG PET. Adv Neurol. 1992;58:213–226.
94.
BaxterLRJr, SchwartzJM, GuzeBH, . PET imaging in obsessive compulsive disorder with and without depression. J Clin Psychiatry. 1990;51:61–69.
95.
JeffriesKJ, SchoolerC, SchoenbachC, . The functional neuroanatomy of Tourette's syndrome: an FDG PET study, III. Functional coupling of regional cerebral metabolic rates. Neuropsychopharmacology. 2002;27:92–104.
96.
ShmidtHAE, van der SchootJB.Nuclear medicine: the state of the art of nuclear medicine in Europe. Stuttgart, Germany: Schattauer; 1991.
97.
RiddleMA, RasmussenAM, WoodsSW, . SPECT imaging of cerebral blood flow in Tourette syndrome. Adv Neurol. 1992;58:207–211.
98.
DilerRS, ReyhanliM, TorosF, . Tc-99m-ECD SPECT brain imaging in children with Tourette's syndrome. Yonsei Med J. 2002;43:403–410.
99.
JankovicJ.A randomized, double-blind, placebo-controlled study of topiramate in the treatment of Tourette Syndrome. Mov Disord. 2009;24:497.
100.
SingerHS.Tourette syndrome and other tic disorders. Handb Clin Neurol. 2012;100:641–657.
101.
DuJC, ChiuTF, LeeKM, . Tourette syndrome in children: an updated review. Paediatr Neonatol. 2010;51:255–264.
ScahillL, ChappellPB, KimYS, . A placebo-controlled study of guanfacine in the treatment of children with tic disorders and attention deficit hyperactivity disorder. Am J Psychiatry. 2001;158:1067–1074.
104.
LeckmanJF, HardinMT, RiddleMA, . Clonidine treatment of Gilles de la Tourette's syndrome. Arch Gen Psychiatry. 1991;48:324–328.
105.
BrowneS, RoeM, LaneA, . Quality of life in schizophrenia: relationship to sociodemographic factors, symptomatology and tardive dyskinesia. Acta Psychiatr Scand. 1996;94:118–124.
106.
KlawansHL, FalkDK, NausiedaPA, . Gilles de la Tourette syndrome after long-term chlorpromazine therapy. Neurology. 1978;28:1064–1066.
107.
StahlSM.Tardive Tourette syndrome in an autistic patient after long-term neuroleptic administration. Am J Psychiatry. 1980;137:1267–1269.
108.
AncaMH, GiladiN, KorczynAD.Ropinirole in Gilles de la Tourette syndrome. Neurology. 2004;62:1626–1627.
109.
GilbertDL, DureL, SethuramanG, . Tic reduction with pergolide in a randomized controlled trial in children. Neurology. 2003;60:606–611.
110.
Muller-VahlKR, SchneiderU, PrevedelH, . Delta 9-tetrahydrocannabinol (THC) is effective in the treatment of tics in Tourette syndrome: a 6-week randomized trial. J Clin Psychiatry. 2003;64:459–465.
111.
Muller-VahlKR, SchneiderU, KoblenzA, . Treatment of Tourette's syndrome with delta 9-tetra-hydrocannabinol (THC): a randomized crossover trial. Pharmacopsychiatry. 2002;35:57–61.
112.
AwaadY.Tics in Tourette syndrome: new treatment options. J Child Neurol. 1999;14:316–319.
113.
TrimbleMR, WhurrR, BrookesG, . Vocal tics in Gilles de la Tourette syndrome treated with botulinum toxin injections. Mov Disord. 1998;13:617–619.
114.
TemelY, Visser-VandewalleV.Surgery in Tourette syndrome. Mov Disord. 2004;19:3–14.
115.
HasslerR, DieckmannG.Stereotaxic treatment of tics and inarticulate cries or coprolalia considered as motor obsessional phenomena in Gilles de la Tourette's disease. Rev Neurol (Paris). 1970;123:89–100.
AckermansL, DuitsA, van der LindenC, . Double-blind clinical trial of thalamic stimulation in patients with Tourette syndrome. Brain. 2011;134:832–844.
120.
PortaM, BrambillaA, CavannaAE, . Thalamic deep brain stimulation for treatment-refractory Tourette syndrome: two-year outcome. Neurology. 2009;73: 1375–1380.
121.
AckermansL, TemelY, Visser-VandewalleV.Deep brain stimulation in Tourette's syndrome. Neurotherapeutics. 2008;5:339–344.
122.
ShahedJ, PoyskyJ, KenneyC, . GPi deep brain stimulation for Tourette syndrome improves tics and psychiatric comorbidities. Neurology. 2007;68: 159–160.
123.
AckermansL, TemelY, CathD, . Deep brain stimulation in Tourette's syndrome: two targets?Mov Disord. 2006;21:709–713.
124.
DiederichNJ, KalteisK, StamenkovicM, . Efficient internal pallidal stimulation in Gilles de la Tourette syndrome: a case report. Mov Disord. 2005;20:1496–1499.
125.
HouetoJL, KarachiC, MalletL, . Tourette's syndrome and deep brain stimulation. J Neurol Neurosurg Psychiatry. 2005;76:992–995.
126.
ShieldsDC, ChengML, FlahertyAW, . Microelectrode-guided deep brain stimulation for Tourette syndrome: within subject comparison of different stimulation sites. Stereotact Funct Neurosurg. 2008;86:87–91.
127.
MinkJW, WalkupJ, FreyKA, . Patient selection and assessment recommendations for deep brain stimulation in Tourette syndrome. Mov Disord. 2006;21:1831–1838.
128.
Visser-VandewalleV, van der LindenC, AckermansL, . Deep brain stimulation in Gilles de la Tourette's syndrome. Neurosurgery. 2006;58:E590.
