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Tourette Syndrome
Ravin V. Patel, MD
Dustin Creech, MD
image BASICS
DESCRIPTION
  • Tourette syndrome (TS) is a movement disorder most commonly seen in school-age children. A childhoodonset neurobehavioral disorder characterized by the presence of multiple motor and at least one phonic tic (see “Physical Exam”).
    • Tics are sudden, brief, repetitive, stereotyped motor movements (motor tics) or sounds (phonic tics) produced by moving air through the nose, mouth, or throat.
    • Tics tend to occur in bouts.
    • Tics can be simple or complex.
      • Motor tics precede vocal tics.
      • Simple tics precede complex tics.
    • Tics often are preceded by sensory symptoms, especially a compulsion to move.
    • Patients are able to suppress their tics, but voluntary suppression is associated with an inner tension that results in more forceful tics when suppression ceases.
    • System(s) affected: nervous
EPIDEMIOLOGY
Incidence
  • The onset occurs before 18 years of age.
  • Predominant age
    • Average age of onset: 7 years (3 to 8 years)
    • Tic severity is greatest at ages 7 to 12 years.
      • 96% present by age 11 years
    • Of children with TS, 50% will experience complete resolution of symptoms by age 18 years (based on self-reporting).
  • Predominant sex: male ≥ female (3:1)
  • Predominant race/ethnicity: clinically heterogeneous disorder, but non-Hispanic whites (2:1) compared with Hispanics and/or blacks
Prevalence
0.77% overall in children
  • 1.06% in boys
  • 0.25% in girls
ETIOLOGY AND PATHOPHYSIOLOGY
Abnormalities of dopamine neurotransmission and receptor hypersensitivity, most likely in the ventral striatum, play a primary role in the pathophysiology.
  • Abnormality of basal ganglia development
  • Thought to result from a complex interaction between social, environmental, and multiple genetic abnormalities.
  • Mechanism is uncertain; may involve dysfunction of basal ganglia-thalamocortical circuits, likely involving decreased inhibitory output from the basal ganglia, which results in an imbalance of inhibition and excitation in the motor cortex
  • Controversial pediatric autoimmune neuropsychiatric disorder association with Streptococcus (PANDAS)
    • TS/OCD cases linked to immunologic response to previous group A &bgr;-hemolytic streptococcal infection (GABHS)
    • Thought to be linked to 10% of all TS cases
    • Five criteria
      • Presence of tic disorder and/or OCD
      • Prepubertal onset of neuropsychosis
      • History of sudden onset of symptoms and/or episodic course with abrupt symptom exacerbation, interspersed with periods of partial/complete remission
      • Evidence of a temporal association between onset/exacerbation of symptoms and a prior streptococcal infection
      • Adventitious movements during symptom exacerbation (e.g., motor hyperactivity)
Genetics
  • Predisposition: frequent familial history of tic disorders and OCD
  • Precise pattern of transmission and genetic origin unknown. Recent studies suggest polygenic inheritance with evidence for a locus on chromosome 17q; sequence variants in SLITRK1 gene on chromosome 13q also are associated with TS.
  • Higher concordance in monozygotic compared with dizygotic twins; wide range of phenotypes
RISK FACTORS
  • Risk of TS among relatives: 9.8-15%
  • First-degree relatives of individuals with TS have a 10- to 100-fold increased risk of developing TS.
  • Low birth weight, maternal stress during pregnancy, severe nausea and vomiting in 1st trimester
COMMONLY ASSOCIATED CONDITIONS
  • OCD (28-67%)
  • ADHD (50-60%)
  • Conduct disorder
  • Depression/anxiety including phobias, panic attacks, and stuttering
  • Learning disabilities (23%)
  • Impairments of visual perception, sleep disorders, restless leg syndrome, and migraine headaches
image DIAGNOSIS
PHYSICAL EXAM
  • Typically, the physical exam is normal.
  • Motor and vocal tics are the clinical hallmarks.
  • Tics fluctuate in type, frequency, and anatomic distribution over time.
  • Multiple motor tics include facial grimacing, blinking, head/neck jerking, tongue protruding, sniffing, touching, and burping.
  • Vocal tics include grunts, snorts, throat clearing, barking, yelling, hiccupping, sucking, and coughing.
  • Tics are exacerbated by anticipation, emotional upset, anxiety, or fatigue.
  • Tics subside when patient is concentrating/absorbed in activities.
  • Motor and vocal tics may persist during all stages of sleep, especially light sleep.
  • Blink-reflex abnormalities may be observed.
  • No known clinical measures reliably predict children who will continue to express tics in adulthood; severity of tics in late childhood is associated with future tic severity.
  • Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) criteria (1)[C]:
    • A. Both multiple motor and one or more vocal tics have been present at some time during the illness, although not necessarily concurrently.
    • B. The tics may wax and wane in frequency but have persisted for more than 1 year since first tic onset.
    • C. Onset is before age 18 years.
    • D. The disturbance is not attributable to the physiologic effects of a substance (e.g., cocaine) or another medical condition (e.g., Huntington disease, postviral encephalitis).
DIFFERENTIAL DIAGNOSIS
  • Chorea/Huntington disease
  • Myoclonus
  • Seizure
  • Ischemic or hemorrhagic stroke
  • Essential tremor
  • Posttraumatic/head injury
  • Headache
  • Dementia
  • Wilson disease
  • Sydenham chorea
  • Multiple sclerosis
  • Postviral encephalitis
  • Toxin exposure (e.g., carbon monoxide, cocaine)
  • Drug effects (e.g., dopamine agonists, fluoroquinolones)
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • No definitive lab tests diagnose TS. Based on clinical features, particularly the presence of multiple motor and vocal tics.
  • Thyroid-stimulating hormone (TSH) should be measured because of association of tics with hyperthyroidism.
  • No imaging studies diagnose TS
  • EEG shows nonspecific abnormalities; useful only to differentiate tics from epilepsy.
Test Interpretation
  • Smaller caudate volumes in patients with TS
  • Striatal dopaminergic terminals are increased, as is striatal dopamine transporter (DAT) density.
image TREATMENT
GENERAL MEASURES
  • Treatment assessment
    • Yale Global Tic Severity Score
    • Tourette-Syndrome Severity Scale
    • Global Assessment of Functioning Scale
    • Gilles de la Tourette Syndrome-Quality of Life Scale
  • A detailed history is crucial to management, because tics and comorbidities are interrelated. Goal of treatment should be to improve social functioning, self-esteem, and quality of life.
  • Educate that tics are neither voluntary nor psychiatric.
  • Many patients require no treatment; patient should play an active role in treatment decisions.
  • Educate patient, family, teachers, and friends to identify and address psychosocial stressors and environmental triggers.
  • No cure for tics: Treatment is purely symptomatic, and multimodal treatment usually is indicated.
  • Neurologic and psychiatric evaluation may be useful for other primary disorders and comorbid conditions (especially ADHD, OCD, and depression).
  • TS clusters with several comorbid conditions; each disorder must be evaluated for associated functional impairment because patients often are more disabled by their psychiatric conditions than by the tics; choice of initial treatment depends largely on worst symptoms (tics, obsessions, or impulsivity).
  • P.1049

  • Nonpharmacologic therapy—reassurance and environmental modification, identification and treatment of trigger, and cognitive behavior therapy
  • When pharmacotherapy is employed, monotherapy is preferred to polytherapy.
MEDICATION
First Line
  • Atypical antipsychotics
    • Risperidone: now recommended for standard therapy (2) [A]
      • Initiate 0.25 BID; titrate to 0.25 to 6 mg/day
      • As effective as haloperidol and pimozide for tics with fewer side effects
      • Effective against comorbidities such as OCD
      • Side effects may limit use: sedation, weight gain, and fatigue.
  • &agr;2-Adrenergic receptor agonists (2)[B]
    • Historically first-line agents due to favorable sideeffect profile, but suboptimal efficacy in limited clinical trials
    • Side effects: sedation and hypotension common
      • Initiate therapy gradually and taper when discontinuing to avoid cardiac adverse events.
    • Clonidine 0.1 to 0.3 mg/day given BID-TID
      • Maximum dose: 0.5 mg/day
      • 25-50% of patients report at least some reduction in tics.
    • Guanfacine 1 to 3 mg/day given daily or BID
      • Less sedating and longer duration of action compared with clonidine
      • Improves motor/vocal tics by 30% in some studies; no better than placebo in others
Second Line
  • Neuroleptics
    • Typical antipsychotics
      • High risk for extrapyramidal symptoms (EPS)
      • Haloperidol: initiate 0.5 mg/day and titrate 0.5 mg/week up to 1 to 4 mg at bedtime (3)[B]
        • FDA-approved for treating tics
        • Considered last option of typical antipsychotics due to lower efficacy and increased side effects compared to similar medications
      • Pimozide: initiate 0.5 mg/day and titrate 0.5 mg/week up to 1 to 4 mg at bedtime (4)[A]
        • FDA-approved for treating tics
        • Risk of cardiac toxicity (prolonged Q-T interval and arrhythmias); must be given under ECG monitoring; long-term use may induce sedation, weight gain, depression, pseudoparkinsonism, and akathisia.
        • Found to work better in long-term control of tics versus acute exacerbations
      • Fluphenazine: 2.5 to 10 mg/day
        • Effective but less favored due to side effects
    • Atypical antipsychotics (3)[C]
      • Olanzapine: initiate 2.5 to 5.0 mg/day; titrate up to 20 mg/day
        • Equally effective as haloperidol and pimozide
        • May cause metabolic disturbances and weight gain
      • Quetiapine: initiate 100 to 150 mg/day; titrate to 100 to 600 mg/day
        • Well tolerated but limited data exists
      • Ziprasidone: 5 to 40 mg/day
      • Aripiprazole: initiate 2 mg/day; titrate up to 20 or 30 mg/day
        • Few studies but favorable side-effect profile
  • Alternative treatments
    • Topiramate: 25 to 200 mg/day (2)[A]; promising data but not sufficient efficacy so far to recommend as first or second line
    • Tetrabenazine
    • Baclofen
  • Treatment of ADHD in patients with tics (5)[A]
    • Stimulants
      • Comorbid tic disorder is not a serious contraindication, as previously held; exacerbation of tics is neither clinically significant nor common.
      • Methylphenidate: 2.5 to 30 mg/day
      • Dextroamphetamine: 5 to 30 mg/day
    • &agr;2-Adrenergic agonists
      • Guanfacine
      • Clonidine
        • The combination of methylphenidate and clonidine has shown superior efficacy in treating both ADHD and tic symptoms compared to monotherapy with either agent in one trial.
    • Other medications
      • Atomoxetine
      • Desipramine
  • Treatment of OCD in patients with tics (6)[B]
    • SSRIs
      • First-line treatment of OCD; can be used in TS as well
      • Side effects include nausea, insomnia, sexual dysfunction, headache, and agitation.
      • Comorbid tic disorder not a contraindication; exacerbation of tics neither clinically significant nor common.
      • Black box warning for suicidality with SSRIs
      • Fluoxetine: 10 to 80 mg/day
      • Fluvoxamine: 50 to 300 mg/day
      • Sertraline: 50 to 200 mg/day
    • Tricyclic antidepressants
      • Clomipramine: 25 to 200 mg/day
        • Can be used in patients refractory to SSRIs or to augment SSRIs in partial responders
        • Side effects: weight gain, dry mouth, lowered seizure threshold, and constipation; ECG changes, including Q-T prolongation and tachycardia
ADDITIONAL THERAPIES
  • Botulinum toxin injections in severe cases or where chronic medication therapy is not preferred.
  • Habit-reversal training provides a viable tic suppression treatment: Works equally for motor and vocal tics.
SURGERY/OTHER PROCEDURES
Thalamic ablation and deep brain stimulation have been used experimentally (7)[C].
COMPLEMENTARY & ALTERNATIVE MEDICINE
Nonpharmacologic therapy
  • Reassurance and environmental modification
  • Identification and treatment of triggers
  • Behavioral therapy: awareness/assertiveness training, relaxation therapy, habit-reversal therapy, and self-monitoring has shown to significantly decrease tic severity.
  • Hypnotherapy
  • Biofeedback
  • Acupuncture
  • Cannabinoids: insufficient evidence to recommend; small trials show small positive effects in some parameters (8)[A].
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
Observe for associated psychiatric disorders.
PATIENT EDUCATION
  • Reassurance that many patients with tics do not need medication; often education and/or therapy is all that is required.
  • National Tourette Syndrome Association: http://www.tsa-usa.org
PROGNOSIS
  • Symptoms will fluctuate throughout illness.
  • Tic severity typically stabilizes by age 25 years.
  • 60-75% of young adults show some improvement in symptoms.
  • 10-40% of patients will exhibit full remission.
REFERENCES
1. Kenney C, Kuo SH, Jimenez-Shahed J. Tourette's syndrome. Am Fam Physician. 2008;77(5):651-658.
2. Huys D, Hardenacke K, Poppe P, et al. Update on the role of antipsychotics in the treatment of Tourette syndrome. Neuropsychiatr Dis Treat. 2012;8:95-104.
3. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Association; 2013.
4. 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(4):173-196.
5. Pringsheim T, Marras C. Pimozide for tics in Tourette's syndrome. Cochrane Database Syst Rev. 2009;(2):CD006996.
6. Pringsheim T, Steeves T. Pharmacological treatment for attention deficit hyperactivity disorder (ADHD) in children with comorbid tic disorders. Cochrane Database Syst Rev. 2011;(4):CD007990.
7. Lombroso PJ, Scahill L. Tourette syndrome and obsessive-compulsive disorder. Brain Dev. 2008;30(4):231-237.
8. Savica R, Stead M, Mack KJ, et al. Deep brain stimulation in Tourette syndrome: a description of 3 patients with excellent outcome. Mayo Clin Proc. 2012;87(1):59-62.
Additional Reading
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Curtis A, Clarke CE, Rickards HE. Cannabinoids for Tourette's syndrome. Cochrane Database Syst Rev. 2009;(4):CD006565.
Codes
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ICD10
F95.2 Tourette's disorder
Clinical Pearls
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  • TS is diagnosed by history and witnessing tics; have parent video patient's tics if not present on exam in your office.
  • Nearly 50% of children with tics also have ADHD. Stimulants may be used as first-line treatment for ADHD (tics are not a contraindication, as previously believed).