BASICS
DESCRIPTION
- Tourette syndrome (TS) is a movement disorder most commonly seen in school-age children. A childhood-onset neurobehavioral disorder characterized by the presence of multiple motor and at least one phonic tic (see "Physical Exam " ť).
- 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 Ž ˛-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
DIAGNOSIS
HISTORY
Diagnosis of TS is based on history and clinical presentation (i.e., observation of tics with/without presence of coexisting disorders). Identify comorbid conditions. ‚
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.
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).
- 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.
- α2-Adrenergic receptor agonists (2)[B]
- Historically first-line agents due to favorable side-effect 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
- α2-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
- 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].
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
11 Kenney ‚ C, Kuo ‚ SH, Jimenez-Shahed ‚ J. Tourette 's syndrome. Am Fam Physician. 2008;77(5):651 " “658.22 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 " “104.33 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Association; 2013.44 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 " “196.55 Pringsheim ‚ T, Marras ‚ C. Pimozide for tics in Tourette 's syndrome. Cochrane Database Syst Rev. 2009;(2):CD006996.66 Pringsheim ‚ T, Steeves ‚ T. Pharmacological treatment for attention deficit hyperactivity disorder (ADHD) in children with comorbid tic disorders. Cochrane Database Syst Rev. 2011;(4):CD007990.77 Lombroso ‚ PJ, Scahill ‚ L. Tourette syndrome and obsessive-compulsive disorder. Brain Dev. 2008;30(4):231 " “237.88 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
Curtis ‚ A, Clarke ‚ CE, Rickards ‚ HE. Cannabinoids for Tourette 's syndrome. Cochrane Database Syst Rev. 2009;(4):CD006565. ‚
CODES
ICD10
F95.2 Tourette 's disorder ‚
ICD9
307.23 Tourette 's disorder ‚
SNOMED
- 5158005 Gilles de la Tourette 's syndrome (disorder)
- 23772009 Dysphonia of Gilles de la Tourette 's syndrome (disorder)
CLINICAL PEARLS
- 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).