GILLES DE LA TOURETTE SYNDROME

GILLES DE LA TOURETTE SYNDROME

Current Diagnosis

• Multiple motor and one or more vocal tics have been present for some time during the illness, although not necessarily concurrently.

• The tics may wax and wane in frequency but have persisted for more than 1 year since first tic onset.

•   Onset occurs before age 18 years.

• The disturbance is not caused by the direct physiologic effects of a substance or a general medical condition.

Gilles de la Tourette syndrome, or Tourette syndrome, was named after French neurologist Georges Gilles de la Tourette, who in 1885 described a series of nine patients with chronic tics. Tourette syndrome is a neuropsychiatric illness that begins in childhood. It is characterized by multiple motor and vocal tics that last for longer than 1 year (see Current Diagnosis box). The prevalence of Tourette syndrome varies greatly among epidemiologic studies, ranging from 0.1% to 3.8%. The prevalence of tic disorders is even higher, especially in children requiring special education.

Simple motor tics are sudden, brief, patterned movements such as eye blinking, facial grimace, head jerk, or shoulder shrug. Complex motor tics can involve a series of simple tics or a seemingly purposeful action, such as jumping, touching, or copropraxia (i.e., performing obscene gestures). Simple vocal tics consist of sounds such as throat clearing, sniffing, and coughing. Patients with complex vocal tics may exhibit echolalia (i.e., repeating others’ words), palilalia (i.e., repeating their own words), or coprolalia (i.e., utterance of foul language).

Older children and adolescents often describe a premonitory urge before their tics. Tics can usually be transiently suppressed and are often diminished during focused mental or physical activities. Unlike myoclonus or chorea, tics usually do not affect activities of daily living or occupational or recreational activities. After the brief suppression, the release of the tic often brings relief to the patient. Tic severity commonly worsens during times of emotional stress. Fatigue or illness may also increase tics. Parents often notice more tics when the child is bored or unoccupied with an activity. Tics can occur during light sleep and rapid eye movement (REM) sleep.

Clinical Course

The onset of tics can occur after children are 3 years old, but they usually begin in children 6 to 7 years old. Children often present with motor tics first, followed by the development of vocal tics. Tics often wax and wane in the course of Tourette syndrome. During the early school years, tics often can go unnoticed or be mislabeled as a habit. If tics are noticed by fellow students, bullying is typically not an issue at this age. However, when parents notice the tics, they are often distressed and frequently tell their children to stop the movements.

Tic severity usually increases in the later elementary school years and into adolescence. This is the time when social interference such as bullying begins to occur. By late adolescence and early adulthood, most patients with Tourette syndrome have minimal tics, and some may “outgrow” tics. Because of this pattern, most individuals presenting for medical attention for tics are children.

Patients with Tourette syndrome frequently present with comorbid attention-deficit/hyperactivity disorder (ADHD) and obsessive- compulsive disorder (OCD). They also tend to have more sleep problems, anxiety, and mood disorders.

Diagnosis and Differential Diagnosis

Diagnosis of tic disorders depends on correctly recognizing that the abnormal movements are tics by means of a careful history and thorough physical examination. Laboratory and imaging studies are rarely needed.

Tics may resemble other abnormal movements, such as stereotypy, chorea, ballism, dystonia, and myoclonus. Stereotypies are repetitive, simple movements that are suppressible and that usually occur when a child is excited. Stereotypies usually start when the child is younger than 3 years. Chorea consists of a sequence of random, continual, involuntary, nonpurposeful, nonrhythmic movements. Choreic movements often flow from one body part to another. Ballism is a large-amplitude choreic movement affecting the proximal limb.

Myoclonus is an involuntary, sudden, shocklike movement. Chorea, ballism, and myoclonus cannot be volitionally suppressed. Dystonia is produced by co-contraction of agonist and antagonist muscles, leading to abnormal postures, and its twisting movements typically are slower than tics.

Vocal tics may sometimes lead to the misdiagnosis of asthma, chronic cough, or allergic rhinitis. Other primary tic disorders include Provisional Tic Disorder, Persistent (Chronic) Motor or Vocal Tic Disorder, Other Specified Tic Disorder and Unspecified Tic Disorder (DSM-5).

Tics are nonspecific and may occur in drug-induced movement disorders, after head trauma, and in a variety of neurodevelopmental and neurodegenerative disorders. Complex or atypical cases with multiple comorbidities or multiple abnormalities identified on a general or neurologic examination should be referred for specialist consultation.

A controversial diagnosis in which tics or OCD may occur is called pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Criteria for this diagnosis classically include abrupt appearance in prepubertal children of tics or OCD on two or more occasions after documented group A β- hemolytic streptococcal (GABHS) infections. The paradigm for this diagnosis is rheumatic (Sydenham’s) chorea; however, PANDAS has no arthritis, carditis, or nephritis and is not thought to be a rheumatic disease. As a result of recent epidemiological studies, tics are no longer considered a primary symptom of PANDAS. The following interventions are not routinely recommended: diagnostic throat cultures and antistreptococcal antibody tests; therapeutic or preventive antibiotics; and immune-modulating therapies such as steroids, intravenous immunoglobulins, or plasmapheresis. Specialty consultation should be considered.

Treatment

There are many factors to consider when treating a patient with Tourette syndrome, including the presence of common symptoms such as inattentiveness, hyperactivity, obsessive or compulsive behaviors, depression, and anxiety (Box 1). When deciding to treat the patient, it is important to prioritize all the neuropsychiatric symptoms and provide accurate educational information. Tics may not always need to be treated medically, and if treatment is needed, tics may not be the first symptom to manage. Daily tic-suppressing medication is considered when there is functional interference, social interference, pain, or classroom or occupational disruption.

Box 1  
Therapeutic Approach for Tourette Syndrome
• Educate the patient and family about tics and how tics often diminish spontaneously. Long-term reductions in tics may occur in the late teens, irrespective of pharmacologic therapy.

• Rank the tics, attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), anxiety, mood problems, learning problems, and behavior problems in order of the patient’s or the family’s perception of severity.

• Consider nonpharmacologic and pharmacologic treatment for each symptom in the order of perceived severity or impairment.

• Provide information to educate teachers and classmates to reduce social impairment.

• If the patient has learning problems, encourage formal assessment through the school or a psychologist. These children may qualify for modified educational methods.

• If ADHD is the most concerning problem, consider treating with clonidine1 (Kapvay), guanfacine1 (Intuniv), atomoxetine (Strattera), or methylphenidate (Ritalin). Stimulants are not absolutely contraindicated in patients with Tourette syndrome. However, if symptoms of OCD, anxiety, or pervasive developmental disorder are present, ticcing or compulsions may escalate on stimulants. If a patient has done well for months to years on stimulants for ADHD before an exacerbation of tics, it usually is not necessary to discontinue stimulants.

• If behavior problems are the most concerning problem or if a first- degree family member has a bipolar or psychotic disorder, refer the patient to a psychologist or psychiatrist.

• Anxious parents often worsen tic severity. If the family’s anxiety is excessive, refer family members to a psychologist.

• If OCD or generalized anxiety disorder is the most severe problem, treatment with a selective serotonin reuptake inhibitor may be considered.

• Do not begin treatment with more than one central nervous system drug simultaneously. Start one, wait 2 to 4 weeks, and then reassess all symptoms before starting the next medication.

•   Monitor the benefits and side effects at regular intervals.

• Maintain stable dosing during the school year; consider tapering medications in the summer.

• Consider weaning tic-suppressing medications in the middle to late teen years if tics wane.

1 Not FDA approved for this  indication.

The first step in treating Tourette syndrome is educating the patient, parents, and other adult caregivers. Parents, teachers, and other adult caregivers are discouraged from telling the child to stop ticcing because this produces emotional anxiety that may worsen the tics.

Educational materials for teachers often promote a conducive environment for the child at school. The patient is encouraged to openly talk about his or her disorder to classmates to promote understanding and minimize bullying. Newer cognitive-behavioral treatments for tic suppression appear to be helpful for children and adolescents, and they should be considered.

Clinical trials enrolling patients with Tourette syndrome are usually small and show small effect sizes. Most commonly used tic- suppressing medications belong to two classes: α2-adrenergic agonists and dopamine receptor blocking agents (Table 1). Other agents may show modest benefit. Because Tourette syndrome is a chronic, nonfatal disorder, it is prudent to start treatment with medications that carry the least side effects. For this reason, α2-adrenergic agonists are usually the first-line treatment. Although it is unclear what the second-line agents should be, it is reasonable in many cases to restrict dopamine receptor blocking agents to the most severe cases.

Table 1

Therapy for Tics in Tourette Syndrome

1  Not FDA approved for this indication.

* The system areas are 3.5 cm2 (Catapres TTS-1), 7.0 cm2 (Catapres TTS-2), and 10.5 cm2 (Catapres TTS-3), and the amount of drug released is directly proportional to the  area.

α2-Adrenergic Agonists

Clonidine (Catapres)1 and guanfacine (Tenex)1 are α2-adrenergic agonists often used to treat tics. Several randomized trials have shown that these agents reduce tic and ADHD symptoms. The main side effects are sedation and lightheadedness due to mild hypotension.

Sedation is more common with clonidine. The clonidine patch (Catapres-TTS)1 may produce less peak sedation, but it commonly produces local skin irritation.

Dopamine Receptor Blocking Agents

Typical and atypical neuroleptics are dopamine receptor blocking agents that can be used to treat tics. Neuroleptics such as pimozide (Orap) and haloperidol (Haldol) can be very effective in tic suppression, but they can cause acute akathisia, dystonic reactions, cognitive blunting, acute anxiety with somatizations and school refusal, sedation, weight gain, metabolic syndrome, and QT prolongation. Monitoring for tardive dyskinesia is also important.

Some experts recommend baseline electrocardiograms, particularly for individuals with personal or family history of cardiac arrhythmias. Weight gain and metabolic syndrome should be considered when starting neuroleptics, particularly risperidone (Risperdal) and aripiprazole (Abilify).1 Some experts recommend obtaining baseline values for weight, blood pressure, fasting glucose, and lipid profile, with follow-up monitoring every 3 months to detect drug-induced metabolic syndrome. Diet modification, routine exercise, or medical therapy may be needed.

Other Tic-Suppressing Medications

Several small, controlled studies show benefit for topiramate (Topamax),1 dopamine agonists,1 baclofen (Lioresal),1 benzodiazepines,1 and botulinum toxin type A (Botox)1 injections for focal, strong tics. Tetrabenazine (Xenazine)1 has been reported to reduce tics.

Behavioral Therapy

Recent clinical trials show that Comprehensive Behavioral Intervention for Tics, in which the patient learns to increase self- awareness of tics and premonitory urges and to perform antagonistic movements, reduces tics.

Treatment of Comorbid Conditions

ADHD and OCD are common comorbid conditions in Tourette syndrome. These comorbid symptoms are often more debilitating than the tics. Concern about stimulant therapy worsening tics was addressed by the Tourette Syndrome Study Group in the landmark Treatment of ADHD in Children with Tics (TACT) study. In this study, children treated with methylphenidate (Ritalin) had, on average, reduced tic severity, contrary to the widely held belief that stimulants exacerbate tics.

Medical treatment options for ADHD include psychostimulants, α2=adrenergic agonists guanfacine (Intuniv) and clonidine (Kapvay), and the selective norepinephrine reuptake inhibitor atomoxetine (Strattera). OCD management includes cognitive-behavioral therapy, clomipramine (Anafranil), and any of the selective serotonin reuptake inhibitors.

Summary

Tourette syndrome is a complex neuropsychiatric illness with many potential symptoms that may need medical and nonmedical therapies. Cooperation among the primary care physician, neurologist, psychiatrist, and psychologist is imperative for the comprehensive care of severely affected patients. If a patient has mild tics and few or no comorbid symptoms, medical therapy may not be needed.

However, if the tics are severe in the presence of many neuropsychiatric symptoms, it is reasonable to refer patients to specialists.

References

1.     Bloch M.H., Panza K.E., Landeros-Weisenberger A., Leckman J.F. Meta-analysis: treatment of attention-deficit/hyperactivity disorder in children with comorbid tic disorders. J Am Acad Child Adolesc Psychiatry. 2009;48:884–893.

2.    Gilbert D.L., Jankovic J. Pharmacological treatment of tourette syndorme. Journal of Obsessive-Compulsive and Related Disorders. 2014;3:407–414.

3.     Leckman J.F., King R.A., Gilbert D.L., et al. Streptococcal upper respiratory tract infections and exacerbations of tic and obsessive-compulsive symptoms: a prospective longitudinal study. J Am Acad Child Adolesc Psychiatry. 2011;50:108–118 e3.

4.    Piacentini J., Woods D.W., Scahill L., et al. Behavior therapy for children with Tourette disorder: a randomized controlled trial. JAMA. 2010;303:1929–1937.

5.     Zinner S.H., Mink J.W. Movement disorders I: tics and stereotypies. Pediatr Rev. 2010;31:223–233.

1  Not FDA approved for this  indication.

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