Pediatric Tourette Syndrome 

Updated: Mar 25, 2015
Author: Jason S Hawley, MD; Chief Editor: Eduardo Dunayevich, MD 

Overview

Background

Tourette syndrome (TS) is a childhood neuropsychiatric disorder characterized by motor and phonic (vocal) tics. It is often associated with behavior disorders, particularly obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD). These behavior disorders often accompany the tics and may dominate the clinical picture in some patients. TS is a genetic condition that runs in families (see Pathophysiology and Etiology). However, the precise genetic abnormality responsible for the phenotype has not yet been elucidated.

In this article, the incidence, genetics, clinical picture, and management of TS are reviewed.

For more information, see Tourette Syndrome and Other Tic Disorders.

Historical perspective

In 1885, Gilles de la Tourette, the French neurologist and student of Charcot, presented 9 cases of childhood-onset tics. These children also had associated coexisting behavior problems, as well as unusual vocalizations that we now recognize as phonic tics. Although Tourette correctly considered this a genetic disorder, the etiology was ascribed to psychogenic causes for nearly a century afterwards.

In the 1960s, with the emergence of neuroleptic medications, the tics of TS were found to respond favorably to these new medications. The fundamental perception of TS changed from that of a psychiatric disorder to a primary neurologic disorder believed to involve focal dysfunction within the brain. Since that time, extensive research has been performed to understand the underlying neurobiology behind TS. Once viewed as a rare psychiatric disorder, TS is now understood to be a relatively common and diverse childhood-onset genetic condition.

Pathophysiology

The precise pathophysiologic mechanisms of TS are yet to be determined. Most studies support the hypothesis that TS is an inherited developmental disorder of synaptic neurotransmission.[1] Further studies are needed to elucidate the physiologic and cellular mechanisms underlying tics and TS.[2]

The basal ganglia, particularly the caudate nucleus and the inferior prefrontal cortex, are implicated in the pathogenesis of TS. Volumetric magnetic resonance imaging studies have shown that children with TS have larger dorsolateral prefrontal regions as well as increased cortical white matter in the right frontal lobe.

The neurobiology of TS is currently accepted to involve the likely disinhibition in cortico-striatal-thalamic-cortical loops, with an overly active caudate nucleus.[3] Similar models have been ascribed to ADHD and OCD. Dysfunction within these circuits results in an inability to suppress unwanted movements, behaviors, or impulses.

Functional neuroimaging studies performed while patients are actively having tics also demonstrate multifocal activation within the brain, involving the following areas:

  • Medial and lateral premotor cortices

  • Anterior cingulated cortex

  • Dorsolateral-rostral prefrontal cortex

  • Inferior parietal cortex

  • Putamen

  • Caudate nucleus

  • Primary motor cortex

  • Broca area

  • Superior temporal gyrus

  • Insula

  • Claustrum

The activity in these regions was found to be synchronous with tic occurrences. This widespread, abnormal activity of interrelated circuits shows extensive involvement of the sensorimotor, language, and paralimbic regions.[2, 4]

While multiple neurotransmitters are likely involved, dopamine has attracted particular interest, given the effectiveness of agents that act on dopamine receptors in controlling the symptoms of TS. Functional neuroimaging studies implicate abnormalities within dopaminergic systems within the striatum and prefrontal cortex. Patients with TS have increased density of the presynaptic dopamine transporter and an increased density of postsynaptic D2 dopamine receptors, suggesting increased uptake and release of dopamine.

The increased density of the dopamine receptors have led some investigators to propose a supersensitivity to dopamine within the striatum, prefrontal cortex, and motor region, leading to the phenotype of tics and other behaviors associated with TS. The dopamine supersensitivity hypothesis may explain why tics are so responsive to the dopamine receptor blockers (neuroleptics).

Genetic aspects

The gene or genes responsible for TS have not been determined. Evidence supports an autosomal dominance inheritance pattern. TS is likely a polygenetic condition with variable penetrance. Twin studies indicate a greater than 90% concordance.[5] In addition, increasing evidence shows a genetic link between tic disorders and OCD.

Immune-mediated pathogenesis

Some researchers have proposed that TS may have an immune-mediated pathogenesis similar to pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). In this model, antecedent infection with group A beta-hemolytic Streptococcus leads to the formation of antineuronal antibodies that cause neuronal dysfunction.

Investigations comparing antineuronal antibody profiles in TS, PANDAS, and age-matched controls did not demonstrate any differences, however. Treatments aimed at this pathophysiologic mechanism, such as plasmapheresis, intravenous immunoglobulin, or antibiotics, are not currently recommended.[6]

Volition

Although some tics may be partly voluntary, physiologic studies indicate that tics are not mediated via the same motor pathways of willed movements. Electrophysiologic data demonstrate the absence of premotor potentials in simple motor tics, suggesting that tics truly are involuntary or occur in response to an external cue.

Sleep studies provide additional evidence that tics are involuntary. Polysomnography of 34 patients with TS demonstrated motor tics in various sleep stages in 23, and vocal tics in 4.

Etiology

The precise cause of TS is unknown, but the preponderance of evidence suggests that TS is an inherited developmental condition. Recently, an alternative autoimmune-mediated theory for the etiology of TS has become of interest.

Genetic theory

Analysis of families with TS suggests an autosomal dominant pattern of inheritance. The concordance rate among monozygotic twins is 53%, compared with 8% for dizygotic twins.[4]

Significant efforts have been made over the past 15 years to determine the precise gene or genes responsible for TS. Genetic studies performed through the Tourette Syndrome Association, as well as studies of 91 families in South Africa, have implicated chromosome 8 as a possible genetic locus. Data also support possible loci on chromosomes 5 and 11.[7]

In the future, major advances in our understanding of the neurobiology of TS will likely depend on progress in elucidating genetic mechanisms.

Autoimmune theory

The autoimmune theory of TS posits that antibodies directed against an antecedent infection (eg, streptococcal infection) cross-react with neuronal structures in the central nervous system. This is the presumed mechanism of action for Sydenham chorea and pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS).

Selected individuals with TS have elevated titers of antistreptococcal antibodies and antineuronal antibodies similar to those found in patients diagnosed with PANDAS. However, no correlation exists between the presence or absence of antineuronal antibodies and the severity of the tics, the onset of TS symptoms, or the presence of neuropsychiatric symptoms.

Examination of serum antibodies in patients with PANDAS and TS compared with age-matched controls failed to differentiate the 2 disorders from age-matched controls.[6]

In summary, although streptococcal infection may trigger the onset of symptoms associated with TS in a small group of patients, further studies are needed to further examine the validity of an autoimmune/postinfectious cause of TS. Currently, treatment of TS with antibiotics or therapy such as immunosuppressives, IVIG, or plasmapheresis is not recommended.

Risk factors

Risk factors for the TS include the following:

  • Male sex

  • Young age

  • Family history of TS

Epidemiology

TS occurs worldwide, in all social classes and races. Cases meeting current diagnostic criteria have been reported in the United States, Europe, New Zealand, Brazil, Japan, China, and the Middle East. The clinical phenomenology appears similar, regardless of ethnicity or culture, suggesting a common genetic basis.

The precise prevalence of TS has been difficult to ascertain, and what once was thought to be a rare condition is now felt to be much more common. Most children with TS have nondisabling symptoms, their tics improve and resolve with age, and they never seek medical attention.

As the clinical criteria for the condition has evolved, most investigators believe that the estimated prevalence is 0.7-4.2%, based on observation studies in public schools. In school-based studies, tics were identified in 26% of students in special education programs, compared with 6% of students in mainstream classrooms.[8, 9]

Sex- and age-related demographics

The male-to-female ratio varies from 2-10:1. However, if OCD is included as a variant of TS, then the male-to-female ratio is 1:1.

Children are much more likely to meet the diagnostic criteria for TS than adults. TS is a childhood-onset condition, and adults who display symptoms of TS are likely to have had the symptoms since childhood.

Symptoms of TS can be seen in infancy, but most children with TS display readily identifiable symptoms at around age 7 years. Symptoms resolve by adulthood in most children with TS. Whether this resolution represents a compensatory process or resolution of the underlying pathology is unclear.

Prognosis

In most cases of TS, symptoms reach their fullest expression some time during adolescence, roughly a decade after onset. At some point, symptoms become more unpredictable, sometimes changing markedly from day to day or week to week. Despite this, the later teenage years are often a time when the severity of tics levels off and remission begins.

Several retrospective studies indicate that many patients, even those with severe tics during childhood, improve considerably during the late teenage to early adult years. Approximately one third of patients experience complete remissions of tics during this period, whereas another one third of patients improve to the point that their tics are relatively mild and do not cause impairment. Some evidence shows that adolescent tic severity may be of more prognostic value.

Two thirds of children with TS can anticipate a significant amelioration of their tics or almost complete remission. Lifelong remissions are rare, however. The continued presence of such tics is often denied or minimized by these parents but is reported by other family members. At times, tics do not occur in a physician's office, and assessment of these very mild, but persistent, tic disorders is difficult.

Approximately one third of patients with TS do not experience a significant amelioration of symptoms as adults. For these patients, little data are available regarding what percentage of patients become worse, what percentage remain much the same, and what percentage improve to some degree. A fair number of patients present in their third, fourth, and fifth decades for treatment after self-diagnosis. Elderly patients who have never been diagnosed are far more rare but also do present for diagnosis.

Patient Education

One of the most important aspects of treating TS is educating the patient and family members about tic disorders and associated behavioral disturbances. The Tourette Syndrome Association is an excellent tool for patient education. In addition to lengthy discussions with the patient and family at the time of diagnosis, a packet of educational brochures prepared by the Tourette Syndrome Association is helpful.

 

Presentation

History

The hallmark clinical features of Tourette syndrome (TS) are tics with coexisting behavior disorders such as attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), or impulse control behaviors. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) has also established criteria for the clinical diagnosis of TS.

DSM-IV-TR diagnostic criteria from for Tourette syndrome

Diagnostic criteria from DSM-IV-TR for Tourette syndrome (307.23) are as follows:

  • Both multiple motor and one or more vocal tics must be present at some time during the illness, although not necessarily concurrently

  • The tics occur many times a day (usually in bouts) nearly every day or intermittently over more than 1 year, during which time there must not have been a tic-free period of more than 3 consecutive months

  • The age at onset is younger than 18 years

  • The disturbance is not due to the direct physiological effects of a substance (eg, stimulants) or a general medical condition (eg, Huntington disease or postviral encephalitis)

A fifth criterion, included in the earlier DSM-IV but deleted from the DSM-IV-TR, was “The disturbance causes marked distress or significant impairment in social, occupational, or other important areas of functioning.” The rationale behind removing this element of the diagnosis was that many patients with mild TS do not have symptoms that interfere with their daily function and job.

Furthermore, this criterion had the potential to lead to patients with TS being stigmatized for having a condition that causes significant impairments in daily function. The DSM-IV-TR authors felt that this could lead to job discrimination and other forms of labeling. The deletion of this criterion reflects the recognition that many patients with TS do not have significant problems related to their condition.

Clinical characteristics of tics

Tics are abnormal movements or vocalizations that are diverse in presentation. Tics can be simple movements or vocalizations such as eye blinking, coughing, or grunting. They also can be highly complex movements such as running, jumping, or vocalizing phrases or repetitive words. This diversity of presentation can be challenging for the examiner to characterize these abnormal and somewhat bizarre movements.

However, distinctive characteristics can help distinguish tics from other abnormal movements, such as tremor, chorea, myoclonus, or dystonia. Tics are considered semivoluntary, meaning that the patient can often volitionally suppress the movement for a period a time, suppressing the emotional urge or uncomfortable feeling that often arises to perform the tic. Furthermore, an emotional release often occurs after the tic or repetitive tics are completed.

Tics are often suggestible, and can be worsened by stress, boredom, and fatigue. After a period of stress, patients with TS often release their tics when they are alone and relaxed. One frequent clinical observation is that children with TS often spend their time at school suppressing tics, only to come home to a more relaxed and secluded environment where they will release their tics. Between tics, no other abnormal movements occur.

Thus, the suppression ability, the emotional urge and relief associated with the movement, and the suggestibility of the movement, are all clinical features that help differentiate tics from other hyperkinetic movement disorders.

Classifications of tics

Tics are diverse and sometimes bizarre. They are typically divided into motor or vocal/phonic tics. Tics can also be categorized as simple or complex, based on the complexity of the movement or vocalization.

Simple motor tics involve a single muscle or group of muscles. The tic may be a brief jerking movement (clonic tic), a slowed sustain movement or posture (dystonic tic) or a tensing of individual muscle groups (tonic tic). Examples of simple motor tics include eye blinking, nose sniffing, coughing, neck twitching or jerking, eye rolling, and jerking or postured movements of the extremities. Simple motor tics typically consist of simple, nonpurposeful movements.

Complex motor tics involve movements that often involve multiple muscle groups and may appear as semipurposeful movements or behaviors. Examples of complex motor tics include touching oneself or others, hitting, jumping, shaking, or performing a simulated motor task. Also included in the spectrum of complex motor tics is copropraxia and echopraxia (imitating movements of others).

Simple phonic tics are simple vocalizations or sounds. Examples include grunting, coughing, throat clearing, swallowing, blowing, or sucking sounds.

Complex phonic tics are vocalizations of words and/or complex phrases. These verbalizations can be complex and sometimes socially inappropriate. Coprolalia is a complex phonic tic characterized by the shouting of socially inappropriate language (obscenities and profanities). Coprolalia occurs in fewer than half of patients with TS, although it can be one of the most distressing symptoms of the condition.

Patients with TS may have complex phonic tics characterized by the repetition of someone else's words (echolalia) or the repetition of one's own words (palilalia).

Premonitory symptoms of tics

Premonitory feelings or sensations precede motor and vocal tics in more than 80% of patients. These premonitory phenomena may be localizable sensations or discomforts, including the following:

  • Burning feeling in the eye before an eye blink

  • Tension or a crick in the neck that is relieved by stretching of the neck or jerking of the head

  • Feeling of tightness or constriction relieved by arm or leg extension

  • Nasal stuffiness before a sniff

  • Dry or sore throat before throat clearing or grunting

  • Itching before a rotatory movement of the scapula

Rarely, these premonitory feelings, termed in one report as extracorporeal phantom tics, involve sensations in other people and objects and are temporarily relieved by touching or scratching them.

Behavioral symptoms

Behavioral symptoms are common in TS. The 2 most common disorders are OCD and ADHD. The symptoms of OCD (as well as ADHD) may be the dominating and debilitating feature of TS in certain patients.

Questionnaire studies for patients with TS have also demonstrated high rates of mood disorders and anxiety disorders, including panic disorder and simple phobias. Compared with the general population, patients with TS have a higher rate of bipolar disorder.

OCD is the most frequent behavior symptom associated with TS. The rates of OCD in patients with TS range from 20-60%. Obsessive-compulsive symptoms have an increased prevalence in first-degree relatives with tics.

Using longitudinal data from mother-completed questionnaires, the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort evaluated 6,768 children and the prevalence of co-occurring neuropsychiatric conditions. The results suggest that co-occurring OCD and ADHD may be lower in TS cases than previously reported; only 8.2% of TS ”intermediate” cases had both OCD and ADHD, and 69% of TS ”intermediate” cases had neither co-occurring OCD or ADHD.[10]

Obsessions are defined by the DSM-IV-TR criteria as recurrent and persistent thoughts, impulses, or images experienced at some time during the disturbance as intrusive and inappropriate and causing marked anxiety and distress. The thoughts, impulses, or images are not simply worries about real-life problems.

Compulsions are repetitive behaviors (eg, hand washing, ordering, checking) or mental acts (eg, praying, counting, repeating words silently) in response to an obsession or according to rules that must be applied rigidly. The behaviors or mental acts are aimed at preventing or reducing distress or preventing some dreaded event or situation; however, these behaviors or mental acts either are not connected in a realistic way with what they are meant to neutralize or prevent or they are clearly excessive.

The rates of ADHD in TS have ranged from 40-70%. Individuals with ADHD have difficulty focusing their attention, with either difficulty inhibiting their attention to nonrelevant stimuli or difficulty focusing and concentrating on relevant tasks for prolonged periods of time (such as schoolwork) without becoming distracted. Unlike OCD, a genetic link between ADHD and tics is not as clear. Studies have not shown an increased incidence of ADHD in first-degree relatives of individuals with TS. The symptoms of ADHD are often recognized before the tics. Typically, ADHD is commonly treated with stimulants, which can worsen tics. Stimulants do not cause TS, but are more likely to bring out the underlying and often unrecognized tics. Like OCD, the symptoms from ADHD may be more limiting than the tics.

While OCD and ADHD are the 2 most common neurobehavioral symptoms of TS, other disorders pertaining to poor impulse control are frequently seen in individuals with TS. Irritability, rage attacks, inappropriate sexual aggressiveness, and antisocial behavior have all been reported. A rare but very challenging behavior associated with TS is self-mutilating behavior. This behavior has components of both obsession and compulsions and can cause significant morbidity. Individuals often damage their own body by scratching, biting, cutting, or hitting themselves. Often an irresistible urge arises to perform these behaviors.

Specific learning disabilities and subtle neurologic signs are more frequent in patients with TS, further complicating management. Children, although intelligent, may have poor academic achievement, and slight motor coordination difficulties may preclude them from doing well in athletic endeavors.

Anxiety and mood disorders are common in TS. Mood disorders are well recognized as being more prevalent in individuals with TS than the general population. The genetic association between these mood disorders and tics/TS is not clear.

Social and functional impairment

Symptoms from TS can lead to significant limitations in otherwise normal activities. Individuals with TS who have severe motor tics frequently avoid situations with high social visibility. Stress and anxiety in those situations frequently worsen or accentuate the tics themselves.

Phonic or vocal tics (sounds or words) can cause significant social embarrassment. Coprolalia (verbalization of inappropriate words or phrases) and copropraxia (making obscene gestures) can cause significant social embarrassment and lead to isolating patients with TS. Moreover, in school-aged children, these tics can frequently be misinterpreted as rude behavior, leading to disciplinary action.

The associated behavior disorders of ADHD, OCD, and other disorders, such as impulse control disorders, often cause more morbidity that the tics themselves. In children, the behavior complications frequently lead to poor academic performance, social isolation, and emotional problems.

Disorders of attention and concentration may not be just secondary to ADHD, as patients with TS frequently have uncontrollable intrusions of thoughts or an obsessive fixation on irrelevant objects. Moreover, the associated tics of TS can be somewhat volitionally suppressed, and the mental and emotional effort used to suppress tics may also interfere with attention and concentration in school and work.

Developmental history

A developmental history, including developmental milestones and growth curves, is important to exclude genetic disorders such as Down syndrome, autistic spectrum disorders, and other developmental and chromosomal disorders. Tics, ADHD, and OCD can be seen in these conditions.

Physical Examination

Aside from the presence of tics, children with TS will have a normal neurologic examination. Similarly, the mental status examination has no particularly abnormal findings with the exception of the presence of tics, which should be commented on in the behavior, speech, and/or psychomotor sections of the mental status examination, as appropriate.

Occasionally, although not consistently, some decreased attention may be noted, if the patient is distracted by their tics. TS is often comorbid with other psychiatric conditions; therefore, features of comorbid conditions may be noted on the examination. For example, depressed or anxious affect may be noted if the patient has a comorbid mood or anxiety disorder, or difficulty focusing, distractibility, or increased psychomotor behaviors may be noted if the patient has comorbid ADHD.

Because of the increased risks of psychiatric comorbidities such as depression, OCD, and anxiety, individuals with TS are suspected to have a slightly increased risk of self-injurious behavior and suicide. Although data remain unclear, in a recent examination on life-threatening behavior in patients with TS, subgroups within the TS population warranted close attention.

A retrospective study showed that individuals with malignant TS, defined as having at least 2 emergency department visits or at least 1 hospitalization for TS symptoms, account for approximately 5% of patients referred for subspecialty evaluation. In this group, mood disorders, self-injurious behavior, suicidal ideation, and poor response to therapy were significantly increased. This group is at risk, and a more detailed examination for suicide risk is recommended for individuals with a history suggesting malignant TS.[11]

It is not unusual for children with TS to suppress their tics during medical evaluation, only to release them when they are out of the physician's office. As with any hyperkinetic movement disorder, direct visualization of the abnormal movement aids significantly in making the diagnosis. Parents should be encouraged to videotape their children at home when they are having frequent tics.

A general neurologic examination is important to exclude other conditions that can present with tics. Moreover, the abnormal movement needs to be correctly characterized as a tic to differentiate it from myoclonus, chorea, tremor, and dystonia.

While TS is the most common cause of inherited tics, other more progressive neurodegenerative conditions can present with tics. These disorders include Huntington disease, neuroacanthocytosis, Wilson disease, Hallervorden-Spatz disease, and primary dystonia. A thorough neurologic examination should examine for features suggestive of these conditions.

The presence of Kayser Fleisher rings in the eye is diagnostic of Wilson disease, and should be assessed for in any young patient with a hyperkinetic movement disorder.

Tics have been described in Huntington disease, and the presence of chorea, motor impersistence, abnormal saccades, and gait difficulties is suggestive of this neurodegenerative disorder. In children, Huntington disease often presents with rigidity and bradykinesia (the Westphal variant).

A thorough gait and motor examination should be performed to assess tone and strength.

Examination of the skin should be performed. Neurocutaneous syndromes such as tuberous sclerosis and neurofibromatosis have been rarely reported to be associated with the presence of tics.

 

DDx

Diagnostic Considerations

Patients with Tourette syndrome (TS) and their families may not necessarily alert the practitioner regarding the symptoms. The excessive movements may be dismissed as twitchiness or anxiety and not necessarily considered a disease.

The practitioner could potentially diagnose tics as chorea or myoclonus, and initiate an unnecessary work up to evaluate these conditions. Phonic tics, such as throat clearing, sniffing or cough, may be mistaken for allergies or asthma.

TS should be differentiated from transient tic disorder of childhood, which is similar to TS but lasts for less than a year. Chronic multiple tic disorder has great similarity to TS but remains present in adulthood. Chronic single tic disorder is a motor or vocal tic in adulthood.

Other neurologic diagnoses to consider are the following:

  • Tuberous sclerosis

  • Neuroacanthocytosis

  • Dystonia

  • Hallervorden-Spatz disease

  • Neurofibromatosis type 1

  • Chromosomal disorders

  • Sydenham chorea

  • Motor restlessness

  • Akathisia

  • Excessive startle

Since patients with TS can have multiple behavioral disorders, psychiatric diagnoses to consider are depression, obsessive-compulsive disorder, and personality disorders.

Differential Diagnoses

 

Workup

Approach Considerations

Tourette syndrome (TS) is a clinical diagnosis; therefore, no specific laboratory or genetic tests exist to help establish the diagnosis. Routine community based neuroimaging studies (CT and MRI) are normal in patients with TS. The keys to diagnosis are recognition and an index of suspicion.

Neuroimaging studies performed on a research basis have yielded subtle abnormalities that may give clues to understanding the pathophysiology of TS. Children and adults with TS have reduced caudate volumes compared with controls. Moreover, recent studies have suggested that the degree of volume reduction within the caudate nucleus correlates with the severity of tics and obsessive-compulsive disorder (OCD).[12]

Functional Magnetic Resonance Imaging

Event-related functional MRI studies of patients with tics have indicated that paralimbic and sensory association areas are critically implicated in tic generation, similar to movements triggered internally by unpleasant sensations, as has been shown for pain or itching.

Positron-Emission Tomography

Positron-emission tomography (PET) studies have also shown increased activity in sensomotor, paralimbic, language, and frontal subcortical regions. This activity was event-related to motor and phonic tics, as well as the compulsions to perform these behaviors.

 

Treatment

Approach Considerations

The management of Tourette syndrome (TS) is multifaceted. The approach is primarily aimed at medical management of frequent or disabling tics, treatment of coexisting behavior symptoms, and patient and family education.

Ideally, patients with mild tics who have made a good adaptation in their lives can avoid the use of medications. Educating patients, family members, peers, and school personnel regarding the nature of TS; restructuring the school environment; and providing supportive counseling are measures that may be sufficient to avoid pharmacotherapy. Information is available through school counselors, psychologists, representatives of local chapters of the Tourette Syndrome Association, or related topical organizations.

Pharmacologic therapy for tics is considered when tics interfere with social interactions, school performance, or activities of daily living. The goal of such therapy is not complete elimination of the tic, but rather control of tics to alleviate the social embarrassment or discomfort due to the tic, therefore improving social functioning.

Various therapeutic agents are now available to treat patients with tics, and each medication should be chosen on the basis of expected efficacy and potential adverse effects. Dosages should be titrated slowly to achieve the lowest satisfactory dosage that is sufficient to attain a tolerable level of symptoms. (See Medication)

Only rarely do patients with TS need hospitalization. Most of the patients who do require hospitalization have comorbid conditions and are a threat to themselves or to others. Patients with the complex tics of coprolalia or copropraxia might need a brief hospitalization if their families have difficulty controlling them.

Treatment of Tics

The alpha2-adrenergic drugs clonidine and guanfacine are first-line agents in treating mild to moderate tics. Clonidine decreases plasma norepinephrine levels and can also reduce the symptoms of attention deficit–hyperactivity disorder (ADHD). The daily dosage range for clonidine is 0.1-0.3 mg in divided doses.

Guanfacine, with a similar mechanism of action as clonidine, has a longer half-life and may treat ADHD symptoms not responsive to clonidine. For guanfacine, the daily dosage range is 0.5-3.0 mg in divided doses. Clonazepam and baclofen can be considered first-line alternatives as well.

The D2 dopamine receptor—blocking medications (neuroleptics) are the most effective medications for treating tics, and many experts use the neuroleptics as the initial agent of choice for that reason. However, the side effect profile, which includes extrapyramidal symptoms/tardive dyskinesia, is often a limitation to using these agents as first-line therapy.

Haloperidol and pimozide, the 2 most studied neuroleptics, have been approved for the treatment of tics in TS by the US Food and Drug Administration (FDA). Well-controlled clinical trials indicate that haloperidol has a response rate approaching 80% for tic suppression.

More recently, the atypical neuroleptics that interact with both serotonin and dopamine receptors and have less extrapyramidal effects have been shown to be effective in suppressing tics. Out of this group, risperidone has been the most studied, showing efficacy equal to that of clonidine. Olanzapine, ziprasidone, and quetiapine have shown promise in small studies.

Aripiprazole is approved by the FDA for pediatric Tourette syndrome. Aripiprazole elicits partial agonistic effect at dopamine D2 and serotonin type 1 (5-HT1A) receptors (thought to help control vocal tics). It also shows antagonist effect at serotonin type 2 (5-HT2A) receptor, which may be helpful in managing some of the comorbidities of Tourette syndrome (e.g., obsessional traits, depression). Its approval was based on an 8-week and 10-week study. In each study, patients taking aripiprazole demonstrated improvement compared to patients taking placebo. The improvement was measured by the Total Tic Score, the Tourette's Syndrome Clinical Global Impression-Improvement Scale, and the Yale Global Tic Severity Scale.[13, 14]

Tetrabenazine, a drug that blocks dopamine and depletes catecholamines at presynaptic terminals may be a potent drug in suppressing tics. Low doses of the dopamine agonist ropinirole have been shown to improve tics in small studies. The dopamine agonist pergolide, although effective, was withdrawn from the US market on March 29, 2007. Botulinum toxin-A has been effective in treating motor and vocal tics in select patients.

Treatment of ADHD

The most effective medications for the treatment of ADHD are the central nervous system stimulants. Methylphenidate and dextroamphetamine are first-line agents for the treatment of ADHD. Unfortunately, these medications may increase the frequency and intensity of tics. However, with prolonged use, the initial worsening of tics may stabilize. The dopamine-blocking agents can be used concurrently with the CNS stimulants for tic suppression.

Alpha2-adrenergic blockers may be helpful in controlling tics and treating symptoms of ADHD. Both clonidine and guanfacine can control the symptoms of ADHD and impulse control.

Other medications that can be effective in treating ADHD symptoms without worsening tics include bupropion and the tricyclic antidepressants.

Treatment of OCD in Tourette Syndrome

The selective serotonin reuptake inhibitors (SSRIs) are the most effective treatment of OCD symptoms in TS. This class of drugs includes fluoxetine, fluvoxamine, paroxetine, sertraline, escitalopram, and citalopram. Clomipramine is also effective due to its serotonin reuptake action. Augmentation of SSRIs with atypical antipsychotics may be beneficial in patients with TS and OCD that are poorly responsive to treatment with SSRIs.[15]

Various psychotherapeutic techniques, including assertiveness training, cognitive therapy, and self-monitoring, have been tried in the treatment of patients with TS.

Deep Brain Stimulation

Surgical approaches for TS have been attempted in patients who are severely disabled and have inadequate responses to other therapies. Deep brain stimulation (DBS) has been suggested as a potential therapy for severe and disabling tics.[16] At this time, only isolated cases report the effectiveness of DBS. Patient selection and criteria formation for controlled trials is currently underway.

Psychotherapeutic Counseling and Support

In addition to patient education, other measures should be taken to nurture self-esteem and self-correction. Individual counseling, cognitive and behavioral therapies, and group therapy should be considered.

Areas of strength should be emphasized, such as talents and skills, interests, any family or peer supports, and psychological resilience. Social skills training can help develop and reinforce more effective methods of confident and prosocial communication. Parents or other guardians may benefit from parent behavior management and discipline training, recognizing that the underlying purpose of discipline is to instill a sense of self-control and responsibility for one's behavior.

Allowances must be made for the child's uncontrollable behaviors that result from the disorder, but some behaviors, such as spitting at others or obscene gestures, have negative social connotations and require special guidance. Methods to help the child manage these behaviors include nonjudgmental acceptance of the child regardless of the nature of the behaviors and working with the child to adapt or substitute alternative, more appropriate behaviors that satisfy premonitory urges, such as spitting into a handkerchief instead of spitting openly.

Parenting skills books, workshops, and trained specialists are widely available and emphasize practical methods in positive reinforcement of desirable behaviors through giving praise or rewards, modeling appropriate behaviors, and administering "time-outs" from rewards or attention for inappropriate or uncontrolled behaviors. Parents also may benefit from group support and education or other topical groups and from individual supportive counseling to cope with accompanying stress.

A local TS support group may be of great benefit to patients and family members. Individual, group, or family counseling may help in facilitating a healthy adaptation to the illness.

Several relaxation or stress management treatment approaches reportedly improve the tics in TS. For example, tics are known to worsen from stress and to improve during periods of relaxation. Whether such therapies have a direct effect on the tics or exert an indirect influence by allowing patients to deal more productively with life stresses is unclear.

Consultations

Treatment of patients with TS should be a collaborative effort. The neurologist, psychiatrist, psychologist, family members, and school professionals all have important roles.

 

Medication

Medication Summary

Alpha2-adrenergic agonists and D2 dopamine receptor blocking medications are used primarily for tic suppression. The alpha2-adrenergic agonists may be effective at treating underlying ADHD symptoms, although CNS stimulants and atypical neuroleptics can be used concurrently. Selective serotonin reuptake inhibitors (SSRIs) are predominantly used to treat obsessive-compulsive disorder (OCD) symptoms in Tourette syndrome (TS). Aripiprazole, an atypical antipsychotic, has been approved by the FDA for pediatric TS.

Neuroleptic drugs

Class Summary

Dopamine-receptor antagonists are the most predictably effective tic-suppressing agents.

Haloperidol (Haldol)

Haloperidol and droperidol are of the butyrophenone class and are noted for high potency and low potential for causing orthostasis. A high potential for extrapyramidal symptoms/dystonia exists.

Pimozide (Orap)

Pimozide is a dopamine-receptor antagonist that alters effects of dopamine in the CNS. It possesses anticholinergic and alpha-adrenergic blocking activity. Because of its long half-life (55 h), a single daily dose may be feasible.

Fluphenazine (Prolixin)

Fluphenazine blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors in the brain. This agent exhibits strong alpha-adrenergic and anticholinergic effects and may depress the reticular activating system.

Trifluoperazine (Stelazine)

Fluphenazine blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors in the brain. This agent exhibits strong alpha-adrenergic and anticholinergic effects and may depress the reticular activating system.

Atypical neuroleptic drugs

Class Summary

These agents are selective dopamine receptor D2 and serotonin (5-HT2) antagonists.

Aripiprazole (Abilify)

Aripiprazole is indicated for Tourette syndrome in children aged 6-18 years. It elicits partial agonistic effect at dopamine D2 and serotonin type 1 (5-HT1A) receptors (thought to help control vocal tics).

Risperidone (Risperdal)

Risperidone is a selective monoaminergic antagonist with high affinity for serotonergic 5-HT2 and dopaminergic D2 receptors. It is postulated to antagonize dopamine receptors in the limbic system only. It exhibits selective serotonin blockade in the mesocortical tract. Dopamine levels and transmission increase.

Olanzapine (Zyprexa)

Olanzapine is considered a second-line agent for tic suppression. Of the atypical neuroleptics, risperidone has been more thoroughly studied than olanzapine.

Ziprasidone (Geodon)

This agent is an atypical antipsychotic approved by the FDA in 2001. It may cause less weight gain than olanzapine.

Alpha2-adrenergic agonists

Class Summary

Alpha2-adrenergic agonists are first-line agents for pharmacotherapy of tics

Clonidine (Catapres, Duraclon, Nexiclon, Kapvay)

Clonidine stimulates alpha2-adrenoreceptors in the brain stem, activating an inhibitory neuron, which in turn results in reduced sympathetic outflow. These effects result in a decrease in vasomotor tone and heart rate. Clonidine is a first-line agent for tic suppression and treatment of ADHD in TS.

Guanfacine (Tenex, Intuniv)

Guanfacine is considered a first-line agent for treatment of tics. It has a longer half-life than clonidine and can be less sedating.

Benzodiazepines

Class Summary

These agents inhibit calcium ions from entering slow channels, select voltage-sensitive areas, or smooth muscle.

Clonazepam (Klonopin)

Clonazepam suppresses muscle contractions by facilitating inhibitory gamma aminobutyric acid (GABA) neurotransmission and other inhibitory transmitters.

Dopamine agonists

Class Summary

Dopamine agonists are hypothesized to reduce dopamine receptor supersensitivity, which is one proposed theory of the underlying pathophysiology of TS. Evidence for the effectiveness of dopamine agonists in TS is encouraging but limited; further research needs to be done for this class of medications in TS.

Pergolide, a dopamine agonist, was withdrawn from the US market March 29, 2007, because of heart valve damage resulting in cardiac valve regurgitation. Pergolide should not be stopped abruptly. Health care professionals should assess patients’ need for dopamine agonist (DA) therapy and consider alternative treatment. If continued treatment with a DA is needed, another DA should be substituted for pergolide. For more information, see FDA MedWatch Product Safety Alert and Medscape Alerts: Pergolide Withdrawn From US Market.

Ropininirole (Requip)

Ropinirole is considered a third-line agent for treatment of TS. Lower doses than those used in Parkinson disease have been shown to be effective.

This agent is a nonergot dopamine agonist that has high relative in vitro specificity and full intrinsic activity at D2 subfamily of dopamine receptors, binding with higher affinity to D3 than to D2 or D4 receptor subtypes. It has moderate affinity for opioid receptors. Metabolites have negligible affinity for dopamine D1, 5HT-1, 5HT-2, benzodiazepine, GABA, muscarinic, alpha1-, alpha2- and beta-adrenoreceptors.

Discontinue ropinirole gradually over a 7-day period. Decrease frequency of administration from tid to bid for 4 days. For the remaining 3 days, decrease frequency to once daily prior to complete withdrawal of ropinirole.

Pergolide (Permax)

Pergolide has been withdrawn from the US market. A mixed ergot derivative dopamine agonist, it was proven effective for tic suppression

Neuromuscular blocker agents

Class Summary

These agents inhibit muscle contractions.

Botulinum toxin (BOTOX®)

A neurotoxin produced from fermentation of Clostridium botulinum type A, this agent exerts neuromuscular blockade by binding to receptor sites on presynaptic motor nerve terminals and inhibiting calcium-dependent release of acetylcholine from vesicles situated within nerve endings. Partial chemical denervation of muscle results, which diminishes muscle activity in area of injection.