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  • Updated 03.01.2024
  • Released 04.19.1993
  • Expires For CME 03.01.2027

Tourette syndrome

Author
Joseph Jankovic MD
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Introduction

Overview

Tourette syndrome is a chronic neurodevelopmental disorder consisting of motor and phonic tics. The onset is in childhood, and as many as 2% of children are affected, but epidemiological studies have shown that 20% to 30% of children exhibit tics at some time during childhood. Its peak severity usually occurs just prior to adolescence. Although the majority of patients have at least a partial remission in their tics after the age of 18, for most patients, Tourette syndrome is a lifelong condition, often associated with numerous behavioral comorbidities, including obsessive-compulsive disorder and attention deficit hyperactivity disorder. In this article, the author provides a succinct but thorough review of the current knowledge regarding the phenomenology, pathogenesis, and treatment of Tourette syndrome.

Key points

• Tourette syndrome is a neurobehavioral disorder chiefly manifested by motor and phonic tics.

• Most patients with Tourette syndrome have a variety of behavioral comorbidities, including obsessive-compulsive behavior, attention deficit disorder with or without hyperactivity, and impulse control disorder.

• Although no consistently present gene mutation has been identified, Tourette syndrome is considered a genetic disorder, often inherited bi-lineally (from both parents).

• Treatment of Tourette syndrome must be individualized and tailored to the needs of each patient.

Historical note and terminology

Georges Gilles de la Tourette was a French neurologist, a trainee of Charcot at the Salpetriere Hospital in Paris (126). In 1885, he described nine patients with motor and phonic tics, some of whom had echo phenomena, repeating other people’s words and phrases (echolalia) and repeating other people’s gestures (echopraxia). In addition, five of the nine individuals were uttering or shouting obscenities and profanities (coprolalia). He considered the condition to be closely related to a group of startle disorders that included "the jumping Frenchmen of Maine,” described by Beard in 1880. For many years, the etiology of Tourette syndrome was ascribed to psychogenic causes. Observations were made in the 1960s that neuroleptic drugs that act by blocking dopamine receptors were effective in treating Tourette syndrome, and this refocused attention from a psychological etiology to an organic central nervous system etiology. Although Gilles de la Tourette himself believed this condition was hereditary, it was not until the late 1970s that a familial, genetic etiology for Tourette syndrome was fully recognized (105; 204; 114). Once considered a rare psychiatric curiosity, Tourette syndrome is now recognized as a relatively common neurobehavioral disorder. There has been speculation that many notable historical figures, including Dr. Samuel Johnson and possibly Wolfgang Amadeus Mozart (11), were afflicted with Tourette syndrome.

Clinical manifestations

Presentation and course

Tics are brief, sudden, irregularly occurring, repetitive movements or sounds.

  • Tourette syndrome with blocking and phonic tics
    Tourette syndrome with blocking and phonic tics
    This young man with Tourette syndrome demonstrates a blocking tic during which he holds his breath. Then he has expiratory phonic tics. (Contributed by Dr. Joseph Jankovic.)
  • Tourette syndrome with abdominal tic in pregnancy
    Tourette syndrome with abdominal tic in pregnancy
    This 15-year-old girl was filmed in her sixth month of pregnancy. She displays abdominal tics characterized by tonic, isometric contractions of the rectus abdominis accompanied by simple and complex expiratory vocalizations. Soon ...

Tics generally have a more coordinated appearance than other dyskinesias and, although performed at inappropriate times, often resemble purposeful movements.

The two major categories of tics are motor and phonic (also known as vocal tics), but this division is artificial as phonic are essential motor ticks involving the nose, mouth, throat, and larynx. Each category is further subdivided into simple and complex types according to the perceived intricacy of the movement or sound. Motor tics characteristically first appear in the face, manifested by frequent blinking and facial grimacing, but multiple body regions can be involved. Rhythmical clonic tics may rarely resemble tremor or rhythmical myoclonus, such as palatal myoclonus (03). Although typical tics are clonic (jerk-like), many patients with Tourette syndrome also exhibit dystonic tics, produced by more prolonged muscle contractions resulting in briefly sustained abnormal posture or a squeezing movement such as blepharospasm. Some patients with Tourette syndrome have also been reported to manifest dystonia, including dopa-responsive dystonia (258). The third type of motor tic, referred to as tonic tic, is associated with an isometric muscle contraction without observable movement (94).

Tourette syndrome with clonic and dystonic tics and vocalizations
Tourette syndrome with clonic and dystonic tics and vocalizations
This 18-year-old woman has longstanding motor and phonic tics. Examination shows motor tics in the arms, especially repetitive, rotatory movements of the scapula, a very typical dystonic tic. She also displays stereotypic movement...

Simple phonic tics are usually inarticulate noises, such as sniffing, grunting, barking, and throat clearing, whereas complex phonic tics generally involve words and phrases. Gilles de la Tourette stressed the importance of coprolalia, but this affects only a minority of patients. In a study of 597 individuals with Tourette syndrome from seven countries, coprolalia occurred at some point in the course of the disease in 19.3% of males and 14.6% of females, and copropraxia in 5.9% of males and 4.9% of females (70). Over time, individual tics tend to come and go. Talking about individual types of tics may “suggest” their performance to patients, even tics the patients have not expressed for a long time. Suggestibility, suppressibility, and exacerbation during stress are among the reasons why the disorder has been wrongly thought to be primarily psychological in origin. Although emotional stress may exacerbate tics, the onset of Tourette syndrome is not necessarily related to stressful life events (88).

Common tics include the following:

(1) Simple motor tics: blinking, eye-rolling, grimacing, mouth opening, head tossing, shoulder shrugging, fist clenching, and toe curling.

  • Tourette syndrome with obsessive-compulsive disorder and "whiplash" tics
    Tourette syndrome with obsessive-compulsive disorder and "whiplash" tics
    This 10-year-old boy has a 7-year history of multifocal motor and phonic tics. He exhibits stereotypic tics of his fingers and arms, associated with phonic tics. (Contributed by Dr. Joseph Jankovic.)
  • Tourette syndrome with whiplash tics preceded by premonitory sensation
    Tourette syndrome with whiplash tics preceded by premonitory sensation
    This young man with Tourette syndrome displays whiplash tics, which are preceded by a well-defined premonitory sensation (Kwak et al 2003a; Prado et al 2008). (Contributed by Dr. Joseph Jankovic.)
  • Tourette syndrome with eye-blinking tic
    Tourette syndrome with eye-blinking tic
    This young woman with Tourette syndrome displays a blinking tic that interferes with her vision. She also exhibits "shuddering" tics. (Contributed by Dr. Joseph Jankovic.)

(2) Complex motor tics: jumping, touching, smelling, rubbing, shaking, echopraxia, and copropraxia.

  • Tourette syndrome with complex tics (repetitive somersaults)
    Tourette syndrome with complex tics (repetitive somersaults)
    This 15-year-old boy was diagnosed at age 5 years with attention deficit disorder and, subsequently, obsessive-compulsive disorder. He developed complex motor tics characterized by falling to the ground and rolling at age 9 years,...
  • Tourette syndrome with coprolalia, copropraxia, and obsessive-compulsive and self-injurious behavior
    Tourette syndrome with coprolalia, copropraxia, and obsessive-compulsive and self-injurious behavior
    This young man with typical Tourette syndrome has motor and phonic tics, including coprolalia and copropraxia, associated with obsessive-compulsive and self-injurious behavior. (Contributed by Dr. Joseph Jankovic.)
  • Tourette syndrome with coprolalia, improved by botulinum toxin
    Tourette syndrome with coprolalia, improved by botulinum toxin
    This young man has Tourette syndrome with severe coprolalia, which improved after botulinum toxin injections into the vocal cords. (Contributed by Dr. Joseph Jankovic.)
  • Tourette syndrome with complex motor tics and simple phonic tics
    Tourette syndrome with complex motor tics and simple phonic tics
    This young man presented at the age of 12 years with a 5-year history of multiple motor and phonic tics. He exhibits severe complex motor tics that consist mostly of compulsively banging his back into the wall. He also displays si...

(3) Simple phonic tics: throat clearing, grunting, sniffing, snorting, growling, barking, clicking, and moaning.

Tourette syndrome with obsessive-compulsive disorder and disabling vocalizations
Tourette syndrome with obsessive-compulsive disorder and disabling vocalizations
This 39-year-old college professor has a 2-year history of disabling, complex phonic and motor tics. He denies having tics when he was younger. The very loud involuntary vocalizations interfere with social and occupational activit...

(4) Complex phonic tics: singing, whistling, humming, coprolalia, echolalia, and palilalia.

Tourette syndrome with screaming tic
Tourette syndrome with screaming tic
This young man with Tourette syndrome has a loud screaming tic. His mother, although never diagnosed with tics or Tourette syndrome, has blinking tics. He describes symptoms of coprolalia and echolalia. (Contributed by Dr. Joseph ...

According to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) (08), the following are criteria for the diagnosis of Tourette syndrome:

A. Both multiple motor and one or more vocal tics are present at some time during the illness, although not necessarily concurrently.

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

C. Onset is before age 18 years of age.

D. The disturbance is not attributable to the physiological effects of a substance (eg, cocaine) or a general medical condition (eg, Huntington disease, postviral encephalitis).

According to DSM-5, if a child has tics of less than 1-year duration, the most appropriate diagnosis is provisional tic disorder (PTD), which replaced the term transient tic disorder (21). The point prevalence of provisional tic disorder varies with age, but it has been estimated that about 20% of children aged 5 to 10 years have a provisional tic disorder, although the lifetime prevalence is much higher. Most children whose tics started within the previous year will continue to have tics, and only about 32% remain completely tic-free over the next 5 to 10 years.

A core element of the diagnosis of tics is the presence of premonitory urge. Many patients can state that their tics are a response to an involuntary urge (often described in sensory terms such as tingling, aching, or itching) to perform a certain movement or make a certain sound (15; 134; 256), rather than a completely involuntary movement arising without their conscious knowledge. In one study, Bereitschafts potential were identified before tics in 6/14 (43%) of patients with Tourette syndrome (245). Although the investigators could not correlate the presence of Bereitschaftspotential with the premonitory sensation, the physiology of the premovement phenomenon requires further studies. Some investigators have suggested that premonitory urges result from a “sensorimotor gating” dysfunction and are an example of the sensory aspect of movement disorders (200; 182). Using magnetoencephalography in 12 patients with Tourette syndrome, the investigators showed a biphasic modulation of cortical beta activity during the second before tic onset with transient decrease in beta power, resembling the typical pattern noted during the preparatory phase of voluntary movements (171). However, only the initial phase of the biphasic modulation, manifested by an increase in beta power, positively correlated with the intensity of motor urges preceding tics. This is consistent with the findings of another study that utilized centromedian and cortical recordings and an increase in low-frequency power (3 to 10 Hz) in the thalamus that was time-locked to the tic but not present during voluntary movement and a decrease in beta power in the primary cortex that was present during tics and voluntary movements (35). Thus, the premonitory phenomenon may represent a failure of compensatory motor inhibitory mechanisms.

Many individuals with Tourette syndrome, however, are unaware of their tics (179). Most people who are cognizant of their tics can suppress them for periods of a few minutes to more than half an hour (15). Patients may describe a gradually increasing inner tension as tic suppression is maintained, and a rebound effect of a flurry of tics occurs when the tics are finally expressed. However, formal objective studies of tic frequency during and after voluntary suppression have failed to detect a rebound increase (84; 161). Patients may report having to repeat a tic until they perform it “just right” (139). As is true of other dyskinesias, stress typically worsens tics, but tics are often more prominent when they are released after a period of suppressibility in social situations. For these and other unknown reasons, tic severity and frequency may wax and wane and vary from one moment or sound to another, hour to hour, day to day, week to week, and month to month. In a 3-month-interval study, patients with a later onset and shorter duration of their tic disorders, better school performance, and more complete remissions (73).

The majority of all patients with Tourette syndrome also have obsessive-compulsive behaviors, some of which qualify for a DSM-5 diagnosis of obsessive-compulsive disorder (47).

  • Tourette syndrome with stereotypic, compulsive tic
    Tourette syndrome with stereotypic, compulsive tic
    This girl with Tourette syndrome demonstrates stereotypic, compulsive tics. She feels compelled to repeat the tics 6 times when she feels the urge. (Contributed by Dr. Joseph Jankovic.)
  • Tourette syndrome with self-injurious behavior preceded by severe premonitory urge (compulsion)
    Tourette syndrome with self-injurious behavior preceded by severe premonitory urge (compulsion)
    This young woman with Tourette syndrome has self-injurious behavior preceded by a severe premonitory urge (compulsion). A "stress ball" helps by serving as a substitute target for what would otherwise be self-injurious activity. (...

As a result, many patients with Tourette syndrome admit to repetitive checking, excessive orderliness, or ritualistic behavior (108). In fact, there is a clear parallel between tics and compulsions in the performance of intentional repetitive behaviors in response to psychic impulses. Many patients with Tourette syndrome, most of them male, have attention deficit hyperactivity disorder characterized by a shortened attention span, distractibility, impulsivity, and motoric hyperactivity (201; 204). Some of these problems are indirectly attributable to interference from tics, but for some children, attention deficit hyperactivity disorder precedes the development of tics. Depression is common in Tourette syndrome and correlates with the severity of tics, obsessive-compulsive symptoms, and attention deficit hyperactivity disorder (85; 204). In a cross-sectional structured diagnostic interview conducted in 1374 patients with Tourette syndrome and in 1142 unaffected Tourette syndrome family members, the lifetime prevalence of any psychiatric comorbidity among individuals with Tourette syndrome was 85.7%; 57.7% of the population had two or more psychiatric disorders, and 72.1% of the individuals met the criteria for obsessive-compulsive disorder or attention deficit disorder/hyperactivity disorder (85). Other associated problems include learning disabilities such as dyslexia (31), mania, anxiety disorders, phobias, and self-injurious behavior (158), antisocial behavior, oppositional defiant behavior, sleep disorders, and personality disorders (128). In school, half of the patients experience moderate to severe academic and peer problems (176). Approximately one third of children with Tourette syndrome have school difficulties severe enough to warrant extra measures such as tutoring or special education, and Tourette syndrome may account for one quarter of students in special education classes (131). In one large study in Sweden, individuals with Tourette syndrome were less likely to finish upper secondary education, start a university degree, or finish a university degree and experienced substantial academic underachievement (187).

Although Tourette syndrome is a childhood-onset disorder, many patients face challenges into adulthood, and their symptoms impair social interactions as well as employment opportunities and performance. Forty-three adults with Tourette syndrome who were referred to the Movement Disorders Clinic at Baylor College of Medicine over the past 5 years were compared to 100 patients with Tourette syndrome aged 18 years old or younger (102). The adult patients with Tourette syndrome had significantly more facial and truncal tics, as well as a greater prevalence of substance abuse and mood disorders; however, they had fewer phonic tics and lower rates of attention deficit/hyperactivity disorder and oppositional behavior than children with Tourette syndrome. Furthermore, adult Tourette syndrome largely represented a re-emergence or exacerbation of childhood-onset Tourette syndrome. During the course of Tourette syndrome, phonic and complex motor tics, self-injurious behaviors, and attention deficit/hyperactivity disorder tend to improve, but facial, neck, and trunk tics dominate the adult Tourette syndrome phenotype.

A phenomenon of paroxysmal outbursts of extreme anger, known as “episodic rages” or “explosive outbursts,” may affect as many as 30% of patients with Tourette syndrome. These are more likely to occur in patients with comorbid attention deficit hyperactive disorder or obsessive-compulsive disorder (30). Other comorbidities include migraine headaches (135), restless legs syndrome (144), and other sleep disorders (205). In a study of 109 patients with Tourette syndrome, Ghosh and colleagues found either migraine headaches or tension-type headaches in 55% of the patients; the rate of migraine headache within the Tourette syndrome group was found to be four times greater than that of the general pediatric population (74). Unfortunately, the interpretation of these data is difficult because the investigators did not administer the same questionnaire to a control, age-matched population without Tourette syndrome. This limitation, coupled with the selected population of patients from a tertiary referral center, may make the findings not generalizable. Several studies have identified a variety of sleep abnormalities in patients with Tourette syndrome, including insomnia, excessive daytime sleepiness, disorders of arousal (sleepwalking, sleeptalking, sleep terrors, and enuresis), a persistence of tics during sleep, and presence of periodic limb movements during sleep, especially in those with comorbid attention deficit hyperactivity disorder (110; 23; 163).

In some cases, the tics and behavioral comorbidities may be so severe and disabling that they may be life-threatening, hence the term “malignant” Tourette syndrome for this small subgroup of patients. Of 332 patients with Tourette syndrome evaluated at Baylor College of Medicine Movement Disorders Clinic during a 3-year period, 17 (5.1%) met the criteria for malignant Tourette syndrome, defined as two or more emergency room visits or one or more hospitalizations for Tourette syndrome symptoms or its associated behavioral comorbidities (41). The patients exhibited tic-related injuries, self-injurious behavior, uncontrollable violence and temper, and suicidal ideation/attempts. Compared to patients with nonmalignant Tourette syndrome, those with malignant Tourette syndrome were significantly more likely to have a personal history of obsessive-compulsive behavior/disorder, complex phonic tics, coprolalia, copropraxia, self-injurious behavior, mood disorder, suicidal ideation, and poor response to medications. Self-injurious behavior is one of the most serious manifestations of Tourette syndrome but may be encountered in many other neurobehavioral disorders (67).

The most widely used instrument to assess tics is the Yale Global Tic Severity Scale, which consists of two broad domains: total tic severity (with two sub-domains: motor and phonic tics) and impairment. Within each category, there are five dimensions, scored 0 to 5: number of tics, frequency, intensity, complexity, and interference. The total tic score ranges from 0 to 50, and the usual ranges in most studies are from 15 to 30. A health-related quality of life scale has been developed and validated for internal consistency and test-retest reliability and against other clinical scales (37). Utilization of the health-related quality of life scale showed that attention deficit hyperactivity disorder and obsessive-compulsive disorder, rather than tic severity, are more predictive of the long-term outcome.

Prognosis and complications

After onset in early childhood, the severity of Tourette syndrome tends to peak just before adolescence (222). In a study designed to address the long-term prognosis of Tourette syndrome, 46 children with Tourette syndrome underwent a structured interview at a mean age of 11.4 years and again at 19.0 years (24). The mean worst-ever tic severity occurred at a mean age of 10.6 years. This first prospective longitudinal study also showed that only 22% continued to experience tic symptoms at follow-up, whereas nearly one third were in complete remission of tic symptoms at follow-up. Although some patients do not demonstrate any improvement of their tics in adulthood, the general long-term prognosis for Tourette syndrome is favorable. A 15-year follow-up study of initially school-aged patients found that tic severity declined on average by 59% and that 44% of patients were free or virtually free of symptoms (179). In another longitudinal study involving 314 patients with Tourette syndrome with an age range from 5 to 19 years followed for up to 6 years (n = 227), there was a 0.8 point decline on the Yale Global Tic Severity Scale; 17.7% of patients had no tics after age 16, but 59.5% had minimal or mild tics, and 22.8% had moderate or severe tics (81). At follow-up, only 37.0% had pure Tourette syndrome; the remainder had a variety of comorbidities. Only 13% to 22% of adult patients with Tourette syndrome still take medication for tics (32; 179). However, many adults with childhood-onset Tourette syndrome who believe they have become free of tics still have them (179), and 22% to 24% of adult patients with Tourette syndrome have moderate or severe tics (80; 24). When 40 children and 31 adults with Tourette syndrome were compared, no difference in tic phenomenology or severity was found, but children were more frequently managed without medications, and sedation was more common in adults, but weight gain was more common in children (49).

The natural history of the associated behavioral disorders is less well-defined than that of the tic disorder. It has been reported that, for many children with Tourette syndrome, symptoms of attention deficit hyperactivity disorder antedate the appearance of tics by an average of 2.5 years (46). Park and colleagues found it unusual for attention deficit hyperactivity disorder or obsessive-compulsive disorder to be absent at the time of initial diagnosis of Tourette syndrome and then to appear later on; only 4% to 6% of patients followed this course (180). On the other hand, disruptive behaviors (20%) and school problems (13%) appeared more frequently over time. As children with Tourette syndrome mature and start driving, because of their tics, such as blinking and blepharospasm or dystonic neck and trunk tics and a variety of other complex tics, coupled with comorbid attention deficit, they should be screened for such troublesome tics that could possibly put them or others in danger while driving (Makhoul and Jankovic 2021; 247; 150). Furthermore, impulsive behavior, coprophenomenon, and alcohol and substance abuse may eventually lead to involvement with the law enforcement and legal system and criminal convictions (106; 247). Individuals with Tourette syndrome are significantly more likely (2x) not only to experience assault but also to be perpetrators of violent (including sexual) assaults (3x) (157).

Biological basis

Etiology and pathogenesis

There is no single etiologic factor responsible for all cases of Tourette syndrome. This disorder may arise from a variety of genetic and environmental mechanisms (22; 82; 204). It appears that most cases of Tourette syndrome have some hereditary basis, and the offspring of affected parents are at increased risk of developing Tourette syndrome, obsessive-compulsive disorder, and attention deficit hyperactivity disorder (160). However, the genetic basis of Tourette syndrome is complex (183) and may be different in different families. For males, penetrance is nearly complete when strictly tic disorders (Tourette syndrome or chronic multiple tic disorder) are included, whereas penetrance is only 56% in females. However, when obsessive-compulsive disorder is considered an alternative expression of the Tourette syndrome trait, penetrance estimates rise to 70% for females. The observation that bilineal transmission is common in Tourette syndrome families and that it appears to influence symptom severity (83; 145) suggests that genetic homozygosity or polygenic factors (such as the inheritance of susceptibility loci) may be important.

Finding a genetic marker, and ultimately a gene, has been the highest priority in Tourette syndrome research for more than 2 decades (53; 210). That goal was finally achieved in 2005 when Abelson and colleagues identified an individual with a chromosome inversion at 13q31.1-31.3 (01). Subsequent screening of a regional candidate gene in a cohort of 174 patients yielded one with a frameshift mutation due to a single-base deletion in SLITRK1. One of four family members had the same mutation and had exhibited trichotillomania but not tics. Two unrelated patients from the cohort were found to have a noncoding variant in an RNA binding site of SLITRK1 (01). Although clearly of importance for only a small minority of patients with Tourette syndrome (54; 63), the discovery of the etiologic role of SLITRK1 has established the pathogenic plausibility of single-gene disruption. Another genetic abnormality implicated in Tourette syndrome is the L-histidine decarboxylase gene (HDC) mutation W317X, located on 15q21.1-15q21.3, inherited in an autosomal dominant fashion in a 2-generation family (61).

There are many other genes that have been linked to Tourette syndrome, but none have been replicated in large populations of Tourette syndrome (235; 91; 255). Genome scans and studies of chromosomal abnormalities have identified numerous candidate susceptibility loci (10; 263; 48; 246; 50; 51; 56; 181; 140). However, no overall consistencies have emerged from these studies. Polymorphisms in the DRD4 and MOA-A genes have been associated with Tourette syndrome in family-based association studies (57). Based on GWAS meta-analysis, genetic enrichment analyses, and other genetic studies in 4,819 patients with Tourette syndrome and 9,488 control subjects, genetic variants spanning evolutionarily conserved regions significantly explained 92.4% of Tourette syndrome heritability (261).

Although the concept of a hereditary foundation for Tourette syndrome is widely accepted, genetics do not explain the entire clinical picture, and environmental (including intrauterine) factors appear to influence the clinical expression of the disorder (138). In some cases, Tourette syndrome may have an autoimmune basis, but at present, there is insufficient evidence to justify routine immune-based therapy (87). Walker and colleagues have reported that six of 42 patients with rheumatic, or Sydenham, chorea later developed PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection, discussed under Differential Diagnosis), and five Tourette syndrome (250). Some patients with Tourette syndrome have detectable antineuronal or antinuclear antibodies. When sera from these patients are infused in rats, they have been found to increase oral stereotypies in the animals (240). Comorbid attention deficit hyperactivity disorder may be due to a single nucleotide polymorphism in the tyrosine phosphatase (ACP1) gene (26). Potential immune mechanisms of Tourette syndrome have been reviewed in reports (90).

The anatomic localization and the biochemical nature of Tourette syndrome are unknown. It is generally accepted that dysfunction of cortico-striato-thalamo-cortical pathways is involved (227; 86). Several lines of evidence support the notion that dopaminergic striatal and prefrontal dysfunction contributes to tic disorders (221; 06). Foremost are the clinical observations that dopamine receptor antagonists suppress tics, whereas dopaminergic agents such as amphetamines may exacerbate them. The phenomenon of tardive tics following chronic dopamine receptor antagonist therapy suggests that dopamine receptor supersensitivity can cause a syndrome similar to Tourette syndrome. Fluorodopa accumulation on PET studies is elevated in the regions of substantia nigra and caudate nucleus (62). Striatal dopamine transporter binding, as assessed by SPECT ligands, is increased in patients with Tourette syndrome (40; 215). Amphetamine induces excessive release of dopamine in the putamen in patients compared to controls (228). A postmortem study of Tourette syndrome brains demonstrated an increased density of presynaptic dopamine nerve terminals, which was attributed to dopamine hyperinnervation of the striatum (224). Some have hypothesized that there is early termination of nigrostriatal neuron maturation in Tourette syndrome (213). A postmortem study of three patients found elevated concentrations of D2 receptor protein in prefrontal cortex (164), lending weight to the notion that dysfunction of a cortico-striato-thalamo-cortical circuit rather than a single structure underlies the pathogenesis of Tourette syndrome. An autopsy study of three Tourette brains found consistent increases in dopamine transporter and D2 receptor as well as D1 and alpha-2A density, suggesting that dopaminergic hyperfunction in the frontal lobe may play a role in the pathophysiology of Tourette syndrome (259). In support of the “tryptophan hypothesis” is a study that used alpha-[(11)C]methyl-L-tryptophan PET to assess global and focal brain abnormalities of tryptophan metabolism in 26 children with Tourette syndrome and nine controls. The findings indicate that tryptophan uptake is significantly decreased in the dorsolateral prefrontal cortex and increased in the thalamus of patients with Tourette syndrome (16).

Numerous other neurochemical systems have been investigated, and it is possible that multiple presynaptic and postsynaptic mechanisms play roles in producing this disorder (229). In addition to the dopaminergic system, the GABAergic and glutamatergic pathways have been also implicated in Tourette syndrome. Using PET scan and [11C]flumazenil as a GABAergic ligand, Lerner and colleagues found decreased binding of [11C]flumazenil in bilateral ventral striatum, bilateral thalamus right insula, and bilateral amygdala and increased binding in bilateral substantia nigra, eft periaqueductal grey, right posterior cingulate cortex, and bilateral cerebellum and dentate nuclei (143). This study suggests widespread abnormality in the GABAergic system in patients with Tourette syndrome. In another study, neurochemical profile was assessed in 37 well-characterized, drug-free adult patients with Tourette syndrome and 36 age/gender-matched healthy control subjects via 3 Tesla magnetic resonance spectroscopy (115). The study found significant reductions in striatal and thalamic concentrations of glutamate and glutamine. It has also been hypothesized that a disturbance of sex hormone influences in normal brain development may contribute to the appearance of Tourette syndrome (190). The observed benefit in patients with obsessive-compulsive symptoms from drugs that are inhibitors of serotonin reuptake implicates this neurotransmitter system in the development of this associated disorder. SPECT with 123I beta-CIT has shown a significant reduction in serotonin transporter binding in patients with Tourette syndrome (168). The serotonergic system may also underlie the beneficial effect of stimulants for attention deficit hyperactivity disorder (71).

Although there are no animal models that express all the typical features of Tourette syndrome, studies of stereotypies in animals may provide insight into the pathogenesis of habits, rituals, and tic-like and impulsive behaviors in humans. However, several animal models of tics have been developed (28; 257). The mechanism of self-injurious behavior associated with Tourette syndrome is not well understood, but an animal model may shed some light on this very important behavior that is occasionally associated with Tourette syndrome. A mouse with genetic deletion of Sapap3, a gene that codes for postsynaptic scaffolding protein at excitatory striatal synapses, is characterized by excessive compulsive grooming, resulting in self-injurious behavior, such as facial hair loss and skin lesions. The similarity of this phenotype to obsessive-compulsive disorder is further supported by the observation that the mice markedly improved after treatment with a selective serotonin reuptake inhibitor (252).

Several animal models of tics have been developed, including microinjections of bicuculline into the sensorimotor putamen and primary motor cortex of a monkey (28; 159), injections of axonal tracers into the primate striatum (257), and numerous other primate and rodent models (28).

Volumetric magnetic resonance imaging studies have revealed reduced volumes of the caudate nuclei (191) and of the left lenticular nucleus (189) and enlargement of the left thalamus (141) in patients with Tourette syndrome compared to controls. Despite reports of some abnormalities in imaging studies in patients, these findings could not be confirmed in a cohort of children with medication-free Tourette syndrome (109). Nevertheless, abnormal development in Tourette syndrome is supported by other imaging studies that have found an abnormal structural pattern of cortical sulci, which correlates with the severity of clinical symptoms (166). Using 3 Tesla structural neuroimaging, the investigators compared sulcal depth, opening, length, and thickness of sulcal gray matter in 52 adult patients with Tourette syndrome and 52 matched controls. Patients with Tourette syndrome had lower depth and reduced thickness of gray matter in the pre- and postcentral as well as superior, inferior, and internal frontal sulci.

Diffusion-tensor MRI used to investigate the structural integrity of basal ganglia and thalamus in 23 children with Tourette syndrome found increased mean water diffusivity bilaterally in the putamen and decreased anisotropy in the right thalamus, indicating impairment of white matter integrity in the fronto-striatal-thalamic circuit at a microstructural level (151). Additional imaging studies have identified frontal and parietal cortical thinning, most prominent in ventral portions of the sensory and motor homunculi in patients with Tourette syndrome (232). Using resting-state functional connectivity MRI in 33 adolescents with Tourette syndrome, Church and colleagues found anomalous connections primarily in the frontoparietal network, suggesting widespread immature functional connectivity, particularly in regions related to adaptive online control (44). When resting-state functional MRI was performed in 13 adults with Tourette syndrome and 13 matched controls, the right dorsal anterior insula demonstrated higher connectivity, especially with the frontostriatal nodes of the urge-tic network and bilateral supplementary motor area, even though the patients did not exhibit any overt tics (243). These findings suggest that the right dorsal anterior insula is part of the urge-tic network and could influence the urge- and tic-related cortico-striato-thalamic regions in Tourette syndrome. The dorsal anterior part of the insula has been found to integrate sensory and emotional information with cognitive valuation. The right dorsal anterior insula also participates in urge suppression in healthy subjects (93; 122).

PET and SPECT studies have shown deficiencies in the basal ganglia, most often the left ventral striatum (189). Using [18F]fluorodeoxyglucose, two patterns of abnormalities have been identified in patients with Tourette syndrome. Pattern 1 is reportedly associated with tics, and pattern 2 correlates with the overall severity of Tourette syndrome. In a follow-up study involving 12 adult patients with Tourette syndrome (untreated for more than 2 years) and 12 controls, the investigators found a Tourette syndrome-related metabolic pattern that was characterized by increased premotor cortex and cerebellum activity and reduced resting activity of the striatum and orbitofrontal cortex (195). With voxel-by-voxel analysis, the investigators found increased [11C]dihydrotetrabenazine binding in the ventral striatum (right greater than left) in patients with Tourette syndrome as compared to age-matched controls. However, in a subsequent PET study involving 33 adults with Tourette syndrome and utilizing not only [11C]dihydrotetrabenazine but also [11C]methylphenidate, a ligand for dopamine transporter binding, Albin and colleagues found no differences between subjects with Tourette syndrome and controls (05). Infantile sonographic lenticulostriate vasculopathy may represent an early radiologic marker (218).

Structures other than the basal ganglia have been implicated in the pathogenesis of tics. Electrophysiological studies indicate that hyperexcitable brainstem neurons are found in patients with Tourette syndrome, whereas magnetic stimulation discloses increased excitability of the motor cortex (17). PET studies of regional cerebral metabolic rates show positive functional coupling between motor and lateral orbitofrontal circuits, a reversal of the normal interrelationship, implicating impaired limbic-motor interactions (107). Impaired frontal cortical inhibition has been documented by recording event-related brain potentials (112). One case report documented the conversion of a simple motor tic disorder into full-blown Tourette syndrome with obsessive-compulsive disorder following temporal lobectomy for intractable epilepsy (39).

Epidemiology

Tourette syndrome is among the most common movement disorders. Various epidemiological studies have shown that 20% to 30% of children exhibit tics sometime during childhood and 2% to 3% of children develop some features of Tourette syndrome, although the worldwide prevalence of Tourette syndrome in children has been reported to range from 0.3% to 0.8% (38). Correctly ascertaining its prevalence is fraught with difficulty (239), though, and an accurate lifetime prevalence rate for Tourette syndrome has not been established. It is clear that systematic searches for Tourette syndrome turn up much higher prevalence rates than those obtained through conventional means. Examination of affected kindreds indicates many cases are mild and do not come to medical attention. Prevalence estimates for chronic tic disorders generally hover in the 0.4% to 2% range (89; 203; 111; 120). The prevalence is considerably higher in special education classes (130; 203). Various epidemiological studies have shown that 20% to 30% of children exhibit tics sometime during childhood and 2% to 3% of children develop some features of Tourette syndrome, although the worldwide prevalence of Tourette syndrome in children has been reported to range from 0.3% to 0.8% (38). There is no known geographic predilection. Males consistently outnumber females in large studies by a ratio of around 4:1 (69; 251; 136). In one survey of nearly 10,000 children in China, the ratio of affected males to females was greater than 10:1 (111). Rarely, a disorder identical to Tourette syndrome will arise de novo in adults (42), and this may carry a poorer prognosis (60). The new onset of tics in an adult should prompt consideration of a secondary cause. Meta-analysis of 13 studies of children yielded a prevalence of Tourette syndrome of 0.77% (95% confidence interval, 0.39-1.51%); the boys-to-girls ratio was 1.06%: 0.25%, and meta-analysis of two studies assessing adults with Tourette syndrome revealed a prevalence of 0.05% (95% confidence interval, 0.03-0.08%) (123). The prevalence of tic disorders was higher in all studies performed in the special education population. Similar findings were reported based on a prospective cohort study following 6768 children in Avon, United Kingdom, where 0.3% of 13-year-old children met the criteria for clinically definite Tourette syndrome and 0.7% with clinically probable Tourette syndrome (209). It is not known why tics disappear in a majority of children and further studies are needed to understand the mechanisms of conversion from pre-Tourette syndrome state to Tourette syndrome. Among the 21 population-based prevalence studies, the pooled Tourette syndrome population prevalence estimate was 0.52% (95% confidence interval: 0.32 to 0.85), 0.3% to 0.9% in children, but the true prevalence was thought to be much higher (208).

Prevention

Genetic counseling regarding family planning may influence a couple's decision to have a child at risk for Tourette syndrome. There is no biological marker to detect an affected fetus during pregnancy. There is no known way to modulate the onset of tics in children at risk.

Differential diagnosis

Tourette syndrome is a member of a group of primary tic disorders. Transient tic disorder, which occurs in up to 2% of children, differs from Tourette syndrome by its duration of less than 1 year, leaving no residual manifestations. Patients with a chronic simple tic disorder (motor or vocal) experience only one type of tic. Chronic multiple tic disorder (motor or vocal) differs from Tourette syndrome in that either motor or vocal tics, but not both, are present. Tourette syndrome, chronic multiple tic disorder, transient tic disorder, and possibly chronic simple tic disorder are generally viewed as clinical variants of the same genetic defect.

Tourette syndrome accounts for most chronic tics, but secondary causes of tics are increasingly recognized. These include infections, toxins, trauma (149), stroke (133), degenerative diseases (185), metabolic disorders (212), chromosomal disorders, and others (162). In these conditions, tics are usually ancillary features to obvious neurologic manifestations that are not part of the Tourette syndrome spectrum. Dopamine receptor blockers can cause a tardive syndrome resembling Tourette syndrome (202). Stimulant drugs have long been blamed for causing or aggravating tics (in a reversible fashion), but longitudinal studies indicate that the severity of tics does not increase with long-term methylphenidate therapy (178). Functional (psychogenic) tics were thought to be quite rare (238; 13), but since the onset of COVID, there have been many reports of functional tics and functional tourettism. Some of these cases were clearly triggered or influenced by social media, particularly TikTok (72; 92; 197; 33; 262).

Patients with acute onset, or sudden exacerbations, of obsessive-compulsive disorder or tic disorder have shown a significant association with group A beta-hemolytic streptococcal antibody titers (170). These patients may represent a syndrome known as PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection) (231). Although diagnostic criteria for this syndrome include prepubertal symptom onset (142), a similar disorder may affect adults (25). The concept of PANDAS is not universally embraced (226; 77; 211). Strong supportive evidence has come from finding antibasal ganglia antibodies in more than 20% of patients with Tourette syndrome (43), and in 64% of patients with PANDAS versus 9% of those with uncomplicated active Group A streptococcal infection (184). However, even this finding has been disputed (221; 223; 155). A placebo-controlled trial of immunomodulatory treatment (plasma exchange or intravenous immunoglobulin) demonstrated dramatic benefit in acute postinfectious obsessive-compulsive and tic disorders (188). Patients treated in this fashion have shown benefit for up to 5 years (142). In an attempt to address the controversy surrounding PANDAS, an entity termed “pediatric acute-onset neuropsychiatric syndrome” (PANS) has been proposed to acknowledge that there is a subgroup of children presenting with an abrupt onset of obsessive-compulsive disorder (OCD) and acute neuropsychiatric symptoms, accompanied by a variety of comparably severe and acute neuropsychiatric symptoms (237). In contrast to PANDAS, the diagnostic criteria for PANS no longer include tics.

Tics must be differentiated from other hyperkinetic movement disorders, including myoclonus, blepharospasm, stereotypies, and hyperekplexia (94). Because of the young onset, tics are often mistaken for rheumatic, or Sydenham, chorea. It may be difficult to differentiate complex motor tics and compulsions. In contrast to tics, compulsions are more closely associated with obsessions, performed in response to nonmotor obsessional thoughts, and may be performed according to certain rules (rituals), such as in a specified order or a specified number of times. Compulsive rituals, but not tics, may be performed with the thought of preventing discomfort or a dreaded event.

Diagnostic workup

There is no diagnostic laboratory test for Tourette syndrome, so it remains a clinical diagnosis. Routine neuroimaging and other diagnostic studies are generally not required and do not help identify most of the secondary causes of tics noted above. Detailed assessments, including psychiatric evaluations and testing with standardized neuropsychologic measures of attention and obsessive-compulsive behavior, may help define associated behavioral disturbances.

Management

One of the most important aspects of management is proper education and correction of misconceptions regarding Tourette syndrome and its behavioral complications. Parents should be informed that their child has a limited capacity to control the tics, which will be most prominent when the child feels his or her tics are unobserved or unlikely to provoke a negative social response, such as at home. Parents should tell the child's teachers of the diagnosis and prescribed medication, if any. Patients and families should know of the Tourette Syndrome Association as a valuable resource for informative literature.

Different forms of nonpharmacological therapeutic interventions, such as behavioral modification and transcranial magnetic stimulation, have been recommended since the disorder was first described, but few studies of such treatments have been subjected to rigorous scientific scrutiny (233; 175; 96; 97; 18; 99).

Comprehensive behavioral intervention for tics (CBIT) is primarily based on habit reversal therapy, which employs competing-response training; CBIT is different from deliberate tic suppression in that it teaches the patient to initiate a voluntary behavior to manage the premonitory urge. CBIT also includes relaxation training and functional intervention. In a multicenter study designed to test the efficacy of CBIT, 126 children ages 9 to 17 with moderate to severe Tourette syndrome were randomly assigned to receive either CBIT or supportive counseling and education about Tourette syndrome (193). About one third of the children in the study were on a stable dose of anti-tic medication. Behavioral intervention led to a significantly greater decrease on the Yale Global Tic Severity Scale (24.7 vs. 17.1) from baseline to endpoint, compared with very minimal change in the control treatment group (24.6 vs. 21.1), with the overall effect size of 0.68. Furthermore, 52.5% of children receiving CBIT were rated as significantly improved, compared to 18.5% of those in the control group. The decrease of 7.6 points (31% from baseline) on the Total Tic score of the Yale Global Tic Severity Scale in the CBIT group is less than the decrease reported in clinical trials of antipsychotic medications or topiramate (102). Although in one review “half the subjects in the CBIT trials did not show a positive response,” some have suggested “CBIT can be considered a first-line treatment for persons with tic disorders” (207).

The decision to intervene in a tic disorder is based on a relative evaluation of the severity of the tics versus the consequences of potential side effects on schooling or work. Most patients with mild tics who have made a good adaptation in their lives can avoid the use of medications (137; 251). Educating patients, family members, peers, and school personnel regarding the nature of Tourette syndrome, restructuring the school or work environment, and providing supportive counseling are measures that may be sufficient to avoid medications (220). Drug therapy is considered if the symptoms of Tourette syndrome are functionally disabling and not remediable by nonpharmacological interventions (78; 95; 219). Medications are chosen on the basis of specific target symptoms and potential side effects. For many patients with Tourette syndrome, the principal morbidity comes not from tics, but from the associated features of obsessive-compulsive symptoms, attention deficit hyperactivity disorder, and other behavioral disturbances. If practical, observing a patient for a period of time before using medication allows for a better appreciation of the baseline disorder and the difficulties encountered at home, at school, at work, and with peers.

Tics can rarely be eradicated entirely, so the goal of medication is to achieve maximum control with minimal side effects. All medications are initiated at the lowest possible dose and gradually increased until sufficient benefit is obtained or until intolerable side effects supervene. Those patients who receive medication should be re-evaluated approximately every 3 months and more frequently after dosage or medication changes. Clonazepam (0.5 to 5 mg/day) may be taken as a once-a-day medication at bedtime. It may relax patients just enough to give them control of mild to moderate tics and may also help coexistent emotional and behavioral disorders. Clonidine (0.05 to 0.5 mg/day) appears to have tic-suppressing effects and may be particularly useful for children with associated attention deficit hyperactivity disorder. Clonidine is available as a weekly patch, but this formulation often causes hypersensitivity reactions. Guanfacine has also been recommended as first-line therapy for tics (236), but it has caused syncope in Tourette children (121). Despite “strong recommendation” made by some investigators for the use of clonidine and guanfacine in children with Tourette syndrome (233), we find the drug less effective than the antidopaminergic drugs in the treatment of tics in children and adults.

The most effective agents against tics are neuroleptic (antidopaminergic) drugs. There are only three drugs approved by the United States Food and Drug Administration for the treatment of Tourette syndrome: haloperidol, pimozide, and aripiprazole. These medications, however, have a variety of potentially serious side effects, including tardive dyskinesia; therefore, these drugs are not considered the first line of treatment (96). The most commonly used typical neuroleptics include haloperidol (0.25 to 15 mg/day), pimozide (1 to 10 mg/day), and fluphenazine (1 to 15 mg/day) (254). Pimozide and fluphenazine tend to produce less sedation than haloperidol, but pimozide therapy has led to prolongation of the Q-T interval and other changes on the ECG. The full spectrum of drug-induced movement disorders, from acute dystonic reactions to tardive syndromes, may complicate the use of these agents. Furthermore, some patients become refractory to medications. In one survey, 45 of the 68 (69%) patients were judged refractory due to lack of efficacy at the highest tolerated dose (147). The medications to which selected patients were judged as refractory were aripiprazole, clonidine, risperidone, haloperidol, pimozide, tiapride, and sulpiride. In addition to tardive dyskinesia, the typical and atypical antipsychotics (neuroleptics) can be associated with weight gain and metabolic syndrome, although patients with Tourette syndrome may be at a higher-than-expected risk for metabolic and cardiovascular disorders irrespective of their exposure to these drugs (27; 66).

Presynaptic dopamine depletors, such as tetrabenazine, deutetrabenazine, and valbenazine, which act by inhibiting the central inhibitor of vesicular monoamine transporter type 2 (VMAT2), are emerging as the most effective and safest medications in the treatment of troublesome tics (97; 18; 99; 101). Tetrabenazine (12.5 to 100 mg three times daily) is effective in a majority of patients with Tourette syndrome and is considered the first-line treatment in patients with troublesome motor and phonic tics (119; 118; 96). Generally well tolerated, tetrabenazine may cause drowsiness, parkinsonism, depression, insomnia, akathisia, and other less frequent, dose-related side effects. The drug’s advantage over conventional neuroleptics is that it does not cause tardive dyskinesias. Tardive disorders appear to be relatively rare in the Tourette syndrome population, but tardive dystonia may be more common than currently believed (230; 124). Besides little or no risk for tardive dyskinesia, tetrabenazine appears to be associated with less weight gain than the typical neuroleptics (174). Besides the potential side effects noted above, there are other limitations of tetrabenazine, including its relatively short half-life, necessitating at least three times per day administration. This is one reason why other dopamine depleters with longer duration of action are being investigated; these include deutetrabenazine and valbenazine, which are administered two times or once per day, respectively (97). In a pilot study involving 23 children with Tourette syndrome, the mean (SD [standard deviation]) baseline YGTSS Total Tic Severity Score (TTS) of 31.6 (7.9) decreased by 11.6 (8.2) points at week 8, a 37.6% reduction in tic severity (p< 0.0001) (97). Other measures of Tourette syndrome also improved in this open-label 8-week study, suggesting that deutetrabenazine may be a safe and effective treatment of tics associated with Tourette syndrome. The improvement observed in the open-label studies, however, could not be replicated in two randomized double-blind, placebo-controlled trials: 30046 ARTISTS 1 (flexible-dose titration) (101) and 30060 ARTISTS 2 (fixed dose) (45). This, unfortunately, parallels the results of similar studies with valbenazine in pediatric and adult Tourette syndrome populations. There are many possible explanations for the unexpected results, including difficulties in assessing a highly variable disorder and subtherapeutic dosing. The latter explanation is supported by the observation of very low frequency of adverse effects and observed efficacy in a long-term open-label trial (101). Although the VMAT2 inhibitors are considered the treatment of choice in patients with tic disorders, they are often difficult to access because of cost and denials by third-party payers (172; 18).

The development of atypical neuroleptics such as olanzapine (244), quetiapine, aripiprazole (177), and ziprasidone may make it possible to avoid these side effects in the future. In a phase 3, randomized, double-blind, placebo-controlled trial of aripiprazole involving 133 patients with Tourette syndrome, significant improvement in YGTSS and other measures were noted (206). The most common adverse events were sedation and fatigue. Although no tardive dyskinesia was reported in this trial other studies have found that aripiprazole can cause this adverse effect (186). Unfortunately, experience gathered with most of these agents over the years indicates that only clozapine can be considered a truly “atypical” agent in terms of reducing the risk of tardive complications (64). Patients with Tourette syndrome need to be educated regarding possible neuroleptic side effects (125). Although D2 receptor blockers can cause tardive dyskinesia, it is possible that D1 receptor blocking agents will have a lower risk of this potentially disabling side effect. In this regard, a D1 receptor antagonist, ecopipam, has been reported to have potential benefits in patients with Tourette syndrome (79; 75).

A variety of other medications – including calcium channel blockers (verapamil, nifedipine), ondansetron, carbamazepine, baclofen, naltrexone, buspirone, nicotine (in smoke, gum, and transdermal patches), and cannabinoids – may suppress tics in certain patients with Tourette syndrome (203; 167). In general, however, the response to these medications is less predictable than with the aforementioned neuroleptic drugs. An open-label trial of levetiracetam recorded a benefit for tic severity in all 60 participants and in behavior and school performance for the majority (12). Topiramate has been found to be effective in some open-label studies as well as in a multicenter, placebo-controlled trial (103). A seemingly paradoxical treatment for tics is dopamine agonists, probably based on presynaptic inhibition at low doses (76; 09). Selected patients, particularly those with painful dystonic tics, may respond to local intramuscular injections of botulinum toxin (132; 153; 04; 98; 100). A variety of behavioral techniques, including massed (negative) practice, operant conditioning, anxiety management, habit-reversal training (36; 52), and hypnosis have been employed in the treatment of tics (192). Electroconvulsive therapy has been used successfully in a patient with Tourette, psychosis, and self-injurious behavior (116). The use of “alternative” medications among patients with Tourette syndrome is common and warrants systematic study in the future (152).

A number of antidepressant medications are effective for obsessive-compulsive symptoms, most notably serotonin-specific reuptake inhibitors (59). Fluoxetine (20 to 60 mg/day), sertraline (50 to 200 mg/day), paroxetine (20 to 60 mg/day), fluvoxamine (50 mg/day and up), and citalopram (20 to 40 mg/day) may all improve obsessive-compulsive symptoms without affecting tic severity. Serotonin-specific reuptake inhibitors may be less effective for obsessive-compulsive symptoms in the presence of tics (146), and doses higher than standard antidepressant doses are often required. Clomipramine (initiated at 25 mg/day) is equally effective but less well tolerated due to anticholinergic, cardiotoxic, and seizure-potentiating effects. Other pharmacologic agents for obsessive-compulsive symptoms include tryptophan, monoamine oxidase inhibitors, mianserin (a selective serotonin antagonist), and benzodiazepines. Because of its serotoninergic action, pimavanserin has been tried in Tourette syndrome with modest benefits on tics and obsessive-compulsive behavior (19).

Clonidine is often used as a first-line drug for children with Tourette syndrome who have impaired school performance due to attention deficit hyperactivity disorder because this medication may also be useful in suppressing tics. Another alpha 2-receptor agonist, guanfacine, may be used in a similar fashion. The selective norepinephrine reuptake inhibitor atomoxetine is effective for both attention deficit hyperactivity disorder and tics in Tourette syndrome (07). When these drugs are ineffective, the use of stimulants should be considered. Treatment of Tourette syndrome with stimulants is somewhat controversial because these drugs have been thought to exacerbate and even precipitate tics in some patients. Studies indicate that stimulants are safe and effective for attention deficit hyperactivity disorder in patients with Tourette syndrome (178). Methylphenidate (0.1 to 0.3 mg/kg twice daily) is the stimulant of choice in this situation, and its use may actually reduce tic severity (127). A sustained-release preparation of methylphenidate is available. For patients experiencing an unacceptable worsening of tics during stimulant therapy, a neuroleptic can be added. Tricyclic antidepressants such as imipramine (10 to 25 mg/day) and desipramine (25 to 100 mg/day) have also been effective treatments for attention deficit hyperactivity disorder in children with Tourette syndrome. Due to potential cardiotoxicity, ECG monitoring is recommended before and during treatment with desipramine. Selegiline may be beneficial for children with attention deficit hyperactivity disorder and tics (65). Paroxetine may be particularly useful for the unprovoked attacks of anger known as "episodic rages" (29). Pramipexole, a D3 and D2 receptor agonist, has not been found to be effective in a double-blind, placebo-controlled trial (129).

Psychological counseling may help with general difficulties in coping with Tourette syndrome, a chronic illness with specific behavioral features.

There has been a long line of surgical procedures for tics (241), and experience has expanded. Zhang and colleagues have performed unilateral pallidotomies on 22 patients and obtained a significant reduction of tic frequencies (264). Sun and colleagues reported that bilateral anterior capsulotomy resulted in greater than 80% tic reduction in five patients in whom the posterior third of the anterior limbs of the internal capsules was targeted (234). In the same study, a lesser, but still greater than 50%, benefit was obtained in seven patients in whom the anterior one third of the anterior limbs was lesioned. The technology of deep brain stimulation has been applied to Tourette syndrome. Deep brain stimulation of the thalamus has shown marked success in ameliorating tics in a small number of patients (248). Comparable benefit has been achieved targeting the internal globus pallidus (58; 02; 249). More modest improvement was reported in one patient with deep brain stimulation and electrode implantation in the anterior internal capsule (68). Globus pallidus interna (Gpi) has been increasingly used as the target in patients with disabling tics (217; 249). Stimulation of various targets involved in the limbic striatopallidal-thalamocortical system could be beneficial in treating various aspects of Tourette syndrome (14). Based on a double-blind assessment of five patients with Tourette syndrome undergoing bilateral thalamic deep brain stimulation, there was a significant improvement in several measures of tic and behavioral severity (148). In the largest reported series, 18 patients with Tourette syndrome underwent bilateral deep brain stimulation of the centromedian parafascicular and ventralis oralis complex of the thalamus (216). Followed up to 18 months, most patients apparently showed improvement in tics as well as obsessive-compulsive disorder, self-injurious behavior, and other comorbidities. In a prospective 24-month follow-up of 15 of the original 18 patients, there continued to be marked improvement in tics, obsessive-compulsive disorder, anxiety, and depression with subjective perception of improved social functioning and quality of life (194). It would be helpful to know what happened to the three patients not included in this open-label, observational study. Also, a blinded review of videos before and after treatment would provide a more objective measure of efficacy (20). Finally, the observation that vagal nerve stimulation also favorably modifies the frequency and intensity of facial tics suggests that the brainstem plays a role in the generation of modulation of tics (55). One of the largest controlled trials of GPi deep brain stimulation in Tourette syndrome involved 15 patients (11 men, 4 women; mean age 34.7 years [SD 10.0]), 14 patients of whom were randomly assigned and 13 completed assessments (117). The mean YGTSS total score in these 13 patients was 80.7 (SD 12·0) for the off-stimulation period and 68.3 (SD 18·6) for the on-stimulation period, with a mean improvement of 12.4 points (95% CI 0.1-24.7, p=0.048), equivalent to a difference of 15.3%. The authors concluded that GPi stimulation led to a significant improvement in tic severity, with an overall acceptable safety profile. In another study involving 16 patients with Tourette syndrome randomly assigned to deep brain stimulation of the anterior globus pallidus internum or sham stimulation, no significant difference in the Yale Global Tourette Syndrome Scale was noted between the beginning and the end of the 3-month double-blind period (253). One interpretation of this negative result is that 3 months of stimulation may not be sufficient to decrease tic severity. This is supported by a 1-year follow-up of 185 patients with Tourette syndrome treated with deep brain stimulation included in a public registry (154). This showed that the Yale Global Tourette Syndrome Scale mean total score improved from 75.0 at baseline to 41.2 at 1 year after implantation (p < .001) and the motor and phonic tic subscores also improved significantly (both p < .001). The overall adverse event rate was 35.4%, with intracranial hemorrhage occurring in 1.2% of patients, infection in 2.5%, and lead explantation in 1%; the most common stimulation-induced side effects were dysarthria (6.3%) and paresthesia (8.2%). In a retrospective analysis of clinical data and imaging from 13 international sites in 110 patients with Tourette syndrome who were implanted in the centromedial thalamus (n = 51), globus pallidus internus (n = 47), nucleus accumbens/anterior limb of the internal capsule (n = 4), or a combination (n = 8), tics and obsessive-compulsive behavior significantly improved over time (p < 0.01) (113). The median time was 13 months to reach a 40% improvement in tics. There were no significant differences across targets (p = 0.84). A randomized, double-blind, sham-controlled trial of deep brain stimulation in 10 patients with Tourette syndrome suggested that the initial effect targeting globus pallidus internus was superior to thalamic target; long-term benefits seemed greater with the latter target (169). Deep brain stimulation continues to be evaluated in patients with Tourette syndrome, and future advances should lead to a better selection of patients and better long-term outcomes (156; 34).

The American Academy of Neurology issued practice guidelines based on a systematic review of the literature on the treatment of Tourette syndrome (198; 199). They concluded that there was high confidence that the Comprehensive Behavioral Intervention for Tics was more likely than psychoeducation and supportive therapy to reduce tics. There was moderate confidence that haloperidol, risperidone, aripiprazole, tiapride, clonidine, onabotulinum toxin A injections, 5-ling granule, and Ningdong granule were probably more likely than placebo to reduce tics. There was low confidence that pimozide, ziprasidone, metoclopramide, guanfacine, topiramate, tetrahydrocannabinol, and deep brain stimulation of the globus pallidus were possibly more likely than placebo to reduce tics.

Special considerations

Pregnancy

Some worsening of tics during pregnancy has been observed, although not predictably (173). The use of haloperidol should be restricted to the second and third trimesters due to potential embryotoxicity. Other therapies, such as pimozide and clonidine, have not been evaluated in pregnancy.

Anesthesia

Because of the risk of injury from sudden movements, patients with Tourette syndrome may require general anesthesia for typically outpatient procedures such as routine dental interventions (260). No problems were encountered in two patients undergoing general anesthesia after sufficient preoperative reassurance of patients and families that the tics would not interfere with the surgery or anesthesia and that the anesthetic agents would not aggravate the tic disorder (165). A 21-year-old woman with Tourette syndrome successfully underwent general anesthesia for Caesarean section without perioperative complications (214).

Media

References

01
Abelson JF, Kwan KY, O’Roak BJ, et al. Sequence variants in SLITRK1 are associated with Tourette's syndrome. Science 2005;310(5746):317-20. PMID 16224024
02
Ackermans L, Temel Y, Cath D, et al. Deep brain stimulation in Tourette's syndrome: Two targets. Mov Disord 2006. PMID 16463374
03
Adam OR, Ferrara JM, Jankovic J. Motor-phonic tic mimicking essential palatal myoclonus. Mov Disord 2009;24(13):2030-2. PMID 19672987
04
Aguirregomozcorta M, Pagonabarraga J, Diaz-Manera J, Pascual-Sedano B, Gironell A, Kulisevsky J. Efficacy of botulinum toxin in severe Tourette syndrome with dystonic tics involving the neck. Parkinsonism Relat Disord 2008;14(5):443-5. PMID 18337152
05
Albin RL, Koeppe RA, Wernette K, et al. Striatal [11C]dihydrotetrabenazine and [11C]methylphenidate binding in Tourette syndrome. Neurology 2009;72(16):1390-6. PMID 19380698
06
Albin RL, Mink JW. Recent advances in Tourette syndrome research. Trends Neurosci 2006;29(3):175-82. PMID 16430974
07
Allen AJ, Kurlan RM, Gilbert DL, et al. Atomoxetine treatment in children and adolescents with ADHD and comorbid tic disorders. Neurology 2005;65(12):1941-9. PMID 16380617
08
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5), 2013.
09
Anca MH, Giladi N, Korczyn AD. Ropinirole in Gilles de la Tourette syndrome. Neurology 2004;62(9):1626-7. PMID 15136698
10
Anonymous. A complete genome screen in sib pairs affected by Gilles de la Tourette syndrome. The Tourette Syndrome Association International Consortium on Genetics. Am J Hum Genet 1999;65(5):1428-36. PMID 10521310
11
Ashoori A, Jankovic J. Mozart's movements and behaviour: a case of Tourette's syndrome. J Neurol Neurosurg Psychiatry 2007;78:1171-5. PMID 17940168
12
Awaad Y, Michon AM, Minarik S. Use of levetiracetam to treat tics in children and adolescents with Tourette syndrome. Mov Disord 2005;20(6):714-8. PMID 15704204
13
Baizabal-Carvallo JF, Jankovic J. The clinical features of psychogenic movement disorders resembling tics. J Neurol Neurosurg Psychiatry 2014;85(5):573-5. PMID 24259592
14
Bajwa RJ, de Lotbiniere AJ, King RA, et al. Deep brain stimulation in Tourette's syndrome. Mov Disord 2007;22:1346-50. PMID 17580320
15
Banaschewski T, Woerner W, Rothenberger A. Premonitory sensory phenomena and suppressibility of tics in Tourette syndrome: developmental aspects in children and adolescents. Dev Med Child Neurol 2003;45:700-3. PMID 14515942
16
Behen M, Chugani HT, Juhász C, et al. Abnormal brain tryptophan metabolism and clinical correlates in Tourette syndrome. Mov Disord 2007;22:2256-62. PMID 17708557
17
Berardelli A, Curra A, Fabbrini G, Gilio F, Manfredi M. Pathophysiology of tics and Tourette syndrome. J Neurol 2003;250:781-7. PMID 12883917
18
Billnitzer A, Jankovic J. Current management of tics and Tourette syndrome: behavioral, pharmacologic, and surgical treatments. Neurotherapeutics 2020;17(4):1681-93. PMID 32856174
19
Billnitzer A, Jankovic J. Pilot study to evaluate pimavanserin for the treatment of motor and behavioral symptoms of Tourette syndrome. Mov Dis Clin Pract 2021. [In press]
20
Black KJ. Patient page. Deep brain stimulation for Tourette syndrome. Neurology 2009;73(17):e87-90. PMID 19858454
21
Black KJ, Black ER, Greene DJ, Schlaggar BL. Provisional tic disorder: what to tell parents when their child first starts ticcing. F1000Res 2016;5:696. PMID 27158458
22
Black KJ, Jankovic J, Hershey T, McNaught KS, Mink JW, Walkup J. Progress in research on Tourette syndrome. J Obsessive Compuls Relat Disord 2014;3(4):359-62. PMID 25436182
23
Blaty JL, DelRosso LM. Tourette disorder and sleep. Biomed J 2022;45(2):240-9. PMID 35031507
24
Bloch MH, Peterson BS, Scahill L, et al. Adulthood outcome of tic and obsessive-compulsive symptom severity in children with Tourette syndrome. Arch Pediatr Adolesc Med 2006;160(1):65-9. PMID 16389213
25
Bodner SM, Morshed SA, Peterson BS. The question of PANDAS in adults. Biol Psychiatry 2001;49:807-10. PMID 11331090
26
Bottini N, MacMurray J, Rostamkani M, McGue M, Iacono WG, Comings DE. Association between the low molecular weight cytosolic acid phosphatase gene ACP1A and comorbid features of Tourette syndrome. Neurosci Lett 2002;330:198-200. PMID 12231445
27
Brander G, Isomura K, Chang Z, et al. Association of Tourette syndrome and chronic tic disorder with metabolic and cardiovascular disorders. JAMA Neurol 2019;76(4):454-61. PMID 30640363
28
Bronfeld M, Bar-Gad I. Tic disorders: what happens in the basal ganglia. Neuroscientist 2013;19(1):101-8. PMID 22596263
29
Bruun RD, Budman CL. Paroxetine treatment of episodic rages associated with Tourette's disorder. J Clin Psychiatry 1998;59:581-4. PMID 9862603
30
Budman CL, Bruun RD, Park KS, Lesser M, Olson M. Explosive outbursts in children with Tourette's disorder. J Am Acad Child Adolesc Psychiatry 2000;39:1270-6. PMID 11026181
31
Burd L, Freeman RD, Klug MG, Kerbeshian J. Tourette Syndrome and learning disabilities. BMC Pediatr 2005;5:34. PMID 16137334
32
Burd L, Kerbeshian PJ, Barth A, Klug MG, Avery PK, Benz B. Long-term follow-up of an epidemiologically defined cohort of patients with Tourette syndrome. J Child Neurol 2001;16(6):431-7. PMID 11417610
33
Buts S, Duncan M, Owen T, et al. Paediatric tic-like presentations during the COVID-19 pandemic. Arch Dis Child 2022;107(3):e17. PMID 34824091
34
Cagle JN, Okun MS, Cernera S, et al. Embedded human closed-loop deep brain stimulation for Tourette syndrome: a nonrandomized controlled trial. JAMA Neurol 2022;79(10):1064-8. PMID 36094652
35
Cagle JN, Okun MS, Opri E, et al. Differentiating tic electrophysiology from voluntary movement in the human thalamocortical circuit. J Neurol Neurosurg Psychiatry 2020;91(5):533-9. PMID 32139653
36
Carr JE, Chong IM. Habit reversal treatment of tic disorders: a methodological critique of the literature. Behav Modif 2005;29(6):858-75. PMID 16204420
37
Cavanna AE, Schrag A, Morley D, et al. The Gilles de la Tourette syndrome-quality of life scale (GTS-QOL): development and validation. Neurology 2008;71(18):1410-6. PMID 18955683
38
Centers for Disease Control and Prevention. Prevalence of diagnosed Tourette syndrome in persons aged 6-17 years - United States, 2007. MMWR Morb Mortal Wkly Rep 2009;58(21):581-5. PMID 19498335
39
Chemali Z, Bromfield E. Tourette's syndrome following temporal lobectomy for seizure control. Epilepsy Behav 2003;4:564-6. PMID 14527500
40
Cheon KA, Ryu YH, Namkoong K, Kim CH, Kim JJ, Lee JD. Dopamine transporter density of the basal ganglia assessed with [(123)I]IPT SPECT in drug-naive children with Tourette's disorder. Psychiatry Res 2004;130:85-95. PMID 14972371
41
Cheung MY, Shahed J, Jankovic J. Malignant Tourette syndrome. Mov Disord 2007;22:1743-50. PMID 17566119
42
Chouinard S, Ford B. Adult onset tic disorders. J Neurol Neurosurg Psychiatry 2000;68(6):738-43. PMID 10811697
43
Church AJ, Dale RC, Lees AJ, Giovannoni G, Robertson MM. Tourette's syndrome: a cross sectional study to examine the PANDAS hypothesis. J Neurol Neurosurg Psychiatry 2003;74:602-7. PMID 12700302
44
Church JA, Fair DA, Dosenbach NU, et al. Control networks in paediatric Tourette syndrome show immature and anomalous patterns of functional connectivity. Brain 2009;132(Pt 1):225-38. PMID 18952678
45
Coffey B, Jankovic J, Claassen DO, et al. Efficacy and safety of fixed-dose deutetrabenazine in children and adolescents for tics associated with Tourette syndrome: a randomized clinical trial. JAMA Netw Open 2021;4(10):e2129397. PMID 34661664
46
Comings DE, Comings BG. Tourette syndrome: clinical and psychological aspects of 250 cases. Am J Hum Genet 1985;37:435-50. PMID 3859204
47
Como PG, LaMarch J, O’Brien KA. Obsessive-compulsive disorder in Tourette's syndrome. Adv Neurol 2005;96:249-61. PMID 16383224
48
Crawford FC, Ait-Ghezala G, Morris M, et al. Translocation breakpoint in two unrelated Tourette syndrome cases, within a region previously linked to the disorder. Hum Genet 2003;113:154-61. PMID 12698358
49
Cubo E, Chmura T, Goetz CG. Comparison of tic characteristics between children and adults. Mov Disord 2008;23(16):2407-11. PMID 18855922
50
Cuker A, State MW, King RA, Davis N, Ward DC. Candidate locus for Gilles de la Tourette syndrome/obsessive compulsive disorder/chronic tic disorder at 18q22. Am J Med Genet 2004;130(1):37-9. PMID 15368493
51
Curtis D, Brett P, Dearlove AM, et al. Genome scan of Tourette syndrome in a single large pedigree shows some support for linkage to regions of chromosomes 5, 10 and 13. Psychiatr Genet 2004;14(2):83-7. PMID 15167693
52
Deckersbach T, Rauch S, Buhlmann U, Wilhelm S. Habit reversal versus supportive psychotherapy in Tourette's disorder: a randomized controlled trial and predictors of treatment response. Behav Res Ther 2006;44(8):1079-90. PMID 16259942
53
Deng H, Gao K, Jankovic J. The genetics of Tourette syndrome. Nat Rev Neurol 2012;8(4):203-13. PMID 22410579
54
Deng H, Le WD, Xie WJ, Jankovic J. Examination of the SLITRK1 gene in Caucasian patients with Tourette syndrome. Acta Neurol Scand 2006;114:400-2. PMID 17083340
55
Diamond A, Kenney C, Jankovic J. The effect of vagal nerve stimulation in a case of Tourette’s syndrome and complex partial epilepsy. Mov Disord 2006;21:1273-5. PMID 16703589
56
Diaz-Anzaldua A, Joober R, Riviere JB, et al. Association between 7q31 markers and Tourette syndrome. Am J Med Genet 2004a;127(1):17-20. PMID 15103711
57
Diaz-Anzaldua A, Joober R, Riviere JB, et al. Tourette syndrome and dopaminergic genes: a family-based association study in the French Canadian founder population. Mol Psychiatry 2004b;9(3):272-7. PMID 15094788
58
Diederich NJ, Kalteis K, Stamenkovic M, Pieri V, Alesch F. Efficient internal pallidal stimulation in Gilles de la Tourette syndrome: a case report. Mov Disord 2005;20(11):1496-9. PMID 16037913
59
Dougherty DD, Rauch SL, Jenike MA. Pharmacotherapy for obsessive-compulsive disorder. J Clin Psychol 2004;60(11):1195-202. PMID 15389617
60
Eapen V, Lees AJ, Lakke JP, Trimble MR, Robertson MM. Adult-onset tic disorders. Mov Disord 2002;17:735-40. PMID 12210863
61
Ercan-Sencicek AG, Stillman AA, Ghosh AK, et al. L-histidine decarboxylase and Tourette's syndrome. N Engl J Med 2010;362(20):1901-8. PMID 20445167
62
Ernst M, Zametkin AJ, Jons PH, Matochik JA, Pascualvaca D, Cohen RM. High presynaptic dopaminergic activity in children with Tourette's disorder. J Am Acad Child Adolesc Psychiatry 1999;38:86-94. PMID 9893421
63
Fabbrini G, Pasquini M, Aurilia C, et al. A large Italian family with Gilles de la Tourette syndrome: clinical study and analysis of the SLITRK1 gene. Mov Disord 2007;22:2229-34. PMID 17712845
64
Farah A. Atypicality of atypical antipsychotics. Prim Care Companion J Clin Psychiatry 2005;7(6):268-74. PMID 16498489
65
Feigin A, Kurlan R, McDermott M, et al. A controlled trial of deprenyl in children with Tourette's syndrome and attention deficit hyperactivity disorder. Neurology 1996;46(4):965-8. PMID 8780073
66
Fernández de la Cruz L, Mataix-Cols D. General health and mortality in Tourette syndrome and chronic tic disorder: a mini-review. Neurosci Biobehav Rev 2020;119:514-20. PMID 33188819
67
Fischer JF, Mainka T, Worbe Y, Pringsheim T, Bhatia K, Ganos C. Self-injurious behaviour in movement disorders: systematic review. J Neurol Neurosurg Psychiatry 2020;91(7):712-9. PMID 32430438
68
Flaherty AW, Williams, ZM, Amirnovin R, et al. Deep brain stimulation of the anterior internal capsule for the treatment of Tourette syndrome: technical case report. Neurosurgery 2005;57(4 Suppl):E403. PMID 16234657
69
Freeman RD, Fast DK, Burd L, Kerbeshian J, Robertson MM, Sandor P. An international perspective on Tourette syndrome: selected findings from 3,500 individuals in 22 countries. Dev Med Child Neurol 2000;42:436-47. PMID 10972415
70
Freeman RD, Zinner SH, Müller-Vahl KR, et al. Coprophenomena in Tourette syndrome. Dev Med Child Neurol 2009;51(3):218-27. PMID 19183216
71
Gainetdinov RR, Wetsel WC, Jones SR, Levin ED, Jaber M, Caron MG. Role of serotonin in the paradoxical calming effect of psychostimulants on hyperactivity. Science 1999;283(5400):397-401. PMID 9888856
72
Ganos C. Tics and tic-like phenomena-old questions on a grand new scale invited editorial on TikTok and tics. Mov Disord Clin Pract 2021;8(8):1198-9. PMID 34765686
73
Garcia-Ribes A, Marti-Carrera I, Martinez-Gonzalez MJ, Garaizar C, Prats-Vinas JM. Factors related to the short term remission of tics in children with Tourette syndrome. Rev Neurol 2003;37(10):901-3. PMID 14634915
74
Ghosh D, Rajan PV, Das D, Datta P, Rothner AD, Erenberg G. Headache in children with Tourette syndrome. J Pediatr 2012;161(2):303-7. PMID 22424951
75
Gilbert DL, Dubow JS, Cunniff TM, Wanaski SP, Atkinson SD, Mahableshwarkar AR. Ecopipam for Tourette syndrome: a randomized trial. Pediatrics 2023;151(2):e2022059574. PMID 36628546
76
Gilbert DL, Dure L, Sethuraman G, Raab D, Lane J, Sallee FR. Tic reduction with pergolide in a randomized controlled trial in children. Neurology 2003;60:606-11. PMID 12601100
77
Gilbert DL, Kurlan R. PANDAS: horse or zebra. Neurology 2009;73(16):1252-3. PMID 19794126
78
Gilbert DL, Lipps TD. Tourette's Syndrome. Curr Treat Options Neurol 2005;7(3):211-9. PMID 15814074
79
Gilbert DL, Murphy TK, Jankovic J, et al. Ecopipam, a D1 receptor antagonist,for treatment of tourette syndrome in children: a randomized, placebo-controlled crossover study. Mov Disord 2018;33(8): PMID 30192018
80
Goetz CG, Tanner CM, Stebbins GT, Leipzig G, Carr WC. Adult tics in Gilles de la Tourette's syndrome: description and risk factors. Neurology 1992;42:784-8. PMID 1565232
81
Groth C, Mol Debes N, Rask CU, Lange T, Skov L. Course of Tourette syndrome and comorbidities in a large prospective clinical study. J Am Acad Child Adolesc Psychiatry 2017;56(4):304-12. PMID 28335874
82
Hallett M. Tourette syndrome: update. Brain Dev 2015;37(7):651-5. PMID 25604739
83
Hanna PA, Janjua FN, Contant CF, Jankovic J. Bilineal transmission in Tourette syndrome. Neurology 1999;53(4):813-8. PMID 10489047
84
Himle MB, Woods DW. An experimental evaluation of tic suppression and the tic rebound effect. Behav Res Ther 2005;43(11):1443-51. PMID 16159587
85
Hirschtritt ME, Lee PC, Pauls DL, et al. Lifetime prevalence, age of risk, and genetic relationships of comorbid psychiatric disorders in Tourette syndrome. JAMA Psychiatry 2015;72(4):325-33. PMID 25671412
86
Hoekstra PJ, Anderson GM, Limburg PC, Korf J, Kallenberg CG, Minderaa RB. Neurobiology and neuroimmunology of Tourette's syndrome: an update. Cell Mol Life Sci 2004;61(7-8):886-98. PMID 15095010
87
Hoekstra PJ, Minderaa RB. Tic disorders and obsessive-compulsive disorder: is autoimmunity involved. Int Rev Psychiatry 2005;17:497-502. PMID 16401548
88
Horesh N, Zimmerman S, Steinberg T, Yagan H, Apter A. Is onset of Tourette syndrome influenced by life events. J Neural Transm 2008;115(5):787-93. PMID 18217190
89
Hornsey H, Banerjee S, Zeitlin H, Robertson M. The prevalence of Tourette syndrome in 13-14-year-olds in mainstream schools. J Child Psychol Psychiatry 2001;42(8):1035-9. PMID 11806685
90
Hsu CJ, Wong LC, Lee WT. Immunological dysfunction in Tourette syndrome and related disorders. Int J Mol Sci 2021;22(2):853. PMID 33467014
91
Huang AY, Yu D, Davis LK, et al. Rare copy number variants in NRXN1 and CNTN6 increase risk for Tourette syndrome. Neuron 2017;94(6):1101-11.e7. PMID 28641109
92
Hull M, Parnes M, Jankovic J. Increased incidence of functional (psychogenic) movement disorders in children and adults amid the COVID-19 pandemic: a cross-sectional study. Neurol Clin Pract 2021;11(5):e686-90. PMID 34840884
93
Jackson SR, Loayza J, Crighton M, Sigurdsson HP, Dyke K, Jackson GM. The role of the insula in the generation of motor tics and the experience of the premonitory urge-to-tic in Tourette syndrome. Cortex 2020;126:119-33. PMID 32070809
94
Jankovic J. Tourette’s syndrome. N Engl J Med 2001;345:1184-92. PMID 11642235
95
Jankovic J. Treatment of hyperkinetic movement disorders. Lancet Neurol 2009;8(9):844-56. PMID 19679276
96
Jankovic J. Therapeutic developments for tics and myoclonus. Mov Disord 2015;30(11):1566-73. PMID 26315614
97
Jankovic J. Dopamine depleters in the treatment of hyperkinetic movement disorders. Expert Opin Pharmacother 2016;17(18):2461-70. PMID 27819145
98
Jankovic J. Botulinum toxin: state of the art. Mov Disord 2017;32(8):1131-8. PMID 28639368
99
Jankovic J. Treatment of tics associated with Tourette syndrome. J Neural Transm (Vienna) 2020;127(5):843-50. PMID 31955299
100
Jankovic J. An update on new and unique uses of botulinum toxin in movement disorders. Toxicon 2018;147:84-8. PMID 28888928
101
Jankovic J, Coffey B, Claassen DO, et al. Safety and efficacy of long-term deutetrabenazine use in children and adolescents with tics associated with Tourette syndrome: an open-label extension study. Mov Disord Clin Pract 2023;10(9):1388-98. PMID 37772282
102
Jankovic J, Gelineau-Kattner R, Davidson A. Tourette’s syndrome in adults. Mov Disord 2010b;25(13):2171-5. PMID 20690167
103
Jankovic J, Jimenez-Shahed J, Brown LW. A randomised, double-blind, placebo-controlled study of topiramate in the treatment of Tourette syndrome. J Neurol Neurosurg Psychiatry 2010a;81(1):70-3. PMID 19726418
104
Jankovic J, Jimenez-Shahed J, Budman C, et al. Deutetrabenazine in tics associated with Tourette syndrome. Tremor Other Hyperkinet Mov (N Y) 2016;6:422. PMID 27917309
105
Jankovic J, Kurlan R. Tourette syndrome: Evolving concepts. Mov Disord 2011;26(6):1149-56. PMID 21484868
106
Jankovic J, Kwak C, Frankoff R. Tourette's syndrome and the law. J Neuropsychiatry Clin Neurosci 2006 Winter;18(1):86-95. PMID 16525075
107
Jeffries KJ, Schooler C, Schoenbach C, Herscovitch P, Chase TN, Braun AR. The functional neuroanatomy of Tourette's syndrome: an FDG PET study III: functional coupling of regional cerebral metabolic rates. Neuropsychopharmacology 2002;27(1):92-104. PMID 12062910
108
Jenike MA. Clinical practice. Obsessive-compulsive disorder. N Engl J Med 2004;350(3):259-65. PMID 14724305
109
Jeppesen SS, Debes NM, Simonsen HJ, Rostrup E, Larsson HB, Skov L. Study of medication-free children with Tourette syndrome do not show imaging abnormalities. Mov Disord 2014;29(9):1212-6. PMID 24867681
110
Jiménez-Jiménez FJ, Alonso-Navarro H, García-Martín E, Agúndez JAG. Sleep disorders in tourette syndrome. Sleep Med Rev 2020;53:101335. PMID 32554211
111
Jin R, Zheng RY, Huang WW, et al. Epidemiological survey of Tourette syndrome in children and adolescents in wenzhou of p.R. China. Eur J Epidemiol 2005;20(11):925-7. PMID 16284870
112
Johannes S, Wieringa BM, Nager W, et al. Tourette Syndrome and obsessive-compulsive disorder: event-related brain potentials show similar mechanisms of frontal inhibition but dissimilar target evaluation processes. Behav Neurol 2003;14(1-2):9-17. PMID 12719634
113
Johnson KA, Fletcher PT, Servello D, et al. Image-based analysis and long-term clinical outcomes of deep brain stimulation for Tourette syndrome: a multisite study. J Neurol Neurosurg Psychiatry 2019;90(10):1078-90. PMID 31129620
114
Johnson KA, Worbe Y, Foote KD, Butson CR, Gunduz A, Okun MS. Tourette syndrome: clinical features, pathophysiology, and treatment. Lancet Neurol 2023;22(2):147-58. PMID 36354027
115
Kanaan AS, Gerasch S, García-García I, et al. Pathological glutamatergic neurotransmission in Gilles de la Tourette syndrome. Brain 2017;140(1):218-34. PMID 28007998
116
Karadenizli D, Dilbaz N, Bayam G. Gilles de la Tourette syndrome: response to electroconvulsive therapy. J ECT 2005;21(4):246-8. PMID 16301887
117
Kefalopoulou Z, Zrinzo L, Jahanshahi M, et al. Bilateral globus pallidus stimulation for severe Tourette's syndrome: a double-blind, randomised crossover trial. Lancet Neurol 2015;14(6):595-605. PMID 25882029
118
Kenney C, Hunter C, Mejia N, Jankovic J. Tetrabenazine in the treatment of Tourette syndrome. J Pediatr Neurol 2007;5:11-16.
119
Kenney C, Jankovic J. Tetrabenazine in the treatment of hyperkinetic movement disorders. Expert Rev Neurother 2006;6(1):7-17. PMID 16466307
120
Khalifa N, von Knorring AL. Tourette syndrome and other tic disorders in a total population of children: clinical assessment and background. Acta Paediatr 2005;94:1608-14. PMID 16352498
121
King A, Harris P, Fritzell J, Kurlan R. Syncope in children with Tourette's syndrome treated with guanfacine. Mov Disord 2006;21(3):419-20. PMID 16229000
122
Kleimaker M, Kleimaker A, Weissbach A, et al. Non-invasive brain stimulation for the treatment of Gilles de la Tourette syndrome. Front Neurol 2020;11:592258. PMID 33244309
123
Knight T, Steeves T, Day L, et al. Prevalence of tic disorders: a systematic review and meta-analysis. Pediatr Neurol 2012;47(2):77-90. PMID 22759682
124
Kompoliti K, Goetz CG. Tourette syndrome. Clinical rating and quantitative assessment of tics. Neurol Clin 1997;15:239-54. PMID 9106419
125
Kompoliti K, Goetz CG, Morrissey M, Leurgans S. Gilles de la Tourette syndrome: patient's knowledge and concern of adverse effects. Mov Disord 2006;21:248-52. PMID 16161137
126
Kramer H, Daniels C. Pioneers of movement disorders: Georges Gilles de la Tourette. J Neural Transm 2004;111(6):691-701. PMID 15168216
127
Kurlan R. Tourette's syndrome: are stimulants safe. Curr Neurol Neurosci Rep 2003;3:285-8. PMID 12930697
128
Kurlan R, Como PG, Miller B, et al. The behavioral spectrum of tic disorders: a community-based study. Neurology 2002;59(3):414-20. PMID 12177376
129
Kurlan R, Crespi G, Coffey B, et al. A multicenter randomized placebo-controlled clinical trial of pramipexole for Tourette's syndrome. Mov Disord 2012;27(6):775-8. PMID 22407510
130
Kurlan R, McDermott MP, Deeley C, et al. Prevalence of tics in schoolchildren and association with placement in special education. Neurology 2001;57(8):1383-8. PMID 11673576
131
Kurlan R, Whitmore D, Irvine C, McDermott MP, Como PG. Tourette's syndrome in a special education population: a pilot study involving a single school district. Neurology 1994;44:699-702. PMID 8164829
132
Kwak CH, Hanna PA, Jankovic J. Botulinum toxin in the treatment of tics. Arch Neurol 2000;57:1190-3. PMID 10927800
133
Kwak CH, Jankovic J. Tourettism and dystonia after subcortical stroke. Mov Disord 2002;17:821-5. PMID 12210884
134
Kwak C, Vuong KD, Jankovic J. Premonitory sensory phenomenon in Tourette’s syndrome. Mov Disord 2003a;18:1530-3. PMID 14673893
135
Kwak C, Vuong KD, Jankovic J. Migraine headache in patients with Tourette syndrome. Arch Neurol 2003b;60:1595-8. PMID 14623732
136
Lanzi G, Zambrino CA, Termine C, et al. Prevalence of tic disorders among primary school students in the city of Pavia, Italy. Arch Dis Child 2004;89:45-7. PMID 14709503
137
Leckman JF. Tourette's syndrome. Lancet 2002;360(9345):1577-86. PMID 12443611
138
Leckman JF, Cohen DJ, Goetz CG, Jankovic J. Tourette syndrome: pieces of the puzzle. Adv Neurol 2001a;85:369-90. PMID 11530445
139
Leckman JF, Peterson BS, King RA, Scahill L, Cohen DJ. Phenomenology of tics and natural history of tic disorders. Adv Neurol 2001b;85:1-14. PMID 11530419
140
Lee CC, Chou IC, Tsai CH, Wang TR, Li TC, Tsai FJ. Dopamine receptor D2 gene polymorphisms are associated in Taiwanese children with Tourette syndrome. Pediatr Neurol 2005;33:272-6. PMID 16194726
141
Lee JS, Yoo SS, Cho SY, Ock SM, Lim MK, Panych LP. Abnormal thalamic volume in treatment-naive boys with Tourette syndrome. Acta Psychiatr Scand 2006;113:64-7. PMID 16390372
142
Leonard HL, Swedo SE. Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). Int J Neuropsychopharmacol 2001;4:191-8. PMID 11466169
143
Lerner A, Bagic A, Boudreau EA, et al. Neuroimaging of neuronal circuits involved in tic generation in patients with Tourette syndrome. Neurology 2007;68(23):1979-87. PMID 17548547
144
Lesperance P, Djerroud N, Diaz Anzaldua A, Rouleau GA, Chouinard S, Richer F. Restless legs in Tourette syndrome. Mov Disord 2004;19(9):1084-7. PMID 15372602
145
Lichter DG, Dmochowski J, Jackson LA, Trinidad KS. Influence of family history on clinical expression of Tourette's syndrome. Neurology 1999;52(2):308-16. PMID 9932949
146
Lochner C, Stein DJ. Heterogeneity of obsessive-compulsive disorder: a literature review. Harv Rev Psychiatry 2003;11:113-32. PMID 12893502
147
Macerollo A, Martino D, Cavanna AE, et al. Refractoriness to pharmacological treatment for tics: a multicentre European audit. J Neurol Sci 2016;366:136-8. PMID 27288792
148
Maciunas RJ, Maddux BN, Riley DE, et al. Prospective randomized double-blind trial of bilateral thalamic deep brain stimulation in adults with Tourette syndrome. J Neurosurg 2007;107:1004-14. PMID 17977274
149
Majumdar A, Appleton RE. Delayed and severe but transient Tourette syndrome after head injury. Pediatr Neurol 2002;27:314-7. PMID 12435574
150
Makhoul K, Jankovic J. Driving impairment in movement disorders. Mov Disord Clin Pract 2023;10(3):369-81. PMID 36949799
151
Makki MI, Behen M, Bhatt A, Wilson B, Chugani HT. Microstructural abnormalities of striatum and thalamus in children with Tourette syndrome. Mov Disord 2008;23(16):2349-56. PMID 18759338
152
Mantel BJ, Meyers A, Tran QY, Rogers S, Jacobson JS. Nutritional supplements and complementary/alternative medicine in Tourette syndrome. J Child Adolesc Psychopharmacol 2004;14:582-9. PMID 15662150
153
Marras C, Andrews D, Sime E, Lang AE. Botulinum toxin for simple motor tics: a randomized, double-blind, controlled clinical trial. Neurology 2001;56:605-10. PMID 11245710
154
Martinez-Ramirez D, Jimenez-Shahed J, Leckman JF, et al. Efficacy and safety of deep brain stimulation in Tourette syndrome: the International Tourette Syndrome Deep Brain Stimulation Public Database and Registry. JAMA Neurol 2018;75(3):353-9. PMID 29340590
155
Martino D, Dale RC, Gilbert DL, Giovannoni G, Leckman JF. Immunopathogenic mechanisms in tourette syndrome: A critical review. Mov Disord 2009;24(9):1267-79. PMID 19353683
156
Martino D, Deeb W, Jimenez-Shahed J, et al. The 5 pillars in Tourette syndrome deep brain stimulation patient selection: present and future. Neurology 2021;96(14):664-76. PMID 33593864
157
Mataix-Cols D, Virtanen S, Sidorchuk A, et al. Association of Tourette syndrome and chronic tic disorder with violent assault and criminal convictions. JAMA Neurol 2022;79(5):459-67. PMID 35311941
158
Mathews CA, Waller J, Glidden D, et al. Self injurious behaviour in Tourette syndrome: correlates with impulsivity and impulse control. J Neurol Neurosurg Psychiatry 2004;75:1149-55. PMID 15258218
159
McCairn KW, Iriki A, Isoda M. Global dysrhythmia of cerebro-basal ganglia-cerebellar networks underlies motor tics following striatal disinhibition. J Neurosci 2013;33(2):697-708. PMID 23303948
160
McMahon WM, Carter AS, Fredine N, Pauls DL. Children at familial risk for Tourette's disorder: child and parent diagnoses. Am J Med Genet 2003;121B:105-11. PMID 12898584
161
Meidinger AL, Miltenberger RG, Himle M, Omvig M, Trainor C, Crosby R. An investigation of tic suppression and the rebound effect in Tourette's disorder. Behav Modif 2005;29:716-45. PMID 16046662
162
Mejia NI, Jankovic J. Secondary tics and tourettism. Rev Bras Psiquiatr 2005;27:11-7. PMID 15867978
163
Mi Y, Zhao R, Sun X, et al. Sleep disturbances and sleep patterns in children with tic disorder: a case-control study. Front Pediatr 2022;10:911343. PMID 35979406
164
Minzer K, Lee O, Hong JJ, Singer HS. Increased prefrontal D2 protein in Tourette syndrome: a postmortem analysis of frontal cortex and striatum. J Neurol Sci 2004;219(1-2):55-61. PMID 15050438
165
Morrison JE Jr, Lockhart CH. Tourette syndrome: anesthetic implications. Anesth Analg 1986;65:200-2. PMID 3455803
166
Muellner J, Delmaire C, Valabrégue R, et al. Altered structure of cortical sulci in gilles de la Tourette syndrome: further support for abnormal brain development. Mov Disord 2015;30(5):655-61. PMID 25820811
167
Müller-Vahl KR. Treatment of Tourette syndrome with cannabinoids. Behav Neurol 2013;27(1):119-24. PMID 23187140
168
Muller-Vahl KR, Meyer GJ, Knapp WH, et al. Serotonin transporter binding in Tourette Syndrome. Neurosci Lett 2005;385:120-5. PMID 15936877
169
Müller-Vahl KR, Szejko N, Saryyeva A, et al. Randomized double-blind sham-controlled trial of thalamic versus GPi stimulation in patients with severe medically refractory Gilles de la Tourette syndrome. Brain Stimul 2021;14(3):662-75. PMID 33857664
170
Murphy TK, Sajid M, Soto O, et al. Detecting pediatric autoimmune neuropsychiatric disorders associated with streptococcus in children with obsessive-compulsive disorder and tics. Biol Psychiatry 2004;55(1):61-8. PMID 14706426
171
Niccolai V, Korczok S, Finis J, et al. A peek into premonitory urges in Tourette syndrome: temporal evolution of neurophysiological oscillatory signatures. Parkinsonism Relat Disord 2019;65:153-8. PMID 31182372
172
Niemann N, Jankovic J. Real-world experience with VMAT2 inhibitors. Clin Neuropharmacol 2019;42(2):37-41. PMID 30870235
173
O'Brien CF, Kurlan R. Movement disorders in pregnancy. In: Goldstein PJ, Stern BJ, editors. Neurological disorders of pregnancy. Mt. Kisco: Futura, 1992:181-201.
174
Ondo WG, Jong D, Davis A. Comparison of weight gain in treatments for Tourette syndrome: tetrabenazine versus neuroleptic drugs. J Child Neurol 2008;23(4):435-7. PMID 18192650
175
Orth M, Munchau A. Transcranial magnetic stimulation studies of sensorimotor networks in Tourette syndrome. Behav Neurol 2013;27(1):57-64. PMID 23187144
176
Packer LE. Tic-related school problems: impact on functioning, accommodations, and interventions. Behav Modif 2005;29:876-99. PMID 16204421
177
Padala PR, Qadri SF, Madaan V. Aripiprazole for the treatment of Tourette's disorder. Prim Care Companion J Clin Psychiatry 2005;7:296-9. PMID 16498492
178
Palumbo D, Spencer T, Lynch J, Co-Chien H, Faraone SV. Emergence of tics in children with ADHD: impact of once-daily OROS methylphenidate therapy. J Child Adolesc Psychopharmacol 2004;14:185-94. PMID 15319016
179
Pappert EJ, Goetz CG, Louis ED, Blasucci L, Leurgans S. Objective assessments of longitudinal outcome in Gilles de la Tourette's syndrome. Neurology 2003;61:936-40. PMID 14557563
180
Park S, Como PG, Cui L, Kurlan R. The early course of the Tourette's syndrome clinical spectrum. Neurology 1993;43:1712-5. PMID 8414018
181
Paschou P, Feng Y, Pakstis AJ, et al. Indications of linkage and association of Gilles de la Tourette syndrome in two independent family samples: 17q25 is a putative susceptibility region. Am J Hum Genet 2004;75(4):545-60. PMID 15303240
182
Patel N, Jankovic J, Hallett M. Sensory aspects of movement disorders. Lancet Neurol 2014;13(1):100-12. PMID 24331796
183
Pauls DL. An update on the genetics of Gilles de la Tourette syndrome. J Psychosom Res 2003;55(1):7-12. PMID 12842226
184
Pavone P, Bianchini R, Parano E, et al. Anti-brain antibodies in PANDAS versus uncomplicated streptococcal infection. Pediatr Neurol 2004;30(2):107-10. PMID 14984902
185
Pellecchia MT, Valente EM, Cif L, et al. The diverse phenotype and genotype of pantothenate kinase-associated neurodegeneration. Neurology 2005;64:1810-2. PMID 15911822
186
Pena MS, Yaltho TC, Jankovic J. Tardive dyskinesia and other movement disorders secondary to aripiprazole. Mov Disord 2011;26(1):147-52. PMID 20818603
187
Pérez-Vigil A, Fernández de la Cruz L, Brander G, et al. Association of tourette syndrome and chronic tic disorders with objective indicators of educational attainment: a population-based sibling comparison study. JAMA Neurol 2018;75(9):1098-105. PMID 29813161
188
Perlmutter SJ, Leitman SF, Garvey MA, et al. Therapeutic plasma exchange and intravenous immunoglobulin for obsessive-compulsive disorder and tic disorders in childhood. Lancet 1999;354(9185):1153-8. PMID 10513708
189
Peterson BS. Neuroimaging studies of Tourette syndrome: a decade of progress. Adv Neurol 2001;85:179-96. PMID 11530427
190
Peterson BS, Leckman JF, Scahill L, et al. Steroid hormones and CNS sexual dimorphisms modulate symptom expression in Tourette's syndrome. Psychoneuroendocrinology 1992;17(6):553-63. PMID 1287677
191
Peterson BS, Thomas P, Kane MJ, et al. Basal ganglia volumes in patients with Gilles de la Tourette syndrome. Arch Gen Psychiatry 2003;60:415-24. PMID 12695320
192
Piacentini J, Chang S. Behavioral treatments for Tourette syndrome and tic disorders: state of the art. Adv Neurol 2001;85:319-31. PMID 11530440
193
Piacentini J, Woods DW, Scahill L, et al. Behavior therapy for children with Tourette disorder: a randomized controlled trial. JAMA 2010;303(19):1929-37. PMID 20483969
194
Porta M, Brambilla A, Cavanna AE, et al. Thalamic deep brain stimulation for treatment-refractory Tourette syndrome: two-year outcome. Neurology 2009;73(17):1375-80. PMID 19858459
195
Pourfar M, Feigin A, Tang CC, et al. Abnormal metabolic brain networks in Tourette syndrome. Neurology 2011;76(11):944-52. PMID 21307354
196
Prado HS, Rosario MC, Lee J, Hounie AG, Shavitt RG, Miguel EC. Sensory phenomena in obsessive-compulsive disorder and tic disorders: a review of the literature. CNS Spectr 2008;13(5):425-32. PMID 18496480
197
Pringsheim T, Ganos C, McGuire JF, et al. Rapid onset functional tic-like behaviors in young females during the COVID-19 pandemic. Mov Disord 2021;36(12):2707-13. PMID 34387394
198
Pringsheim T, Holler-Managan Y, Okun MS, et al. Comprehensive systematic review summary: treatment of tics in people with Tourette syndrome and chronic tic disorders. Neurology 2019a;92(19):907-15. PMID 31061209
199
Pringsheim T, Okun MS, Müller-Vahl K, et al. Practice guideline recommendations summary: treatment of tics in people with Tourette syndrome and chronic tic disorders. Neurology 2019b;92(19):896-906. PMID 31061208
200
Rajagopal S, Seri And S, Cavanna AE. Premonitory urges and sensorimotor processing in Tourette syndrome. Behav Neurol 2013;27(1):65-73. PMID 23187151
201
Rappley MD. Clinical practice. Attention deficit-hyperactivity disorder. N Engl J Med 2005;352:165-73. PMID 15647579
202
Reid SD. Neuroleptic-induced Tardive Tourette treated with clonazepam: a case report and literature review. Clin Neuropharmacol 2004;27:101-4. PMID 15190229
203
Robertson MM. Diagnosing Tourette syndrome. Is it a common disorder. J Psychosom Res 2003;55:3-6. PMID 12842225
204
Robertson MM, Eapen V, Singer HS, et al. Gilles de la Tourette syndrome. Nat Rev Dis Primers 2017;3:16097. PMID 28150698
205
Romano A, Cundari G, Bruni O, Cardona F. Tic disorders and arousal dysfunction: clinical evaluation of 49 children and adolescents. Minerva Pediatr 2004;56:327-34. PMID 15252381
206
Sallee F, Kohegyi E, Zhao J, et al. Randomized, double-blind, placebo-controlled trial demonstrates the efficacy and safety of oral aripiprazole for the treatment of Tourette's disorder in children and adolescents. J Child Adolesc Psychopharmacol 2017;27(9):771-81. PMID 28686474
207
Scahill L, Woods DW, Himle MB, et al. Current controversies on the role of behavior therapy in Tourette syndrome. Mov Disord 2013;28(9):1179-83. PMID 23681719
208
Scharf JM, Miller LL, Gauvin CA, Alabiso J, Mathews CA, Ben-Shlomo Y. Population prevalence of Tourette syndrome: a systematic review and meta-analysis. Mov Disord 2015;30(2):221-8. PMID 25487709
209
Scharf JM, Miller LL, Mathews CA, Ben-Shlomo Y. Prevalence of Tourette syndrome and chronic tics in the population-based Avon longitudinal study of parents and children cohort. J Am Acad Child Adolesc Psychiatry 2012;51(2):192-201. PMID 22265365
210
Scharf JM, Yu D, Mathews CA, et al. Genome-wide association study of Tourette’s syndrome. Mol Psychiatry 2013;18(6):721-8. PMID 22889924
211
Schrag A, Gilbert R, Giovannoni G, Robertson MM, Metcalfe C, Ben-Shlomo Y. Streptococcal infection, Tourette syndrome, and OCD. Is there a connection. Neurology 2009;73(16):1256-63. PMID 19794128
212
Sedel F, Friderici K, Nummy K, et al. Atypical Gilles de la Tourette Syndrome with beta-mannosidase deficiency. Arch Neurol 2006;63:129-31. PMID 16401745
213
Segawa M. Neurophysiology of Tourette's syndrome: pathophysiological considerations. Brain Dev 2003;25(Suppl 1):S62-9. PMID 14980375
214
Sener EB, Kocamanoglu S, Ustun E, Tur A. Anesthetic management for cesarean delivery in a woman with Gilles de la Tourette's syndrome. Int J Obstet Anesth 2006;15(2):163-5. PMID 16434179
215
Serra-Mestres J, Ring HA, Costa DC, et al. Dopamine transporter binding in Gilles de la Tourette syndrome: a [123I]FP-CIT/SPECT study. Acta Psychiatr Scand 2004;109:140-6. PMID 14725596
216
Servello D, Porta M, Sassi M, Brambilla A, Robertson MM. Deep brain stimulation in 18 patients with severe Gilles de la Tourette syndrome refractory to treatment: the surgery and stimulation. J Neurol Neurosurg Psychiatry 2008;79(2):136-42. PMID 17846115
217
Shahed J, Poysky J, Kenney C, Simpson R, Jankovic J. GPi deep brain stimulation for Tourette syndrome improves tics and psychiatric comorbidities. Neurology 2007;68(2):159-60. PMID 17210901
218
Shen EY, Weng SM, Kuo YT, Chiu NC, Ho CS. Serial sonographic findings of lenticulostriate vasculopathy. Acta Paediatr Taiwan 2005;46:77-81. PMID 16302583
219
Shprecher D, Kurlan R. The management of tics. Mov Disord 2009;24(1):15-24. PMID 19170198
220
Silay YS, Jankovic J. Emerging drugs in Tourette syndrome. Expert Opin Emerg Drugs 2005;10:365-80. PMID 15934872
221
Singer HS. Tourette's syndrome: from behaviour to biology. Lancet Neurol 2005;4:149-59. PMID 15721825
222
Singer HS. Discussing outcome in Tourette syndrome. Arch Pediatr Adolesc Med 2006;160:103-5. PMID 16389220
223
Singer HS, Gause C, Morris C, Lopez P; Tourette Syndrome Study Group. Serial immune markers do not correlate with clinical exacerbations in pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. Pediatrics 2008;121(6):1198-205. PMID 18519490
224
Singer HS, Hahn IH, Moran TH. Abnormal dopamine uptake sites in postmortem striatum from patients with Tourette's syndrome. Ann Neurol 1991;30:558-62. PMID 1838678
225
Singer HS, Hong JJ, Yoon DY, Williams PN. Serum autoantibodies do not differentiate PANDAS and Tourette syndrome from controls. Neurology 2005;65:1701-7. PMID 16207842
226
Singer HS, Loiselle C. PANDAS. A commentary. J Psychosom Res 2003;55:31-9. PMID 12842229
227
Singer HS, Minzer K. Neurobiology of Tourette's syndrome: concepts of neuroanatomic localization and neurochemical abnormalities. Brain Dev 2003;25(Suppl 1):S70-84. PMID 14980376
228
Singer HS, Szymanski S, Giuliano J, et al. Elevated intrasynaptic dopamine release in Tourette's syndrome measured by PET. Am J Psychiatry 2002;159:1329-36. PMID 12153825
229
Singer HS, Wendlandt JT. Neurochemistry and synaptic neurotransmission in Tourette syndrome. Adv Neurol 2001;85:163-78. PMID 11530426
230
Singh S, Jankovic J. Tardive dystonia in patients with Tourette’s syndrome. Mov Disord 1988;3:274-80. PMID 2904122
231
Snider LA, Swedo SE. PANDAS: current status and directions for research. Mol Psychiatry 2004;9(10):900-7. PMID 15241433
232
Sowell ER, Kan E, Yoshii J, et al. Thinning of sensorimotor cortices in children with Tourette syndrome. Nat Neurosci 2008;11(6):637-9. PMID 18488025
233
Steeves T, McKinlay BD, Gorman D, et al. Canadian guidelines for the evidence-based treatment of tic disorders: behavioural therapy, deep brain stimulation, and transcranial magnetic stimulation. Can J Psychiatry 2012;57(3):144-51. PMID 22398000
234
Sun B, Krahl SE, Zhan S, Shen J. Improved capsulotomy for refractory Tourette's syndrome. Stereotact Funct Neurosurg 2005;83:55-6. PMID 15990467
235
Sun N, Tischfield JA, King RA, Heiman GA. Functional evaluations of genes disrupted in patients with Tourette's disorder. Front Psychiatry 2016;7:11. PMID 26903887
236
Swain JE, Leckman JF. Tourette's syndrome in children. Curr Treat Options Neurol 2003;5:299-308. PMID 12791197
237
Swedo SE, Leckman JF, Rose NR. From Research Subgroup to Clinical Syndrome: Modifying the PANDAS Criteria to Describe PANS (Pediatric Acute-onset Neuropsychiatric Syndrome). Pediatr Therapeut 2012;2:2-8.
238
Tan EK. Psychogenic tics: diagnostic value of the placebo test. J Child Neurol 2004;19:976-7. PMID 15704874
239
Tanner CM, Goldman SM. Epidemiology of Tourette syndrome. Neurol Clin 1997;15:395-402. PMID 9115469
240
Taylor JR, Morshed SA, Parveen S, et al. An animal model of Tourette's syndrome. Am J Psychiatry 2002;159(4):657-60. PMID 11925307
241
Temel Y, Visser-Vandewalle V. Surgery in Tourette syndrome. Mov Disord 2004;19:3-14. PMID 14743354
242
Thenganatt MA, Jankovic J. Recent advances in understanding and managing Tourette syndrome. F100Res 2016;5. PMID 26918185
243
Tinaz S, Malone P, Hallett M, Horovitz SG. Role of the right dorsal anterior insula in the urge to tic in Tourette syndrome. Mov Disord 2015;30(9):1190-7. PMID 25855089
244
Van den Eynde F, Naudts KH, De Saedeleer S, van Heeringen C, Audenaert K. Olanzapine in Gilles de la Tourette syndrome: beyond tics. Acta Neurol Belg 2005;105:206-11. PMID 16482870
245
van der Salm SM, Tijssen MA, Koelman JH, van Rootselaar AF. The bereitschaftspotential in jerky movement disorders. J Neurol Neurosurg Psychiatry 2012;83(12):1162-7. PMID 22952323
246
Verkerk AJ, Mathews CA, Joosse M, Eussen BH, Heutink P, Oostra BA. Cntnap2 is disrupted in a family with Gilles de la Tourette syndrome and obsessive compulsive disorder. Genomics 2003;82:1-9. PMID 12809671
247
Virtanen S, Sidorchuk A, Fernández de la Cruz L, et al. Association of Tourette syndrome and chronic tic disorder with subsequent risk of alcohol- or drug-related disorders, criminal convictions, and death: a population-based family study. Biol Psychiatry 2021;89(4):407-14. PMID 33229038
248
Visser-Vandewalle V, Temel Y, Boon P, et al. Chronic bilateral thalamic stimulation: a new therapeutic approach in intractable Tourette syndrome. Report of three cases. J Neurosurg 2003;99:1094-100. PMID 14705742
249
Viswanathan A, Jimenez-Shahed J, Baizabal-Carvallo F, Jankovic J. Deep brain stimulation for Tourette syndrome: target selection. Stereotact Funct Neurosurg 2012;90(4):213-24. PMID 22699684
250
Walker K, Lawrenson J, Wilmshurst J. Neuropsychiatric movement disorders following streptococcal infection. Dev Med Child Neurol 2005;47:771-5. PMID 16225742
251
Wang HS, Kuo MF. Tourette's syndrome in Taiwan: an epidemiological study of tic disorders in an elementary school at Taipei County. Brain Dev 2003;25(Suppl 1):S29-31. PMID 14980369
252
Welch JM, Lu J, Rodriguiz RM, et al. Cortico-striatal synaptic defects and OCD-like behaviours in Sapap3-mutant mice. Nature 2007;448:894-900. PMID 17713528
253
Welter ML, Houeto JL, Thobois S, et al. Anterior pallidal deep brain stimulation for Tourette's syndrome: a randomised, double-blind, controlled trial. Lancet Neurol 2017;16(8):610-9. PMID 28645853
254
Wijemanne S, Wu LJ, Jankovic J. Long-term efficacy and safety of fluphenazine in patients with Tourette syndrome. Mov Disord 2014;29(1):126-30. PMID 24150997
255
Willsey AJ, Fernandez TV, Yu D, et al. De novo coding variants are strongly associated with Tourette disorder. Neuron 2017;94(3):486-99.e9. PMID 28472652
256
Woods DW, Piacentini J, Himle MB, Chang S. Premonitory Urge for Tics Scale (PUTS): initial psychometric results and examination of the premonitory urge phenomenon in youths with Tic disorders. J Dev Behav Pediatr 2005;26:397-403. PMID 16344654
257
Worbe Y, Sgambato-Faure V, Epinat J, et al. Towards a primate model of Gilles de la Tourette syndrome: anatomo-behavioural correlation of disorders induced by striatal dysfunction. Cortex 2013;49(4):1126-40. PMID 23040317
258
Yaltho TC, Lotze T, Jankovic J. The association of Tourette syndrome and dopa-responsive dystonia. Mov Disord 2011;26(2):359-60. PMID 21412842
259
Yoon DY, Gause CD, Leckman JF, Singer HS. Frontal dopaminergic abnormality in Tourette syndrome: a postmortem analysis. J Neurol Sci 2007;255:50-6. PMID 17337006
260
Yoshikawa F, Takagi T, Fukayama H, Miwa Z, Umino M. Intravenous sedation and general anesthesia for a patient with Gilles de la Tourette's syndrome undergoing dental treatment. Acta Anaesthesiol Scand 2002;46:1279-80. PMID 12421203
261
Yu D, Sul JH, Tsetsos F, et al. Interrogating the genetic determinants of tourette's syndrome and other tic disorders through genome-wide association studies. Am J Psychiatry 2019;176(3):217-27. PMID 30818990
262
Zea Vera A, Bruce A, Garris J, et al. The phenomenology of tics and tic-like behavior in TikTok. Pediatr Neurol 2022;130:14-20. PMID 35303587
263
Zhang H, Leckman JF, Pauls DL, et al. Genomewide scan of hoarding in sib pairs in which both sibs have Gilles de la Tourette syndrome. Am J Hum Genet 2002;70(4):896-904. PMID 11840360
264
Zhang XH, Li YJ, ZuahngP. A study on outcome and mechanism of surgical treatment for Tourette's syndrome. Zhonghua Wai Ke Za Zhi 2005;43:608-11. PMID 15938938

Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Author

  • JankovicJ2

    Joseph Jankovic MD

    Dr. Jankovic, Director of the Parkinson's Disease Center and Movement Disorders Clinic at Baylor College of Medicine has no relevant financial relationships to disclose.

    See Profile

Former Authors

  • Roger Kurlan MD
  • David E Riley MD

Patient Profile

Age range of presentation
  • 1 month to 64 years
Sex preponderance
  • male>female, >2:1
Heredity
  • heredity typical
  • heredity may be a factor
  • autosomal dominant
Population groups selectively affected
  • none selectively affected
Occupation groups selectively affected
  • none selectively affected

ICD & OMIM codes

ICD-9
  • Tourette’s disorder (motor-verbal tic): 307.23
  • Obsessive-compulsive disorders: 300.3
ICD-10
  • Combined vocal and multiple motor tic disorder [de la Tourette]: F95.2
  • Other obsessive-compulsive disorders: F42.8
OMIM
  • Gilles de la Tourette syndrome: #137580
  • Modifier of Tourette syndrome: 309840

Questions or Comment?

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