Tourette syndrome: Difference between revisions

Tourette syndrome
Tourette syndrome
Other names	Tourette's syndrome, Tourette's disorder, Gilles de la Tourette syndrome (GTS)
	Georges Gilles de la Tourette (1857–1904), namesake of Tourette syndrome
Specialty	Pediatrics, neurology
Symptoms	Tics
Usual onset	Typically in childhood
Duration	Long term
Causes	Genetic with environmental influence
Diagnostic method	Based on history and symptoms
Management	Education, behavioral therapy
Medication	Usually none, occasionally antipsychotics and noradrenergics
Prognosis	Improvement to disappearance of tics beginning in late teens
Frequency	About 1%

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Tourette syndrome (TS or simply Tourette's) is a neurodevelopmental disorder with onset in childhood,^[4] characterized by multiple movement (motor) tics and at least one vocal (phonic) tic. Some common tics are blinking, coughing, throat clearing, sniffing, and facial movements. These tics are typically preceded by an unwanted urge or sensation in the affected muscles, can sometimes be suppressed temporarily, and characteristically change in location, strength, and frequency. Tics are often unnoticed by casual observers.

Once regarded as a rare and bizarre syndrome, Tourette's has popularly been associated with coprolalia (the utterance of obscene words or socially inappropriate and derogatory remarks), but this symptom is present in only a minority of people with Tourette's. It is no longer considered a rare condition; about 1% of school-age children and adolescents are estimated to have Tourette's,^[1] though many go undiagnosed or never seek medical care. There are no specific tests for diagnosing Tourette's; it is not always correctly identified because most cases are mild and the severity of tics decreases for most children as they pass through adolescence. Extreme Tourette's in adulthood, though sensationalized in the media, is rare. Tourette's does not affect intelligence or life expectancy.

Education is an important part of any treatment plan, and explanation and reassurance alone are often sufficient.^[1]^[5] In most cases, medication for tics is not necessary, and behavioral therapies are the first-line treatment. Among those who are seen in specialty clinics, attention-deficit hyperactivity disorder (ADHD) and obsessive–compulsive disorder (OCD) are present at higher rates. These co-occurring diagnoses often cause more impairment to the individual than the tics; hence, it is important to correctly distinguish co-occurring conditions and treat them.

Tourette's is defined as part of a spectrum of tic disorders. While the exact cause is unknown, it is believed to involve a combination of genetic and environmental factors. The mechanism appears to involve dysfunction in neural circuits between the basal ganglia and related structures in the brain. Compared to the success in genetic research seen in other conditions, funded research into the genetics of Tourette's is lagging in the US. The condition was named by French neurologist Jean-Martin Charcot on behalf of his resident, Georges Gilles de la Tourette, who published an account of nine patients with Tourette's in 1885.

Classification

Tourette syndrome is classified as a motor disorder (disorders of the nervous system that cause abnormal and involuntary movements). It is listed in the neurodevelopmental disorder category of the fifth version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), published in May 2013.^[6] Tourette's is at the more severe end of the spectrum of tic disorders, requiring multiple motor tics, and at least one vocal tic to be present for more than a year. Tics due to other known conditions or substances taken are excluded.^[7] Tics are sudden, repetitive, nonrhythmic movements (motor tics) and utterances (phonic tics) that involve discrete muscle groups.^[8] Neurologist Joseph Jankovic describes vocal or phonic tics as "motor tics that involve respiratory, laryngeal, pharyngeal, oral, and nasal musculature".^[9]

Other conditions on the spectrum include persistent (chronic) motor or vocal tics, where one type of tic (motor or vocal, but not both) has been present for more than a year, and provisional tic disorder, where motor or vocal tics have been present less than one year.^[10]^[11] DSM-5 replaced what had been called transient tic disorder in DSM-IV-TR with provisional tic disorder, recognizing that "transient" can only be defined in retrospect.^[12]^[13]^[14] Some experts believe that TS and persistent (chronic) motor or vocal tic disorder should be considered the same condition, because vocal tics are also muscular contractions, albeit of nasal or respiratory muscles,^[3] and should not be distinguished from motor tics.^[11]

Tic disorders are defined only slightly differently by the World Health Organization (WHO); in its ICD-10, the International Statistical Classification of Diseases and Related Health Problems, TS is described as "combined vocal and multiple motor tic disorder [de la Tourette]".^[4]^[15] Most published research on TS is from the United States, and the DSM is preferred over the WHO classification system for international research.^[12]

Genetic studies indicate that tic disorders fall along a spectrum and "not into the distinct categories implied by the current diagnostic framework".^[7] Since 2008, studies have suggested that Tourette's is not a unitary condition with a distinct mechanism as described in the existing classification systems, rather that subtypes should be recognized to distinguish "pure TS" from TS when it is accompanied by attention-deficit hyperactivity disorder (ADHD), obsessive–compulsive disorder (OCD) or other disorders.^[4]^[7]^[10] Elucidation of these subtypes (such as in type 1 and type 2 diabetes) awaits fuller understanding of the genetic and other causes of tic disorders.^[12]

Characteristics

Tics

Examples of tics

Tics are movements or sounds that take place "intermittently and unpredictably out of a background of normal motor activity",^[16] having the appearance of "normal behaviors gone wrong".^[17] The tics associated with Tourette's change in number, frequency, severity and anatomical location, and each individual experiences a unique pattern of fluctuation in their severity and frequency. Tics may also occur in "bouts of bouts", which vary for each person.^[8] The variation in tic severity may occur over hours, days, or weeks.^[10] Tics may increase when an individual is experiencing stress, fatigue, anxiety, or illness,^[7]^[18] or when engaged in relaxing activities like watching TV. They sometimes decrease when an individual is engrossed in or focused on an activity like playing a musical instrument.^[7]^[19]

In contrast to the abnormal movements of other movement disorders such as choreas, dystonias, myoclonus, and dyskinesias, the tics of Tourette's are temporarily suppressible, nonrhythmic, and often preceded by an unwanted urge.^[20] The ability to suppress tics varies among individuals, and may be more developed in adults than children.^[21] Individuals with tics are sometimes able to suppress them for limited periods of time, but doing so often results in tension or mental exhaustion.^[1]^[22] People with Tourette's may seek a secluded spot to release their symptoms, or there may be a marked increase in tics after a period of suppression at school or at work.^[10]^[17] Children may suppress tics while in the doctor's office, so may need to be observed while they are not aware of being watched.^[23]

Over time, about 90% of individuals with Tourette's feel an urge that precedes tic onset,^[10] similar to the need to sneeze or scratch an itch. The urges and sensations that precede the expression of a tic are referred to as premonitory sensory phenomena or premonitory urges. These urges may be physical or mental.^[24] Individuals describe the urges as a need to express the tic as a buildup of tension, pressure, or energy^[25]^[26] which they consciously choose to release, as if they "had to do it"^[27] to relieve the sensation^[25] or until it feels "just right".^[27]^[28] Examples of this urge are the feeling of having something in one's throat, or a localized discomfort in the shoulders, leading to the need to clear one's throat or shrug the shoulders. The actual tic may be felt as relieving this tension or sensation, similar to scratching an itch or blinking to relieve an uncomfortable feeling in the eye. Because of the urges that precede them, tics are described as semi-voluntary or "unvoluntary",^[1]^[16] rather than specifically involuntary; they may be experienced as a voluntary, suppressible response to the unwanted premonitory urge.^[19]^[22] Some people with Tourette's may not be aware of the premonitory urge associated with tics. Children may be less aware of it than are adults,^[10] but their awareness tends to increase with maturity;^[16] by the age of ten, most children recognize the premonitory urge.^[19] So, although a preceding urge to resolve a tension or sensation is identified in published accounts as a core symptom of the syndrome, it is not included in the diagnostic criteria.^[24]^[26]^[29]

Complex tics related to speech include coprolalia, echolalia and palilalia. Coprolalia (the spontaneous utterance of socially objectionable or taboo words or phrases) is the most publicized symptom of Tourette's, but it is not required for a diagnosis, and only about 10% of people with Tourette's exhibit it.^[1]^[22] Echolalia (repeating the words of others) and palilalia (repeating one's own words) occur in a minority of cases.^[8] Corresponding complex motor tics include copropraxia (obscene or forbidden gestures, or inappropriate touching), echopraxia (repetition or imitation of another person's actions) and palipraxia (repeating one's own movements).^[21]

Onset and progression

There is no such thing as a typical case of Tourette syndrome,^[30] however the condition follows a fairly reliable course in terms of the age of onset and the history of the severity of symptoms. Although onset may occur anytime before the age of eighteen, the typical age of onset of tics is from five to seven, and it is usually before adolescence.^[1] A 1998 study published by Leckman and colleagues from the Yale Child Study Center^[31] showed that tic severity then increased with age, reaching the highest point between eight and twelve years old. Severity declines steadily for most children as they pass through adolescence, when half to two-thirds of children see a dramatic decrease in tics.^[32]

The first tics to appear usually affect the head, face, and shoulders, and include blinking, facial movements, sniffing and throat clearing.^[10] Vocal tics often appear months or years after motor tics, although they can appear first.^[11]^[12] Complex tics may develop in people who experience more severe tics, such as "arm straightening, touching, tapping, jumping, hopping and twirling".^[10] In contrasting disorders, such as the autism spectrum, there are different movements such as self-stimulation and stereotypies. These stereotyped movements typically have an earlier age of onset; are more symmetrical, rhythmical and bilateral; and involve the extremities (for example, flapping the hands).^[33]

The severity of symptoms varies widely among people with Tourette's, and many cases may be undetected.^[1]^[4]^[8]^[11] Most cases are mild and almost unnoticeable.^[34]^[35] Adults with TS presenting in clinics are atypical.^[1]

Co-occurring conditions

Children with milder symptoms are unlikely to be referred to specialty clinics, so studies of Tourette's have an inherent bias towards more severe cases.^[39] When symptoms are severe enough to warrant referral to clinics, ADHD and OCD are often also found.^[1] In specialty clinics, 30% of individuals with TS also have mood or anxiety disorders, or disruptive behaviors.^[10]^[40] In the absence of ADHD, tic disorders do not appear to be associated with disruptive behavior or functional impairment,^[41] while impairment in school, family, or peer relations is greater in individuals who have more comorbid conditions.^[17]^[42] When ADHD is present along with tics, the occurrence of conduct disorder and oppositional defiant disorder increases.^[10] Aggressive behaviors and angry outbursts in people with TS are not well understood; they are not associated with severe tics, but are associated with the presence of ADHD.^[43]

Compulsions that resemble tics are present in some individuals with OCD; "tic-related OCD" is hypothesized to be a subgroup of OCD, distinguished from non-tic related OCD by the type and nature of obsessions and compulsions.^[44] Compared to the more typical compulsions of OCD without tics that relate to contamination, tic-related OCD presents with more "counting, aggressive thoughts, symmetry and touching" compulsions.^[10] Compulsions associated with OCD without tics are usually related to obsessions and anxiety, while those in tic-related OCD are more likely to be a response to a premonitory urge.^[10]

Among individuals with TS studied in clinics, between 2.9% and 20% have been reported to have autism spectrum disorders,^[45] but one study indicates that a high association of autism and TS may be partly due to difficulties distinguishing between tics and tic-like behaviors or OCD symptoms seen in people with autism.^[46]

Not all people with Tourette's have ADHD or OCD or other comorbid conditions, although in clinical populations, a high percentage of those under care do have ADHD.^[28]^[47] Over time, 85% of people with Tourette's will develop a co-occurring condition, according to Dale (2017).^[10] Denckla (2006) reported that a review of patient records revealed that about 40% of people with Tourette's have "TS-only" or "pure TS".^[48]^[49] Dure and DeWolfe (2006) reported that 57% of individuals presenting with tic disorders had uncomplicated tics, while 43% had tics plus comorbid conditions.^[17] In a 2017 literature review, Sukhodolsky, et al. stated that 37% of individuals in clinical samples have pure TS.^[47] Children and adolescents with pure TS are not significantly different from their peers without TS on ratings of aggressive behaviors or conduct disorders, or measures of social adaptation.^[4] Similarly, adults with pure TS do not appear to have the social difficulties present in those with TS plus ADHD.^[4]

Neuropsychological function

There are no major impairments in neuropsychological function among people with Tourette's, but conditions that occur along with tics can cause variation in neurocognitive function. A better understanding of comorbid conditions is needed to untangle any neuropsychological differences between TS-only individuals and those with comorbid conditions.^[42]

Only slight impairments are found in intellectual ability, attentional ability, and nonverbal memory—but ADHD, other comorbid disorders, or tic severity could account for these differences. In contrast with earlier findings, visual motor integration and visuoconstructive skills are not found to be impaired, while comorbid conditions may have a small effect on motor skills. Comorbid conditions and severity of tics may account for variable results in verbal fluency, which can be slightly impaired. There might be slight impairment in social cognition, but not in the ability to plan or make decisions.^[42] Children with TS-only do not show cognitive deficits, they are faster than average for their age on timed tests of motor coordination, and constant tic suppression may lead to an advantage in switching between tasks because of increased inhibitory control.^[4]^[49]

Causes

The exact cause of Tourette's is unknown, but it is well established that both genetic and environmental factors are involved.^[7]^[10]^[50] Genetic epidemiology studies have shown that the overwhelming majority of cases of Tourette's are inherited, but the exact mode of inheritance is not known and no gene has been identified.^[51]^[52]^[53]

A person with Tourette's has about a 50% chance of passing the gene or genes to his or her child. Tourette's is a condition of variable expression and incomplete penetrance;^[7]^[54] thus, not everyone who inherits the genetic vulnerability will show symptoms. Only a minority of the children who inherit the genetic vulnerability have symptoms severe enough to require medical attention.^[55] Gender appears to affect the expression of the genetic vulnerability: males are more likely than females to express tics.^[23]

Non-genetic, environmental, or psychosocial factors—while not causing Tourette's—can affect the severity of TS in vulnerable individuals.^[4]^[30]^[50] Autoimmune processes may affect the onset of tics or exacerbate them. Both OCD and tic disorders may arise in a subset of children as a result of a post-streptococcal autoimmune process.^[34] Its potential effect is described by the hypothesis called PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections), which proposes five criteria for diagnosis in children.^[56]^[57] The controversial hypothesis includes the newer PANS (pediatric acute-onset neuropsychiatric syndrome) hypothesis, and both are the focus of clinical and laboratory research, but remain unproven. There is also a broader hypothesis that links immune system abnormalities and immune dysregulation with TS.^[10]^[22]^[34]

There is evidence that pre-natal and peri-natal events increase the risk of tic disorders or comorbid OCD in those with a genetic vulnerability. These include complications of pregnancy or delivery; stress or severe nausea during pregnancy; smoking, consuming caffeine or drinking alcohol during pregnancy; paternal age; and forceps delivery. Babies who are born premature with low birthweight, or who have low Apgar scores, are also at increased risk; in premature twins, the lower birthweight twin is more likely to develop TS.^[4]

Some forms of OCD may be genetically linked to Tourette's,^[28] although the genetic factors in OCD with and without tics may differ.^[7] The genetic relationship of ADHD to Tourette syndrome, however, has not been fully established.^[49]

Mechanism

The exact mechanism affecting the inherited vulnerability to Tourette's is not well established.^[7] Tics are believed to result from dysfunction in cortical and subcortical brain regions: the thalamus, basal ganglia and frontal cortex.^[58] Neuroanatomic models suggest failures in circuits connecting the brain's cortex and subcortex;^[30] imaging techniques implicate the frontal cortex and basal ganglia.^[52] Neuroimaging and postmortem brain studies, animal and genetic studies^[42]^[59] in the 2010s made progress towards better understanding the neurobiological mechanisms leading to Tourette's.^[42] These studies support the basal ganglia model, in which neurons in the striatum are activated and inhibit outputs from the basal ganglia.^[43]

Cortico-striato-thalamo-cortical (CSTC) circuits, or neural pathways, provide inputs to the basal ganglia from the brain's cortex. These CSTC circuits connect the basal ganglia with other areas of the brain to communicate information that regulates planning and control of movements, behavior, decision-making, and learning.^[42] Behavior is regulated by cross-connections that "allow the integration of information" from these circuits.^[42] Involuntary movements may result from impairments in these CSTC circuits,^[42] including the sensorimotor, limbic, language and decision making pathways; abnormalities in these circuits may be responsible for tics and premonitory urges.^[60]

The caudate nuclei may be smaller in those with tics compared to subjects without tics, supporting the hypothesis of pathology in CSTC circuits in Tourette's.^[42] The ability to suppress tics depends on brain circuits that "regulate response inhibition and cognitive control of motor behavior".^[59] Children with TS are found to have a larger prefrontal cortex, which may be the result of an adaptation to help regulate tics.^[59] It is likely that tics decrease with maturity as the capacity of the frontal cortex increases.^[59] Cortico-basal ganglia (CBG) circuits may also be impaired, contributing to "sensory, limbic and executive" features.^[10] The release of dopamine in the basal ganglia is higher in people with Tourette's, implicating biochemical changes from "overactive and dysregulated dopaminergic transmissions".^[50]

In the pathophysiology of TS, the role of histamine and the H3 receptor came into focus after 2010^[10]^[61] as integral in the modulation of striatal circuitry.^[62]^[63] A reduced level of histamine in the H3 receptor may result in an increase in other neurotransmitters, causing tics.^[64] Postmortem studies have also implicated "dysregulation of neuroinflammatory processes".^[7]

Diagnosis

According to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), Tourette's may be diagnosed when, over a period of one year, a person exhibits both multiple motor tics and one or more vocal tics; the motor and vocal tics need not be concurrent. The onset must have occurred before the age of 18 and cannot be attributed to the effects of another condition or substance (such as cocaine).^[6] Hence, other medical conditions that include tics or tic-like movements—such as autism or other causes of tics—must be ruled out before conferring a Tourette's diagnosis. The DSM has recognized since 2000 that individuals who meet all the criteria for Tourette's may not have distress or impairment.^[65]^[66]^[67] Diagnosis does not require the presence of a comorbid condition, such as ADHD or OCD.^[22]

There are no specific medical or screening tests that can be used in diagnosis;^[28] the diagnosis is made based on observation of the individual's symptoms and family history,^[22] and after ruling out secondary causes of tic disorders.^[68] Most cases are diagnosed merely by observing a history of tics.^[30] In individuals with a typical onset and a family history of tics or OCD, a basic physical and neurological examination may be sufficient.^[69] If another condition might better explain the tics, tests may be done; for example, if there is diagnostic confusion between tics and seizure activity, an EEG may be ordered. An MRI can rule out brain abnormalities,^[70] but such brain imaging studies are not usually warranted.^[70] Measuring TSH levels in blood can rule out hypothyroidism, which can be a cause of tics. In teenagers and adults presenting with a sudden onset of tics and other behavioral symptoms, a urine drug screen for cocaine and stimulants might be necessary. If there is a family history of liver disease, serum copper and ceruloplasmin levels can rule out Wilson's disease.^[69]

Tourette's may be misdiagnosed because of the wide expression of severity, ranging from mild (in the majority of cases) or moderate, to severe (the rare but more widely recognized and publicized cases).^[31] About 20% of people with Tourette syndrome do not recognize that they have tics.^[30] Tics that appear early in the course of TS are often confused with other conditions, such as allergies, asthma, and vision problems. Pediatricians, allergists and ophthalmologists are typically the first to identify a child as having tics.^[8] Coughing, blinking, and tics that mimic unrelated conditions such as asthma are commonly misdiagnosed.^[22] In the UK, there is an average delay of three years between symptom onset and diagnosis.^[4] Tics that may appear to mimic those of Tourette's—but are associated with disorders other than Tourette's—are known as tourettism.^[71] These conditions, including dystonias, choreas, and other genetic conditions, should be ruled out in the differential diagnosis for Tourette syndrome.^[69]^[71] Most of these conditions are rarer than tic disorders, and a thorough history and examination may be enough to rule them out without medical or screening tests.^[30]

Screening

Main screening and assessment tools^[72]^[73]

Yale Global Tic Severity Scale (YGTSS), recommended in international guidelines to assess "frequency, intensity, complexity, distribution, interference and impairment" of or due to tics

Tourette Syndrome Clinical Global Impression (TS-CGI) and Shapiro TS Severity Scale (STSS), for a briefer assessment of tics than YGTSS

Tourette's Disorder Scale (TODS), to assess tics and comorbidities

Premonitory Urge for Tics Scale (PUTS), for individuals over age ten

Motor tic, Obsessions and compulsions, Vocal tic Evaluation Survey (MOVES), to evaluate complex tics and other behaviors

Autism—Tics, AD/HD, and other Comorbities (A—TAC), to screen for other conditions

Although not all those with Tourette's have comorbid conditions, most presenting for clinical care exhibit symptoms of other conditions along with their motor and phonic tics.^[49] Learning disabilities and sleep disorders may be present;^[22] complications may include depression, social discomfort, self-injury,^[69] anxiety, personality disorders, oppositional defiant disorder, and conduct disorders.^[74] A higher rate of migraines than the general population and sleep disturbances are reported.^[75] Disruptive behaviors, impaired functioning, or cognitive impairment in individuals with comorbid Tourette's and ADHD may be accounted for by the comorbid ADHD, highlighting the importance of identifying comorbid conditions.^[10]^[22]^[28]^[76] Disruption from tics is commonly overshadowed by comorbid conditions that present greater interference to the child.^[3]^[30]

Because comorbid conditions such as OCD and ADHD can be more impairing than tics, and cause greater impact on overall functioning, these conditions are included in an evaluation of people presenting with tics. "It is critical to note that the comorbid conditions may determine functional status more strongly than the tic disorder", according to Samuel Zinner.^[30] A thorough evaluation for comorbidity is called for when symptoms and impairment warrant.^[69]^[77] The initial assessment of a person referred for a tic disorder includes a family history of tics, ADHD, obsessive–compulsive symptoms, and other chronic medical, psychiatric and neurological conditions. Children and adolescents with TS who have learning difficulties are candidates for psychoeducational testing, particularly if the child also has ADHD.^[70]^[77]

Management

Practice guidelines for the treatment of tics were published by the American Academy of Neurology in 2019.^[78] The management of Tourette's is individualized and involves a collaboration between the clinician, patient and caregivers where applicable.^[78] Treatment is focused on identifying the most troubling or impairing symptoms and helping the individual manage them.^[22] When comorbid conditions are present, they are often a larger source of impairment than the tics themselves,^[70] and are often a priority in treatment.^[78]

There is no cure for Tourette's, and no medication effectively treats all cases of TS without significant adverse effects. Knowledge, education and understanding are uppermost in management plans for tic disorders.^[22] Symptom management may include behavioral, pharmacological and psychological therapies. While pharmacological intervention is reserved for more severe symptoms, other treatments, such as psychotherapy or cognitive behavioral therapy (CBT), may help to avoid or ameliorate depression and social isolation, and to improve family support. Because most cases are mild,^[22]^[79] psychobehavioral therapy, education, and reassurance is often sufficient. In particular, educating the patient and their family and surrounding community (such as friends, school, and church) is a key management strategy.^[80] Watchful waiting "is an acceptable approach" for those who are not functionally impaired.^[78] The decision to use behavioral or pharmacological treatment is "usually made after the educational and supportive interventions have been in place for a period of months, and it is clear that the tic symptoms are persistently severe and are themselves a source of impairment in terms of self-esteem, relationships with the family or peers, or school performance".^[73]

Behavioral

Behavioral therapies using habit reversal training (HRT) and exposure and response prevention (ERP) are first-line interventions,^[81] and have been shown effective.^[7] Because tics are somewhat suppressible, when people with TS are aware of the premonitory urge that precedes a tic, they can be trained to develop a response to the urge that competes with the tic.^[10]^[81]

Comprehensive behavioral intervention for tics (CBIT) is based on HRT, the best researched behavioral therapy for tics.^[81] CBIT has been shown with a high level of confidence to be more likely to lead to a reduction in tics than other behavioral therapies or psychoeducation.^[3] CBIT has some limitations. Children under ten may not understand the treatment, and people with severe tics or ADHD may not be able to suppress their tics or sustain the focus required to benefit from behavioral treatments. There is a lack of therapists trained in behavioral interventions,^[82] and finding practitioners outside of specialty clinics can be difficult.^[7] Costs may also limit accessibility.^[81] TS experts debate whether the increased awareness of tics stemming from HRT/CBIT can lead to an increase in tics later in life.^[81]

When comorbid disruptive behaviors exist, anger control training and parent management training can be effective.^[4]^[83]^[84] CBT is a useful treatment when OCD is present.^[10] Relaxation techniques, such as exercise, yoga and meditation, may be useful in relieving the stress that may aggravate tics. Beyond HRT, the majority of behavioral interventions for Tourette's (such as relaxation training and biofeedback) have not been systematically evaluated and are not empirically supported.^[85]

Medication

Children with tics typically present to physicians when their tics are most severe, but because tics wax and wane, medication is not started immediately or changed often.^[30] Tics may subside with education, reassurance and a supportive environment.^[30] When medication is used, the goal is not to eliminate symptoms. Instead, the lowest dose that manages symptoms without adverse effects is used, because adverse effects may be more disturbing than the symptoms being treated with medication.^[30]

The classes of medication with proven efficacy in treating tics—typical and atypical neuroleptics—can have long-term and short-term adverse effects.^[70] Some antihypertensive agents are also used to treat tics; studies show variable efficacy but a lower side effect profile than the neuroleptics.^[86] There is moderate evidence that the antihypertensive clonidine, along with aripiprazole, haloperidol, risperidone, and tiapride, reduce tics more than placebo.^[3] Clonidine may produce sedation; aripiprazole and risperidone are likely to lead to weight gain and sedation or fatigue; haloperidol may increase prolactin levels; and tiapride may produce sleep disturbances and tiredness. Risperidone and haloperidol may also produce extrapyramidal symptoms.^[3]

Stimulants and other medications may be useful in treating ADHD when it co-occurs with tic disorders. Drugs from several other classes of medication can be used when stimulants fail.^[70] There is moderate evidence supporting that methylphenidate alone (or combined with clonidine) reduces tics more than placebo when ADHD is also present; desipramine also reduces tics but is rarely used following reports of sudden death in children.^[3] Atomoxetine, another treatment for ADHD, does not increase tics but may lead to weight loss and an increased heart rate.^[3]

Clomipramine, a tricyclic, and SSRIs—a class of antidepressants including fluoxetine, sertraline, and fluvoxamine—may be prescribed when a person also has OCD, and they can augment the effect of cognitive behavioral therapy.^[10]^[70]

Other

Complementary and alternative medicine approaches, such as dietary modification, neurofeedback and allergy testing and control have popular appeal, but they have no proven benefit in the management of Tourette syndrome.^[87]^[88] Despite this lack of evidence, anecdotal reports indicate that parents, caregivers and individuals with TS are using dietary approaches and nutritional supplements.^[18] There is low confidence that tics are reduced with tetrahydrocannabinol,^[3] and insufficient evidence for other cannabis-based medications in the treatment of Tourette's.^[78]

There is no good evidence supporting the use of acupuncture or transcranial magnetic stimulation; neither is there evidence supporting intravenous immunoglobulin, plasma exchange, or antibiotics for the treatment of PANDAS.^[4]

Deep brain stimulation (DBS) has become a valid option for individuals with severe symptoms that do not respond to conventional therapy and management.^[50] There is low-quality, limited evidence that DBS is safe, well tolerated, and yields symptom reduction ranging from no change to complete remission.^[50] Selecting candidates who may benefit from DBS is challenging, and "age, tic severity, and treatment refractoriness are important factors to consider", according to Fraint and Pal (2016).^[89] The ideal brain location to target has not been identified as of 2019.^[78]^[90]

Prognosis

Tourette syndrome is a spectrum disorder—its severity ranges over a spectrum from mild to severe.^[68] Many people with TS may not realize they have tics. Because tics are more commonly expressed in private, TS may go unrecognized or undetected,^[93] and casual observers might not notice tics. Symptoms typically subside as children pass through adolescence.^[50] In a group of ten children at the average age of highest tic severity (around ten or eleven), almost four will see complete remission by adulthood. Another four out of those ten will have minimal or mild tics in adulthood, but not complete remission. The remaining two will have moderate tics as adults, but only rarely will they have increased severity of tics.^[32]

Regardless of symptom severity, individuals with Tourette's have a normal life span. Symptoms may be lifelong and chronic for some, but the condition is not degenerative or life-threatening.^[94] Intelligence is normal in those with Tourette's, although there may be learning disabilities.^[22] The severity of tics early in life does not predict their severity in later life.^[22] There is no reliable means of predicting the course of symptoms for a particular individual,^[75] but the prognosis is generally favorable.^[75]

Tics may be at their highest severity at the time that they are diagnosed, and often improve with understanding of individuals with the condition from their families and friends. Studies report that almost eight out of ten children with Tourette's experience a reduction in the severity of their tics by adulthood,^[10]^[32] but adults may not be aware that they continue to tic. A study using videotape to record tics in adults found that nine out of ten adults still had tics, and half of the adults who considered themselves tic-free displayed evidence of mild tics.^[10]^[95]

Children with Tourette's may suffer socially if their tics are viewed as "bizarre". If a child has disabling tics, or tics that interfere with social or academic functioning, supportive psychotherapy or school accommodations can be helpful.^[68] In children with tics, the additional presence of ADHD is associated with functional impairment, disruptive behavior, and tic severity.^[74] Decreased measures in quality of life are observed in children whose tics are accompanied by ADHD, which can severely impact the child's well-being in all realms, and extend into adulthood.^[96] As ADHD symptoms improve with maturity, adults report less negative impact in their occupational lives than do children in their educational lives.^[96] Adults are more likely to report a reduced quality of life due to depression or anxiety.^[96]

A supportive family and environment generally give those with Tourette's the skills to manage the disorder.^[96]^[97]^[98] People with Tourette's may learn to camouflage socially inappropriate tics or to channel the energy of their tics into a functional endeavor. Outcomes in adulthood are associated more with the perceived significance of having severe tics as a child than with the actual severity of the tics. A person who was misunderstood, punished or teased at home or at school is likely to fare worse than a child who enjoyed an understanding environment.^[8]

Epidemiology

Tourette syndrome is a common but underdiagnosed condition found among all social, racial and ethnic groups that has been reported in all parts of the world.^[4]^[22]^[28]^[99] It is three to four times more frequent in males than in females.^[47] Tics tend to remit or subside with maturity; thus, a diagnosis may no longer be warranted for many adults, and observed prevalence rates are higher among children than adults.^[31] Up to 1% of the overall population experiences tic disorders, including chronic tics and transient tics of childhood.^[41] Chronic tics affect 5% of children and transient tics affect up to 20%.^[47]^[84]

Most individuals with tics do not seek a diagnosis, so epidemiological studies of TS "reflect a strong ascertainment bias" towards those with co-occurring conditions.^[52] The reported prevalence of TS varies "according to the source, age, and sex of the sample; the ascertainment procedures; and diagnostic system",^[28] with a range reported between 0.15% and 3.0% for children and adolescents.^[47] Sukhodolsky, et al. wrote in 2017 that the best estimate of TS prevalence in children was 1.4%,^[47] and Stern stated in 2018 that the prevalence in children was 1%.^[1] Prevalence rates in special education populations are higher.^[34]

Fernandez, State and Pittenger wrote in 2018 that the rate of Tourette's in the general population is between 0.5 and 0.7%,^[7] and Robertson (2011) suggested 1%.^[34] A prevalence range of 0.1% to 1% yields an estimate of 53,000 to 530,000 school-age children with Tourette's in the United States, using 2000 census data.^[41] In the United Kingdom, a prevalence estimate of 0.1% in 2001 means that about 553,000 people aged five or older would have Tourette's.^[35]

Tourette syndrome was once thought to be rare: in 1972, the US National Institutes of Health (NIH) believed there were fewer than 100 cases in the United States,^[100] and a 1973 registry reported only 485 cases worldwide.^[101] However, numerous studies published since 2000 have consistently demonstrated that the prevalence is much higher.^[102] The discrepancy between current and prior prevalence estimates arises from several factors: the ascertainment bias caused by samples that were drawn from clinically referred cases; assessment methods that failed to detect milder cases; and the use of different diagnostic criteria and thresholds.^[102] There were few broad-based community studies published before 2000, and most older epidemiological studies were based only on individuals referred to tertiary care or specialty clinics.^[103] People with mild symptoms may not have sought treatment and physicians may have avoided an official diagnosis of TS in children due to concerns about stigmatization.^[93] Studies are vulnerable to further error because tics vary in intensity and expression, are often intermittent, and are not always recognized by clinicians, individuals with TS, family members, friends or teachers.^[30]^[104] Recognizing that tics may often be undiagnosed and hard to detect, newer studies use direct classroom observation and multiple informants (parents, teachers and trained observers), and therefore record more cases than older studies.^[79]^[105] As the diagnostic threshold and assessment methodology have moved towards recognition of milder cases, the estimated prevalence has increased.^[102]

History

The first presentation of Tourette syndrome is thought to be in the 15th-century book Malleus Maleficarum (Hammer of Witches), which describes a priest whose tics were "believed to be related to possession by the devil".^[106]^[107]

A French doctor, Jean Marc Gaspard Itard, reported the first case of Tourette syndrome in 1825,^[108] describing the Marquise de Dampierre, an important woman of nobility in her time.^[109] In 1884, Jean-Martin Charcot, an influential French physician, assigned his resident Georges Gilles de la Tourette, to study patients at the Salpêtrière Hospital, with the goal of defining a condition distinct from hysteria and chorea.^[110] In 1885, Gilles de la Tourette published an account in Study of a Nervous Affliction of nine people with "convulsive tic disorder", concluding that a new clinical category should be defined.^[111]^[112] The eponym was bestowed by Charcot after and on behalf of Gilles de la Tourette.^[23]

Following the 19th-century descriptions, a psychogenic view prevailed and little progress was made in explaining or treating tics until well into the 20th century.^[23] The possibility that movement disorders, including Tourette syndrome, might have an organic origin was raised when an encephalitis lethargica epidemic from 1918 to 1926 was linked to an increase in tic disorders.^[23]^[113]

During the 1960s and 1970s, as the beneficial effects of haloperidol (Haldol) on tics became known, the psychoanalytic approach to Tourette syndrome was questioned.^[114] The turning point came in 1965, when Arthur K. Shapiro—described as "the father of modern tic disorder research"^[115]—used haloperidol to treat a person with Tourette's, and published a paper criticizing the psychoanalytic approach.^[113] In 1975, The New York Times headlined an article with "Bizarre outbursts of Tourette's disease victims linked to chemical disorder in brain", and Shapiro said: "The bizarre symptoms of this illness are rivaled only by the bizarre treatments used to treat it."^[116]

During the 1990s, a more neutral view of Tourette's emerged, in which an inherited vulnerability was seen to interact with environmental factors.^[23]^[30] In 2000, the American Psychiatric Association revised its diagnostic criteria so that symptoms of tic disorders were no longer required to cause distress or impair functioning,^[65] recognizing that clinicians often see people who meet all the other criteria for Tourette's, but do not experience distress or impairment.^[66]^[67]

Research since 1999 has advanced knowledge of Tourette's in the areas of genetics, neuroimaging, neurophysiology, and neuropathology, but questions remain about how best to classify it and how closely it is related to other movement or psychiatric disorders.^[4]^[7]^[10]^[11] Good epidemiologic data are still lacking, and available treatments are not without risk and are not always well tolerated.^[117]

Society and culture

Not everyone with Tourette's wants treatment or a "cure", especially if that means they may "lose" something else in the process.^[118]^[119] The researchers Leckman and Cohen believe that there may be latent advantages associated with an individual's genetic vulnerability to developing Tourette syndrome that may have adaptive value, such as heightened awareness and increased attention to detail and surroundings.^[120]

Accomplished musicians, athletes, public speakers and professionals from all walks of life are found among people with Tourette's.^[121] The athlete Tim Howard, described by the Chicago Tribune as the "rarest of creatures—an American soccer hero",^[122] and by the Tourette Syndrome Association as the "most notable individual with Tourette Syndrome around the world",^[123] says that his neurological makeup gave him an enhanced perception and an acute focus that contributed to his success on the field.^[92]

Samuel Johnson is a historical figure who likely had Tourette syndrome, as evidenced by the writings of his friend James Boswell.^[124]^[125] Johnson wrote A Dictionary of the English Language in 1747, and was a prolific writer, poet, and critic. There is little support for speculation that Mozart had Tourette's:^[126] the potentially coprolalic aspect of vocal tics is not transferred to writing, so Mozart's scatological writings are not relevant; the composer's available medical history is not thorough; the side effects of other conditions may be misinterpreted; and "the evidence of motor tics in Mozart's life is doubtful".^[127]

Likely portrayals of TS or tic disorders in fiction predating Gilles de la Tourette's work are "Mr. Pancks" in Charles Dickens's Little Dorrit and "Nikolai Levin" in Leo Tolstoy's Anna Karenina.^[128] The entertainment industry has been criticized for depicting those with Tourette syndrome as social misfits whose only tic is coprolalia, which has furthered the public's misunderstanding and stigmatization of those with Tourette's.^[129]^[130]^[131] The coprolalic symptoms of Tourette's are also fodder for radio and television talk shows in the US^[132] and for the British media.^[133] High-profile media coverage focuses on treatments that do not have established safety or efficacy, such as deep brain stimulation, and alternative therapies involving unstudied efficacy and side effects are pursued by many parents.^[134]

Research directions

Modeled after genetic breakthroughs seen with large-scale efforts in other neurodevelopmental disorders, three groups are collaborating in research of the genetics of Tourette's:

The Tourette Syndrome Association International Consortium for Genetics (TSAICG)
Tourette International Collaborative Genetics Study (TIC Genetics)
European Multicentre Tics in Children Studies (EMTICS)

Compared to the success in genetic research seen in other conditions (autism, schizophrenia and bipolar disorder), the funded efforts in the United States are lagging.^[7]^[135]

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^ Zinner SH (August 2004). "Tourette syndrome—much more than tics" (PDF). Contemporary Pediatrics. 21 (8): 22–49. Archived from the original (PDF) on September 30, 2007. Retrieved May 20, 2019.
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^ Baxter, Kevin (October 5, 2019). "Column: Tim Howard, whose career is likely to end Sunday, will retire as the best U.S. goalkeeper ever". Los Angeles Times. Retrieved December 28, 2019.
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^ Novotny M, Valis M, Klimova B (2018). "Tourette syndrome: a mini-review". Front Neurol (Review). 9: 139. doi:10.3389/fneur.2018.00139. PMC 5854651. PMID 29593638.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^ Pappert EJ, Goetz CG, Louis ED, Blasucci L, Leurgans S (October 2003). "Objective assessments of longitudinal outcome in Gilles de la Tourette's syndrome". Neurology. 61 (7): 936–40. doi:10.1212/01.wnl.0000086370.10186.7c. PMID 14557563.
^ ^a ^b ^c ^d Evans J, Seri S, Cavanna AE (September 2016). "The effects of Gilles de la Tourette syndrome and other chronic tic disorders on quality of life across the lifespan: a systematic review". Eur Child Adolesc Psychiatry (Review). 25 (9): 939–48. doi:10.1007/s00787-016-0823-8. PMC 4990617. PMID 26880181.
^ Leckman & Cohen (1999), p. 37. "For example, individuals who were misunderstood and punished at home and at school for their tics or who were teased mercilessly by peers and stigmatized by their communities will fare worse than a child whose interpersonal environment was more understanding and supportive."
^ Cohen DJ, Leckman JF, Pauls D (1997). "Neuropsychiatric disorders of childhood: Tourette's syndrome as a model". Acta Paediatr Suppl. 422. Scandinavian University Press: 106–11. doi:10.1111/j.1651-2227.1997.tb18357.x. PMID 9298805. The individuals with TS who do the best, we believe, are: those who have been able to feel relatively good about themselves and remain close to their families; those who have the capacity for humor and for friendship; those who are less burdened by troubles with attention and behavior, particularly aggression; and those who have not had development derailed by medication.
^ Gulati, S (206). "Tics and Tourette Syndrome - Key Clinical Perspectives: Roger Freeman (ed)". Indian J Pediatr. 83: 1361. doi:10.1007/s12098-016-2176-1. Tic disorder is a common neurodevelopmental disorder of childhood. It is one of the commonest condition encountered by a pediatrician in office practice, especially in developed countries.
^ Cohen, Jankovic & Goetz (2001), p. xviii.
^ Abuzzahab FE, Anderson FO (June 1973). "Gilles de la Tourette's syndrome; international registry". Minn Med. 56 (6): 492–96. PMID 4514275.
^ ^a ^b ^c Scahill L. "Epidemiology of tic disorders" (PDF). Medical letter: 2004 retrospective summary of TS literature. Tourette Syndrome Association. Archived from the original (PDF) on December 25, 2010. Retrieved June 11, 2007.
^ Bloch, State, Pittenger 2011. See also Zohar AH, Apter A, King RA, et al (1999). "Epidemiological studies" in Leckman & Cohen (1999), pp. 177–92.
^ Hawley JS (June 23, 2008). "Tourette syndrome". eMedicine. Archived from the original on August 4, 2009. Retrieved August 10, 2009.
^ Leckman JF (November 2002). "Tourette's syndrome". Lancet (Review). 360 (9345): 1577–86. doi:10.1016/S0140-6736(02)11526-1. PMID 12443611.
^ Teive HA, Chien HF, Munhoz RP, Barbosa ER (December 2008). "Charcot's contribution to the study of Tourette's syndrome". Arq Neuropsiquiatr (Historical biography). 66 (4): 918–21. doi:10.1590/s0004-282x2008000600035. PMID 19099145. As reported in Finger S (1994). "Some movement disorders." Origins of neuroscience: the history of explorations into brain function. New York: Oxford University Press. pp. 220–39.
^ Germiniani FM, Miranda AP, Ferenczy P, Munhoz RP, Teive HA (July 2012). "Tourette's syndrome: from demonic possession and psychoanalysis to the discovery of gene". Arq Neuropsiquiatr (Historical review). 70 (7): 547–49. doi:10.1590/s0004-282x2012000700014. PMID 22836463.
^ Itard J (1825). "Mémoire sur quelques functions involontaires des appareils de la locomotion, de la préhension et de la voix". Arch Gen Med. 8: 385–407. As cited in Newman S (2006). "Study of several involuntary functions of the apparatus of movement, gripping, and voice by Jean-Marc Gaspard Itard (1825)" (PDF). History of Psychiatry. 17 (3): 333–39. doi:10.1177/0957154X06067668. PMID 17214432.
^ "What is Tourette syndrome?". Tourette Syndrome Association. Archived from the original on January 14, 2012. Retrieved January 14, 2012.
^ Rickards H, Cavanna AE (2009). "Gilles de la Tourette: the man behind the syndrome". J Psychosom Res. 67 (6): 469–74. doi:10.1016/j.jpsychores.2009.07.019. PMID 19913650.
^ Gilles de la Tourette G, Goetz CG, Llawans HL (1982). "Étude sur une affection nerveuse caractérisée par de l'incoordination motrice accompagnée d'echolalie et de coprolalie". Advances in Neurology: Gilles de la Tourette Syndrome. 35: 1–16.. As discussed at Black KJ (March 30, 2007). "Tourette syndrome and other tic disorders". eMedicine. Archived from the original on August 22, 2009. Retrieved August 10, 2009.
^ Robertson MM, Reinstein DZ (1991). "Convulsive tic disorder: Georges Gilles de la Tourette, Guinon and Grasset on the phenomenology and psychopathology of Gilles de la Tourette syndrome". Behavioural Neurology. 4 (1): 29–56. doi:10.1155/1991/505791. PMID 24487352.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^ ^a ^b Blue T (2002). Tourette syndrome. Essortment, Pagewise Inc. Retrieved on August 10, 2009.
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^ Gadow KD, Sverd J (2006). "Attention deficit hyperactivity disorder, chronic tic disorder, and methylphenidate". Adv Neurol (Review). 99: 197–207. PMID 16536367.
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^ Walkup, Mink & Hollenback (2006), pp. xvi–xviii.
^ Sacks O (1985). The Man Who Mistook His Wife for a Hat. Harper and Row, New York. pp. 92–100. ISBN 0-684-85394-9
^ Leckman & Cohen (1999), p. 408.
^ Leckman & Cohen (1999), pp. 18–19, 148–51, 408.
^ Portraits of adults with TS. Tourette Syndrome Association. Retrieved from July 16, 2011 archive.org version on December 21, 2011.
^ Keilman J (January 22, 2015). "Reviews: The Game of Our Lives by David Goldblatt, The Keeper by Tim Howard". Chicago Tribune. Archived from the original on April 2, 2015. Retrieved March 21, 2015.
^ Tim Howard receives first-ever Champion of Hope Award from the National Tourette Syndrome Association. Archived March 30, 2015, at the Wayback Machine Tourette Syndrome Association. October 14, 2014. Retrieved on March 21, 2015.
^ Samuel Johnson. Tourette Syndrome Association. Retrieved from April 7, 2005 archive.org version on December 30, 2011.
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^
Mozart:
- Kammer T (2007). "Mozart in the neurological department - who has the tic?" (PDF). Front Neurol Neurosci (Historical biography). Frontiers of Neurology and Neuroscience. 22: 184–92. doi:10.1159/000102880. ISBN 978-3-8055-8265-0. PMID 17495512. Archived from the original (PDF) on February 7, 2012.
- Ashoori A, Jankovic J (November 2007). "Mozart's movements and behaviour: a case of Tourette's syndrome?". J. Neurol. Neurosurg. Psychiatry (Historical biography). 78 (11): 1171–75. doi:10.1136/jnnp.2007.114520. PMC 2117611. PMID 17940168.
- Sacks O (1992). "Tourette's syndrome and creativity". BMJ (Editorial comment). 305 (6868): 1515–16. doi:10.1136/bmj.305.6868.1515. PMC 1884721. PMID 1286364.
^ Voss H (October 2012). "The representation of movement disorders in fictional literature". J. Neurol. Neurosurg. Psychiatry (Review). 83 (10): 994–99. doi:10.1136/jnnp-2012-302716. PMID 22752692.
^ Calder-Sprackman S, Sutherland S, Doja A (March 2014). "Tourette syndrome in film and television" (PDF). The Canadian Journal of Neurological Sciences. 41 (2): 226–32. doi:10.1017/S0317167100016620. PMID 24534035.
^ Lim Fat MJ, Sell E, Barrowman N, Doja A (2012). "Public perception of Tourette syndrome on YouTube". Journal of Child Neurology. 27 (8): 1011–16. CiteSeerX 10.1.1.997.9069. doi:10.1177/0883073811432294. PMID 22821136.
^ Holtgren B (January 11, 2006). "Truth about Tourette's not what you think". Cincinnati Enquirer. As medical problems go, Tourette's is, except in the most severe cases, about the most minor imaginable thing to have. ... the freak-show image, unfortunately, still prevails overwhelmingly. The blame for the warped perceptions lies overwhelmingly with the video media—the Internet, movies and TV. If you search for 'Tourette' on Google or YouTube, you'll get a gazillion hits that almost invariably show the most outrageously extreme examples of motor and vocal tics. Television, with notable exceptions such as Oprah, has sensationalized Tourette's so badly, for so long, that it seems beyond hope that most people will ever know the more prosaic truth.
^
US media:
- "Oprah and Dr. Laura" (Press release). Tourette Syndrome Association. May 31, 2001. Archived from the original on October 6, 2001. Retrieved December 21, 2011.
- "Letter of response to Dr. Phil" (Press release). Tourette Syndrome Association. Archived from the original on August 31, 2008. Retrieved December 21, 2011.
- "Letter of response to Garrison Keillor radio show" (Press release). Tourette Syndrome Association. Archived from the original on February 7, 2009. Retrieved December 21, 2011.
^
UK media:
- Guldberg H (May 26, 2006). "Stop celebrating Tourette's". Spiked. Archived from the original on March 14, 2017. Retrieved December 26, 2006.
^ Swerdlow NR (September 2005). "Tourette syndrome: current controversies and the battlefield landscape". Curr Neurol Neurosci Rep. 5 (5): 329–31. doi:10.1007/s11910-005-0054-8. PMID 16131414.
^ Georgitsi M, Willsey AJ, Mathews CA, State M, Scharf JM, Paschou P (2016). "The genetic etiology of Tourette syndrome: large-scale collaborative efforts on the precipice of discovery". Front Neurosci. 10: 351. doi:10.3389/fnins.2016.00351. PMC 4971013. PMID 27536211.{{cite journal}}: CS1 maint: unflagged free DOI (link)

Book sources

Cohen DJ, Jankovic J, Goetz CG, eds (2001). Advances in Neurology, Tourette Syndrome. 85. Philadelphia, PA: Lippincott, Williams & Wilkins. ISBN 0-7817-2405-8
Leckman JF, Cohen DJ (1999). Tourette's Syndrome—Tics, Obsessions, Compulsions: Developmental Psychopathology and Clinical Care. John Wiley & Sons, Inc., New York. ISBN 0-471-16037-7
Martino D, Leckman JF, eds (2013). Tourette syndrome. Oxford University Press. ISBN 978-0199796267.
- Bloch MH (2013). "Clinical course and adult outcome in Tourette syndrome". In Martino D, Leckman JF, eds. Tourette syndrome. Oxford University Press. pp. 107–20.
Sukhodolsky DG, Gladstone TR, Kaushal SA, Piasecka JB, Leckman JF (2017). "Tics and Tourette Syndrome". In Matson JL, ed. Handbook of Childhood Psychopathology and Developmental Disabilities Treatment. Autism and Child Psychopathology Series. Springer. pp. 241–56. doi:10.1007/978-3-319-71210-9_14.
Walkup JT, Mink JW, Hollenback PJ, eds (2006). Advances in Neurology, Tourette Syndrome. 99. Philadelphia, PA: Lippincott, Williams & Wilkins. ISBN 0-7817-9970-8.

External links

Template:Clips of tics

Template:Curlie

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 The exact [[pathophysiology|mechanism]] affecting the inherited vulnerability to Tourette's is not well established.<ref name= Fernandez/> Tics are believed to result from dysfunction in [[Cerebral cortex|cortical]] and subcortical brain regions: the [[Human thalamus|thalamus]], [[basal ganglia]] and [[frontal lobe|frontal cortex]].<ref name=AN2intro>Walkup, Mink & Hollenback (2006), p. xv.</ref> [[Neuroanatomic]] models suggest failures in circuits connecting the brain's cortex and subcortex;<ref name=Zinner /> [[Neuroimaging|imaging techniques]] implicate the frontal cortex and basal ganglia.<ref name=Bloch2011 /> Neuroimaging and [[Postmortem studies|postmortem brain studies]], [[animal studies|animal]] and [[Genetic analysis|genetic studies]]<ref name= Morand/><ref name= Sukhodolsky246>Sukhodolsky, et al (2017), p. 246.</ref> in the 2010s made progress towards better understanding the neurobiological mechanisms leading to Tourette's.<ref name= Morand/> These studies support the basal ganglia model, in which neurons in the [[striatum]] are activated and inhibit outputs from the basal ganglia.<ref name= Sukhodolsky245/>
-[[Cortico-basal ganglia-thalamo-cortical loop|Cortico-striato-thalamo-cortical]] (CSTC) [[Neural circuit#Circuitry|circuits]] provide inputs to the basal ganglia from the brain's cortex. There are five CSTC circuits that communicate information for "planning, movement execution and inhibition, motivational regulation of behavior, error detection, and associative learning".<ref name= Morand/> Behavior is regulated by cross-connections that "allow the integration of information" from these CSTC circuits.<ref name= Morand/> Involuntary movements may result from impairments in these CSTC circuits.<ref name= Morand/> The [[caudate nuclei]] may be smaller in those with tics compared to subjects without tics, supporting the hypothesis of pathology in CSTC circuits in Tourette's.<ref name= Morand/> The ability to suppress tics depends on brain circuits that "regulate response inhibition and cognitive control of motor behavior".<ref name= Sukhodolsky246/>
+[[Cortico-basal ganglia-thalamo-cortical loop|Cortico-striato-thalamo-cortical]] (CSTC) [[Neural circuit#Circuitry|circuits]], or neural pathways, provide inputs to the basal ganglia from the brain's cortex. These CSTC circuits connect the basal ganglia with other areas of the brain to communicate information that regulates planning and control of movements, behavior, decision-making, and learning.<ref name= Morand/> Behavior is regulated by cross-connections that "allow the integration of information" from these circuits.<ref name= Morand/> Involuntary movements may result from impairments in these CSTC circuits,<ref name= Morand/> including the [[sensorimotor cortex|sensorimotor]], [[limbic system|limbic]],  [[Cerebral_cortex#Association_areas|language]] and [[Orbitofrontal cortex|decision making]] pathways; abnormalities in these circuits may be responsible for tics and premonitory urges.<ref>{{cite journal |vauthors=Cox JH, Seri S, Cavanna AE |title=Sensory aspects of Tourette syndrome |journal=Neurosci Biobehav Rev |volume=88 |issue= |pages=170–76 |date=May 2018 |pmid=29559228 |doi=10.1016/j.neubiorev.2018.03.016 |type= Review}}</ref>
-Studies have found thinning of the [[sensorimotor cortex]] in those with Tourette's, with greater thinning related to higher tic severity.<ref name= Morand/> Children with TS are found to have a larger [[prefrontal cortex]], which may be the result of an adaptation to help regulate tics.<ref name= Sukhodolsky246/> It is likely that tics decrease with maturity as the capacity of the frontal cortex increases.<ref name= Sukhodolsky246/> Cortico-basal ganglia (CBG) circuits may also be impaired, contributing to "sensory, [[limbic]] and executive" features.<ref name= Dale2017/> The release of [[dopamine]] in the basal ganglia is higher in people with Tourette's, implicating biochemical changes from "overactive and dysregulated dopaminergic transmissions".<ref name= Baldermann/>
+The [[caudate nuclei]] may be smaller in those with tics compared to subjects without tics, supporting the hypothesis of pathology in CSTC circuits in Tourette's.<ref name= Morand/> The ability to suppress tics depends on brain circuits that "regulate response inhibition and cognitive control of motor behavior".<ref name= Sukhodolsky246/> Children with TS are found to have a larger [[prefrontal cortex]], which may be the result of an adaptation to help regulate tics.<ref name= Sukhodolsky246/> It is likely that tics decrease with maturity as the capacity of the frontal cortex increases.<ref name= Sukhodolsky246/> Cortico-basal ganglia (CBG) circuits may also be impaired, contributing to "sensory, [[limbic]] and executive" features.<ref name= Dale2017/> The release of [[dopamine]] in the basal ganglia is higher in people with Tourette's, implicating biochemical changes from "overactive and dysregulated dopaminergic transmissions".<ref name= Baldermann/>
 In the pathophysiology of TS, the role of [[histamine]] and the [[H3 receptor]] came into focus after 2010<ref name= Dale2017/><ref>{{cite journal |vauthors=Rapanelli M, Pittenger C |title=Histamine and histamine receptors in Tourette syndrome and other neuropsychiatric conditions |journal=Neuropharmacology |volume=106 |issue= |pages=85–90 |date=July 2016 |pmid=26282120 |doi=10.1016/j.neuropharm.2015.08.019| type= Review}}</ref> as integral in the modulation of striatal circuitry.<ref>{{cite journal |vauthors=Rapanelli M |title=The magnificent two: histamine and the H3 receptor as key modulators of striatal circuitry |journal=Prog. Neuropsychopharmacol. Biol. Psychiatry |volume=73 |issue= |pages=36–40 |date=February 2017 |pmid=27773554 |doi=10.1016/j.pnpbp.2016.10.002 |type= Review}}</ref><ref>{{cite journal |vauthors=Bolam JP, Ellender TJ |title=Histamine and the striatum |journal=Neuropharmacology |volume=106 |issue= |pages=74–84 |date=July 2016 |pmid=26275849 |pmc=4917894 |doi=10.1016/j.neuropharm.2015.08.013 |type= Review}}</ref> A reduced level of histamine in the H3 receptor may result in an increase in other neurotransmitters, causing tics.<ref>{{cite journal |vauthors=Sadek B, Saad A, Sadeq A, Jalal F, Stark H |title=Histamine H3 receptor as a potential target for cognitive symptoms in neuropsychiatric diseases |journal=Behav. Brain Res. |volume=312 |issue= |pages=415–30 |date=October 2016 |pmid=27363923 |doi=10.1016/j.bbr.2016.06.051 |type= Review}}</ref> Postmortem studies have also implicated "dysregulation of neuroinflammatory processes".<ref name= Fernandez/>

Classification	D ICD-10: F95.2 ICD-9-CM: 307.23 OMIM: 137580 MeSH: D005879 DiseasesDB: 5220
External resources	MedlinePlus: 000733 eMedicine: med/3107 neuro/664 GeneReviews: Tourette Disorder

v t e Tourette syndrome
Main	Causes and origins History Management Societal and cultural aspects
Terms	Coprolalia Copropraxia Echolalia Echophenomenon Echopraxia Palilalia Palipraxia PANDAS Premonitory urge Sensory phenomena Tic Tic disorder Tourettism
Assessment tools	Yale Global Tic Severity Scale Premonitory Urge for Tics Scale Shapiro TS Severity Scale Tourette Syndrome Clinical Global Impression Tourette's Disorder Scale Autism—Tics, AD/HD, and other Comorbities Motor tic, Obsessions and compulsions, Vocal tic Evaluation Survey
People	Jean-Martin Charcot Donald J. Cohen Georges Gilles de la Tourette Tim Howard Jean Marc Gaspard Itard Samuel Johnson James F. Leckman Arthur K. Shapiro
Organizations	Tourette Association of America Tourette Canada Tourettes Action Yale Child Study Center
Media	75 Watts Front of the Class Hichki I Have Tourette's but Tourette's Doesn't Have Me John's Not Mad Las Estrellas "Le Petit Tourette" Maze Motherless Brooklyn Quit It The Secret Life of Lele Pons The Tic Code Tic Talk: Living with Tourette Syndrome