Characteristics of Tics

Tics are abrupt, recurrent, and stereotyped but nonrhythmic movements. They can affect any body part, can be simple or complex, and manifest with motor or vocal actions. Examples of simple motor tics are eye blinking, nose twitching, eye rolling, and head nodding, and simple verbal tics include sniffing, throat clearing, or coughing. Examples of complex motor tics are jumping, touching, or twirling, and complex verbal tics include barking or uttering a string of words. Many patients experience a premonitory sensation before a tic, which can be localized or generalized. Characteristically, tics increase with stress and anxiety, but also with relaxation, and can be suppressed for a period of time by concentration. However, this typically leads to a buildup of tension, and there is often a rebound after the suppression of tics.

In Gilles de la Tourette syndrome, tics wax and wane over time, moving from one body part to another or changing characteristics. In addition to tics, other phenomena in this syndrome include echolalia (copying what other people say), echopraxia (copying what other people do), palilalia (repeating the last word or part of a sentence) and palipraxia (repeating the last action). Coprolalia (inappropriate, involuntary swearing) and copropraxia (inappropriate, involuntary obscene gestures) occur only in about 10% to 15% of patients with Gilles de la Tourette syndrome and are frequently disguised (e.g., by coughing or transformation of the word). The onset of motor tics in this syndrome is in childhood and occurs between ages 2 and 21 years; on average, onset occurs at ages 5 to 7 years. Verbal tics typically manifest a few years later, and coprolalia has a mean onset at age 15 years.

Differential Diagnosis of Tics

Other brief movement disorders may be difficult to distinguish from tics. Tics may particularly resemble dystonia, tremor, myoclonus, chorea, and akathisia (for a review of hyperkinetic movement disorders, see Chapters 33 to 37 Chapter 34 Chapter 35 Chapter 36 Chapter 37). They also need to be distinguished from mannerisms (bizarre execution of purposeful acts), stereotypies (purposeless, repetitive movements often over long periods of time, as in a learning disability), and other medical conditions, such as coughing or sniffing in upper respiratory tract infections or eye blinking in allergy or blepharospasm. Particularly difficult may be the distinction between tics and other features of Gilles de la Tourette syndrome, such as obsessive-compulsive behaviors (OCBs), attention deficit/hyperactivity disorder (ADHD), antisocial behaviors and movement disorders associated with treatment.⁴ These differentiations are particularly important for appropriate pharmacological management.

Epidemiology

Tics occur in 3% to 22% of children at some stage during their development⁵ but are transient in the majority. The more severe Gilles de la Tourette syndrome affects approximately 1% of chil dren, and prevalence rates range from 0.4 to 1.8%.^6–13 However, although the disorder typically starts in childhood, on average between the ages of 5 and 7 years,¹⁴,¹⁵ and typically increases until the age of 13 years, it often improves in adolescence so that by the age of 18 years, 50% of those affected are virtually free of tics.¹⁶ The prevalence rate is higher in special educational populations, such as those with learning difficulties¹⁷ or autism.¹⁸ About three to four times as many boys as girls are affected.¹⁴ Prevalence rates and clinical characteristics are broadly similar across countries.¹⁴

In rare cases, tic disorders with both motor tics and verbalizations begin in adulthood. Some of these patients have been described to have had compulsive tendencies in childhood or a family history of tics or OCB. In comparison with patients with Gilles de la Tourette syndrome that started in childhood, patients with adult-onset tic disorder more often had a potential trigger event, have more severe symptoms and greater social morbidity, and increased sensitivity and poorer response to neuroleptics.¹⁹

Diagnosis

Tics and Gilles de la Tourette syndrome are clinical diagnoses. In cases of classic Gilles de la Tourette syndrome, no diagnostic tests are required. However, atypical cases, such as those without waxing and waning over time, those with adult onset, and particularly those with abnormalities on neurological examination, should be further investigated, including measurements of copper and ceruloplasmin for Wilson’s disease, full blood count for acanthocytes, and magnetic resonance imaging of the brain. Neuroimaging has also provided insight in the pathophysiology of Gilles de la Tourette syndrome: reduced volumes and abnormal asymmetry as well as altered dopamine metabolism of the basal ganglia, particularly the caudate²⁰,²¹, and frontal lobe abnormalities,²² all of which implicate the frontal-striatal-thalamic-frontal circuitry.

Etiology

Tics can be symptomatic; for example, in neurodegenerative conditions, such as Huntington’s disease, they can be the first manifesting symptom. They can also represent a sequela of trauma or encephalitis, or they can represent extrapyramidal side effects of neuroleptic medication or cocaine abuse. However, the most common cause for chronic tic disorders is Gilles de la Tourette syndrome; this applies to adults, with childhood tics that have recurred or in whom previous tics may have been unnoticed or forgotten until an increase in tic severity brought them to medical attention.

Suggestions for the etiology of Gilles de la Tourette syndrome have included genetic influences, infections, and perinatal difficulties. There is a wealth of evidence pointing toward genetic causes, including family studies, which suggested an autosomal dominant inheritance pattern with variable expression and penetrance.^23–25 There is also growing evidence for bilineal transmission, with the father typically affected by childhood tics and the mother by symptoms of obsessive-compulsive disorder (OCD).^26–28 Genetic studies have led to the identification of several regions of interest on chromosomes 2, 4, 8, and 11^29–32 and, more recently regions of interest on the chromosomes 5, 10, 13,³³ 7,³⁴ and 18.³⁵ In addition, the DRD4 and MOA-A genes have been implicated,³⁴,³⁶ and linkage to chromosome 17 has been demonstrated.³⁷ However, despite many years of research by a number of groups worldwide, no single genetic cause has been found for Gilles de la Tourette syndrome. This suggests that other factors also play a role in the etiology of this disorder.

An increasingly popular hypothesis suggests that Gilles de la Tourette syndrome is the product of an interaction between a genetic vulnerability and environmental factors. Stressors at various times of the life cycle have been implicated, particularly perinatal injury, but also stressors during pregnancy, such as severe nausea, vomiting, and antiemetic medication, which may alter dopaminergic receptors.¹⁶,^38–41

Particularly intriguing has been the association of group A β-hemolytic streptococcal infections with a syndrome of sudden-onset neuropsychiatric disturbances, including OCD, tics, and other psychopathology in children. This syndrome has been termed pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS).⁴² More recently, laboratory evidence of streptococcal infection in patients with Gilles de la Tourette syndrome has been reported, including elevated antistreptolysin O titers and anti–basal ganglia antibodies in up to 25% of patients with Gilles de la Tourette syndrome.⁴³,⁴⁴ An autoimmune mechanism has therefore been suggested as a contributor to the development of tics in this syndrome.⁴⁴,⁴⁵ Although the majority of studies have supported this notion,^43–46 others have disputed this association,⁴⁷,⁴⁸ and whether anti–basal ganglia antibodies play a role in the development of Gilles de la Tourette syndrome currently remains a controversy.¹⁷

Although it seems clear that there is a strong genetic component in the etiology of Gilles de la Tourette syndrome and it seems that streptococcal infection causes the syndrome, it may be that individuals inherit a susceptibility to this syndrome and that environmental factors such as perinatal injury or an autoimmune response to streptococcal infections trigger the development of this syndrome in some individuals.

Psychopathology

Gilles de la Tourette syndrome is associated with increased rates of a number of comorbid psychiatric conditions (see Robertson, 2000⁴⁹ and 2003⁵⁰). Although some of these are likely to represent a manifestation of or be integral to Gilles de la Tourette syndrome, others may be the consequence of the social and emotional consequences of this disorder. An investigation of 3500 patients with Gilles de la Tourette syndrome worldwide demonstrated that across all ages, 88% of individuals had associated psychiatric comorbidity, and male patients were more likely to have comorbid disorders.¹⁴ Only those with comorbid disorders had more severe behavioral problems such as anger control problems and self-injurious behavior, as well as sleep difficulties and coprolalia. The presence of such behavioral problems should therefore alert the clinician to the possible presence of comorbidity, the management of which is often at least as important as tic reduction.

The spectrum of comorbid disorders includes OCD, other anxiety disorders, mood disorders, ADHD, and other behavior disorders, including self-injurious behavior.⁵¹ Although the exact relationship of these to Gilles de la Tourette syndrome is unclear, a strong association exists between Gilles de la Tourette syndrome and OCD and OCB, and a number of studies have suggested that these reflect the variable expression of a single disorder.²⁴,²⁶,²⁷,⁵⁰ OCD in patients with Gilles de la Tourette syndrome has, however, been found to differ in clinical manifestation from primary OCD, with predominant checking, counting, and symmetry obsessions and less frequent obsessions with contamination and violence.^52–57 The rate of ADHD is also increased in patients with Gilles de la Tourette syndrome, and although the relationship between Gilles de la Tourette syndrome and ADHD is less clear, it has been suggested that some types are related genetically to Gilles de la Tourette syndrome. Depending on whether or not the International Classification of Diseases and Health-Related Problems, 10th Revision, or DSM-IV-TR criteria are used, the prevalence of ADHD in youngsters is between 1% and 9%.⁵⁸ In patients with Gilles de la Tourette syndrome, the prevalence of ADHD is much greater and may be as high as 60%.¹⁴ This is not confined to chronic populations: Even in an epidemiological study conducted on members of the Israeli Defense Force, the prevalence of ADHD in Gilles de la Tourette syndrome was 8%, in comparison with 4% in the population without Gilles de la Tourette syndrome, a difference that was statistically significant.⁵⁹ Personality disorders in adulthood in patients with Gilles de la Tourette syndrome are likely to be related to comorbid ADHD in childhood rather than to the syndrome itself. Whether other psychiatric comorbid conditions such as conduct disorder, oppositional-defiant disorder, personality disorder, rage, and impulsivity are clearly more prevalent in patients with Gilles de la Tourette syndrome or their apparent prevalence is a result of referral bias in Gilles de la Tourette syndrome clinics is currently unknown. The multiple medications used for Gilles de la Tourette syndrome (see later discussion) may lead to increase. Anxiety and cognitive disorders, and anxiety may occur as a result of having Gilles de la Tourette syndrome and its social and personal consequences. The rate of depression, on the other hand, is clearly increased among patients with Gilles de la Tourette syndrome and is likely to be multifactorial in origin.^60–63

Prognosis

Clearly, for symptomatic tics in the context of another neurological disorder or as a drug effect, the prognosis is associated with the underlying disorder. The prognosis of individuals with Gilles de la Tourette syndrome varies widely; whereas those with mild tics without coprolalia or associated comorbidity mostly do not suffer impairment of social or personal function, those at the other end of the spectrum can be severely disabled. Children may be disadvantaged in school, particularly if comorbidity is present,⁶⁴,⁶⁵ but, as mentioned previously, tics often improve in adolescence.¹⁵,⁵⁷ When the affected individuals and their environments receive appropriate explanation of this disorder and understand it, most do not need regular follow-up. Adult-onset cases appear to have worse morbidity and worse response to treatment, but this is rare. Overall, health-related quality of life has been shown to be worse in patients with Gilles de la Tourette syndrome than in controls, although it is better than in patients with intractable epilepsy.³ Factors associated with poorer health-related quality of life in this study in a tertiary referral center were employment status, tic severity, obsessive-compulsive symptoms, anxiety, and depression.

Management

Many individuals with mild Gilles de la Tourette syndrome are not aware of their tics or do not find them bothersome and may never come to medical attention. For those who have come to medical attention, a diagnosis of their condition, explanation, and reassurance are often all that is required. When medication is considered in more severe cases, patient and physician should take into account the severity, frequency, and interference of tics; the presence and severity of comorbid conditions; the patient’s life style, requirements, expectations, and attitudes; and the long-term nature of pharmacological treatments, which may have reversible or irreversible side effects. Ideally, treatment should be multidisciplinary.