TS is a neurobiological condition characterized by vocal and motor tics that change over time and wax and wane in severity. TS is part of a spectrum of tic disorders, including transient tic disorder and chronic tic disorder ( Table 1 ). Diagnosis is based on history and observation, with no specific diagnostic tests available (Bagheri, Kergeshian & Burd, 1999; Kiessling, 2001). In reviewing family-genetic and epidemiological studies, some researchers suggest that there is little evidence to support the diagnostic distinction between, for example, chronic tics and TS (Peterson, Pine, Cohen & Brook, 2001).
Tics can be defined as "sudden, repetitive, stereotyped motor movements or phonic productions that involve discrete muscle groups" (Leckman, King, & Cohen, 1999, p. 24). In contrast to other movement disorders, such as chorea or dystonia, tics are exaggerations and repetitions of normal movements (Bagheri et al., 1999; Leckman, Peterson, King, Scahill, & Cohen, 2001). Primary tics such as TS have no identifiable cause or may be genetic in origin (Jankovic, 2001). Conditions that could cause secondary tics include head trauma, encephalitis, and some medications. There is an increased incidence of tics in children with pervasive developmental disorder (Kiessling, 2001).
Tics are commonly classified as simple or complex. Shoulder shrugging, neck twitching, and facial movements are examples of simple motor tics. Touching objects, skipping, and squatting in a rhythmic sequence (such as every four steps) are examples of complex motor tics. Simple vocal tics include sniffing, barking, coughing, yelling, and hiccupping. Complex vocal tics include repeating parts of words or phrases, talking to oneself, assuming different intonations, and uttering obscenities (Bagheri et al., 1999; Leckman et al., 1999).
There is a growing body of literature suggesting that tics are intentional responses to unwanted sensations or urges (Coffey & Park, 1997; Jankovic, 1997). Up to 90% of older children and adults with TS report some premonitory sensations related to their tics, while children under 10 are more likely to view their tics as completely involuntary (Leckman et al., 1999). Although many children are able to suppress their tics for some period of time, the urge to tic remains, and the tics must eventually be "released." Some children are able to remain relatively tic-free during school hours, only to engage in bouts of tics for several hours at home (Leckman et al.; Packer, 1997). Others report that tics are quiescent while they are engaged in an absorbing mental or physical task (Jankovic, 1997). Stress can exacerbate tics, but they can also increase when a child is in a relaxed state, such as watching television, and can be present during sleep (Jankovic, 1997). While this cycle of relative suppressibility and release is characteristic of tics in TS, it can lead to confusion and misguided attempts on the part of parents and teachers to use discipline or conditioning to stop the tics (Packer, 1997).
Presentation and Classification of Tic Disorders
As many as 10-20% of all school-age children have transient motor and, less commonly, vocal tics lasting less than 1 year (Bagheri et al., 1999; Zohar et al., 1999). The majority of these children present with tics in the head, neck, or upper extremities (Leckman et al., 2001). In children who are eventually diagnosed with TS, almost half report that eye blinking was their initial tic, followed by other head and facial tics. Others report vocal tics such as throat clearing and sniffing to be an early symptom of TS (Jankovic, 1997) and less commonly of transient tic disorder (Leckman et al., 2001). In many children with transient tic disorder, symptoms resolve before the family seeks medical attention (Leckman et al., 2001).
In 3-4% of school age children, symptoms of either motor or vocal tics, but not both, persist for more than 1 year (Leckman et al., 2001). These children would be considered to have a chronic tic disorder, and they may or may not have associated behavioral and developmental conditions discussed below (Leckman et al., 2001). Children with both vocal and motor tics that persist for more than 1 year generally fulfill the criteria for TS.
The diagnostic criteria for TS have changed over time (Leckman et al., 2001). The DSM IV (APA, 1994, p. 103) criteria for TS are Both multiple motor and one or more vocal tics have been present at some time during the illness, although not necessarily concurrently. The tics occur many times a day (usually in bouts), nearly every day or intermittently throughout a period of more than 1 year, and during this period there was never a tic-free period of more than 3 consecutive months. The disturbance causes marked distress or significant impairment in social, occupational, or other important areas of functioning. Onset is before age 18 years. The disturbance is not due to the direct physiological effects of a substance (e.g., stimulants) or a general medical condition (e.g., Huntington's disease or post-viral encephalitis).
There is some controversy about this definition, which has significant changes from the DSM-III-R (APA, 1987) and from the TS Classification Study Group (1993). The primary concern is that the DSM-IV definition relies on an undefined and subjective criterion of "distress," rather than a more objective measure of symptom severity (Erenberg & Fahn, 1996; Leckman et al., 2001). Many researchers and clinicians in the field continue to use DSM III-R criteria in order to maintain a more uniform definition of TS (Bawden, Stokes, Camfield, Camfield & Salisbury, 1998; Carter et al., 2000; Coffey et al., 2000; Sherman, Shepard, Joschko & Freeman, 1998; Spencer et al., 1998). For a child who fulfills all criteria except psychological dysfunction or distress, an ICD-9 code can be used instead of a DSM diagnosis (Leckman et al., 2001).
Etiology, Course, and Prognosis of TS
First documented in the 19th century and named after a French neurologist, Gilles de la Tourette, TS was thought for a long time to have psychiatric origins (Coffey & Park, 1997). Contemporary research on dopamine receptors and the limbic system evolved after it was noticed that empiric treatment with neuroleptics such as haloperidol reduced tic severity (Coffey & Park, 1997). It is currently felt that there is an underlying defect of either excess dopamine or hypersensitivity of postsynaptic dopamine receptors (Bagheri et al., 1999).
Recent studies suggest that basal ganglia dysfunction may be involved in TS (Sherman et al., 1998). According to Leckman and Cohen (1999), some of the circuits that convey information from the cortex throughout the basal ganglia are selectively disinhibited in both TS and OCD, making them unusually sensitive to alterations in the environment. In this conceptual model, TS is seen as a disorder in which individuals are unable to inhibit premonitory sensory urges, leading to the emergence of motor and phonic behavior. In OCD, individuals are unable to inhibit specific innate worries, leading to the emergence of intense obsessions and compulsions.
In a cross-sectional study of 36 children with TS who were contacted 7 years after diagnosis, Leckman et al. (1998) found that the mean onset of tics at 5.6 years of age was followed by progressive worsening of tics, peaking at age 10. While 22% of the sample had tics that were severe enough to jeopardize or prevent their functioning in school at the peak of tic symptoms, the tics steadily declined during adolescence, with 50% of the individuals virtually tic-free by age 18. Most of the remaining 18-year-olds experienced minimal to mild symptoms, while only 10% reported moderate or marked tics.
TS and Genetics
Several studies have reported a risk for TS of 11.5% in brothers and 4.8% in sisters of children with TS (Tourette Syndrome Association International Consortium for Genetics, 1999). Based on extended family studies, most researchers associate TS, chronic tics, OCD, and OCS as part of a spectrum of expression of the same underlying genetic disorder (Alsobrook & Pauls, 1997). They suggest an autosomal dominant model with sex-specific penetrance, accounting for the higher incidence of TS among boys, but cannot rule out a multifactorial or intermediate mode of inheritance (Alsobrook & Pauls, 1997; Haasstedt, Leppert, Filloux, van de Wetering, & McMahon, 1995). While some researchers have suggested possible locations for the "TS gene," their findings have not been replicated (Alsobrook & Pauls, 1997).
Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcus (PANDAS) There has been some research into the association of TS and OCD with streptococcal infections, noting that Sydenham's chorea, which involves abnormal movements, OCD-like symptoms, and emotional lability, is felt to be caused by a reaction between antibodies to Group A Beta hemolytic streptococcus and neuronal tissue (Müller et al., 2001; Perlmutter et al., 1999). In some children, infection with streptococcus, borrelia burgdorfi (Lyme's disease), and mycoplasma appear to exacerbate TS symptoms (Müller et al., 2001). These researchers hypothesize that a subset of children with TS belong to a category known as PANDAS (Müller et al., 2001). Criteria that would suggest PANDAS include abrupt onset of symptoms associated with a streptococcal infection, periods of remission, and exacerbations after additional streptococcal infections (Perlmutter et al., 1999). Müller et al. (2001) noted that adults with TS have higher levels of specific antibodies to streptococcus than controls without TS. Perlmutter et al. (1999) found that children with TS who fit the PANDAS criteria had their TS and OCD symptoms significantly reduced after being treated with either intravenous immune globulin or plasma exchange. At the moment, identification and treatment of PANDAS remains experimental, with many questions left unanswered (Hollenbeck, 2000).