Chapter 16 Tics and Tourette syndrome
Introduction
Tourette syndrome (TS), which should be more appropriately called Gilles de la Tourette syndrome, is a neurologic disorder manifested by motor and vocal or phonic tics usually starting during childhood and often accompanied by obsessive-compulsive disorder (OCD), attention-deficit hyperactivity disorder (ADHD), poor impulse control, and other comorbid behavioral problems (Shapiro and Shapiro, 1992; Cohen and Leckman, 1994; Hyde and Weinberger, 1995; Feigin and Clarke, 1998; Leckman and Cohen, 1999; Freeman et al., 2000; Robertson, 2000; Jankovic, 2001a; Leckman et al., 2001; Leckman, 2002; Stein, 2002; Singer, 2005; Albin and Mink, 2006; Leckman et al., 2006; Bloch et al., 2011; Jankovic and Kurlan, 2011). Once considered a rare psychiatric curiosity, TS is now recognized as a relatively common and complex neurobehavioral disorder (Table 16.1). There has been speculation that many notable historical figures, including Dr Samuel Johnson and possibly Wolfgang Amadeus Mozart (Simkin, 1992; Ashoori and Jankovic, 2007), were afflicted with TS.
Table 16.1 Summary of epidemiologic studies in Tourette syndrome (TS)
|
• 6.1% (135/553 children, K–6th grade) had persistent tics (TS); 24% observed to have motor tics during at least one month of the 8-month study
|
One of the earliest reports of TS dates to 1825, when Itard (1825) described a French noblewoman with body tics, barking sounds, and uncontrollable utterances of obscenities. Sixty years later, the French neurologist and a student of Charcot, Georges Gilles de la Tourette (1885) reviewed Itard’s original case and added eight more patients. He noted that all nine patients shared one feature: they all exhibited brief involuntary movements or tics; additionally, six made noises, five shouted obscenities (coprolalia), five repeated the words of others (echolalia), and two mimicked others’ gestures (echopraxia) (Goetz and Klawans, 1982; Kushner, 1999). Although Tourette considered the disorder he described to be hereditary, the etiology was ascribed to psychogenic causes for nearly a century following the original report. The perception of TS began to change in the 1960s, when the beneficial effects of neuroleptic drugs on the symptoms of TS began to be recognized (Shapiro and Shapiro, 1968). This observation helped to refocus attention from psychogenic etiology to central nervous system (CNS) etiology. Despite these advances TS is still often misunderstood and wrongly labeled as a mental or psychiatric disorder. For example, insurance compensation for patients with TS is often compromised because the TS-related diagnostic codes (307.22 = Tic Disorder, 307.23 = Tourette Syndrome) are currently included in the ICD-9 series for mental disorders (290–319). Therefore, the code 333.3 = Tics of Organic Origin or 349.9 = Unspecified Nervous System Disorder may result in more appropriate compensation. If payment is denied, an appeal letter to the insurance company specifying that TS is a neurologic disorder along with some literature and links to a credible website may be required.
The cause of TS is yet unknown, but the disorder appears to be inherited in the majority of patients (Pauls et al., 1988, 1991; Tolosa and Jankovic, 1998; Jankovic, 2001a; Leckman, 2002; Paschou et al., 2004; Singer, 2005). The clinical expression of this genetic defect varies from one individual to another, fluctuations in symptoms are seen within the same individual, and different manifestations occur in various family members (Kurlan, 1994). This variable expression from one individual to another, even within members of the same family, contributes to diagnostic confusion. Without a specific biologic marker, the diagnosis depends on a careful evaluation of the patient’s symptoms and signs by an experienced clinician. Educational efforts directed to physicians, educators, and to the general public have increased awareness about TS. In addition, the media have drawn increasing public attention to this condition. As a result of this improved awareness, the self-referral rate of patients has increased, and the correct diagnosis is made earlier than was the case in the past. Many patients, however, still remain undiagnosed, or their symptoms are wrongly attributed to habits, allergies, asthma, dermatitis, hyperactivity, nervousness, and many other conditions (Jankovic et al., 1998; Hogan and Wilson, 1999).
Phenomenology of tics
Tics, the clinical hallmark of TS, are relatively brief and intermittent movements (motor tics) or sounds (vocal or phonic tics). Recognition of the full spectrum of phenomenology of tics is critical to the diagnosis of TS (Jankovic, 2008). Motor tics typically consist of sudden, abrupt, transient, often repetitive and coordinated (stereotypical) movements that may resemble gestures and mimic fragments of normal behavior, vary in intensity, and are repeated at irregular intervals (Videos 16.1 to 16.8). Currently accepted criteria for the diagnosis of TS require both types of tics to be present (Robertson, 1989; Golden, 1990; Tourette Syndrome Classification Study Group, 1993; Jankovic, 1997; Singer, 2000). This division into motor and vocal/phonic tics, however, is artificial, because vocal/phonic tics are actually motor tics that involve respiratory, laryngeal, pharyngeal, oral, and nasal musculature. Contractions of these muscles may produce sounds by moving air through the nose, mouth, or throat. The term phonic tic is preferable, since not all sounds produced by TS patients involve the vocal cords. 
To better understand the categorization of tics and how they fit in the general schema of movement disorders, it might be helpful to provide a simple classification of movements (Jankovic, 1992). All movements can be categorized into one of four classes:
Recent studies have shown that automatic, learned behaviors appear to be encoded in the sensorimotor portion of the striatum (Jog et al., 1999). Some support for the proposed classification is provided by the findings of Papa and colleagues (1991). They recorded normal premovement (readiness) electroencephalographic, slow, negative potential (the Bereitschaftspotential) 1–1.5 seconds prior to self-induced, internally generated (voluntary) movement in normal individuals but not before externally triggered movement induced by electrical stimulation (Colebatch, 2007). Most tics can be categorized as either semivoluntary (unvoluntary) or involuntary (suppressible). In some cases, learned voluntary motor skills are incorporated into the tic repertoire. This is exemplified by a case of a woman with TS who incorporated sign language into her tic behavior, suggesting that semantics is more important than phonology in the generation of tics (Lang et al., 1993).
Tics may be simple or complex. Simple motor tics involve only one group of muscles, causing a brief, jerk-like movement. They are usually abrupt in onset and rapid (clonic tics), but they may be slower, causing a briefly sustained abnormal posture (dystonic tics) or an isometric contraction (tonic tics) (Jankovic and Fahn, 1986; Jankovic, 1992). Examples of simple clonic motor tics include blinking, nose twitching, and head jerking. Rhythmical clonic tics may rarely resemble tremor or rhythmical myoclonus, such as palatal myoclonus (Schwingenschuh et al., 2007; Adam et al., 2009). Simple dystonic tics include blepharospasm, oculogyric movements, bruxism, sustained mouth opening, torticollis, and shoulder rotation (Videos 16.3 and 16.9). Tensing of abdominal or limb muscles is an example of a tonic tic (Video 16.10). To characterize clonic and dystonic tics further, 156 patients with TS were studied; 89 (57%) exhibited dystonic tics, including oculogyric deviations (28%), blepharospasm (15%), and dystonic neck movements (7%) (Jankovic and Stone, 1991). Since patients with dystonic tics did not differ significantly on any clinical variables from those with only clonic tics, we concluded that despite previous reports (Feinberg et al., 1986), the presence of dystonic tics should not be considered atypical or unusual. In fact, on subsequent observation, the patient in Feinberg and colleagues’ case report was shown to be a case of TS with typical dystonic tics (Fahn, 1987). Dystonic tics should be distinguished from persistent dystonia, which is typically seen in patients with primary dystonia (Jankovic and Fahn, 2002). Dystonic (and tonic) muscle contraction might be responsible for so-called blocking tics (Video 16.11). These blocking tics are due to either prolonged tonic or dystonic tics that interrupt ongoing motor activity such as speech (intrusions) or a sudden inhibition of ongoing motor activity (negative tic). Clonic and dystonic tics may occasionally occur in patients with primary dystonia more frequently than in the general population. In nine patients with coexistent TS and persistent primary dystonia, the onset of tics was at a mean age of 9 years, while dystonia followed the onset of tics by a mean of 22 (10–38) years (Stone and Jankovic, 1991). Other reports have drawn attention to the possible association of tics and dystonia, although the two disorders may coexist by chance alone (Pringsheim et al., 2007). The occasional co-occurrence of tics and dystonia in the same family, however, provides additional evidence for a possible etiologic relationship between the two disorders (Németh et al., 1999; Yaltho et al., 2010). Dopa-responsive dystonia with mutations in the GCH1 gene and TS was found in various members of a large Danish family (Romstad et al., 2003). 
Motor (particularly dystonic) and phonic tics are preceded by premonitory sensations in over 80% of patients (Cohen and Leckman, 1992; Banaschewski et al., 2003; Kwak et al., 2003a; Woods et al., 2005; Prado et al., 2008). This premonitory phenomenon consists of localizable sensations or discomforts, such as a burning feeling in the eye before an eye blink, tension or a crick in the neck that is relieved by stretching of the neck or jerking of the head, a feeling of tightness or constriction that is relieved by arm or leg extension, nasal stuffiness before a sniff, a dry or sore throat before throat clearing or grunting, and itching before a rotatory movement of the scapula. Rarely, these premonitory sensations, termed in one report extracorporeal phantom tics, involve sensations in other people and objects and are temporarily relieved by touching or scratching them (Karp and Hallett, 1996). In one study, premonitory sensations were experienced by 92% of 135 patients with TS, and these were localized chiefly to the shoulder girdle, palms, midline abdominal region, posterior thighs, feet, and eyes (Cohen and Leckman, 1992). We administered a questionnaire regarding various aspects of premonitory sensations associated with their motor tics to 50 TS patients with a mean age of 23.6 ± 16.7 years (Kwak et al., 2003a). Forty-six of 50 (92%) subjects reported some premonitory sensations, the most common of which was an urge to move and an impulse to tic (“had to do it”). Other premonitory sensations included an itch, tingling/burning, numbness, and coldness. Thirty-seven (74%) also reported intensification of premonitory sensations if the patient was prevented from performing a motor tic; 36 (72%) reported relief of premonitory sensations after performing the tic; and 24 (48%) stated that their motor tic would not have occurred if they had had no premonitory sensation. Twenty-seven of 40 patients (68%) described a motor tic as a voluntary motor response to an involuntary sensation rather than as a completely involuntary movement. Besides the local or regional premonitory sensations, this premonitory phenomenon may be a nonlocalizable, less specific, and poorly described feeling, such as an urge, anxiety, anger, and other psychic sensations. The observed movement or sound sometimes occurs in response to these premonitory phenomena, and these movements or sounds have been previously referred to as sensory tics (Kurlan et al., 1989; Chee and Sachdev, 1997). In a study of 60 patients with tic disorders, 41 (68%) thought that all their tics were intentionally produced, and 15 (25%) additional patients had both voluntary and involuntary movements; thus, 93% of the tics were perceived to be “irresistibly but purposefully executed” (Lang, 1991). This “intentional” component of the movement may be a useful feature in differentiating tics from other hyperkinetic movement disorders, such as myoclonus and chorea. The sensations or feelings that often precede motor tics usually occur out of a background of relative normalcy and are clearly involuntary, even though the movements (motor tics) or noises (phonic tics) that occur in response to these premonitory symptoms may be regarded as semivoluntary or unvoluntary. Chee and Sachdev (1997) suggest that sensory tics, which we and others refer to as premonitory sensations, “represent the subjectively experienced component of neural dysfunction below the threshold for motor and phonic tic production.” Many patients report that they have to repeat a particular movement to relieve the uncomfortable urge until “it feels good.” The “just right” feeling has been associated with compulsive behavior, and as such, the “unvoluntary” movement may be regarded as a compulsive tic (Leckman et al., 1994). While many patients describe a gradually increasing inner tension as tic suppression is maintained and a rebound effect of a flurry of tics when the tics are finally expressed, formal objective studies of tic frequency during and after voluntary suppression have failed to detect a rebound increase (Meidinger et al 2005; Himle and Woods 2005) and, when reinforced, tic suppression may last at least 40 consecutive minutes (Woods et al., 2008).
Complex motor tics consist of coordinated, sequenced movements resembling normal motor acts or gestures that are inappropriately intense and timed (Videos 16.6, 16.12, and 16.13). They may be seemingly nonpurposeful, such as head shaking or trunk bending, or they may seem purposeful, such as touching, throwing, hitting, jumping, and kicking. Additional examples of complex motor tics include gesturing “the finger” and grabbing or exposing one’s genitalia (copropraxia) or imitating gestures (echopraxia). Burping, vomiting, and retching have been described as part of the clinical picture of TS, but it is not clear whether this phenomenon represents a complex tic or some other behavioral manifestation of TS (Rickards and Robertson, 1997). Air swallowing is another unusual tic described in TS (Weil et al., 2008). Another unusual tic is ear dyskinesia, which consists of anterior-posterior displacement of the external ear (Cardoso and Faleiro, 1999). Complex motor tics may be difficult to differentiate from compulsions, which frequently accompany tics, particularly in TS. A complex, repetitive movement may be considered a compulsion when it is preceded by, or associated with, a feeling of anxiety or panic, as well as an irresistible urge to perform the movement or sound because of fear that if it is not promptly or properly executed, “something bad” will happen. However, this distinction is not always possible, particularly when the patient is unable to verbalize such feelings. Some coordinated movements resemble complex motor tics but may actually represent pseudovoluntary movements (parakinesias) that are designed to camouflage the tics by incorporating them into seemingly purposeful acts, such as adjusting one’s hair during a head jerk. 
In contrast to other hyperkinetic movement disorders, tics are usually intermittent and may be repetitive and stereotypic (Table 16.2). Tics may occur as short-term bouts or bursting or long-term waxing and waning (Peterson and Leckman, 1998). They vary in frequency and intensity and often change distribution. Typically, tics can be volitionally suppressed, although this might require intense mental effort (Banaschewski et al., 2003). Suppressibility, although characteristic and common in tics, is not unique or specific for tics, and this phenomenon has been well documented in other hyperkinetic movement disorders (Walters et al., 1990). Using functional magnetic resonance imaging (MRI), Peterson and colleagues (1998a) showed decreased neuronal activity during periods of suppression in the ventral globus pallidus, putamen, and thalamus. There was increased activity in the right caudate nucleus, right frontal cortex, and other cortical areas that are normally involved in the inhibition of unwanted impulses (prefrontal, parietal, temporal, and cingulate cortices). Using event-related functional magnetic resonance imaging in 26 children with bipolar disorder, deficits in the ability to engage striatal structures and the right ventral prefrontal cortex were found during unsuccessful inhibition, thus suggesting that deficits in motor inhibition contribute to impulsivity and irritability in children with bipolar disorder and possibly also with TS (Leibenluft et al., 2007).
| A. Primary |
Besides temporary suppressibility, tics are characterized by suggestibility and exacerbation with stress, excitement, boredom, fatigue, and exposure to heat (Lombroso et al., 1991). Emotional stress associated with life events or other stresses have been documented to potentially markedly exacerbate tics, but onset of TS is not necessarily related to stressful life events (Wood et al., 2003; Hoekstra et al., 2004; Horesh et al., 2008). Tics may also increase during relaxation after a period of stress.
In contrast to other hyperkinetic movement disorders that are usually completely suppressed during sleep, motor and phonic tics may persist during all stages of sleep (Cohrs et al., 2001; Jankovic et al., 1984; Silvestri et al., 1990; Fish et al., 1991; Hanna and Jankovic, 2003; Rothenberger et al., 2001). In addition, patients with TS often have disturbances of sleep, such as increased sleep fragmentation, higher frequency of arousals, decreased rapid eye movement (REM) sleep, and enuresis (Hanna and Jankovic, 2003). Many patients note a reduction in their tics when they are distracted while concentrating on mental or physical tasks (such as when playing a video game or during an orgasm). Other patients experience increased frequency and intensity of their tics when distracted, especially when they no longer have the need to suppress the tics. Tics are also typically exacerbated by dopaminergic drugs and by CNS stimulants, including methylphenidate and cocaine (Cardoso and Jankovic, 1993). Finally, it should be noted that there is a broad spectrum of movements that may be present in patients with TS that can be confused with tics, such as akathisia, chorea, dystonia, compulsive movements, and fidgeting as part of hyperactivity associated with ADHD (Jankovic, 1997; Kompoliti and Goetz, 1998; Wilens et al., 2004).
Clinical features of Tourette syndrome
Motor symptoms
TS, the most common cause of tics, is manifested by a broad spectrum of motor and behavioral disturbances (Table 16.3). This clinical heterogeneity often causes diagnostic difficulties and presents a major challenge in genetic linkage studies. To aid in the diagnosis of TS, the Tourette Syndrome Classification Study Group (1993) formulated the following criteria for definite TS: (1) Both multiple motor and one or more phonic tics have to be present at some time during the illness, although not necessarily concurrently. (2) Tics must occur many times a day, nearly every day, or intermittently throughout a period of more than 1 year. (3) The anatomic location, number, frequency, type, complexity, or severity of tics must change over time. (4) Onset must be before age 21. (5) Involuntary movements and noises cannot be explained by other medical conditions. (6) Motor and/or phonic tics must be directly witnessed by a reliable examiner at some point during the illness or must be recorded by videotape or cinematography. Probable TS type 1 meets all the criteria except for number 3 and/or number 4, and probable TS type 2 meets all the criteria except for number 1; it includes either a single motor tic with phonic tics or multiple motor tics with possible phonic tics. In contrast to the criteria outlined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) (1994), the Tourette Syndrome Classification Study Group criteria do not include a statement about “impairment.” There is considerable controversy about the DSM-IV criteria, which require that “marked distress or significant impairment in social, occupational or other important areas of functioning” be present. Therefore, patients with mild tics that do not produce an impairment would not satisfy the diagnostic criteria for TS, according to DMS-IV. This criterion will be deleted from the fifth edition of the DSM. Kurlan (1997) suggested another set of diagnostic criteria for genetic studies and introduced the term Tourette disorder for patients who have “functional impairment.” This, however, does not take into account the marked fluctuation in symptoms and severity; some patients may be relatively asymptomatic at one time and clearly functionally impaired at another time. The TSA International Genetic Collaboration developed the Diagnostic Confidence Index, which consists of 26 confidence factors, with weightings given to each of them and a total maximum score of 100. The most highly weighted diagnostic confidence factors include history of coprolalia, complex motor or vocal tics, a waxing and waning course, echophenomenon, premonitory sensations, an orchestrated sequence, and age at onset. The Diagnostic Confidence Index was found to be a useful instrument in assessing the lifetime likelihood of TS (Robertson et al., 1999). Several instruments, some based on ratings of videotapes, have been developed to measure and quantitate tics, but they all have some limitations (Goetz and Kompoliti, 2001; Goetz et al., 2001). The most widely used instrument to assess tics is the Yale Global Tic Severity Scale (YGTSS), 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, score 0–5: number of tics, frequency, intensity, complexity, and interference. The total tic score ranges from 0 to 50; the usual ranges in most studies is 15 to 30. A health-related quality of life scale (HR-QOL) has been developed and validated for internal consistency, test–retest reliability and against other clinical scales (Cavanna et al., 2008). Utilization of the HR-QOL scale showed that comorbidities such as ADHD and OCD rather than tic severity are more predictive of the long-term outcome.
Table 16.3 Demographic and clinical features in a large database of patients with TS (Tourette International Consortium) (Freeman et al., 2009)
| Number (80 sites; 60% North America; 66% Psychiatry: 27% Neurology) | 6805 |
| Male : Female ratio | 4.4 : 1 |
| Mean age at onset of tics | 6.4 years |
| Mean age at diagnosis of TS | 13.2 years |
| Delay in diagnosis | 6.4 years |
| Family history | 51.7% |
| TS only, no comorbidity | 14.2% |
| Attention-deficit hyperactivity disorder | 55.6% |
| Obsessive-compulsive disorder/behavior | 54.9% |
| Conduct/oppositional defiant disorder | 12.3% |
| Anger control problems | 27.6% |
| Learning disability | 22.0% |
| Mood disorder | 16.9% |
| Anxiety disorder | 16.8% |
| Pervasive developmental disorder | 4.6% |
The clinical criteria are designed to assist in accurate diagnosis, in genetic linkage studies and in differentiating TS from other tic disorders (Jankovic, 1993b) (Table 16.2). There is a body of evidence to support the notion that many, if not all, patients with other forms of idiopathic tic disorders represent one end of the spectrum in a continuum of TS (Kurlan et al., 1988). The most common and mildest of the idiopathic tic disorders is the transient tic disorder (TTD) of childhood. This disorder is essentially identical to TS except the symptoms last less than 1 year and therefore the diagnosis can be made only in retrospect. Transient tic disorder has been estimated to occur in up to 24% of schoolchildren (Shapiro et al., 1988). Chronic multiple tic disorder is also similar to TS, but the patients have either only motor or, less commonly, only phonic tics lasting at least 1 year. Chronic single tic disorder is the same as chronic multiple tic disorder, but the patients have only a single motor or phonic tic. This separation into transient tic disorder, chronic multiple tic disorder, and chronic single tic disorder seems artificial because all can occur in the same family and probably represent a variable expression of the same genetic defect (Kurlan et al., 1988).
Although the diagnostic criteria require that the onset is present before the age of 21, in 96% of patients the disorder is manifested by age 11 (Robertson, 1989). In 36–48% of patients, the initial symptom is eye blinking, followed by tics involving the face and head. Blink rate in TS is about double of that of normal, age-matched controls (Tulen et al., 1999). During the course of the disease, nearly all patients exhibit tics involving the face or head, two-thirds have tics in the arms, and half have tics involving the trunk or legs. According to one study, the average age at onset of tics is 5.6 years, and the tics usually become most severe at age 10; by 18 years of age, half of the patients are tic-free (Leckman et al., 1998). In a study of 58 adults who had been diagnosed with TS during childhood, Goetz and colleagues (1992) found that tics persisted in all patients but were moderate or severe in only 24%, although 60% had moderate or severe tics during the course of the disease. Tic severity during childhood had no predictive value for the future course, but patients with mild tics during the preadult period had mild tics during adulthood. In a longitudinal study that involved structured interviews of 976 children aged 1–10 years, 776 of whom were reassessed 8, 10, and 15 years later, tics and ADHD symptoms were associated with OCD symptoms in late adolescence and early adulthood (Peterson et al., 2001). Furthermore, ADHD was associated with lower IQ and lower social status, whereas OCD was associated with higher IQ. These findings are similar to those of another study designed to address the long-term prognosis of children with TS as they reach adulthood (Bloch et al., 2006). In this study 46 children with TS underwent a structured interview at a mean age of 11.4 years, and again at 19.0 years. The mean worst-ever tic severity score was 31.6 out of a possible 50 on the YGTSS, and occurred at a mean age of 10.6 years. By the time of the second interview, mean YGTSS score decreased to 10. This first prospective longitudinal study also showed that only 22% continued to experience mild or greater tic symptoms (YGTSS scores, ≥10) at follow-up, while nearly one-third were in complete remission of tic symptoms at follow-up. In contrast to the study by Goetz et al. (1992), the severity of childhood tics was predictive of increased tic severity at follow-up. The peak OCD severity occurred 2 years after peak tic severity. Interestingly, a 10-point increase in baseline IQ increased the risk of OCD symptoms at follow-up by 2.8-fold. The authors point out that the later average onset of OCD symptoms indicates the importance of counseling parents about the possibility of OCD development in children recently diagnosed with tics. Although the long-term prognosis for TS is generally favorable for most patients, a minority of cases may have persistent, severe tic symptoms which may be resistant to medications (Eapen et al., 2002). In another study, the investigators reviewed videotapes of 31 patients, with an average age of 24.2 ± 3.5 years, approximately 12 years after their initial video and found that 90% of the adults still had tics, even though they often considered themselves tic-free (Pappert et al., 2003). There was, however, a significant improvement in tic disability and tic severity. When 40 children and 31 adults with TS 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 (Cubo et al., 2008).
Although the vast majority of tics in adults represent recurrences of childhood-onset tics, rare patients may have their first tic occurrence during adulthood (Chouinard and Ford, 2000). In adults with new-onset tics, it is important to search for secondary causes, such as infection, trauma, stroke (Kwak and Jankovic, 2002; Gomis et al., 2008), multiple sclerosis (Nociti et al., 2009), cocaine use, neuroleptic exposure, and peripheral injury (Video 16.14) (Chouinard and Ford, 2000; Jankovic, 2001b; Jankovic and Mejia, 2006). One study of eight patients with adult-onset tics (three of whom had childhood-onset OCD and three of whom had a family history of tics and OCD) found that in comparison to the patients with more typical childhood-onset tics, the former group had more severe symptoms, greater social morbidity, and less favorable response to medications (Eapen et al., 2002). Poor motor control, which can lead to poor penmanship and, at times, almost illegible handwriting, can contribute to the academic difficulties faced by many patients with TS. 
Tics, although rarely disabling, can be quite troublesome for TS patients because they cause embarrassment, interfere with social interactions, and at times can be quite painful or uncomfortable. Rarely, cervical tics may be so forceful and violent, the so-called “whiplash tics,” that they may cause secondary neurologic deficits, such as cervical artery dissection (Norris et al., 2000), and noncompressive (Isaacs et al., 2010) or compressive cervical myelopathy (Krauss and Jankovic, 1996) (Video 16.2). The truncal bending tics, which resemble intermittent, repetitive camptocormia, may cause secondary degenerative changes in the thoracic spine (Azher and Jankovic, 2005) (Video 16.5). These disabling tics and other severe symptoms of TS draw attention to the subset of patients with TS so severe that they may be life-threatening, hence labeled as “malignant” TS (Table 16.4). Of 332 TS patients evaluated at Baylor College of Medicine Movement Disorders Clinic during a 3-year period, 17 (5.1%) met criteria for malignant TS, defined as ≥2 emergency room (ER) visits or ≥1 hospitalizations for TS symptoms or its associated behavioral comorbidities (Cheung et al., 2007). The patients exhibited tic-related injuries, self-injurious behavior (SIB), uncontrollable violence and temper, and suicidal ideation/attempts. Compared to patients with nonmalignant TS, those with malignant TS were significantly more likely to have a personal history of obsessive-compulsive behavior/disorder (OCB/OCD), complex phonic tics, coprolalia, copropraxia, SIB, mood disorder, suicidal ideation, and poor response to medications. Severe or malignant TS, associated with SIB and other disabling features, has been also reported in families, including consanguineous kindreds (Motlagh et al., 2008). 
Table 16.4 Clinical features of severe (“malignant”) TS
Vocalizations have been reported as the initial symptom in 12–37% of patients, throat clearing being the most common (Robertson, 1989). Phonic tics can be quite troublesome for patients and those around them. In addition to involuntary noises, some patients have speech dysfluencies that resemble developmental stuttering, and up to half of all patients with developmental stuttering have been thought to have undiagnosed TS (Abwender et al., 1998). Coprolalia, perhaps the most recognizable and certainly one of the most distressing symptoms of TS, is actually present in only half of patients (Videos 16.8 and 16.15). When describing the distress caused by his severe coprolalia, one of our patients remarked that immediately after shouting an obscenity, he reaches out with his hand in an attempt to “catch the word and bring it back before others can hear it.” Coprolalia appears to be markedly influenced by cultural background. Although in one retrospective analysis of 112 children with TS, only 8% exhibited coprolalia (Goldenberg et al., 1994), the true prevalence of coprolalia in TS children and adults is about 50% in the US population, when mental coprolalia (without actual utterance) is included. In a study of 597 individuals with TS 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 (Freeman et al., 2009). Coprolalia has been reported to occur in only 26% of Danish patients and 4% of Japanese patients (Robertson, 1989). Copropraxia has been found in about 20% of patients, echolalia in 30%, echopraxia in 25%, and palilalia in 15%. Although coprolalia is a characteristic feature of TS and, based on functional MRI studies, attributed to abnormal activation particularly in the left middle frontal gyrus and right precentral gyrus, and possibly the caudate nucleus, cingulate gyrus, cuneus, left angular gyrus, left inferior parietal gyrus, and occipital gyri (Gates et al., 2004), this language abnormality is not universally present or specific for TS. 
Except for tics, the neurologic examination in patients with TS is usually normal. In one case-control study, TS patients were found to have a shorter duration of saccades, but the saccades were performed with a greater mean velocity than in normal controls, and the TS patients had fewer correct antisaccade responses, suggesting a mild oculomotor disturbance in TS (Farber et al., 1999). Although the ability to inhibit reflexive saccades is normal, TS patients make more timing errors, indicating an inability to appropriately inhibit or delay planned motor programs (LeVasseur et al., 2001).
Behavioral symptoms
Patients with TS generally have normal intelligence and may even perform better and faster than age-matched controls on certain tasks that require grammar skills that depend on procedural, rather than declarative memory (Walenski et al., 2007). While TS patients have no cognitive deficits, they often exhibit a variety of behavioral symptoms, particularly ADHD and OCD (Figs 16.1 and 16.2) (Gaze et al., 2006). In the Tourette International Consortium (TIC) database, which includes information on 3500 patients with TS evaluated by neurologists or psychiatrists, only 12% had tics only, without other comorbidities (Freeman et al., 2000). Kurlan and colleagues (2002) interviewed 1596 children, aged 9–17, in schools in Rochester and Monroe Counties, New York, and identified tics in 339 children (21%) after 60–150 minutes of observation. They found the following behavioral problems more frequently (P < 0.05) in children with tics than in those without tics: OCD, ADHD, separation anxiety, overanxious disorder, simple phobia, social phobia, agoraphobia, mania, major depression, and oppositional defiant behavior. Also, children with tics were younger (mean age: 12.5 vs. 13.3 years) and were more likely to require special education services (27% vs. 19.8%).
Figure 16.1 An overlap of disorders typically coexisting in patients with TS.
Redrawn from Jankovic J: Tourette’s syndrome. N Engl J Med 2001;345:1184–1192.
