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Tourette Syndrome in Infancy and Early Childhood

Zinner, Samuel H. MD

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Abstract

HISTORY AND EPIDEMIOLOGY

Tourette syndrome (TS) was first described medically in 1885 (Gilles de la Tourette, 1885). Yet, this chronic motor and phonic tic disorder is a relative newcomer among customary neurodevelopmental diagnostic considerations. For example, a 1956 study at Johns Hopkins Hospital, examining factors associated with the development of tics, explained its small sample size by stating, “tics are among the less common neuropsychiatric disorders of childhood” (Pasamanick & Kawi, 1956). In contrast, today, we recognize that tics occur in up to a quarter of schoolchildren at some time during childhood (Snider et al., 2002). Much of this growth in recognition stems from tremendous awareness campaigns by nonprofit groups. Still, misconceptions regarding its most basic features persist and are encouraged by media caricatures. For example, the utterance of foul language (coprolalia) is an often-lampooned symptom but, in reality, only 10% to 15% of clinically referred children with TS actually experience this feature (Freeman et al., 2000; Goldenberg, Brown, & Weiner, 1994), with perhaps even far fewer of the nonreferred children with TS having this quality. Because of these misconceptions and other factors, tics often go undetected by family members, healthcare professionals, and educators, even when frequent or severe. The movements may also be dismissed or imputed to some other category of behavior, such as “habit” or “nerves.” Such oversight results in underdiagnosis and misdiagnosis of tic disorders, and, often more consequentially, of related “comorbid” conditions (ie, nontic conditions common in people with TS) that will be discussed in this article.

Tic features

Tics are highly variable from person to person, and even within individuals. Tics can be characterized by frequency, severity, complexity, suppressibility, and other features. They may be described as purposeless, hyperkinetic expressions, or sometimes as exaggerated bits of semipurposeful behaviors. A common and often first-presenting motor tic is an eye blink, but tics can range from simple single-muscle group actions to highly orchestrated sequences of motor and/or phonic elaborations. Tics customarily first appear during early childhood (3–7 years), and have been reported as early as 4 months of life (Burd & Kerbeshion, 1987). A second wave of children first shows tics in late childhood (9–11 years). When chronic (lasting more than a year), tics usually show a waxing and waning course and occur in bouts over time. Chronic tics often appear transient at first, disappearing after a few weeks, only to reappear later (Leckman, Kin, & Cohen, 1999). Early tic onset is highly associated with a maternal history of tics (Freeman et al., 2000). Often, tics peak in severity during early adolescence, then remit or disappear later in adolescence and adulthood.

Other movement disorders in infants and young children

Although infants are less likely to manifest tics compared with toddlers and older children, they are more likely to experience transient movement disorders. These disorders can be confused with tics, and may include jitteriness, shuddering, involuntary eye movements, various spasms, or infant dystonia (sustained muscle contractions). A useful overview is available (Fernandez-Alvarez, 1998). Other phenomena in infants that may mimic tics include infantile spasms (seizures) and underrecognized infant masturbation.

Among toddlers, speech dysfluency is common (such as repetition of syllables or of whole words before completing the rest of a phrase or sentence) and may be consistent with developmental stuttering if the dysfluencies occur frequently. In addition, associated behaviors can occur with stuttering, such as head, torso, or limb movements. Such movements may include eye blinking or squeezing the eyes shut during stuttering, among other tic-like productions (Zebrowski, 2003). Although not customarily considered tics, developmental stuttering and these associated behaviors may occur more commonly in children with tics and may have overlapping neural mechanisms (Abwender et al., 1998). Therefore, the distinction between stuttering and tics may be unclear.

Categories of tic disorders

Tourette syndrome is identified by the presence of both motor and vocal tics, although not necessarily concurrent, that occur nearly daily for at least 1 year, without 3 consecutive tic-free months during that qualifying year, and first manifesting prior to 18 years of age. The diagnostic criteria for TS are listed in Table 1. Other tic disorders include chronic motor or vocal tic disorder (CTD) and transient tic disorder (duration <1 year). These diagnostic criteria change over time, reflecting the evolving understanding and views regarding the nature of tic disorders. As such, the distinction between TS and CTD may or may not be clinically relevant, and may be semantic. Pointedly, vocal tics are motor tics that produce noise, sometimes considered “epiphenomena” of motor tics. The term “phonic” in place of “vocal” is often used in describing noise-producing tics and in qualifying the diagnosis of TS. So, for example, tongue-clicking or sniffing are both phonic tics, although neither sound is produced by voice (vocal). Motor and vocal tics fall into 1 of 2 classifications: “simple” (generally involving one muscle group) and “complex” (involving more than one muscle group, often with sequences of productions). The natural history of tic disorders is variable, but motor tics usually precede vocal tics in onset, and simple tics usually precede complex ones. A preschool child with tics will most likely only have simple tics; complex tics may later emerge during the school years. Many children with simple tics, however, never develop complex tics. Examples of simple and complex motor and vocal tics are provided in Table 2.

Table 1
Table 1:
Diagnostic criteria for Tourette syndrome*
Table 2
Table 2:
Examples of simple and complex motor and vocal tics

Associated, or comorbid, conditions

As we learn more about the complexity of tic disorders, their overlap with related neurological disorders grows clearer. It is inadequate to consider TS without regard for the possible comorbid neurologically related developmental disorders that will further uniquely characterize each child affected with TS. As a result, two individuals are likely to show completely disparate symptoms, yet both still have TS. As is true for many neurodevelopmental disorders, clinical aspects of TS and its associated problems exist on a spectrum of severity. Problems in mood and anxiety, in learning and cognitive efficiency, in social behavior or impulse control and aggression, and in other neurodevelopmental channels may exist in TS as manifestations resulting from common underlying neurochemical and/or neuroanatomical flaws. As such, children with TS may be diagnosed multiply with attention deficit disorders, learning disabilities (LD), obsessive-compulsive behaviors, mood and anxiety disorders, delayed or atypical developmental patterns, self-injurious behaviors and other challenges among the panoply of possible neurodevelopmental diagnostic labels.

Although it is not possible to predict whether a child will develop TS, or to determine the course of TS in a diagnosed child, care providers, developmental specialists, and educators can take advantage of their customary surveillance practices to recognize warning signs for developmental concerns early, and to be particularly on the alert for children who are more likely to reveal neurodevelopmental problems. Early identification of affected and at-risk children, along with appropriate interventions, offers the best assurances for healthy, positive adaptation, growth, and self-esteem.

ETIOLOGY-NEUROPHYSIOLOGY AND GENETICS

The origin of tics and some related disorders appears to arise from a failure in the processing of behavior-linked information along brain circuits connecting regions of the cerebral cortex (the outer parts of the brain responsible for conscious thought, sensations, and general movements) to the basal ganglia and thalamus (nerve cells deep within the brain whose functions include refining, initiating, and inhibiting general movements) (Singer & Minzer, 2003; Swerdlow & Young, 2001) (Fig 1). The neurochemical systems discussed generally focus on dopamine and serotonin, although other neurotransmitters play important roles in the etiology of tics.

Figure 1
Figure 1:
The location of the basal ganglia and thalamus, ghosted into a semitransparent brain. Reprinted/adapted with permission from the publisher: Carlson physiology of behavior (8th ed.). Boston, MA: Allyn and Bacon. Copyright 2004, Pearson Education.

A failure in filtering

One customary proposed mechanism behind TS implicates basal ganglia dysfunction alone. It is important to emphasize that, although specific regions of the basal ganglia are almost certainly implicated in the pathogenesis of tics, newer evidence implicates processing defects in other circuit segments as well, including the cerebral cortex and the thalamus. With regard to tics, the model suggests that areas of the cerebral cortex involved in movement and planning generate impulses for movement preparation. These impulses are sent to the basal ganglia, but the basal ganglia fail to filter these impulses adequately. The basal ganglia are thereby unable to suppress other brain regions, including the thalamus, appropriately (Leckman & Riddle, 2000). The uninhibited thalamus, in turn, sends hyperexcited messages to motor cerebral cortex regions. As a consequence, the child perceives an urge to have a tic, referred to as a “premonitory” sensation. The urge is a psychic or physical sensation experienced in the muscle or muscle groups afflicted, which is alleviated only upon committing the tic. As an analogy, the sensation may be likened to an “itch,” and this “itch” persists and may build in intensity such that only the “scratching” (here, performing a tic) will relieve the “itch.”

This proposed flawed filtering mechanism links tic disorders with related disorders that are associated, or comorbid, with tics (Sheppard, Bradshaw, Purcell, & Pantelis, 1999). In a similar mechanism that results in unwanted tics, such filtering defects may result in unwanted disinhibited emotions, impulsive actions, or compulsive behaviors (Zinner, 2000). As an example, obsessive thoughts (such as an unyielding doubt that a stove has been turned off) may not be sufficiently filtered, so that repeating a confirming activity, or a compulsion such as checking the stove over and over, temporarily alleviates the cognitive distress. Like tics, the resultant moods or behaviors associated with these linked filtering defects may reflect excessive and inappropriate pieces of ordinarily purposeful functions or behavioral sequences; when functioning properly, such sequences serve to ensure operational necessities such as attention, defense, social awareness, and learned habit formation.

Brain structural pathology?

At a molecular level, TS may originate from early brain development. For example, if there are abnormalities in brain proteins produced only during brain development, then abnormalities in the brain's basic structure may result. As the infant and child grow, these structural defects may become functionally apparent. Over the course of childhood, symptoms begin to emerge as a result of these structural areas of the brain becoming more fully employed. However, since the proteins are no longer being produced, the defects are nonprogressive (a “static encephalopathy” of sorts), so that symptoms may decrease or normalize entirely over time; in fact, in many neurodevelopmental disorders such as TS, symptoms do improve. Larger brain anatomical and functional abnormalities are also found in subjects (usually adult) with TS, but the clinical significance of these findings is unknown. An excellent review and interpretation of the available limited data from brain imaging studies in TS is provided by Gerard and Peterson (2003).

Genes-the truth…

Although a genetic basis for TS is now clear, a gene locus has not been identified. Monozygotic (“identical”) twins both are much more likely to have TS than are dizygotic (“fraternal”) twins, with 53% versus 8% twin-pair co-occurrence, respectively, among 43 pairs of same-sex twins evaluated (Price, Kidd, Cohen, Pauls, & Leckman, 1985), and the co-occurrence increases to 77% and 23%, respectively, when qualifying the presence of any tics. A prospective study found that among 34 children without tics aged between 3 and 6 years whose parents had TS, 29% developed a tic disorder within 5 years; no children in a control group developed tics (McMahon, Carter, Fredine, & Pauls, 2003). Results of these and other family, linkage and candidate gene studies leave little doubt about the genetic underpinnings of TS (Pauls, 2003). Among the prevailing theories is that tic disorders result from an interplay of several genes rather than a single gene, and that the propensity toward developing tics and/or comorbid conditions is inherited in an autosomal dominant mode, but without complete penetrance. Some of the genes probably exert only minor influence, whereas other genes are more strongly influential. The combination of genetic and symptom variability certainly thwarts identifying the accountable genes.

… And the whole truth: Nongenetic associations

At the same time, in nearly half of affected identical twin pairs, just one twin has TS, so nongenetic influences are strongly suggested (Hyde, Aaronson, Randolph, Rickler, & Weinberger, 1992). Also, poorer global neuropsychological function is noted in monozygotic twins in the twin affected with more severe tics when the twin pair is discordant either for the presence of tics or for tic severity (Randolph, Hyde, Gold, Goldberg, & Weinberger, 1993). Risk factors (Table 3) that may contribute to the presence and severity of symptoms of tics and/or comorbid conditions are inconclusive and based on a limited number of studies and case reports, but may include lower birth weight, intrauterine growth retardation, maternal stress during pregnancy, and abnormal electrophysiological brain activity (noted as increased theta activity) (Hyde et al., 1992; Hyde, Emsellem, Randolph, Rickler, & Weinberger, 1994; Leckman et al., 1990). Other possible risk-increasing influences may include perinatal complications (neonatal anoxia and forceps-assisted deliveries) and in utero exposure to high levels of coffee, cigarettes, or alcohol (Burnstein 1992; Santangelo et al., 1994), the latter exposures specific to TS with comorbid obsessive-compulsive disorder (OCD). Burd, Severud, Klug, and Kerbeshian (1999) report a positive association between early and more numerous prenatal care visits and the likelihood to develop TS, noting that the relationship should not be presumed to be causal; rather, a pregnancy marked with early problems and/or compulsive behaviors in the mother might result in earlier and increased prenatal visits.

Table 3
Table 3:
Risk factors for the development of tics and/or comorbid conditions

It is important to emphasize the association without presuming causality, however. These risk factors may serve as markers for underlying in utero events that result in damage to or altered structural organization of the developing fetal brain, changes in the sensitivity of specific neurotransmitter receptors, or other mechanisms, lending susceptibility to the later expression of tics and associated conditions. For example, factors that limit oxygen and nutrient delivery to the developing fetal nervous system and result in a specific TS phenotype (Leckman & Peterson, 1993) are also factors that limit optimal fetal body growth.

Male gender serves as another important risk factor for TS and for some other neurodevelopmental conditions. About 4 times as many boys have TS as do girls; this ratio is similar to that found in hyperactivity, stuttering, and the pervasive developmental disorders. A less robust male predominance is found in bed-wetting. This source for the gender differences may relate to activity of androgenic steroids in key neurodevelopmental processes (Peterson et al., 1992). Such processes may include guiding the early brain in its mapping of neuronal migration and connectivity as well as the pruning and refinement of cell connections once made (a mechanism defective in Fragile X syndrome).

“PANDAS”-an endangered theory?

A very controversial potential risk factor links exposure to infectious agents (primarily group A beta-hemolytic streptococcal [GABHS] pharyngitis) with tics and/or OCD. The term “PANDAS” (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) describes this intriguing and hotly debated topic. Although a full discussion is beyond the scope of this article, a brief description is indicated. Similar to the mechanism and symptoms of rheumatic fever and Sydenham chorea, the PANDAS model proposes that infection with GABHS stimulates antibody production. These antibodies are designed to recognize and attack GABHS specifically, but mistakenly they cross-react with sites on the basal ganglia, damaging the filtering mechanism described earlier, resulting in specific symptoms, including tics and OCD. For further discussion and suggested guidelines, the reader is referred to Kurlan and Kaplan (2004) for a discussion on the limitations of this connection and Swedo, Leonard, and Rapoport (2004) for a presentation of the evidence for PANDAS.

DEVELOPMENTAL AND BEHAVIORAL FINDINGS

Given the range of potential associated features of the TS predisposition and the uncertain environmental influences, it is not possible to predict the ultimate phenotypic expression for any single affected individual. An estimated 12% of patients with TS have no comorbidity (Freeman et al., 2000). With the presence of each comorbid condition, the likelihood of further comorbid conditions increases. For example, a young child with TS and attention-deficit/hyperactivity disorder (ADHD) is more likely to develop a learning disability than another child with TS who has no identified comorbid conditions. Because tics and comorbid conditions may share a common root cause, tics may more accurately be considered a description of one of many possible symptoms, rather than a classification of a separate disorder. At the same time, it is also possible that any of these comorbid conditions may also occur independent of the common gene(s), with separate behavioral or developmental expressions and outcomes from those occurring as comorbid conditions in children with TS.

Statistics collected from a growing international database of patients with TS (Freeman et al., 2000) and related tic disorders (Kurlan et al., 2002) reveal a striking behavioral spectrum (Table 4), including attention deficit disorders, obsession-compulsive behaviors, mood and anxiety disorders including separation anxiety—and a variety of simple phobias, learning difficulties and more significant learning disability, executive dysfunctions, self-injurious behaviors, autism and other pervasive developmental disorders, anger dysregulation, oppositional defiant behaviors, sleep disorders, and nocturnal enuresis.

Table 4
Table 4:
Comorbid conditions of tics dis-orders*

Comorbid ADHD

The most frequent comorbid condition for TS is ADHD, affecting between 50% and 70%. The significance of the impact of this comorbid condition is amplified when understood that half of all child psychiatric clinical practice addresses management of ADHD, TS notwithstanding. Several studies suggest a more significant global impairment among children with TS who are comorbid for ADHD, with symptoms of disruptive behavior, mood disturbance, anxiety disorders, and cognitive dysfunctions likely accounted for by comorbidity with ADHD rather than by TS alone (Spencer et al., 1998). The ADHD subtype “hyperactive-impulsive” is more commonly diagnosed among preschool-aged children than the “inattentive” or “combined” subtypes, and may relate to brain maturational processes or to diagnostic oversight. Girls are less likely to be identified at this age, owing perhaps to their decreased incidence of the hyperactive-impulsive subtype, making them less noticeable. Children aged as young as 4 years with ADHD have been identified by their teachers as being less popular or cooperative, and more actively disliked by classmates, than age-matched peers (Lahey et al., 1998), a consequence with persistence of poor peer relationships (Bawden, Stokes, Camfield, Camfield, & Salisbury, 1998) and family functioning (Sukhodolsky et al., 2003) into later childhood and adolescence. In addition, parents of these young children diagnosed with the hyperactive-impulsive subtype report more unintentional self-injury caused by the child's behavior than comparison children, implicating a significant health risk.

Comorbid motor problems with ADHD

An often reported, but clinically overlooked, warning sign in young children with ADHD is the comorbid presence of developmental coordination disorder (Gillberg & Kadesjo, 2003), or general clumsiness, which is a useful red flag to alert to the possibility of ADHD, as well as other neurodevelopmental disorders, such as autism spectrum disorders (Baron-Cohen, Mortimore, Moriarty, Izaguirre, & Robertson, 1999; Baron-Cohen, Scahill, Izaguirre, Hornsey, & Robertson, 1999; Kadesjo & Gillberg, 2000). Limited studies in TS are available, but suggest that neuromotor dysfunction in children with TS is specific to comorbid ADHD affliction (Schuerholz, Cutting, Mazzocco, Singer, & Denckla, 1997).

Comorbid executive dysfunctions with ADHD

Among children with TS who are comorbid for ADHD, we see an increase in the incidence and severity of other developmental problems, including executive dysfunctions (Harris et al., 1995). Executive functions refer to self-regulating behaviors unique to humans that allow us to monitor our actions speedily and according to goals or rules, using skills of attention, planning and adjustment, working memory, organization, and inhibition of inappropriate or inefficient behaviors. These functions are largely under the control of the prefrontal cortex (the very front of the cerebral cortex), with a regulating role played by the basal ganglia, as described earlier. Problems in executive function may be subtle though apparent early in life, but become increasingly apparent in areas of social and cognitive functions (Channon, Crawford, Vakili, & Robertson, 2003), including scholastic achievement, social skills, and activities of daily living. Early-life clues to poor executive functions, although quite variable, may be witnessed as frustration or tantrums, poor motivation during challenging tasks, fleeting attention, difficulty in following simple verbal directions or understanding social cues from parents and others such as facial expressions or rules on the playground, or delays in the mastery of developmental adaptive skills.

Comorbid obsessive-compulsive behaviors

Obsessive-compulsive behaviors and OCD are highly comorbid with TS, with epidemiologic studies showing rates in the range of 35% among clinically referred subjects with TS. Compulsive behaviors may include excessive grooming, self-injurious behaviors (nail biting or hair-pulling), skin-picking, cleansing, self-mutilation, checking, counting, hoarding, and others. As with tics, OCD symptoms show a bimodal distribution for age of onset, with early onset presenting at 6 or 7 years of life and more likely associated with tic disorders than late onset (presenting in the late teens or beyond) (Rosario-Campos et al., 2001). Also, early-onset OCD may have a stronger genetic influence than late onset, showing higher familiality (Nestadt et al., 2000). Compulsive behaviors are more likely to be tic-like among children with TS (eg, needing to stretch one's neck a specific number of times in a sequence of tics) relative to those without TS; similarly, among females, tics early in onset may have compulsive qualities (Santangelo et al., 1994). Some ritualistic, repetitive, and compulsive-like behaviors are common in typically developing children, especially aged between 2 and 4 years, and may not indicate aberrant developmental behavior patterns (Evans et al., 1997).

Comorbid learning difficulties

Learning disabilities are often overlooked and undertreated complications of neurodevelopmental disorders, including TS. Roughly 40% of children with TS will develop an LD, particularly if a child also has comorbid ADHD. Children with TS are particularly prone to LDs in visual-motor integration (which may become apparent early as difficulty in using crayons or coloring within the lines), as well as general executive dysfunctions (such as disorganization or poor ability to plan). As children with TS advance in school, many additional problems outside the responsibility of LDs can interfere with learning, including the tics themselves, as well as problems secondary to ADHD, mood disturbances, sleep disruption, fine motor difficulties, and other conditions. Learning disability present in the preschool child may not be suspected until the school years when the child is academically challenged with tasks requiring particular skill sets. However, there are often early clues to LD that can assist in prompt identification. Early childhood warning signs may include poor language development, difficulties with letters or numbers or sounds, difficulties in coordination, and poor attention span.

Comorbid rage attacks

Although garden-variety temper tantrums are part of the behavioral repertoire expected in virtually all toddlers, “rage attacks” seen in a minority of children with TS (usually no longer toddlers) are not. These explosive and recurrent episodes of anger or aggression appear age inappropriate, and are more likely to occur in children with comorbid ADHD and/or OCD (Stephens & Sandor, 1999). Rage attacks are severe in magnitude and may result in significant property damage, and parents generally regard this comorbid aspect of TS as the most impairing of all symptoms (Budman, Rockmore, Stokes, & Sossin, 2003). Often, rage attacks lack obvious precipitants.

Comorbid autism spectrum disorders

Children with autism as a primary diagnosis are increasingly being recognized with comorbid TS, currently estimated at about 5% (Baron-Cohen, Scahill, et al., 1999). Given this comorbidity, the presence of stereotyped movements, or “stereotypies,” often seen in young children with autism spectrum disorders, can be of significant diagnostic confusion when considering tics. Stereotypies may include rocking, hand or head banging, repetitive hand or finger movements, gyrating, or hand-flapping. Stereotypies may also be seen in deaf children and in children blind from birth, but are also seen among otherwise typically developing children. These movements may relate to responses to altered sensory experience (such as sensory deprivation or heightened sensitivity to sensory input), distinct from tics. Both stereotyped behaviors and tics are hyperkinetic movement disorders, with controversial distinctions and potential for misdiagnosis, even among experts (Ringman & Jankovic, 2000). Kano, Ohta, Nagai, Yokota, and Shimizu (1988) offer various qualities to assist in making the distinction, although several recommendations require the patient's ability to relate subjective experience, which is not possible in young children or most children with autism. Other potential areas for confusion relate to complex vocal tics, such as echolalia, or the repetition of another person's word or phrase, which are behaviors also commonly associated with autism.

Comorbid sudden infant death syndrome?

A limited series of 5 case reports documents an increased risk for sudden infant death syndrome (SIDS) among children with family histories of TS. The author posits that altered sleep-related respiratory control and arousal mechanisms, possibly intrinsic in some children who are at increased risk to develop TS on the basis of family history, may render them susceptible to SIDS (Sverd & Montero, 1993). However, no further reports have been published, and interpretation should be considered highly speculative at this point.

SCREENING FOR YOUNG CHILDREN AT RISK FOR TS

Vigilance is essential for early detection of delayed or atypical developmental patterns. Children suspected of having special needs require a reliable “Medical Home” approach. Medical Home is a partnership between a primary care clinician and the child's family that assure nonmedical and medical needs are met. The National Center of Medical Home Initiatives (Appendix A) provides information on resources and tools to build a Medical Home. Although by definition (Table 1), TS can first appear anytime prior to 18 years of age, it is important to recognize that most children who develop TS first manifest tics between 3 and 7 years of age; atypical or delayed developmental patterns prior to this age may be common among children who will later develop TS, but a diagnosis of TS during the preschool years is unusual.

Considering the diagnosis: Teamwork

General developmental surveillance is optimal when all educators and care providers in contact with children consider cognitive-adaptive, fine and gross motor, speech and nonspeech communication, and social streams. A heightened sensitivity to subtle variations in development may serve as a key link to more focused assessments that are geared to identifying patterns of concern. Developmental and behavioral concerns raised by caretakers should not be considered lightly.

Information regarding a child's function at home, at school, and with peers is necessary; remember that even preschool children will exclude peers with difficult behaviors. Parents, educators, and developmental specialists may benefit from carefully documenting behavioral and developmental observations of the child in these settings, and sharing these observations with each other and with the child's primary care provider.

Hearing or vision impairment can result in a wide array of behavioral and developmental disturbances in infants and toddlers; blind toddlers may show stereotyped behaviors such as eye pressing and eye poking, rocking, or unusual hand or finger movements (Fazzi et al., 1999), whereas deaf infants express nonlinguistic vocalizations or repetitive movements to engage communication (Lederberg & Everhart, 1998; Smith-Gray & Koester, 1995). Ideally, all infants now undergo early hearing screening, with periodic rescreening during child development. Verifying completion of reliable hearing screening is essential, with appropriate referral made for any suspected or confirmed deficits. Formal visual assessment is not customarily performed in the newborn or young child, which depends on routine neurological screening during well-child visits. Any concerns regarding healthy vision should prompt immediate referral.

Early warning signs for comorbid conditions

Remembering that children with TS and CTDs are likely to have comorbid conditions, and that these conditions often first become apparent prior to tic onset, will help identify children at risk for tic disorders. Early warning signs for ADHD and LDs may include motor concerns such as difficulties with fine or gross motor coordination, including clumsiness or graphomotor (ie, movements required for writing) problems. Also, poor or fleeting attention, although not specific to ADHD or LD, is common and warrants further investigation. Some investigations reveal temperamental difficulties in young children who later are diagnosed with ADHD; these difficulties may include disinhibited speech, tendency to approach novel stimuli or situations with limited impulse control, or disruptive behaviors (Hirshfeld-Becker et al., 2002), as well as difficulty in establishing rhythms or routines in eating or sleeping and other behavioral problems. Early clues to executive function problems may result in frustration or temper tantrums, developmental delays, or other difficulties as described previously. Early signs of anxiety may manifest themselves temperamentally, or as problems with separation from primary caregiver. Anxiety can also exacerbate speech dysfluencies in children with developmental stuttering; as discussed earlier, these children may be more prone to having tic disorders, or perhaps their speech dysfluencies and associated behaviors may represent tic manifestations.

Social, cognitive, language, and motor development are reflected in a child's play, and targeted observations of play are very useful in identifying possible developmental problems. Normally, play will evolve beyond infancy from sensorimotor (eg, mouthing toys or banging them) to exploratory and functional (eg, rolling toy cars or making choo-choo noises), and then to imaginative pretend play (eg, brief role playing with dolls).

Tic suppression

Younger children who develop tic disorders are less likely to suppress their tics compared with older children. This is due to a number of reasons, including lack of awareness of tics, absence of social pressure to suppress tics, milder degree of tics, and inability to appreciate premonitory sensations. As a result, when tics are present in young children, there may be an opportunity to witness them in the clinical setting or classroom that is often unavailable when observing older children with tic disorders. Baseline tic observations are helpful to note, and can be assisted by classroom, in-therapy, and home use of tic rating scales, such as the Tic Severity Form (Appendix A). Tics are rare in infants, and a differential diagnosis was addressed earlier. In older children, the ability to suppress tics (and in particular, the ability to describe a premonitory discomfort—often not appreciated in children younger than 10 years or so) may discriminate tics from other movement disorders. Simple motor and vocal tics are usually straightforward, but more complex movements may be diagnostically confusing, and require a specialist's assessment. Also, parents may be unaware that their child has tics; surprisingly, this lack of parental awareness is not uncommon even among parents who themselves have tic disorders (McMahon et al., 2003).

Comprehensive medical screening

A primary care provider should gather information gleaned from carefully guided prenatal, medical, social, and family histories to help to determine vulnerabilities to tic disorders and related neurodevelopmental and psychosocial risks or concerns. The family history should include inquiries about tic disorders as well as comorbid diagnoses, and in particular, OCD, ADHD, LD, and mood or anxiety disorders. A general comprehensive screening physical examination should be performed, and includes investigation of the neurological and musculoskeletal systems. A careful search for signs of self-injurious behaviors may uncover chapping around the lips (from frequent licking), various scabs (from repetitive picking), or a spotty, moth-eaten appearance to the scalp (from “trichotillomania,” pulling out one's hair). Extended and multiple appointments may be necessary for adequate evaluation, ideally with all parents or guardians present. Their presence will also allow a more complete psychosocial assessment to include the clinician's direct observations.

MANAGEMENT AND INTERVENTION

Early childhood healthcare providers and educators have a wide range of abilities to assess neurodevelopmental problems. Providers are encouraged to become familiar and comfortable with general developmental screening as discussed in this article. Children found to have delays or atypical patterns of development can be referred for further evaluation and interventions. Preferably, primary care providers will participate centrally in the family's Medical Home, helping to navigate referral and intervention sources, serving as an ongoing advocate for the family and child, keeping abreast of consultative information and scholastic progress, and monitoring growth and development over time.

Aim for early intervention

Birth to Three “Early Intervention” programs evaluate young children in at-risk categories of development. Children older than 3 years can be referred through their school districts for psychoeducational assessments. Optimally, interdisciplinary assessments are available (school districts, university medical settings, or privately) for comprehensive and integrated evaluation approaches. Selected disciplines may include combinations of a pediatric neurology, psychiatry, or neurodevelopmental-behavioral pediatrics; neuropsychology; social work; speech-language pathology; physical or occupational therapy; nutrition; and others—with disciplines chosen on the basis of availability and developmental concerns.

It is most important to educate the child's family about TS, help to answer questions, dispel misconceptions, offer assurance, and direct them to additional sources of guidance and support. For many, if not most, families with children who have TS, this intervention alone is adequate. Depending upon developmental and behavioral areas of concern, several support and education resources exist, some of which are listed in Appendices A and B.

Since children with TS who have comorbid ADHD or OCD are at increased risk for aggressive behaviors and poorer peer relations, early identification and management of each of the behavioral difficulties is essential. Interventions may include parenting skills development, behavioral modifications, special education services, psychological support, and, sometimes, psychotropic medication. An important point not to be overlooked is that in order to help the child, the parents must be treated, too. An overarching principle in developmental pediatrics is that the child alone is not the patient, but rather only in the context of his or her family can we most accurately understand and help the child. This principle becomes increasingly salient when recognizing the potential impact of the same disabilities present in the parents and siblings of a child with TS. Prevention goes a long way. Children can learn to enhance prosocial abilities and frustration tolerance, build skills in organization, and develop healthy self-esteem, which, first and foremost, must be modeled in the home. Disciplinary guidance should incorporate positive parenting concepts and reinforcement methods. Predictable consequences should be meted out swiftly and with emotional control; punishment ought to be minimized. Directing families to appropriate parenting resources is pivotal. Consistency in behavioral plans at home and school helps to generalize expectations for the child. Attention must be paid to potential language-processing difficulties and other cognitive challenges including executive dysfunctions, and to general anxiety, separation anxiety, susceptible situations, or tendency to emotional dysregulation in vulnerable children.

Attention-deficit/hyperactivity disorder and/or LD must be identified and treated with special education services (when eligible) and behavioral and other accommodations. Educators should learn about TS and the variable expressions of tics in their students who have the disorder. Most of the time, tics are overlooked and can be safely ignored. As tics become more interfering, classroom accommodations can be tailored to each child, and a wide range of recommendations for such strategies are available through the Tourette Syndrome Association (Appendix B). Teachers must respond sensitively in their reactions to children with TS, mindful that they serve as role models.

Tic management

In a minority of children with tic disorders, the tics are functionally interfering or cause distress or injury, and several tic control options are available. Behavioral tactics for tic control are effective for some children; in particular, “habit reversal therapy” (Azrin & Nunn, 1973; Piacentini & Chang, 2001) takes advantage of premonitory sensations antecedent to tics, teaching the child to use and alleviate the sensation by expressing a reduced or decelerated tic. Because most children younger than 10 years are not aware of premonitory sensations, however, and also because tics tend to be mild in very young children, habit reversal therapy is reserved for motivated older children, adolescents, and adults with mild to moderate tics.

NEUROPHARMACOLOGY

Medication use in TS is imperfect and often controversial (Pappadopulos, Tate Guelzow, Wong, Ortega, & Jensen, 2004; Sandor, 2003). Concerns address a lack of controlled trials in children and the unknown potential impact of psychotropic medications on young and developing brains. At the same time, some argue that there are potential consequences to brain and social development in not medicating. Medications are available for a wide range of TS symptoms, including tics, hyperactivity, poor concentration, anxiety, sleep disturbances, and others. These medications are approved for use in the United States, but few of them are labeled by the Food and Drug Administration (FDA) for use with children, and even fewer for children younger than 5 years. The use of these medications in the pediatric population is referred to as “off-label.” This does not mean that the medications cannot be prescribed and used by children, but that the sponsor and the FDA have not included children in the indications for use (cf, Committee on Drugs, American Academy of Pediatrics, 2002). Most drugs used to treat tic disorders and related comorbid conditions are prescribed as off-label uses. Many primary care providers may not be experienced or comfortable in managing psychotropic medication, and referral to a specialist may be indicated, particularly when complicated regimens are considered. Details regarding the range of medication options and approaches are beyond the scope of this article, but a few important points will be made.

Considerations in medicating for tic control

Most children with tic disorders will not require medication to reduce tics. Psychotropic medications, when indicated, usually target symptoms of comorbid conditions, and should be prescribed only as part of a comprehensive management strategy, as discussed. When medications are prescribed for tic reduction, goals should be restricted to tic reduction, not eradication (which is not possible), and to doses and schedules that minimize potential side effects. Ideally, a single agent is used, although often, more than one medication is prescribed.

Considerations in medicating for comorbid ADHD

Concerns regarding tic exacerbation with the use of psychostimulant medications are not supported by recent studies (Law & Schachar, 1999; Tourette's Syndrome Study Group, 2002). For a minority of children, these agents may cause transient tic exacerbation, although even this result is not clear. It is important to consider use of stimulant medication, given the number of children with tic disorders who have (and often first present with) comorbid ADHD. Psychostimulants enjoy the longest record of use in treating ADHD, and are the most effective medication class. Methylphenidate and mixed amphetamine salts have shown efficacy and tolerability in behavioral improvement among preschool children with ADHD (Short, Manos, Findling, & Schubel, 2004), and should be considered in management of comorbid ADHD.

Considerations in medicating for PANDAS

With regard to PANDAS, customary approaches to managing “strep throat” should be followed; any child suspicious for this infection on the basis of abrupt onset or dramatic exacerbations of tics or obsessive-compulsive symptoms concurrent with illness should have a throat culture taken. Positive throat culture results should be treated conventionally (Swedo et al., 2004). Some practitioners consider using prophylactic antibiotics to treat children who have a pattern of recurrent tic exacerbation associated with documented group A streptococcal pharyngitis (strep throat). This prevention approach, however, is generally not considered tenable because research data to support this practice are very limited (Kurlan & Kaplan, 2004) and the risks and liabilities to using antibiotics are quite real.

Complementary and alternative healthcare in TS

There is a strong and growing interest in the use of complementary and alternative agents for children with TS and comorbid conditions (Mantel, Meyers, Tran, Rogers, & Jacobson, 2004). To date, no such agents are proven effective for any aspect of TS, although currently a study of omega-3 fatty acids (fish oil) in children with TS is underway (Gabbay, Coffey, Castellanos, & Alonso, 2003). Although allopathic-trained providers should not prescribe or recommend agents that have not shown efficacy derived from rigorous study, it is important to recognize the widespread use of such agents and to inquire about their use specifically and direct families to credible resources for health information, such as the National Center for Complementary and Alternative Medicine (Appendix B). In addition, providers and consumers should make themselves aware of health risks and product quality associated with alternative agents that are not FDA-regulated. Risks may be inherent to a particular agent, but there are also risks for potential interactions with prescribed pharmaceutical agents. As is true for FDA-regulated drugs, less is known about the efficacy of herbal and other unregulated remedies in children compared with their efficacy in adults (De Smet, 2004).

PROGNOSIS

Most preschool children who develop TS will experience the greatest frequency and severity in tic expression between 10 and 12 years of age, followed by a gradual decline in tics by early adolescence, and complete remission in up to half by adulthood. The available research data that address prognosis in TS are very limited and somewhat contradictory (Coffey et al., 2000). Recent data suggest that TS-related psychosocial impairment (ie, self-esteem, family life, social acceptance, or school functioning) also improves over time (Coffey et al., 2004). Tic severity and age of onset do not predict the course of the tic disorder. Degree, number, and type of comorbid condition(s) are likely to have more impact on functional outcome and quality of life than do tics. Most important, each comorbid condition may follow its own independent course, irrespective of the course of tics or other comorbid or environmental influences. Symptoms of comorbid conditions can emerge before, during, or after the preschool years and/or the emergence of tic symptoms.

CONCLUSIONS

Tourette syndrome is a neurodevelopmental disorder, which, by definition, indicates growth and change. Many children with tic disorders will have a mild disease course. Ongoing monitoring for the emergence of tics and signs of comorbid conditions in young children who are either at risk to develop TS, or who have been diagnosed with TS and/or with a comorbid condition, ensures the likeliest opportunities for early identification and intervention. Children and families are best served when they develop a partnership with a supportive and involved provider, building a stable Medical Home. When indicated, access to effective psychosocial, educational, behavioral, and medical supports is indispensable for successful outcomes. Remember to emphasize strengths in children and their families. National and international research and advocacy efforts are underway to enable earlier identification, more effective treatments and services for children and families affected by TS, and exploration of genetic underpinnings.

REFERENCES

Abwender, D. A., Trinidad, K. S., Jones, K. R., Como, P. G., Hymes, E., & Kurlan, R. (1998). Features resembling Tourette's syndrome in developmental stutterers. Brain and Language, 62, 455–464.
Azrin, N. H., & Nunn, R. G. (1973). Habit reversal: A method of eliminating nervous habits and tics. Behaviour Research and Therapy, 11, 619–628.
Baron-Cohen, S., Mortimore, C., Moriarty, J., Izaguirre, J., & Robertson, M. (1999). The prevalence of Gilles de la Tourette's syndrome in children and adolescents with autism. Journal of Child Psychology and Psychiatry and Allied Disciplines, 40, 213–218.
Baron-Cohen, S., Scahill, V. L., Izaguirre, J., Hornsey, H., & Robertson, M. M. (1999). The prevalence of Gilles de la Tourette syndrome in children and adolescents with autism: A large scale study. Psychological Medicine, 29, 1151–1159.
Bawden, H. N., Stokes, A., Camfield, C. S., Camfield, P. R., & Salisbury, S. (1998). Peer relationship problems in children with Tourette's disorder or diabetes mellitus. Journal of Child Psychology and Psychiatry and Allied Disciplines, 39, 663–668.
Budman, C. L., Rockmore, L., Stokes, J., & Sossin, M. (2003). Clinical phenomenology of episodic rage in children with Tourette syndrome. Journal of Psychosomatic Research, 55, 59–65.
Burd, L., & Kerbeshian, J. (1987). Onset of Gilles de la Tourette' syndrome before 1 year of age. American Journal of Psychiatry, 144, 1066–1067.
Burd, L., Severud, R., Klug, M. G., & Kerbeshian, J. (1999). Prenatal and perinatal risk factors for Tourette disorder. Journal of Perinatal Medicine, 27, 295–302.
Burnstein, M. H. (1992). Tourette's syndrome and neonatal anoxia: Further evidence of an organic etiology. Journal of Psychiatry & Neuroscience, 17, 89–92.
Channon, S., Crawford, S., Vakili, K., & Robertson, M. D. (2003). Real-life-type problem solving in Tourette syndrome. Cognitive and Behavioral Neurology, 16, 3–15.
Coffey, B. J., Biederman, J., Geller, D., Frazier, J., Spencer, T., Doyle, R., et al. (2004). Reexamining tic persistence and tic-associated impairment in Tourette's Disorder. The Journal of Nervous and Mental Disease, 192, 776–780.
Coffey, B. J., Biederman, J., Geller, D. A., Spencer, T., Park, K. S., Shapiro, S. J., et al. (2000). The course of Tourette's disorder: A literature review. Harvard Review of Psychiatry, 8, 192–198.
Committee on Drugs, American Academy of Pediatrics. (2002). Uses of drugs not described in the package insert (off-label uses). Pediatrics, 110, 181–183.
De Smet, P. A. G. M. (2004). Health risks of herbal remedies: An update. Clinical Pharmacology & Therapeutics, 76, 1–17.
Evans, D. W., Leckman, J. F., Carter, A., Reznick, J. S., Henshaw, D., King, R. A., et al. (1997). Ritual, habit, and perfectionism: The prevalence and development of compulsive-like behavior in normal young children. Child Development, 68, 58–68.
Fazzi, E., Lanners, J., Danova, S., Ferrarri-Ginevra, O., Gheza, C., Luparia, A., et al. (1999). Stereotyped behaviours in blind children. Brain & Development, 21, 522–528.
Fernandez-Alvarez, E. (1998). Transient movement disorders in children. Journal of Neurology, 245, 1–5.
Freeman, R. D., Fast, D. K., Burd, L., Kerbeshian, J., Robertson, M. M., & Sandor, P. (2000). An international perspective on Tourette syndrome: Selected findings from 3500 individuals in 22 countries. Developmental Medicine & Child Neurology, 42, 436–447.
Gabbay, V., Coffey, B., Castellanos, F., & Alonso, C. (2003). The efficacy of fish oil in children with Tourette's disorder [Abstract B35]. Program and abstracts of the American Academy of Child & Adolescent Psychiatry 50th Annual Meeting, October 14–19, 2003, Miami, FL.
Gerard, E., & Peterson, B. S. (2003). Developmental processes and brain imaging studies in Tourette syndrome. Journal of Psychosomatic Research, 55, 13–22.
Gillberg, C., & Kadesjo, B. (2003). Why bother about clumsiness? The implications of having developmental coordination disorder (DCD). Neural Plasticity, 10, 59–68.
Gilles de la Tourette, G. (1885). Étude sur une affection nerveuse caracterisée par l'incoordination motrice accompagnée d'écholalie et de coprolalie. Archives de Neurologie [Paris], 9, 19–42, 158–200.
Goldenberg, J. N., Brown S. B., & Weiner, W. J. (1994). Coprolalia in younger patients with Gilles de la tourette syndrome. Movement Disorders, 9, 622–625.
Harris, E. L., Schuerholz, L. J., Singer, H. S., Reader, M. J., Brown, J. E., Cox, C., et al. (1995). Executive function in children with Tourette syndrome and/or attention deficit hyperactivity disorder. Journal of the International Neuropsychological Society, 1, 511–516.
Hirshfeld-Becker, D. R., Biederman, J., Faraone, S. V., Violette, H., Wrightsman, J., & Rosenbaum, J. F. (2002). Temperamental correlates of disruptive behavior disorders in young children: Preliminary findings. Biological Psychiatry, 50, 563–574.
Hyde, T. M., Aaronson, B. A., Randolph, C., Rickler, K. C., & Weinberger, D. R. (1992). Relationship of birth weight to the phenotypic expression of Gilles de la Tourette's syndrome in monozygotic twins. Neurology, 42, 652–658.
Hyde, T. M., Emsellem, H. A., Randolph, C., Rickler, K. C., & Weinberger, D. R. (1994). Electroencephalographic abnormalities in monozygotic twins with Tourette's syndrome. British Journal of Psychiatry, 164, 811–817.
Kadesjo, B., & Gillberg, C. (2000). Tourette's Disorder: Epidemiology and comorbidity in primary school children. Journal of the American Academy of Child & Adolescent Psychiatry, 39, 548–555.
Kano, Y., Ohta, M., Nagai, Y., Yokota, K., & Shimizu, Y. (1988). Tourette's disorder coupled with infantile autism: A prospective study of two boys. Japanese Journal of Psychiatry and Neurology, 42, 49–57.
Kurlan, R., Como, P. G., Miller, B., Palumbo, D., Deeley, C., Andresen, E. M., et al. (2002). The behavioral spectrum of tic disorders: A community-based study. Neurology, 59, 414–420.
Kurlan, R., & Kaplan, E. L. (2004). The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) etiology for tics and obsessive-compulsive symptoms: Hypothesis or entity? Practical considerations for the clinician. Pediatrics, 113, 883–886.
Lahey, B. B., Pelham, W. E., Stein, M. A., Loney, J., Trapani, C., Nugent, K., et al. (1998). Validity of DSM-IV attention-deficit/hyperactivity disorder for younger children. Journal of the American Academy of Child & Adolescent Psychiatry, 37, 695–702.
Law, S. F., & Schachar, R. J. (1999). Do typical clinical doses of methylphenidate cause tics in children treated for attention-deficit hyperactivity disorder? Journal of the American Academy of Child & Adolescent Psychiatry, 38, 944–951.
Leckman, J. F., Dolnansky, E. S., Hardin, M. T., Clubb, M., Walkup, J. T., Stevenson, J., et al. (1990). Perinatal factors in the expression of Tourette's syndrome: An exploratory study. Journal of the American Academy of Child & Adolescent Psychiatry, 29, 220–226.
Leckman, J. F., King, R. A., & Cohen, D. J. (1999). Tics and tic disorders. In J. F. Leckman & D. J. Cohen (Eds.), Tourette's syndrome—Tics, obsessions, compulsions: Developmental psychopathology and clinical care (pp. 23–42). New York: Wiley.
Leckman, J. F., & Peterson, B. S. (1993). The pathogenesis of Tourette's syndrome: Epigenetic factors active in early CNS development. Biological Psychiatry, 34, 425–427.
Leckman, J. F., & Riddle, M. A. (2000). Tourette's syndrome: When habit-forming systems form habits of their own? Neuron, 28, 349–354.
Lederberg, A. R., & Everhart, V. S. (1998). Communication between deaf children and their hearing mothers: The role of language, gesture, and vocalizations. Journal of Speech, Language, and Hearing Research, 41, 887–899.
Mantel, B. J., Meyers, A., Tran, Q. Y., Rogers, S., & Jacobson, J. S. (2004). Nutritional supplements and complementary/alternative medicine in Tourette syndrome. Journal of Child and Adolescent Psychopharmacology, 14, 582–589.
McMahon, W. M., Carter, A. S., Fredine, N., & Pauls, D. L. (2003). Children at familial risk for Tourette's disorder: Child and parent diagnoses. American Journal of Medical Genetics, 121B, 105–111.
Nestadt, G., Samuels, J., Riddle, M., Bienvenu, O. J., Liang, K. Y., La Buda, M., et al. (2000). A family study of obsessive-compulsive disorder. Archives of General Psychiatry, 57, 358–363.
Pappadopulos, E. A., Tate Guelzow, B., Wong, C., Ortega, M., & Jensen, P. S. (2004). A review of the growing evidence base for pediatric psychopharmacology. Child and Adolescent Psychiatry Clinics of North America, 13, 817–855.
Pasamanick, B., & Kawi, A. (1956). A study of the association of prenatal and paranatal factors with the development of tics in children; a preliminary investigation. Journal of Pediatrics, 48, 596–601.
Pauls, D. L. (2003). An update on the genetics of Gilles de la Tourette syndrome. Journal of Psychosomatic Research, 55, 7–12.
Peterson, B. S., Leckman, J. F., Scahill, L., Naftolin, F., Keefe, D., Charest, N. J., et al. (1992). Steroid hormones and CNS sexual dimorphisms modulate symptom expression in Tourette's syndrome. Psychoneuroendocrinology, 17, 553–563.
Piacentini, J., & Chang, S. (2001). Behavioral treatments for Tourette syndrome and tic disorders: State of the art. Advances in Neurology, 85, 319–331.
Price, R. A., Kidd, K. K., Cohen, D. J., Pauls, D. L., & Leckman, J. F. (1985). A twin study of Tourette syndrome. Archives of General Psychiatry, 42, 815–820.
Randolph, C., Hyde, T. M., Gold, J. M., Goldberg, T. E., & Weinberger, D. R. (1993). Tourette's syndrome in monozygotic twins—Relationship of tic severity to neuropsychological function. Archives of Neurology, 50, 725–728.
Ringman, J. M., & Jankovic, J. (2000). Occurrence of tics in Asperger's syndrome and autistic disorder. Journal of Child Neurology, 15, 394–400.
Rosario-Campos, M. C., Leckman, J. F., Mercadante, M. T., Shavitt, R. G., Prado, H. S., Sada, P., et al. (2001). Adults with early-onset obsessive-compulsive disorder. American Journal of Psychiatry, 158, 1899–1903.
Sandor, P. (2003). Pharmacological management of tics in patients with TS. Journal of Psychosomatic Research, 55, 41–48.
Santangelo, S. L., Pauls, D. L., Goldstein, J. M., Faraone, S. V., Tsuang, M. T., & Leckman, J. F. (1994). Tourette's syndrome: What are the influences of gender and comorbid obsessive-compulsive disorder? Journal of the American Academy of Child & Adolescent Psychiatry, 33, 795–804.
Schuerholz, L. J., Cutting, L., Mazzocco, M. M. M., Singer, H. S., & Denckla, M. B. (1997). Neuromotor functioning in children with Tourette syndrome with and without attention deficit hyperactivity disorder. Journal of Child Neurology, 12, 438–442.
Sheppard, D. M., Bradshaw, J. L., Purcell, R., & Pantelis, C. (1999). Tourette's and comorbid syndromes: Obsessive compulsive and attention deficit hyperactivity disorder. A common etiology? Clinical Psychology Review, 19, 531–552.
Short, E. J., Manos, M. J., Findling, R. L., & Schubel, E. A. (2004). A prospective study of stimulant response in preschool children: Insights from ROC analyses. Journal of the American Academy of Child & Adolescent Psychiatry, 43, 251–259.
Singer, H. S., & Minzer, K. (2003). Neurobiology of Tourette's syndrome: Concepts of neuroanatomic localization and neurochemical abnormalities. Brain & Development, 25(Suppl. 1), S70–S84.
Smith-Gray, S., & Koester, L. S. (1995). Defining and observing social signals in deaf and hearing infants. American Annals of the Deaf, 140, 422–427.
Snider, L. A., Seligman, L. D., Ketchen, B. R., Levitt, S. J., Bates, L. R., Garvey, M. A., et al. (2002). Tics and problem behaviors in schoolchildren: Prevalence, characterization, and associations. Pediatrics, 110, 331–336.
Spencer, T., Biederman, J., Harding, M., O'Donnell, D., Wilens, T., Faraone, S., et al. (1998). Disentangling the overlap between Tourette's disorder and ADHD. Journal of Child Psychology and Psychiatry and Allied Disciplines, 39, 1037–1044.
Stephens, R. J., & Sandor, P. (1999). Aggressive behaviour in children with Tourette syndrome and comorbid attention-deficit hyperactivity disorder and obsessive-compulsive disorder. Canadian Journal of Psychiatry, 44, 1036–1042.
Sukhodolsky, D. G., Scahill, L., Zhang, H., Peterson, B. S., King, R. A., Lombroso, P. J., et al. (2003). Disruptive behavior in children with Tourette's syndrome: Association with ADHD comorbidity, tic severity, and functional impairment. Journal of the American Academy of Child & Adolescent Psychiatry, 42, 98–105.
Sverd J., & Montero, G. (1993). Is Tourette syndrome a cause of sudden infant death syndrome and childhood obstructive sleep apnea? American Journal of Medical Genetics, 46, 494–496.
Swedo, S. E., Leonard, H. L., & Rapoport, J. L. (2004). The Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) subgroup: Separating fact from fiction. Pediatrics, 113, 907–911.
Swerdlow, N. R., & Young, A. B. (2001). Neuropathology in Tourette syndrome: An update. Advances in Neurology, 85, 151–161.
Tourette's Syndrome Study Group. (2002). Treatment of ADHD in children with tics: A randomized controlled trial. Neurology, 58, 527–536.
Zebrowski, P. M. (2003). Developmental stuttering. Pediatric Annals, 32, 453–458.
Zinner, S. H. (2000). Tourette disorder. Pediatrics in Review, 21, 372–383.

Appendix A

Resources for Primary Care Providers

Appendix B

Educational and Support Resources for Providers, Parents, and Educators

Keywords:

attention-deficit/hyperactivity disorder; basal ganglia; blinking; child; comorbidity; learning disability; obsessive-compulsive disorder; social support; tics; Tourette syndrome

©2006Lippincott Williams & Wilkins, Inc.