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Tourette Syndrome in Infancy and Early Childhood
Abstract
Although it is the presence of motor and phonic tics that defines Tourette syndrome (TS), explorations over the past two decades have uncovered a complex and multidimensional nature of this genetic-based neurological disorder. Tics customarily first become apparent during the latter half of the first decade of life, although they may occur earlier, including during infancy. However, associated comorbid conditions, rather than tics, usually determine the functional and qualitative experiences for the child with TS. These conditions often become problematic prior to tic onset. Misconceptions regarding the nature of tics and the varied associated conditions are common, placing children with TS at significant risk for underdiagnosis, mismanagement, and missed opportunities for prevention. This article will consider risk factors and associated behaviors, both subtle and more obvious, that can alert the clinician to infants and young children with tics or who are at increased risk to develop TS. Themes in management strategies include interdisciplinary participation, Medical Home foundation, and ongoing monitoring and support.
... Although it is accepted that there is a genetic contribution to TD, the corresponding gene locus has not yet been identified (Zinner, 2006). Twin studies reveal high concordance rates in monozygotic twins but not in dizygotic twins (Robertson, Althoff, Hafez, & Pauls, 2008). ...
... However, genetics is not the only factor because in nearly half of the affected monozygotic twins, only one twin is diagnosed with TD (Hyde, Emsellem, Randolph, Rickler, & Weinberger, 1994). Studies attempting to discern risk factors associated with TD are limited, yet risk factors may include lower birth weight, intrauterine growth retardation, maternal stress during pregnancy, and perinatal complications such as neonatal anoxia (Zinner, 2006). ...
This is a case study of a deaf child with Tourette’s Disorder (TD). Hearing parents and mental health clinicians unfamiliar
with typical behaviors of deaf children may have difficulties differentiating the clinical presentation of symptoms of TD
from the effects of deafness, as well as in implementing appropriate interventions. This case study reports the history, symptoms,
diagnostic process, and treatment interventions. This is relevant for furthering the clinical knowledge of mental health professionals
working with Deaf, deaf, and hard-of-hearing children and adolescents.
... Children suppress or hide tics in the doctor's office, leading many general practitioners to miss tics or mistake those observed as symptoms of allergies or "nervousness," resulting in referrals to ophthalmologists, allergists, or psychologists. This only delays proper diagnosis and treatment, amplifying family distress ( Bruun and Budman, 2005;Zinner, 2006). ...
... Tourette Syndrome has an interesting natural history, or classical pattern of development. Motor tics appear first, around the age of five to seven ( Freeman et al., 2000;Leckman et al., 2006a;Zinner, 2006), joined by vocal tics on average two years later, somewhere between 8-15 years of age (Peterson, 1996;Leckman et al., 2006a). Tics progress in a rostral-caudal manner, first affecting the face and head (e.g., eye blinking, head bobbing, and neck craning), then the torso (e.g., abdominal flexing and shoulder shrugging), and finally the limbs (e.g., finger tapping and knee bouncing; Singer and Walkup, 1991;Bruun and Budman, 2005). ...
Tourette Syndrome begins in childhood and is characterized by uncontrollable repetitive actions like neck craning or hopping and noises such as sniffing or chirping. Worst in early adolescence, these tics wax and wane in severity and occur in bouts unpredictably, often drawing unwanted attention from bystanders. Making matters worse, over half of children with Tourette Syndrome also suffer from comorbid, or concurrent, disorders such as attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). These disorders introduce anxious thoughts, impulsivity, inattention, and mood variability that further disrupt children with Tourette Syndrome from focusing and performing well at school and home. Thus, deficits in the cognitive control functions of response inhibition, response generation, and working memory have long been ascribed to Tourette Syndrome. Yet, without considering the effect of medication, age, and comorbidity, this is a premature attribution. This study used an infrared eye tracking camera and various computer tasks requiring eye movement responses to evaluate response inhibition, response generation, and working memory in Tourette Syndrome. This study, the first to control for medication, age, and comorbidity, enrolled 39 unmedicated children with Tourette Syndrome and 29 typically developing peers aged 10-16 years who completed reflexive and voluntary eye movement tasks and diagnostic rating scales to assess symptom severities of Tourette Syndrome, ADHD, and OCD. Children with Tourette Syndrome and comorbid ADHD and/or OCD, but not children with Tourette Syndrome only, took longer to respond and made more errors and distracted eye movements compared to typically-developing children, displaying cognitive control deficits. However, increasing symptom severities of Tourette Syndrome, ADHD, and OCD correlated with one another. Thus, cognitive control deficits were not specific to Tourette Syndrome patients with comorbid conditions, but rather increase with increasing tic severity, suggesting that a majority of Tourette Syndrome patients, regardless of a clinical diagnosis of ADHD and/or OCD, have symptoms of cognitive control deficits at some level. Therefore, clinicians should evaluate and counsel all families of children with Tourette Syndrome, with or without currently diagnosed ADHD and/or OCD, about the functional ramifications of comorbid symptoms and that they may wax and wane with tic severity.
... 30 Specifically, it has been suggested that improving care coordination -a component of the medical home -may be of particular benefit to children with TS given the complexity of the condition and high prevalence of co-occurring conditions. 10,31 The reported findings are subject to certain limitations. The overall response rate for the 2011-2012 National Survey of Children s Health was low. ...
Objective:
To provide recent estimates of the prevalence of Tourette syndrome among a nationally representative sample of US children and to describe the association of Tourette syndrome with indicators of health and functioning.
Methods:
Data on 65,540 US children aged 6 to 17 years from the 2011-2012 National Survey of Children's Health were analyzed. Parents reported whether a health care provider had ever told them their child had Tourette syndrome or other neurobehavioral or chronic health conditions and whether their child had current Tourette syndrome.
Results:
Based on parents' report, 0.19% of US children had Tourette syndrome; the average age of diagnosis was 8.1 years. Children with Tourette syndrome, compared with those without, were more likely to have co-occurring neurobehavioral and other health conditions, meet criteria for designation as having a special health care need, receive mental health treatment, have unmet mental health care needs, and have parents with high parenting aggravation and parents who were contacted about school problems; they were less likely to receive effective care coordination or have a medical home. After controlling for co-occurring neurobehavioral conditions, the findings on parents being contacted about school problems and children having unmet mental health care needs were no longer significant.
Conclusions:
Tourette syndrome is characterized by co-occurring neurobehavioral and other health conditions, and poorer health, education, and family relationships. The findings support previous recommendations to consider co-occurring conditions in the diagnosis and treatment of Tourette syndrome. Future research may explore whether having a medical home improves outcomes among children with Tourette syndrome.
... [3][4][5] Average age of onset of CTD is 7 years, with onset as early as a few months of age. 6 The prevalence and severity of tic disorders has a peak around age 9 to 12 years, 7 followed by a decrease in prevalence with age, 7,8 with remission or marked attenuation of tic severity in most individuals (65%) by age 18 to 20 years. 2 The early presentation of CTD may be indistinguishable from bouts of transient tics, but then progresses to a more typical chronic waxing and waning course. [8][9][10] Children with only OCD or tics may develop additional symptoms months or years later. ...
Tic disorders, including Tourette’s disorder, present with a wide range of symptom severity and associated comorbidity. This Practice Parameter reviews the evidence from research and clinical experience in the evaluation and treatment of pediatric tic disorders. Recommendations are provided for a comprehensive evaluation to include common comorbid disorders and for a hierarchical approach to multimodal interventions.
Objective:
To review current multidisciplinary care practices in patients with Tourette syndrome (TS).
Background:
Individuals with TS can have multiple symptoms and comorbidities and require treatment to encompass all of their needs. A multidisciplinary research or care model approaches the situation/problem from all sides and uses multiple perspectives.
Methods:
A database search of Medline (using Pubmed), PsychINFO, and Scopus was performed using keywords related to multidisciplinary care and TS. The authors then screened the results for relevant information using a standardized extraction form to collect data. Next, relevant codes from text analysis were extracted with a final list agreed on with author consensus. Finally, we inferred common themes.
Results:
The search revealed 2304 citations, and 87 were selected for full-text analysis. One additional article was identified by manual search. Thirty-one citations were deemed relevant. Multidisciplinary team members typically included a psychiatrist or child psychiatrist, a neurologist or child neurologist, and a psychologist or therapist at the core. Four primary benefits were associated with multidisciplinary care: establishing the diagnosis, managing the complexity of TS and its associated comorbidities, averting complications, and evaluating advanced therapies. Limitations include possible poor team dynamics and rigidity in the approach leading to an algorithmic treatment plan.
Conclusions:
A multidisciplinary care model for TS is the preferred model advocated by patients, physicians, and organizations. This scoping review reveals that the impetus for multidisciplinary care rests on four primary benefits, but there is a lack of empirical evidence for defining and evaluating its use.
Parenting a young person with a tic disorder can present daily challenges to families struggling to manage their child’s tics and establish routines. Research recognises that tics can be problematic to everyday activities, however no attention has been given to mealtimes, arguably an important family activity closely related to quality of life of the family. The current qualitative study aimed to investigate the mealtime experiences of families with a child with a tic disorder from the perspective of mothers, looking at
mealtime challenges, their impact and how these challenges are navigated. Seventeen mothers with children diagnosed with Tourette Syndrome (TS) or a Persistent Tic Disorder (PTD) (aged 3–14) took part in semi-structured interviews. Interpretative phenomenological analysis of 17 semi-structured interviews resulted in seven subthemes which were grouped under two superordinate themes: (1) tics as a barrier to positive mealtime experiences and (2) eating behaviours and other mealtime challenges. The findings highlight tics to create functional mealtime challenges, affecting a young person’s ability to eat, drink and be seated, with mothers noting the family dynamic was often intensified and compounded by additional challenges related to their child’s
tics and comorbidities. Tics also have the power to disrupt the conviviality of
mealtimes. For example, eating out-of-home can be especially challenging,
with restaurants being high-pressure environments for young people with tics
and their families. The cumulative effect of dissatisfaction, stress and additional
foodwork can have a diminishing effect on maternal and familial resilience and wellbeing. Mealtime-related interventions need to be considered to help increase confidence and skills in managing mealtimes.
Chronic tic disorders (CTDs) are a category of movement disorders, including Tourette's syndrome, that typically onset in youth and can be associated with a wide range of topography, complexity, severity and co-occurring conditions. We present an overview of evidence-based recommendations on the assessment and management of CTD for healthcare professionals. In particular, the following article focuses on the assessment and differential diagnosis of CTDs from other movement or psychiatric conditions, pharmacological and behavioral treatments of CTDs, as well as considerations and recommendations for treatment decisions for CTDs.
Aggressive behaviour, defined as sudden, explosive outbursts of rage, has been reported as a clinical problem in approximately 23% to 40% of Tourette syndrome (TS) patients (1-5). Attention-deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) are also reported in 50% to 70% of TS patients (6).
To investigate whether aggressive behaviour was associated with TS directly or found primarily in TS with comorbid ADHD or OCD.
Aggressive behaviour in 33 nonmedicated patients with TS (ages 6 to 14 years) and 6 healthy control subjects (ages 7 to 12 years) was examined by semistructured interview and multiinformant questionnaires.
Aggression subscales on Achenbach's Child Behavior Checklist (CBCL) completed by parents and Teacher's Report Form (TRF) completed by teachers distinguished the TS-only and control groups from the group with TS + Comorbidity (P < 0.046, and P < 0.016) after adjusting for tic severity and age. The conduct disorder subscale on the Conners Parent Rating Scale (CPRS) was also significantly higher (P < 0.005) in the TS + comorbidity group than in the TS-only or control groups, with more problems reported in the older children.
These findings provide additional evidence that aggressive behaviour observed in children with TS may be associated with comorbid ADHD or OCD (6), independent of tic severity or age. This is consistent with the clinical observation that most TS patients have only minimal symptoms, which do not interfere with their daily functioning.
In 43 pairs of same-sex twins, in which at least one co-twin had Tourette syndrome (TS), 30 pairs were probably monozygotic (MZ) and 13 were probably dizygotic (DZ). Concordances for TS were 53% and 8% for MZ and DZ pairs, respectively. When diagnostic criteria were broadened to include any tics in co-twins, concordance rates were 77% and 23% for MZ and DZ pairs, respectively. These concordances are consistent with genetic etiology. However, the fact that only 53% of MZ twins were fully concordant indicates nongenetic factors affect expression of TS. Presence of tics in discordant co-twins and timing of onset in partially concordant co-twins support an association between TS and tics in families with TS present. The data are inconclusive on whether some MZ twins with discordant co-twins are etiologically different from those who are concordant.
An earlier small-scale study of children with autism revealed that 8.1% of such patients were co-morbid for Gilles de la Tourette syndrome (GTS). The present study is a large scale test of whether this result replicates.
Four hundred and forty-seven pupils from nine schools for children and adolescents with autism were screened for the presence of motor and vocal tics.
Subsequent family interviews confirmed the co-morbid diagnosis of definite GTS in 19 children, giving a prevalence rate of 4.3%. A further 10 children were diagnosed with probable GTS (2.2%).
These results indicate that the rate of GTS in autism exceeds that expected by chance, and the combined rate (6.5%) is similar to the rates found in the smaller-scale study. Methodological considerations and alternative explanations for an increased prevalence are discussed.
Obsessive-compulsive disorder (OCD) is a clinically heterogeneous disorder with a bimodal age at onset and range of treatment outcomes. This study attempted to ascertain the importance of the age at OCD symptom onset for a better phenotypic precision. Therefore, the authors compared adult OCD patients with an early symptom onset to OCD patients with a later symptom onset.
Forty-two adult outpatients with OCD were evaluated with semistructured interviews: 21 with symptom onset before the age of 10 (early-onset group) and 21 with symptom onset after the age of 17 (late-onset group).
Early onset was associated with higher scores on the Yale-Brown Obsessive Compulsive Scale, higher frequencies of tic-like compulsions, higher frequency of sensory phenomena, and a higher rate of comorbid tic disorders. The early-onset group also responded less well to treatment with clomipramine and selective serotonin reuptake inhibitors.
The results indicate that age at onset may be an important factor in subtyping OCD and that the phenotypic differences found were not restricted to childhood.
Objective: The purpose of this study was to examine the efficacy of psychostimulant medication in a naturalistic sample of preschoolers. Benefits and side effects for methylphenidate and mixed amphetamine salts (Adderall) were examined. Method: Twenty-eight preschoolers (ages 4.0-5.9) participated in the present investigation. They were obtained consecutively from a large sample of suburban children assessed for attention-deficit/hyperactivity disorder. After having received various dosing levels of a stimulant in a placebo-controlled crossover design, best dose was assigned based on the lowest Abbreviated Symptoms Questionnaire T score received in a given week. All analyses compared best dose ratings to placebo ratings. Results: Preschoolers' behavioral ratings by parents and teachers were improved as a function of stimulant medication. More than 82% of the medicated sample improved their behavioral rating by at least 1 SD as demonstrated by receiver operating characteristic (ROC) analyses, with more than 50% of medicated preschoolers improving by more than 2 SD. Side effects were infrequent at best dose of medication. Conclusions: Clinically significant changes in behavioral ratings of preschoolers were noted in response to stimulant medication. Both stimulants were well tolerated. ROC curves were useful for clearly depicting on a case-by-case basis how much improvement was derived from psychopharmacological treatment.
New regulatory initiatives have been designed to ensure that new drugs and biologicals include adequate pediatric labeling for the claimed indications at the time of, or soon after, approval. However, because such labeling may not immediately be available, off-label use (or use that is not included in the approved label) of therapeutic agents is likely to remain common in the practice of pediatrics. This policy statement was written to address questions practitioners have regarding off-label use. The purpose of off-label use is to benefit the individual patient. Practitioners may use their professional judgment to determine these uses. Practitioners should understand that the Food and Drug Administration does not regulate off-label use.
• In 43 pairs of same-sex twins, in which at least one co-twin had Tourette syndrome (TS), 30 pairs were probably monozygotic (MZ) and 13 were probably dizygotic (DZ). Concordances for TS were 53% and 8% for MZ and DZ pairs, respectively. When diagnostic criteria were broadened to include any tics in co-twins, concordance rates were 77% and 23% for MZ and DZ pairs, respectively. These concordances are consistent with genetic etiology. However, the fact that only 53% of MZ twins were fully concordant indicates nongenetic factors affect expression of TS. Presence of tics in discordant co-twins and timing of onset in partially concordant co-twins support an association between TS and tics in families with TS present. The data are inconclusive on whether some MZ twins with discordant co-twins are etiologically different from those who are concordant.
• Objective.
—To determine whether there is a relationship between tic severity and neuropsychological function in Tourette's syndrome (TS).Design.
—The study employed a case-control series involving monozygotic twin pairs, divided into more severe and less severe groups based on tic severity and tested with a neuropsychological battery of tests.Setting.
—Twin pairs were recruited nationwide and evaluated in the National Institute of Mental Health Neuropsychiatric Research Hospital.Patients.
—Twelve twin pairs (mean age, 10.5 years; range, 8 to 16 years) in which at least one member met criteria for a diagnosis of TS.Results.
—Global neuropsychological performance was significantly worse in the twins with more severe tic symptoms, with significant differences emerging on individual tests of attention, visuospatial perception, and motor function. In each twin pair, the twin with more severe tics had poorer global neuropsychological function.Conclusions.
—The results suggest that the nongenetic factors that influence tic severity in TS exert a similar effect on neuropsychological function, and that these two clinical manifestations of TS may share a common pathophysiologic state.
We have established a multisite, international database of 3500 individuals diagnosed with Tourette syndrome (TS). The male:female ratio is 4.3:1 for the total sample, with wide variation among sites; the male excess occurs at every site. Anger control problems, sleep difficulties, coprolalia, and self-injurious behavior only reach impressive levels in individuals with comorbidity. Anger control problems are strongly correlated with comorbidity, regardless of site, region, or whether assessed by neurologists or psychiatrists. The mean age at onset of tics is 6.4 years. At all ages, about 12% of individuals with TS have no reported comorbidity. The most common reported comorbidity is attention-deficit-hyperactivity disorder. Males are more likely to have comorbid disorders than females. The earlier the age at onset, the greater the likelihood of a positive family history of tics. An understanding of the factors producing these and other variations might assist in better subtyping of TS. Because behavioral problems are associated with comorbidity, their presence should dictate a high index of suspicion of the latter, whose treatment may be at least as important as tic reduction. The established database can be used as the entry point for further research when large samples are studied and generalizability of results is important.
Background:
The treatment of children with attention deficit hyperactivity disorder (ADHD) and Tourette syndrome (TS) has been problematic because methylphenidate (MPH)--the most commonly used drug to treat ADHD--has been reported to worsen tics and because clonidine (CLON)--the most commonly prescribed alternative--has unproven efficacy.
Methods:
The authors conducted a multicenter, randomized, double-blind clinical trial in which 136 children with ADHD and a chronic tic disorder were randomly administered CLON alone, MPH alone, combined CLON + MPH, or placebo (2 x 2 factorial design). Each subject participated for 16 weeks (weeks 1-4 CLON/placebo dose titration, weeks 5-8 added MPH/placebo dose titration, weeks 9-16 maintenance therapy).
Results:
Thirty-seven children were administered MPH alone, 34 were administered CLON alone, 33 were administered CLON + MPH, and 32 were administered placebo. For our primary outcome measure of ADHD (Conners Abbreviated Symptom Questionnaire--Teacher), significant improvement occurred for subjects assigned to CLON (p < 0.002) and those assigned to MPH (p < 0.003). Compared with placebo, the greatest benefit occurred with combined CLON + MPH (p < 0.0001). CLON appeared to be most helpful for impulsivity and hyperactivity; MPH appeared to be most helpful for inattention. The proportion of individual subjects reporting a worsening of tics as an adverse effect was no higher in those treated with MPH (20%) than those being administered CLON alone (26%) or placebo (22%). Compared with placebo, measured tic severity lessened in all active treatment groups in the following order: CLON + MPH, CLON alone, MPH alone. Sedation was common with CLON treatment (28% reported moderate or severe sedation), but otherwise the drugs were tolerated well, including absence of any evident cardiac toxicity.
Conclusions:
Methylphenidate and clonidine (particularly in combination) are effective for ADHD in children with comorbid tics. Prior recommendations to avoid methylphenidate in these children because of concerns of worsening tics are unsupported by this trial.
Fatigue life evaluations have been carried out on gas tungsten arc welded (GTAW) load-carrying cruciform joints of AISI 304L stainless steel with lack of penetration (LOP) using conventional S-N and crack initiation-propagation (I-P) methods. The crack process normally comprises two major phases: (1) the crack initiation life (Ni): and (2) the crack propagation life (Np). The local stress-life approach is used to estimate the crack initiation life and a fracture mechanics approach for predicting crack propagation life of welded joints. Constant amplitude fatigue tests with stress ratio, R=0 were carried out using 100 KN servo-hydraulic DARTEC universal testing machine with frequency of 30 Hz. An automatic crack monitoring system based on crack propagation gauges was used to find the crack initiation and propagation data during fatigue process. The predicted lives were compared with the experimental values. It was found that the fatigue lives of the joints with LOP=2 mm for 6 mm thickness plate were relatively higher than those for the joints with other LOP sizes. Test results were compared with BS 5400: part 10 (now replaced by BS 7608) design curve.
Thirty-seven pupils attending a special school for children and adolescents with autism were observed for the presence of motor and vocal tics. Subsequent family interviews confirmed the diagnosis of comorbid Gilles de la Touretteapos;s Syndrome (GTS) in three children with autism, giving a minimum prevalence rate of 8.1%. Family history data also suggested this was heritable. The presence of GTS was not associated with superior intellectual, language, or social development. Results suggest that the rate of GTS in autism may exceed that expected by chance. The limited sample size constrains this conclusion. A large-scale epidemiological study testing this association study would appear merited.
ABSTRACTThe search for nongenetic factors that mediate the expression of a genetic vulnerability to Tourette's syndrome (TS) is an important undertaking that may provide valuable clues concerning the pathophysiology of this disorder as well as potential treatment approaches. In a direct interview study, the perinatal experiences of 31 TS patients were compiled in an effort to identify risk factors associated with tic severity. Severity of maternal life stress during pregnancy, gender of the child, and severe nausea and/or vomiting during the first trimester were found to be significantly associated with current tic severity. Future longitudinal studies of “at-risk” children are needed to confirm these findings. Set in the context of a known chromosomal site for the TS diathesis, such studies will permit the identification and quantification of risk and protective factors in the expression of TS and further develop TS as a model neuropsychiatric disorder for the study of gene–environment interactions.
We present our hypothesis that various steroid hormones play an important role in the symptom expression of Gilles de la Tourette's syndrome (TS) and that androgenic hormones, in particular, are likely to exacerbate symptoms of the disorder. We review the clinical evidence supporting our hypothesis. Sex steroids establish brain sexual dimorphisms early in CNS development, and we suggest mechanisms whereby androgenic and other hormonal changes later in human development might act at dimorphic brain regions to influence the natural history of TS. Finally, we discuss the various ways in which neuroendocrine studies might assist in genetic and neurobiologic research programs in TS.
Studies of Tourette's syndrome have indicated that the etiology may be either primary or secondary. Secondary Tourette's syndrome has been reported in association with numerous neurological conditions, but there have been no previous reports of Tourette's syndrome and its relationship to neonatal anoxia. This report presents the case of a 15-year-old boy with a history of Tourette's syndrome and neonatal anoxia and examines whether or not there is a connection between the two. To test the hypothesis that this is the first documented case of cerebral anoxia at birth followed by Tourette's, a review of the pertinent literature on secondary Tourette's syndrome is presented. Evidence of perinatal anoxia, subsequent Tourette's syndrome, a negative family history, as well as an examination of the statistical chances of anoxia and Tourette's syndrome co-existing and of all previous reports of acquired Tourette's syndrome tend to favor an organic perinatal insult as having caused the later development of Tourette's syndrome in the case of this adolescent.
We studied 16 pairs of monozygotic twins (mean age, 12.8 +/- 1.4 years; age range, 8 to 26 years; sex, 12 male pairs, four female pairs) in whom at least one twin had Gilles de la Tourette's syndrome (TS) to determine the concordance rates for TS and tic disorders and to examine environmental factors accounting for intrapair differences in tic severity. In this cohort, the concordance rate for TS was 56%, and the concordance rate for tic disorders was 94%, supporting a primary genetic basis for TS and tic disorders with a high rate of penetrance for the gene. Thirteen of the pairs had differing birth weights and the lower birth-weight twin had a higher tic score in 12 of these pairs. The magnitude of the intrapair birth-weight difference (BWD) strongly predicted the magnitude of the intrapair tic score difference. The difference in tic severity could not be explained by any postnatal medical events. These findings suggest that crucial events affecting the phenotypic expression of TS occur in utero and that the factors causing the BWD also are related to tic severity.
In a longitudinal study, two boys in the Outpatient Psychiatric Clinic at Tokyo University were found to exhibit Tourette's disorder in addition to the original diagnoses of infantile autism. This paper addresses problems of applying the diagnostic criteria of DSM-III in terms of voluntary tic suppression in diagnosing patients with both disorders. Differences between motor tics and stereotyped movements in patients with both infantile autism and Tourette's disorder have been clearly distinguished. This may enable us to identify more autistic individuals with Tourette's disorder by focusing on these differences. In contrast to Burd et al.'s findings and implications, these two boys have not manifested spurts in language and social relationships nor have their conditions significantly improved, despite the development of Tourette's disorder.
The authors report on three patients in North Dakota with an apparent onset of Gilles de la Tourette's syndrome before 1 year of age. Infantile onset may occur in 4.1% of the child patients with Tourette's disorder in that state. It is suggested that the diagnostic criteria for Tourette's disorder be revised to include patients who develop the illness before they are 1 year old.
No clinical treatment for nervous habits has been generally effective. The present rationale is that nervous habits persist because of response chaining, limited awareness, excessive practice and social tolerance. A new procedure was devised for counteracting these influences: the client practiced movements which were the reverse of the nervous habit, he learned to be aware of each instance of the habit and to differentiate it from its usual response chain and he was given social approval for his efforts to inhibit the habit. The treatment was given during a single session to 12 clients who had diverse nervous habits such as nail-biting, thumb-sucking, eyelash-picking, head-jerking, shoulder-jerking, tongue-pushing and lisping. The habits were virtually eliminated on the very first day for all 12 clients and did not return during the extended follow-up for the 11 clients who followed the instructions.
The objective of this study was to determine the frequency of coprolalia in younger patients with Gilles de la Tourette syndrome (GTS). Coprolalia, which is the least understood and perhaps most unusual symptom of GTS, is reported to occur in 4-60% of all patients with GTS. Most reports indicate a prevalence > 30%. The widely varying prevalence figures for coprolalia may reflect cultural differences, severity of disease, and the age of the population surveyed. This study is a chart review of 112 patients seen in a pediatric neurology clinic in South Florida who met the Diagnostic and Statistical Manual of Mental Disorder (3rd ed., revised) criteria for GTS. Only 8% of the patients in the study exhibited coprolalia. This unusually low frequency of coprolalia suggests that coprolalia may be rarer than previously believed in younger patients. It may also better reflect the frequency of coprolalia in a community-based pediatric neurology practice.
The association of attentional, neuropsychological, and behavioural abnormalities with Tourette's syndrome (TS) suggests that the abnormal function of the disorder extends beyond the motor circuits of the basal ganglia. To explore this possibility we studied, with conventional 18-channel electroencephalography, monozygotic twins ranging from 8 to 26 years of age, where at least one member of the twin pair suffered from TS. In nine out of the 11 twin pairs that differed in clinical severity of the tic disorder, the twin with the more severe course of illness had a significantly more abnormal electroencephalogram (EEG) by qualitative visual analysis. Most of the differences were due to excessive frontocentral theta activity, suggesting dysfunction outside the basal ganglia. There was also a significant relationship between a lower global neuropsychological testing score and a worse overall EEG. In eight of nine twin sets with different global neuropsychological testing scores, the twin with the lower score had a worse EEG. A similar relationship was found between birth weight and overall EEG quality. In the nine sets that differed in birth weight, the twin with a lower birth weight had a worse EEG in seven of the sets. The EEG findings are unlikely to be unlikely to be a medication effect because the same result was seen in the six twin pairs who had been medication-free for at least six months before entry into the study. The origin of this slowing may relate to the interaction between environmental insults to the central nervous system and the genetic component of TS, an interaction producing damage to the cortex, thalamus, or both.
To explore the influence of gender and comorbid obsessive-compulsive disorder (OCD) on the phenomenology of Tourette's syndrome (TS).
TS proband groups defined by gender and comorbid OCD status were compared on a variety of sociodemographic variables, clinical characteristics, and perinatal complications.
Compared to females, males more often onset with rage and had ever experienced any form of simple tics. Females onset with compulsive tics more often than males. Probands with comorbid OCD were more likely than those without OCD to onset with complex tics. Delivery complications, especially forceps deliveries, were associated with being male and with having OCD. Fetal exposure to relatively high levels of coffee, cigarettes, or alcohol predicted OCD in TS probands. Diagnosis of TS occurred at later ages among females than among males. Males and females displayed different age distributions.
Males and females tend to experience different kinds of symptoms at onset. However, the overall experience of TS appears to be similar for both groups. Perinatal brain injury is implicated in the etiology of TS in some boys. Early brain injury may cause or exacerbate the development of OCD in some TS sufferers.
The cause of sudden infant death syndrome (SIDS) is unknown. Sleep-related impairment of respiratory control and arousal are postulated; hyperdopaminergic and hyposerotonergic dysfunction may contribute to events leading to infant apnea and SIDS. Psychosocial adversity and impulsive and compulsive behaviors characterize some families of SIDS victims. Tourette syndrome (TS) is a common hereditary neurobehavioral disorder characterized by the frequent presence of impulsive and compulsive behaviors. Sleep disorders are common and include sleep apnea and abnormal arousal. Hyperdopaminergic and hyposerotonergic abnormalities are postulated to contribute to the pathophysiology of the disorder. The following is a report of the presence of incidents of infant apnea and SIDS in families in which TS was present. In an additional TS family, a child had obstructive sleep apnea syndrome (OSAS). Results of a preliminary survey suggest that TS gene carriers are at increased risk of life-threatening apneas of infancy and that the prevalence of SIDS in such families may be 2 to 5 times the prevalence in the general population. The presence in some pedigrees of sleep apnea in children and adults suggest that in some instances disorders of sleep-related ventilatory control and arousal occurring throughout the life-span share common pathophysiological mechanisms.
To determine whether there is a relationship between tic severity and neuropsychological function in Tourette's syndrome (TS).
The study employed a case-control series involving monozygotic twin pairs, divided into more severe and less severe groups based on tic severity and tested with a neuropsychological battery of tests.
Twin pairs were recruited nationwide and evaluated in the National Institute of Mental Health Neuropsychiatric Research Hospital.
Twelve twin pairs (mean age, 10.5 years; range, 8 to 16 years) in which at least one member met criteria for a diagnosis of TS.
Global neuropsychological performance was significantly worse in the twins with more severe tic symptoms, with significant differences emerging on individual tests of attention, visuospatial perception, and motor function. In each twin pair, the twin with more severe tics had poorer global neuropsychological function.
The results suggest that the nongenetic factors that influence tic severity in TS exert a similar effect on neuropsychological function, and that these two clinical manifestations of TS may share a common pathophysiologic state.
Infant gaze, gestures, and affective expression have become generally accepted as indicators of the infant's efforts to initiate or resume interaction with a partner, particularly during moments when the mother may be temporarily unresponsive as shown experimentally in the maternal "Still-Face" situation. Previous studies comparing deaf and hearing infants using this paradigm have revealed diminished signalling by deaf infants with hearing mothers, when signals were defined by the typical indices mentioned above. This study compares results from both a microanalytic coding system (used with 59 dyads) and a more global examination of efforts by 20 deaf and 20 hearing infants to re-engage their deaf or hearing mothers. Emphasis is on the kinds of infant signals that often remain undocumented due to methodological constraints, but that may be recognized by the mother and elicit a delayed response from her when she is able to resume her normal interactive patterns. Results indicate that when these additional "signal" behaviors are considered (such as repetitive hand, arm, or foot movements, or behaviors previously prohibited by the mother), there are few overall differences in eliciting efforts by deaf and hearing infants.
Young children engage in a significant amount of ritualistic, repetitive, and compulsive-like activity that appears to be part of their normal behavioral repertoire. Empirically, little is known about the onset, prevalence, and developmental trajectory of these phenomena. A parent-report questionnaire, the Childhood Routines Inventory (CRI), was developed to assess compulsive-like behavior in young children, and was administered to 1,492 parents with children between the ages of 8 and 72 months. The CRI has strong overall internal consistency and a distinct two-factor structure. The frequency of compulsive-like behaviors changes with age: Two-, 3-, and 4-year-olds engaged in more compulsive behavior than children younger than 1 year of age and older than 4 years of age. Results are discussed from a developmental psychopathology framework and for their implications for future research in this area.
Neuromotor function was assessed in 94 children of normal intelligence with Tourette syndrome, Tourette syndrome and attention-deficit hyperactivity disorder (ADHD), or ADHD only, using the Physical and Neurological Examination of Subtle Signs (PANESS). Time to complete six motor movements was analyzed separately by side (left and right) and complexity (simple and patterned). All groups performed faster on their preferred, dominant side. Although all groups took longer to complete patterned versus simple movements, the group with ADHD had a larger discrepancy for complexity than the other two groups. The speed for simple and patterned tasks was at or faster than age expectations for 54% of tasks in the group with Tourette syndrome but only 15% of tasks in the other two groups. More children in the group with Tourette syndrome (76%) than the groups with Tourette syndrome with ADHD (54%) or ADHD (54%) or ADHD only (65%) performed movements within normal time limits for age. Findings suggest that Tourette syndrome is not associated with motor slowing.
Tourette Syndrome (TS) in children is associated with various neurobehavioral disorders including attention deficit hyperactivity disorder (ADHD). Children with TS and ADHD show some difficulties with neuropsychological tasks, but we do not know if children with TS alone have neuropsychological deficits. To assess specific cognitive differences among children with TS and/or ADHD, we administered a battery of neuropsychological tests, including 10 tasks related to executive function (EF), to 10 children with TS-only, 48 with ADHD-only, and 32 with TS + ADHD. Children in all groups could not efficiently produce output on a timed continuous performance task [Test of Variables of Attention (TOVA) mean reaction time and reaction time variability]. Children with TS-only appeared to have fewer EF impairments and significantly higher perceptual organization scores than children with TS + ADHD or ADHD-only. These findings suggest that deficiencies in choice reaction time and consistency of timed responses are common to all three groups, but children with TS-only have relatively less EF impairment than children with TS + ADHD or ADHD-only.
Transient movement disorders are quite common in pediatrc practice, occurring mainly in infants. They are underdiagnosed but represent about 20% of cases of movement disorders (tics excluded) seen in a neuropaediatric department. Dystonia, tremor and myoclonus are the most common. Transient idiopathic dystonia of infancy is quite common, and the diagnosis can be suspected on clinical examination. Knowledge of these disorders avoids not only unnecessary tests and treatment, but also familial anxiety.
Developmental stuttering (DS) may be related to the extrapyramidal motor system and shares many clinical similarities with Tourette's syndrome (TS), which is widely believed to be associated with extrapyramidal dysfunction. Twenty-two stutterers were examined for neuropsychiatric features commonly seen in TS, including tics, obsessive-compulsive behaviors (OCB), and attention deficit disorders. Eleven stutterers displayed motor tics, and symptoms of OCB were observed at rates similar to those seen in persons with TS. Few stutterers demonstrated significant attentional deficits. Findings are consistent with models suggesting extrapyramidal involvement in DS and raise the possibility that DS and TS are pathogenetically related.
Little is known about the validity of the diagnosis of attention-deficit/hyperactivity disorder (ADHD) in young children. Moreover, the results of the DSM-IV field trials raised concerns that inclusion of the new predominantly hyperactive-impulsive type of ADHD in DSM-IV might increase the likelihood of the diagnosis being given to active but unimpaired preschool and primary school children.
The validity of DSM-IV criteria for each subtype of ADHD was evaluated in 126 children, aged 4 through 6 years, and 126 matched comparison children. Probands and controls were classified by using structured diagnostic interviews of the parent and a DSM-IV checklist completed by the teacher.
Children who met DSM-IV criteria for each subtype of ADHD according to parent and teacher reports differed consistently from controls on a wide range of measures of social and academic impairment, even when other types of psychopathology and other potential confounds were controlled.
When diagnosed by means of a structured diagnostic protocol, all three DSM-IV subtypes of ADHD are valid for 4- through 6-year-old children in the sense of identifying children with lower mean scores on measures of adaptive functioning that are independently associated with ADHD.
Peer relationships, social skills, self-esteem, parental psychopathology, and family functioning of children with Tourette's disorder and a chronic disease control group of children with diabetes mellitus were compared. Children with Tourette's disorder had poorer peer relationships than their classmates and were more likely to have extreme scores reflecting increased risk for peer relationship problems than children with diabetes mellitus, but did not report self-esteem problems or social skills deficits. Measures of peer relationships were not related to severity or duration of tics. Children with Tourette's disorder and Attention Deficit Hyperactivity Disorder were at increased risk for poor peer relationships. The psychosocial problems of children with Tourette's disorder do not appear to be the generic result of having a chronic disease.
In the present longitudinal study, 20 deaf and 20 hearing children were observed during free play with their hearing mothers when the children were 22 months and 3 years of age. Compared to hearing children, deaf children were severely language delayed, with deaf 3-year-olds using less language (speech or sign) than hearing 22-month-olds. Deaf children communicated primarily through nonlinguistic vocalizations, with increasing use of gesture from 22 months to 3 years of age. Although mothers of deaf children used more visual communication than mothers of hearing children, they still primarily communicated through speech. In addition, deaf children did not visually attend to much of their mothers' communication. Therefore, deaf children received much less communication than hearing children. These results suggest that intervention efforts should be focused on increasing the quantity of perceived linguistic input by the child.
To identify similarities and differences in neuropsychiatric correlates in children with Tourette's syndrome (TS) and those with ADHD.
The sample consisted of children with Tourette's syndrome with ADHD (N = 79), children with Tourette's syndrome without ADHD (N = 18), children with ADHD (N = 563), psychiatrically referred children (N = 212), and healthy controls (N = 140).
Disorders specifically associated with Tourette's syndrome were obsessive compulsive disorder (OCD) and simple phobias. Rates of other disorders, including other disruptive behavioral, mood, and anxiety disorders, neuropsychologic correlates, and social and school functioning were indistinguishable in children with Tourette's and ADHD. However, children with Tourette's syndrome plus ADHD had more additional comorbid disorders overall and lower psychosocial function than children with ADHD.
These findings confirm previously noted associations between Tourette's syndrome and OCD but suggest that disruptive behavioral, mood, and anxiety disorders as well as cognitive dysfunctions may be accounted for by comorbidity with ADHD. However, Tourette's syndrome plus ADHD appears to be a more severe condition than ADHD alone.
Thirty-seven pupils attending a special school for children and adolescents with autism were observed for the presence of motor and vocal tics. Subsequent family interviews confirmed the diagnosis of comorbid Gilles de la Tourette's Syndrome (GTS) in three children with autism, giving a minimum prevalence rate of 8.1 %. Family history data also suggested this was heritable. The presence of GTS was not associated with superior intellectual, language, or social development. Results suggest that the rate of GTS in autism may exceed that expected by chance. The limited sample size constrains this conclusion. A large-scale epidemiological study testing this association study would appear merited.
To determine whether typical clinical doses of methylphenidate (MPH) cause tics or exacerbate preexisting mild to moderate tics.
Ninety-one children with attention-deficit hyperactivity disorder, with and without comorbid tics (excluding severe tics and Tourette's syndrome), were randomly assigned to receive MPH or a placebo in a 1-year prospective study. The target dose was titrated to balance behavior change and side effects. Parents and teachers were the observers.
Crossover from the placebo to MPH was common because of poor behavioral response. One MPH-treated subject dropped out; the final MPH group had 72 subjects; the placebo group, 18. The average dose of MPH was 0.5 mg/kg twice daily. Clinically significant tics developed in 19.6% of the subjects without preexisting tics receiving MPH and in 16.7% of those receiving the placebo (Fisher exact test, p = .59, not significant; relative risk = 1.17, confidence interval = 0.31-4.40). Deterioration of tics was observed in 33% of subjects with preexisting tics receiving MPH and in 33% of those receiving the placebo (Fisher exact test, p = .70, not significant; relative risk = 1.0, confidence interval = 0.40-1.85).
Doses of MPH based on the typical clinical titration procedure did not produce significantly more tics than the placebo in children with or without preexisting (mild to moderate) tics.
Tourette's syndrome (TS), a neuropsychiatric movement disorder that manifests itself in childhood, is often associated with comorbid symptomatology, such as obsessions, compulsions, hyperactivity, distractibility, and impulsivity. Epidemiological studies suggest that a substantial number of TS patients develop clinical levels of obsessive-compulsive disorder (OCD) and/or attention deficit hyperactivity disorder (ADHD). This review aims to provide an integrated account of the three disorders in terms of their comorbidity. Neuroimaging studies suggest that all three disorders involve neuropathology of the basal-ganglia thalamocortical (BGTC) pathways: TS in the sensorimotor and limbic BGTC circuits; OCD in the prefrontal and limbic BGTC pathways; and ADHD in the sensorimotor, orbitofrontal, and limbic BGTC circuits. The pattern of comorbidity and other evidence indicates that the TS gene(s) may be responsible for a spectrum of disorders, including OCD and ADHD, but also that the disorders OCD and ADHD can exist in their own right with their own etiologies.
To identify pre- and perinatal risk factors for Tourette disorder.
Case control study. We matched names of patients who met DSM criteria for Tourette disorder with their birth certificates. For each case five controls were selected. The controls were matched by sex, year and month of birth.
Univariate analysis of the 92 cases and the 460 matched controls identified 4 risk factors; one categorical variable--trimester prenatal care begun and 3 continuous variables--apgar score at 5 minutes, month prenatal began and number of prenatal visits. Logistic modeling to control for confounding produced a three variable model (apgar score at 5 minutes (OR = 1.31), number of prenatal visits (OR = .904) and fathers age (OR = .909). The model parameters were: chi 2 = 19.76; df = 3; p < .001.
This is an inexpensive methodology to identify potential risk factors of patients with Tourette disorder and other mental illness.
Stereotyped behaviours occur frequently in blind children. Most authors attribute stereotyped mannerisms to factors such as hospitalisation, motor limitations, and reduced capacity for exploration. There seems to be a specific association between blindness and behavioural mannerisms, such as eye pressing and eye poking, which have been observed in children with peripheral blindness. We studied the prevalence of stereotyped motor behaviours in a sample of congenitally blind children with and without other neurodevelopmental disabilities in order to assess the types and features of such stereotyped behavioural traits. Twenty-six congenitally blind children (11 male and 15 female) were assessed through videotape recording and through a questionnaire focusing on the type, frequency, form of manifestation and duration of the children's stereotyped behaviours. Stereotyped behavioural traits were observed in 19 (73%) of the patients. Stereotyped behaviours most frequently observed were body rocking (8; 30.7%), repetitive handling of objects (8; 30.7%), hand and finger movements (7; 26.9%), eye pressing and eye poking (8; 30.7%), and lying face downwards (6; 22.8%) and jumping (3; 11.4%). We found that a reduction in stereotyped behavioural traits could be obtained by stimulating appropriate adaptive behaviour in children, while these behaviours were increased by restricted environmental conditions, reduced sensory stimulation and reduced motility.
The causes of obsessive-compulsive disorder (OCD) are as yet unknown. Evidence of familial aggregation is one approach for investigating the role of genetics in the etiology of this condition. The current study was conducted to determine ifOCD is familial and to investigate possible familial subtypes.
Eighty case probands were identified in 5 specialty OCD clinics and 73 community control probands were identified by random-digit dialing. These probands and their first-degree relatives (343 case and 300 control relatives) were blinded to group and evaluated by psychiatrists and doctoral-level clinical psychologists using semistructured instruments. Final diagnoses were assigned by a blinded-consensus procedure. The results were analyzed using logistic regression by the method of generalized estimating equations.
The lifetime prevalence of OCD was significantly higher in case compared with control relatives (11.7% vs 2.7%) (P<.001). Case relatives had higher rates of both obsessions and compulsions; however, this finding is more robust for obsessions. Age at onset of obsessive-compulsive symptoms in the case proband was strongly related to familiality (odds ratio, 0.92; confidence interval, 0.85-0.99) (P = .05); no case of OCD symptoms was detected in the relatives of probands whose age at onset of symptoms was 18 years or older. Probands with tics or obsessive-compulsive personality disorder were not more likely to have relatives with OCD than those without these features.
Obsessive-compulsive disorder is a familial disorder. Obsessions are more specific to the phenotype than are compulsions. Age at onset of OCD is valuable in characterizing a familial subtype.
To study prevalence and comorbidity of Tourette's disorder in the general population of children and in a clinical setting.
School-age children in the general population and children attending a county-wide tic disorder clinic were screened and examined by the same doctor. Behavioral-psychometric instruments with demonstrated reliability and validity were used.
Depending on the sample characteristics, 0.15% to 1.1% of all children had Tourette's disorder. Boys outnumbered girls by 4:1 through 6:1. Attention deficits and empathy/autism spectrum problems (including Asperger's disorder) were very common, each type of comorbidity affecting approximately two thirds of individuals with Tourette's disorder. Overall behavior problem scores were high, and affected children exhibited a marked degree of functional impairment.
Tourette's disorder is a common disorder with high rates of significant comorbidity. In most cases, attention deficits and empathy problems are likely to cause more suffering than the tics per se.
Asperger's syndrome is a condition in the autistic spectrum in which language development is normal. Patients with Asperger's syndrome frequently exhibit repetitive movements (stereotypies), and can have motor and phonic tics in addition to other behavioral abnormalities. We present 12 patients with autistic spectrum disorders who were referred to our Movement Disorders Clinic for evaluation of tics. Eight of the 12 had normal language development and therefore met criteria for Asperger's syndrome. All patients exhibited stereotypic movements; in addition, seven had tics and six of these met diagnostic criteria for Tourette syndrome. Of the six patients with clinical features of both Asperger's syndrome and Tourette syndrome, three had severe congenital sensory deficits. The autistic patients in our series were clinically heterogeneous and though tics were clearly present, other aberrant movements demonstrated by them were harder to classify. Our series confirms the wide range of clinical manifestations in Asperger's syndrome and autism, including tics and other features of Tourette syndrome. Furthermore, it suggests that sensory deprivation contributes to the development of adventitious movements in this population.
With the goal of evaluating the available literature on the course of Tourette's disorder, we conducted a systematic literature search through electronic databases for pertinent scientific articles in English with a minimum of 20 subjects. We also examined bibliographies of papers identified in this manner for additional sources. We found only 16 articles; most consisted of retrospective reports on treated samples. Overall, the available literature suggests that Tourette's disorder follows a remitting course in a sizeable number of individuals. Little has been published regarding predictors of remission or persistence. More work is needed using longitudinal prospective studies to better define the course and outcome of Tourette's disorder.
Current conceptualizations of TS have been shaped by advances in systems neuroscience and the emerging understanding of the role of the basal ganglia in implicit learning and habit formation. Although the evidence that the same mechanisms are involved in both habit formation and tics is circumstantial, recent progress in neuroanatomy, systems neuroscience, and functional in vivo neuroimaging has set the stage for a major advance in our understanding of TS. Continued success in these areas will lead to the targeting of specific brain circuits for more intensive study. Diagnostic, treatment, and prognostic advances can also be anticipated, e.g., which circuits are involved and to what degree? How does that degree of involvement affect the patient's symptomatic course and outcome? Will it be possible to track treatment response using neuroimaging techniques? And will specific circuit-based therapies using deep-brain stimulation emerge to treat refractory cases (Vandewalle et al. 1999xStereotactic treatment of Gilles de la Tourette syndrome by high frequency stimulation of thalamus. Vandewalle, V, van der Linden, C, Groenewegen, H.J, and Caemaert, J. Lancet. 1999; 353: 724Abstract | Full Text | Full Text PDF | PubMedSee all ReferencesVandewalle et al. 1999)?The identification of susceptibility genes in TS will doubtless point in new therapeutic directions for treatment, as will the characterization of the putative autoimmune mechanisms active in the PANDAS subgroup of patients. Given this potential, TS can be considered a model disorder to study the dynamic interplay of genetic vulnerabilities, epigenetic events, and neurobiological systems active during early brain development. It is likely that the research paradigms utilized in these studies and many of the empirical findings resulting from them will be relevant to other disorders of childhood onset and to our understanding of normal development.‡To whom correspondence should be addressed (e-mail: james.leckman@yale.edu).
The unique clinical presentation of Tourette syndrome (TS) and its symptomatic response to dopamine antagonists are widely cited as evidence for the central role of the limbicmotor interface in the pathophysiology of TS. Nonetheless, the true neuropathology of TS remains elusive, even though significant advances have been made in understanding complex interconnected circuitries within the limbic system and basal ganglia. Neuropathologic and neuroimaging studies - plagued by small samples, clinical heterogeneity, and a number of interpretative problems are generally supportive of pathology within the orbitofrontal cortex, striatum, and their efferent projections in TS. The specific patterns of abnormalities vary widely across these studies, clouding attempts to define a unifying neuropathology for this disorder. Converging yet circumstantial evidence for frontal cortical, and basal ganglia pathology in TS comes also from studies in fields ranging from neuroimmunology to neuropsychology, and from the clinical overlap between TS and disorders such as obsessive-compulsive disorder, attention- deficit/hyperactivity disorder, and Sydenham's chorea. As a 'model' neuropsychiatric disorder, TS has stimulated advances in several areas of neurobiology research, yet we still await a real understanding of its pathophysiology in order to move from empirically driven therapeutics to the development of targeted effective treatments.