Tourette syndrome: Evolving concepts

Tourette syndrome is a common childhood‐onset neurobehavioral disorder characterized by multiple motor and phonic tics affecting boys more frequently than girls. Premonitory sensory urges prior to tic execution are common, and this phenomenon helps to distinguish tics from other hyperkinetic movement disorders. Tourette syndrome is commonly associated with attention deficit hyperactivity disorder, obsessive‐compulsive disorder, learning difficulties, and impulse control disorder. The pathophysiology of this complex disorder is not well understood. Involvement of basal ganglia–related circuits and dopaminergic system has been suggested by various imaging and postmortem studies. Although it is considered a genetic disorder, possibly modified by environmental factors, an intense search has thus far failed to find causative genes. Symptomatic treatment of tics chiefly utilizes various alpha adrenergic agonists, antidopaminergic drugs, topiramate, botulinum toxin, and deep brain stimulation. Habit reversal therapy and other behavioral approaches may be a reasonable option for some cases. Improved understanding of Tourette syndrome should lead to better symptomatic and more effective pathogenesis‐targeted therapies. © 2011 Movement Disorder Society     

Tourette syndrome: recent advances

Clinical and genetic studies have allowed the limits of Tourette syndrome to be broadened. There is now strong evidence that chronic motor tics and Tourette syndrome are different manifestations of an autosomal dominant gene with high penetrance. A genetic link with obsessive-compulsive disorder also appears to have been established. Up to 10% of cases of Tourette syndrome may be nongenetic phenocopies, however. There is also an association between Tourette syndrome and attention deficit hyperactivity disorder. This complicates therapy, as psychostimulant drugs may precipitate or exacerbate tics in some individuals. A high proportion of patients with Tourette syndrome also has neuropsychological deficits and learning disabilities. The pathophysiology is incompletely understood. The best supported hypothesis is that there is dopamine receptor supersensitivity, although there are strong suggestions of abnormalities in serotonin metabolism. The possibility of abnormalities in neuropeptide systems is being explored. Treatment of tics relies primarily on neuroleptics with dopamine receptor blocking activity. Clonidine may be useful in some patients, especially those with behavior problems. Obsessive-compulsive symptoms can be treated using appropriate pharmacologic agents. The treatment of attention deficit disorder in patients with tics should begin with behavioral strategies. Clonidine can be tried as the first-line drug, and psychostimulants should be used only if necessary and with great caution. In rare instances it may be necessary to combine a psychostimulant and a neuroleptic.     

The behavioral spectrum of tic disorders: a community-based study

BACKGROUND: Tourette syndrome (TS) and related tic disorders are commonly associated with obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD). It has been argued, however, that any observed association between TS and these and other psychopathologies may be due to ascertainment bias in that individuals with multiple problems are more likely to be referred for medical evaluation. METHODS: In order to overcome the potential confounding by ascertainment bias, the authors conducted a community-based study of school children using direct interviews to determine the prevalence of tic disorders and any comorbid psychopathology. A standard psychiatric interview and standardized rating scales were utilized to diagnose childhood behavioral disorders. RESULTS: Of the 1,596 children interviewed, 339 were identified as having tics. The following psychopathologies were found more commonly (p < 0.05) in the children with tics: OCD, ADHD, separation anxiety, overanxious disorder, simple phobia, social phobia, agoraphobia, mania, major depression, and oppositional defiant behavior. CONCLUSION: The behavioral spectrum of tic disorders includes OCD, other anxiety disorders, a mood disorder, and attention-deficit and disruptive behavior disorders.     

Treatment of children and adolescents with tics and Tourette syndrome

Tics, patterned movements distinct from stereotypies, myoclonus, and other hyperkinetic movements, are quite common in children, particularly among those with developmental and psychiatric disorders. Thus, tics can indicate the presence of atypical neurodevelopment or broader difficulties with cognition or mood. Tics are also the cardinal feature of Tourette syndrome, a childhood-onset neurobehavioral disorder characterized by a chronic inability to suppress or an urge to perform patterned, repetitive movements. Patients with Tourette syndrome most commonly have, in addition to tics, symptoms of inattention, hyperactivity, obsessiveness, or anxiety. Achieving the most effective treatment of a child with tics is contingent on proper diagnosis of the movement disorder and thorough assessment for other problems, followed by consideration of both nonpharmacologic and pharmacologic interventions for any and all symptoms interfering with the child's function and quality of life. This review focuses primarily on the diagnosis and medical treatment of tics in children and adolescents with Tourette syndrome.     

Tics and its disorders

Tourette syndrome (TS) is familial neuropsychiatric disorder that is characterized by motor and phonic tics that begin in childhood. Once thought of as a rare and debilitating disorder, in the last decade new scientific knowledge suggests that TS and related tic disorders are more common and less debilitating for the majority of individuals. Evidence points toward a spectrum of TS symptomatology that extends beyond the tics disorder to probably include obsessive-compulsive disorder, attention deficit hyperactivity disorder, and mood disorders. Tourette syndrome and its differential diagnosis are discussed in this article with a focus on new developments in classification, etiology, epidemiology, genetics, pathophysiology, and clinical management.     

The relationship between tourette syndrome, attention deficit hyperactivity disorder, and stimulant medication: a critical review

The relationship between tic disorders and attention deficit hyperactivity disorder (ADHD) is of great clinical importance because both disorders can lead to emotional, social, and academic difficulties. To further complicate this interrelationship is the concern that the use of psychostimulant medication to treat ADHD will help the hyperactivity and attention problems but will lead to the onset of tics or will worsen preexisting tics. The first part of this review investigates how often Tourette syndrome (TS) is associated with ADHD and finds that ADHD has been reported in 35% to 90% of children with TS. The second part of the review looks at whether the ADHD seen in TS is the same as in children who do not have tics. Recent studies lead to the conclusion that the ADHD seen in TS is the same, although the attentional difficulties seen in TS are influenced also by the distraction of the tics themselves as well as by internal distractions such as is seen in comorbid anxiety or obsessive-compulsive behavior. The final part of the review investigates the question of whether psychostimulants worsen or cause tics. Twenty-two studies were found that investigated this possible relationship. Earlier studies were confounded by the natural pattern seen in TS in which tics spontaneously wax and wane in occurrence, intensity, and frequency. More recent double-blind, placebo-controlled studies have shown that psychostimulants are equally effective in improving ADHD symptoms whether the disorder is associated with tics or not. When group data are analyzed, there is no significant increase in tics when psychostimulants are used in patients with tics compared with controls. Individual patients, however, may experience an increase in tics. This increase is not appreciated in analysis of group data. In conclusion, it is medically appropriate to provide treatment with psychostimulant medication in persons with tics where the ADHD symptoms are significantly disturbing their quality of life.     

Tourette syndrome and chronic tics in a sample of children and adolescents

Forty-eight subjects with Tourette syndrome (M 36, F 12; mean age 11.2 years) and 48 with chronic tic disorder (M 33, F 15; mean age 12.1 years) were recruited in order to study the vertical transmission within families of a vulnerability to tic disorders or to other psychiatric disorders, the role of adverse pre- and perinatal events, and the presence of comorbid psychiatric conditions. As control group, 30 matched, psychiatrically unaffected subjects (M 20, F 10; mean age 10.8 years) were chosen. Screening measures included detailed anamnestic data, focused on family history of tics and other psychiatric disorders, prenatal events and birth. Subjects and parents were also questioned about psychiatric comorbidity. Group differences were compared using Fisher Test. Subjects with Tourette syndrome and those with chronic tic were similar to each other and different from controls in family history of tic disorders, pre- and perinatal events, and some comorbid psychiatric disorders (attention deficit hyperactivity disorder, sleep problems, and mood disorders). Tourette syndrome and chronic tic group were different in family history of obsessive-compulsive disorder and in comorbidity for obsessive-compulsive disorder and other anxiety disorders. Tourette syndrome and obsessive-compulsive disorder were significantly associated in this sample. These findings seem to indicate that Tourette syndrome and chronic tic disorder are part of the same disease entity, with Tourette syndrome being a more severe and complex form of tic disorder.     

Co-occurring psychiatric disorders in children and adolescents with Tourette syndrome

More than half of all children and adolescents with Tourette syndrome show evidence of psychiatric comorbidity, exhibiting symptoms of attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder, and other anxiety and mood disorders. Although the prevalence of co-occurring conditions varies depending on the clinical setting, it is crucial for clinicians to be familiar with these disorders because they are often more impairing than tics and can influence the initial treatment choice. Left untreated, these conditions can negatively affect important developmental outcomes, such as academic and social functioning. We review the most common co-occurring disorders, the relationship of these co-occurring disorders to Tourette syndrome, and treatment recommendations for co-occurring conditions when tic symptoms are present.     

Clinique du syndrome de Gilles de la Tourette chez l’adulte

The Gilles de la Tourette syndrome's is a neuropsychiatric disorder characterized by motor and vocal tics. Psychiatric symptoms, i.e. repetitive behaviours, attention deficit disorders, hyperactivity and impulsivity are very often associated with it. It can be the cause of major suffering and disability. Several types of treatment, ranging from psychotherapeutic approaches to drug therapy should be offered to all patients according to the impact of the patient's tics and comorbid disorders on his/her personal life.     

Clinical phenomenology and phenotype variability in Tourette syndrome

Tourette syndrome (TS) is a neurodevelopmental disorder with a rich phenomenology that includes simple and complex motor and vocal tics as well as multiple comorbidities. From a nosological perspective, it is evident that a continuum of tic severity exists, of which TS is the most severe and rare form, while transient tics and chronic tics represent milder forms. From a psychopathology perspective, TS is often concurrent with obsessive–compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD); these disorders appear to define TS “types” TS only, TS+OCD, and TS+OCD+ADHD. Additional clinical aspects of TS include more frequent than expected occurrence of anger episodes, anxiety disorders, mood disorders, impulse control disorders, learning disorders, and pervasive developmental disorders. Data reduction techniques have been used more recently to define a “simple” and “complex” tic symptom clusters or factors. Phenomenologic approaches can be used in TS to guide future pathophysiologic research.     

Cognitive and psychiatric phenotypes of movement disorders in children: a systematic review

Aim The cognitive and psychiatric aspects of adult movement disorders are well established, but specific behavioural profiles for paediatric movement disorders have not been delineated. Knowledge of non‐motor phenotypes may guide treatment and determine which symptoms are suggestive of a specific movement disorder and which indicate medication effects. Method The goal of this review is to outline the known cognitive and psychiatric symptoms associated with paediatric movement disorders. We used a systematic approach, via PubMed, and reviewed over 400 abstracts of studies of selected disorders, of which 88 papers reporting paediatric non‐motor symptoms are summarized. Results Obsessive–compulsive disorder was manifest in children with paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections and Sydenham chorea. Children with opsoclonus–myoclonus syndrome had, for the most part, cognitive and behavioural problems, and attention‐deficit–hyperactivity disorder was reported as a major comorbidity in Tourette syndrome, stereotypies, and restless legs syndrome. Symptoms of depression and anxiety were more frequent in individuals with idiopathic dystonia. Affective disorders were suggestive of Wilson disease. Cognitive decline was common in children with juvenile Huntington disease. A limitation of this review was the lack of systematic assessment in paediatric movement disorders for evaluation and uniform definitions. Interpretation Although the literature in non‐motor phenomena is still emerging, recognition of salient cognitive and psychiatric phenomena may facilitate management of paediatric movement disorders.     

Comorbidity of attention deficit hyperactivity disorder with conduct, depressive, anxiety, and other disorders

OBJECTIVE: Attention deficit hyperactivity disorder is a heterogeneous disorder of unknown etiology. Little is known about the comorbidity of this disorder with disorders other than conduct. Therefore, the authors made a systematic search of the psychiatric and psychological literature for empirical studies dealing with the comorbidity of attention deficit hyperactivity disorder with other disorders. DATA COLLECTION: The search terms included hyperactivity, hyperkinesis, attention deficit disorder, and attention deficit hyperactivity disorder, cross-referenced with antisocial disorder (aggression, conduct disorder, antisocial disorder), depression (depression, mania, depressive disorder, bipolar), anxiety (anxiety disorder, anxiety), learning problems (learning, learning disability, academic achievement), substance abuse (alcoholism, drug abuse), mental retardation, and Tourette's disorder. FINDINGS: The literature supports considerable comorbidity of attention deficit hyperactivity disorder with conduct disorder, oppositional defiant disorder, mood disorders, anxiety disorders, learning disabilities, and other disorders, such as mental retardation, Tourette's syndrome, and borderline personality disorder. CONCLUSIONS: Subgroups of children with attention deficit hyperactivity disorder might be delineated on the basis of the disorder's comorbidity with other disorders. These subgroups may have differing risk factors, clinical courses, and pharmacological responses. Thus, their proper identification may lead to refinements in preventive and treatment strategies. Investigation of these issues should help to clarify the etiology, course, and outcome of attention deficit hyperactivity disorder.     

Tourette’s syndrome: Are stimulants safe?

Clinicians commonly encounter children with comorbid attention deficit hyperactivity disorder (ADHD) and the tic disorder Tourette’s syndrome. The pharmacologic treatment of children with this particular combination of conditions has been problematic because of long-standing warnings against using psychostimulants due to concerns about worsening tics. The basis for these warnings was anecdotal clinical observations. A recent group of placebo-controlled, double-blinded clinical trials have consistently shown that certain stimulants, particularly methylphenidate and dextroamphetamine, are effective, well tolerated, and safe when administered to treat ADHD in children with tics. Methylphenidate appears to be the best-tolerated stimulant compound, with tics often lessening during treatment.     

Clinique du syndrome de Gilles de la Tourette et comorbidités psychiatriques associées chez l’enfant

Tourette's syndrome is recognised of affecting one per cent of school-aged children. Its severity ranges from mild and simple motor and vocal tics, to severely intrusive movement disorder, with marked fluctuations. It frequently cooccurs with attention deficit/hyperactivity disorder and obsessive compulsive disorder, and mood and anxiety disorders. These comorbid conditions are often the major source of impairment for the affected child.     

Clinical phenomenology and phenotype variability in Tourette syndrome

Tourette syndrome (TS) is a neurodevelopmental disorder with a rich phenomenology that includes simple and complex motor and vocal tics as well as multiple comorbidities. From a nosological perspective, it is evident that a continuum of tic severity exists, of which TS is the most severe and rare form, while transient tics and chronic tics represent milder forms. From a psychopathology perspective, TS is often concurrent with obsessive–compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD); these disorders appear to define TS “types” TS only, TS+OCD, and TS+OCD+ADHD. Additional clinical aspects of TS include more frequent than expected occurrence of anger episodes, anxiety disorders, mood disorders, impulse control disorders, learning disorders, and pervasive developmental disorders. Data reduction techniques have been used more recently to define a “simple” and “complex” tic symptom clusters or factors. Phenomenologic approaches can be used in TS to guide future pathophysiologic research.     

A Review and Update on Tourette Syndrome: Where Is the Field Headed?

Tourette syndrome (TS) is a childhood onset neurologic disorder with manifestations including multiple motor and phonic tics, and in most cases a variety of behavioral comorbidities such as attention deficit hyperactivity disorder, obsessive compulsive disorder, and other impulse control disorders. Although it is considered a hereditary disorder, likely modified by environmental factors, genetic studies have yet to uncover relevant causative genes and there is no animal model that mimics the broad clinical phenomenology of TS. There has been a marked increase in the number of neurophysiological, neuroimaging, and other studies on TS. The findings from these studies, however, have been difficult to interpret because of small sample sizes, variability of symptoms across patients, and comorbidities. Although anti-dopaminergic drugs are the most widely used medications in the treatment of TS, there has been increasing interest in other drugs, behavioral therapies, and surgical approaches including deep brain stimulation. Herein, we review the current literature and discuss the complexities of TS and the challenges in understanding its pathophysiology and in selecting the most appropriate treatment. We also offer an expert’s view of where the field of TS may be headed.     

Tourette syndrome and tic disorders: a decade of progress

OBJECTIVE: This is a review of progress made in the understanding of Tourette syndrome (TS) during the past decade including models of pathogenesis, state-of-the-art assessment techniques, and treatment. METHOD: Computerized literature searches were conducted under the key words "Tourette syndrome," "Tourette disorder," and "tics." Only references from 1996-2006 were included. RESULTS: Studies have documented the natural history of TS and the finding that tics usually improve by the end of the second decade of life. It has also become clear that TS frequently co-occurs with attention-deficit/hyperactivity disorder), obsessive-compulsive disorder, and a range of other mood and anxiety disorders. These comorbid conditions are often the major source of impairment for the affected child. Advances have also been made in understanding the underlying neurobiology of TS using in vivo neuroimaging and neurophysiology techniques. Progress on the genetic front has been less rapid. Proper diagnosis and education (involving the affected child and his or her parents, teachers, and peers) are essential prerequisites to the successful management of children with TS. When necessary, modestly effective antitic medications are available, although intervening to treat the comorbid attention-deficit/hyperactivity disorder and/or obsessive-compulsive disorder is usually the place to start. CONCLUSIONS: Prospective longitudinal studies and randomized clinical trials have led to the refinement of several models of pathogenesis and advanced our evidence base regarding treatment options. However, fully explanatory models are needed that would allow for more accurate prognosis and the development of targeted and efficacious treatments.     

Disease-Specific Quality of Life in Young Patients With Tourette Syndrome

Tourette syndrome is a neurodevelopmental disorder characterized by multiple tics and is often associated with comorbid behavioral problems. Research with generic instruments in child populations showed that comorbid disorders can have a greater impact on health-related quality of life than tic severity. This study investigated the usefulness of a newly developed disease-specific instrument, the Gilles de la Tourette Syndrome–Quality of Life Scale for Children and Adolescents (GTS-QOL-C&A), in assessing health-related quality of life in young patients with Tourette syndrome with and without behavioral comorbidity. We recruited 75 patients with Tourette syndrome (60 males; age 12.4 ± 3.2 years). All participants were evaluated by a neuropsychiatrist and completed a standardized psychometric battery, including the GTS-QOL-C&A, Child Depression Inventory, and Multidimensional Anxiety Scale for Children. Forty-two patients (56%) fulfilled diagnostic criteria for at least one comorbidity: obsessive-compulsive disorder (n = 25 patients [33.3%]); attention deficit/hyperactivity disorder (n = 6 patients [8%]); both (n = 11 patients [14.7%]). The GTS-QOL-C&A demonstrated usefulness in differentiating “pure” Tourette syndrome from Tourette syndrome “plus” behavioral problems with regard to health-related quality of life scores for the obsessive-compulsive subscale. In addition to focusing on core tic symptoms, the GTS-QOL-C&A showed sensitivity to the impact of behavioral comorbidities on health-related quality of life and can usefully complement existing nonspecific instruments.     

Chasing Tics in the Human Brain: Development of Open,Scheduled and Closed Loop Responsive Approaches to Deep Brain Stimulation for Tourette Syndrome

Tourette syndrome is a childhood-onset disorder characterized by a combination of motor and vocal tics, often associated with psychiatric comorbidities including attention deficit and hyperactivity disorder and obsessive-compulsive disorder. Despite an onset early in life, half of patients may present symptoms in adulthood, with variable degrees of severity. In select cases, the syndrome may lead to significant physical and social impairment, and a worrisome risk for self injury. Evolving research has provided evidence supporting the idea that the pathophysiology of Tourette syndrome is directly related to a disrupted circuit involving the cortex and subcortical structures, including the basal ganglia, nucleus accumbens, and the amygdala. There has also been a notion that a dysfunctional group of neurons in the putamen contributes to an abnormal facilitation of competing motor responses in basal ganglia structures ultimately underpinning the generation of tics. Surgical therapies for Tourette syndrome have been reserved for a small group of patients not responding to behavioral and pharmacological therapies, and these therapies have been directed at modulating the underlying pathophysiology. Lesion therapy as well as deep brain stimulation has been observed to suppress tics in at least some of these cases. In this article, we will review the clinical aspects of Tourette syndrome, as well as the evolution of surgical approaches and we will discuss the evidence and clinical responses to deep brain stimulation in various brain targets. We will also discuss ongoing research and future directions as well as approaches for open, scheduled and closed loop feedback-driven electrical stimulation for the treatment of Tourette syndrome.