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     

A controlled study of sensory tics in Gilles de 1a Tourette syndrome and obsessive-compulsive disorder using a structured interview.

OBJECTIVE: To determine the prevalence and characteristics of sensory tics in the Gilles de la Tourette syndrome (GTS), and a matched population of patients with obsessive-compulsive disorder (OCD) using a structured assessment. METHODS: 50 subjects each of GTS, OCD, and healthy controls were studied to determine the prevalence and phenomenology of sensory tics, and diagnose tic disorders, OCD, and affective disorders according to DSM-III-R criteria. The severity of tics and obsessive-compulsive symptoms were quantified using the Tourette syndrome global scale (TSGS) and Yale-Brown obsessive-compulsive scale (Y-BOCS) respectively. RESULTS: The GTS group (28%) had significantly-greater life-time prevalence of sensory tics than the OCD (10%) and healthy (8%) groups (P < 0.05). The sensory tics in both the GTS and OCD groups were predominantly located in rostral anatomical sites. Multiple sensory tics occurred in some patients with GTS or OCD, but not in healthy subjects. Within the OCD group, those who had sensory tics had significantly higher TSGS scores (P < 0.0001), and a higher prevalence of GTS (P < 0.005). CONCLUSIONS: Sensory tics seem to be a common and distinctive feature of GTS and that subpopulation of patients with OCD predisposed to tic disorders. Neurophysiologically, a possible explanation for sensory tics is that they represent the subjectively experienced component of neural dysfunction below the threshold for motor and vocal tic production.     

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.     

感觉性抽动的立体定向苍白球射频毁损术

目的研究分析22例Tourette综合征（TS）的感觉性抽动特点及实施单侧苍白球腹后部毁损术的治疗作用。方法对22例经过系统的精神科药物及心理行为治疗失败的TS患者实施立体定向苍白球射频毁损术,应用YGTSS评分量表和感觉性先兆问卷对运动性抽动和感觉性抽动进行评估。结果22例患者中18例（81.8%）有各种类型的感觉性抽动,位于头/面部者最多（72.2%）,术后感觉性抽动发作频率较术前均有所下降,YGTSS各项评分均显著下降（P〈0.01）,其中运动抽动的改善率最高。结论感觉性抽动是TS的常见症状,单侧苍白球腹后部毁损术能全面减轻TS各种症状,但远期疗效有待进一步观察。     

Pathophysiology and treatment of secondary obsessive-compulsive behaviors and tics

Advances in neurobiological research suggest that certain frontal-subcortical circuits play important roles in idiopathic obsessive-compulsive disorder and Tourette's syndrome. Tics and obsessive-compulsive behaviors secondary to neurologic insult appear to involve the same neural circuitry. There are few systematic studies of the treatment of obsessive-compulsive behaviors and tics associated with neurologic disorders. However knowledge of the circuitry and associated neurochemistry of these disorders can help to outline a rational approach to these behaviors.     

Tics

PURPOSE OF REVIEW: This paper reviews the recent literature concerning Tourette syndrome and related disorders. RECENT FINDINGS: Tourette syndrome is a common disorder in children and adolescents, with an established association with attention deficit hyperactivity disorder, obsessive compulsive disorder, and a number of other psychiatric disorders. Both autoimmune and genetic mechanisms are implicated in the pathophysiology of the syndrome, while neuroimaging studies have identified abnormalities in the composition of the basal ganglia and frontal lobe white matter, as well as alterations in dopaminergic activity. When necessary, treatment of tics can be successful with neuroleptics and alpha-2-adrenergic agonists. The use of stimulants in children with Tourette syndrome and comorbid attention deficit hyperactivity disorder does not appear to worsen tics. SUMMARY: As a result of the recent literature, clinicians can feel comfortable treating children with co-morbid attention deficit hyperactivity disorder and Tourette syndrome with stimulant medications. It has also been established that transient tics are very common in children, and for the most part, non-disabling. In those children with persistent tics, behavioural disorders are associated which may impair success in school and psychosocial functioning. Clinicians have a number of therapeutic options, with recent double-blinded randomized trials of clonidine, risperidone, and desipramine showing benefit. Scientists continue to search for the cause of Tourette syndrome.     

Tics and tourette's: A continuum of symptoms?

Analysis of the families of 39 unselected children with Tourette syndrome revealed other members with tic disorders in twenty kindreds. In eight families there were 13 individuals with chronic multiple tics, usually motor, not vocal. Twelve different families contained 18 subjects with Tourette syndrome other than the index patient. In three of these families there were 6 additional individuals with chronic motor tics, forming a bridge to the first group. An autosomal dominant mode of inheritance was suggested in all cases. Tourette syndrome and chronic motor tics appear to represent conditions along a continuum and have, in many instances, a hereditary basis.     

Tics in a patient with Parkinson's disease

A patient with Gilles de la Tourette syndrome later developed Parkinson's disease in middle age. This was accompanied by a marked reduction in the frequency of tics but levodopa toxicity exacerbated the tics. The dopamine hypothesis of tic disorders is supported by this observation.     

Syndrome de Gilles de la Tourette : défis de la recherche pour améliorer la pratique clinique

Tourette syndrome is a neurodevelopmental disorder which is characterized by the presence of motor and phonic tics. These tics are generally more prevalent in childhood. Tics typically reach their maximum severity before puberty, around age 10 to 12. In most patients, tic severity usually decreases during late adolescence and adulthood. However, this is not true for all individuals. To date, the developmental trajectory leading to the persistence of tics into adulthood is still poorly understood. There are very few markers that can predict the evolution of tic symptoms from childhood to adulthood. Yet, while we cannot cure Tourette syndrome, it is possible to reduce tic severity with various treatments. The most common treatments are pharmacotherapy and behavioral and cognitive-behavioral therapy. However, there appears to be a limit to the proportion of tics that can be treated, since most treatments offer an average reduction in tics of no more than 50%. Thus, at first, this article reviews recent advances in treatment and symptom progression. Next, we propose some lines of research to improve the management and treatment of people 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.     

Prevalence of tic disorders and Tourette syndrome in a Swedish school population

The aim of the study was to find the epidemiological distribution of tic disorders and Tourette syndrome (TS) in Swedish school children aged 7 to 15 years. A total population of 4,479 children and their parents were asked to fill in a questionnaire covering both motor and vocal tics. A three-stage procedure was used: screening, interview, and clinical investigation. Two hundred and ninety-seven children (190 males, 107 females) were found to have tics. TS, according to DSM-IV criteria, was found in 0.6% of the total population, another 0.8% had chronic motor tics, and 0.5% had chronic vocal tics. Further, 4.8% of the children had transient tics. All together 6.6% of 7- to 15-year-old children currently had or had experienced some kind tic disorder during the last year. Prevalence of different tic disorders was higher among younger children and in males, and was highly associated with school dysfunction. The prevalence of TS was higher than was previously thought but other tic disorders were more common in this childhood population.     

Tics: from Itard to the neuroleptics

When the six DSM-III (1980) diagnostic criteria are applied to the nine cases reported by Gilles de la Tourette in 1885, six of them are found to be in accordance with the diagnosis of Gilles de la Tourette's syndrome (cases nos 4, 5 and 7 do not involve vocal tics). Gilles de la Tourette deserves credit, not only for having regrouped fragmented observations into one remarkably well described clinical entity which held over time (such as Itard's observations nos 9 and 10 in 1825; the latter is the famous Marquise of D ... seen several times by Charcot and the only one which, along with no 1, appears in Gilles de la Tourette's paper), but also for having described the course of this chronic and fluctuating disease. Why Gilles de la Tourette did not use the term "tic", a term which had been in use for a long time in both veterinary and human medicine, to describe "the motor incoordination" of these patients? Did Charcot take some distance from his student's paper as early as 1885? He viewed tics as the basis of "the disease described by Gilles de la Tourette". In addition to coprolalia and echolalia, he alsa reported the existence of "mental tics". How have French neurologists and psychiatrists been able to perpetuate Brissaud's error who, contrary to Gilles de la Tourette, mentioned that the illness "can be associated with severe mental disorders which often lead to dementia"?(ABSTRACT TRUNCATED AT 250 WORDS)     

High-frequency pallidal stimulation eliminates tic-related neuronal activity in a nonhuman primate model of Tourette syndrome

High-frequency deep brain stimulation targeting the output nucleus of the basal ganglia, the globus pallidus internus, has been suggested as a treatment modality for intractable Tourette syndrome and basal-ganglia-mediated motor tics. Recent studies on the modeling of motor tics induced by focal injections of bicuculline to the striatum, a putative model of Tourette syndrome, have shown that tics induce a widespread modulation within both segments of the globus pallidus. The purpose of this study was to investigate, using the bicuculline-induced Tourette syndrome model, whether and how high-frequency deep brain stimulation targeted to the globus pallidus internus could modulate tic-related activity in the pallidum. The perievent rate changes coinciding with tic expression under the on-stimulation and off-stimulation conditions were examined to determine the effect of high-frequency stimulation on pallidal activity. The results showed that the stimulation blocked tic-related phasic changes in the firing pattern of pallidal cells in parallel with a reduction of the peak amplitude of tic events in the electromyography record. This finding supports the premise that deep brain stimulation targeted to the globus pallidus internus could be a viable treatment option for Tourette syndrome, and the use of pallidal stimulation for motor tics warrants further study.     

Differences in clinical characteristics between Tourette syndrome patients with and without 'generalized tics' or coprolalia

Abstract  The purpose of this study is to examine whether there are differences in clinical characteristics between Tourette syndrome (TS) patients with and without 'generalized tics' (GT) which involve the entire body, and/or coprolalia. Subjects were 64 patients (55 males and 9 females, mean age, 17.4 ± 7.2 years) who visited Tokyo University's outpatient clinic of neuropsychiatry from 1974 to 1993 and who met criteria for Tourette's disorder of DSM-III-R. Data on clinical characteristics, including tic symptoms and courses of their development, complications and developmental histories, treatment and severity, were collected by systematic chart review of all subjects. Tourette syndrome patients with 'generalized tics' tended to show multiple complex vocal tics more frequently than TS patients without GT. Tourette syndrome patients with coprolalia tended to show significantly higher rates of copropraxia, echolalia, and 'cleaning/washing' compulsion than did the TS patients without coprolalia. Tourette syndrome patients with both GT and coprolalia were classified as the severest group in terms of tic symptoms and social impairment. Tourette syndrome patients who had neither of these morbidities were classified into the mildest group in all aspects. Generalized tics and coprolalia seemed to indicate the severest end of the TS spectrum and seemed to be related with a need of intensive treatment.     

Gilles de la Tourette syndrome in Oriental children.

Seventy-four cases of tic syndromes were classified into four groups: chronic multiple tics, subacute multiple tics, chronic simple tics and transient simple tics, and 37 cases of chronic multiple tics (Tourette syndrome) were investigated. Clinical evaluation suggested that a transition existed between the four groups. Posture abnormalities were found in 27% of Tourette syndrome and a relation to dystonia was implied. Clinical evaluation and studies of catecholamine blockers' effectiveness suggested the validity of subtyping Tourette syndrome into four groups whose topographical or biochemical abnormalities differ. It was argued that the neurochemical basis of Tourette syndrome might lie in a multiplicity of biochemical abnormalities including disturbances of dopaminergic and noradrenergic pathways.     

New-onset functional tics during the COVID-19 pandemic: Clinical characteristics of 105 cases from a single centre

Background and purpose

The COVID-19 pandemic has been associated amongst other things with a sharp increase in adolescents and young adults presenting acutely with functional tics. Initial reports have suggested clinically relevant differences between functional tics and neurodevelopmental tics seen in primary tic disorders such as Tourette syndrome. We aimed to provide confirmatory findings from the largest single-centre cohort to date.

Methods

In the present study we present data from 105 consecutive patients who developed functional tics during a 3-year period overlapping with the COVID-19 pandemic (April 2020–March 2023). All patients underwent a comprehensive neuropsychiatric assessment at a single specialist centre for tic disorders.

Results

Female adolescents and young adults accounted for 69% of our sample. Functional tics had an acute/subacute onset in most cases (75% with a peak of severity within 1 month). We found a disproportionately high frequency of complex movements (81%) and vocalizations (75%). A subset of patients (23%) had a pre-existing primary tic disorder (Tourette syndrome with functional overlay). The most common psychiatric co-morbidities were anxiety (70%) and affective disorders (40%). Moreover, 41% of patients had at least one functional neurological disorder in addition to functional tics. Exposure to tic-related social media content was reported by half of the patients.

Conclusions

Our findings confirm substantial clinical differences between functional tics developed during the pandemic and neurodevelopmental tics. Both patient- and tic-related red flags support the differential diagnostic process and inform ongoing monitoring in the post-pandemic era.     

European clinical guidelines for Tourette syndrome and other tic disorders—version 2.0. Part I: assessment

In 2011 a working group of the European Society for the Study of Tourette Syndrome (ESSTS) has developed the first European assessment guidelines for Tourette syndrome (TS). Now, we present an updated version 2.0 of these European clinical guidelines for Tourette syndrome and other tic disorders, part I: assessment. Therefore, the available literature has been thoroughly screened, supplemented with national guidelines across countries and discussions among ESSTS experts. Diagnostic changes between DSM-IV and DSM-5 classifications were taken into account and new information has been added regarding differential diagnoses, with an emphasis on functional movement disorders in both children and adults. Further, recommendations regarding rating scales to evaluate tics, comorbidities, and neuropsychological status are provided. Finally, results from a recently performed survey among ESSTS members on assessment in TS are described. We acknowledge that the Yale Global Tic Severity Scale (YGTSS) is still the gold standard for assessing tics. Recommendations are provided for scales for the assessment of tics and psychiatric comorbidities in patients with TS not only in routine clinical practice, but also in the context of clinical research. Furthermore, assessments supporting the differential diagnosis process are given as well as tests to analyse cognitive abilities, emotional functions and motor skills.

     

Tourette syndrome: the self under siege

Tourette syndrome is a neurodevelopmental disorder characterized by motor and vocal tics--rapid, repetitive, stereotyped movements or vocalizations. Tourette syndrome typically has a prepubertal onset, and boys are more commonly affected than girls. Symptoms usually begin with transient bouts of simple motor tics. By age 10 years, most children are aware of nearly irresistible somatosensory urges that precede the tics. These urges likely reflect a defect in sensorimotor gating because they intrude into the child's conscious awareness and become a source of distraction and distress. A momentary sense of relief typically follows the completion of a tic. Over the course of hours, tics occur in bouts, with a regular intertic interval. Tics increase during periods of emotional excitement and fatigue. Tics can become "complex" in nature and appear to be purposeful. Tics can be willfully suppressed for brief intervals and can be evoked by the mere mention of them. Tics typically diminish during periods of goal-directed behavior, especially those that involve both heightened attention and fine motor or vocal control, as occur in musical and athletic performances. Over the course of months, tics wax and wane. New tics appear, often in response to new sources of somatosensory irritation, such as the appearance of a persistent vocal tic (a cough) following a cold. Over the course of years, tic severity typically peaks between 8 and 12 years of age. By the end of the second decade of life, many individuals are virtually tic free. Less than 20% of cases continue to experience clinically impairing tics as adults. Tics rarely occur in isolation, and other coexisting conditions--such as behavioral disinhibition, hypersensitivity to a broad range of sensory stimuli, problems with visual motor integration, procedural learning difficulties, attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder, depression, anxiety, and emotional instability--are often a greater source of impairment than the tics themselves. Emerging behavioral treatments of Tourette syndrome are based in part on an understanding of the moment-to-moment experience of somatosensory urges and motor response. With identification of specific genes of major effect and advances in our understanding of the neural circuitry of sensorimotor gating, habit formation, and procedural memory--together with insights from postmortem brain studies, in vivo brain imaging, and electrophysiologic recordings--we might be on the threshold of a deeper understanding of the phenomenology and natural history of Tourette syndrome.     

Identification of pyruvate kinase as an antigen associated with Tourette syndrome

Immune responses to beta-hemolytic streptococcal infections are hypothesized to trigger tic disorders and early-onset obsessive-compulsive disorder (OCD) in some pediatric populations. Here we identify the M1 isoform of the glycolytic enzyme, pyruvate kinase (PK) as an autoimmune target in Tourette syndrome and associated disorders. Antibodies to PK reacted strongly with surface antigens of infectious strains of streptococcus, and antibodies to streptococcal M proteins reacted with PK. Moreover, immunoreactivity to PK in patients with exacerbated symptoms who had recently acquired a streptococcal infection was 7-fold higher compared to patients with exacerbated symptoms and no evidence of a streptococcal infection. These data suggest that PK can function as an autoimmune target and that this immunoreactivity may be associated with Tourette syndrome, OCD, and associated disorders.     

Transcranial magnetic stimulation in Gilles de la Tourette syndrome

The cause of Gilles de la Tourette syndrome (GTS), a chronic motor and vocal tic disorder of childhood onset, remains unknown. Abnormalities in basal ganglia-thalamo-cortical circuits presumably play an important role in the pathophysiology underlying the involuntary tics. The use of transcranial magnetic stimulation (TMS), a noninvasive and painless tool to examine the excitability of several different circuits in the human motor cortex has advanced our understanding of the pathophysiology. Motor thresholds are similar in GTS and healthy subjects; in the resting state, recruitment of motor evoked potentials (MEPs) above threshold is more gradual in patients than controls. In contrast, recruitment of MEPs during preactivation is similar in both groups, as is the duration of the cortical silent period. This suggests that the distribution of excitability in the corticospinal system in patients at rest is different to that in healthy individuals. Importantly, correlation analysis showed that reduced levels of excitability at rest relate, in pure GTS patients, to video ratings of complex tics, and hand and finger tics, with less excitability predicting fewer tics. The correlations disappear for measures made during voluntary activation. This suggests that this is an adaptive response to abnormal basal ganglia-motor cortex inputs in an effort to reduce unwanted movements, a notion supported by electroencephalography-coherence studies that show increased cortico-cortical coupling.Compared to the healthy control group, short intracortical inhibition (SICI) thresholds are similar. However, above-threshold SICI recruitment and sensory afferent inhibition (SAI), a paradigm to examine sensory motor integration, are reduced in patients. This is consistent with the suggestion that reduced excitability of cortical inhibition is one factor that contributes to the difficulty that patients have in suppressing involuntary tics. In addition the reduced SAI indicates that impaired intracortical inhibition may not be limited to the motor cortex but also involves circuits linking sensory input and motor output.GTS with attention deficit hyperactivity disorder comorbidity is associated with more extensive changes in the excitability of motor cortex circuits than pure GTS or GTS+obsessive–compulsive disorder. The extent to which various different neuronal circuits are affected may be relevant for the phenotype of Tourette spectrum disorders.