«123»Seite
3 articles, page 1 of 3

Review article

Tourette Syndrome and Other Tic Disorders in Childhood, Adolescence and Adulthood

Dtsch Arztebl Int 2012; 109(48): 821-8; DOI: 10.3238/arztebl.2012.0821

Ludolph, A G; Roessner, V; Münchau, A; Müller-Vahl, K

Department of Child- and Adolescent Psychiatry and Psychotherapy, Ulm University Hospital:
Prof. Dr. med. Ludolph
Clinic and Policlinic of Child- and Adolescent Psychiatry and Psychotherapy, Dresden University of Technology: Prof. Dr. med. Roessner
Department of Neurology, University Medical Center Hamburg-Eppendorf: Prof. Dr. med. Münchau
Clinic of Psychiatry, Socialpsychiatry and Psychotherapy, Hannover Medical School: Prof. Dr. med. Müller-Vahl

Background: Tourette syndrome is a combined motor and vocal tic disorder that begins in childhood and takes a chronic course. It arises in about 1% of all children, with highly varying severity. Transient and usually mild tics are seen in as many as 15% of all children in elementary school. The diagnosis is often delayed by several years.

Methods: We selectively reviewed the pertinent literature, including the guidelines of the European Society for the Study of Tourette Syndrome for the diagnosis and treatment of tic disorders.

Results: Tic disorders usually take a benign course, with spontaneous improvement in adolescence in about 90% of patients. Psychoeducation is the basis of treatment in each case and almost always brings marked emotional relief. Specific treatment is needed only for more severe tics and those that cause evident psychosocial impairment. 80–90% of patients with Tourette syndrome have comorbidities (attention deficit–hyperactivity disorder, obsessive-compulsive disorder, depression, anxiety, emotional dysregulation, autoaggression), which often impair their quality of life more than the tics do and therefore become the main target of treatment. There is little evidence for the efficacy of treatment for tics. Small-scale controlled studies with a brief follow-up period have been carried out for some neuroleptic drugs. Behavior therapy should be tried before drug treatment. A further option for very severely affected adults is deep brain stimulation.

Conclusion: Because of the low level of the available evidence, no definitive recommendations can be made for the treatment of tics.

Tourette syndrome is a neuropsychiatric disorder that begins in childhood and is characterized by motor and vocal tics. It is named after Georges Albert Édouard Brutus Gilles de la Tourette (18571904), a pupil of Charcot at the Salpêtrière, who published the first case series of patients with this disorder. The motor and vocal tics typically fluctuate in number, frequency, intensity, and complexity over the course of the disease. Until very recently, Tourette syndrome was thought to be exceedingly rare (an “orphan disease”); epidemiologic studies have revealed, however, that tic disorders are actually quite common, and that their diagnosis is often delayed (e1). Many patients with tics suffer from stigmatization and prejudice for years until the true nature of their problem is recognized.

This review is based on pertinent publications from 2000 onward that were retrieved by a search in the PubMed, PsycINFO, and EMBASE databases with the key words “Tourette syndrome” and “tic disorder,” and on the guidelines of the European Society for the Study of Tourette Syndrome (ESSTS), published in early 2011. The ICD-10 diagnostic criteria, clinical features, diagnostic assessment, and treatment options for Tourette syndrome are presented from a combined child/adolescent psychiatric, neurological, and adult psychiatric perspective. The purpose of this review is to improve physicians’ understanding of this complex neuropsychiatric disorder and of the comorbidities that often accompany it.

Definition and clinical features

A tic is a rapid, repeated, non-rhythmic movement or sound production that occurs suddenly, serves no purpose, and is experienced as meaningless. Tics are classified by their quality (motor or vocal) and their degree of complexity (simple or complex). They can appear isolated or in combination, and they can be either transient or chronic.

Tics in children of elementary-school age are often mild and transient and cause no impairment, so they cannot be called a disease in the narrow sense of the term. Their correct diagnosis is important, however, so that the child’s parents can be told what the problem is and what to expect, preventive action can be taken against prejudice and teasing, and inadequate treatments can be avoided. Even today, the time to diagnosis is often as long as 5 to 10 years (1, e1).

Typically, tics are preceded by a unpleasant “premonitory urge,” i.e., the feeling that a certain type of tic is about to be produced; the feeling disappears as soon as the tic is actually produced (e2). Another typical feature of tics is that they can be voluntarily suppressed, though usually only briefly. Both of these phenomena – the premonitory urge and voluntary suppressibility – are age-dependent, being more prominent in adults than in children (2).

Motor tics

Simple motor tics, by definition, affect only a small number of muscle groups and involve only short-lasting, circumscribed movements. They are most often seen in the face and head, with ocular tics being particularly common. In contrast, complex motor tics are defined as those that involve multiple muscle groups and/or seem to fulfill a purpose. Copropraxia, echopraxia, and palipraxia are special types of complex motor tics (Box 1).

Box 1
Examples of simple and complex motor tics

Vocal tics

Throat-clearing and sniffling are the most common kinds of vocal tic; exclamations and shouts are much rarer. Especially in children, tics are often misdiagnosed as an airway disease such as asthma or an allergy. Coprolalia, echolalia, and palilalia are complex vocal tics (Box 2).

Box 2
Examples of simple and complex vocal tics

Coprolalia is the clinical manifestation that the public most commonly associates with Tourette syndrome, although it is present in only 19–32% of patients (3). It usually involves the uttering of short words that are considered to be foul language, often of an obscene nature (Box 2). Coprolalia is more common in more severe cases of Tourette syndrome with multiple comorbidities (3).

The ICD-10 diagnostic criteria for tic disorders

Tourette syndrome – Tourette syndrome is a combined vocal and motor tic disorder with, by definition, at least two types of motor tic and at least one type of vocal tic. The ICD-10 diagnostic criteria further require the onset of illness in childhood or adolescence, duration of at least one year (though there may be symptom-free intervals lasting several months), and fluctuation of the the tics over time. No particular degree of severity is required.

Chronic motor tic disorder – Chronic motor tic disorder differs formally from Tourette syndrome exclusively in the absence of vocal tics. The motor tics are usually milder than those seen in patients with Tourette syndrome, and the comorbidities are rarer and generally less severe.

Chronic vocal tic disorder – Chronic vocal tic disorder is rare. It is characterized by the persistent occurrence of exclusively vocal tics. Comorbidities are just as frequent as in Tourette syndrome.

Transient tic disorder – Transient tic disorder is seen only in children and is characterized by tics that disappear within one year. These are usually mild, simple motor tics that the children themselves may not even notice (Box 3).

Box 3
ICD-10 classification of primary tic disorders

Epidemiology and clinical course

The worldwide prevalence of Tourette syndrome is thought to be about 1% (4). It is assumed that as many as 10–15% of children in elementary school have transient simple motor tics. Boys and men are affected about four times as often as girls and women (4, e3).

Tics usually appear with gradually increasing intensity between the ages of 6 and 8 years (5, e1). There is no relation between the age of onset and the severity of the tic (e3). Motor tics appear, on the average, two to three years earlier than vocal tics. Typically, the initial manifestations of the disease are simple motor tics involving the face and head. No particular criteria (“markers”) have yet been identified that could be used to predict the future course of the disease (5). The tics are at their most severe, on average, between the ages of 10 and 12 (5, e4). About 90% of patients have spontaneous improvement after the tics reach their peak. This is reflected in the much lower prevalence of Tourette syndrome in adults (6). There is still debate, however, over whether chronic tic disorders ever fully disappear, and, if so, how often (1, e3, e5e7). In all cases, there are spontaneous fluctuations in the localization, number, frequency, complexity, type, and severity of the tics.

Most patients say that the tics become more frequent when they are under emotional stress (e8, e9) and less common with relaxation or concentration (e10). Tics are suggestible and can sometimes be evoked by external stimuli, e.g., a discussion of tics during a medical consultation. So-called echo phenomena can involve imitation not only of the voluntary movements of other persons, but also of other patients’ tics (e11).

Diagnosis

Tic disorders are clinically diagnosed on the basis of a detailed history and a neurological and psychiatric examination. Further diagnostic evaluation is only rarely needed, e.g., when the manifestations are atypical or when a secondary tic disorder is suspected (7).

The term “tic” should be used only to denote hyperkinesias and sound productions that meet the defined diagnostic criteria. Neither conversion disorders with tic-like movements nor movement disorders of unknown origin should be designated as tics.

Tics are usually easy to distinguish from other types of hyperkinetic movement, such as:

  • chorea,
  • dyskinesia,
  • hemifacial spasm,
  • restless legs syndrome, and
  • focal epileptic seizures.

Differential diagnosis

The disorders that are most difficult to distinguish from tic disorders are the following:

  • dissociative movement disorders
  • compulsive behaviors
  • generalized hyperactivity
  • mannerisms
  • stereotypies (e12, e13), and
  • (less commonly) dystonia and myoclonus (7).

In rare cases, tics can arise as a manifestation of another disease (e.g., Wilson’s disease, neuroacanthocytosis, Fragile X syndrome, Sydenham’s chorea, Huntington’s disease); they can also be iatrogenic or substance-induced (e.g., by carbamazepine, phenytoin, lamotrigine, amphetamines, dopaminergic drugs, or cocaine). Tardive tics are a rare complication of neuroleptic use (7).

Comorbidities

80–90% of patients with Tourette syndrome have not only tics, but also psychiatric manifestations (8). The number and severity of accompanying disorders rise as the tics become more severe (5).

Among patients of all ages with Tourette syndrome, children are the most likely (50–90%) to suffer additionally from attention deficit–hyperactivity disorder (ADHD) (8, e14, e15). Other common comorbidities in childhood that often markedly impair psychosocial functioning are the following:

  • obsessive-compulsive behavior and anxiety (e16)
  • impulse-control disorders (in the terminology of the DSM IV-TR, “intermittent explosive disorder”)
  • emotional dysregulation
  • disorders of social behavior
  • autism spectrum disorders (ASD)
  • disorders of individual skills (e17e21).

Adults often have obsessive-compulsive symptoms or behavior as well as auto-aggression, depression, and sleep disorders; addiction and autism spectrum disorders are less common (1, 5, 8).

As studies have shown, the health-related quality of life of patients with Tourette syndrome is impaired above all by the accompanying psychiatric disorders—in children, mainly obsessive-compulsive disorder and ADHD; in adults, mainly depression (9, 10).

Etiology

Structural and functional imaging have revealed abnormalities in the motor and somatosensory portions of the corticostriatal-thalamocortical circuit (11, 12, e22, e23). In addition, recent studies have shown that structures outside this circuit are also involved—in particular, the limbic system (13). A major pathophysiological role for the dopaminergic system has been presumed ever since the discovery that dopamine-receptor antagonists can alleviate tics. It seems most likely that an abnormality of presynaptic regulation exists in combination with phasic dysfunction of dopaminergic transmission (14). Further transmitter systems seem to be involved as well; impaired functioning of the serotoninergic system is postulated (15).

Genetic and environmental factors

Family studies and molecular genetic studies have revealed that tic disorders have a major genetic component (e24e29). It is currently estimated that the first-degree relatives of a patient with Tourette syndrome have a 5% to 15% risk of developing the disease themselves and a 10% to 20% risk of developing any sort of tic (16). Many candidate genes have been identified, and the pattern of inheritance seems to be complex (Box 4) (1719, e29, e30). In addition to genetic factors, environmental influences seem to play a major role as well. It is presumed that a combination of genetic vulnerability and environmental influences results in the development of tic disorders (20, e24, e26, e28) (Box 5).

Box 4
Susceptibility genes associated with tic disorders
Box 5
Non-genetic risk factors

Treatment

For many patients and their families, the diagnosis itself brings considerable relief. If the patient is a child, it is important that his or her teachers and other significant adults should also understand the nature of the condition. Thorough patient education should include not only information about the cause and future course of the disease, but also counseling on social issues such as the various types of compensatory aid that are available, how to request certification as a disabled or severely disabled person, the issue of driving, and the choice of an occupation (e31). Psychoeducation should always be the first step of treatment (Figure). It is not at all rare for patients to feel stress as a result of their tic disorder for no other reason than the way others respond to it (intolerance, teasing) (e31).

Figure
Flowchart for the treatment of tics

Tics cannot be cured, nor is there any causal therapy. Even symptomatic treatment is problematic, as no form of treatment is available that can simultaneously alleviate all of the manifestations of Tourette syndrome and its comorbidities. Tics should be treated symptomatically when they produce marked physical or psychosocial impairment. None of the available treatments affect the course of tic disorders. Whenever the efficacy of a treatment is assessed, the characteristic spontaneous fluctuations of tics must be taken into account.

Although there have been many publications about treatments for chronic tic disorders, the evidence for the efficacy of any particular treatment is weak. Controlled trials are available for some typical neuroleptic drugs (haloperidol, pimozide) and some atypical ones (risperidone, ziprasidone), but all of these were carried out on small groups of subjects over periods of no more than 8 weeks (2123). A Cochrane review that was slated for publication could not be prepared because of the poor state of the data (Pierce & Rickards, DOI: 10.1002/14651858.CD008151). In controlled studies, behavior-therapeutic approaches have been found moderately efficacious (up to EF 0.68) against moderately severe tics (24, 25).

Pharmacotherapy

In Germany, dopamine-receptor antagonists (neuroleptic drugs) are considered the substances of first choice for the treatment of tics (26). Haloperidol is the only medication that is approved in Germany for the treatment of Tourette syndrome, and its use for this purpose is supported by the highest level of evidence (EBM level I); nevertheless, it is hardly used any more because of its known side effects. Nearly all medically treated patients now receive off-label treatment with atypical neuroleptic drugs, although there have been only a few controlled trials of their use for this indication (26). Their most common adverse effects are fatigue, increased appetite, weight gain, sexual dysfunction, and akathisia (26).

Treatment with dopamine-receptor antagonists should be started at a low dose that is then gradually increased until either a therapeutic benefit is seen or intolerable side effects arise. The dose may need to be adjusted later because of spontaneous fluctuations of the tic(s); in children, the dose may need to be increased to keep up with bodily growth. Tolerance can also develop (26). The agents of first choice for use in children are currently tiapride, risperidone, and aripiprazole; for adults, the German Neurological Association, in its guidelines, recommends tiapride, sulpiride, and risperidone (recommendation level A for each), as well as aripiprazole (recommendation level B) (Table). A retrospective open-label trial of sulpiride for the treatment of Tourette syndrome has been published, with 63 participating patients (27), but there has not yet been any study of amisulpride, which might have a more favorable side-effect profile (28).

Table
The treatment of tics

Unfortunately, the very poor state of the data currently allows no definitive recommendation about treatment (26). Aripiprazole seems to have a better side-effect profile than other atypical neuroleptic drugs (e32). Further alternatives include other atypical neuroleptic drugs, pimozide, combinations of the substances just named, tetrabenazine, topiramate, and (in selected cases) local botulinum-toxin injections and cannabinoids (Table). Clonidine is used preferentially in English-speaking countries (29), even though its tic-suppressing effect is rather weak in comparison to that of the neuroleptics mentioned above (e33, e34).

Behavior therapy

Habit reversal training (HRT) was recently introduced as an alternative to drug therapy for tics. In HRT, the patient prevents the occurrence of a tic by performing a previously learned alternative behavior instead. This method lessens the frequency of tics by about 30% (24, 25). Comparable results can be obtained with exposure and response prevention (ERP), a strategy for interrupting the automatism described by many patients in which a premonitory urge is necessarily followed by a tic. A European expert commission recently recommended that behavior therapy (if available) should always be tried before drug treatment (24). Behavior therapy often fails because of inadequate motivation, particularly in children.

Deep brain stimulation

Very severely affected adult patients with medically intractable Tourette syndrome may benefit from deep brain stimulation (30, 31). The initial findings of open uncontrolled trials and small controlled trials suggest that deep brain stimulation not only lessens the frequency of tics but also improves comorbid psychiatric disorders, including obsessive-compulsive symptoms, depression, anxiety, and autoaggression. The optimal target for deep brain stimulation has not yet been conclusively identified (30). The procedure is occasionally complicated by infection and rarely by intracerebral hemorrhage. The most common stimulation-induced side effects are fatigue, lack of energy, visual disorders, and dizziness (32) (Table).

The treatment of comorbidities

It is recommended that psychiatric disorders accompanying Tourette syndrome should be treated in the same way as when they occur in the absence of Tourette syndrome. Alongside drug therapy, psychotherapeutical interventions are an important component of the multimodal treatment concept, particularly for children. Selective serotonin reuptake inhibitors (SSRI) are the mainstay of drug treatment for obsessive-compulsive symptoms, anxiety, and depression; fluoxetine is the only one approved for use in children aged 8 or older. Methylphenidate is the drug of first choice for treatment of ADHD in patients with comorbid tics. Multiple independent trials and a meta-analysis have unequivocally shown that methylphenidate does not cause any lasting worsening of the tics (e33, e35). Alternative drugs include atomoxetine and clonidine, alone or in combination with methylphenidate (1, e35).

Conclusions

Many patients with chronic tic disorders and Tourette syndrome have such mild tics that they need no treatment. Psychoeducation of the patient, his or her family, and other persons who interact with the patient in everyday life is essential to prevent stigmatization. For tic disorders that are severe enough to require treatment, the available therapeutic options are still unsatisfactory. Genetic studies are expected to provide the basis for new approaches to the pharmacotherapy of tic disorders.

Conflict of interest statement

Prof. Ludolph has served as a paid consultant for, and has received reimbursement for travel costs from Shire Pharmaceuticals. She has received lecture honoraria from Janssen-Cilag, Medice Pharma, and Lilly as well as support for research from Novartis and has carried out clinical trials in cooperation with the Janssen-Cilag, Otsuka, Shire, and Boehringer Ingelheim companies.

Prof. Roessner has received payment for consulting and writing activities from Lilly, Novartis, and Shire Pharmaceuticals, lecture honoraria from Lilly, Novartis, Shire Pharmaceuticals, and Medice Pharma, and support for research from Shire and Novartis. He has carried out (and is currently carrying out) clinical trials in cooperation with the Novartis, Shire, and Otsuka companies.

Prof. Münchau has served as a paid consultant Pharm Allergan. He has received reimbursement of travel costs and medical conference attendance fees from Merz Pharmaceuticals and Pharm Allergan, lecture honoraria from Merz Pharmaceuticals, Pharm Allergan, and Ipsen Pharma, and financial support for research from Merz Pharmaceuticals, Pharm Allergan, Ipsen Pharma, and Medivation Inc.

Prof. Müller-Vahl has received financial support for research from the Lundbeck company and has carried out (and is currently carrying out) clinical trials in cooperation with the Otsuka Pharma and Boehringer Ingelheim companies.

Manuscript submitted on 27 July 2011, revised version accepted on 7 August 2012.

Translated from the original German by Ethan Taub, M.D.

Corresponding author
Prof. Dr. med. Andrea G. Ludolph
Klinik für Kinder- und Jugendpsychiatrie und Psychotherapie
Steinhoevelstr. 5, 89075 Ulm, Germany
andrea.ludolph@uni-ulm.de

@For eReferences please refer to:
www.aerzteblatt-international.de/ref4812

1.
Müller-Vahl K: Tourette-Syndrom und andere Tic-Erkrankungen im Kindes- und Erwachsenenalter. 1st edition. Berlin: Medizinisch Wissenschaftliche Verlagsgesellschaft 2010.
2.
Banaschewski T, Woerner W, Rothenberger A: Premonitory sensory phenomena and suppressibility of tics in Tourette syndrome: developmental aspects in children and adolescents. Dev Med Child Neurol 2003; 45: 700–3. CrossRef MEDLINE
3.
Freeman RD, Zinner SH, Müller-Vahl KR, Fast DK, Burd LJ, Kano Y, et al.: Coprophenomena in Tourette syndrome. Dev Med Child Neurol 2009; 51: 218–27. CrossRef MEDLINE
4.
Robertson MM: The prevalence and epidemiology of Gilles de la Tourette syndrome. Part 1: the epidemiological and prevalence studies. J Psychosom Res 2008; 65: 461–72. CrossRef MEDLINE
5.
Freeman RD, Fast DK, Burd L, Kerbeshian J, Robertson MM, Sandor P: An international perspective on Tourette syndrome: selected findings from 3,500 individuals in 22 countries. Dev Med Child Neurol 2000; 42: 436–47. CrossRef MEDLINE
6.
Knight T, Steeves T, Day L, Lowerison M, Jette N, Pringsheim T: Prevalence of tic disorders: a systematic review and meta-analysis. Pediatr Neurol 2012; 47: 77–90. CrossRef MEDLINE
7.
Cath DC, Hedderly T, Ludolph AG, Stern JS, Murphy T, Hartmann A, et al.: European clinical guidelines for Tourette syndrome and other tic disorders. Part I: assessment. Eur Child Adolesc Psychiatry 2011; 20: 155–71. CrossRef MEDLINE PubMed Central
8.
Khalifa N, von Knorring AL: Psychopathology in a Swedish population of school children with tic disorders. J Am Acad Child Adolesc Psychiatry 2006; 45: 1346–53. CrossRef MEDLINE
9.
Müller-Vahl K, Dodel I, Müller N, Münchau A, Reese JP, Balzer-Geldsetzer M, et al.: Health-related quality of life in patients with Gilles de la Tourette’s syndrome. Mov Disord 2010; 25: 309–14. CrossRef MEDLINE
10.
Pringsheim T, Lang A, Kurlan R, Pearce M, Sandor P: Understanding disability in Tourette syndrome. Dev Med Child Neurol 2009; 51: 468–72. CrossRef MEDLINE
11.
Ludolph AG, Juengling FD, Libal G, Ludolph AC, Fegert JM, Kassubek J: Grey-matter abnormalities in boys with Tourette syndrome: magnetic resonance imaging study using optimised voxel-based morphometry. Br J Psychiatry 2006; 188: 484–5. CrossRef MEDLINE
12.
Thomalla G, Siebner HR, Jonas M, Bäumer T, Biermann-Ruben K, Hummel F, et al.: Structural changes in the somatosensory system correlate with tic severity in Gilles de la Tourette syndrome. Brain 2009; 132: 765–77. CrossRef MEDLINE
13.
Ludolph AG, Pinkhardt EH, Tebartz van Elst L, Libal G, Ludolph AC, Fegert JM, et al.: Are amygdalar volume alterations in children with Tourette syndrome due to ADHD comorbidity? Dev Med Child Neurol 2008; 50: 524–9. CrossRef MEDLINE
14.
Yeh CB, Lee CS, Ma KH, Lee MS, Chang CJ, Huang WS: Phasic dysfunction of dopamine transmission in Tourette’s syndrome evaluated with 99mTc TRODAT-1 imaging. Psychiatry Res 2007; 156: 75–82. CrossRef MEDLINE
15.
Müller-Vahl KR, Meyer GJ, Knapp WH, Emrich HM, Gielow P, Brücke T, et al.: Serotonin transporter binding in Tourette Syndrome. Neurosci Lett 2005; 385: 120–5. CrossRef MEDLINE
16.
Tourette Syndrome Association International Consortium for Genetics. Genome scan for Tourette disorder in affected-sibling-pair and multigenerational families. Am J Hum Genet 2007; 80: 265–72. CrossRef MEDLINE PubMed Central
17.
Abelson JF, Kwan KY, O’Roak BJ, Baek DY, Stillman AA, Morgan TM, et al.: Sequence variants in SLITRK1 are associated with Tourette’s syndrome. Science 2005; 310: 317–20. CrossRef MEDLINE
18.
Scharf JM, Moorjani P, Fagerness J, Platko JV, Illmann C, Galloway B, et al.: Lack of association between SLITRK1var321 and Tourette syndrome in a large family-based sample. Neurology 2008; 70: 1495–6. CrossRef MEDLINE
19.
Ercan-Sencicek AG, Stillman AA, Ghosh AK, Bilguvar K, O’Roak BJ, Mason CE, et al.: L-histidine decarboxylase and Tourette’s syndrome. N Engl J Med 2010; 362: 1901–8. CrossRef MEDLINE PubMed Central
20.
Martino D, Dale RC, Gilbert DL, Giovannoni G, Leckman JF: Immunopathogenic mechanisms in tourette syndrome: A critical review. Mov Disord 2009; 24: 1267–79. CrossRef MEDLINE
21.
Sallee FR, Kurlan R, Goetz CG, Singer H, Scahill L, Law G, et al.: Ziprasidone treatment of children and adolescents with Tourette’s syndrome: a pilot study. J Am Acad Child Adolesc Psychiatry 2000; 39: 292–9. CrossRef MEDLINE
22.
Dion Y, Annable L, Sandor P, Chouinard G: Risperidone in the treatment of tourette syndrome: a doubleblind, placebo-controlled trial. J Clin Psychopharmacol 2002; 22: 31–9. CrossRef MEDLINE
23.
Scahill L, Leckman JF, Schultz RT, Katsovich L, Peterson BS: A placebo-controlled trial of risperidone in Tourette syndrome. Neurology 2003; 60: 1130–5. CrossRef MEDLINE
24.
Verdellen C, van de Griendt J, Hartmann A, Murphy T: European clinical guidelines for Tourette syndrome and other tic disorders. Part III: behavioural and psychosocial interventions. Eur Child Adolesc Psychiatry 2011; 20: 197–207. CrossRef MEDLINE
25.
Piacentini J, Woods DW, Scahill L, et al.: Behavior therapy for children with Tourette disorder: a randomized controlled trial. JAMA 2010; 303: 1929–37. CrossRef MEDLINE PubMed Central
26.
Roessner V, Plessen KJ, Rothenberger A, Ludolph AG, Rizzo R, Skov L, et al.: European clinical guidelines for Tourette syndrome and other tic disorders. Part II: pharmacological treatment. Eur Child Adolesc Psychiatry 2011; 20: 173–96. CrossRef MEDLINE PubMed Central
27.
Robertson MM, Schnieden V, Lees AJ: Management of Gilles de la Tourette syndrome using sulpiride. Clin Neuropharmacol 1990; 13: 229–35. CrossRef MEDLINE
28.
Müller-Vahl KR: Die Benzamide Tiaprid, Sulpirid und Amisulprid in der Therapie des Tourette-Syndroms. Nervenarzt 2007; 78: 264–71. CrossRef MEDLINE
29.
Pringsheim T, Doja A, Gorman D, et al.: Canadian guidelines for the evidence-based treatment of tic disorders: pharmacotherapy. Can J Psychiatry 2012; 57: 133–43. MEDLINE
30.
Müller-Vahl KR, Cath DC, Cavanna AE, Dehning S, Porta M, Robertson MM, et al.: European clinical guidelines for Tourette syndrome and other tic disorders. Part IV: deep brain stimulation. Eur Child Adolesc Psychiatry 2011; 20: 209–17. CrossRef MEDLINE
31.
Steeves T, McKinlay BD, Gorman D, et al.: Canadian guidelines for the evidence-based treatment of tic disorders: behavioural therapy, deep brain stimulation, and transcranial magnetic stimulation. Can J Psychiatry 2012; 57: 144–51. MEDLINE
32.
Kuhn J, Gründler TOJ, Lenartz D, Sturm V, Klosterkötter J, Huff W: Tiefe Hirnstimulation bei psychiatrischen Erkrankungen. Dtsch Arztebl Int 2010; 107(7): 105–13. VOLLTEXT
e1.
Mol Debes NM, Hjalgrim H, Skov L: Limited knowledge of Tourette syndrome causes delay in diagnosis. Neuropediatrics 2008; 39: 101–5. MEDLINE
e2.
Leckman JF, Walker DE, Cohen DJ: Premonitory urges in Tourette’s syndrome. Am J Psychiatry 1993; 150: 98–102. MEDLINE
e3.
Leckman JF, Zhang H, Vitale A, Lahnin F, Lynch K, Bondi C, Kim YS, Peterson BS: Course of tic severity in Tourette syndrome: the first two decades. Pediatrics 1998; 102: 14–9. MEDLINE
e4.
Khalifa N, von Knorring AL: Prevalence of tic disorders and Tourette syndrome in a Swedish school population. Dev Med Child Neurol 2003; 45: 315–9. MEDLINE
e5.
Burd L, Kerbeshian PJ, Barth A, Klug MG, Avery PK, Benz B: Long-term follow-up of an epidemiologically defined cohort of patients with Tourette syndrome. J Child Neurol 2001; 16: 431–7. MEDLINE
e6.
Ohta M, Kano Y: Clinical characteristics of adult patients with tics and/or Tourette’s syndrome. Brain Dev 2003; 25: 32–6. CrossRef MEDLINE
e7.
Pappert EJ, Goetz CG, Louis ED, Blasucci L, Leurgans S: Objective assessments of longitudinal outcome in Gilles de la Tourette’s syndrome. Neurology 2003; 61: 936–40. MEDLINE
e8.
Hoekstra PJ, Steenhuis MP, Kallenberg CG, Minderaa RB: Association of the small life events with self reports of tic severity in pediatric and adult tic disorder patients: a prospective longitudinal study. J Clin Psychiatry 2004; 65: 426–31. CrossRef MEDLINE
e9.
Lin H, Yeh CB, Peterson BS, Scahill L, Grantz H, Findley DB, Katsovich L, Otka J, Lombroso PJ, King RA, Leckman JF: Assessment of symptom exacerbations in a longitudinal study of children with Tourette’s syndrome or obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry 2002; 41: 1070–7. MEDLINE
e10.
Sacks O: A surgeon’s life. An Anthropologist on Mars: Seven Paradoxical Tales. New York: Alfred A. Knopf 1995.
e11.
Finis J, Moczydlowski A, Pollok B, Biermann-Ruben K, Thomalla G, Heil M, Krause H, Jonas M, Schnitzler A, Münchau A: Echoes from childhood-imitation in Gilles de la Tourette Syndrome. Mov Disord 2012; 27: 562–5. MEDLINE
e12.
Singer HS: Motor stereotypies. Semin Pediatr Neurol 2009; 16: 77–81. MEDLINE
e13.
Singer HS: Stereotypic movement disorders. Handb Clin Neurol 2011; 100: 631–9. CrossRef MEDLINE
e14.
Banaschewski T, Neale BM, Rothenberger A, Roessner V: Comorbidity of tic disorders & ADHD: conceptual and methodological considerations. Eur Child Adolesc Psychiatry 2007; 16: 5–14. MEDLINE
e15.
Brown L, Dure LS: The treatment of comorbid attention-deficit disorder and Tourette’s syndrome. In: Kurlan R (ed.). Handbook of Tourette’s syndrome and related tic and behavioural disorders. New York: Marcel Dekker 2005; 455–65.
e16.
Lebowitz ER, Motlagh MG, Katsovich L, King RA, Lombroso PJ, Grantz H, Lin H, Bentley MJ, Gilbert DL, Singer HS, Coffey BJ: the Tourette Syndrome Study Group, Kurlan RM, Leckman JF: Tourette syndrome in youth with and without obsessive compulsive disorder and attention deficit hyperactivity disorder. Eur Child Adolesc Psychiatry 2012; 21: 451–7. MEDLINE
e17.
Burd L, Kerbeshian PJ, Barth A, Klug MG, Avery PK, Benz B: Long-term follow-up of an epidemiologically defined cohort of patients with Tourette syndrome. J Child Neurol 2001; 16: 431–7. MEDLINE
e18.
Budman CL, Bockmore L, Stokes J, Sossin M: Clinical phenomenology of episodic rage in children with Tourette syndrome. J Pediatr Psychol 2003; 27: 203–8.
e19.
Budman CL, Bruun RD, Park KS, Olson ME: Rage attacks in children and adolescents with Tourette’s disorder: a pilot study. J Clin Psychiatry 1998; 59: 576–80. MEDLINE
e20.
Budman CL, Rockmore L, Stokes J, Sossin M: Clinical phenomenology of episodic rage in children with Tourette syndrome. J Psychosom Res 2003; 55: 59–65. CrossRef MEDLINE
e21.
Burd L, Freeman RD, Klug MG, Kerbeshian J: Tourette syndrome and learning disabilities. BMC Pediatr 2005; 5: 34–40. CrossRef MEDLINE PubMed Central
e22.
Worbe Y, Malherbe C, Hartmann A, Pélégrini-Issac M, Messé A, Vidailhet M, Lehéricy S, Benali H: Functional immaturity of cortico-basal ganglia networks in Gilles de la Tourette syndrome. Brain 2012; 135: 1937–46. MEDLINE
e23.
Neuner I, Ludolph AG: Neurobiology, clinical characteristics and therapy in Tourette’s syndrome. Fortschr Neurol Psychiatr 2011; 79: 724–32. CrossRef MEDLINE
e24.
Hyde TM, Aaronson BA, Randolph C, Rickler KC, Weinberger DR: Relationship of birth weight to the phenotypic expression of Gilles de la Tourette’s syndrome in monozygotic twins. Neurology 1992; 42: 652–8. MEDLINE
e25.
Nee LE, Caine ED, Polinsky RJ, Eldridge R, Ebert MH: Gilles de la Tourette syndrome: clinical and family study of 50 cases. Ann Neurol 1980; 7: 41–9. MEDLINE
e26.
Pauls DL: An update on the genetics of Gilles de la Tourette syndrome. J Psychosom Res 2003; 55: 7–12. CrossRef
e27.
Price RA, Kidd KK, cohen DJ: A twin study of Tourette syndrome. Arch Gen Psychiatry 1985; 42: 815–20. MEDLINE
e28.
Remschmidt H, Hebebrand J: Das Tourette-Syndrom: Eine zu selten diagnostizierte Tic-Störung? Dtsch Arztebl 1993; 90(24): A-1805–10. VOLLTEXT
e29.
Deng H, Gao K, Jankovic J: The genetics of Tourette syndrome. Nat Rev Neurol 2012; 8: 203–13. MEDLINE
e30.
State MW: The genetics of Tourette Disorder. Curr Opon Genet Dev 2011; 21: 302–9. MEDLINE PubMed Central
e31.
Marcks BA, Berlin KS, Woods DW, Davies WH: Impact of Tourette Syndrome: a preliminary investigation of the effects of disclosure on peer perceptions and social functioning. Psychiatry 2007; 70: 59–67. CrossRef MEDLINE
e32.
Wenzel C, Kleimann A, Bokemeyer S, Müller-Vahl KR: Aripiprazole for the treatment of tourette syndrome: a case series of 100 patients. J Clin Psychopharmacol 2012; 32: 548–50. MEDLINE
e33.
Tourette’s Syndrome Study Group: Treatment of ADHD in children with tics: a randomized controlled trial. Neurology 2002; 58: 527–36. CrossRef MEDLINE
e34.
Müller-Vahl KR: The treatment of Tourette’s syndrome: current opinions. Expert Opin Pharmacother 2002; 3: 899–914. CrossRef MEDLINE
e35.
Bloch MH, Panza KE, Landeros-Weisenberger A, Leckman JF: Meta-analysis: treatment of attention-deficit/hyperactivity disorder in children with comorbid tic disorders. J Am Acad Child Adolesc Psychiatry 2009; 48: 884–93. MEDLINE
e36.
Shapiro A, Shapiro E, Young JG, Feinberg TE: Signs, symptoms, and clinical course. In: Shapiro A, Shapiro E, Young JG, Feinberg TE (Hrsg.). Gilles de la Tourette Syndrome. 2nd edition. Raven Press, New York 1988: 127–93. MEDLINE