Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contact us Login 
  • Users Online:1198
  • Home
  • Print this page
  • Email this page


 
 Table of Contents  
SPECIAL ARTICLE
Year : 2019  |  Volume : 7  |  Issue : 2  |  Page : 277-283

Gilles de la Tourette syndrome: An overview


1 Department of Psychology, GCS.fMRI, Koelliker Hospital; Department of Psychology, FOCUS Lab, University of Turin, Turin, Italy
2 Department of Neuropsychiatry, Michael Trimble Neuropsychiatry Research Group, BSMHFT and University of Birmingham; Department of Neuropsychiatry, School of Life and Health Sciences, Aston University, Birmingham;Sobell Department of Motor Neuroscience and Movement Disorders, UCL and Institute of Neurology, London, England, United Kingdom

Date of Submission27-Aug-2019
Date of Decision15-Sep-2019
Date of Acceptance18-Sep-2019
Date of Web Publication16-Dec-2019

Correspondence Address:
Prof. Andrea E Cavanna
Department of Neuropsychiatry, The Barberry National Centre for Mental Health, 25 Vincent Drive, Birmingham B15 2FG, England
United Kingdom
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/amhs.amhs_122_19

Rights and Permissions
  Abstract 


Gilles de la Tourette syndrome (GTS) is a neurodevelopmental condition characterized by multiple motor and vocal tics with a chronic course. With its multifaceted range of symptoms, GTS lies at the crossroads of neurology and psychiatry. This review article provides an outline of GTS, encompassing its extended clinical phenomenology, pathophysiology, and treatment options. Tics are the most common hyperkinetic manifestations in childhood, and the majority of patients present with comorbid behavioral conditions, such as obsessive-compulsive disorder, attention-deficit hyperactivity disorder, anxiety, and affective symptoms. Most patients report that their tics are preceded by sensory experiences (premonitory urges), i.e., unpleasant sensations characterized by pressure, tension, tightness, pain, itch, or vague inner discomfort. Tics can be temporarily suppressed and delayed for seconds to minutes, at the expense of mounting inner tension until the subjective feeling becomes unbearable, and the tic must be released. A better understanding of the mechanisms at the root of tic production can pave the way to the development of more effective treatment interventions for patients with GTS in order to improve their health-related quality of life (QOL). Specific instruments for measuring health-related QOL based on standardized assessments allow to appraise the impact of both tics and behavioral comorbidities and tailor treatment strategies to individual patients.

Keywords: Behavior, Gilles de la Tourette syndrome, health-related quality of life, premonitory urges, tics


How to cite this article:
Nani A, Cavanna AE. Gilles de la Tourette syndrome: An overview. Arch Med Health Sci 2019;7:277-83

How to cite this URL:
Nani A, Cavanna AE. Gilles de la Tourette syndrome: An overview. Arch Med Health Sci [serial online] 2019 [cited 2020 Oct 20];7:277-83. Available from: https://www.amhsjournal.org/text.asp?2019/7/2/277/273056




  Introduction Top


Gilles de la Tourette syndrome (GTS) was famously described as a complex tic disorder by the French physician Georges Gilles de la Tourette.[1] Although Gilles de la Tourette's landmark paper dates back to 1885, GTS is still poorly understood and largely underdiagnosed.[2] Current epidemiological studies show that GTS has a prevalence ranging between 0.4% and 1% across all cultures.[3],[4] Tics as isolated symptoms are known to be more common than GTS, potentially affecting around 5% of the general population, albeit prevalence figures are highly variable.[5],[6] Overall, the prevalence of tic disorders in the pediatric population could be around 3%, with declining prevalence figures in adulthood.[3],[7]

GTS is a neurodevelopmental disorder characterized by the presence of multiple tics with a chronic course: according to the current diagnostic criteria, at least two motor tics and one vocal tic.[8],[9],[10] Tics are defined as rapid, sudden, involuntary, recurrent, nonrhythmic movements and vocalizations, usually accompanied by specific behavioral symptoms and considered to be the result of altered neurodevelopmental pathways.[11],[12] In consideration of its multifaceted clinical features, it is not surprising that GTS is present in both neurological and psychiatric classification systems, such as those developed by the Movement Disorders Society[13] and the American Psychiatric Association.[8] Furthermore, the clinical heterogeneity of GTS makes it a challenging condition in terms of identifying therapeutic targets and implementing effective treatment interventions aimed at improving patients' health-related quality of life (QOL).[14],[15]

Progress in research over the last few years has led to a better understanding of the sensorimotor processes at the basis of GTS, paving the way for the development of evidence-based therapeutic interventions tailored to the needs of individual patients. Key advances in translating research findings into clinical settings have been facilitated by the availability of disease-specific instruments for the assessment of health-related QOL in both children and adults with GTS.[16],[17] The present article provides an overview of GTS, encompassing its diagnostic criteria, epidemiology, clinical features, behavioral comorbidities, etiology, pathophysiology, and treatment options.


  Diagnostic Criteria and Classification of Tics Top


Individuals affected by chronic tic disorders characteristically exhibit a tic repertoire which is both dynamic and stereotyped, with the re-occurrence of specific tic types at multiple life stages.[11],[12] Tics have an average age at onset of 6–8 years and are reported three to four times more frequently by males than females.[18] In the majority of patients, motor tics develop earlier than vocal tics, and the most frequently observed motor tic at onset is eye blinking.[19]

Both motor and vocal tics can be simple or complex.[20],[21] Commonly reported simple motor tics include eye blinking, eye rolling, face grimacing, mouth opening, neck jerking, shoulder shrugging, abdominal contractions, arm stretching, and kicking. Among the most frequently reported simple vocal tics are grunting, sniffing, coughing, throat clearing, humming, snorting, and squeaking. Complex motor tics usually develop after the onset of simple motor tics and are characterized by the engagement of several muscular segments, often resembling intentional actions. Complex motor tics can result in copropraxia (involuntary production of obscene gestures), palipraxia (repetition of own movements a set number of times or until they feel “just right”), and echopraxia (imitation of others' movements). Complex vocal tics often include recognizable and meaningful words, resulting in coprolalia (involuntary swearing), palilalia (repeating own words and movements a set number of times or until they feel “just right”), and echolalia (repeating others' words). Other complex vocal tics include the production of apparently random words and animal sounds. Complex tics involving coprophenomena are characteristically accompanied by attempts at camouflaging and can be followed by sincere apologies. Despite their extensive coverage in the media and in lay literature, coprophenomena are not included within the current diagnostic criteria for any tic disorder. It has been estimated that these socially inappropriate symptoms affect a minority of patients with GTS, about 10% in the community and up to 30% in specialist clinics, where more severe and complex cases tend to be referred.[16],[22]

All primary tic disorders are currently classed as hyperkinetic movement disorders that develop before 18 years of age.[8] Similar to GTS, persistent motor or vocal tic disorders are characterized by the chronic presence of motor or vocal tics, but their diagnostic criteria reflect the presence of only one category of tics. In the current classification system (Diagnostic and Statistical Manual of Mental Disorders. 5th Edition), the diagnosis of “transient tic disorder” was replaced by “provisional tic disorder,” reflecting the uncertainties about the evolution of tic symptomatology, that is, if newly developed tics will improve and disappear or become chronic [Table 1].
Table 1: Key diagnostic features of primary tic disorders (onset before 18 years)

Click here to view



  Sensorimotor Components of Tics Top


Patients with GTS can exhibit a variety of tics with different degrees of severity; some tics can be mild and hardly noticeable, whereas other tics can be forceful and compel the person to produce violent movements or loud noises, resulting in physical and/or psychological distress. Both categories of tics (motor and vocal) typically fluctuate over time, following a waxing and waning course, usually with a peak in severity during early teenage years and improvement in adulthood.[23],[24],[25] Of note, environmental tic-modulating factors have been consistently reported in clinical research.[9],[10],[14] Anxiety, stress, excitement, tiredness, and boredom are among the conditions known to induce and exacerbate tics. Tics can also be triggered by talking about them or by seeing other persons with tics. In contrast, when patients are engaged in certain activities requiring both mental and physical effort, such as playing music or sports, tic severity and/or frequency can improve.[26]

Most patients with GTS report that tics are preceded and/or accompanied by specific sensations that are often referred to as “premonitory urges.”[27] Premonitory urges are unpleasant sensory experiences characterized by pressure, tension, tightness, pain, itch, or vague inner discomfort, often localized in the muscular districts involved by tics.[28],[29] These sensations have been suggested to be similar to the sensations preceding an itch or a sneeze: tic expression provides temporary relief from premonitory urges, similar to the relief that follows scratching an itch or sneezing.[30] Importantly, most patients with GTS can voluntarily suppress their tics for a variable length of time (from a few seconds to several minutes). However, tic suppression is typically accompanied by a distressing sensation of mounting inner tension, until the tension caused by the premonitory urge becomes unbearable and the tic has to be released.[31],[32] Recent research has provided confirmation to the clinical observations that premonitory urges are related to interoceptive awareness.[33],[34]

The mechanisms underlying tic expression are complex and poorly understood, reflecting the blurred distinction between voluntary and involuntary movements. The compelling nature of premonitory urges leads to repetitive behaviors that are performed against the individual's will; however, the decision to release the tic is usually perceived as voluntary.[35],[36] Therefore, it has been suggested that the tics released in response to specific urges might be thought of as “unvoluntary,” to indicate a third category of movements that is halfway between voluntary and involuntary actions.[37] The simultaneous presence of both voluntary and involuntary components in the expression of tics is in line with the hypothesis that tics may have the same neurophysiologic substrate as voluntary acts, even though they are misperceived as being involuntary. This interpretation supports the view of GTS as a hyperkinetic movement disorder affecting the conscious experience of action.[36],[38]

The assessment of sensory experiences is of central importance to the diagnosis of GTS, which remains essentially clinical. Based on the presence and characteristics of the premonitory urges, clinicians can reliably discriminate GTS from other hyperkinetic movement disorders.[39] Moreover, patients' awareness of their urges to tic is a prerequisite for some of the most frequently used behavioral treatment approaches for tic management, such as habit-reversal training.[40] Over the last few years, there has been progress in our understanding of the neural correlates of premonitory urges, as neuroimaging studies have shown patterns of activation in extramotor regions, including the insula and the cingulate cortex, that are implicated in the conscious monitoring of the internal environment.[17],[34],[41],[42]


  Comorbid Behavioral Symptoms Top


It has been reported that in about 90% of cases, patients with GTS present with behavioral symptoms in addition to tics[43],[44],[45] [Table 2].
Table 2: Examples of comorbid behavioral symptoms in patients with Gilles de la Tourette syndrome

Click here to view


Importantly, GTS is not related to intellectual disability; on the contrary, among individuals with GTS, there are persons with exceptional talents in different fields.[46] Obsessive-compulsive disorder (OCD) and attention-deficit hyperactivity disorder (ADHD) are the most commonly associated behavioral comorbidities. Prevalence figures for comorbid ADHD in children and adolescents with GTS vary from 38% (in community settings) to over 60% (in specialist clinics).[43] The diagnosis of comorbid ADHD can be challenging and requires in-depth assessments by experienced clinicians: by definition, tics implicate restlessness and hyperactivity, and the continuous effort to suppress tics can interfere with the patient's ability to sustain concentration.[47] Distressing and time-consuming repetitive behaviors (compulsions) and/or thoughts (obsessions) are commonly reported by patients with GTS, with prevalence figures for comorbid OCD ranging from 11% to 66%.[48] Of note, converging evidence from multiple clinical studies has shown that patients with tics tend to report specific obsessive-compulsive symptoms, which are different from the ones described by patients with OCD only. For instance, evening-up behaviors, obsessional counting (arithmomania), ordering, concerns for symmetry, and “just right” perceptions have been shown to be more prevalent in patients with GTS, whereas concerns for contamination and cleaning/washing rituals have been shown to be more prevalent in patients with pure forms of OCD.[48] Such phenomenological differences are likely to reflect different pathophysiological underpinnings and have clinically relevant implications for both diagnosis and treatment.

Patients with GTS often report problems with impulse control, anxiety, and affective symptoms.[49],[50],[51] The relationship between GTS and its behavioral comorbidities is not fully elucidated. For example, the relationship between GTS and depression is thought to be multifactorial. It is not surprising that living with a potentially disabling and stigmatizing condition can lead to depression. Moreover, disruption in the corticostriatal system, especially within monoaminergic pathways, has been associated with both motor dysfunction and emotional dysregulation. Finally, treatment of tics with antidopaminergic agents can exacerbate affective symptoms.[52] With regard to autism spectrum disorder, it has been shown that there is a high frequency of both tics and stereotypies in patients with pervasive developmental disorders.[53] Clinical data show that there might be an association between GTS and specific personality disorders, although the relationship between tics and personality traits is likely to be mediated by the presence of psychiatric comorbidities.[54]

Both diagnostic approaches and treatment strategies for patients with GTS are complicated by the presence of comorbid behavioral conditions. From a clinical perspective, it has been proposed to differentiate different groups of patients with GTS, based on neurobehavioral presentations and care needs, as follows: patients with motor and vocal tics only (“pure” GTS); patients who report additional complex tics and tic-related symptoms (“full-blown” GTS); and patients with behavioral comorbidities (GTS “plus”). In particular, the therapeutic management of this last group of patients poses considerable challenges and requires the input of experienced clinicians.[21],[55]

Little is known about the factors capable of influencing the long-term prognosis of patients with GTS. A few longitudinal studies have investigated the influence of tic severity and behavioral comorbidities on health-related QOL.[24],[56],[57] Recently developed disease-specific tools to measure health-related QOL in patients with GTS of all ages (GTS-QOL and C and A-GTS-QOL) can assist clinicians in the assessment of the impact of both tics and related behavioral symptoms on patients' lives.[58],[59] A more detailed understanding of the neurobehavioral spectrum of GTS can promote informed decisions about treatment interventions and contribute to an improved assessment of therapeutic outcomes.


  Etiological and Pathophysiological Mechanisms Top


Both genetic and environmental factors are thought to have a role in the etiology of tics. GTS is a complex neurodevelopmental disorder characterized by a high clinical heterogeneity, suggesting an equally complex interplay of pathophysiological mechanisms. In particular, it has been proposed that GTS may originate from the interaction between heterogeneous genetic vulnerability patterns and environmental factors, such as pre- and perinatal difficulties and postinfectious autoimmunity.[60],[61]

Genetic tests do not currently play any role in the diagnostic process of GTS; however, both twin and family studies have provided evidence that GTS is one of the most heritable, non-Mendelian neurodevelopmental disorders, characterized by a heritability risk of 0.77.[62],[63],[64] The risk can be higher and more accurately predictable in families where specific chromosomal abnormalities have been detected.[65],[66],[67],[68]

Although the role of autoimmune mechanisms in GTS has been questioned, the hypothesis that a subgroup of patients with GTS presents with a set of conditions called “pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections” is still under investigation.[69],[70] The findings of epidemiological studies have shown that pregnancy-related noxious exposures (especially maternal smoking and prenatal life stressors) may be more frequent in pregnancies of children who will develop GTS.[71] The mechanisms by which pre- and perinatal adversities could lead to the development of GTS or tic severity are unknown, but have been suggested to be possibly related to changes in the dopaminergic system as a result of early brain injury.[72]

The precise brain mechanisms underlying tic expression are still largely unknown. Dopaminergic dysfunction in the cortico-striato-cortico-frontal circuitries has been suggested to play a key role in the pathophysiology of GTS, though other neurochemical systems (in particular histaminergic and noradrenergic pathways) have been proposed to be possibly involved.[73],[74],[75] The possible effects of brain plastic remodeling in response to both tic expression and tic suppression across the lifespan are among the brain mechanisms underlying GTS that deserve further investigation.[76]


  Treatment Approaches Top


Pharmacotherapy, behavioral strategies, and functional neurosurgery (deep brain stimulation [DBS]) have been used as therapeutic strategies for GTS. In 2011, the European Society for the Study of Tourette Syndrome published the first set of evidence-based guidelines on four key aspects of GTS care, namely assessment, pharmacological therapy, behavioral and psychosocial interventions, and DBS.[77],[78],[79],[80] The European guidelines were complemented by expert consensus on the optimal management of GTS.[81],[82] At around the same time, the Canadian guidelines for the evidence-based treatment of tic disorders were published.[83],[84] After these collaborative enterprises, experts from the United States proposed a practice parameter for the assessment and treatment of children and adolescents with tic disorders,[85] and the International Deep Brain Stimulation Database and Registry Study Group published a set of recommendations on the use of DBS in GTS.[86] In 2016, a team of experts based in the United Kingdom published a health technology assessment on the treatment strategies for tics in children and adolescents with GTS.[87] More recently, an international group of experts developed the American Academy of Neurology practice guideline recommendations on the treatment of tics in people with GTS and other chronic tic disorders.[88],[89]

The most effective treatments for tics are pharmacological agents, although patients' response is characterized by high interindividual variability. Anti-tic medications can be divided into antidopaminergic and nonantidopaminergic agents. First-generation antidopaminergic medications (neuroleptics) such as haloperidol have long been employed, despite the high prevalence of adverse effects (sedation, depression, metabolic adverse effects, and extrapyramidal symptoms). Selected second-generation antidopaminergic medications (atypical antipsychotics) such as risperidone have been shown to have similar efficacy but better tolerability (especially in terms of extrapyramidal symptoms) compared to neuroleptics. Aripiprazole, a partial dopamine agonist that is sometimes referred to as a third-generation antidopaminergic agent, is characterized by a particularly favorable efficacy-to-tolerability ratio and is currently included among the first-line pharmacological options for the treatment of tics. The presynaptic dopamine depletor tetrabenazine is frequently employed as a second- or third-line option because of its adverse effects. Overall, tolerability is often the main limiting factor for the use of antidopaminergic agents in patients with GTS.[90] With regard to nondopaminergic agents, alpha-2 agonists (clonidine and guanfacine) have proven useful both for the treatment of tics and ADHD symptoms. Pharmacological studies have indicated that other medications, such as antiepileptic drug topiramate, can have good efficacy against tics.[88],[89],[91]

With regard to the behavioral strategies for tic management, habit-reversal training and exposure and response prevention are among the most extensively investigated techniques.[92],[93] Habit-reversal training is a method based on sustained resistance to the premonitory urge with the help of tic-specific competing responses; it is a key component of a broader treatment intervention called comprehensive behavioral intervention for tics.[94] The role of cognitive behavioral therapy in patients with GTS might be particularly relevant, in consideration of the neurobehavioral spectrum that characterizes most clinical presentations.[95],[96],[97]

More invasive treatment approaches, such as DBS, have been used in severe and refractory cases of GTS. Among the potential brain targets, the pars interna of the globus pallidus and the centromedian–parafascicular nuclei of the thalamus have been shown to be associated with more favorable outcomes.[86] There are both similarities and differences in the perspectives on the use of DBS for GTS across different specialist centers and countries.[98],[99]


  Conclusion Top


In consideration of its multifaceted range of symptoms, including both motor and nonmotor features, GTS lies at the crossroads of neurology and psychiatry. There is growing evidence that GTS is not a unitary condition, as originally believed, but a cluster of different clinical phenotypes. An improved understanding of the multiple clinical presentations of GTS results in an increased attention to their individual care needs. Operationalization and standardization of both assessment and treatment strategies, promoted by the publication of national and international sets of guidelines and by the development of disease-specific instruments to evaluate health-related QOL, have considerably improved the standards of care for this patient population. A number of questions remain open for future research. These include the characterization of phenotype–genotype correlations and the elucidation of the complex interplay between genetic and environmental factors. A better understanding of these aspects will be of key importance to implement more accurate diagnostic protocols and more effective treatment interventions to improve the quality of patients' lives.

Acknowledgments

The authors are grateful to Tourettes Action-UK and Tourette Association of America for their support.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Rickards H, Cavanna AE. Gilles de la Tourette: The man behind the syndrome. J Psychosom Res 2009;67:469-74.  Back to cited text no. 1
    
2.
Robertson MM, Eapen V, Cavanna AE. The international prevalence, epidemiology, and clinical phenomenology of Tourette syndrome: A cross-cultural perspective. J Psychosom Res 2009;67:475-83.  Back to cited text no. 2
    
3.
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.  Back to cited text no. 3
    
4.
Scharf JM, Miller LL, Gauvin CA, Alabiso J, Mathews CA, Ben-Shlomo Y. Population prevalence of Tourette syndrome: A systematic review and meta-analysis. Mov Disord 2015;30:221-8.  Back to cited text no. 4
    
5.
Blackburn JS, Mink JW, Augustine EF. Pediatric movement disorders: Five new things. Neurol Clin Pract 2012;2:311-8.  Back to cited text no. 5
    
6.
Ong MT, Mordekar SR, Seal A. Fifteen minute consultation: Tics and Tourette syndrome. Arch Dis Child Educ Pract Ed 2016;101:87-94.  Back to cited text no. 6
    
7.
Yang J, Hirsch L, Martino D, Jette N, Roberts J, Pringsheim T. The prevalence of diagnosed Tourette syndrome in Canada: A national population-based study. Mov Disord 2016;31:1658-63.  Back to cited text no. 7
    
8.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Washington, DC: American Psychiatric Publishing; 2013.  Back to cited text no. 8
    
9.
Cavanna AE, Seri S. Tourette's syndrome. BMJ 2013;347:f4964.  Back to cited text no. 9
    
10.
Hallett M. Tourette syndrome: Update. Brain Dev 2015;37:651-5.  Back to cited text no. 10
    
11.
Ganos C, Martino D. Tics and Tourette syndrome. Neurol Clin 2015;33:115-36.  Back to cited text no. 11
    
12.
Ganos C, Münchau A, Bhatia KP. The semiology of tics, Tourette's, and their associations. Mov Disord Clin Pract 2014;1:145-53.  Back to cited text no. 12
    
13.
Fahn S. Classification of movement disorders. Mov Disord 2011;26:947-57.  Back to cited text no. 13
    
14.
Martino D, Leckman JF. Tourette Syndrome. Oxford: Oxford University Press; 2013.  Back to cited text no. 14
    
15.
Evans J, Seri S, Cavanna AE. The effects of Gilles de la Tourette syndrome and other chronic tic disorders on quality of life across the lifespan: A systematic review. Eur Child Adolesc Psychiatry 2016;25:939-48.  Back to cited text no. 15
    
16.
Eddy CM, Cavanna AE. 'It's a curse!': Coprolalia in Tourette syndrome. Eur J Neurol 2013;20:1467-70.  Back to cited text no. 16
    
17.
Cox JH, Seri S, Cavanna AE. Sensory aspects of Tourette syndrome. Neurosci Biobehav Rev 2018;88:170-6.  Back to cited text no. 17
    
18.
Cohen SC, Leckman JF, Bloch MH. Clinical assessment of Tourette syndrome and tic disorders. Neurosci Biobehav Rev 2013;37:997-1007.  Back to cited text no. 18
    
19.
Martino D, Cavanna AE, Robertson MM, Orth M. Prevalence and phenomenology of eye tics in Gilles de la Tourette syndrome. J Neurol 2012;259:2137-40.  Back to cited text no. 19
    
20.
Martino D, Madhusudan N, Zis P, Cavanna AE. An introduction to the clinical phenomenology of Tourette syndrome. Int Rev Neurobiol 2013;112:1-33.  Back to cited text no. 20
    
21.
Cavanna AE. The neuropsychiatry of Gilles de la Tourette syndrome: The état de l'art. Rev Neurol (Paris) 2018;174:621-7.  Back to cited text no. 21
    
22.
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.  Back to cited text no. 22
    
23.
Bloch MH, Leckman JF. Clinical course of Tourette syndrome. J Psychosom Res 2009;67:497-501.  Back to cited text no. 23
    
24.
Hassan N, Cavanna AE. The prognosis of Tourette syndrome: Implications for clinical practice. Funct Neurol 2012;27:23-7.  Back to cited text no. 24
    
25.
Groth C, Mol Debes N, Rask CU, Lange T, Skov L. Course of Tourette syndrome and comorbidities in a large prospective clinical study. J Am Acad Child Adolesc Psychiatry 2017;56:304-12.  Back to cited text no. 25
    
26.
Caurín B, Serrano M, Fernández-Alvarez E, Campistol J, Pérez-Dueñas B. Environmental circumstances influencing tic expression in children. Eur J Paediatr Neurol 2014;18:157-62.  Back to cited text no. 26
    
27.
Brandt VC, Beck C, Sajin V, Baaske MK, Bäumer T, Beste C, et al. Temporal relationship between premonitory urges and tics in Gilles de la Tourette syndrome. Cortex 2016;77:24-37.  Back to cited text no. 27
    
28.
Crossley E, Cavanna AE. Sensory phenomena: Clinical correlates and impact on quality of life in adult patients with Tourette syndrome. Psychiatry Res 2013;209:705-10.  Back to cited text no. 28
    
29.
Crossley E, Seri S, Stern JS, Robertson MM, Cavanna AE. Premonitory urges for tics in adult patients with Tourette syndrome. Brain Dev 2014;36:45-50.  Back to cited text no. 29
    
30.
Eddy CM, Cavanna AE. Premonitory urges in adults with complicated and uncomplicated Tourette syndrome. Behav Modif 2014;38:264-75.  Back to cited text no. 30
    
31.
Kwak C, Dat Vuong K, Jankovic J. Premonitory sensory phenomenon in Tourette's syndrome. Mov Disord 2003;18:1530-3.  Back to cited text no. 31
    
32.
Leckman JF, Bloch MH, Scahill L, King RA. Tourette syndrome: The self under siege. J Child Neurol 2006;21:642-9.  Back to cited text no. 32
    
33.
Ganos C, Garrido A, Navalpotro-Gómez I, Ricciardi L, Martino D, Edwards MJ, et al. Premonitory urge to tic in Tourette's is associated with interoceptive awareness. Mov Disord 2015;30:1198-202.  Back to cited text no. 33
    
34.
Cavanna AE, Black KJ, Hallett M, Voon V. Neurobiology of the premonitory urge in Tourette's syndrome: Pathophysiology and treatment implications. J Neuropsychiatry Clin Neurosci 2017;29:95-104.  Back to cited text no. 34
    
35.
Lang A. Patient perception of tics and other movement disorders. Neurology 1991;41:223-8.  Back to cited text no. 35
    
36.
Cavanna AE, Nani A. Tourette syndrome and consciousness of action. Tremor Other Hyperkinet Mov (N Y) 2013;3. pii: Tre-03-181-4368-1.  Back to cited text no. 36
    
37.
Definitions and classification of tic disorders. The Tourette syndrome classification study group. Arch Neurol 1993;50:1013-6.  Back to cited text no. 37
    
38.
Moretto G, Schwingenschuh P, Katschnig P, Bhatia KP, Haggard P. Delayed experience of volition in Gilles de la Tourette syndrome. J Neurol Neurosurg Psychiatry 2011;82:1324-7.  Back to cited text no. 38
    
39.
van der Salm SM, de Haan RJ, Cath DC, van Rootselaar AF, Tijssen MA. The eye of the beholder: Inter-rater agreement among experts on psychogenic jerky movement disorders. J Neurol Neurosurg Psychiatry 2013;84:742-7.  Back to cited text no. 39
    
40.
Brabson LA, Brown JL, Capriotti MR, Ramanujam K, Himle MB, Nicotra CM, et al. Patterned changes in urge ratings with tic suppression in youth with chronic tic disorders. J Behav Ther Exp Psychiatry 2016;50:162-70.  Back to cited text no. 40
    
41.
Shelley BP, Trimble MR. The insular lobe of reil – Its anatamico-functional, behavioural and neuropsychiatric attributes in humans – A review. World J Biol Psychiatry 2004;5:176-200.  Back to cited text no. 41
    
42.
Rajagopal S, Seri And S, Cavanna AE. Premonitory urges and sensorimotor processing in Tourette syndrome. Behav Neurol 2013;27:65-73.  Back to cited text no. 42
    
43.
Cavanna AE, Rickards H. The psychopathological spectrum of Gilles de la Tourette syndrome. Neurosci Biobehav Rev 2013;37:1008-15.  Back to cited text no. 43
    
44.
Martino D, Ganos C, Pringsheim TM. Tourette syndrome and chronic tic disorders: The clinical spectrum beyond tics. Int Rev Neurobiol 2017;134:1461-90.  Back to cited text no. 44
    
45.
Cavanna AE. Gilles de la Tourette syndrome as a paradigmatic neuropsychiatric disorder. CNS Spectr 2018;23:213-8.  Back to cited text no. 45
    
46.
Cavanna AE. The possible talents of Tourette syndrome. In: Priller J, Rickards H, editors. Neuropsychiatry Case Studies. Berlin: Springer; 2016. p. 61-5.  Back to cited text no. 46
    
47.
Termine C, Selvini C, Balottin U, Luoni C, Eddy CM, Cavanna AE. Self-, parent-, and teacher-reported behavioral symptoms in youngsters with Tourette syndrome: A case-control study. Eur J Paediatr Neurol 2011;15:95-100.  Back to cited text no. 47
    
48.
Eddy CM, Cavanna AE. Tourette syndrome and obsessive compulsive disorder: Compulsivity along the continuum. J Obsessive Compuls Relat Disord 2014;3:363-71.  Back to cited text no. 48
    
49.
Eddy CM, Cavanna AE, Gulisano M, Calì P, Robertson MM, Rizzo R. The effects of comorbid obsessive-compulsive disorder and attention-deficit hyperactivity disorder on quality of life in Tourette syndrome. J Neuropsychiatry Clin Neurosci 2012;24:458-62.  Back to cited text no. 49
    
50.
Robertson MM, Cavanna AE, Eapen V. Gilles de la Tourette syndrome and disruptive behavior disorders: Prevalence, associations, and explanation of the relationships. J Neuropsychiatry Clin Neurosci 2015;27:33-41.  Back to cited text no. 50
    
51.
Piedad JC, Cavanna AE. Depression in Tourette syndrome: A controlled and comparison study. J Neurol Sci 2016;364:128-32.  Back to cited text no. 51
    
52.
Kompoliti K, Goetz CG, Morrissey M, Leurgans S. Gilles de la Tourette syndrome: Patient's knowledge and concern of adverse effects. Mov Disord 2006;21:248-52.  Back to cited text no. 52
    
53.
Kern JK, Geier DA, King PG, Sykes LK, Mehta JA, Geier MR. Shared brain connectivity issues, symptoms, and comorbidities in autism spectrum disorder, attention deficit/Hyperactivity disorder, and Tourette syndrome. Brain Connect 2015;5:321-35.  Back to cited text no. 53
    
54.
Trillini MO, Müller-Vahl KR. Patients with Gilles de la Tourette syndrome have widespread personality differences. Psychiatry Res 2015;228:765-73.  Back to cited text no. 54
    
55.
Eapen V, Robertson MM. Are there distinct subtypes in Tourette syndrome? Pure-Tourette syndrome versus Tourette syndrome-plus, and simple versus complex tics. Neuropsychiatr Dis Treat 2015;11:1431-6.  Back to cited text no. 55
    
56.
Cavanna AE, David K, Orth M, Robertson MM. Predictors during childhood of future health-related quality of life in adults with Gilles de la Tourette syndrome. Eur J Paediatr Neurol 2012;16:605-12.  Back to cited text no. 56
    
57.
Eapen V, Cavanna AE, Robertson MM. Comorbidities, social impact, and quality of life in Tourette syndrome. Front Psychiatry 2016;7:97.  Back to cited text no. 57
    
58.
Cavanna AE, Schrag A, Morley D, Orth M, Robertson MM, Joyce E, et al. The Gilles de la Tourette syndrome-quality of life scale (GTS-QOL): Development and validation. Neurology 2008;71:1410-6.  Back to cited text no. 58
    
59.
Su MT, McFarlane F, Cavanna AE, Termine C, Murray I, Heidemeyer L, et al. The English version of the Gilles de la Tourette syndrome-quality of life scale for children and adolescents (C&A-GTS-QOL). J Child Neurol 2017;32:76-83.  Back to cited text no. 59
    
60.
Paschou P. The genetic basis of Gilles de la Tourette syndrome. Neurosci Biobehav Rev 2013;37:1026-39.  Back to cited text no. 60
    
61.
Abdulkadir M, Tischfield JA, King RA, Fernandez TV, Brown LW, Cheon KA, et al. Pre- and perinatal complications in relation to Tourette syndrome and co-occurring obsessive-compulsive disorder and attention-deficit/hyperactivity disorder. J Psychiatr Res 2016;82:126-35.  Back to cited text no. 61
    
62.
Pauls DL, Fernandez TV, Mathews CA, State MW, Scharf JM. The inheritance of Tourette disorder: A review. J Obsessive Compuls Relat Disord 2014;3:380-385.  Back to cited text no. 62
    
63.
Browne HA, Hansen SN, Buxbaum JD, Gair SL, Nissen JB, Nikolajsen KH, et al. Familial clustering of tic disorders and obsessive-compulsive disorder. JAMA Psychiatry 2015;72:359-66.  Back to cited text no. 63
    
64.
Mataix-Cols D, Isomura K, Pérez-Vigil A, Chang Z, Rück C, Larsson KJ, et al. Familial risks of Tourette syndrome and chronic tic disorders. A Population-based cohort study. JAMA Psychiatry 2015;72:787-93.  Back to cited text no. 64
    
65.
Robertson MM, Shelley BP, Dalwai S, Brewer C, Critchley HD. A patient with both Gilles de la Tourette's syndrome and chromosome 22q11 deletion syndrome: Clue to the genetics of Gilles de la Tourette's syndrome? J Psychosom Res 2006;61:365-8.  Back to cited text no. 65
    
66.
Shelley BP, Robertson MM, Turk J. An individual with Gilles de la Tourette syndrome and Smith–Magenis microdeletion syndrome: Is chromosome 17p11.2 a candidate region for Tourette syndrome putative susceptibility genes? J Intellect Disabil Res 2007;51:620-4.  Back to cited text no. 66
    
67.
Katuwawela I, Cavanna AE. Good response to clonidine in Tourette syndrome associated with chromosomal translocation involving the IMMP2L gene. J Neuropsychiatry Clin Neurosci 2012;24:E17.  Back to cited text no. 67
    
68.
Prontera P, Napolioni V, Ottaviani V, Rogaia D, Fusco C, Augello B, et al. DPP6 gene disruption in a family with Gilles de la Tourette syndrome. Neurogenetics 2014;15:237-42.  Back to cited text no. 68
    
69.
Martino D, Zis P, Buttiglione M. The role of immune mechanisms in Tourette syndrome. Brain Res 2015;1617:126-43.  Back to cited text no. 69
    
70.
Schrag A, Martino D, Apter A, Ball J, Bartolini E, Benaroya-Milshtein N, et al. European multicentre tics in children studies (EMTICS): Protocol for two cohort studies to assess risk factors for tic onset and exacerbation in children and adolescents. Eur Child Adolesc Psychiatry 2019;28:91-109.  Back to cited text no. 70
    
71.
Hoekstra PJ, Dietrich A, Edwards MJ, Elamin I, Martino D. Environmental factors in Tourette syndrome. Neurosci Biobehav Rev 2013;37:1040-9.  Back to cited text no. 71
    
72.
Chao TK, Hu J, Pringsheim T. Prenatal risk factors for Tourette syndrome: A systematic review. BMC Pregnancy Childbirth 2014;14:53.  Back to cited text no. 72
    
73.
Leckman JF, Bloch MH, Smith ME, Larabi D, Hampson M. Neurobiological substrates of Tourette's disorder. J Child Adolesc Psychopharmacol 2010;20:237-47.  Back to cited text no. 73
    
74.
Yael D, Vinner E, Bar-Gad I. Pathophysiology of tic disorders. Mov Disord 2015;30:1171-8.  Back to cited text no. 74
    
75.
Cox JH, Seri S, Cavanna AE. Histaminergic modulation in Tourette syndrome. Expert Opinion Orphan Drugs 2016;4:205-13.  Back to cited text no. 75
    
76.
Cavanna AE, Stecco A, Rickards H, Servo S, Terazzi E, Peterson B, et al. Corpus callosum abnormalities in Tourette syndrome: An MRI-DTI study of monozygotic twins. J Neurol Neurosurg Psychiatry 2010;81:533-5.  Back to cited text no. 76
    
77.
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.  Back to cited text no. 77
    
78.
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.  Back to cited text no. 78
    
79.
Verdellen C, van de Griendt J, Hartmann A, Murphy T. ESSTS Guidelines Group. European clinical guidelines for Tourette syndrome and other tic disorders. Part III: Behavioural and psychosocial interventions. Eur Child Adolesc Psychiatry 2011;20:197-207.  Back to cited text no. 79
    
80.
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.  Back to cited text no. 80
    
81.
Cavanna AE, Rickards H, Worrall R, Hoekstra PJ, Plessen KJ, Roessner V. From ipse dixit to evidence-based guidelines: On the optimal management of Tourette syndrome. Eur J Paediatr Neurol 2012;16:310-1.  Back to cited text no. 81
    
82.
Rickards H, Cavanna AE, Worrall R. Treatment practices in Tourette syndrome: The European perspective. Eur J Paediatr Neurol 2012;16:361-4.  Back to cited text no. 82
    
83.
Pringsheim T, Doja A, Gorman D, McKinlay D, Day L, Billinghurst L, et al. Canadian guidelines for the evidence-based treatment of tic disorders: Pharmacotherapy. Can J Psychiatry 2012;57:133-43.  Back to cited text no. 83
    
84.
Steeves T, McKinlay BD, Gorman D, Billinghurst L, Day L, Carroll A, 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.  Back to cited text no. 84
    
85.
Murphy TK, Lewin AB, Storch EA, Stock S; American Academy of Child and Adolescent Psychiatry (AACAP) Committee on Quality Issues (CQI). Practice parameter for the assessment and treatment of children and adolescents with tic disorders. J Am Acad Child Adolesc Psychiatry 2013;52:1341-59.  Back to cited text no. 85
    
86.
Schrock LE, Mink JW, Woods DW, Porta M, Servello D, Visser-Vandewalle V, et al. Tourette syndrome deep brain stimulation: A review and updated recommendations. Mov Disord 2015;30:448-71.  Back to cited text no. 86
    
87.
Hollis C, Pennant M, Cuenca J, Glazebrook C, Kendall T, Whittington C, et al. Clinical effectiveness and patient perspectives of different treatment strategies for tics in children and adolescents with Tourette syndrome: A systematic review and qualitative analysis. Health Technol Assess 2016;20:1-450, vii-viii.  Back to cited text no. 87
    
88.
Pringsheim T, Okun MS, Müller-Vahl K, Martino D, Jankovic J, Cavanna AE, et al. Practice guideline recommendations summary: Treatment of tics in people with Tourette syndrome and chronic tic disorders. Neurology 2019;92:896-906.  Back to cited text no. 88
    
89.
Pringsheim T, Holler-Managan Y, Okun MS, Jankovic J, Piacentini J, Cavanna AE, et al. Comprehensive systematic review summary: Treatment of tics in people with Tourette syndrome and chronic tic disorders. Neurology 2019;92:907-15.  Back to cited text no. 89
    
90.
Gulisano M, Calì PV, Cavanna AE, Eddy C, Rickards H, Rizzo R. Cardiovascular safety of aripiprazole and pimozide in young patients with Tourette syndrome. Neurol Sci 2011;32:1213-7.  Back to cited text no. 90
    
91.
Cavanna AE, Nani A. Antiepileptic drugs and Tourette syndrome. Int Rev Neurobiol 2013;112:373-89.  Back to cited text no. 91
    
92.
Frank M, Cavanna AE. Behavioural treatments for Tourette syndrome: An evidence-based review. Behav Neurol 2013;27:105-17.  Back to cited text no. 92
    
93.
Fründt O, Woods D, Ganos C. Behavioral therapy for Tourette syndrome and chronic tic disorders. Neurol Clin Pract 2017;7:148-56.  Back to cited text no. 93
    
94.
McGuire JF, Ricketts EJ, Piacentini J, Murphy TK, Storch EA, Lewin AB. Behavior therapy for tic disorders: An evidenced-based review and new directions for treatment research. Curr Dev Disord Rep 2015;2:309-17.  Back to cited text no. 94
    
95.
O'Connor KP, Laverdure A, Taillon A, Stip E, Borgeat F, Lavoie M. Cognitive behavioral management of Tourette's syndrome and chronic tic disorder in medicated and unmedicated samples. Behav Res Ther 2009;47:1090-5.  Back to cited text no. 95
    
96.
Cavanna AE. Back to the future: Stoic wisdom and psychotherapy for neuropsychiatric conditions. Future Neurol 2019;14:1.  Back to cited text no. 96
    
97.
Cavanna AE. Stoic philosophy and psychotherapy: Implications for neuropsychiatric conditions. Dialouge Philos Ment Neuro Sci 2019;12:10-24.  Back to cited text no. 97
    
98.
Porta M, Sassi M, Ali F, Cavanna AE, Servello D. Neurosurgical treatment for Gilles de la Tourette syndrome: The Italian perspective. J Psychosom Res 2009;67:585-90.  Back to cited text no. 98
    
99.
Cavanna AE, Eddy CM, Mitchell R, Pall H, Mitchell I, Zrinzo L, et al. An approach to deep brain stimulation for severe treatment-refractory Tourette syndrome: The UK perspective. Br J Neurosurg 2011;25:38-44.  Back to cited text no. 99
    



 
 
    Tables

  [Table 1], [Table 2]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Diagnostic Crite...
Sensorimotor Com...
Comorbid Behavio...
Etiological and ...
Treatment Approaches
Conclusion
References
Article Tables

 Article Access Statistics
    Viewed948    
    Printed61    
    Emailed0    
    PDF Downloaded136    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]