Tics are defined as sudden, rapid, recurrent, non-rhythmic motor movements or vocalizations usually appearing in bouts while waxing and waning in frequency, intensity and kind of tic [1]. Tic disorders including Gilles de la Tourette or Tourette Syndrome (TS) typically onset in childhood mostly at the age of 5 to 6 years [2, 3]. TS encompasses the combination of chronic (more than 1 year) motor and vocal tics. TS is often underdiagnosed and many patients do not receive adequate information and care [5, 6], and thus suffer from psychosocial impairment for a long time. On average, it takes more than 5 years from first onset of symptoms to diagnosis [7]. Patients and their families are frequently unable to correctly identify the symptoms and patients sometimes get stigmatised as a consequence of their tics. Therefore, they often experience a great relief to get a diagnosis because this allows them to better cope with the situation. There is no cure for TS, therefore, treatment aims to diminish tic severity and frequency. Often it is more important to manage the commonly comorbid conditions in order to improve psychosocial functioning and development. So far, to the best of our knowledge, only in Germany explicit guidelines for the diagnosis and treatment of TS exist (German Guidelines of child and adolescent psychiatry [8] and neurology [9]). In the past years, there has been an increasing interest in research on aetiology, pathophysiology, diagnosing and treatment of TS, leading to valuable new insights on many aspects of the syndrome. Therefore, experts of the European Society for the Study of Tourette Syndrome (ESSTS) have developed the first European guideline in four parts (this issue). This part deals with the assessment of tic disorders in children, adolescents and adults.

The mean age at onset is around 5 years although lower ages at onset are reported in up to 40% of persons. Waxing and waning is the rule. Complex tics generally appear later than simple ones and phonic tics appear later than motor tics [15], usually after 1 or 2 years, with <5% of patients developing phonic tics first [16]. For most patients, the worst ever period of tics occurs between 8–12 years of age [17, 18].

The course of tics is relatively favourable over time. Clinical as well as population-based studies indicate that up to 80% of persons who have presented with a tic disorder before age 10 experience a significant tic decrease during adolescence, and by age 18 tic intensity and frequency has decreased to such an extent that the person no longer experiences any impairment from tics, although objective ratings indicate that most persons still have mild tics [19]. Yet, a small proportion of patients (20%) does not experience a decrease in tic intensity, and in this group some individuals not only experience tic worsening in adulthood but develop the most severe and debilitating forms of tic disorders. Reports on whether certain types of tics in childhood predict tics or comorbidity in adulthood are somewhat conflicting [20–26]. Frequency and severity of tics in childhood is hardly predictive of tic severity in adulthood [22]. However, children and adolescents with tics experience worse quality of life than healthy children (but better than psychiatric controls) [27], and poorer quality of life is related to increased tic severity [28]. Poor quality of life in adults with TS is associated with persistence of OCD [29]. Comorbid OC symptoms in children with TS onset at a somewhat later age (around 10 years) than tics and, in children with tics, tend to remit in only about 40% of patients [29]. Further new onset of OCD at a later age might occur [12]. Interestingly, persistence of OC symptoms into adulthood is particularly related to high IQ, and to smaller caudate volume measures in children [23, 30].

ADHD symptoms in TS children occur in the majority of cases before tic onset, and in one third of children after tic onset [31]. ADHD symptoms tend to decrease in 20% of children during adolescence but later than tics. Interestingly, OC symptoms in childhood predict OC symptoms and more ADHD symptoms in adolescence and adulthood, and ADHD in childhood predicts more OCD in adulthood [17, 26]. Finally, persistence of ADHD into adulthood is related to poorer psychosocial functioning. In conclusion, the following picture emerges: as tics in childhood hardly predict long-term outcome, comorbid OCD and ADHD are associated with poorer psychosocial functioning.

Family studies of TS consistently show a 10- to 100-fold increase in the rates of tics and TS in first degree relatives of TS patients compared to control families, indicating a strong genetic component to be operant in the disease [31–33]. Tic severity increases with bi-lineal transmission [34]. Further, independently of whether the proband has concurrent OCD, first degree family members of TS patients have elevated rates of early-onset OCD, especially the female relatives, suggesting that—in TS—OCD is an alternate expression of the TS phenotype [32]. With respect to ADHD transmission, the picture is slightly different; although rates in first degree relatives of TS families are significantly elevated, ADHD is mostly comorbid with tics in the relatives, pointing into the direction of shared aetiology, i.e. associated but not comorbid in the strict sense [35], and not ADHD as an alternate expression of the disease [31]. In summary, these family studies strongly indicate a genetic component to be operant in TS, with shared genetic influences between tic and OCD, but it is unclear for ADHD. A large Genome Wide Association Study within the TSA genetic consortium is underway [36] (for a review on the genetics of TS: see O’Rourke et al. [37]).

For DSM-V (expected in 2013), only minor changes have been recommended, designed to clarify and simplify the diagnostic criteria, and reduce the use of the tic disorder not otherwise specified category. A European commentary on recent DSM-V version can be found in this Journal [48]. Specific recommendations include a.o: (1) simplification of the duration criterion for the tic disorders; any person who has tic symptoms of less than 12 month duration but more than 4 weeks duration receives the diagnosis ‘provisional tic disorder’; (2) establishing new tic disorder categories for substance induced tic disorder and tic disorder due to a general medical condition; (3) including a motor tic only and vocal tic only specifier for the chronic motor or vocal tic disorder category [49].

To establish a diagnosis of TS, a person must have (1) the combination of two or more motor tics and one (or more) phonic tic, that have been present at some time during the illness although not necessarily concurrently; (2) tics occur many times daily nearly every day through a period of more than 1 year; (3) onset before 18 years of age; and (4) are not directly caused by a general medical condition or by substance use.

Motor tics are described as brief, sudden, irresistible, inapposite and non-rhythmic recurrent movements in voluntary muscles or muscle groups [50]. Most common tics occur in the face, neck or shoulder musculature and encompass a.o.: eye blinking, nose and mouth twitches and shoulder jerks.

Vocal tics are defined as sounds elicited by a flow of air through the vocal cords, mouth or nose and the most common vocal tics are: throat clearing, grunts, high-pitched sounds and sniffing. Amongst the most well-known vocal tics is coprolalia (i.e. the uttering of socially inappropriate words), which occurs only in between 14 and 20% of patients [51]. Tics can be suppressed or inhibited depending on the situation. The suppression, however, causes an uncomfortable sensation.

Three essential ‘tic’ features can be recognised that are closely interwoven, i.e.: (1) temporary tic suppression [16]; (2) inner tension that accompanies tic suppression; (3) the feeling of active involvement in performing a tic, especially in adults. Although patients cannot permanently suppress the tic they might experience the tic as a conscious, intentional and self-directed movement executed to relieve a premonitory urge [52]. This feeling of intentionality is rarely present in children between age 4 and 8 but increases with age, and by age 12 the majority of patients recognises a premonitory urge preceding and exacerbating a tic [15]. This subjective perception is an important distinguishing feature from other hyperkinetic movement disorders [52].

Tics usually start in the face and tend to extend caudally, with a remaining preference for head, neck, shoulders and arms. Tics tend to significantly decrease during sleep, although—in contrast with previous notions—they often do not disappear [53]. Up to 60% of TS children and adults complain about disturbed sleep [54]. Polysomnography and simultaneous video recording during sleep in TS patients has revealed both an increased number of regular movements and more tics in all sleep stages but especially during REM sleep [53, 55, 56]. Patients show decreased sleep efficiency and slow wave sleep percentage, increased sleep latency, more awakeness and awakenings and more sleep stage changes during sleep. Severity of TS is positively associated with number of awakenings and sleep stage changes and negatively with sleep efficiency. Comorbid ADHD, a condition in which increased motor activity during sleep is found as well, seems to significantly add to the sleep problems in TS [56–58].

The intensity of tics depends in most cases on environmental cues, such as exciting or stressful events, although the nature of these environmental mediators has hardly been investigated systematically yet. In apparent contrast to this, tics can exacerbate during relaxation, for example whilst watching television. Situations or activities that require focused attention from the patient often diminish tics, both in children and adults [59].

Tics can be classified according to: type, complexity, whether they are isolated or multiple, and according to location, number, frequency and duration [6]. They also vary in terms of intensity or ‘forcefulness’ [69].

In children and in adults, it is paramount to assess degree of impairment due to tics or comorbid conditions, although as described here above, in DSM-IV-TR [4] and in future DSM-V [49], the distress item has been omitted that was obligatory to establish a tic diagnosis in previous classifications. Impairment entails that the disorder is time consuming, causes significant distress and interferes with major domains of daily life of both children and adults, such as school, work status and (social) relationships. Impairment can be reliably measured with various instruments, including the impairment item on the Yale Global Tic Severity Scale (YGTSS), which separately rates impairment due to motor or vocal tics, on 0–4 scales [69]. Alternatively, impairment can be assessed using a Global Assessment of Functioning, both in children (C-GAS) [70] and in adults according to axis five of DSM-IV TR (2002 [47]). The scale runs from 0–90, with 0 indicating complete dependence on care by others, and 90 being healthy and excellently functioning in all areas of development, school/work and psychosocial functioning. Further, in children as well as adults the Clinical Global Impression Scale (CGI-S [71]) can be rated by the clinician. The CGI-S assesses change in global daily functioning (between 0 = much deteriorated and, via 3 = no change, to 6 = very much improved). The CGI-S has shown good face validity and is extremely easy to use, although interrater reliability is somewhat low [72].

Recently, a Quality of Life scale has been developed specifically for tic disorder patients [73, 74]. This 27 item scale is based on the health-related quality of life scale (HR-QOL) [75] with response ranges between 0 and 4, and assesses quality of life in four domains: psychological problems, cognitive problems, physical/Activity of Daily Living problems and obsessive–compulsive themes. Internal consistency as well as test–retest reliability are excellent. TS patients report elevated scores, predominantly in the domains of psychological and cognitive problems [73].

In clinical series, the large majority of cases (79%) have comorbid psychopathology, with attention deficit/hyperactivity disorder (ADHD) predominantly of the inattentive or combined subtype, being the most frequent comorbid disorder in up to 60% of the cases in both children and adults [31], followed by Obsessive–Compulsive Disorders (OCD), merely in adolescents and adults, anger control problems, sleep disorder, learning disorders, mood disorders, anxiety disorders and conduct and oppositional defiant disorders (CD/ODD). Sex differences occur with respect to this comorbidity, with predominance of males over females for ADHD, CD/ODD, anger control problems and learning disorders, and a female preponderance for OCD and self-injurious behaviour. Other comorbidities include impulsive, self-injurious and aggressive behaviour, autism spectrum disorders and sleep disorders [76]. Especially in adults, comorbidity often forms the main reason to seek help.

A general physical and a specialised neurological examination is mandatory to ensure correct diagnosis and exclude severe or progressive neurological disorders [128]. The necessity for any further investigation is determined at this early diagnostic stage. In practice, the typical features of TS virtually rule out alternative major diagnoses. Atypical features such as apparent adult onset or severe deterioration or progression in symptoms should always lead to detailed consideration and investigation to include EEG and neuro-imaging.

Neurological examination is performed to distinguish tics from other movement disorders, most importantly myoclonic dystonias, some forms of epilepsia and stereotypies. In practice, myoclonus—brief shock-like movements of ‘non-functional’ muscle groups which are not suppressible and usually do not have an associated urge—are the most difficult movements to distinguish from tics. With the presence of sustained or dynamic abnormal postures, it is useful to enquire about and examine for signs of dystonia. A good technique to identify kinesogenic involuntary movements is to for instance observe the writing of the patients; an individual with a myclonic dystonia will need to steady the pen-holding hand with the other to avoid shock-like movements affecting the manoeuvre. Also, observation of fine motor tasks such as putting the lid on a pen is useful to exacerbate/test for myoclonus. Whilst ‘dystonic tics’ are well recognised, focal or generalised dystonias should not be mistaken for a tic disorder.

Additional investigation with the aid of MRI scanning or EEG is rarely indicated except in those cases where the presentation is not typical in terms of either the semiology of the movement disorder or the presence of features suggestive of the differential diagnoses mentioned above. Indeed, the more common situation is over-investigation, for instance with EEG in cases where a typical tic disorder is mistaken for epilepsy or myoclonus. It is worthwhile seeking expert opinion if doubt exists about the extent of investigation to pursue. Certain neurological conditions can be associated with tic-like movements (Table 4). It is usually straightforward to differentiate these conditions with a thorough history and examination.

The physical examination includes careful examination for dysmorphic features to identify any indication of genetic syndromes. Unusual features may prompt specific genetic testing by consulting a clinical geneticist. Further, in the presence of additional learning difficulties or autism spectrum diagnosis it might be advisable to consult a clinical geneticist as well, as in some cases this high resolution array might reveal a rare genetic aetiology of these heterogeneous disorders.

Patients with ‘uncomplicated’ TS show barely any impairment on all the main areas of cognitive functioning [129–132]. It should also be noted that no ecologically valid measure of manual speed or dexterity (e.g. typing) has been evaluated in children with TS that shows practically relevant results. Of note, enhanced cognitive function has been identified on tasks of response inhibition in TS patients, with children with ‘uncomplicated’ TS showing enhanced cognitive control on an oculomotor switching task [133]. Authors suggest that this heightened ability to control inhibition may be a result of tic suppression over time. This finding needs confirmation in subsequent studies. In sum, based on current evidence, no specific clinical neuropsychological assessment is advised in children with ‘uncomplicated’ TS.

A body of evidence suggests that the main comorbid conditions, ADHD and OCD, have a detrimental influence on the cognitive performance of children with TS [134].

Children with TS + ADHD exhibit cognitive dysfunction. The main negative impact on cognitive performance seems determined by ADHD, independent of the coexisting tic disorder [131]. This might explain why comorbid ADHD is the main predictor of poorer psychosocial health [135, 136] and the main determinant of the burden of disability [137] in TS patients. However, it is unclear how much of the negative effects of ADHD on disability and social/academic functioning in TS patients is caused by ADHD-related intellectual dysfunction. ADHD comorbidity seems to impact on the general intellectual function of children with TS, as the majority of reports suggest that a lower Full-Scale IQ is accounted for by the presence of the comorbidity [138–140]. Moreover, learning disabilities and other problems concerning academic achievement are estimated to occur in approximately 23% of children with a diagnosis of TS and appear to be highly influenced by coexisting ADHD [140, 141]. Specifically, numerical skills [140] and written language [134] have been highlighted as prevalent in TS.

The performance on manual dexterity (Purdue Pegboard test) or visual-motor integration (Beery Visual-Motor Integration test) tasks does not differ significantly between patients with TS + ADHD and ‘uncomplicated’ GTS [132, 142, 143]. In line with children with ADHD only, children with TS + ADHD have been demonstrated to show marked impairment on visual attention (e.g. the Trail Making Test [144]) and sustained attention (Continuous Performance Tests; [132, 145]). Other cognitive domains in which children with TS + ADHD show impairments, compared to patients with ‘uncomplicated’ TS, are: planning skills [142, 146], response inhibition [131, 147, 148] and cognitive flexibility/set shifting [35, 148, 149]. The meaning of these cognitive impairments to predict outcome in children with TS remains inconclusive. However, the neuropsychological tests described here-above may provide clinically useful additional information on the cognitive profile of children with TS + ADHD.

There is very limited evidence on the neuropsychological profile of children with TS + OCD. It is unclear whether this comorbidity is associated with selective cognitive impairment in children with TS. The cognitive profile of OCD appears to be one of the primary executive dysfunctions, mainly affecting response inhibition and cognitive flexibility [150]. Although memory may be affected as well, these deficits are thought to be secondary to a failure of organisational strategies during encoding [150]. In line with this, patients with TS + OCD demonstrate executive function deficits primarily in response inhibition [151] and set shifting paradigms [152]. As underscored for the other two TS subgroups, information is lacking on the prognostic indicators of this dysfunction on social, academic and psychological wellbeing in children with TS + OCD. For TS + OCD patients, a neuropsychological assessment focused on executive function, primarily response inhibition and cognitive flexibility, may be clinically indicated.

To conclude, in children who are diagnosed with TS in combination with comorbid ADHD or OCD should undergo neuropsychological evaluation encompassing intellectual function, academic attainments, motor skills, attention, executive function and memory. Neuropsychological tests of certain test-batteries with good psychometric properties for the country in question are suggested from published studies and more ecologically applicable screens.

Tic disorders represent a wide range of tics and co-existing symptoms with a varied and heterogeneous presentation. In this guideline, we have recommended a broad range of assessments and investigations to capture the tic/TS phenotype, taking developmental issues into account. In our opinion, it is highly advisable to choose instruments that cover the whole age range between infancy and adulthood, so that the time course of symptoms across ages and life stages can adequately be captured. In most situations, a standard interview with a few additional questionnaires and rating scales are sufficient to guide diagnosis and treatment. However, psychiatric comorbidity occurs in more than three quarters of cases that are referred for specialised care. Further, in a minority of cases a more extensive neurological and psychiatric screen is necessary to differentiate tics from other hyperkinetic disorders and from psychogenic disorders. Finally, neuropsychological assessment can be useful because of the high concurrence of tics with learning disorders, especially in children who have not yet finished education or professional training.