, Alberto J. Espay2, Alfonso Fasano3 and Francesca Morgante4
(1)
Neurology Department, King’s College Hospital NHS Foundation Trust, London, UK
(2)
James J. and Joan A. Gardner Center for Parkinson’s Disease and Movement Disorders, University of Cincinnati, Cincinnati, Ohio, USA
(3)
Division of Neurology, University of Toronto Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson’s Disease Toronto Western Hospital, UHN, Toronto, Ontario, Canada
(4)
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
3.1 An Introductory Note
This group of abnormal motor behaviours consists of a diverse spectrum of discrete, unwanted and potentially disabling motor routines, which exhibit two major common features: (1) may all be suppressed by volition or inhibited on demand to a varying extent and (2) may be preceded by an antecedent drive (e.g. a discomforting sensory experience, a psychic tension directed towards a reward, a disturbing or anxiogenic thought) and may at times be perceived by the subject as uncontrollable responses to this drive (stereotypies usually do not present this characteristic).
Based on the type of abnormal motor behaviour, these may range from brief, rapid movements involving single muscle groups (e.g. simple tics) to highly complex and structured motor routines involving several muscle groups (e.g. impulsive and compulsive behaviours). For the differential diagnosis of this group of abnormal motor behaviours, several clinical features should be taken into account that include: (a) the degree of repetitiveness; (b) whether the movements are goal-directed or purposeless; (c) the degree to which these movements are voluntarily suppressible; and (d) the association with sensory symptoms, emotional states, or specific ideational content. Table 3.1 provides a practical guide to discriminate, on the basis of these core clinical features, between the various types of motor behaviours within this group.
Table 3.1
Differential diagnosis of involuntary motor behaviours
Repetitiveness | Goal directed | Volitional control | Sensory antecedent | Emotional antecedent | Cognitive- ideational antecedent | |
|---|---|---|---|---|---|---|
Tics | ++ (occur in discrete bouts) | − | ++ | +++ (before) | + | − |
Stereotypies | +++ (occur unchanged for long periods of time) | − | + | + (after) | − | − |
Akathisia | + (variable, small repetitiveness) | − | + | +++ (before) | − | − |
Motor hyperactivity | + (variable, small repetitiveness) | +/− | +++ | − | − | + |
Impulsive behaviours | ++ (patterned, occur intermittently) | + | +++ | − | ++ | − |
Compulsions | ++ (patterned, occur intermittently) | + | +++ | − | +++ | +++ |
Mannerisms | ++ (patterned, occur intermittently) | + | ++ | − | − | − |
Restless legs | ++ (limited variability, moderate repetitiveness) | − | + | +++ (urge to move legs) | − | − |
3.2 Tics
3.2.1 How to Recognize
Tics are unwanted, non-goal-directed movements involving discrete muscle groups. Their basic phenomenological features are: (1) a repetitive and patterned presentation; (2) inter- and intra-individual variability of type of movement and severity; (3) association with preceding sensory phenomena, also known as premonitory urges; and (4) partial or complete suppressibility by volition [1, 2].
Repetitive and patterned presentation. Tics are patterned and occur repetitively within a discrete period of time. These features are important to differentiate tics from chorea, which presents as highly unpredictable in movement amplitude, direction and speed.
Variability. Although a single tic is performed repetitively by each individual, tics are variable within subjects and across different subjects in their type, body location and severity over time. Tics may involve different body regions at the same time, and each tic may wax and wane over the course of time. The list of possible movements included in the repertoire of human tics is very long, and practically any body muscle may be involved, although the majority of tics involve the head, neck and upper body. The frequency of tics is also variable, with tic-free intervals of different duration over time. This coexistence of repetitive and fluctuating character is one of the exclusive features of tics and may also be helpful to differentiate ‘slower’ and more sustained tics (often referred to as ‘dystonic’ or ‘tonic’ tics) from dystonia [3] and from some dyskinesias. Likewise, the changing pattern of tics differentiates them from stereotypies. Finally, tics are never rhythmic and are therefore easily distinguishable from tremor.
The variability of tics is reflected also in the classifications used to distinguish different types of tics. Tics are conventionally classified in different subtypes based on the body segment involved and their degree of complexity [4]. Tics leading to overt movements of body regions in space are defined motor, whereas tics consisting of contractions of nasal, buccal, laryngeal and respiratory muscles causing audible sounds are known as phonic. The most common group of phonic tics are those that lead to vocalizations, which are therefore labelled as vocal tics; although the term phonic is more comprehensive than the term vocal, the latter is conventionally used to refer to the whole spectrum of phonic tics. Tics are also subdivided into simple or complex, depending on whether they involve a single muscle group or present as distinct, coordinated patterns of movements involving several muscle groups [5].
The broad rubric of complex tics comprises also discrete stereotyped behaviours that include: echophenomena (echopraxia, echolalia), i.e. non-voluntary repetition of movements or vocalizations made by another person [6]; paliphenomena (palilalia, palipraxia), i.e. non-voluntary repetition of the patient’s own vocalizations (usually syllables, words or phrases) and movements [7]; coprophenomena (coprolalia, copropraxia), i.e. non-voluntary utterance or performance of obscene words or gestures or socially inappropriate remarks or gestures [8]. Echo-, pali- and coprophenomena are relatively frequent in Tourette syndrome (TS), the most representative and better known among primary tic disorders (see below).
The degree of interference of tics with voluntary actions or speech varies significantly within the same patient and across different patients. The most intrusive tics may interrupt the normal flow of speech and voluntary motor behaviour. The degree of this interference is influenced by the patients’ focus of attention to the voluntary suppression of tics. In general, tics may cause impairment in various areas of social, academic and professional functioning [9–11], and some tics may have a forceful character that can even lead to physical trauma [12].
Premonitory urges. The most common antecedent drive for tics consists of sensory experiences [13], known as premonitory urges (PU). These are defined as uncomfortable sensations that build up in intensity immediately before tics and are markedly alleviated immediately after tic release [14]. PU have great diagnostic value, since no other type of discrete abnormal movement shows the same consequentiality of occurrence with well-defined sensory experiences. For example, the sensory tricks observed in association with dystonia lead to a reduction of the related dystonic posture or movement, whereas patients with tics may describe the latter as ‘motor responses’ which help to alleviate the discomfort generated by the PU. Patients with akathisia or restless legs also experience discomforting sensations preceding the abnormal movement, but their movements are not discrete and stereotyped like tics. Very often there is topographical correspondence between tics and PU, e.g. a throat clearing tic may be preceded by an itchy feeling in the larynx, or a dystonic tic consisting of a slow head movement may be triggered by tension in the neck muscles [15]. Some PU have a more ‘somatic’ quality and are similar to bodily sensations like an itch or the sensory discomfort triggering a sneeze; others exhibit mixed ‘somatic’ and ‘psychic’ quality, being reported as feeling of restlessness, a build-up of inner tension or a pressure over a body part [16]. The self-awareness of the ‘urge-tic’ complex typically increases with age, increasing from about 25 % in patients of 8–10 years of age, to about 35 % in the 11–14 age range, and to about 60 % in patients aged 15–19 [17]. PU have a negative impact on health-related quality of life in patients with tic disorders [18].
‘Just-right’ phenomena are another form of sensory phenomena associated with tics, consisting of the need of patients to compulsively reiterate sensory experiences of physical objects until these feel ‘just right’ [7, 19, 20]. The most common repetitive behaviour associated with ‘just-right’ phenomena is the forced touching of objects, surfaces and other people. Typically, before a certain sensory stimulus is perceived as ‘just right’, it is felt by the subject as being ‘not right’, and the repeated exposure to the stimulus finally leads to fulfilling the ‘just-right’ perception [21]. ‘Just-right’ phenomena are more common in patients with comorbid obsessive–compulsive disorder [19].
Voluntary suppressibility. The ability to suppress tics is age related, i.e. higher in adults than in children, and varies across patients. The voluntary active suppression of tics may generate a build-up of the intensity of the associated PU, but the ability to hold tics in may not be related to the quality or severity of the PU [22]. However, the ability to suppress tics is related to the distribution of tics, as the body parts that exhibit the fewest tics (e.g. limbs or trunk) are also the ones for which tic inhibition is most effective [23]. In line with the susceptibility of tics to environmental contingencies, high levels of stress and anxiety may reduce one’s ability to suppress tics voluntarily. On the other hand, active tic suppression is very demanding in terms of attention and mental energy, to the point that it may have a negative impact over attention-demanding tasks, including learning processes during school years [24]. Contrary to previous beliefs, prolonged tic suppression often does not lead to a rebound worsening of tics [25].
3.2.1.1 Other Accompanying Features
Tics are highly susceptible to changes to the environmental context. The degree of exposure to a variety of contextual factors influences the fluctuating severity of tics. Psychosocial stress is probably the most important contextual factor that modulates tic severity on the short term [26]. Likewise, anxiety levels, physical and mental fatigue and negative feelings of boredom or frustration may all increase tic severity. Sometimes tics may be worsened by making them the main focus of conversation or during direct, explicit observation of tics. At the same time, some contingencies or voluntary activities may exert a beneficial influence over tics, such as relaxation, concentration upon attention-demanding tasks, physical exercise and reduced sympathetic tone [27, 28]. The worsening effect of certain activities over tics may lead to their avoidance, with subsequent negative impact on patients’ quality of life and functioning [11].
Patients with tics may exhibit an unusual focus of their attention on external stimuli which are repetitive, faint and generally poorly salient. This phenomenon has been named somatic hypersensitivity [29] or site sensitization [30]. These patients manifest otherwise normal ability in discriminating between sensory stimuli of different intensities. Some patients report excessive irritation by environmental noise, also termed misophonia [31]. The origin of somatic hypersensitivity in tic disorders is still not very well understood but may be related to abnormalities of sensorimotor gating. Whereas magnetoencephalography suggested abnormal sensory processing in patients with tic disorders [32], findings from research on a surrogate measure of sensory gating, prepulse inhibition, are still not conclusive due to the high interindividual variability of this marker [33]. Importantly, reduced prepulse inhibition of the startle reflex was reported in both patients and laboratory mice bearing a mutation in the L-histidine-decarboxylase (HDC) gene, potentially implicated in the pathogenesis of tic disorders [34].
Up to 90 % of patients with chronic tics are diagnosed with other psychiatric disorders, although the frequency of each of these comorbidities varies across studies and depends mainly on whether estimates are obtained from a community or a clinic-based population [35]. Obsessive–compulsive symptoms (OCS) are present in at least 30–50 % of patients with the most representative of chronic tic disorders, i.e. Tourette syndrome (TS), and are also more frequent in relatives of patients with tic disorders. The main features of OCS are summarized in Table 3.2. Tic-related OCS may be more prevalent in males, may have earlier onset and are more likely to persist in adulthood. These are more frequently characterized by obsessional thoughts related to symmetry/exactness or aggressive or sexually inappropriate content, and counting, ordering/arranging and ‘just-right’ compulsions, compared to non-tic-related ones, and may be less responsive to selective serotonin reuptake inhibitors.
Table 3.2
Type and phenomenology of complex repetitive goal-directed pathological behaviours
Core description | Non-motor accompanying features | Most common underlying diagnoses | |
|---|---|---|---|
Impulsivity or impulsive behaviours | Sequences of motor actions potentially leading to self-harm or harm to others and which the subject perceives as rewarding Examples: gambling, plucking out bodily hair (trichotillomania), skin picking (dermatillomania), starting fires (pyromania), vandalizing, behaving aggressively in a manner which is disproportionate to any given stressor, stealing (kleptomania), binge eating, sexual behaviour, excessive or damaging use of the Internet, shopping or buying | Excessive, almost uncontrollable focus of volition and attention towards the impulsive behavioural pattern | 1. Primary Impulse Control Disorder (includes ADHD) 2. Treatment with dopamine agonists 3. Other medical conditions, e.g. carcinoid syndrome |
Compulsions | Repetitive sequences of motor actions performed to alleviate anxiety, driven or not by obsessions Examples: counting, doing actions in specific patterns or numbers, ordering, arranging, checking, hoarding, touching, washing | Obsessions, i.e. intrusive thoughts (e.g. related to fear of harm to self or others, to religious or sexual content, etc.), associated with raised anxiety levels | 1. Primary OCD 2. Paediatric acute neuropsychiatric syndromes (PANS) 3. Structural lesions of the medial frontal lobe |
Mannerisms | Repetitive sequences of routine motor actions, such as walking, talking, etc., performed in specific patterns, but not associated with alleviation of anxiety | Symptoms suggestive of psychosis | 1. Psychotic illness (e.g. schizophrenia) 2. Autistic spectrum disorder or other learning disabilities |
Attention deficit hyperactivity disorder (ADHD) is diagnosed in approximately 40–50 % of children with TS, although clinic-based studies often yield larger estimates. The co-occurrence of ADHD is associated with greater academic and social impairment, with higher frequency of deficits in motor skills, cognitive flexibility, written expression and attention. Disruptive behaviours may also be more common in children with TS and comorbid ADHD than in those with TS alone [36]. From a clinical standpoint, it is important not to misinterpret as attention deficit the problems with concentration experienced by patients with tic disorders when they engage in the active suppression of tics.
Impulse control disorders (ICDs) are relatively common in patients with tics (Table 3.2). Impulsive behaviours are driven by an attempt to obtain arousal and gratification or reward. Impulsivity in patients with chronic tics may lead to easy distractibility, general tendency towards disinhibited behaviour, prioritizing decisions associated with immediate reward and problems in delaying gratification [37]. More structured disruptive behaviours typical of intermittent explosive disorder may occur in 23–40 % of TS patients [38]. Rage attacks belong to this category of disruptive behaviours and manifest as sudden, unpredictable anger tantrums that may at times be associated also with overt aggressiveness. These manifestations occur in 50–60 % of TS patients with both ADHD and OCD. Self–injurious behaviours (SIBs) are another form of ICD in TS, documented in 15–30 % of patients, and include head banging, face punching or slapping (Fig. 3.1), banging the body against a hard object, eye poking with a sharp object and tongue or lip biting [39, 40].
Fig. 3.1
Self-injurious behaviour
Depressive symptoms in TS specialist clinics may range between 13 and 76 %, with a lifetime risk at least equal to 10 % [41]. Depression seems associated with severity and duration of tics and PU and coexistence of complex repetitive behaviours, e.g. SIBs or coprophenomena, sleep disturbances, OCD, aggressiveness and other conduct disorders.
Personality disorders may be more common in TS patients than expected. 64 % of adult TS patients were found to have at least one comorbid personality disorder, which include borderline, depressive, obsessive–compulsive, paranoid, passive aggressive and avoidant among the most common [42].
3.2.1.2 Examination and Assessment of Severity
The diagnosis of tics is based on the recognition of the core phenomenological features described above. When a patient clearly manifests tics during a consultation, describes convincingly the PU preceding these tics and shows directly to the examiner his/her ability in suppressing them, and this happens in association with a fair account of the fluctuating pattern of tics in body location and time, the diagnosis of tic disorder is straightforward. In routine clinical practice, however, things may not always be easy. The reassuring setting of a hospital or office consultation may have a beneficial effect over tic severity and strongly diminish their expression and/or improve the patient’s ability to suppress them. There are cases in which patients do not show any tic in front of the physician but, if left alone and observed without them knowing it, may exhibit tics at a variable degree of severity. In general, though, collecting this type of evidence is not feasible in routine clinical practice, and, if tics are not detectable during direct observation, physicians should rely on the account of the patient and/or of reliable informants, e.g. parents, partner, etc. [43]. The use of diagnostic inventories, such as the tic checklist contained in the first part of the Yale Global Tic Severity Scale (YGTSS), the most widely used severity rating scale for TS [44], or the checklist of the National Hospital Interview Schedule [45], may aid physicians in the identification of a history of tics. Direct questions on the temporal variability and the changing repertoire of tics over time, as well as on PU and suppressibility of tics, are necessary to confirm that the abnormal movements are indeed tics. Figure 3.2 summarizes the main phases of the clinical assessment of patients with chronic tic disorders.
Fig. 3.2
Assessment plan in Tourette syndrome. PUTS Premonitory Urge for Tics Scale [47], OCD obsessive–compulsive disorder, [C]Y-BOCS [Children]Yale–Brown Obsessive–Compulsive Scale [48], SNAP Swanson, Nolan and Pelham questionnaire [49], SCARED Screen for Child Anxiety and Related Emotional Disorders [50], BDI Beck Depression Inventory [51], BAI Beck Anxiety Inventory [52], DBRS Disruptive Behavior Rating Scale [53], ASSQ Autism Spectrum Screening Questionnaire [54, 55]
3.2.2 How to Distinguish from Related Disorders and Reach a Diagnosis
Most patients with tics fulfil diagnostic criteria for one of the primary tic disorders (Box 3.1), although a long list of causes of secondary tics has been reported (Box 3.2; Fig. 3.3). Typically, primary tic disorders have a childhood onset but may persist into adulthood. Primary tic disorders are classified as transient or chronic and are defined as conditions in which tics cause distress or significant impairment in social, occupational or other relevant domains of functioning. Tourette syndrome (TS) is the most important of primary tic disorders. According to the DSM-V diagnostic criteria [46], patients with TS have childhood or adolescence onset of multiple motor and vocal tics with a duration of at least 1 year. Tic disorders lasting longer than 1 year with only motor or vocal tics are labelled as persistent (chronic) motor or vocal tic disorders. Provisional tic disorders are characterized by a duration of less than 1 year, and this diagnosis can therefore only be made retrospectively (i.e. when tics cease). This may represent an exaggerated version of ‘physiological tics’, although it is possible that its severity may reach a degree for which the label of ‘disorder’ is appropriate. ‘Physiological tics’ commonly occur during normal childhood development and reflect a stage of the physiological synaptogenesis within connections between basal ganglia and frontal lobes; another example of a similar ‘physiological’, transient motor phenomenon is the mild choreiform movements of infancy. The vast majority of children with new onset of tics will have resolution within the year.
Fig. 3.3
Diagnostic flow chart for tic disorders. *(unless a new pathogenic link with an underlying genetic or metabolic condition is clearly demonstrated). ** PANDAS paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection. The clinical definition of this entity is still debated and caution in the diagnosis is highly recommended. HD Huntington’s disease, NA neuroacanthocytosis syndromes, NBIAs neurodegeneration with brain iron accumulation syndromes. RLS restless legs syndrome
Box 3.1. DSM-V Diagnostic Criteria for Primary Tic Disorders
Tourette Syndrome (TS) |
For a person to be diagnosed with TS, he or she must meet the following criteria: |
A. The person must have both motor tics (e.g. blinking or shrugging the shoulders) and vocal tics (e.g. humming, clearing the throat or yelling out a word or phrase), although they might not always happen at the same time. |
B. The person must have had tics for at least a year. The tics can occur many times a day (usually in bouts) nearly every day or off and on. |
C. The person’s tics must begin before he or she is 18 years of age. |
D. The person’s symptoms must not be due to taking medicine or other drugs or to having another medical condition (e.g. seizures, Huntington’s disease or postviral encephalitis). |
Persistent (or Chronic) Motor or Vocal Tic Disorder |
For a person to be diagnosed with a persistent tic disorder, he or she must meet the following criteria: |
A. The person must have one or more motor tics (e.g. blinking or shrugging the shoulders) or vocal tics (e.g. humming, clearing the throat or yelling out a word or phrase), but not both. |
B. The person must have tics that occur many times a day nearly every day or on and off throughout a period of more than a year. |
C. The person’s tics must start before he or she is 18 years of age. |
D. The person’s symptoms must not be due to taking medicine or other drugs or to having another medical condition (e.g. seizures, Huntington’s disease, or postviral encephalitis). |
E. The person must not have been diagnosed with TS. |
Provisional Tic Disorder |
For a person to be diagnosed with this disorder, he or she must meet the following criteria: |
A. The person must have one or more motor tics (e.g. blinking or shrugging the shoulders) or vocal tics (e.g. humming, clearing the throat or yelling out a word or phrase). |
B. The person must have tics for no longer than 12 months in a row. |
C. The person’s tics must start before he or she is 18 years of age. |
D. The person’s symptoms must not be due to taking medicine or other drugs or to having another medical condition (e.g. Huntington’s disease or postviral encephalitis). |
E. The person must not have been diagnosed with TS or persistent motor or vocal tic disorder. |
Box 3.2. Secondary Causes of Tics
Neurodevelopmental disorders |
Learning disabilities of undefined origin |
Autistic spectrum disorders (including Asperger’s syndrome) of undefined origin |
Genetic and chromosomal abnormalities |
Rett syndrome, X-linked mental retardation (MRX23), Albright hereditary osteodystrophy, Duchenne muscular dystrophy, factor VIII haemophilia, fragile X syndrome, Lesch–Nyhan syndrome, triple X and 9p mosaicism, 47 XXY karyotype, partial trisomy 16, 9p monosomy, Beckwith–Wiedemann syndrome, tuberous sclerosis, congenital adrenal hyperplasia secondary to 21-hydroxylase deficiency, phenylketonuria, corpus callosum dysgenesis, craniosynostosis, Klinefelter syndrome, neurofibromatosis |
Developmental stuttering of undefined origin |
Acute brain lesions |
Post-traumatic |
Vascular |
Infectious: Varicella zoster virus striatal encephalitis, herpes simplex virus encephalitis, mycoplasma pneumoniae encephalitis, neuroborreliosis |
Postinfectious |
PANDAS (controversial) |
Proposed criteria |
Presence of a tic disorder or obsessive–compulsive disorder |
Prepubertal age (usually between 3 and 12 years old) at onset |
Abrupt symptom onset or episodic course of symptom severity |
Temporal association between symptom exacerbations and streptococcal infections |
Presence of neurologic abnormalities during periods of symptom exacerbation |
Sydenham’s chorea |
Neurodegenerative diseases |
Huntington’s disease |
Neuroacanthocytosis syndromes |
Neurodegeneration with brain iron accumulation |
Other systemic diseases |
Behcet’s disease |
Antiphospholipid syndrome |
Medications and toxins |
Amphetamines |
Cocaine |
Heroin |
Methylphenidate |
Pemoline |
Antipsychotics (D2 blockers): fluphenazine, perphenazine, thiothixene |
Antidepressants |
Antiepileptics: carbamazepine, phenytoin, phenobarbital, lamotrigine |
L-dopa |
Functional ‘tic–like’ jerks |
The natural history of primary tic disorders is highly supportive of the diagnosis. Tics typically begin between 5 and 8 years of age and in up to 95 % between ages 4 and 13. At onset, tics are frequently simple and involve cranial muscles (usually in the face). The most common initial tics are eye blinking and sniffing. With time, the global severity of tics may increase, reaching a peak in the peri-puberal period (age 10–12). During this period, complex tics may appear, and the spread of tics follows a rostro-caudal direction, involving in variable combination larynx, shoulders, torso and limbs [56]. During the second decade of life, tics usually decrease in severity. In most cases the severity of tics during adulthood is considerably lower than during the developmental period. The persistence of clinically significant tics in adulthood was found to be more likely in patients with high tic severity, lower caudate volumes and poor performance on tasks involving visuomotor skills like the Purdue Pegboard test during childhood [57]. However, these clinical and endophenotypical traits are not routinely examined in clinic.
The vast majority of patients manifesting tics are affected by a primary tic disorder of variable severity. Secondary tics are much less common. Apart from accompanying features and age of onset, secondary tics do not appear to be phenomenologically different from primary tics, although clinical evidence-based data on this aspect are currently very limited.
When a patient’s tics show their first appearance in the first two decades and tics occur either in isolation or in association with the behavioural comorbidities described above (OCD, ADHD, oppositional defiant or conduct disorder, ICD, mood or anxiety disorder or a personality disorder), the diagnostic work-up is limited to a thorough history assessment (which should ideally include previous exposure to drugs or toxins) plus a complete neurological examination and a psychiatric evaluation (Figs. 3.2 and 3.3).
If coexisting with an autism spectrum disorder (ASD) or another form of learning disability (LD), generally tics do not represent the prominent clinical manifestation or the principal reason for medical attention. The frequency of concurrent ASD or LD in primary tic disorders is known to be higher than in the general population, suggesting a possible pathobiological overlap between these different neurodevelopmental disorders [58, 59]. ASD and LD may present also with stereotypies. Differentiating between tics and stereotypies in patients with learning disabilities or autistic traits may be clinically difficult, given the limited access to patient-reported information such as PU or suppressibility of abnormal movements. Tics are also reported to occur in a number of genetic and chromosomal abnormalities (Box 3.2), but this observation stems mainly from isolated case reports or very small case series.
Collecting accurate information on drug and toxin exposure in the first two decades is less crucial than in patients in whom tics first appear later. Nevertheless, it is important not to miss the rare cases of drug– or toxin–induced tics in paediatric years (Box 3.2).
It has been proposed that children in prepubertal years who present with an abrupt onset of tics and/or OCD, with a climax of severity reached within 24–48 h from the onset may have a postinfectious form of tic disorder [60]. This has been particularly linked to the exposure to a preceding infection by group A beta-haemolytic streptococcus. Children with this syndrome, known as paediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS), may exhibit a relapsing-remitting course in which clinical re-exacerbations are triggered by infections and where there may be coexisting ‘choreiform’ movements especially of the hands [60, 61]. The definition of PANDAS, and particularly the occurrence of tics as a primary manifestation of PANDAS, is currently being re-appraised, and new diagnostic classifications are under discussion [62, 63]. Moreover, different infectious triggers are thought to play a role, albeit smaller than the one played by psychosocial stressors, in modulating the course of TS. Finally, we lack a reliable diagnostic biomarker for this proposed subgroup of tic disorders. Until more reliable and accepted criteria for postinfectious tic disorders are formulated, it remains doubtful whether paediatric patients with a fluctuating course of tics in association or not with OCS should undergo extensive diagnostic work-up or receive immune-modulating or antibiotic treatments.
Rarely, in childhood and adolescence, tics may co-occur in association with other movement disorders (e.g. chorea, parkinsonism, dystonia or pyramidal dysfunction) in the context of neurodegenerative conditions like Huntington’s disease, neuroacanthocytosis syndromes and neurodegeneration with brain iron accumulation.
A reported first appearance of tics at age 16 or above is less likely to be due to primary tic disorders and should prompt to the exclusion of secondary causes. A more accurate collection of the patient’s history may, in some of these unusual cases, unveil the occurrence of tics even for a very brief period during childhood or adolescence, thus supporting the diagnosis of primary chronic tic disorder.
If isolated tics occurring for the first time in adulthood are not associated with any previous history of tics, particularly in the absence of a family history of tics, a secondary cause is more likely. Exposure to drugs or toxic substances should be explored before other possible causes. Different psychotropic substances may trigger tics [64]. Psychostimulants (e.g. amphetamines, methylphenidate, pemoline, cocaine, heroin) used for therapeutic or recreational purposes may lead to the exacerbation or onset of tics. However, it is more difficult to infer a pathogenic link between the use of psychostimulants to treat a comorbid ADHD and the occurrence of tics. This is due to the high degree of comorbidity between ADHD and primary tic disorders. In patients who experienced remission of tics, it is not uncommon to observe the reappearance of tics during adulthood following exposure to stimulants like cocaine or ecstasy [65]. Tardive tics, i.e. as delayed side effect of prolonged treatment with antipsychotics or other dopamine receptor blockers, are relatively rare but have been reported [66]. Box 3.2 presents a list of the psychotropic substances that have been associated with onset or significant worsening of tics.
If there is no exposure to psychotropic substances, it is important to rule out the rare occurrence of structural lesions within frontostriatal circuits, especially if tics have an abrupt onset and are associated with the similarly rapid onset of other neurological signs or symptoms or if there is a history of cranial trauma. Tic-inducing structural brain lesions may include traumatic brain injury [67, 68] and ischaemic or haemorrhagic stroke [69–71], tumour and inflammation (e.g. viral encephalitis secondary to herpes viruses or HIV-1 [72, 73]; multiple sclerosis [74]). Magnetic resonance imaging of the brain and, where appropriate, cerebrospinal fluid analysis may be necessary to confirm these diagnoses. Neurodegenerative diseases primarily affecting the same structures may also manifest with tics; among these, Huntington’s disease [75], neuroacanthocytosis syndromes [76] and pantothenate kinase-associated neurodegeneration are the most common [77, 78].
The familial co-occurrence in adult patients of tics and other movement disorders has recently been highlighted. The coexistence of tics and dystonia (most commonly, cervical) is characterized by a later age of onset and lower severity of tics [79]. Restless legs syndrome (RLS) and TS may also co-segregate in families [80]. As for the coexistence of tics and ASD or LD in childhood, the co-occurrence of tics and these movement disorders in families may either be the result of overlapping pathobiological mechanisms or be coincidental; for either of these interpretations, the diagnosis of primary, rather than secondary, tic disorder seems prudent.
Finally, there are some forms of jerky movements in adulthood which bear many similarities with tics but present also other features which are suggestive of a ‘functional’ motor disorder. This differential diagnosis may be difficult as some features of tics and ‘functional’ jerky movements overlap, such as variability over time, distractibility, inducibility and partial voluntary suppressibility. The ability to diagnose this as yet poorly understood group of patients will certainly increase with a better understanding of the specific phenomenological features of ‘functional’ motor disorders, an area in which more research is needed. Table 3.3 summarizes the clinical differences between tics and functional tic-like movements.
Table 3.3
Differential diagnosis between organic tics and functional tic-like jerky movements
Organic tics | Functional tic-like ‘jerks’ | |
|---|---|---|
Typical age at onset | Children | Young adults |
Gender predominance | Male | Female |
Sudden onset | Rare | Frequent |
Premonitory sensation | Common | Uncommon |
Suppressibility | Common | Uncommon |
Distractibility | Partial | Highly variable |
Suggestibility | Partial | Common |
Family history of tics | Common | Rare |
Response to dopamine receptor blockers | Frequent, but variable | Rare |
Electrophysiology (Bereitschaftspotential) | Early component absent (late component found present) | Early component commonly present |
3.2.3 How to Treat
Patients with tic disorders can be very different regarding the average severity of symptoms, time course of symptoms, associated comorbid disorders, quality of life and functional impairment. Hence, management should always be tailored on the individual patient’s requirements (Fig. 3.4 presents a decision tree for the treatment of tics within primary tic disorders). A considerable proportion of patients with chronic tics is not clinically disabled and may not even require medical attention. Of the whole subgroup of patients who request medical attention, a good proportion needs appropriate education on the condition and simply needs reassurance on the nature of the disorder. When tic-related disability is greater or comorbidities represent a treatment priority, then management should involve more active interventions than mere psychoeducation [83].
Fig. 3.4
Decision tree for the treatment of tics (specifically focused on Tourette syndrome and other primary tic disorders) (From Roessner et al. [83])
Before choosing the most suitable management approach, it is crucial to collect a comprehensive medical history of the patient’s ailments and recapitulate the history of symptoms, ideally with a suitable informant. An array of screening instruments and assessment rating scales is available to diagnose comorbidities and measure the current severity of tics and related features, primarily obsessive–compulsive symptoms, features of ADHD, as well as anxiety and depressive symptoms. Gauging tic severity in clinic may be problematic, given the high dependency of tics on the environmental context. Tic severity may improve considerably in front of the specialist if the patient perceives the clinical environment as a safe one: this might lead to an underestimation of the actual severity of symptoms, which sometimes is better reported by parents or partners.
In general, the first mandatory part of management of a tic disorder is psychoeducation [84]. Physicians and allied health professionals (nurse specialists, clinical psychologists, etc.) should inform patients and families about the natural history of chronic tic disorders, the relevance of contextual factors and the main behavioural comorbidities. This initial intervention facilitates acceptance of symptoms, promotes coping and adaptive strategies and enables the care team to assess the current or future requirements of more ‘invasive’ interventions [85].
A smaller proportion of patients can exhibit tics which are violent (e.g. tics consisting of violent head, trunk or limb movements) or even harmful (e.g. myelopathy secondary to violent head thrusts). Pain secondary to tics (particularly headache) remains an underestimated symptom in patients with TS or other tic disorders. Tics may be stigmatizing in an inadequate school environment, causing isolation and favouring victimization and bullying and leading to subsequent increase of anxiety levels, reduction in self-confidence and self-esteem, depression and ultimately damaging school performance [83].
3.2.3.1 Pharmacological Treatment
Guidelines on pharmacological treatment for tics have been published in recent years [83, 86]. Unfortunately, the overall quality of randomized placebo-controlled trials of medications to treat tic disorders has been generally low, due to the use of relatively small samples, brief follow-up duration and the limited number of active comparator trials between different medications and between pharmacological and non-pharmacological treatments (Table 3.4). A general problem in measuring the responsiveness of tics to a given treatment is their fluctuation in severity for external causes, like psychosocial stress or other contextual factors. Observing patients for a sufficient period of time or gathering accurate information on the natural course of tics over time from patients is usually advised before initiating a new treatment. Coexisting behavioural disorders like ADHD or OCD may also influence tic severity. Moreover, we have limited information also on the medium- and long-term tolerability of medications in TS patients.
Table 3.4
Medications tested in clinical trials for the treatment of tics
Treatment | Daily dose (mg) | Side effects | Comments |
|---|---|---|---|
Haloperidola,b Pimozidea,b Fluphenazine | 0.5–20 0.5–10 0.5–20 | Rigidity, parkinsonism, tardive involuntary movements and akathisia; appetite changes; weight gain; salivary changes; constipation; depression, anxiety; fatigue, sedation; hyperprolactinaemia (galactorrhoea, gynecomastia, irregular menses, sexual dysfunction) | Pimozide and fluphenazine are slightly less effective than haloperidol, but have a better tolerability profile |
Sulpiride | 50–200 | Sedation; less commonly, paradoxical depression, restlessness, sleep problems, weight gain, hyperprolactinaemia | Mild antidepressant and anxiolytic properties; more commonly used in Europe (UK, Germany) than in North America |
Risperidonea,b | 0.5–16 | Sedation, fatigue, depression and acute phobic reactions, weight gain | Some evidence of larger efficacy with comorbid obsessive–compulsive symptoms or aggressive behaviour |
Olanzapineb | 2.5–20 | Sedation, weight gain and increased appetite, dry mouth, transient hypoglycaemia | Some evidence of effect on aggressive behaviour |
Aripiprazole | 5–30 | Less commonly than other antipsychotics: weight gain, headaches, fatigue, sedation, akathisia, sleep problems; probably lower risk of QT prolongation than with other antipsychotics | Probably the best candidate for a future large randomized controlled trial |
Clonidinea,b Guanfacine | 0.05–0.5 0.5–4 | Sedation, dry mouth, headache, irritability, midsleep awakenings, rebound hypertension, tics and anxiety following abrupt discontinuation; possible higher risk of syncope and mania in children with personal or family history of bipolar disorders | Best therapeutic advantage of clonidine in patients with TS + ADHD; half-life of guanfacine > half-life of clonidine |
Tetrabenazine | 25–200 | Sedation, fatigue, nausea, depression, insomnia, akathisia, parkinsonism (less commonly) | Lower risk of extrapyramidal symptoms or weight gain than with antipsychotics; requires very slow discontinuation |
Ropinirole Pramipexolea | 0.5–1 not superior to placebo | Very well tolerated at very low doses | Mild effect on comorbid ADHD symptoms with pramipexole |
Clonazepam | 0.5–10 | Sedation | |
Baclofena | 60 | Fatigue | Improved tic-related impairment but not tic severity |
Levetiracetama,b | not superior to placebo | Irritability | |
Topiramatea | 50–150 | Weight loss, paraesthesia | |
Ondansetron | 8–16 | Abdominal pain, constipation | |
Delta-9-tetrahydrocannabinola | 10 | Anxiety, mood changes, memory loss, psychosis, blurred vision | Mild-to-moderate effect on tic severity |
Flutamidea | Risk for acute idiosyncratic liver reaction | ||
Botulinum toxina | Focal weakness, hypophonia | Effective on focal, disabling tics, including phonic tics |
There is evidence in favour of a relevant role of dopaminergic neurotransmission in the pathophysiology with tics. Three main hypotheses of the dopaminergic involvement in tic generation have been formulated: hyperinnervation of the striatum by dopaminergic terminals, increased number or affinity of striatal dopamine receptors and increased presynaptic striatal dopa decarboxylase activity [87]. One of the strongest elements in support of dopaminergic involvement in tic disorders is the efficacy of antipsychotic medications in ameliorating tics.
Antipsychotic drugs were reported as effective in reducing tics since the earliest open-label studies in the 1970s and 1980s, which focused primarily on D2 dopamine receptor blockers. In these early works, first-generation antipsychotics improved tics in up to 70 % of patients [88]. Several randomized controlled trials (RCTs) documented the greater efficacy, with respect to placebo, of pimozide and haloperidol [89]. When compared directly to one another, pimozide and haloperidol were not significantly different in reducing total tic scores, although haloperidol was less tolerated, mainly due to its extrapyramidal side effects [90]. Fluphenazine is still frequently used, particularly in North America, on the basis of its better tolerability profile compared to haloperidol [91]. A number of retrospective medical records reviews, open-label studies and one single-blind, placebo-controlled crossover study provide support in favour of the use of this agent. Metoclopramide has also shown superiority to placebo in treating tics in paediatric patients in a single RCT [92]. Overall, however, the use of first-generation antipsychotics is limited today by side effects that include increased anxiety and dysphoria (also after withdrawal), hyperprolactinaemia (leading to gynecomastia, galactorrhoea, irregular menses and sexual dysfunction), hypotension, electrocardiographic changes and weight gain [93]. Pimozide was also found to be associated with significant increases in glycaemia in children with tic disorders [94]. Benzamides like tiapride and sulpiride are more frequently used in Europe, especially in Germany and the United Kingdom [83]. Their efficacy is supported by small controlled studies [95]. Sedation remains a relatively common problem when using sulpiride.
Since the advent of second- and third-generation antipsychotics, risperidone and aripiprazole are the two agents for which we have the highest-quality evidence supporting their efficacy in treating tics. Five RCTs have confirmed the superiority over placebo of risperidone and similar efficacy to pimozide and clonidine in active comparator trials [93]. One meta-analysis found no significant difference in efficacy between risperidone (daily dose range 1–6 mg), haloperidol, pimozide and ziprasidone, confirming significant superiority over placebo for all the four agents [96]. There is initial evidence that risperidone could be advantageous in TS patients with comorbid obsessive–compulsive symptoms and impulse control disorder. However, risperidone requires accurate monitoring for motor and metabolic side effects [97]. There is limited and mixed evidence of efficacy for olanzapine [98, 99], which also carries a significant risk of metabolic side effects (body mass index increases and alteration in lipid profile). Aripiprazole has D2 antagonistic properties in hyperdopaminergic conditions and agonist effects in hypodopaminergic states. Open-label studies on relatively large clinical samples suggest significant reduction in tic severity in approximately 60 % of children and adults with TS treated with this drug, with effects lasting over 1 year in up to 50 % of responders [100]; moderate effectiveness on co-occurrent ADHD symptoms was also reported [101]. A 10-week, double-blind, placebo-controlled RCT has confirmed the efficacy of aripiprazole; adverse effects included decreased serum prolactin concentration and increase of mean body weight, body mass index and waist circumference [102]. The tolerability profile of this drug in TS patients seems slightly more favourable than that of other new-generation antipsychotics, particularly with regard to electrocardiographic (QT interval prolongation) and motor abnormalities [103]. There is no convincing evidence that the use of very low doses of dopamine agonists like ropinirole and pramipexole is efficacious [93], despite the observation of a moderate effect on comorbid ADHD [104].
Alpha–2 agonists have been considered effective treatments for tics for more than three decades [105]. Six RCTs of variable overall quality demonstrated a moderate degree of evidence in favour of superiority of clonidine over placebo for both the oral and the transdermal formulations [106]. Two RCTs and two open-label studies assessed the efficacy of guanfacine in children with TS; this drug has longer half-life than clonidine and can be used in an extended-release formulation administered in a single daily dose. These two medications are considered first-line therapy in the USA and Canada, primarily due to their preferable side effect profile, compared with antipsychotics, whereas in Europe they are generally less commonly used than antipsychotics [83, 86]. One meta-analysis confirmed superiority over placebo for both alpha-2-agonists, although only for young TS with comorbid ADHD [96]. Patients on clonidine should be monitored for hypotension, sedation, headache, irritability, dysphoria and interrupted night sleep [107]. Clonidine should be titrated gradually to minimize toxicity and tapered off gradually to avoid rebound hypertension [108].
Baclofen and topiramate were moderately efficacious in two small, double-blind RCTs that recruited patients across different age classes [109, 110]. Topiramate moderately improved tic severity from baseline over a 70-day period in 29 patients.
Tetrabenazine blocks the vesicular VMAT2 protein leading to presynaptic dopamine depletion with relatively minor postsynaptic D2 blockade. Its use in the treatment of tics is supported by one small open-label trial and retrospective cohort studies, which showed long-lasting (18–24 months) improvement of tic severity in more than 80 % of patients [111]. Tetrabenazine does not lead to weight gain but may cause drowsiness, fatigue, nausea and depression.
Botulinum toxin injections are considered very useful for the treatment of persistent and localized simple motor and vocal tics, including coprolalia and upper face or neck tics, with potential reduction also of premonitory urges. Evidence of efficacy for botulinum toxin treatment of tics is supported by one RCT [112], three retrospective cohort studies and a number of case reports or small case series [106]. Hypophonia is a very common side effect of botulinum toxin injections for vocal tics.
Other medications. Ondansetron, an 5HT3 receptor antagonist, improved tic severity in one small placebo-controlled trial [113]. Two small RCTs evaluated the tic-relieving effect of delta–9–tetrahydrocannabinol, the main active compound of cannabis, in 28 adults with TS, reporting a modest benefit and acceptable tolerability [114]. A single controlled trial of nicotine chewing gums and three controlled studies of transdermal nicotine patches, used as add-on to antipsychotic treatment, showed mild reduction of tic frequency but intolerable gastrointestinal side effects [115]. Other compounds including naloxone, naltrexone, calcium channel blockers, flutamide, lecithin, physostigmine, citalopram, fluvoxamine and propranolol, have been tried in patients with a chronic tic disorder, but evidence is mainly anecdotal or limited to poor quality trials. Finally, a double-blind, placebo-controlled RCT of omega–3 fatty acids showed reduced tic-related impairment in children and adolescents with TS, although there was no direct benefit over tics [116].
3.2.3.2 Behavioural Treatment
The availability of dedicated behavioural treatment (BT) for tics has significantly grown during the last decade, demonstrating a reduction in the severity of motor and vocal tics. The most effective treatment approaches of this kind are Habit Reversal Training (HRT), a related and expanded version of the HRT package called Comprehensive Behavioural Intervention for Tics (CBIT) and Exposure Response Prevention (ERP) for tics.
The main scope of HRT is to train patients to gain control over their tics in real time. It consists of three main components: (1) awareness training, whereby patients learn to recognize their premonitory urges and tics when these occur in real time; (2) competing response training, whereby patients select and implement a motor behaviour through which they may counteract the occurrence of tics; and (3) social support, whereby a designed support person promotes the use of HRT strategies outside of therapy. Six randomized controlled trials and several smaller observational studies showed that HRT reduces tic severity effectively [117]. Moreover, a meta-analysis detected a large treatment effect size, similar to that observed in other widely used behavioural interventions for conditions like OCD or anxiety disorders [118].
Comprehensive Behavioural Intervention for Tics (CBIT) is the most popular and investigated extension of HRT, which focuses on relaxation training as a stress management tool and on psychoeducational interventions. The implementation of relaxation training, per se not sufficiently effective to improve tics in monotherapy [119], may aid tic suppression as a form of stress management tool. A similar beneficial addition is provided by the addition of psychoeducation, the crucial role of which has been highlighted above. CBIT is delivered in 1-h long weekly sessions, with a fixed protocol of homework assignments. Overall, the efficacy of HRT and CBIT upon tic reduction is not inferior to that provided by some pharmacological interventions. HRT showed efficacy in children, adolescents and adults ages 8–65 years with TS, regardless of comorbid psychological conditions, use of anti-tic medications and type of tics produced. Two multi-site randomized controlled trials, one with children [120] and one with adults [121], involved 8 weekly sessions followed by booster sessions every 3 months and demonstrated its superiority to supportive therapy plus psychoeducation by a threefold factor and its very good tolerability. An improvement of psychopathological comorbidities was also observed.
Exposure and Response Prevention (ERP) has been originally validated and is very widely used for OCD. In respect to its application in tic disorders, ERP consists of prolonged exposure to premonitory urges through prolonged suppression of tics [117]; this should lead to habituation to the urge and gradual reduction of the motivation of the patient to tic (a counterconditioning type of approach). Only one randomized controlled trial has shown non-inferiority of ERP to HRT [122], although this approach is generally longer and less cost-effective than HRT and some of its extensions, such as CBIT.
The main drawbacks of BT in TS are the still relatively restricted number of well-trained teams of therapists, its length of application (2–3 months on average) and its costs. More research is also needed to increase knowledge of predictors of good response to BT and patient selection criteria, which might help tailor the therapeutic intervention, i.e. deciding whether to treat with BT or not and which BT approach to use in the individual patient.
3.2.3.3 Surgery
Over the last decade, there has been increasing experience and experimental evidence of the efficacy and tolerability of functional neurosurgery, in particular of deep brain stimulation (DBS), for TS. Recommended selection criteria have been proposed (Table 3.5), which should include, among other aspects, a confirmed DSM-V diagnosis of TS by expert clinicians, refractoriness to less invasive treatments and stable comorbidities and psychosocial environment [123–125]. To date, DBS in TS is limited to patients with highly disabling tics persisting into adulthood, who have not been helped by pharmacological and non-pharmacological (e.g. CBIT) approaches, hence in a subset of more severe and ‘resistant’ patients.
Table 3.5
Proposed set of criteria for eligibility to deep brain stimulation surgery in Tourette syndrome (TS) patients
Inclusion criteria |
DSM-V diagnosis of TS by expert clinician |
Local ethics committee involvement for cases involving patients <18 years and for ‘urgent’ cases (e.g. self-injurious tics like violent head tics at risk of head banging or cervical cord damage) |
Tic severity high (proposal: >35 on Yale Global Tic Severity Scale, severity subscore) |
Tics refractory to conservative therapy (3 classes of medications should have failed to provide benefit + behavioural therapy should have been failed to provide benefit or should at least have been offered to the patient) with demonstrated ability to adhere to recommended treatments |
Tics as prominent feature and primary cause of disability |
Stable and optimized treatment of medical, cognitive and behavioural comorbidities for 6 months |
Expected compliance during monitoring (stable psychosocial environment) |
Neuropsychological profile indicating that candidate can tolerate surgery, post-operative follow-up and possibility of poor outcome |
Exclusion criteria |
Active suicidal or homicidal ideation or substance abuse within 6 months |
Structural lesions on brain MRI |
Medical, neurological or psychiatric disorders increasing the risk of surgical failure or interfering with post-operative monitoring |
Uncertain diagnosis of TS (including psychogenic or ‘functional’ tics) |
Validated and universally accepted guidelines on the ideal anatomical target are still lacking, and the main reason for this limitation is the lack of active comparator trials. At present, the most promising targets are the centromedian/parafascicular–substantia periventricularis–nucleus ventralis oralis internus crosspoint of the thalamus [126], and the globus pallidus pars interna with a higher number of reported successful cases when the anteromedial, or limbic, portion is targeted [127–129]. DBS has general potential complications which apply to all anatomical targets and indications, e.g. haemorrhage and infection of the electrode implant site. More specific adverse events associated with thalamic DBS in TS include sedation, abulia, fatigue, apathy, sexual dysfunction and visual disturbances. Importantly, it has been shown by longitudinal observational studies that thalamic DBS does not lead to long-term adverse cognitive sequelae. The opportunity to apply a ‘tailored’ approach, based on the clinical manifestations exhibited by each patients within the Tourette spectrum, as well as a scheduled, rather than continuous, DBS paradigm, has recently been discussed [130].
3.3 Stereotypies
3.3.1 How to Recognize
Stereotypies are (1) patterned and repetitive but not goal-directed movements, which are (2) continuous (for at least 4 weeks), pervasive and highly consistent over time within each individual, often limiting considerably all other motor activities; (3) are not associated with a specific type of antecedent sensory phenomena, mental urge or specific ideational content; and (4) may be distractible at a variable degree, although active voluntary suppression is rare [131].
Stereotyped, repetitive and not goal–directed presentation. As their name indicates, stereotypies are movements which are patterned and repeated over and over again in the same fashion by the same individual. This feature may, however, be applicable also to other types of complex abnormal movements like tics and some forms of impulsive behaviours; hence, it is not specific of stereotypies. Although anatomical distribution is probably not a useful criterion to differentiate tics from stereotypies, the most common simple tics affect the face (e.g. blinking, eye movements, grimacing), which is less frequently affected by stereotypies. Like tics, stereotypies are not goal-directed movements. This characteristic is shared by the majority of abnormal movements, but it is very important to differentiate between stereotypies and impulsive behaviours, compulsions and mannerisms (Tables 3.1 and 3.2).
Continuous and highly consistent over time. Stereotypies typically consist of the same motor routine constantly repeated over time, unlike the more heterogeneous and intermittent repertoire of tics. Moreover, whereas tics typically present with a repertoire that fluctuates in quality and severity over a time period of days, weeks or months, stereotypies are characterized by the same movement(s) in a much more stable fashion across different time scales (minutes, hours, days, weeks, months or even years). Patterned automatic behaviours resembling stereotypies may represent epileptic seizures, but these are obviously paroxysmal and often accompanied by an altered state of consciousness.
Lack of association with a specific drive. Stereotypies are neither specifically preceded by sensory or mental experiences, such as the urges that trigger tics or impulsive behaviours nor by specific thoughts, such as the obsessions that give rise to compulsions.
Distractibility. Like tics, stereotypies may be influenced by the surrounding environment and are often described as distractible. Intense emotional states and fatigue may facilitate stereotypies, but this seems true also for states of boredom or their opposite, i.e. being engrossed in highly demanding activities such as computer games. Stereotypies may be actively distracted by surrounding stimuli, although this depends on both the intensity of the environmental stimulus and the severity of the illness underlying the stereotypies.
The severity of stereotypies can be assessed using various rating scales. Among these instruments, the repetitive behaviour scale revised (RBS-R) is an empirically derived parent- or caregiver-rated report of the wide spectrum of repetitive behaviours comprising 43 items across 6 subscales [132]. Another instrument is the Stereotypy Severity Scale, which has two components, one for the motor characteristics of the behaviour (rated along four dimensions: number, frequency, intensity, interference) and the other addressing the global effects of movements [133].
3.3.2 How to Distinguish from Related Disorders and Reach a Diagnosis
In the vast majority of cases, stereotypies occur in childhood. In children stereotypies may either be isolated or associated with other clinical manifestations. When isolated, stereotypies may represent a non-disabling variant of normal behaviour and are often referred to as primary stereotypies. Singer [134] proposed three different types of primary stereotypies: common, head nodding and complex motor stereotypies. Common primary stereotypies consist of movements that may be defined as habits, i.e. movements that share all the main clinical features with stereotypies and may be non-goal-directed, but do not lead to any impairment or disability, being well tolerated by subjects performing them and by their families or carers. During infancy and early childhood, common stereotypies comprise body rocking and thumb (or other finger) sucking; during preschool years, stereotypies often consist of making faces or thumb sucking, whereas in school age children, chewing, biting nails (onicophagia) and hair twisting are the most common. Adult common stereotypies may also display a vast repertoire. Head nodding may resemble a ‘no’ or a ‘yes’ movement of the head, or, in addition, these patients may present with a shoulder-to-shoulder movement. Head nodding stereotypies have an earlier age of onset than other primary motor stereotypies and should be differentiated from a number of similar conditions, including Sandifer syndrome, the ‘bobble–head doll syndrome’ (secondary to a diencephalic or basal ganglia lesions with or without ventricle dilatation, particularly of the third ventricle), spasmus nutans, congenital nystagmus and cerebellar disorders. Finally, complex motor stereotypies of hands and arms may co-occur with other, less prominent types of stereotypies. These are typically associated with specific triggers, particularly excitement or happy sensations, and are engrossed in attention-demanding activities, anxiety, stress, fatigue or intense imagery [135]. Only in a very small minority of cases, complex motor primary stereotypies in children occur within the third year of age [136]. The duration of continuous stereotypies is highly variable, ranging from few seconds to several hours. Interestingly, natural history data suggest that in the vast majority of cases, primary stereotypies persist over time, in most instances improving or maintaining the same severity [137]. Differences in frequency and intensity tend to increase with age, but this is more marked for patients with secondary stereotypies.
The aetiology and pathogenesis of secondary stereotypies are heterogeneous, with potential interaction between a pathological genetic substrate and specific environmental inputs. Stereotypies may result from self-stimulatory behaviour associated with sensory deprivation and/or low interest in or limited ability to interact with the surrounding environment. Reduced environmental stimulation is a common trigger for most secondary stereotypies. In some cases secondary stereotypies may develop into self-injurious behaviours (e.g. eye poking, biting, head banging, complex hand movements).
The main causes of secondary stereotypies are neurodevelopmental disorders, that include severe learning disabilities and autistic spectrum disorders, associated or not with chromosomal aberrations, e.g. Down syndrome, Williams syndrome [138], fragile X syndrome [139], cri-du-chat syndrome, Smith–Magenis syndrome [140] and confinement and/or sensory deprivation (‘deprivation’ stereotypies) linked to restricted visual or auditory abilities, including blindness or deafness [136, 141]. ‘Deprivation’ permanent stereotypies are typically observed in patients with congenital sensory deprivation, whereas late-onset acquired deprivation (e.g. acquired blindness) usually does not give rise to permanent stereotypies.
Stereotypies may originate also from specific neurochemical mechanisms. Rett syndrome is an X-linked, neurodegenerative illness that typically presents with stereotypies in the developmental period. This condition may be caused by several types of mutations in the MECP2 gene, which codes for a protein that acts as a transcriptional repressor binding to methylated DNA [142]. Stereotypies affecting the hands appear to differ between Rett syndrome and autistic spectrum disorders (Table 3.6). Typically, Rett syndrome is diagnosed in young girls but should also be suspected in adult women with stereotypies and psychomotor retardation [143].
Table 3.6
Different characteristics of stereotypies in Rett syndrome and autistic spectrum disorders
Rett syndrome | Autistic spectrum disorders | |
|---|---|---|
Temporal course | Continuous | Intermittent |
Body distribution | Predominantly located in hands, mouth, axial district | More randomly distributed (distal more than proximal) |
Involvement of objects | Common | Not common |
Involvement of fingers
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