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Chapter 17 Stereotypies

Stereotypies may be defined as involuntary or unvoluntary (in response to or induced by inner sensory stimulus or unwanted feeling), coordinated, patterned, repetitive, rhythmic, seemingly purposeless movements or utterances (Jankovic, 1994, 2005; Singer, 2009; Sanger et al., 2010; Singer et al., 2010). Although stereotypies typically occur in children with autism or other pervasive developmental disorders, they can also occur in adults. Each child tends to have his or her own repertoire of movements, but typical motor stereotypies encountered in children with autism include body rocking, head nodding, head banging, hand waving, covering ears, fluttering of fingers or hands in front of the face, repetitive and sequential finger movements, eye deviations, lip smacking, and chewing movements, pacing, object fixation, and skin picking. Phonic stereotypies include grunting, moaning, and humming. Stereotypies are usually either continuous, such as those seen in patients with tardive dyskinesias and Rett syndrome, or intermittent, as seen in autism (see Chapter 1). Tics in Tourette syndrome (TS), although mostly intermittent movements, are usually stereotypic in that the movements repeat themselves. In their classic monograph on tics, Meige and Feindel (1907) distinguished between stereotypies and motor tics by describing the latter as acts that are impelling but not impossible to resist, whereas the former, while illogical, are without an irresistible urge. The word “stereotypic,” however, has been removed from the description of tics in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V), expected to be published in 2013. Mannerisms, which are gestures that are peculiar or unique to the individual, may at times seem stereotypic (patterned), but they are usually not continuous. Automatisms in patients with seizures can be viewed as paroxysmal stereotypies (Sadleir et al., 2009). There is often an overlap between stereotypies and self-injurious behavior, such as biting, scratching, and hitting (Jankovic et al., 1998; Schroeder et al., 2001; Lutz et al., 2003).

In addition to motor and phonic types, stereotypies can be classified as either simple (e.g., foot tapping, body rocking) or complex (e.g., complicated rituals, repeatedly sitting down and rising from a chair). Stereotypies can also be described according to the distribution of the predominant site of involvement (orolingual, hand, leg, truncal). The term stereotypy should be used to describe a phenomenologic, not an etiologic, category of hyperkinetic movement disorders. However, recognition of stereotypy as a distinct movement disorder can logically lead from a phenomenologic to an etiologic diagnosis (Table 17.1). Thus, stereotypy is a motor-behavioral disorder that is found most frequently in patients who are in the borderland between neurology and psychiatry.

Table 17.1 Classification of stereotypies


Pathophysiology of stereotypies

There is no clear anatomic-clinical correlation for stereotypies, although it is believed that both cortical and subcortical structures are involved. While dysfunction in the basal ganglia has been implicated in the pathogenesis of certain stereotypies, some studies have also provided evidence for the role of the mesolimbic system, particularly the nucleus accumbens–amygdala pathway, in the pathogenesis of stereotypic movements. Stereotypies with or without associated obsessive-compulsive behavior (OCB) have been observed in patients with structural lesions in different anatomic areas, including bilateral lesions of the medial frontoparietal cortices (Sato et al., 2001; Kwak and Jankovic, 2002) and cerebellum (Hottinger-Blanc et al., 2002). Studies of stereotypies in animals may provide insight into the pathogenesis of habits, rituals, and other repetitive behaviors in humans (Graybiel, 2008).

Stereotypic behavior is common in animals in lower species up to and including the primates and are particularly common in farm and zoo animals that are housed in restraining environments with low stimulation (Garner et al., 2003; Lutz et al., 2003) (Video 17.1). Self-injurious behavior, observed in 14% of housed monkeys, may be viewed as a form of stereotypy (Novak, 2003). Therefore, stereotypy has been viewed as either a self-generating sensory stimulus or a motor expression of underlying tension and anxiety. The repetitive and ritualistic behavior that some animals display has been used as an experimental model of obsessive-compulsive disorder (OCD). Indeed, studies of animal and human stereotypies have provided important insights into relationships between motor function and behavior. Some veterinarian scientists have even suggested changing the nomenclature of stereotypies to OCB, but there is little evidence to indicate that the stereotypic behavior that is observed in animals is driven by underlying obsessions and represents compulsive behavior (Garner et al., 2003; Low, 2003). A study of 136 Romanian children with a history of early institutional care showed that in comparison to those placed in foster care, institutional care was associated with much higher frequency of stereotypies, again highlighting the importance of restrained environment in the pathogenesis of streotypies (Bos et al., 2010). image

Most studies of stereotypic behavior in experimental animals have focused on the role of dopaminergic systems in the basal ganglia and limbic structures. Intrastriatal injection of dopamine and systemic administration of both presynaptically active dopaminergic drugs, such as amphetamine, and postsynaptically active dopamine agonists, such as apomorphine, in rats produce dose-related repetitive sniffing, gnawing, licking, biting, rearing, head bobbing, grooming, and other stereotyped learned activities.

The observation that self-biting behavior induced by dopaminergic drugs in 6-hydroxydopamine rats and monkeys with a unilateral lesion in the ventral medial tegmentum can be blocked by a selective D1 antagonist SCH 23390 suggests that self-injurious behavior is mediated primarily by the D1 receptors (Schroeder et al., 2001). Selective dopamine receptor agonists and antagonists have been used in experimental models to study different effects of D1 and D2 receptors on stereotypic behavior. SKF 38393, a D1 agonist, produced no stereotypic behavior in normal rats, but it did enhance stereotypy induced by apomorphine, a mixed D1 and D2 agonist (Koller and Herbster, 1988). This suggests that the D2 dopamine receptors mediate stereotypic behavior and that activation of the D1 receptors potentiates these D2-mediated effects. Additional evidence for the role of D2 dopamine receptors in the pathogenesis of stereotypies is the observation that upregulation of D2 receptors (e.g., with haloperidol, a selective D2 antagonist) but not of D1 receptors (e.g., with SCH 23390, a selective D1 antagonist), enhanced apomorphine-induced stereotypies (Chipkin et al., 1987). Drug-induced models of stereotypy, however, might not accurately reflect spontaneous or disease-related repetitive behaviors. Using several selective dopaminergic agonists (apomorphine, SKF81297, and quinpirole) as well as intrastriatal administration of the D2 receptor antagonist raclopride to study stereotypic behaviors in the deer mouse model of spontaneous and persistent stereotypy showed that spontaneously emitted and drug-induced stereotypies may have different mechanisms (Presti et al., 2004). Nevertheless, these studies suggest that the striatal dopaminergic system is significantly involved in stereotypic behaviors. Oral and forelimb stereotypies can be induced in the rat with injections of amphetamine into the ventrolateral striatum (Canales et al., 2000), and certain genes can be activated in the striosomes with these drugs when they are administered orally (Canales and Graybiel, 2000). These studies provide further support for basal ganglia involvement in stereotypies. Although there is experimental evidence from rodent and primate studies to support the notion that differential activation of striosomes in the basal ganglia plays an important role in pathophysiology of stereotypies (Saka and Graybiel, 2003), some recent studies found that motor stereotypies do not require enhanced activation of striosomes (Glickstein and Schmauss, 2004). In addition to the basal ganglia, the pontine tegmentum has been implicated in certain stereotypies, particularly repetitive involuntary leg movements that are somewhat similar to the leg movements in patients with restless legs syndrome (Lee et al., 2005). Indeed, bilateral 6-hydroxydopamine (6-OHDA) lesioning in the A11 nucleus of C57BL/6 mice has been associated with an increase in motor, stereotypic, behavior resembling restless legs syndrome activity (Qu et al., 2007).

Besides the classic neurotransmitters, evidence is accumulating in support of involvement of neuropeptides as modulators of stereotypic behavior. For example, microinjection of cholecystokinin and neurotensin into the medial nucleus accumbens markedly potentiated apomorphine-induced stereotypy (Blumstein et al., 1987). Since injection of these peptides into the striatum had no effect on the apomorphine-induced stereotypy, these studies provide additional evidence for the involvement of the limbic system in the pathogenesis of this movement disorder. Improvement in self-injurious behavior observed in autistic children after administration of the opiate blockers naloxone and naltrexone has been interpreted as evidence for the role of endogenous opiates (e.g., β-endorphins) in this abnormal behavior (Sandman, 1988). Additional support for the role of endorphins in self-injurious and stereotypic behavior is the finding of elevated plasma and cerebrospinal fluid levels of β-endorphins in autistic patients with these behavioral abnormalities (Sandman, 1988). More recently, the emphasis has shifted to the serotonin system, supported by the observation that certain animal behaviors improve with serotonin uptake inhibitors (Hugo et al., 2003; Andersen et al., 2010).

Physiologic stereotypies

Certain stereotypies, such as hair twisting, drumming with fingers, tapping of the feet, adduction–abduction, and crossing–uncrossing and other repetitive movements of the legs, may be part of a repertoire of movements, also referred to as mannerisms or habits, seen in otherwise healthy individuals (Bonnet et al., 2010). Developmental and benign movement disorders in childhood include: benign jitteriness or myoclonus of newborn, sleep-related rhythmic movements, spasmus nutans, paroxysmal tonic gaze, benign paroxysmal torticollis, shuddering attacks, transient dystonia of infancy, gratification (masturbatory) behavior, mirror movements, Sandifer syndrome and a variety of normal stereotypies (Bonnet et al., 2010). In infants and children, there seems to be a progression of normal stereotypies (Castellanos et al., 1996). For example, thumb sucking and hand sucking in infancy are later replaced by body rocking, head rolling, and head banging. Some infants demonstrate head stereotypies that resemble bobble-head doll syndrome, sometimes associated with ataxia but without any other neurologic deficit and normal subsequent development (Hottinger-Blanc et al., 2002). A review of 40 “normal” children, aged 9 months to 17 years, with complex hand and arm stereotypies, such as flapping, shaking, clenching, posturing, and other “ritual” movements, showed that the movements can be temporarily suppressed in nearly all when cued (Mahone et al., 2004). Although the children were classified as “normal,” 25% had comorbid attention-deficit hyperactivity disorder (ADHD), and 20% had learning disability, probably due to referral bias, since this group is also known for their work in TS. This referral bias was supported by a relatively high family history of sterereotypies (25%) and tics (33%). A variety of stereotypies can be observed in children (Castellanos et al., 1996; Tan et al., 1997) and young adults (Niehaus et al., 2000) without any other neurologic deficits. We have observed otherwise normal children with persistent head stereotypies similar to the bobble-head syndrome but without abnormal neuroimaging studies. Stereotypies may also occur during development of otherwise normal children who are congenitally blind (Troster et al., 1991) or deaf (Bachara and Phelan, 1980).

Head banging is seen in up to 15% of normal children (Sallustro and Atwell, 1978). Some girls exhibit stereotypic crossing and extending of legs, which actually represents a self-gratifying or masturbatory behavior (Mink and Neil, 1995; Yang et al., 2005; Bonnet et al., 2010) (Video 17.2). Otherwise normal children can also develop bruxism, nail biting, trichotillomania, and other stereotypic behaviors. These behaviors have been often attributed to underlying generalized anxiety disorder or OCD. While motor stereotypies most frequently occur in a setting of mental retardation or autism, in a clinical cohort of 100 normally developing children with motor stereotypies, some involuntary or unvoluntary movements were continued in 62% of the children followed for over 5 years (Harris et al., 2008). Nearly half the children with continuing stereotypies exhibit other comorbidities, including ADHD (30%), tics (18%), and OCB or OCD (10%). It is possible, however, that many of these children had TS, as suggested by the comorbidities typically associated with TS and positive family histories of involuntary movements in 25%. The study also suggested that the clinical course of children who exhibit head nodding may be more favorable than that of children whose motor stereotypy predominantly involves the hands and arms. In another study designed to better characterize stereotypic movements and differentiate them from tics, Freeman and colleagues (2010) evaluated 40 children (31 males), with mean age at onset of stereotypies at 17 months, without self-injurious behavior, intellectual disability, sensory impairment, or an autistic spectrum disorder and found neuropsychiatric comorbidity in 30 (ADHD in 16, tics in 18, developmental coordination disorder in 16, and OCD in 2). In contrast to their parents, children liked their movements, which were usually associated with excitement or imaginative play. Of the 39 children followed for longer than 6 months, the behavior stopped or occurred primarily privately in 25. image

Thus, while stereotypies can occur in otherwise normal individuals, when accompanied by other behavioral and neurologic findings, this form of hyperkinesia usually indicates the presence of an underlying neurologic and/or psychiatric disorder.

Developmental disorders

It is beyond the scope of this chapter to review the current notions about the clinical features and pathogenesis of mental retardation, but the reader is referred to a review of this topic (Nokelainen and Flint, 2002). In one study of 102 institutionalized mentally retarded people, with a mean age of 35 years (range: 21–68 years), 34% exhibited at least one type of stereotypy (rhythmic movement, 26%; bizarre posturing, 13%; object manipulation, 7%; and others) (Dura et al., 1987). In another study, 100 individuals with severe or profound intellectual disability were randomly selected and followed for 26 years (Thompson and Reid, 2002). Their behavior was recorded through carer and psychiatrist ratings using the Modified Manifest Abnormality Scale of the Clinical Interview Schedule. The follow-up evaluations found that stereotypies, emotional abnormalities, eye avoidance, and other behavioral symptoms persist. Although there seems to be an inverse correlation between stereotypies and IQ, stereotypic behavior may be seen even in those who are mildly retarded. In some mental retardation disorders, typically Lesch–Nyhan syndrome, stereotypies are associated with self-injurious behavior (Videos 17.3 and 17.4). Supersensitivity of D1 receptors, possibly in response to abnormal arborization of dopamine neurons in the striatum, has been postulated as a possible mechanism of self-injurious behavior in Lesch–Nyhan syndrome (Jankovic et al., 1988

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Autism is a type of pervasive developmental disorder (PDD), sometimes referred to as autistic spectrum disorders, with onset during infancy or childhood, characterized by impairment in reciprocal social and interpersonal interactions, impairment in verbal and nonverbal communication, markedly restricted repertoire of activities and interests, and stereotyped movements (Bodfish et al., 2001; Gritti et al., 2003; Lam et al., 2008) (Table 17.2). Many autistic patients also exhibit other abnormal behaviors, such as preoccupations, circumscribed interest patterns, abnormal object attachments, cognitive rigidity, and exaggerated sensory responses. Earlier studies have suggested that about 0.1% of all children are autistic (Sugiyama and Abe, 1989), but more recent epidemiologic studies have estimated that the prevalence of autistic disorders and related pervasive developmental disorders ranges between 0.3% (Yeargin-Allsopp et al., 2003) and 0.6% (Chakrabarti and Fombonne, 2001). In children and adults with autism of any cause, stereotypies and other self-stimulatory activities constitute the most recognizable symptoms. Typical stereotypies that are seen in autistic individuals include facial grimacing, staring at flickering light, waving objects in front of the eyes, producing repetitive sounds, arm flapping, rhythmic body rocking, repetitive touching, feeling and smelling of objects, jumping, walking on toes, and unusual hand and body postures. In a study of motor stereotypies recorded during 15 minutes of videos of standardized play sessions in 277 children (209 males, 68 females), 129 with autistic disorder and 148 cognitively-matched non-autistic developmentally disordered children, hand/finger repetitive movements and pacing, jumping, and spinning movements during gait were two types of stereotypies that were especially suggestive of autism (Goldman et al., 2009).

Table 17.2 Clinical features associated with autism

The motor manifestations are often associated with insensitivity or excessive sensitivity to sensory stimuli including pain and extremes of temperature, preoccupations with perceptual sensations such as lights or odors, insistence on preservation of sameness, and absence of fear or other emotional reactions. Self-stimulatory and self-injurious behaviors, such as self-biting and head banging, are also common. In addition to these and other behavioral and developmental abnormalities, some autistic individuals have isolated areas of remarkable and sometimes spectacular mental skills, the so-called savant syndrome (Miller, 1999; Treffert, 1999). The mechanism of the savant phenotype in the setting of autism is not well understood but studies of one genetic model of autism, the Shank1 knock-out mice, may provide some insight (Hung et al., 2008). The Shank family of postsynaptic scaffold proteins has been found to be abundantly present in the postsynaptic density of central excitatory synapses. When these postsynaptic proteins are altered as in Shank1 knock-out mice, surprisingly the mice displayed enhanced performance in a spatial learning task, although their long-term memory retention in this task was impaired (Hung et al., 2008). The authors suggested that the superior learning ability of these mutant mice was similar to what has been observed human autistic savants.

There are many causes of autism, including fragile X syndrome and a variety of eponymically classified types such as Kanner, Heller, Asperger, Down, and Rett syndromes (Ringman and Jankovic, 2000). Asperger syndrome is one of the most common forms of autism, found in 1 to 3 children in 1000 (Gillberg, 1989). Characterized by social isolation in combination with odd and eccentric behavior, Asperger syndrome shares many features with infantile autism. Several studies have indeed noted an overlap in various clinical and demographic characteristics between Asperger syndrome and infantile autism (Szatmari et al., 1989

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