Stereotypies

Introduction

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 ( , ; ; ; ). Although each child tends to have his or her own repertoire of movements, typical motor stereotypies include body rocking, head nodding, head banging, hand waving, covering ears, fluttering of fingers in front of the face, repetitive and sequential finger movements, eye deviations, lip smacking, and chewing movements, pacing, object fixation, skin picking; phonic stereotypies include grunting, moaning, and humming. Stereotypies are usually either continuous (uninterrupted), such as those seen in patients with tardive dyskinesia, intellectual disability or autism, or continual (with interruption), such as the stereotypic tics seen in patients with Tourette syndrome (TS). They can be either continual or intermittent in patients with intellectual disability or autism. Mannerisms, which are gestures that are peculiar or unique to the individual, may at times seem stereotypic (patterned), but they are usually not continual.

Automatisms in patients with seizures can be viewed as paroxysmal stereotypies ( ). These are usually manifested by repetitive, rhythmic behaviors that occur during frontal lobe seizures and in a reproducible pattern for a given patient. In 17 patients with frontal lobe epilepsy who manifested motor and/or verbal stereotypies during recordings with depth electrodes (stereoelectroencephalography) as part of presurgical evaluation, the progression of stereotypies correlated with a rostrocaudal gradient within the frontal lobes ( ).

One unusual form of stereotypic seizures is the “sunflower syndrome”, a form of photosensitive epilepsy characterized by paroxysmal episodes of hand waving stereotypies, induced by the patients when they look toward a light source, often the sun, and wave one hand with abducted fingers in front of their face ( ; ). This may be associated with eye fluttering or blinking, and this may evolve into generalized tonic-clonic and other seizures. EEG usually shows a normal background with 3–4 Hz spike waves ± polyspike waves as well as a photoparoxysmal response ( ). It usually responds to valproate or lamotrigine, but not to levetiracetam.

There is often an overlap between stereotypies and self-injurious behavior (SIB), such as biting, scratching, and hitting ( ; ; ; ). SIB, defined as “deliberate, repetitive and persistent behaviors that are directed towards the body and lead to physical injury”, may be seen in a variety neurological, developmental, metabolic and genetic disorders ( ).

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, sitting down in and rising from a chair). Stereotypies also can 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 16.1 ). Thus, stereotypy is a motor-behavioral disorder that is found most frequently in patients who are in the borderland between neurology and psychiatry.

There are no validated stereotypy scales designed to measure severity and response to treatment. In one study of behavioral intervention, the Stereotypy Severity Scale was used, which was modified from the Yale Global Tic Severity Scale ( ).

Pathophysiology of stereotypies

There is no clear anatomic-clinical correlation for stereotypies, although it is thought that both cortical and subcortical structures are involved. Although 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 ( ; ) and cerebellum ( ). Some have suggested motor stereotypy is a manifestation of poor sensorimotor integration, but further studies are needed to elucidate the pathophysiologic processes of this hyperkinetic disorder ( ).

Studies of stereotypies in animals may provide insight into the pathogenesis of habits, rituals, and other repetitive behaviors in humans ( ). 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 ( ; ; ) ( Video 16.1 ). SIB, observed in 14% of housed monkeys, may be viewed as a form of stereotypy ( ). 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 ( ; ).

Video 16.1 Animal stereotypies.

The pathophysiology of stereotypies is not well understood. In one study of children with “primary motor stereotypies” movement-related cortical potentials (MRCPs), which precede and are associated with activation of cortical areas involved in the generation of self-initiated voluntary movements, no such potentials were found before the occurrence of a complex stereotypy ( ). Because the premotor cortical areas are apparently not involved in the preparation of these complex movements, stereotypies may be viewed as truly involuntary movements. It is not clear whether the underlying pathophysiologic mechanisms are different in other forms of stereotypies.

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 SIB is mediated primarily by the D1 receptors ( ). 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 ( ). 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 ( ). 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) and 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 ( ). 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 ( ), and certain genes can be activated in the striasomes with these drugs when they are administered orally ( ). These studies provide further support for a 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 ( ), some studies found that motor stereotypies do not require enhanced activation of striosomes ( ).

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 movement in patients with restless legs syndrome (RLS) ( ).

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 ( ). Because 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 SIB 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., beta-endorphins) in this abnormal behavior ( ; ). Additional support for the role of endorphins in self-injurious and stereotypic behavior is the finding of elevated plasma and cerebrospinal fluid levels of beta-endorphins in autistic patients with these behavioral abnormalities ( ). The emphasis has shifted to the serotonin system, supported by the observation that certain animal behaviors improve with serotonin uptake inhibitors ( ).

Physiologic stereotypies

Physiologic stereotypies are stereotypic movements that are not due to any identifiable cause or associated with abnormal pathologic features. They are reported in about 2% to 4% of otherwise normally developing children ( ). 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 normal individuals ( ). 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 behavior, mirror movements, Sandifer syndrome, and a variety of normal stereotypies ( ). In infants and children, there seems to be a progression of normal stereotypies ( ). 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 ( ). 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 ( ). Although the children were classified as “normal,” 25% had comorbid attention deficit–hyperactivity disorder (ADHD), and 20% had learning disability, probably the result of referral bias, because this group is also known for their work in TS. This was supported by a relatively high family history of stereotypies (25%) and tics (33%). A variety of stereotypies can be observed in children ( ; ) and young adults ( ) 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 ( ) or deaf ( ).

Head banging is seen in up to 15% of normal children ( ). Some girls exhibit stereotypic crossing and extending of legs, which actually represents a self-gratifying or masturbatory behavior ( ; ; ) ( Video 16.2 ). Otherwise normal children can also develop bruxism, nail biting, trichotillomania, and other stereotypic behaviors. These behaviors often have been attributed to underlying generalized anxiety disorder or OCD. However, when stereotypy is accompanied by other behavioral and neurologic findings, it usually indicates the presence of a serious underlying neurologic and/or psychiatric disorder. Although motor stereotypies most frequently occur in a setting of intellectual disability or autism, in a clinical cohort of 100 normally developing children with motor stereotypies, some involuntary or unvoluntary movements continued in 62% of the children followed for over 5 years ( ). Nearly half the children 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 those whose motor stereotypy predominantly involves the hands and arms. In another study designed to better characterize stereotypic movements and differentiate them from tics, evaluated 40 children (31 males), with mean age at onset of stereotypies at 17 months, without SIB, 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 was occurred primarily privately in 25. In one study, based on a telephone survey of parents of 49 patients with primary stereotypies (mean age at time of follow-up 13.1 ± 3.2 years, range 9.0 to 20.8 years) the involuntary movements began in nearly all children before the age of 3 years and persisted for 10 to 15 years in half of the subjects ( ). Furthermore, over a third had a family history of stereotypies. In this series, 21% of had stereotypies less than once a day (continual). Because patients with comorbid tics and ADHD, noted in 22% and 63% of subjects, respectively, were included in the study, it is not clear whether the findings are generalizable to a population without these comorbidities.

Video 16.2 Self-gratifying behavior.

Pathologic stereotypies