Juvenile Huntington disease
Oct. 24, 2022
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Stereotypic behaviors are seen in a number of neurologic and psychiatric conditions, as well as in normal people and in animals. They are common in autism; Tourette syndrome; retardation; psychotic disorders, including N-methyl-d-aspartate receptor antibody (NMDAR) encephalitis; neuroleptic-induced tardive syndromes and may be present in some degenerative disorders. Some are medication induced. Head-banging and rocking behaviors are seen in normal children who outgrow them. They are on a continuum with obsessive compulsive spectrum disorders, the umbrella term now used for tics, hair pulling, and a variety of other repetitive, purposeless behaviors. In this article, the authors review these behaviors and put them into the context of the various disorders in which they occur. Stereotypies help define some of the autistic disorders. Treatment is discussed only briefly because evidence to support any intervention is scant.
• Stereotypies are common behaviors present in humans as well as animals and may or may not reflect pathology.
• Stereotypies may represent a transient phenomenon in children, but may be associated with a variety of severe neurologic disorders, including specific biochemical disorders such as Rett syndrome and Lesch Nyhan disease, but also in the whole spectrum of autistic disorders and pervasive developmental disorders.
• Stereotypic disorders may require intervention, especially when harmful, but often do not. Treatment is highly individualized, involving medications or behavioral interventions and often unsuccessful.
• Stereotypies may occur in neurdegenerative dementing illnesses.
There have been numerous definitions given for the term “stereotypy.” Generally, it has been considered to mean a purposeless, fixed form of expression or response that may interfere with normal behavior. Stereotypies have long been recognized as a possible sign of behavioral pathology. Its occurrence in those with intellectual disability, autism, and schizophrenia has been well established. Perhaps less well appreciated is its occurrence in normal children in the form of head banging, head rolling, and body rocking (95; 76).
Authors writing at the beginning of the 20th century described stereotypy as a central problem in schizophrenia. "The tendency to stereotype produces the inclination to cling to one idea to which the patient then returns again and again," stated Bleuler about schizophrenia (16). This tendency causes, "derailment of . . . associational activity" leading to fixed answers to various questions as well as fixed patterns of motor activities (16). Motor stereotypy is still encountered in schizophrenia, more obviously late in the course (73), but early as well (29), and may occur in catatonia as well (100).
Art depicting the insane and depraved with bizarre facial expressions, abnormal postures, and peculiar gestures consistent with stereotypy predate modern medicine (61).
Caged animals that develop stereotyped pacing have undoubtedly been observed since time immemorial. Pacing occurs in imprisoned humans as well. Experiments on primates in the 1950s revealed that certain stereotyped behaviors, due to social and sensory deprivation in particular, led to permanent stereotypies that could not be altered if the deficit occurred during critical periods in brain development (89). Stereotypies in commercially raised animals have raised concerns about the increasingly efficient but less humane conditions of modern animal husbandry (31). However, laboratory scientists have pointed out that pacing behavior may be pathologic in some species but not others (86). In certain strains of horses, stereotyped behaviors are common (75). Human studies in autistic children reported that stereotypy interfered with learning (56) and implied that controlling stereotypic behavior was a necessary precondition for learning. Thus, understanding stereotypy became more important for developing rational therapies.
It must be noted that stereotypies may also occur during development of congenitally blind (111) or deaf children (07; 101; 17; 96) who are otherwise normal. Certain movements that give an appearance of restlessness may be part of an individual’s repertoire of movements, also referred to as mannerisms or habits, and are seen in otherwise normal individuals. One of the more common stereotypies manifests as restless movements in the legs, described as “leg stereotypy disorder” (52) or leg stereotypy syndrome (63), which is defined as a repetitive, continuous movement present almost exclusively in the legs while the patient is seated. In contrast to restless legs syndrome, which usually occurs at night, there is no diurnal variation in leg stereotypy disorder, and many individuals affected by this condition may not be aware that they have the repetitive movement until it is pointed out to them. Frequently familial, the epidemiology, pathophysiology, or treatment of leg stereotypy disorder have not been studied. Comparing 92 subjects with restless legs syndrome, Parkinson disease, Tourette syndrome, and tardive dyskinesia with their companions of similar age, Lotia and colleagues reported leg stereotypy syndrome in 7% of individuals in the control group and 17% in the movement disorder group (63). The movements involved predominantly one leg, and all had a family history of a similar disorder.
The concept of a "tardive stereotypy" (104; 51; 70; 83) was introduced to describe a neuroleptic drug-induced condition that had previously been classified as a complex set of superimposed tardive movement disorders centering about dystonia but also including dyskinesias (choreoathetosis) and pseudoakathisia. There are differences of opinion about the nomenclature of the phenomenological distinctions between tardive stereotypies and tardive dyskinesias, as the latter usually do not clearly fit the definition of a choreoathetoid movement.
Until the 1990s, the concept of stereotypic behaviors, both as a part of a pathologic mental syndrome and as a movement disorder, fell outside the usual purview of neurology and within the disciplines of psychiatry, developmental medicine, and psychology. As the border between neurology and psychiatry continues to blur, stereotypy has become a subject of concern for neurologists, psychiatrists, and pediatricians (62; 50; 08). With the recognition of dopamine agonist-induced compulsive behaviors in Parkinson disease, such as gambling, hypersexuality, “punding,” and, to a lesser extent, in restless legs syndrome, the underlying mechanisms of “forced” behaviors have attracted increasing scientific attention.
This review of stereotypy is devoted to movements alone and not to stereotypic verbal responses to stimuli. The exact definition of stereotypy varies with different authors. Lohr and Wisniewski have described stereotypies as appearing to be "fragments of a normal action that are continually repeated without purposes . . . Some may simply be reiterated bizarre purposeless acts . . . " without conscious control, although consciousness is intact. "The movements are usually uniform, but at times incomplete forms of a given stereotypy may be observed" (62). Jankovic defines stereotypy as an "involuntary or unvoluntary [unvoluntary defined as a physical response to an inner driving force such as restlessness or psychic pain] . . . coordinated, patterned, repetitive, rhythmic, purposeless but seemingly purposeful or ritualistic, movement, posture or utterance" (50). Tan and colleagues, however, believe that stereotypies "can be suppressed voluntarily without a buildup of inner tension," thus, distinguishing them from tics (107). Another definition defines motor stereotypies as “involuntary, patterned, coordinated, repetitive, rhythmic, and nonreflexive features, (which) typically last for seconds to minutes, tend to occur in clusters, appear many times per day, and are associated with periods of stress, excitement, fatigue, or boredom” and are readily suppressible (64). Another definition was offered in 2012 in an attempt to distinguish stereotypies from tics and other repeated movement disorders (33): “a non–goal-directed movement pattern that is repeated continuously for a period of time in the same form and on multiple occasions, and which is typically distractible.” In farm animals, a consensus definition of stereotypy is a repetitive action, fixed in form and orientation, that serves no obvious function (28).
Stereotypies can be classified into simple movements (such as rocking, tapping, hugging, and lip biting) and complex movements (which include ritualistic behaviors such as spitting into a hand and smearing it in a particular fashion, or running forward a set number of paces then running backwards, repeated raising and lowering of the arms, waving and flapping of the arms and hands, and finger wiggling) (50; 64).
The most typical stereotypies include rocking, flapping, hugging, self-touching, patting, grunting, foot tapping, leg swinging, and hair pulling.
Review of videos of patients, such as those with autism, may be useful in characterizing and classifying stereotypies (41).
In normal development, children may rock back and forth, roll (or even bang) their heads. These behaviors have been reported to occur in approximately 20% of normal children (57; 95) in isolation and, therefore, not evidence of pathology. They are generally part of sleep behavior, seen in sleep transitions and are considered “soothing” behaviors. They become less common with age. Certain patterned motor behaviors are considered normal in adults and include foot tapping, crossing and uncrossing the legs, and tapping fingers on a chair arm. Some stereotypic behaviors may be associated with obsessive compulsive symptoms; it may not be clear where normal ends and pathology begins (78). In a study of normal and autistic children with stereotypies, the authors noted that stereotypies associated with neurologic disorders tended to be longer in duration, more frequently present, more complex, and more often to contain vocalizations (38).
Stereotypies must be distinguished from mannerisms, tics, and other complex repetitive acts. A mannerism is an odd, idiosyncratic method of performing a task that is unique to an individual and serves no apparent function (ie, a person who cocks an arm in a peculiar way in order to drink from a cup; a ballplayer who performs ritualistic acts "for luck."). However, this use of the term "mannerism" is not universally agreed on, and Lohr and Wisniewski assert that inherent in a manneristic behavior is an obvious "unusual or grotesque" component that would signal to anyone in any culture the obvious abnormality of the behavior (62).
Compulsions such as repetitive hand washing, touching, checking, hair pulling, spitting, as well as the more complex ritualistic behavior that also occurs in obsessive compulsive disorder form another category of stereotypic behavior. In these cases, the activity serves an inner psychic need that may be overwhelming. In Lesch-Nyhan syndrome, for example, children will ask to be restrained to keep themselves from painful self-mutilation. When these movements occur in response to a cognitive rather than a sensory intrusion, the movement is considered to be a manifestation of obsessive compulsive disorder (114).
The term “obsessive compulsive spectrum disorder” is now used to describe obsessive behaviors that result from sensory rather than cognitive intrusions (114). Nail biting, hair pulling, and tics are classified as obsessive compulsive spectrum disorder.
Simple tics are abrupt in onset, brief, simple movements. Complex tics such as repetitive head shaking, stooping, throwing oneself on the ground, and gesturing may be difficult to distinguish from the movements associated with obsessive compulsive disorder that so frequently accompanies Tourette syndrome. Occasionally, children with Tourette syndrome are misdiagnosed as suffering from autism as a result of these stereotypies (50). Vocalizations may be part of a stereotypy repertoire (65).
Akathisia is defined by the inability to keep still due to an inner need to move. Patients with akathisia tend to stand after being seated for more than a few seconds, march in place when standing, shift weight from 1 foot to the other, and sometimes rub their hands over their arms. Akathisia comes in an acute form induced by dopamine-blocking drugs, a tardive form, also induced by neuroleptics, and occurs in association with idiopathic Parkinson disease.
A perseveration is a repeated movement. It generally occurs immediately following a normal goal directed action, but may break down into a fragment of the original movement. The perseverated movement will stop, but will be replaced by an entirely new behavior, unrelated to the previous one and will not recur spontaneously, unlike a stereotypy, which recurs endlessly.
Although stereotypies vary from syndrome to syndrome, there is a great deal of overlap. They are common in the autistic, the intellectually disabled, the severely psychotic, and the congenitally blind, but not in other populations. Although it is common to find stereotypy in all of these syndromes, it is much more likely to be associated with autism (66). Autism is a specific behavioral syndrome, resulting from abnormal brain development. It is distinct from the more general term intellectual disability, although most autistic children have IQ scores below 70 (37). Stereotypy is a prominent feature of this syndrome. The most common stereotypies are facial grimacing, staring at flickering lights, waving objects in front of the eyes, producing repetitive sounds, arm flapping, rhythmic body rocking, repetitive touching, feeling and smelling objects, jumping, walking on toes, and unusual hand and body gesturing (50). It has even been proposed that stereotypies are relatively specific indicators of autism in children with communication problems (19; 66). Stereotypic behaviors are associated with more bizarre and less integrated behavior in Down syndrome (25). All individuals with Rett syndrome have stereotypies, which differ between typical and atypical syndrome variants, eg, the latter is more likely to have hand flapping, hair pulling, bruxism, retropulsion, and lip protrusion (27). A study of 1123 girls and women with Rett syndrome found that 922 had stereotypies involving the hands (105), with hand mouthing and clapping or tapping seen more often than the classic hand wringing/washing. These tended to become less severe over time, but the change in severity had an uncertain relationship to hand function.
Congenitally blind children display similar stereotypies to the mentally retarded and autistic, but with less self-injurious behavior. Eye poking is the most common movement, but body rocking, repetitive manipulation, finger sucking, head rocking, and other movements occur as well (111).
"Punding," a peculiar stereotypy induced by amphetamine and cocaine use in adults, is a repetitive handling and intense fascination in handling common objects, such as moving a ball in one's hand, or repeated aimless self-injurious picking (34; 20). It may involve repetitive dismantling and rebuilding of an object. In children, amphetamine poisoning may induce head banging, finger biting, and violent purposeless movements (35). This has been described as an uncommon but not rare problem in Parkinson disease patients treated with dopamine agonists (72). Two published cases have been ascribed to strokes: 1 in the putamen and the other in the brainstem (67; 77).
Tardive stereotypies, those induced by chronic (greater than 3-month) exposure to neuroleptic drugs, occur in a high percentage of patients with tardive dyskinesia (104; 51; 70). These stereotypies are most common in the orolingual-facial region, followed by the lower limbs, upper limbs, trunk, and pelvis. The orolingual-facial movements involve lip puckering as well as tongue writhing and protrusion. Vocalizations are humming and belching. Leg movements are tapping, crossing and swinging legs, and kicking. Arm movements are rubbing, picking, and thumb twiddling. These movements can be difficult to distinguish from the stereotypies in neuroleptic-exposed children with autism (69).
The stereotypies in psychotic patients are not significantly different from those in other disorders; however, stereotypies tend to develop in the later stages of the disease (73). Distinguishing a psychosis-driven behavior (ie, pacing, rocking, or jumping) from akathisia can be impossible when the patient is uncommunicative. Stereotypies are an important component of catatonia, a syndrome most commonly seen in psychotic affective disorders and schizophrenia. Stereotypies may be seen in “functional” disorders, that is, disorders that are either forms of malingering or conversion disorders. They are often abrupt in onset and are not part of a typical neurologic or psychiatric disorder associated with stereotypes (09). They are also part of the spectrum of levodopa-induced dyskinesias in treated Parkinson disease patients (52).
In the syndromes of autism and intellectual disability, stereotypies are often associated with self-injurious behavior (90). Body rocking in particular has been associated with self-hitting (91). Typical clinical syndromes include nail biting, finger biting, punching objects, hitting oneself, and head banging. However, self-injury may also be seen in Tourette syndrome, Lesch-Nyhan syndrome, neuroacanthocytosis, tuberous sclerosis, and in psychiatric patients. Some patients require special apparatuses or environments to reduce the injuries. Self-injuries due to psychosis tend to be the result of a few major traumas (ie, the result of an angry outburst, a suicide attempt, or deliberate self-mutilation). For example, a schizophrenic enucleated 1 eye after killing her baby because of command hallucinations. Persistent head banging, eye poking, hitting, and self-chewing at a low level that results in injury is uncommon even among severely psychotic patients.
Hyperkinetic movements, including stereotypies, are a discerning characteristic of a syndrome caused by GNAO1 mutations and may be seen in 1 form of the mutation of the FOXG1 gene, but not others (30; 118). It has also been reported in other genetic disorders (99).
Stereotypies may accompany dementias, particularly fronto-temporal dementias, in which motor and vocal stereotypies occur in over 75% of patients whose diagnosis was confirmed by autopsy (08). New-onset stereotypies have been noted in Down syndrome patients who, for reasons so far not understood, undergo acute cognitive declines (71).
Automatisms due to complex partial seizures should be easy to distinguish from stereotypies. Automatisms are sudden in onset, occur in a clouded sensorium, are time limited, do not reliably occur following periods of stress, may occur during sleep, may be followed by a postictal behavioral change, and occur randomly.
In a likely stretch of the term, 1 author posited that yawning was a form of genetically stereotyped behavior induced by certain emotional stimuli (115).
Catatonia is a disorder that may occur as part of a primary psychiatric disorder, usually an affective disorder, but also schizophrenia, defined by the presence of certain features, most of which may also be present in other psychiatric disorders, including stereotypies (22). Interestingly, NMDA receptor antibody encephalitis, produces catatonia in 60%, one third of whom exhibit stereotypies (100), generally as a late feature.
Stereotypy can also be a functional (psychogenic) movement disorder with important distinguishing features being abrupt onset, distractibility, movements not consistent with known disorders, and unexplained fluctuations in symptom severity (09). Functional stereotypies most commonly manifest as orolingual, limb, or trunk movements and least commonly as respiratory movements.
The prognosis for stereotypies is variable. For most childhood-onset stereotypies they appear to plateau at some stage, worsening transiently with stress. In a study of 10 non-mentally retarded, nonautistic children under the age of 8 years, who developed the stereotypies between the ages of 4 months and 6 years, all but 2 continued to have the movements after 3.5 to 10 years after initial evaluation (107). A study from a university movement disorders clinic in the U.S. (80), hence, a highly skewed population, reported long-term follow-up on children who were otherwise normal except for their stereotypies and found that at a mean of 13 years after evaluation, 48 of 49 still had the stereotypies. Thirty-seven had improved and only 1 reported worse movements. A high percentage developed obsessive compulsive disorders, attention deficit disorders, anxiety, or Tourette syndrome. Almost all achieved average or above average grades in school. In congenital blindness the children improve after the second year. One review article found support for vitamin B12 in treating behaviors and stereotypies (92). In tardive stereotypy, however, the process may worsen with continued drug exposure, although data are scant. Usually, patients with tardive stereotypy require an antipsychotic agent, but their medications are frequently changed in order to try to ameliorate the dyskinesia, making interpretation of changes over time difficult.
The major complication of stereotypy is self-injurious behavior. Stereotypy may interfere with learning (116) and adaptation, and it clearly interferes with socialization.
An elderly man with dementia began to pick at his skin to the point of causing bleeding and occasional infections. He denied itching and appeared more to be probing than scratching. He was not thought to be psychotic, although he claimed that he was digging insects from his skin.
The mechanisms for stereotypy are unknown. It is generally accepted that some stereotypies, if not most, occur as the result of self-stimulatory behavior, for instance, in congenitally blind children or in animals that are deprived of their mothers. This hypothesis is extrapolated from the similarity of the phenomenology as well as the fact that many retarded and autistic children are less interactive with their environment than normals, and that stereotypies clearly arise with sensory deprivation (ie, caging) or congenital blindness and deafness (43). Because certain stereotyped behaviors induced early in animal development may become permanent, and because certain stereotypies are due to degenerative neurologic disorders or drugs, it is clear that some stereotypies are due either to structural or biochemical brain disorders. A large body of literature points to the involvement of dopamine and the basal ganglia in stereotyped behaviors in both humans and animals, but this most likely represents only 1 potential mechanism. It is of interest that neuroleptics are sometimes useful in reducing stereotypies, yet a case of postencephalitic stereotyped involuntary movements associated with parkinsonism responded to L-dopa (84), and another responded to electroconvulsive therapy (60). Amphetamine, which enhances catecholamine secretion, induces similar behavioral stereotypies in animals as it does in humans, with repetitive sniffing, picking, repeated explorations, etc.
Stereotypies are induced by microinjections of amphetamine into the striatum of rats and blocked by dopamine receptor blocking agents. Mice bred to be dopamine deficient will develop intense stereotypies when treated with carbidopa-levodopa. These are blocked by dopamine D1 receptor blockade (26) but not dopamine D2 receptor antagonists. Frontal lesions will cause similar stereotypies in primates as amphetamine; in rats, they will exacerbate amphetamine effects (88). Stereotypies also have been rarely the result of stroke (68).
It is unlikely that simple neurochemical or neurophysiological explanations will be found for stereotypies. Although dopamine is implicated in the treatment and development of stereotypic behavior, animal work implicates neuropeptides as well (87).
It is clear that there are multiple distinct causes for stereotypies that may not share common anatomical or biochemical pathways. Genetics plays an important role as well. In a study of genetic influences in Rett syndrome, a disorder of girls in which hand stereotypies are a cardinal feature, it was found that the presence or absence of an abnormality in the MECP2 gene conferred altered probabilities of having stereotypies other than hand wringing (108). In an analysis of 83 patients with Rett syndrome, 53 with MECP2 gene mutation, 62% had hand stereotypies, and in combination with bruxism, these features seemed to differentiate between Rett patients with and without mutation (109). Although typically diagnosed in young girls, the diagnosis of Rett syndrome should be also considered adult women with stereotypies and psychomotor retardation (93). Another gene implicated in autism is the CNTNAP2 gene on chromosome 7q35 that codes for contactin-associated protein-like 2, a neurexin family member involved in myelination of axons (06).
Rare causes for stereotypy include stroke (67; 77), nonketotic hyperglycemia (10), and Wilson disease (119). Infectious encephalitis, and the anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, may also cause stereotypies (98). NMDAR encephalitis is of particular concern because these patients are most commonly initially seen by psychiatrists due to abnormal behavior, but movement disorders, including stereotypies are common (11; 58).
Frequently there are numerous mechanisms to explain stereotypic motor behaviors, both simple and complex. For example, such relatively simple maneuvers as hand clasping ("washing," "wringing"), which are typical of Rett syndrome (46; 42), have been reported as a tardive stereotypy induced by neuroleptic (53), and they occur in depressed or despondent people as well as in normals. Some work points to a developmental pattern in which low interest in objects in the environment precedes the onset of stereotypies in some inherited disorders (97), suggesting a “natural” progression of behaviors.
Stereotypy is induced in primates simply by caging them (89). When put in cages alone, pacing, circling, and jumping frequently occur. These may progress to self-injurious behavior. Studies of stereotypies in animals may provide insight into the pathogenesis of habits, rituals, and other repetitive behaviors in humans (45).
Social isolation and sensory deprivation also induce "deprivation" stereotypies in monkeys, which include body rocking, head rolling, self-clasping, and digit sucking. Self-mutilation in the form of biting, head banging, eye-poking, and complex hand movements also occur (89). Well-developed deprivation stereotypies are sometimes impossible to reverse and are believed to be the result of permanent deprivation-induced changes in the central nervous system in a manner analogous to the inability of kittens to develop a normal visual system when deprived of light during the critical period in development. The congenitally blind may develop stereotypies (54) that do not occur in late acquired blindness. The similarity of these behaviors to those seen in autistic children suggests the possibility that autistic stereotypies may be deprivation stereotypies due to abnormal sensation or social isolation and, hence, a secondary phenomenon.
Although the stereotyped behaviors that are common in all forms of intellectual disability suggest a nonspecific response to diffuse abnormal brain function, the typical occurrence of specific stereotypies in specific disorders implies a specific pathophysiology for stereotypies in some cases. In Rett syndrome, an X-linked disorder, hand wringing is typically seen.
The genetic abnormality in Rett syndrome has been identified. Although the disorder is primarily sporadic, several different genetic lesions have been found, including missense, nonsense, and frame shift mutations. The abnormal protein binds to methylated DNA causing abnormal packing of chromatin. The abnormal protein, thus, acts as a transcriptional repressor leading to a loss of function (04; 02). An increase in stereotyped behaviors has been noted in families in which there are 2 autistic children, suggestive of a possible genetic link (85). Several candidate genes have been identified for various autistic spectrum disorders (74). It is likely that particular stereotypic behaviors will reflect environmental input affecting a disordered substrate. With amphetamine psychosis, "punding" occurs, with repetitive simple or complex maneuvers. Neuroleptic-induced tardive stereotypy is fairly characteristic and usually easy to identify (104; 70), so that specific stereotypies may result from specific brain alterations, whereas other stereotypies may be nonspecific and either pathologic or normal.
Stereotypies in children, abnormal and normal, are different in different social situations (117), depending on whether the child is happy or distressed.
It is difficult to extrapolate from animal studies to people. Much animal work has focused on dopaminergic systems. Systemic amphetamines and dopamine agonists produce sniffing, gnawing, licking, biting, and other repetitive behaviors in rats (50). In monkeys, interestingly, amphetamine reduced the cage-induced stereotypy before it induced new stereotyped behaviors such as staring, self-grooming, and grabbing at the air (89). In rodents, the stereotyped behavior induced by dopamine agonists and amphetamine, which increases catecholaminergic release, is blocked by neuroleptics. Oral and forelimb stereotypies can be induced in the rat with injections of amphetamine into the ventrolateral striatum (23) and are blocked by lidocaine injections into the pars reticulata of the substantia nigra in the same model. This suggests that basal ganglia motor circuits are involved in the development of some stereotypies. Studies in rats sensitive to cocaine, in which increased dopamine secretion is induced, indicate that during the time of the strong motor stereotypic behavior, there is a marked increase in dopamine release and also a marked decrease in cholinergic transmission in the basal ganglia (03). This suggests the possible utility of cholinergic benefit in stereotypies induced by dopaminergic stimulation, such as punding. The development of stereotypies produced by oral medications appears to be associated with the activation of certain genes in striosomes (24), again supporting a basal ganglia circuit involvement in stereotypies, and also suggesting a nonneurotransmitter receptor alteration. To date, however, morphologically identifiable changes have not been found in the basal ganglia of autistic children. The numbers studied have been small, and neuropathological techniques are evolving quickly, so this observation may change at any time (82).
Rhythmic movement disorder, which includes head-banging and body-rocking, occurs in up to 67% of normal children under 1 year of age and is typically outgrown by 4 years of age.
The epidemiology of stereotypy varies with the underlying etiology and the severity of the condition. Rett syndrome occurs only among females because the absence of a normal allele on the X chromosome in males is lethal. It has an incidence of about 1 in 10,000 to 15,000 girls. Autism is about 4 times more common in boys than girls and has an incidence of 4 to 5 per 100,000 births. Intellectual disability syndromes also vary in frequency by gender, with fragile X syndrome being considerably more common among males, although not completely bypassing carrier females. Because fragile X is the most common cause of intellectual disability among males, it shifts the epidemiology of childhood-onset stereotypies to a male preponderance. In a study of 102 "severe and profoundly retarded" nonambulatory adult in-patients at 1 institution, 34% exhibited at least 1 of 5 noted stereotypic behaviors (rhythmic movement such as rocking or hand flapping, bizarre posturing, self-restraint, object manipulation, or other movements). Rhythmic movements occurred in 26% and were twice as common as the second most common stereotypy, "bizarre posturing" (32). These profoundly mentally retarded adults presumably represented a wide spectrum of etiologies.
There are many forms of pervasive developmental disorders, such as infantile autism and Asperger syndrome, in which stereotypies represent a significant motor component. Asperger syndrome is characterized by social isolation in combination with odd and eccentric behavior, as well as poor motor skills, stiff and awkward gait (without arm-swing), and delayed speech development (40; 106). MRI may show nonspecific evidence of cortical and subcortical abnormalities (15). Because the Asperger children are generally brighter, it has been suggested that this syndrome merely represents a mild variant of autism. Their stereotypies have been found to be very similar in type and frequency to intelligence-matched children with other forms of autism (103).
A study of 85 congenitally blind but otherwise normal children revealed stereotypy occurring in all of the children at some point in a 1-week period. Over 30% of the children displayed stereotypies hourly. Stereotypies worsened between years 1 and 2, then decreased (111).
Tardive stereotypy, the most common adult-acquired stereotypy, was more common in "women of advanced age" but may be seen in any age group, including children (104; 70).
Stereotypy as a manifestation of psychosis mainly occurs prior to treatment with neuroleptics. Because the antipsychotic drugs induce tardive stereotypy, it may no longer be possible to study stereotypy in untreated psychosis. However, of 138 consecutively admitted patients to a psychiatric ward 42 displayed moderate to severe mannerisms or stereotypy (81).
Self-injurious behavior occurs in 10% to 20% of the institutionalized retarded and is rated as severe in up to half of these cases. The incidence and severity of the self-injurious behavior correlates with the severity of the underlying impairment. The most common self-injurious behaviors are biting, hitting, and head banging (14). A study of patients with epilepsy and intellectual disability residing at a tertiary epilepsy center found that self-injurious behavior was present in 35% of patients, stereotyped behavior in 60%, and aggressive behavior in 63% (112).
In a study of nonhandicapped children aged 10 months to 11 years living in residential facilities, over half exhibited stereotypies at least once daily, including thumb sucking, nail biting, etc. (110).
Stereotypies are being increasingly identified in dementing syndromes. As might be anticipated by the differences in behavior among the syndromes, there might be differences in stereotypy. Stereotypic behaviors such as counting, clock watching, rigid adherence to routine, eating and doing the same thing repeatedly without seeking variation are significantly more common in the frontotemporal dementias than in dementia and age-matched Alzheimer disease patients (79). This discrepancy may help to more accurately diagnose the disorder.
Stereotypies are also reported in occasional cases of amyotrophic lateral sclerosis (39).
It is unclear whether stereotypies can be prevented. The conditions that induce these behaviors are mostly unavoidable. Tardive stereotypies can be reduced if dopamine-blocking drugs are given as judiciously as possible. Substituting clozapine or other new antipsychotics for the "typical" neuroleptic when tardive dyskinesia is first recognized may reduce the risk of worsening, but this is unknown. Extended use of antiemetics and metoclopramide should be discouraged.
Whether early intervention to reduce stereotypy in intellectual disability, autism, or blindness makes a difference is not known.
By themselves no stereotypes are diagnostic. Stereotypic movements represent 1 sign only in diagnosis and are always part of a larger syndrome when pathological. Hand wringing as a feature of Rett syndrome is probably the stereotypy that comes closest to being diagnostic.
Clearly, diagnosis depends on the company the stereotypy keeps. The most common stereotypies are probably related to intellectual disability of all causes. Stereotypy induced by blindness should be clear. Deprivation due to lack of human contact can only be diagnosed on history, which may be unreliable in such cases.
In children, head banging, body rocking, and head rolling occur in over 19% of normals and has been associated with early achievement, not delay, of milestones (95). These behaviors, however, were always of limited duration, generally under 15 minutes at a time. Therefore, the occurrence of these movements in a child does not, by itself, carry any indication of pathology. Persistent stereotypies in children, however, suggest the possibility of intellectual disability or autism once blindness has been excluded. Autism is defined by behavioral characteristics only. To be classified as autistic, the child must have problems in social behavior and attachment, abnormal responses to sensory stimuli, reduced eye contact, stereotypic motor behaviors, abnormal language and cognition, and normal appearance by 36 months (13). Unlike retarded children, autism has no known etiology, and delayed motor milestones occur in only half the cases. Autistic children also may have isolated areas of fairly normal or even supranormal function (94). Autism can be subdivided into different subsyndromes (40), and stereotypy is less common in the less affected. The occurrence of stereotypies in a retarded child does not help narrow the differential diagnosis; however, as intellectual disability induced by any hereditary, perinatal, or later-acquired disorder can cause this. For example, fragile X syndrome, Down syndrome, hypoxia, encephalitis, and head trauma can all cause retardation and stereotypies.
Stereotypies that are acquired after early childhood are due to a limited number of etiologies. These can be classified into psychiatric, drug-induced, and those associated with degenerative conditions.
• Normal child development
• Autistic syndromes
- tardive dyskinesia
- Rett syndrome
- acute decline in Down syndrome
• Hereditary nondegenerative
- restless legs syndrome
• Epileptic automatisms
The reoccurrence of stereotypy in a young child should raise the question of blindness, deafness, intellectual disability, autism, or seizure. If a neurologic evaluation is normal, it is likely that the behavior, if it occurs in relatively brief episodes, is normal. Autism is defined by clinical signs, whereas retardation occurring without a known explanation such as in utero or perinatal problem requires a chromosomal study for fragile X syndrome, a brain imaging study and any other diagnostic test deemed relevant, if a neurodegenerative process is thought to be on the differential diagnostic list. Rett syndrome also is diagnosed on clinical grounds alone.
For adult-acquired stereotypy the workup is limited. Usually the history will reveal either psychosis, neuroleptic drug use, or amphetamine abuse. A psychiatric evaluation to diagnose obsessive compulsive disorder, or distinguish amphetamine psychosis from schizophrenia may be helpful. A toxicology screen may be useful when the history is unreliable. Neuroacanthocytosis requires examination of a blood smear for acanthocytes. Acanthocytes present in greater than 3% of 500 red blood cells examined in a thin smear is considered significant (47).
Stereotypy requires treatment only if it is harmful to the patient. Interventions include medication, behavior modification, and restraints for self-injurious behavior (59; 14). Behavior modification may employ rewards, punishment, alteration of the environment, attempts to redirect the behavior, vestibular stimulation, and a host of other interventions. Results of all approaches have been mixed (59; 44). Certain aversive therapies (ie, electric shocks) have been ethically challenged, although others (ie, saying "no" loudly on each occurrence of a behavior) are accepted as routine. There have been many studies of drug interventions in the treatment of self-injurious behavior and stereotypy in the retarded and autistic. It is interesting that neuroleptics have been found in methodologically sound studies to selectively reduce stereotypic behaviors in subjects who are not self-abusive, whereas these drugs reduce self-injurious behavior only by suppressing "all behavior," acting as general depressants (14). This is most likely due to the higher doses required and the greater neurologic impairment in the self-injurious behavior group. The benefit of neuroleptic intervention must be balanced by the risk of inducing tardive dyskinesia. Although several other drugs have been tried for the treatment of self-injurious behavior, including opiate antagonists, their benefits are unclear. Naltrexone reduces self-injurious behavior in about half the cases, but naloxone is not effective. Buspirone has been proposed for stereotypies associated with dementia (49), and the diabetes medication pioglitazone may have potential for younger patients (18).
Tardive stereotypies have been treated successfully with tetrabenazine, a catecholamine-depleting drug now available commercially in the United States, approved for the treatment of chorea associated with Huntington disease (55; 36). Reserpine, a drug with similar properties, is somewhat less effective. Tardive movement disorders can often be lessened by increasing the drugs that caused the problem, but doing so will only worsen the condition in the long term. The rationale for using catecholamine-depleting drugs is that they have not been implicated in causing tardive dyskinesia or worsening already present tardive dyskinesia. In 2017, the FDA approval of valbenazine for the treatment of tardive dyskinesia, including tardive stereotypies, marked a special milestone as it is the first medication to achieve this distinction. A randomized, placebo-controlled trial demonstrated a reduction in the abnormal involuntary movements scale by 1.9 in the 40 mg group, 3.7 in the 80 mg group, and 0.1 in the placebo group (48). Deutetrabenazine was the subject of a randomized, placebo-controlled trial that evaluated 3 doses of the drug versus placebo and found the 2 higher doses treated tardive dyskinesia more effectively (05).
A study evaluating the effectiveness of a home-based, therapist-assisted, parent-provided therapy in 38 young children with complex motor stereotypies demonstrated statistically significant improvement in stereotypies as measured by the Stereotypy Severity Scale (102).
A metaanalysis of 23 studies showed that repetitive transcranial magnetic stimulation had a significant, but moderate, effect on stereotyped behaviors in autism spectrum disorder (12).
Akathisia may be acute or tardive. Acute akathisia may respond to propranolol or other beta antagonists, anticholinergics (especially if associated with drug-induced parkinsonism), or benzodiazepines, but can be refractory until the offending drug is stopped (01). Tardive akathisia is best treated with catecholamine-depleting drugs such as tetrabenazine (21; 55; 36).
There are no particular risks known for anesthesia, but the obvious problems that can be caused by stereotypies following surgery need to be considered, such as pain or disruption of the surgical site by involuntary movements. In general, the risks of anesthesia are related to the underlying condition that induced the stereotypy.
Joseph H Friedman MD
Dr. Friedman, Chief, Division of Movement Disorders, Department of Neurology, at the Warren Alpert Medical School of Brown University and Stanley Aronson Chair in Neurodegenerative Disorders at Butler Hospital received consultant fees from EPI-Q.See Profile
Umer Akbar MD
Dr. Akbar of Alpert Medical School of Brown University has no relevant disclosures.See Profile
Robert Fekete MD
Dr. Fekete of New York Medical College received consultation fees from Acadia, Acorda, Adamas, Amneal/Impax, Kyowa Kirin, Lundbeck, Neurocrine, and Teva.See Profile
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