Referrals to neurologists because of abnormal movements are common in children. Although many children who present with a chief complaint of “abnormal movements” are found to have a benign, self-resolving etiology, it is critical that neurologists accurately recognize benign versus pathologic movements in children to ensure appropriate intervention.
Children may present with an isolated hyperkinetic or hypokinetic movement disorder; however, mixed movement disorders are more common in young patients than in adults. Pediatric movement disorders may present at any point during infancy or childhood. They can affect tone, posture, strength, and all phases of movement (planning, initiation, and execution) and can consist of aberrant voluntary or involuntary movements. As in adults, abnormal movements in children may be categorized as ataxia, spasticity, dystonia, chorea, myoclonus, tremor, or parkinsonism. However, given the overlap of symptoms as well as variability of presentation in most pediatric movement disorders, classification into four main categories serves as a helpful framework: (1) transient developmental disorders, (2) paroxysmal movement disorders, (3) secondary noninherited disorders, and (4) hereditary or metabolic disorders.
The emergence of a movement disorder in the setting of the developing nervous system presents a unique set of challenges to the managing physician. As many childhood movement disorders are self-resolving, benign, or both, recognition of benign versus pathologic movements in children is essential to accurate diagnosis and management. Understanding the fundamental principles of motor development is key to recognition of benign versus pathologic movements in infants and children. Diagnostic competency relies heavily on a thorough history, a detailed neurologic examination, and astute recognition of phenomenology (practiced pattern recognition) of both normal and abnormal movements.
This article is designed to help the clinician identify and manage the most common pediatric movement disorders and to recognize benign versus pathologic movements in infancy and childhood.
NORMAL DEVELOPMENT OF MOTOR CONTROL
Effective diagnosis of movement disorders in children first requires recognition of normal versus abnormal movements across ages. Understanding several basic principles of motor development is essential to making this distinction.
Control of voluntary movement begins at the head and neck and progresses to the trunk and then the extremities. This “top-down” development of motor control occurs in concert with progressively diminishing primitive reflexes (eg, startle, palmar and plantar grasp) and emergence of postural reflexes (eg, lateral propping and parachuting). This rostrocaudal developmental pattern strategically protects the brain from injury: infants must attain head control and the ability to catch themselves when falling (lateral propping, parachuting) before they are able to achieve more gravity-defying skills such as sitting, standing, and walking. Thus, retained primitive reflexes and/or failure to develop postural reflexes are important hallmarks of motor delay.
Movement Employs the “Whole Brain”
The basal ganglia are essential for integration of inhibitory and excitatory signaling from throughout the nervous system. The roles of the deep gray matter, spinal cord, and motor cortex are certainly well established, but it is important to remember that motor function also involves coordinated signaling from the brainstem, limbic system, cerebellum, and frontal cortices as well as nonmotor pathways. Appreciation of the complex integration of signaling from both motor and nonmotor circuitry supports a much deeper understanding that voluntary movement is truly a “whole brain” process.
Movement Requires a Fine Balance of Inhibitory and Excitatory Signaling
A balance of inhibitory γ-aminobutyric acid–mediated (GABA-ergic) or “brake” signaling and excitatory glutamatergic or “gas” signaling is essential to coordinated movement. Dopamine plays the important role of moderator between these “stop and go” signals and is key to fine motor coordination, a balance of selection of desired movements and inhibition of unwanted movements. In children, this fine balance develops slowly over time. Control of inhibitory signaling is a feature of advanced motor development and can be slow to emerge even in typically developing children. As an example, consider the typical, very active 7-year-old child whose behavior may be described as “all gas and no brake,” which is evidence of normal, still-maturing motor inhibition.
Voluntary Movement Is Multiphasic
Voluntary movement is the result of at least three key overlapping phases: planning, initiation, and execution. The anatomic areas associated with each phase certainly overlap, but motor planning (which includes learning, selection, and timing of movements) is typically associated with the cortical association areas, cerebellum, thalamus, and basal ganglia. The thalamus and motor cortex are central to motor initiation, and complex signaling from the cortex, cerebellum, brainstem, spinal cord, and musculoskeletal system is integrated during motor execution. Impairment of any or several of these phases may result in disordered movement. Recognizing which phase or phases of movement are impaired may be helpful in guiding some treatment decisions.
OBTAINING AN EFFECTIVE PEDIATRIC MOVEMENT DISORDER HISTORY
Effective diagnosis and treatment of pediatric movement disorders begins with a comprehensive history. Ideally, this history can be obtained directly from the child, with supporting information from the caregiver(s). It is important to ask for details from even young children, as their level of insight may be surprisingly informative. Although efficiency is important, often a little extra time and patience during the history portion can go far toward gaining an accurate understanding of the phenomenology of the child’s movement of concern.
Phenomenology and History of Present Illness
A movement disorder history begins with a focus on primary phenomenology, or pattern recognition, to aid in identifying and categorizing the movement of concern. It is important to determine the onset, duration, location or distribution, severity, and provoking and relieving factors. Are the movements episodic or continuous? Do they wax and wane throughout the day? Are there times when the movements worsen or resolve? Do they continue during sleep? Is the child aware of the movements and, if so, is the child bothered by them? Do the movements occur in multiple environments (home, school)? Can the child control the movement? Can the child stop or start the movement on command? Is the movement associated with any premonitory urge? Has the child developed any techniques to stop, suppress, or interrupt the movements? Are the movements painful, embarrassing, or annoying to the child?
Ask if the child has tried any medications or supplements to relieve the movements. Has the child seen other providers to address the movements? What have others (providers, family members, teachers, friends) said about the movements? This question can be an opportunity to understand the child’s thoughts and feelings about the movements and to provide needed education or dispel any misleading information that may have been encountered. For example, a child with unrecognized chorea who has been reprimanded for an inability to sit still may feel very embarrassed by the chorea and work very hard to minimize the movements. Or the child whose concerns have previously been dismissed may be unintentionally embellishing the movements in effort to be taken seriously.
A birth history should be obtained for any pediatric complaint but can be especially important when evaluating for a movement disorder. This includes maternal pregnancy history and history of any other pregnancy loss or infant death. Maternal medication use during pregnancy is important when considering abnormal movements in the neonate such as jitteriness or abnormal tone. History of prematurity, birth trauma, or hyperbilirubinemia (treated or untreated) may pose risk for abnormal movements related to underlying brain injury. The clinician should ask specifically about any maternal risk factors or illnesses during pregnancy, birth weight, gestation age, head circumference at birth, method of delivery, use of forceps or vacuum extraction, and resuscitation needed at the time of delivery. Perinatal infections, history of neonatal intensive care unit hospitalization, or other infection or illness in the neonatal period may also be informative.
A detailed developmental history is important even for those children who seem to be developing typically. Outlining a specific timeline of achievement of milestones (or failure to do so) in all domains including gross motor, fine motor, speech and language, and cognition can point to subtle signs of delay that could be otherwise overlooked. For children with previously identified delay, understanding the presence or absence of, timing of, and response to interventions such as physical, occupational, or speech therapy will help narrow the differential diagnosis.
Medical and Surgical History
Caregivers may not think chronic illnesses such as asthma are relevant to a movement complaint, so it is important to ask directly if the child has any other diagnoses or uses medication for any condition. This is a good time to ask if the child had any abnormal or extra movements in the past. Ask about early episodes of atypical eye movements, torticollis, colic, or abnormal posturing in infancy and early childhood. Was the child particularly clumsy or slow to toilet train, or did they struggle to learn to use utensils to feed themselves?
A thorough family history is essential, and constructing a complete multigeneration genogram can be revealing, especially if a genetic condition is suspected. Often, especially with benign movement disorders such as tics and stereotypies, there is a positive history of similar movements in one or both parents in childhood. Encourage the parent to ask their own family members (the grandparents, aunts, and uncles of the patient) if the parent had any similar movements or “habits” as a child; the parent may not remember or may not be aware of their own movements that resolved in early childhood. Examination of family members can be very helpful when considering diagnoses with high generational penetrance such as essential tremor and primary dystonias.
The psychosocial history is essential in the evaluation of a child with a movement disorder. Ask about family living arrangements, who lives at home, and where the child spends their time. Has anything recently changed about the child’s living arrangements? If care is split between multiple households, are expectations and routines similar or very different between locations? Have caregivers recently changed jobs, moved, or undergone other major upheavals?
As previously mentioned, nonmotor and limbic circuitry also influences voluntary movement. Emotions directly affect normal voluntary and involuntary movements, and the same is true for disordered movements. Stress and anxiety are increasingly common even in young children and may have a dramatic impact on a child’s clinical presentation for both benign and pathologic movement disorders. Thoughtful screening for anxiety, depression, obsessive-compulsive disorder, eating disorders, self-harm, and suicidality is critical in building a full understanding of the complexity of a child’s motor function. Making an effort to normalize the concept of anxiety for children and their families is important and can be powerful. Often children and their caregivers deny a history of anxiety but can more easily identify with the concept of “worries.” Reinforce that worry is normal and is part of how human beings have evolved—without worry, we would not look both ways before crossing the street or behave safely in the world. We all have worries; does this child worry more than others or have specific worries that take up more time than they feel is appropriate?
Work to understand the impact of a child’s movement disorder on their learning and education. Ask about inattention, hyperactivity, and attention deficit hyperactivity disorder as well as school performance. Have the movements directly or indirectly affected the child’s learning or academic performance in any way? Are the movements contributing to any behavioral challenges at school or in other environments? These details may aid in deciding whether to offer symptomatic treatment.
PEDIATRIC MOVEMENT EXAMINATION
The essential components of the neurologic examination are similar in children and adults. Children are more likely to present with mixed movement disorders, which, when coupled with the moving target of ongoing development, can make the pediatric neurologic examination challenging to interpret. The successful completion of a neurologic examination focused on pediatric movement disorders relies on several key skills.
Know the Developmental Milestones of Infancy and Childhood
The timing and pattern of emergence of developmental milestones are key to understanding motor development. The clinician must also appreciate the developmental relationship between resolution of primitive reflexes and emergence of postural reflexes and how that relates to the acquisition of motor milestones.
The majority of the neurologic examination can be completed by observation. Recognizing and developing observational examination skills helps ensure that nearly any patient encounter, in person or virtual, provides high-yield examination data. Watching a child play provides detailed information about mental status, intellectual function, cranial nerve function, fine and gross motor function, tone, strength, endurance, coordination, and gait. Observational examination skills are particularly relevant today as we incorporate more virtual visits into regular clinical practice. Before the COVID-19 pandemic, it was difficult to imagine completing a relevant movement disorder examination remotely, yet now many of us find ourselves well practiced in eliciting valuable examination findings by video examination. Perhaps neurologists were particularly well prepared for this expansion of our skill set given our common practice of using video examinations regularly for teaching and consulting on challenging cases. It has long been common practice to ask a caregiver to capture a movement of concern not observed in the office on home video for review by the examiner. Real-time telehealth video examination can provide valuable observation of the patient in their home, school, or other primary environment. It may be advantageous to ask the family to schedule the telehealth visit at the same time as ongoing in-home services such as physical or occupational therapy, or to conduct the visit at the therapy office to coordinate with valuable input from ancillary service providers who know the child well. Caregivers can be quickly taught to demonstrate many parts of the infant examination on video such as eliciting primitive and postural reflexes, demonstrating tone and reactivity through positioning the infant in vertical and horizontal suspension, and repeating any provoking stimuli for movements of concern on video (feeding, diaper changing, etc). Even examination maneuvers such as handwriting samples or Archimedes spiral testing for tremor can be completed via telehealth by using technology such as screen sharing of virtual whiteboards and electronic pencils used on tablet devices.
Build Engagement Deliberately
Some children are very quick to engage with the examiner, but others may be shy or frightened by the appointment. For all children, starting the visit with a calm, friendly introduction directly to the child will help the examiner gauge the child’s willingness to engage. For those children who seem fearful or shy, give them time and space. It can be helpful to turn attention to the caregiver, allowing the child to explore the room on their own terms before redirecting your attention to the child. Consider body language; sit down and allow space between yourself and the child, with free access for the child to move easily to their caregiver. Allow the child to become comfortable as you speak with the caregiver. It may help to allow the child to think you are ignoring them. Try leaving some enticing toys close by to see if they engage. Watch how the child sits, clings to their parents, or plays with an electronic device of their own. Ask the child or caregiver about the child’s interests. During telehealth visits, the examiner may encourage the child to engage by asking about their toys, books, or pets visible on the screen. Siblings can be a distraction or a great ally: younger children will often copy their older siblings quickly; older siblings will often engage if they are asked to “help” demonstrate something for a younger sibling or even to their pet. It is also fine to ask the family to take a moment to remove a child from the room or to allow the patient to run off and play in the background. Use of child-friendly virtual backgrounds by the examiner can be particularly engaging; children can be asked to identify characters seen on screen or count objects, identify colors, and so forth. Older children and adolescents may engage with a background of their favorite or rival sports team, school, or activity. If virtual backgrounds are not available to the examiner, consider keeping a supply of engaging toys nearby to help maintain the child’s focus and attention. Cooperative pets belonging to the examiner can be particularly engaging to young children on screen, but be sure to ask the parent before engaging an animal to ensure that the child is not fearful of that type of animal.
Cognitive flexibility on the part of the examiner is essential. As neurologists, we are often trained to perform the neurologic examination in a specific order in an effort to stay organized and be thorough and efficient. This ritual can be very reassuring to the examiner. However, when examining children, it pays to “meet the child where they are” in terms of cooperativity and use whatever activity they are actively engaged in at the moment as part of the examination. It may be helpful to think of the pediatric neurologic examination in several phases with key components intermixed between phases: (1) initial impression (opportunity to assess mental status, intellectual function, social interaction, ability to engage, basic cranial nerve function, basic assessment of motor function and milestone attainment); (2) the child’s behavior and level of function when the examiner’s attention is directed to the caregiver (opportunity to assess the child’s ability to independently maintain attention to conversation not directly involving them, and perform self-soothing, engagement, or self-entertainment and to observe the child’s basic level of motor function); (3) the child’s active behavior when examiner’s attention is directed to the child (child’s ability to attend, cooperate, and perform specific tasks requested by the examiner).
Use Creative Play
Children are not always cooperative or able to perform desired examination maneuvers, so developing creative ways to observe specific movements is highly valuable. For example, for a toddler with tremor, providing an engaging activity such as coloring, using a puzzle, or reaching to help the examiner turn the pages of a book can aid assessment of tremor qualities in different positions and during different tasks. Anxious children may be calmed by “taking a walk” and moving the encounter to the hallway, stairwell, or even outside, where it may be easier to observe important gross motor activities such as walking, running, and climbing.
Tone Is Dynamic
The intricacies of muscle tone are evidence of the elegance of finely tuned and balanced central nervous system motor circuitry as the basis of human movement. Too often, tone is thought of as a passive, single-state quality. Effective assessment of tone requires demonstration not only at rest but also with activation, with attention to reactivity, recruitment, and coordinated relaxation. Normal infants can appear quite hypotonic when sleeping and may seem nearly rigid when crying and distraught, a striking example of the high variability and dynamic nature of appropriate muscle tone.
A Word About Motor Assessment Tools
Several rating scales are available to quantify normal and abnormal movement in adults and children. These are described in more detail in subsequent sections where relevant. Although some scales may be useful in monitoring improvement or deterioration over time, many fall short of fully depicting the impact of movement disorders on the lives of affected children. These assessment tools can be used as helpful adjunct measures, but they should not replace or supersede clinical assessment based on the provider’s obtained history and physical examination.
TRANSIENT DEVELOPMENTAL DISORDERS
Transient developmental disorders include benign and common pediatric movement disorders. Infants and children commonly demonstrate movements that are confusing or alarming to their caregivers, resulting in a steady influx of referrals of typically developing children to neurologists for “abnormal movements.” Caregivers often seek medical care with an underlying fear that the movements exhibited by their child could signal a serious neurologic problem such as a seizure or brain tumor and may present with a high level of anxiety and sense of urgency regarding their child’s movements. Evaluating these children in a timely manner can help ensure that the child is healthy and safe and provide appropriate reassurance to caregivers.
Most benign movements in children are transient and typically hyperkinetic, with phenomenology similar to myoclonus, dystonia, or dyskinesias. It is helpful to group these conditions by typical age of presentation. Although some of these conditions are common in children with concurrent developmental disorders, all of these movements can and often do present in typically developing children. Nevertheless, these movements can be very stressful for families and, although not associated with neurodegeneration, can have a significant impact on the quality of life of the affected child or their caregivers; they may necessitate continued management and monitoring by the clinician.
Benign movements presenting in infancy include diagnoses such as stereotypies, benign neonatal sleep myoclonus, jitteriness, shuddering, paroxysmal tonic upgaze, torticollis (including benign paroxysmal torticollis), head nodding, spasmus nutans, benign dystonia of infancy, reflux (Sandifer syndrome), colic, and self-stimulation. Older children and adolescents may present with stereotypies, tics, and Tourette syndrome. Stereotypies and tics are the most common of these benign disorders and are discussed below, with other disorders briefly summarized in table 11-1.
Stereotypies are benign, repetitive stereotyped movements typically involving the hands, face, or both. Movements can range from appearing relatively simple and subtle to quite complex. Frequency and duration are variable, and stereotypies may be intermittent or persistent. Unlike tics, stereotypies are not typically associated with a sense of urge. For a detailed review, see the article by Katherine. Although the child may appear very engaged in the movements, as a rule, stereotypies are interruptible and the child remains responsive (although they may be inattentive to someone attempting to interrupt or distract them from the movements). Families often worry that the presence of motor stereotypies in their typically developing child is a harbinger of autism or another pervasive developmental disorder. Reassurance is key, and repeated evaluation at regular intervals can help ensure that the family is confident moving forward with conservative management. Although many typically developing children outgrow their stereotypies by early school age, others may continue to perform stereotypies into adulthood. Many older children with retained motor stereotypies report that they enjoy performing these movements, and some describe accompanying intense visual imagery. The clinician should ask older children what they are thinking or visualizing when they are performing their stereotypies. Some may report very vivid descriptions of an imaginative world, as if they were playing an exciting video game in their head. Realizing that their child is not distressed by their stereotypies but is actually enjoying performing the movements can be reassuring for worried parents.
Stereotypies typically do not require intervention. Often, stereotypies wane with development, especially as children gain more advanced language skills and are better able to express themselves verbally. For those children who have particularly intense stereotypies that are interfering with their ability to pay attention and learn in school, or if the child is bothered by their own stereotypies, some behavioral interventions (modification of environment, scheduled breaks, quiet space for destimulation) or therapy methods (habit reversal, competing response) may be helpful. Stereotypies typically do not respond to medications, and daily treatment with medication for stereotypy suppression is not indicated.
Tics and Tourette Syndrome
Chronic motor and vocal tics or Tourette syndrome is a common diagnosis in school-aged children and adolescents. Correct diagnosis of tics and Tourette syndrome is essential to appropriate management. Tics are stereotyped movements or sounds, typically associated with an urge to perform, and have some element of suppressibility. A diagnosis of Tourette syndrome requires tic onset before the age of 18, with a combination of at least one vocal and one motor tic occurring over a duration of 1 year or more (motor and vocal tics do not need to co-occur), with tics occurring nearly daily, with tic-free periods of less than 3 months in duration. Children with tics who do not meet diagnostic criteria for Tourette syndrome may be classified as having transient tic disorder. It is important to ask about prior tics or “habits” that may have gone unrecognized at a younger age. Additionally, the sense of urge and suppressibility are often difficult for the young patient to recognize or report. It can be helpful to ask the child if they “feel like the tics have to come out,” or “What happens if you try to stop the tics?” Children may give very creative descriptions or drawings of their tic-associated urge if asked to do so.
Tics may be simple (blinking, grimacing, throat clearing) or complex and can involve any part of the body. Unlike pathologic movement disorders, tics commonly pause during voluntary movement and speech and may quickly resume when the child is no longer engaged in speaking or another activity. Tics fluctuate in severity and frequency over time and may wax and wane within the hour, day, or week. This timing may correlate with more exciting or stressful times of day (in the morning on the way to school, at the end of the school day), week (improved on weekends, worse during the weekdays), or year (classically increased at the start of the school year, improved over the summer). Tics typically do not occur during sleep but may worsen at times of transition to sleep such as bedtime or when waking in the middle of the night. Consider provoking factors, including other medications (especially stimulants), caffeine intake, and emotional or physical stressors. Typical tic comorbidities include anxiety, depression, obsessive-compulsive disorder, and attention deficit hyperactivity disorder.
Although many children with tics or Tourette syndrome will never require medication, appropriate use of tic-suppressing medications in those who develop tics that are painful, embarrassing, or interfering with learning, in addition to appropriate management of tic comorbidities, is essential to management. Nonpharmacologic intervention such as Comprehensive Behavioral Intervention for Tics (CBIT) should be considered for patients who acknowledge their tics and are motivated to learn to suppress them. CBIT can be completed in person or using online resources. Understanding the association with urge can be helpful in guiding tic suppression therapies such as CBIT. Several algorithms for tic treatment have been published.
Recognition of tic comorbidities is essential to optimizing medication choices for patients. In general, first-line tic treatment includes CBIT with or without α2-adrenergic agonists (ie, guanfacine, clonidine); second-line agents are typically non–dopamine blockers (eg, topiramate, selective serotonin reuptake inhibitors [SSRIs] and serotonin norepinephrine reuptake inhibitors [SNRIs], and muscle relaxants such as baclofen); and third-line agents include dopamine blockers (such as typical and atypical antipsychotics). The most common side effects of first- and second-line agents include fatigue (guanfacine, clonidine, baclofen), mood changes (SSRI/SNRI), and appetite suppression (topiramate) but are typically well tolerated and dose dependent. Dopamine-blocking agents have a more complex side effect profile and require closer monitoring and are thus typically reserved for more severe and/or medication-refractory tics. Surgical intervention using deep brain stimulation (DBS) is typically reserved for adult patients with severe, medication-refractory, and highly disabling Tourette syndrome. Medication selection can be optimized by paying particular attention to identifying key drivers for an individual with tics. For example, in a child who is particularly anxious, treating the anxiety can contribute to dramatic tic reduction.
PATHOLOGIC MOVEMENT IN CHILDREN
Movement disorders in children can present with phenomenology similar to that in adults and may be categorized as chorea, dystonia, myoclonus, tremor, ataxia, spasticity, and parkinsonism. Unlike adults, children often present with a mixed movement disorder; thus, discerning the primary phenomenology can be challenging but remains the foundation of accurate and timely diagnosis and treatment. Using the categories of paroxysmal movement disorders, disorders with secondary noninherited causes, and hereditary or metabolic disorders can help to build an informed differential diagnosis (table 11-2). As the field of neurogenomics moves forward, the list of identifiable etiologies of pediatric movement disorders is rapidly growing. A detailed review of each of these disorders is outside the scope of this article. The focus here is on accurate identification of clinical movement disorder phenomenology in children and the most common diagnoses for each phenomenology.
Chorea consists of brief, variable, unpredictable, nonstereotyped, nonsuppressible irregular movements (case 11-1). Movements can be fast and chaotic or may have an athetotic quality with slow, writhing action. Chorea can affect the entire body and is most commonly seen in the head and neck and upper extremities. Chorea is not sustained like dystonia and is slower and more fluid than myoclonus. Amplitude is variable. Chorea often worsens with voluntary movement, and specific examination maneuvers can be used to elicit chorea. Children with mild low-amplitude chorea may seem fidgety, restless, or hyperactive. Higher-amplitude chorea may present as ballismus, with the arms or legs appearing to fling away from the body in an uncontrolled manner. Children often attempt to minimize the chorea, sometimes sitting on their hands or adopting other positions to reduce intrusions and excessive movement. Young children, especially those who are prone to inattention and hyperactivity, may have very mild choreiform movements that can be considered normal, classified as physiologic chorea. Thus, careful history taking to explore timing, symptom onset, comorbidities, and other factors is essential to determine the appropriate workup.
A 5-year-old boy with hypoplastic left heart with remote surgical repair presented to the emergency department with new uncontrolled movements 10 days after discharge from a recent hospitalization for multiple infections. His mother reported that he could no longer sit, walk, or feed himself independently. Typically a very talkative child, he was now refusing to speak.
On examination, he was afebrile with normal vital signs. He was in no distress, with normal breathing, good perfusion, soft abdomen, and no rashes. He had a well-healed sternotomy scar, consistent with his history of cardiac surgery. He appeared very wiggly and restless and seemed irritable but was oriented, alert, and able to at least attempt to follow commands, although he was limited by his inability to control his arms, legs, and head. He was lying in bed, refusing to sit up or speak. His gaze was conjugate and his extraocular movements were intact, but his excessive head wiggling caused him to blink frequently and struggle to follow the examiner around the room. When supported in a seated position, he was unable to hold his head still, and he had nearly continuous writhing movements of his trunk. When reaching for objects he demonstrated a variety of extra movements, which worsened with intentional voluntary movement. In particular, his fingers appeared to hyperextend when he was asked to open his hands, and, upon squeezing the examiner’s fingers on command, he exhibited repetitive squeezing movements of both hands. When asked to stick out his tongue, although he seemed compliant, he could not keep his tongue still enough for the examiner to adequately examine his mouth.
It was discovered that during his recent hospitalization he was diagnosed with COVID-19 complicated by a group B streptococci superinfection. He had been treated for both infections appropriately and was discharged home, where he was well until onset of these new movements.
Brain MRI and EEG were normal. Tests for erythrocyte sedimentation rate and anti-deoxyribonuclease B (anti-DNase B) were equivocal (video 11-1).
The patient was diagnosed with Sydenham chorea and treated with a course of steroids. He experienced dramatic improvement within days of treatment.
The timing of chorea onset can be very informative with regard to etiology. Acute chorea in children is most commonly due to toxic ingestion or infectious or postinfectious causes.
The most common type of acute-onset chorea in school-aged, previously healthy children is Sydenham chorea, a postinfectious autoimmune chorea. Sydenham chorea classically occurs as a sequela of group A β-hemolytic streptococci infection but has been noted to occur in association with other infectious causes. Sydenham chorea develops quickly, over hours to days. History should reveal prior infection (fever, cough, sore throat) in the past 6 months. Prior infection may have been mild or subtle. If there is no history of a clear infection but suspicion for Sydenham chorea is high, then antistreptolysin O (ASO) and anti-deoxyribonuclease B (anti-DNase B) titers should be obtained. If history and examination suggest Sydenham chorea, then elevated ASO or anti-DNase B titers can serve as relatively sensitive predictors of the disorder. If suspicion for Sydenham chorea is low, then ASO and anti-DNase B titers are less useful, and interpretation of these results can be complicated. In a child with subacute chorea and absence of elevated ASO or anti-DNase B titers, an alternative diagnosis of systemic lupus erythematosus (SLE) or antiphospholipid antibody syndrome should be considered. Of course, other etiologies such as toxic (ingestion) or structural (stroke) must be considered at the time of diagnosis, depending on history and other examination findings. Although brain MRI is not necessary for children with clear cases of Sydenham chorea, it is often obtained in an effort to rule out other causes of acute-onset chorea.
Symptom severity in Sydenham chorea is highly variable, but children commonly present with complaints of new clumsiness (dropping items, falling), gait instability, irritability, poor coordination, and possible changes in speech and behavior. On examination, classic findings of spooning sign (child is asked to hold hands outstretched in front of them at shoulder height resulting in hyperextension of fingers interrupted by choreic intrusions), touchdown sign (child is asked to sit still with arms at shoulder height with elbows flexed at 90 degrees and hands facing forward resulting in choreic intrusions disrupting arm position), milkmaid’s grip (child is asked to use all fingers of one hand to squeeze the examiner’s hand, but the child’s grip is interrupted with choreic intrusions denoting motor impersistence), and tongue darting can help solidify the diagnosis. These findings are not specific to Sydenham chorea but can be observed in other forms of chorea and are not necessary to provide the diagnosis of Sydenham chorea.
Sydenham chorea is a form of rheumatic disease; thus, screening and monitoring for associated cardiac involvement are imperative. Chronic penicillin prophylaxis is indicated to reduce the risk of recurrent chorea but also for protection against carditis and development of secondary cardiac valve disease. ECG, echocardiography, and evaluation by a cardiologist are appropriate. Steroid treatment can shorten the duration of chorea and reduce symptom severity.
Other acute chorea
In children with congenital heart disease who have undergone surgical repair or bypass, postpump chorea should be considered in the case of acute onset of choreiform movements in the postoperative period.
Chronic chorea may be acquired, as in children with structural brain injury such as hypoxic-ischemic encephalopathy, cerebral palsy, and stroke; toxin induced; autoimmune; or iatrogenic. Genetic causes of chorea should be considered in any child with new-onset subacute progressive chorea, especially if accompanied by other neurologic or psychiatric features. Genetic causes of chorea in children include benign hereditary chorea, several neurodegenerative diseases (Huntington disease, glutaric aciduria, Wilson disease, GNAO1 encephalopathy, mitochondrial disease, Lesch-Nyhan syndrome, phenylketonuria, neuroacanthocytoses), ataxia syndromes (Friedreich ataxia, ataxia-telangiectasia, ataxia with oculomotor apraxia types 1 and 2, dentatorubral-pallidoluysian atrophy, spinocerebellar ataxia), and many other disorders (ie, ADCY5, PDE10A, NKX2-1, GLUT-1, FOXG-1).
For an in-depth review of other causes of chorea, refer to the article “Chorea” by Erin Furr Stimming, MD, FAAN, and Danny Bega, MD, in this issue of Continuum.
Dystonia is characterized by involuntary simultaneous contraction of opposing muscles, leading to abnormal posture and impaired function of the affected area (case 11-2). Dystonia can involve a particular part or region (focal, segmental) or all (generalized) of the body. Dystonia is commonly mistaken for spasticity in children who present with abnormal increased tone. Dystonia will often “melt” away during sleep or with relaxation, whereas spastic muscles will remain tight regardless of state. Dystonia often worsens with activity and may be task-dependent, occurring only with specific motor sequences (as can be seen in disorders such as writer’s cramp or musician’s dystonia). Also, unlike with spasticity, patients with dystonia may be able to perform a “dystonic trick” or geste antagoniste, a maneuver specific to the affected individual that allows them to relieve the dystonia. Dystonic tremor may have a “null point,” a position in which the tremor is minimized. In children, the clinical distinction between dystonia and spasticity (and other movement disorders) is essential in determining accurate disease etiology and appropriate treatments. Children with increased tone are too often given the diagnosis of cerebral palsy, potentially leading to a missed opportunity for appropriate diagnosis and intervention. Children with basal ganglia injury related to cerebral palsy, stroke, or another insult may present with a combination of movement disorders and can have concurrent spasticity, dystonia, and chorea. Understanding which movement disorder is most prominent can guide treatment decisions and avoid unintended worsening of a concurrent movement problem. For example, in a child with spasticity and dystonia, surgical intervention must be considered carefully, as certain interventions for spasticity (selective dorsal rhizotomy) may improve the spasticity but “unmask” concurrent dystonia, resulting in worsened motor function.
An 11-year-old boy presented with a 6- to 8-year history of progressive generalized dystonia that reportedly began in one ankle (it was thought to be related to a minor sprain) and progressed over the next several years to involve his entire body. He initially had some symptomatic relief with benzodiazepines, but over time his dystonia spread and worsened in severity, and it had become refractory to multiple medications including clonazepam, baclofen, trihexyphenidyl, levodopa, and botulinum toxin injections.
He was referred to the movement disorders clinic for further evaluation. On initial examination, he had severe generalized dystonia with notable cervical dystonia featuring retrocollis and laterocollis, jaw opening dystonia for which his mother had tied a scarf under his chin to aid with jaw closure, risus sardonicus, dystonic tremor, and dystonic posturing of his arms and legs. His dystonia worsened with muscle activation for voluntary movement. His truncal dystonia had contributed to notable scoliosis. He was exceptionally thin with well-defined musculature and minimal body fat. He was cognitively intact, and receptive language was intact. Expressive language was severely limited by orolingual dystonia and dystonic dysarthria; however, he could attempt to follow verbal commands to participate in examination maneuvers such as the finger-nose-finger test and manual muscle testing (video 11-2). He was dependent on nasogastric feeding, as he was unable to swallow safely, and he used a wheelchair. His current medications were levodopa/carbidopa, trihexyphenidyl, baclofen, clonazepam, gabapentin, dantrolene, and regular-interval botulinum toxin injections; all interventions were optimized to maximum tolerated doses.
Prior brain MRI demonstrated nonprogressive mild cerebellar atrophy with no other abnormality. He underwent extensive genetic testing including whole exome and whole genome sequencing, which were unrevealing.
After multidisciplinary evaluation by specialists in orthopedic surgery, child neurology, pediatric neurosurgery, physical and occupational therapy, speech therapy, neuropsychology, and social work and review by the institutional deep brain stimulation (DBS) review board, the patient underwent successful implantation of bilateral globus pallidus internus DBS stimulators. He had marked improvement in his dystonia and was able to wean off nearly all of his medications with the exception of low-dose clonazepam.
Although the history supported a high suspicion for DYT1 as a cause of this child’s progressive generalized dystonia, genetic testing did not identify a cause. It is important to consider pallidal DBS even in cases where genetic testing is unrevealing.
Dystonia should be considered in any child with sustained abnormal postures. Unlike tics, dystonia is not associated with urge, suppressibility, or a sense of relief. Although some tics may appear to have dystonic features, careful history and observation will help the examiner distinguish between the two.
Dystonia can be primary (related to a genetic cause) or secondary (acquired, often with a structural etiology such as cerebral palsy, infection, kernicterus, stroke, toxins, trauma, or autoimmune etiologies) (table 11-3). Dystonia is a prominent feature in several syndromes (table 11-4).
Treatment options are similar to those in adults and include both medications and surgical interventions such as DBS. It is always prudent to trial levodopa for any child with dystonia to rule out a treatable dopa-responsive dystonia. For a detailed discussion of medical and surgical treatment of dystonia, including dystonic storm, refer to the article “The Dystonias” by Christopher Stephen, MB ChB, FRCP, SM, in this issue of Continuum.
Myoclonus is characterized by rapid and short muscle jerks that are simple movements. Myoclonus is unpredictable and appears much faster than voluntary twitching or jerking. It is helpful to identify and describe the distribution (focal, segmental, multifocal, generalized), origin (cortex, brainstem, spinal cord), state (spontaneous at rest or with activity versus stimulus induced), and timing (irregular versus rhythmic). Both positive (occurring as sudden muscle contraction) and negative (occurring as sudden muscle relaxation) myoclonus may be observed.
It is important to recognize benign forms of myoclonus in children. Examples of benign physiologic myoclonus include hiccups, exercise- or anxiety-induced myoclonus, benign neonatal sleep myoclonus, or hypnic jerks in older children. One of the most common myoclonus-related neurology consultations is for the infant with benign neonatal sleep myoclonus. Parents may present with their otherwise healthy infant with reports of “jerking” while falling asleep or during sleep (typically during states of arousal). Key findings include an otherwise normal healthy infant with reported absence of jerks while awake and a history consistent with cessation of jerks when the infant is awakened. These babies are often admitted to the hospital by a concerned provider for continuous EEG to rule out infantile spasms, but careful history taking and examination can avoid unnecessary testing and medical escalation. Education and reassurance of caregivers are appropriate, and no medication or other treatment is indicated.
In contrast to benign physiologic myoclonus, children may present with hyperekplexia (a stimulus-induced exaggerated startle response), which warrants additional evaluation with genetic testing. Symptomatic treatment with clonazepam or other benzodiazepines may be effective. Some hereditary hyperekplexias spontaneously improve or resolve, whereas others may be associated with other neurologic impairments such as cognitive delay or epilepsy.
Additional conditions associated with prominent myoclonus in childhood are listed in table 11-5.
Tremor is a rhythmic, relatively symmetric oscillatory involuntary movement of a body part. Tremor can occur as an isolated phenomenon or in conjunction with other movement disorders in children. The most common causes of tremor in children are the primary tremors: developmental tremor, enhanced physiologic tremor, and essential tremor. Secondary tremor results from injury affecting circuitry in the basal ganglia, brainstem, or cerebellum and may be caused by a variety of mechanisms including toxins, medications, structural lesions, and genetic or metabolic disorders.
On examination, fine and gross motor movements should be observed. Tremor can be enhanced by asking the child to perform specific tasks such as pouring water between cups, bringing a cup or bottle to their mouth, reaching for small objects, coloring, or drawing. Even very young children can often cooperate with handwriting or drawing samples and freehand spiral testing. The child can be observed buttoning their coat, collecting toys into a bag, or manipulating their parent’s smartphone. In infants and toddlers, feeding can be observed. Children will naturally find ways to minimize their tremor. Encourage the child to sit without leaning against a wall or the back of a chair to brace themselves. The examiner should pay careful attention to when the tremor is present and when it is absent. Is the tremor present at rest or only with action? Is it unilateral or bilateral? Are there other accompanying neurologic signs such as abnormal eye movements, ataxia, complaints of headache or dizziness, or changes in speech or behavior?
Developmental tremor and enhanced physiologic tremors tend to fluctuate and may be intermittent or observed only during specific tasks. The frequency is often faster and the amplitude lower than with essential tremor. Developmental tremor typically improves with age, whereas essential tremor persists or worsens. Careful family history and examination of accompanying family members at the time of neurologic examination is especially important in ruling in or out essential tremor, although a family history of tremor does not ensure that a child’s diagnosis is essential tremor, and other etiologies should be considered.
Education about the importance of lifestyle management is central to empowering young patients to attain good tremor control. Typical tremor-provoking stimuli include fatigue, poor sleep, anxiety, caffeine intake (coffee, tea, energy drinks), skipping meals, many medications commonly used in children and adolescents (SSRIs or SNRIs, stimulants, albuterol, antiseizure medications such as valproate and phenytoin), and physiologic as well as emotional stressors. Benign tremor can often be managed with only lifestyle modifications, avoiding use of daily medications. Occupational therapy can be particularly helpful in teaching children strategies to manage tremor as well as provision of individualized tremor tools such as specialized pen or pencil grips or weighted utensils.
For patients with essential tremor, propranolol and primidone are first-line medications. DBS should also be considered for adolescents with intractable essential tremor that interferes with learning or self-esteem.
In the event of acute onset of new tremor, ingestion and withdrawal must be considered.
Metabolic causes of tremor such as thyroid or other endocrine dysfunction should be ruled out. Vitamin and mineral deficiencies should also be considered as potential etiologies for tremor.
Tremor due to an underlying structural abnormality or associated neurologic syndrome is rarer, but it is important to recognize key findings on history and examination that will help the clinician discriminate between enhanced benign and pathologic tremor. Any child who presents with a new-onset tremor in the setting of other neurologic signs or symptoms warrants immediate neuroimaging.
For all young patients with tremor, repeat examination in 6 to 12 months, even for those patients with benign etiologies, can ensure appropriate monitoring and treatment and provide any additional support to optimize function.
Ataxia is defined as “inability to generate a normal or expected voluntary movement trajectory that cannot be attributed to weakness or involuntary muscle activity about the affected joints.” Children with ataxia may present as clumsy or with extra movements and may have abnormal eye movements (nystagmus, oculomotor apraxia), slow or slurred speech, tremor, head or trunk bobbing or instability (titubation), and a wide-based lurching or staggering gait. Subtle ataxia can be easily missed or mistaken for dyskinesia or even hyperactivity. Understanding onset (acute, subacute, or chronic) and presence or absence of progression is key, as it is helpful to think of childhood ataxias grouped by onset and then by mode of genetic inheritance or other accompanying features. table 11-6 provides guidelines for the initial diagnostic approach to the child with ataxia.
A common cause of acute ataxia in children is toxic ingestion. Toxic ingestion is always at the top of the differential diagnosis for acute ataxia and may be accidental in toddlers or related to substance abuse in adolescents. Common substances ingested include alcohol, antiseizure medications, antihistamines, and benzodiazepines. In the absence of clear toxin exposure, traumatic or vascular causes such as stroke or vertebrobasilar dissection should also be considered. Infectious and postinfectious causes must also be considered.
Recurrent acute ataxia may be metabolic in origin (look for a history suggestive of neurometabolic disease); due to migraine (basilar migraine, which may present without head pain), benign paroxysmal vertigo, or episodic ataxia type 1 or 2; or functional in nature.
The differential diagnosis for subacute presentation of ataxia includes acute cerebellar ataxia (usually postinfectious), opsoclonus-myoclonus syndrome, acute disseminated encephalomyelitis (ADEM), Guillain-Barré syndrome including Miller Fisher variant, and posterior fossa tumor.
Chronic-onset ataxias may be progressive or nonprogressive, as outlined in the following sections.
Chronic progressive ataxia can be associated with several genetic mutations and is typically subdivided into three groups: autosomal dominant, autosomal recessive, and spastic-ataxia, with the autosomal recessive ataxias being the most common subgroup to present in children. Examples of autosomal recessive chronic progressive ataxias in children include Friedreich ataxia, ataxia-telangiectasia, ataxia with oculomotor apraxia types 1 and 2, and ataxia with vitamin E deficiency. Friedreich ataxia and ataxia-telangiectasia are the most common autosomal recessive ataxias presenting in children.
Examples of less common autosomal dominant ataxias include many of the spinocerebellar ataxias and dentatorubral-pallidoluysian atrophy (DRPLA).
Ataxia-telangiectasia is an autosomal recessive progressive movement disorder with typical onset of neurologic symptoms between 1 and 4 years of age, characterized by ataxia, chorea, dystonia, athetosis, oculomotor signs, and later development of telangiectasias. It may or may not be accompanied by recurrent sinopulmonary infections. Ataxia may initially be static or slow to progress, potentially delaying accurate diagnosis. Ataxia-telangiectasia is accompanied by immunodeficiency, which, if present, may warrant treatment with intravenous immunoglobulin (IVIg). Ataxia-telangiectasia is detected by elevated serum α-fetoprotein, which is typically sufficient to confirm the diagnosis. Additional testing may include ATM gene sequencing and DNA radiosensitivity testing. Treatment of the movement disorder is symptomatic, with no specific treatment for ataxia.
Friedreich ataxia is the most common autosomal recessive ataxia in White populations and is due to GAA triplet repeat expansion in the FRDA gene. Average age at onset is 15 years, with patients typically presenting with neurologic symptoms after the age of 2 years. Friedreich ataxia is characterized by progressive gait ataxia, dysarthria, limb weakness, axonal neuropathy with impairment of proprioception and vibration, areflexia, and extensor plantar response. Patients with Friedreich ataxia are at high risk for diabetes and dilated cardiomyopathy, the latter of which is a common contributor to early mortality.
Ataxia with oculomotor apraxia types 1 and 2
Ataxia with oculomotor apraxia type 1 (AOA1) and type 2 (AOA2) are progressive autosomal recessive ataxias presenting in childhood. Onset of symptoms in children with AOA1 is anywhere between age 2 and 18 years and includes ataxia, choreoathetosis, oculomotor apraxia, sensory neuropathy, hyporeflexia, and cognitive impairment. AOA1 is associated with a mutation in the PTX gene, with low serum albumin and high cholesterol on laboratory evaluation and cerebellar atrophy on MRI. AOA2 typically presents in the teen years with onset between age 13 and 18 years and features progressive ataxia and areflexia, but oculomotor apraxia is less prevalent. AOA2 is associated with mutation in SETX, with elevated serum α-fetoprotein and diffuse cerebellar atrophy on MRI. No disease-modifying medical treatment is available for either AOA1 or AOA2.
Ataxia with vitamin E deficiency
Ataxia with vitamin E deficiency has onset in early childhood and is characterized by progressive ataxia, retinitis pigmentosa, and dystonia. Diagnostic testing reveals low vitamin E levels. Treatment includes lifelong high daily doses of vitamin E.
In patients with chronic nonprogressive ataxia, neuroimaging can aid in ruling out an associated congenital cerebellar malformation.
Spasticity is a common finding in children with disordered movement and can be secondary to a structural cause or related to a primary genetic cause. The most common cause of spasticity in children is cerebral palsy. It is critical to consider other causes of spasticity in children who present with any of the “red flags” discussed below (table 11-7).
Spasticity is defined as increased tone with increased resistance to passive stretch at a joint and is typically velocity dependent. Children with long-standing spasticity may also have contractures limiting range of motion at a joint, which can make testing for velocity dependence challenging. Dystonia and rigidity are easily mistaken for spasticity. Clinical distinction between spasticity, dystonia, and rigidity is essential for accurate diagnosis and appropriate treatment of the hypertonic child (table 11-8).
The most common cause of spasticity in children is cerebral palsy, resulting from a wide variety of prenatal, perinatal, and postnatal insults (eg, prematurity, hypoxic-ischemic encephalopathy, stroke, infections, developmental brain malformation, vascular malformation, congenital heart disease, trauma, kernicterus, or intracranial hemorrhage). Cerebral palsy is typically classified into four types by primary motor disability: spastic, dyskinetic, ataxic, or mixed type. Although spastic cerebral palsy is the most common type, many children with cerebral palsy present with a mixed movement disorder, with dystonia present in up to 75% of children classified as having the predominant spastic type. Children with spasticity may also have signs of chorea, ataxia, and other abnormal movements. Key principles regarding the diagnosis of cerebral palsy are as follows: (1) Cerebral palsy is a clinical description and not an etiology. (2) Cerebral palsy is a permanent disability. (3) Cerebral palsy is a nonprogressive brain process, but the physical manifestations of the disorder are not necessarily static.
A multitude of neurogenetic disorders masquerade as various types of cerebral palsy, including leukodystrophies, neurotransmitter disorders, neurometabolic disorders, and mitochondrial and genetic disorders. As a rule, cerebral palsy is nonprogressive, and any child with progressive or degenerative central nervous system symptoms requires further diagnostic evaluation. Children with cerebral palsy should also have expected motor symptoms and clear risk factors for the disorder, with neuroimaging supporting the diagnosis. In any child with clinical signs and symptoms suggestive of cerebral palsy but with absence of prenatal or perinatal risk factors or a normal MRI, other possible diagnoses must be considered (table 11-9). Metabolic or genetic testing or both should be considered if neuroimaging reveals a developmental malformation or imaging abnormality is isolated to the globus pallidus or in the presence of any of the following: regression or new or worsening symptoms, episodes of metabolic decompensation, no clear etiology, a positive family history of “cerebral palsy,” a family history of consanguinity, isolated hypotonia, evidence of rigidity, or paraplegia.
Treatment of spasticity is multimodal, relying on interdisciplinary care coordination between primary care, orthopedic surgery, physical and occupational therapy, neurology, physical medicine and rehabilitation, neurosurgery, and often other subspecialties such as gastroenterology and pulmonology.
Oral medications such as baclofen, benzodiazepines, and trihexyphenidyl can be used to treat spasticity that causes discomfort. Additional medications to consider include tizanidine, dantrolene, and gabapentin. Although no data support the efficacy of medical cannabis in cerebral palsy, many families are using cannabidiol or cannabidiol with tetrahydrocannabinol supplements in the hope of relieving spasticity; therefore, it is important to ask families about use of any such supplements. Children with mild spasticity may not need any medications for tone management during early childhood but may need intervention as they grow and pursue more complex motor tasks.
Botulinum toxin injections for focal spasticity are approved by the US Food and Drug Administration (FDA) for children 2 years old and older and may be used in isolation or in conjunction with oral medications. Surgical interventions for spasticity include intrathecal baclofen pump and selective dorsal rhizotomy. Recognition of spasticity and distinction from dystonia and rigidity is particularly important when considering possible etiologies as well as appropriate therapeutic interventions for cerebral palsy. Some surgical procedures targeting spasticity, such as selective dorsal rhizotomy, may actually worsen a patient’s function if their dystonia is mistaken for spasticity. For children with concurrent medication-refractory dystonia, DBS targeting the globus pallidus internus can be considered. A care pathway for children with cerebral palsy with dystonia has been published by the American Academy for Cerebral Palsy and Developmental Medicine.
Parkinsonism in children is rare compared with other phenomenology but can be a manifestation of many different disorders, including toxic exposure or genetic or structural causes. As in adults, parkinsonism in children is characterized by tremor, bradykinesia, akinesia, rigidity, and postural instability. Parkinsonism typically reflects an underlying deficit in dopamine; thus, concurrent dystonia may be present.
Most commonly, acquired parkinsonism in children is secondary to use of dopamine-blocking medications or other medications. The most common autosomal recessive juvenile Parkinson disease is PARK2 disease, due to a mutation in the parkin gene. Other childhood-onset degenerative disorders associated with parkinsonism include Huntington disease, Rett syndrome, neuronal intranuclear inclusion disease, pallido-pyramidal syndrome, Kufor-Rakeb syndrome, PLA2G6-associated neurodegeneration with brain iron accumulation, Fahr syndrome, pantothenate kinase–associated neurodegeneration, Niemann-Pick disease type C, and juvenile neuronal ceroid lipofuscinosis. Injury to the basal ganglia from stroke, tumor, hydrocephalus, encephalitis, or postinfectious autoimmune or inflammatory processes may manifest as parkinsonism or other movement disorders.
Parkinsonism in infants may be difficult to identify as such and should be considered for any infant with hypotonia and reduced movement of undetermined etiology. Parkinsonism can contribute to poor feeding and failure to thrive. Monoamine neurotransmitter disorders are a heterogeneous group of mostly autosomal recessively inherited neurologic disorders that typically present as infantile-onset dystonia-parkinsonism.
Neurotransmitter disorders may result from (1) inability to synthesize adequate or functional neurotransmitter molecules, (2) impaired neurotransmitter transport, (3) mutations leading to difficulties with synthesis of cofactors necessary for appropriate production of neurotransmitters, or (4) inability to appropriately break down neurotransmitters. Examples of primary neurotransmitter synthesis defects include deficiency in the enzyme tyrosine hydroxylase or aromatic l-amino acid decarboxylase ultimately resulting in insufficient production of dopamine, with profound consequences for motor function and development. An example of defective monoamine transport is dopamine transporter deficiency syndrome, in which dopamine cannot be properly cleared from the synapse; this condition typically presents in infancy as a hyperkinetic movement disorder with progression to severe parkinsonism during early childhood. Tetrahydrobiopterin is a cofactor necessary for monoamine synthesis; disorders such as sepiapterin reductase deficiency or GTP cyclohydrolase 1 deficiency, an example of a dopamine-responsive dystonia, impair production of this critical cofactor, resulting in clinical movement disorders characterized by hypotonia, parkinsonism, and dystonia. Neurotransmitter catabolism defects such as monoamine oxidase deficiencies or dopamine β-hydroxylase deficiency may result in insufficient breakdown of dopamine and impaired synthesis of norepinephrine and epinephrine; as an example, monoamine oxidase deficiency typically presents in boys with impaired attention, poor learning, and behavioral problems and can be accompanied by autonomic symptoms such as flushing, sweating, headaches, and diarrhea (reflective of deficiency of epinephrine and norepinephrine).
FUNCTIONAL MOVEMENT DISORDERS
Functional movement disorders (previously referred to as conversion disorders, psychogenic movement disorders, or hysteria) are complex neurobehavioral disorders with poorly understood pathophysiology. These disorders may present in children of any age, although incidence is higher in the teen years. Children may present with features similar in appearance to any of the phenomenologies previously discussed, but the disorders most commonly involve tremor, dystonia, tics, or gait abnormalities. Although incidence is similar between boys and girls at younger ages, there is a female preponderance in adolescents. Historically, functional disorders were considered a “diagnosis of exclusion,” but a modern approach incorporates a balance between exercising due diligence to rule out nonfunctional causes and recognizing key features that support early diagnosis of a functional etiology. Early and accurate diagnosis avoids excessive medical testing and treatment and delayed diagnosis and enables implementation of appropriate interventions. The importance of appropriate management of these diagnoses is further supported by data demonstrating that positive prognostic indicators for a patient with a functional disorder include acceptance of the diagnosis by the patient and their caregivers and identification and management of concurrent psychological stressors or psychiatric disorders.
Clues to a functional etiology include sudden onset with rapid progression of often severely abnormal movements that dramatically affect quality of life in a previously healthy child. Risk factors include unrecognized anxiety, unresolved physical or psychological trauma, and other concurrent neurologic or psychiatric disorders. The neurologist plays an important role as the diagnostician and coordinator of a multidisciplinary intervention integrating psychology, psychiatry, and physical and occupational therapies as well as any additional support services tailored to an individual’s recovery.
Periodically there have been events of mass sociogenic illness presenting as functional movement disorders in children, such as psychogenic gait disorders after H1N1 flu vaccination or sudden onset of ticlike movements in a group of students attending the same high school. Similarly, the incidence of functional tic disorders has noticeably increased in the setting of the current COVID-19 pandemic, with many cases associated with social media use. The patients tend to be girls and young women in their teens and twenties with no prior history of tic disorder who present with sudden, explosive onset of severely disabling ticlike behaviors, often including coprolalia and self-injurious behaviors (features that are rare in children with tic disorders or Tourette syndrome). Patients may share videos of their symptoms on social media sites, leading to increased attention and feedback contributing to the persistence of their symptoms.
RARE BUT TREATABLE NEUROMETABOLIC MOVEMENT DISORDERS NOT TO MISS
Although many pathologic pediatric movement disorders are not curable, several treatable childhood neurometabolic disorders exist, which should not be missed. Efficient and accurate diagnosis of these disorders is essential to timely initiation of appropriate treatment. A detailed review of all neurometabolic diseases manifesting as movement disorders is outside the scope of this article, but key examples that are treatable and appear during childhood are summarized in table 11-10.
Clues to a possible underlying undiagnosed neurometabolic disorder contributing to the clinical presentation of a pediatric movement disorder include (1) diurnal fluctuation of disordered movement such as dystonia (such as dopamine-responsive dystonia [also known as DYT5 and Segawa syndrome], or unrecognized sepiapterin reductase deficiency in a child presumed to have cerebral palsy); (2) progression of symptom severity or accumulation of new symptoms over time (such as is seen with cerebral folate deficiency); (3) clinical signs or symptoms suggestive of a specific neurotransmitter deficiency (such as oculogyric crises with hypotonia and dystonia as seen in aromatic l-amino acid decarboxylase deficiency); and (4) absence of history or other risk factors to support a diagnosis such as cerebral palsy or autism. The neurologist should pursue additional diagnostic evaluation for any child in whom a neurometabolic disorder is suspected.
PEDIATRIC MOVEMENT DISORDER EMERGENCIES
There are several pediatric movement disorder emergencies that a neurologist should be able to recognize and treat. A full review of movement disorder emergencies was published by Kipps and colleagues.
Drug-Induced Movement Disorders
The increased use of psychotropic and stimulant medications in children has contributed to an increased incidence of drug-induced movement disorders in this population. Additionally, young children are at high risk of accidental ingestion of medications and other substances that may trigger abnormal movements manifesting as chorea, dystonia (status dystonicus), parkinsonism (hypokinetic/rigid syndrome), tremor, ataxia, myoclonus, akathisia, stereotypies, tics, or dyskinesias. Such drug-induced movement disorders may be acute or more insidious and can be caused by a wide array of substances. Key clues to a drug-induced movement disorder are rapid onset of new severe symptoms, temporal association with medication administration or recent introduction of new medication, and known use or presence in the household of a dopamine-blocking agent or stimulant medication (including many asthma medications). Potentially life-threatening drug-induced movement disorders include acute dystonic reaction, neuroleptic malignant syndrome, and serotonin syndrome. A common presentation of drug-induced movement disorders is ataxia in a young child due to accidental ingestion. Rapid recognition of the adverse reaction with identification and immediate cessation of the offending agent is essential. In the case of any acute drug-induced movement disorder, careful monitoring of vital signs and respiratory drive is indicated. Acute dystonic reactions are treated with anticholinergic medications (diphenhydramine or benztropine) with or without benzodiazepines.
Baclofen withdrawal is a potentially life-threatening movement disorder emergency. Patients can present with a broad continuum of symptoms with worsened spasticity, irritability or agitation, rigidity, dystonia (status dystonicus), seizures, hypertension or hypotension with shock, tachycardia, hyperthermia, altered mental status, hallucinations, and psychosis. In severe cases, symptoms can proceed to rhabdomyolysis with subsequent cardiac and renal injury, disseminated intravascular coagulation, multisystem organ injury and failure, and death. Withdrawal can occur with sudden cessation of oral or intrathecal baclofen or after recent decrease in dosing, unrecognized empty baclofen pump, baclofen pump failure, or unintentionally turning a baclofen pump off. Treatment includes immediate administration of baclofen and/or oral or IV benzodiazepines in addition to supportive care (table 11-11).
FUNCTIONAL NEUROSURGERY FOR PEDIATRIC MOVEMENT DISORDERS
DBS is an increasingly available treatment for pediatric movement disorders including chorea, dystonia, and tremor, and is an emerging treatment for medication-refractory severe tics. Just as referral for epilepsy surgery is considered best practice for a child with medication-refractory epilepsy after a trial of two antiseizure medications, it is prudent to consider referral for pediatric DBS for a child with medication-refractory dystonia, chorea, or tremor. Historically, DBS was reserved for children with primary dystonia; however, therapeutic applications have broadened, and DBS can be effective for secondary dystonia. Several anatomic targets for DBS for dystonia have been described in the literature, the most common being the globus pallidus internus. Targeted pallidotomy may also be considered in a child with severe dystonia who cannot tolerate DBS.
This article focused on identifying key phenomenology of benign and pathologic movement disorders in children. Following are key principles to remember in assessing children for abnormal movement:
- Children can present with a broad spectrum of abnormal movements, most of which are benign. Recognizing benign movements in children is just as important as recognizing pathologic movement.
- Although children are not just “little adults,” they share many features in common with adults when it comes to movement disorder phenomenology.
- Children are more likely than adults to present with a mixed movement disorder. Recognizing similarities and key differences in movement disorder phenomenology between children and adults and understanding how those phenomenologies present at various stages of development can help the clinician better categorize and treat abnormal movements in children.
- If a child has a neurologic condition, they are highly likely to also have some abnormal movement on examination. Knowing when to treat versus when to reassure is an important balance to strike.
- Appropriate diagnosis and treatment of movement disorders in children can have a major impact on development, learning, and quality of life, even for children with incurable neurologic disorders.
- Developmental control of voluntary movement begins at the head and neck and progresses to the trunk and then the extremities (rostrocaudal gradient).
- Coordinated movement involves the whole brain, not just the basal ganglia and motor cortices but also the brainstem, limbic system, cerebellum, frontal lobes, and nonmotor pathways.
- Voluntary movement involves an intricate balance of “stop and go” signaling, with dopamine playing the role of fine motor modulator.
- Understanding phases of movement (motor planning, initiation, and execution) can help to better identify abnormal movements.
- The clinician should ask the child about their movements: what, where, when, with whom, wax/wane, worsening, why (Why do you think you have these movements?) (What do you want help with?).
- The clinician should pay careful attention to developmental milestones and watch for signs of subtle delay when evaluating a child for movement disorders.
- The clinician should dig deep on family history; encourage parents to ask their families about their own childhood movements when evaluating a child presenting with a movement disorder.
- Understand both the manifestation and functional impact of movements in multiple environments when evaluating a child presenting with a movement disorder.
- Ask about and normalize worry to further explore the role of anxiety when evaluating a child presenting with a movement disorder.
- Understanding of developmental milestones is key to recognizing normal versus abnormal movements.
- Observation is an essential skill for the pediatric movement examination.
- Making the examination fun and using play to elicit movement patterns is key to an efficient and thorough movement examination in children.
- Tone is dynamic. Accurate and thorough understanding of tone demands examination in multiple states (at rest, with activity, while asleep).
- Many abnormal movements in children are benign and will resolve with development.
- Tics and stereotypies are the most common benign movement disorders in childhood.
- Benign motor stereotypies typically do not require intervention.
- Urge and suppressibility are key features of tics.
- Nonpharmacologic interventions for tics include comprehensive behavioral intervention for tics.
- Movement disorders in children can present with phenomenology similar to that in adults and may be categorized as chorea, dystonia, myoclonus, tremor, ataxia, spasticity, and parkinsonism.
- Unlike adults, children often present with a mixed movement disorder; thus, discerning the primary phenomenology can be challenging but remains the foundation of accurate and timely diagnosis and treatment.
- Sydenham chorea is a common cause of treatable acute-onset chorea in children. Early recognition and diagnosis allow for appropriate intervention with steroids for symptom management.
- Symptom severity in Sydenham chorea is highly variable, but children commonly present with complaints of new clumsiness (dropping items, falling), gait instability, irritability, poor coordination, and possible changes in speech and behavior.
- Sydenham chorea is a form of rheumatic disease; thus, screening and monitoring for associated cardiac involvement are imperative.
- Genetic causes for chorea should be considered in any child with new-onset subacute progressive chorea, especially if accompanied by other neurologic or psychiatric features.
- For the child with spasticity and dystonia, surgical intervention must be considered carefully, as certain interventions for spasticity (in particular, selective dorsal rhizotomy) may improve the spasticity but “unmask” concurrent dystonia, resulting in worsened motor function.
- Surgical candidates should be evaluated by a multidisciplinary review board including specialists in neurology, neurosurgery, and physical, occupational, and speech therapy, as well as undergo a thorough psychosocial evaluation.
- Surgical intervention with pallidal deep brain stimulation should not be delayed for children with medication-refractory progressive dystonia.
- It is always prudent to trial levodopa for any child with dystonia to rule out a treatable dopa-responsive dystonia.
- Examples of benign physiologic myoclonus include hiccups, exercise- or anxiety-induced myoclonus, benign neonatal sleep myoclonus, or hypnic jerks in older children.
- The most common causes of tremor in children are the primary tremors: developmental tremor, enhanced physiologic tremor, and essential tremor.
- The clinician should obtain a thorough family history and examination of accompanying family members at the time of neurologic examination for tremor.
- Toxic ingestion is at the top of the differential diagnosis for acute ataxia.
- Clinical distinction between spasticity, dystonia, and rigidity is essential for accurate diagnosis and appropriate treatment of the hypertonic child.
- Although spastic cerebral palsy is the most common type, many children with cerebral palsy present with a mixed movement disorder.
- Key principles regarding the diagnosis of cerebral palsy are as follows: (1) Cerebral palsy is a clinical description and not an etiology. (2) Cerebral palsy is a permanent disability. (3) Cerebral palsy is a nonprogressive brain process, but the physical manifestations of the disorder are not necessarily static.
- Botulinum toxin injections for focal spasticity are approved by the US Food and Drug Administration for children 2 years old and older and may be used in isolation or in conjunction with oral medications.
- Recognition of spasticity and distinction from dystonia and rigidity is particularly important when considering possible etiologies as well as appropriate therapeutic interventions for cerebral palsy.
- Some surgical procedures targeting spasticity, such as selective dorsal rhizotomy, may actually worsen a patient’s function if their dystonia is mistaken for spasticity.
- Parkinsonism in infants may be difficult to identify as such and should be considered for any infant with hypotonia and reduced movement of undetermined etiology.
- Early and accurate diagnosis of functional movement disorders avoids excessive medical testing and treatment and delayed diagnosis and enables implementation of appropriate interventions.
- Diurnal fluctuation of symptoms may point to an underlying neurometabolic disorder.
- Potentially life-threatening drug-induced movement disorders include acute dystonic reaction, neuroleptic malignant syndrome, and serotonin syndrome.
- It is prudent to consider referral for pediatric deep brain stimulation for any child with medication-refractory dystonia, chorea, or tremor.