Chapter 13. Movement and Balance Disorders

Although large-scale epidemiologic studies are lacking, pediatric movement disorders are relatively common. Many movements that are brought to clinical attention are transient and may be associated with normal development. Additionally, the natural history of specific disorders varies and must be interpreted in the context of a child's developmental stage. A careful history, physical examination, and direct observation of the movements in question are critical for diagnosis and management of pediatric movement disorders (Table 13-1). Factors that should prompt consideration of more significant underlying neurological disorder include the progression of symptoms, a family history of a heritable neurological disease, complications during childbirth, a failure of the child to reach developmental milestones, and significant functional impairment. Serological tests, electroencephalography, and imaging studies may contribute in unusual cases, but in the majority of cases it is the clinical impression of the treating physician that drives both diagnosis and treatment of pediatric movement disorders.

Movement disorders can be broadly classified based upon whether they are hyperkinetic or hypokinetic. Hyperkinetic disorders involve excessive involuntary movements, including tics, chorea, myoclonus, dystonia, and tremor. Hypokinetic disorders manifest with bradykinesia (paucity or slowness of movement) and rigidity (abnormal muscle stiffness), as can be seen in parkinsonism. In contrast to adults, the overwhelming majority of movement disorders in children are hyperkinetic. In a tertiary pediatric neurology movement disorders practice, Fernandez-Alvarez and Aicardi reported tics (39%), dystonia (24%), tremor (19%), chorea (5%), myoclonus (3%), akinetic-rigid syndromes (2%), and mixed disorders (8%) out of a sample of 684 children.1 This chapter will focus on the most common types of movement disorders encountered in pediatric neurology practice, emphasizing correct identification and appropriate initial management.

Tics are sudden, rapid, nonrhythmic repetitive movements or vocalizations, usually in the presence of an otherwise normal neurological exam. Most experts regard tic disorders along a spectrum of disease from transient tic disorders, characterized by the presence of simple tics that spontaneously resolve, to Tourette syndrome (TS), a chronic disorder featuring both motor and vocal tics. Since the overall incidence of tics may be as high as 20% in the school-age population,2 the development and resolution of a simple tic in a child could almost be considered a part of normal development. Tic disorders are five times more common in boys than in girls, and the median age of onset is 5 to 6 years.3 Recent epidemiologic studies suggest that approximately 3% of school-age children meet the diagnostic criteria for Tourette syndrome.4-7

Virtually any voluntary movement can manifest as a tic. Simple tics may include eye-blinking or squinting, facial grimacing, licking the lips, head jerking, shoulder shrugging, spasms of the abdominal wall, or rapid arm movements. Complex tics involve more formed or stereotyped movements, such as touching, smelling, shaking, hair combing, or jumping. Vocalizations often include grunting, coughing, throat-clearing, and in a minority of cases, repetition of words (echolalia), screaming, or outbursts of profanities (coprolalia).8 In contrast to other paroxysmal movement disorders, such as stereotypy and myoclonus, tics characteristically migrate from one area of the body to another over time (Table 13-2). Tics have been described as being "suppressible yet irresistible," illustrating how patients may disguise the abnormal movements in public settings, only later to relieve the accumulated urge to perform tics at a higher frequency in private. However, this phenomenon of a "rebound" has come into question with work specifically examining tics after a period of suppression.9

Patients who have either motor or vocal tics satisfy the diagnostic criteria for chronic tic disorder or transient tic disorder, depending upon whether or not the symptoms resolve within 12 months of onset. The DSM-IV criteria for Tourette syndrome require both motor and vocal tics, which do not have to occur simultaneously; a duration of greater than 3 months; onset before age 18; and resultant disability. Additionally, the symptoms must not be explained by drug exposure, or another medical condition such as Huntington disease, cerebral palsy, pervasive developmental disorder, or encephalitis.

Importantly, Tourette syndrome is associated with various behavorial syndromes, including attention deficit–hyperactivity disorder (approximately 50% of TS patients), oppositional-defiant disorder, conduct disorder, rage, obsessive-compulsive symptoms, and depression.10-13 These potential comorbidities can cause disability, which in many cases is more important to address than the tics themselves. Patients with TS are said to have obsessive compulsive behaviors (OCBs) rather than obsessive compulsive disorder (OCD) per se, because patients with TS seldom meet the DSM IV criteria for that diagnosis.14

Stereotypy is in the differential diagnosis of a suspected tic disorder. Motor stereotypies are relatively complex, seemingly purposeful, stereotyped movements, generally of the arms, head, face, or neck. Examples of stereotypy may include recurrent raising or lowering of the arms, flapping of the hands, thumb-sucking, body-rocking, and head-banging. Although stereotypies can be severely disabling if they are sufficiently intrusive or violent, they usually do not interfere with daily function. Characteristically, stereotypies are triggered by excitement, fatigue, or anxiety. The majority of the literature on stereotypy describes such movements in the context of developmental disorders such as autism and Rett syndrome or cases of congenital blindness, although they can occur in developmentally normal children.15-18 Unlike tics, stereotypies do not migrate among different locations nor do the movements themselves evolve significantly over time; and in a study by Mahone and associates, the age of onset of stereotypies in 90% of patients was younger than 3 years.19 Despite this, it may be difficult in some situations to distinguish among complex tics, obsessive compulsive behaviors, and stereotypies, and differentiating these entities may be important, as the pharmacotherapies for tic disorders and obsessive compulsive disorders are different, and there have been no well-designed treatment studies of stereotypies.

Tremor is a rhythmic, repetitive movement oscillation of one or more limbs or of the head. Tremor typically involves alternating contractions of agonist and antagonist muscle groups. Tremor may occur at rest or during posture and action. Rest tremor is very uncommon in children. It is assessed with the patient seated with the arms and legs at rest. Having the patient close his or her eyes or introducing a distraction such as a cognitive task can reveal latent subclinical rest tremor or exacerbate baseline rest tremor. Postural tremor is assessed with the arms extended in front of the patient or with the patient holding a cup of water in the hand. Action tremor may be demonstrated by finger to nose testing or by mimicking drinking or using a spoon or fork.

Both action and postural tremor are common manifestations of essential or familial tremor, which is likely the most common type of tremor in children. As the name implies, familial tremor is often genetic and transmitted in an autosomal dominant manner, although penetrance is variable, and typical essential tremor (ET) can occur sporadically. Despite intense investigations, the identification of a gene associated with familial tremor has remained elusive, supporting a role for multiple gene interactions contributing to the phenotype. Although often characterized as a disease of senescence, reports by Lou and Jankovic and Louis and associates underscore that essential tremor can have childhood onset.20,21 Hornabrook and Nagurney reported adults with essential tremor had a childhood onset in 4.6% of cases.22 Childhood-onset essential tremor is phenomenologically similar to essential tremor in adults, although there is evidence that childhood-onset ET may be more common in boys than in girls.23 ET only rarely causes significant disability in the pediatric population, and many of the children with more severe tremor likely gravitate toward hobbies or professions with which the tremor does not interfere.

Another type of tremor that may be noted in children is enhanced physiologic tremor. A recognizable example of enhanced physiologic tremor can be appreciated upon attempting to write immediately after intense physical activity. The emergent tremor is an exaggeration of typically minimal oscillatory motor activities.24,25 Physiologic tremor may be enhanced by hypoglycemia, pheochromocytoma, thyrotoxicosis, alcohol withdrawal, valproate, lithium, theophylline, corticosteroids, adrenergic agonists, and other medications, and it can also result from intense emotional or physical stress. The disability associated with enhanced physiologic tremor primarily involves very fine hand movements such as writing or repairing a watch. The elimination of exacerbating factors can be very helpful, although some patients may have persistent difficulties and benefit from propranolol prior to such activities.

Some additional tremor syndromes should be mentioned. Jitteriness of infancy is relatively common and usually resolves within the first few hours of life. More prolonged jitteriness may result from drug withdrawal or hypoxic-ischemic encephalopathy, and the tremulousness in these cases almost always resolves within one year.26,27 Geniospasm (hereditary chin trembling) refers to a rapid, repetitive chin tremor and is regarded as an ET variant, as it tends to cluster in families.28,29 Shuddering attacks are benign, brief episodes that occur in infants or young children. These spells have the appearance of shivering with no accompanying loss of consciousness, and they typically last no more than 5 to 7 seconds. The attacks may occur multiple times per day, and shuddering spells may be difficult to diagnose by history and clinical examination alone, because they are seldom observed during a clinic visit. A home videotape recording or video EEG will usually facilitate the diagnosis.30,31 Like geniospasm, shuddering attacks have been considered an early manifestation of ET, as some patients with the attacks have primary relatives with ET.

Although debilitating tremor in children is rare, it usually is associated with other neurological abnormalities such as traumatic brain injury, cerebral palsy, or an underlying degenerative, genetic, or metabolic syndrome. These causes of tremor in children are far less common than essential tremor or enhanced physiologic tremor, and they are often much more difficult to manage medically than more common forms of tremor. A large-amplitude, proximal "wing-beating" tremor may suggest the diagnosis of Wilson disease, particularly if it is accompanied by hepatic dysfunction, dystonia, parkinsonism, and/or psychiatric abnormalities. The so-called Holmes tremor (or rubral tremor) is caused by an interruption of the dentatorubrothalamic tract, usually by trauma or by a demyelinating disease in the midbrain in or around the red nucleus. This tremor arises from interruption of the dentatothalamic outflow tract from the cerebellum to the thalamus and then to motor areas of the cerebral cortex. Rubral tremor is a debilitating, large-amplitude, proximal, low-frequency tremor (2-3 Hz) that characteristically is present both at rest and with posture and action.

Cerebellar tremor can range greatly in severity, but it characteristically presents as an action tremor that increases in amplitude as the target is approached during finger-to-nose testing. Other associated cerebellar findings may include dysarthria, a wide-based, unstable gait; and in severe cases, dysfunction of the cerebellar vermis may result in truncal ataxia, which renders the patient unable to sit up without assistance. Cerebellar tremor may be seen as a result of postinfectious cerebellitis, such as is seen in association with varicella zoster infection.32 Most cases of postviral cerebellitis improve significantly over time; however, a minority of patients are left with persistent disability. Lesions in the posterior fossa from trauma or a neoplasm should be considered in children with the new onset of cerebellar dysfunction, particularly considering that posterior fossa tumors are the most common type of solid tumor in childhood.33 The most common genetic form of cerebellar ataxia is Freidreich ataxia. The genetic basis of the disease is a triplet expansion of the nucleotide sequence of cytosine, adenine, and guanine (CAG) in the protein frataxin; in addition to ataxia, patients also develop peripheral neuropathy, corticospinal tract signs, and dysarthria.34 The mutation is carried in one out of 30,000 to one out of 50,000 persons, and it is inherited in an autosomal recessive fashion. Other genetic causes of ataxia are more rare and beyond the scope of this text, but have been described more extensively elsewhere.35,36

Dystonia is a hyperkinetic involuntary movement disorder in which twisting, writhing movements that produce abnormal postures occur at rest and/or with action, often associated with co-contraction of agonist and antagonist muscle groups. These involuntary movements are slower, with the muscle contractions typically lasting a second or more. The definition of dystonia is complicated by the fact that it refers to a group of symptoms rather than a specific disease, and aspects of dystonia may be present in the context of other neurological abnormalities. Any patient who develops the acute onset of dystonia with no prior history should raise the suspicion of an acute dystonic reaction from antiemetics such as metoclopramide or from a neuroleptic medication. Another cause of acute dystonic movements in early childhood is Sandifer syndrome, in which dystonic postures occur after the intake of food, usually in association with a hiatal hernia or gastroesophageal reflux.37,38

Dystonic movements are usually stereotyped within and across patients. Characteristic dystonic postures in children may include arching of the back or neck with or without kyphosis or scoliosis, a flexed or "spooned" appearance of the hand, or curling or pointing of the toes during walking. In general, dystonia is worsened by voluntary movements and lessened by a lack of movement or by distraction, and although the dystonic postures may appear uncomfortable, pain may not be a prominent complaint.39-43 During the execution of motor tasks, patients with dystonia may exhibit "overflow," in which additional muscle groups are involuntarily recruited, often interfering with the performance of the task. An important characteristic of dystonia that can often aid in its identification is the "sensory trick," which patients use to temporarily alleviate their dystonic movements. A sensory trick involves initiating somatosensory contact in the region of the body affected by dystonia, such as placing a finger on the chin in a patient with spasmodic torticollis or touching the lateral aspect of the orbit in a case of blepharospasm, the result of which is the temporary alleviation of the dystonic movement or posture. In children, the sensory trick may actually be performed by the parent.

Dystonia may be subclassified by the distribution of the body regions affected or by the age of onset of symptoms (eg, juvenile vs. adolescent). By definition, children have childhood-onset dystonia, and they tend to develop generalized dystonia, which typically begins in a lower extremity and spreads to other parts of the body. This underscores that the symptoms of children with idiopathic torsion dystonia are often driven by genetic or metabolic factors, such as the mutation of the protein torsin A in cases of DYT-1 dystonia.42 Focal dystonias, in contrast, affect a single part of the body. Unlike children, adults with the new onset of dystonia are more likely to develop a focal dystonia of the face or neck, and the symptoms are not likely to generalize to other parts of the body over time. Focal dystonias seldom occur in isolation in children; however, it is useful to identify focal dystonia syndromes, as they individually can form the constituents of a segmental or generalized dystonia phenotype. Some focal dystonias commonly seen in adults, such as blepharospasm (repetitive eye-blinking) and task-specific dystonias (writer's cramp or musician's cramp), are rarely seen in children; but other focal dystonias, such as cervical dystonia (torticollis) and opisthotonus, are seen in pediatric populations. Cervical dystonia involves twisting, turning movements of the muscles of the neck (eg, torticollis or retrocollis), and opisthotonus refers to a particularly severe abnormal extension posture of the neck and cervicothoracic spine.

Dystonia is often associated with other neurological symptoms and/or disorders. Secondary dystonias in children may occur in association with cerebral palsy or other causes of spasticity, lesions of the basal ganglia, and with the effects of medications. It is estimated that dystonia is the primary abnormality in as many as 15% of patients with cerebral palsy.39 Although cerebral palsy is regarded as a static condition present since birth, secondary dystonia associated with spasticity can progress as the nervous system matures,40 and a similar evolution of dystonia secondary to upper motor lesion can be observed in adults following stroke and traumatic brain injury.44 Some have referred to dystonic or choreoathetoid cerebral palsy as being nonprogressive but ever-changing, to emphasize how the dystonia phenotype may evolve over time. Wilson disease is a rare but treatable autosomal recessive cause of dystonia and parkinsonism secondary to abnormal copper metabolism, and it usually begins in childhood or early adulthood.

Dystonic tremor refers to the irregular tremor that sometimes accompanies dystonic movements. It has a lower frequency and a more irregular quality than essential tremor or parkinsonian tremor, and it is often exacerbated by certain postures, such that it can appear to be an attempt to return the affected body part to a more normal position. In addition to its association with spasticity and tremor, generalized dystonia may be associated with myoclonus. Some cases of myoclonus-dystonia have been associated with mutations in the protein epsilon sarcoglycan (DYT-11).45 Hemidystonia refers to dystonia present only on one side of the body. Hemidystonia, particularly when it is progressive, is suggestive of secondary dystonia related to a structural lesion (often in the contralateral striatum), and should prompt consideration of neuroimaging.46

Chorea ("to dance") is a hyperkinetic movement disorder in which the involuntary movements are irregular, brief, migratory, purposeless, and unsuppressible. Chorea often involves the proximal limbs, the neck, or the trunk. The superimposition of chorea upon voluntary movements has been described as being "dance-like." Analogous to benign tics, chorea has been described as a manifestation of normal development in some children, and a piano-playing movement with the arms outstretched ("chorea minima"), is present in many children in a general pediatric clinic.47 The most common cause of pathologic chorea in children is Sydenham chorea (SC). It constitutes one of the major criteria in the clinical definition postinfectious rheumatic fever and is associated with prior group A beta-hemolytic Streptococcus infection. The choreatic movements observed in this disorder classically form part of the triad of chorea, emotional lability, and hypotonia.48 Presumably, the hyperkinetic movements in SC are driven by molecular mimicry between antigens on the Streptococcus and the basal ganglia, which are both targeted by antineuronal antibodies.49 Most commonly, Sydenham chorea remits spontaneously within a year, although there are reports of chronic SC and reemergence of chorea during pregnancy (chorea gravidarum).50

Other potential causes of chorea include so-called choreoathetoid cerebral palsy, medication side effects (secondary to digoxin, valproate, or pemoline),51-53 metabolic derangements such as hypoparathyroidism, and electrolyte imbalances. Benign hereditary chorea is rare, but it is usually inherited in an autosomal dominant fashion. The specifics of the family history are very important in such cases, as chorea may be associated rarely with the development of juvenile Huntington disease, although that disease usually presents with dystonia and parkinsonism in children, as described below.

Spasticity is associated with upper motor neuron lesions. An upper motor neuron lesion results from damage to neurons or tracts anywhere rostral to the alpha motor neuron in the ventral spinal cord. On examination, there is characteristically "clasp-knife" or velocity-dependent hypertonia, in which the examiner can detect a change in muscle tone comparing slow and fast rates of passive extremity movement. In spasticity, increased muscle tone is detected at fast rates of passive movements relative to slow rates of passive movement. In children, spasticity is most commonly caused by cerebral palsy, although any upper motor neuron lesion (eg, from brain trauma or stroke) can result in spasticity. Associated examination findings in spastic hypertonia include brisk reflexes, a Babinski sign (an extensor response), ankle clonus, upper extremity extensor weakness, and lower extremity plantar ankle and dorsiflexion weakness (Table 13-3). Ankle clonus is demonstrated by briskly dorsiflexing the ankle, which evokes a rhythmic, continuous oscillating flexion–extension movement, analogous in some ways to tremor. Weakness, in addition to the hypertonicity associated with the spasticity itself, is often the most important cause of disability in these patients, in contrast to patients with a primary dystonia syndrome. In some cases of spasticity, it is the preservation of lower extremity extensor strength that permits a spastic gait ("scissor gait"). As mentioned above, dystonia and spasticity may coexist in a patient, complicating the evaluation, and there is an increasing appreciation of overlapping features between pyramidal (upper motor neuron) and extrapyramidal (basal ganglia) disorders of movement.43,54

Myoclonus is a very rapid, jerking, hyperkinetic movement disorder of the limbs, which is often bilateral. Myoclonus is stereotyped, repetitive, and unsuppressible. Myoclonus may originate from the cerebral cortex, brainstem, or spinal cord, and its differential diagnosis is extensive.55 Myoclonus in isolation in a child is not necessarily an ominous sign. The occurrence of myoclonus immediately after birth or in the neonate is benign and almost always resolves spontaneously.56,57 Nocturnal myoclonus is a normal variant that is very common in the general population. Additionally, myoclonus may be noted with metabolic derangements or in association with medications. Opsoclonus-myoclonus syndrome is characterized by rapid, involuntary, chaotic conjugate movements of the eyes, accompanied by myoclonus. The eye movements can be horizontal, vertical, or rotatory, and they are often accompanied by oscillopsia, or the sensation the world is moving. Like Sydenham chorea, opsoclonus-myoclonus is thought to be autoimmune in origin, and more than half of the pediatric patients with opsoclonus-myoclonus syndrome have underlying neuro-blastoma.58 Other potential associations with opsoclonus may include parainfectious encephalitis, systemic diseases such as celiac disease or AIDS, side effects of medications, or toxins. Myoclonus can also be an associated finding in a variety of neurological syndromes including myoclonus dystonia (DYT-11) and certain forms of epilepsy (juvenile myoclonic epilepsy, Lennox-Gastaut syndrome); therefore, the occurrence of other neurological abnormalities in addition to myoclonus should prompt consideration of such an underlying diagnosis.

Akinetic-rigid syndromes from primary neurological disorders are very rare in children with movement disorders. Parkinsonian syndromes are characterized by muscle rigidity, bradykinesia (slow movements), rest tremor, postural instability, and decreased facial expression. Movements typically are slower and become more difficult with repetition. In all cases, a thorough history and review of the medication records should be undertaken to rule out neuroleptic use, metoclopramide use, or possible ingestion of medications taken by other family members. Although rare, there are juvenile-onset parkinsonian syndromes usually associated with a predominance of dystonia, and these syndromes are generally driven by genetic or metabolic abnormalities, some of which may involve the interruption of normal dopamine synthesis. Examples include dopa-responsive dystonia/parkinsonism (DYT-5), also known as Segawa disease or dystonia with diurnal variations. Juvenile Parkinson disease and Juvenile Huntington disease (HD) both cause early onset of dystonia and parkinsonism as well. A large proportion of cases of levodopa-responsive juvenile parkinsonism are attributed to alterations in both copies of the gene parkin (ie, autosomal recessive).59 In contrast to adult-onset Huntington disease, juvenile HD usually presents initially with dystonia and bradykinetic-rigid parkinsonism rather than isolated chorea.60

A detailed history and neurological examination are the most important components of the evaluation of a patient with a movement disorder. Many movement disorders wax and wane over time or consist of paroxysms, but specific questioning almost always reveals that their onset and evolution are gradual. Acute or subacute onset of a movement disorder in a child suggests that a potentially reversible medication reaction, a metabolic abnormality, or structural lesion may underlie the symptoms.

Movement disorders must be distinguished historically from other causes of neurological dysfunction, such as seizures, neuromuscular disease, or normal variants. Seizures, in contrast to movement disorders, are commonly preceded by an aura, and are usually associated with alteration of consciousness and postictal confusion. Most movement disorders worsen during situations of anxiety or emotional stress, and primary movement disorders only rarely occur during sleep. Relevant details about the delivery of the child and the attainment of developmental milestones must be obtained, and the family history can be very useful in diagnosing both common and rare pediatric movement disorders. In particular, tic disorders along with their behavioral comorbidities and essential tremor are commonly familial, so history and even a brief physical examination of available family members can often be helpful.

Distinguishing pathologic movements from transient, benign abnormalities of movement in children can sometimes be challenging, and the history alone may be insufficient in such cases. Patients with abnormal movements are occasionally evaluated with video electroencephalography; however, families now commonly have portable video cameras, and viewing the activity recorded in the home situation usually is sufficient to make a diagnosis. In particular, video recordings can be invaluable in children who are able to suppress the movements in question while in the clinical setting.

Assessing the movements of a child often requires a great deal of patience on the part of the clinician. The examination of any movement disorder should begin with passive observation while the patient and family are providing the details of the history. The child's level of spontaneous activity should be noted, as well as any hyperkinetic involuntary movements. Vocal tics, in particular, may appear as throat clearing or other easily disguised sounds, and prior to diagnosis, these manifestions of a tic disorder may be misconstrued by the family as upper respiratory symptoms or reflux. The examination of sensory function, complex motor tasks, and higher cognitive function can be unreliable in children, particularly considering their age and developmental history, further underscoring the need for a history of attainment of various developmental milestones.

In many patients, the evaluation of gait is the most important part of the neurological examination, because walking is an important functional measure requiring the integration of multiple neurological subsystems. Specific gait patterns can suggest whether the underlying disorder is hypo- or hyperkinetic, or whether dystonia or spasticity are present. Patients with parkinsonism characteristically take small, shuffling steps with stooped posture and freezing of gait, whereas patients with cerebellar disorders or severe peripheral proprioceptive loss may walk with a wide-based ataxic gait. Dystonic movements and postures are frequently exacerbated or exposed during walking and other voluntary movements.

Despite the importance of classifying movement disorders into one of the categories described previously (tremor, tics, myoclonus, and so forth), such categorization can occasionally be difficult, and in some cases, even experienced movement-disorder clinicians may not agree on the classification of the movement. Comments and some suggested guidelines for the neurological examination of movement disorders are included in Table 13-4.

Table 13-5 contains different classifications of movement disorders in children and potential differential diagnoses within each category. The list is not meant to be exhaustive, but rather to point out the most common diagnostic entities, and to highlight other rare, specific entities that should be considered.

Diagnostic Testing

The neurological history and examination leading to classification of the movements in question may indicate that specific laboratory or radiographic studies are necessary to narrow the differential diagnosis. This being said, the results of extensive laboratory or imaging studies often do not add to the clinical evaluation, as such studies are often normal in patients with movement disorders. In particular, patients with both Tourette syndrome and straightforward cases of essential tremor do not necessarily require further blood tests or imaging studies. As mentioned previously, home video footage of the patient's abnormal movements can be invaluable in making the diagnosis. Video EEG may be helpful in some cases, as an abnormal EEG is not expected in patients with movement disorders; however, a normal EEG does not necessarily rule out seizures. Unexplained focal neurological signs elicited by the history and neurological exam should prompt consideration of imaging studies. The new onset of idiopathic dystonia requires imaging of the brain and cervical spinal cord to rule out mass lesions, although studies in patients with dystonia as an isolated feature are unlikely to be revealing.

All patients with young-onset dystonia or parkinsonism should undergo 24-hour urine collection for copper, serum ceruloplasmin measurement, and an ophthalmologic slit-lamp examination for Kayser–Fleischer rings in the cornea to rule out Wilson disease, as it is a very rare but treatable cause of these symptoms.61 Older patients with Wilson disease may present with neurological manifestions only, with subclinical hepatic disease to progress later. Pediatric-onset cases, in contrast to adults, more often present with hepatic dysfunction alone, which may make the diagnosis more challenging. Only 2% of patients who have neurological symptoms of Wilson disease will not have Kayser–Fleischer rings on slit lamp examination.

Despite the myriad genetic causes of generalized dystonia, routine genetic testing may not be recommended unless the diagnosis of dystonia is in question, particularly if the result of the test will not impact clinical management. In appropriate cases, DYT-1 testing is recommended as an initial screening test, since the well-characterized DTY-1 mutation is the most common genetic cause of generalized limb-onset dystonia ("Oppenheim dystonia"). DYT-1 mutations have variable penetrance, so the absence of family history of dystonia does not necessarily exclude it as a diagnostic possibility.

MRI should be considered for de novo movement disorders, particularly when there are concomitant focal abnormalities on the neurological exam such as spasticity, focal weakness, or other abnormalities not explained historically or with prior investigations. Acute or sub-acute onset of symptoms, in particular, suggests a potentially reversible etiology such as an electrolyte disturbance or adverse effects of medications. Routine screening for electrolyte abnormalities, thyroid dysfunction, vasculitides, the anti-phospholipid syndrome, and vitamin B12 or vitamin E deficiencies are recommended in appropriate cases.

Once the movements in question have been classified and a diagnosis made, initial management must focus on the objective level of disability, the family's perception of the patient's illness, and the family's expectations from therapy. Many patients with mild tics, tremor, or chorea do not develop significant functional disability from the abnormal movements themselves. In these cases, an appreciation of the natural history of the disease in question, that a partial response to pharmacotherapy should be expected, and caveats about common adverse effects from the specific medications are important. With this knowledge, families may be less inclined initially towards pharmacological interventions. Although the abnormal movements are frequently a source of embarrassment or irritation, establishing a diagnosis and counseling the patient on the nature of the disease are critical. Simply having the patient respond to peers who mention the symptoms, saying "I have tics" or "I have tremor," may in many cases begin the process of education. Encouraging the family to develop a supportive, understanding environment for the child at home and among peers is invaluable. Subsequent education of school teachers and peers by the family can also be extremely helpful, since acceptance by others contributes greatly to a child's sense of wellness. In patients who have persistent, disabling symptoms requiring pharmacotherapy, it should be mentioned that no drugs have been formally approved by the FDA for the treatment of pediatric movement disorders. Common practice is to initiate therapy at the lowest dose possible and slowly increase the dose over time while assessing the response to treatment. The maintenance dose should be the lowest dose that provides adequate clinical efficacy.

For more severe tic disorders, if patients choose medical therapy, the natural history of tics is to wax and wane over time, and this can complicate the evaluation of response to therapy.64 Patients frequently improve spontaneously after they reach the state of symptomatic worsening that prompted their initial medical evaluation, simply as a manifestation of the natural ebb and flow of the disease rather than some specific response to a medication. Target symptoms should be identified prior to the initiation of treatment, and patients should not leave the clinic with the expectation that their tics will be eliminated completely. No single pharmacological therapy has been shown to be universally effective for tic disorders; however, a number of agents have been investigated in randomized clinical trials.65 Initial management is often attempted with a presynaptic alpha-2 antagonist, such as clonidine or guanfacine. Adverse effects from treatment may include somnolence, depression, hypotension, and dry mouth. Other potential choices for therapy include haloperidol or atypical neuroleptics. These latter medications are not generally chosen as first-line agents, because of potential adverse effects including sedation, weight gain, acute dystonic reaction, parkinsonism, and, rarely, tardive dyskinesia. Numerous other medications have been advocated for the medical treatment of tic disorders including calcium channel blockers, buspirone, and antidepressants. Dopamine-depleting medications such as tetrabenazine have been reported to be effective for tics in Europe, but use of this agent has been limited in the United States.66 It should be emphasized again that concomitant obsessive-compulsive behaviors, ADHD symptoms, and depression may actually cause more disability than the tics in Tourette syndrome; therefore addressing these comorbidities with a multidisciplinary approach and serotonin reuptake inhibitors may be extremely helpful in such cases. Stimulants such as dextroamphetamine should be used judiciously in patients with ADHD symptoms, since stimulant medications have been reported to exacerbate tic disorders; however, more recent studies suggest this may not be the case.67

Similar to tic disorders, pharmacotherapy for children with tremor may not be necessary after careful consideration of the patient's level of disability. Various medical therapies can be attempted for tremor disorders. Propranolol and primidone are traditional first-line agents for essential treatment, but like tic disorders, complete resolution of the tremor is an unrealistic expectation, and a balance between therapeutic effects of medications and possible side effects such as somnolence and depression must be achieved. Evidence is now available for the use of topiramate for moderate to severe essential tremor in adults.68

Chorea must be assessed carefully clinically prior to treatment since the hyperkinetic movements may not be a cause of significant disability. Symptomatic treatment with neuroleptics, anticonvulsants, or with dopamine-depleting agents such as reserpine or tetrabenazine are often effective, but potential benefits of therapy must be weighed against potential adverse effects such as somnolence, depression, parkinsonism, and in the case of neuroleptics, tardive dyskinesia. In cases of chorea associated with autoimmune disease, cortico-steroids, intravenous immunoglobulin, or plasmapharesis may be considered, but again considering the natural history of the chorea in SC, many patients with mild symptoms may not require treatment.69

All patients with young-onset dystonia or parkinsonism should be treated initially with levodopa, as the symptoms of some patients with Segawa disease (dopa-responsive dystonia) normalize completely with modest doses of levodopa supplementation. Other syndromes may be caused by dysfunction in the enzymes responsible for the metabolic conversion of precursor amino acids into catecholamines in the substantia nigra pars compacta, and guidelines are available for performing lumbar puncture to diagnose neurotransmitter deficiencies including Segawa disease, tyrosine hydroxylase deficiency, and aromatic acid decarboxylase deficiency, if clinical suspicion of such a disorder is present.63 Another diagnostic test that may be considered in addition to a therapeutic levodopa trial is the phenylalanine loading test.63 This assay nonspecifically measures the function of the enzymatic pathway that converts phenylalanine to tyrosine, and it may be useful in cases of dopa-responsive dystonia in which clinical or genetic tests are unrevealing or ambiguous. An abnormal phenylalanine loading test shows prolonged elevation phenylalanine and little or no rise in tyrosine following loading. Interestingly, patients with confirmed dopa-responsive dystonia do not develop the motor complications of levodopa therapy seen in idiopathic Parkinson disease in adults, such as peak-dose dyskinesias and the "wearing off" phenomenon.

The pharmacological treatment of dystonia depends on the etiology of the symptoms. Acute onset of dystonia from neuroleptic medications or antiemetics requires cessation of the offending medication and intravenous treatment with an anticholinergic such as benztropine or diphenhydramine and a subsequent benzodiazepine, if needed. Every child with idiopathic dystonia or parkinsonism should undergo a trial of levodopa to rule out dopa-responsive dystonia. Even children with dystonic cerebral palsy may have a dopamine-responsive element to their symptoms, and the response to therapy may not be immediate.70 Excessive doses of levodopa, however, are generally not necessary to provide symptomatic benefit. Generally, the first-line agent for focal, segmental, or generalized dystonia following a levodopa trial is an anticholinergic. Children may be able to tolerate remarkably high doses of anticholinergics, in particular, and response rates in open label studies have been reported to be as high as 60% with trihexyphenidyl.71 Additional agents may be tried including baclofen, benzodiazepines, and amantadine, and some patients may respond to combinations of therapies based upon trial and error. Paroxysmal dystonias and dyskinesias may respond preferentially to anticonvulsant medications such as carbamezapine.72-74

Deep brain stimulation (DBS) has not been rigorously studied in large populations of pediatric patients; therefore, DBS in children should only be considered for severe, refractory disease in experienced tertiary centers. Appropriate young adults with severely debilitating, medically refractory dystonia or essential tremor should be considered for DBS,75,76 and neurostimulation of the internal segment of globus pallidus, in particular, is very effective for symptoms of severe idiopathic torsion dystonia. More recently DBS has been promoted for refractory Tourette syndrome in adults; however, such an invasive therapy will not be indicated in the vast majority of children with tics, as their symptoms are expected to resolve or improve significantly over time.77,78 Any invasive procedure in the central nervous system carries with it initial risk, but once successfully implanted, deep brain stimulation for dystonia or tremor in many severe cases is superior to medical therapy and can greatly improve quality of life.

Most pediatric patients with movement disorders would be well-served by at least an initial screening visit with a pediatric neurologist or pediatric movement disorders specialist to confirm the diagnosis and suggest options for therapy. However, in the initial stages of a mild tic or tremor disorder, immediate referral to a pediatric movement specialist may not be necessary. Indications for referral include complex cases associated with significant disability, patients where the diagnosis is unclear, and cases in which therapy has been unsuccessful or patients want a thorough discussion of therapeutic options. Occasionally the diagnosis of movement disorders requires longitudinal follow-up. Following the evaluation, a therapeutic strategy can be agreed upon by the clinician and family, and depending upon a variety of factors including disease severity, response to initial attempts at therapy, and practical issues such as distance from the consulting physician's practice, the patient could follow-up with either the referring physician or with the movement disorders specialist.