Movement disorders are associated with abnormalities of the basal ganglia or their connections. The basal ganglia, a group of deep gray matter nuclei, including the caudate, putamen, globus pallidus, and subthalamic nuclei, along with their connections, constitute the extrapyramidal system. This system regulates and controls the motor corticospinal (pyramidal) system. Pyramidal system lesions may cause weakness and spasticity. Although this chapter briefly discusses these impairments because they may accompany movement disorders, particularly in children with cerebral palsy, its focus is on abnormalities of motor control.

Movement disorders are usually stratified as hypokinetic (too little movement) or hyperkinetic (uncontrolled excessive movement). The hyperkinetic disorders include tics, tremor, dystonia, chorea, and myoclonus. Although classification of abnormal movements is based on phenomenology rather than anatomical location, different anatomical sites within the basal ganglia have classic movement associations. For example, lesions of the substantia nigra typically result in bradykinesia and rest tremor; those of the caudate nucleus, chorea; and those of the putamen, dystonia.

The phenomenology of movement disorders is shared between children and adults, but pediatric movement disorders have several distinct clinical characteristics. With the exception of tics, movement disorders appearing in childhood are less common than those appearing in adulthood, are more likely to be a result of an underlying static or progressive disease process (2), and are more likely to have a metabolic or genetic etiology. Therefore a thorough examination, including skin examination, family history, and birth and developmental history, is imperative in the evaluation of every child presenting with a movement disorder. Because earlier-onset disease is more likely to be metabolic, imaging and laboratory evaluations also vary depending on the age at onset of a movement disorder. For example, children with dystonia should undergo magnetic resonance imaging (MRI) to rule out secondary disease (3). The clinical course depends on the time that the insult occurs during development. For instance, dopamine deficiency occurring at an early age is associated with prominent dystonia and some parkinsonism, whereas in adults, it results in parkinsonism with limited dystonia. Furthermore, dystonia starting in childhood is more likely to affect the limbs and progress to the trunk and neck, whereas in adults, it is more likely to start in the arm, neck, or face, and often does not spread (4). Because children’s nervous systems are continually developing, a static injury to the brain can cause variable or progressive symptoms as a child grows (5). This principle becomes imperative when monitoring and treating children with dystonia or chorea resulting from a static encephalopathy.

Although worrisome, not all involuntary movements in children are abnormal. For example, stereotypy, a repetitive purposeless movement of the hands, frequently occurs in impaired children. However, neurologists may see stereotypy in neurodevelopmentally normal children, and in them, it may spontaneously resolve (6). This chapter divides movement disorders primarily by their major phenomenologic subgroups (i.e., parkinsonism, tremor, dystonia and myoclonus, with additional emphasis on Wilson disease, psychogenic movement disorders, and paroxysmal movement disorders).

The prototypical hypokinetic disorder is parkinsonism. In contrast to that in adults, parkinsonism occurs infrequently in children (7). The cardinal features of parkinsonism include bradykinesia, rigidity, rest tremor, and postural instability. Manifestations of bradykinesia are drooling, hypomimia, hypophonic speech, aprosody, loss of spontaneous gesturing, and micrographia. In children with these features, physicians should differentiate true parkinsonism from psychomotor slowing, which is the slowness of movements associated with depression, and assess for additional movements. Features that can be present in parkinsonism and not psychomotor slowing are postural instability and decrementing amplitudes during rapid alternating movements, such as repetitive hand opening and closing.

Whenever childhood parkinsonism is identified, a diagnosis of Wilson disease, a treatable neurodegenerative disorder, should be considered. This important disease is discussed in more detail later. The differential diagnosis of childhood parkinsonism also includes brainstem tumors and strokes, the akinetic juvenile form of HD (Westphal variant), young-onset Parkinson disease, neurodegeneration with brain iron accumulation, some spinocerebellar atrophies, dopa-responsive dystonia, and the juvenile form of neuronal ceroid lipofuscinosis. In each of these disorders, parkinsonism is usually not the sole neurological feature. For example, juvenile HD is associated with eye-movement abnormalities, and many of the others, including dopa-responsive dystonia and young-onset Parkinson disease, may also show dystonia along with parkinsonism (8). As childhood parkinsonism is extremely rare, and its etiologies are varied, its psychiatric comorbidities are not well described. However, higher rates of depression have been observed in patients with young-onset as opposed to older-onset Parkinson disease (9).

The remainder of the chapter focuses on hyperkinetic movement disorders, which are the most frequent movement disorders in children.

Tremor, among the most common of all movement disorders, is defined as the rhythmical oscillation of part of the body around one or more joints (10, 11, 12, 13). Tremors can be classified according to whether they occur (a) at rest, (b) while maintaining a posture, (c) with generalized activity, or (d) during the execution of a specific task. Examinations should include careful observation of patients with their eyes closed and arms resting in their laps, with their arms outstretched (posture holding), while reaching toward objects, such as in the finger-nose-finger task, and while writing and pouring.

Essential tremor (ET) is by far the most common form of action tremor. It is prominent with actions, such as pouring (14), writing and finger-nose-finger task, and with sustained posture. There is a lack of long-term prognostic data for children, but the mean age at onset of ET in a large childhood-onset series was 8.8 years (15). It has been estimated that only 5% of ET has onset in childhood, and it is not known whether childhood-onset ET is more severe or has a worse prognosis than the later-onset variety (16). Whereas adults with ET may exhibit hand, head, and voice tremor, children are much less likely to develop head tremor (17). Amplitude of tremor tends to increase with age (18). Approximately 50% of patients have evidence of other, mild cerebellar signs such as abnormal tandem gait (19). In adults with essential tremor, alcoholism is a frequent psychiatric comorbidity; however this has been less well studied in children (20).

Postural tremor, a 6- to 12-Hz tremor, occurs in both essential and enhanced physiological tremor (13). Enhanced physiological tremor can appear in the setting of the use of sympathomimetic drugs, lithium, steroids, and valproic acid, as well as with metabolic disorders, such as thyrotoxicosis and hypoglycemia. This tremor rarely requires treatment beyond discontinuation of the inciting medication, in those cases in which it may be removed. Children with hereditary and nonhereditary neuropathies may also demonstrate tremor, which is suggestive of enhanced physiologic tremor (21). Tremor occurring predominantly at rest is very rare in children and adolescents. When ET is very severe, it can also appear at rest but will still be more prominent with action (22). Intention tremor, a 2- to 4-Hz action tremor, elicited by finger-nose-finger testing, may be seen with cerebellar disease. Cerebellar tremor is different from ET in that the child has difficulty hitting the target and there is a widening arc in reaching for the target (dysmetria). The tremor is usually due to disease in the cerebellum or its outflow pathways. A directional tremor, tending toward a particular posture, termed dystonic tremor, is described in this chapter’s section on dystonia. Jerky, fast, irregular tremor may be a manifestation of myoclonus. Psychogenic tremor may also present in childhood, and this also is discussed later in the section on psychogenicity.

When tremor significantly affects handwriting and other activities of a child’s daily life, treatment is warranted. There is little evidence for the treatment of ET in children. First-line medications for ET in adults include propranolol and primidone. Propranolol is the most effective tremor-suppressing medication (23). Although they do not achieve central nervous system (CNS) penetration like propranolol, other β-blockers also are efficacious, suggesting that the therapeutic effect may be partially mediated by peripheral β-adrenergic receptors (24). Primidone is a barbiturate with antitremor activity (25). Starting with a very low dose and slowly titrating the dose to the lowest effective dose may prevent side effects, particularly sedation and nausea. When propranolol is contraindicated, as in asthmatics or children with depression, topiramate and clonazepam also may be effective (26).

Wilson disease, a rare disorder of copper metabolism, deserves special mention because it is treatable and hereditary. This disorder results from deficient excretion of copper into the bile, leading to toxic accumulations of copper in the liver, kidney, brain, and cornea (27). It is progressively degenerative unless identified and treated. In about 15% of cases, neuropsychiatric symptoms such as cognitive decline, impulsive behavior, antisocial behavior, and personality change occur before the onset of abnormal movements (1,28). Although symptoms may be subtle, features that meet criteria for anxiety disorder or manic-depressive disorder may develop. Approximately 40% of cases present with neurological symptoms, usually after age 12, whereas another 40% present with liver disease, usually before age 12 (29). The manifestations of Wilson disease are diverse, but three
general clinical presentations are seen, each of which may overlap: (a) an akinetic-rigid syndrome resembling parkinsonism, (b) a generalized dystonic syndrome, and (c) “pseudosclerosis” with postural and action wing-beating tremor. Symptoms usually appear between ages 11 and 25 years but can appear as early as 4 years (30). Dystonia is a frequent feature and can affect the face and oropharynx, resulting in the characteristic “risus sardonicus,” or the appearance of a forced grin, as well as drooling.

Because of its treatability and protean spectrum of clinical manifestations, physicians should consider Wilson disease in any child with a movement disorder. Kaiser-Fleisher rings are visible in virtually all patients with neurological Wilson disease, and low ceruloplasmin levels occur in all but 5% of patients. Ceruloplasmin levels can be falsely low in protein-loss states and falsely elevated in pregnancy. Copper levels in 24-hour urine collections are more diagnostically reliable: rates less than 50 μg per 24 hours exclude the disease, and most patients with Wilson disease will have rates of greater than 100 μg per 24 hours. In inconclusive cases, a liver biopsy showing copper deposition is the definitive test.

Wilson disease is an autosomal recessive disorder due to mutations in a coppertransporting adenosine triphosphatase (ATPase) gene on chromosome 13 (31,32). It may be caused by either two copies of one mutation (homozygous) or one copy of two different mutations (compound heterozygote). Because a multitude of causal mutations occur, genetic testing is unwieldy (27).

Treatment of neurological Wilson disease had centered on d-penicillamine, but this drug can result in irreversible neurological worsening. Therefore current first-line treatment is the drug tetrathiomolybdate (33). This drug both blocks copper absorption and binds to copper in a nontoxic way, making it beneficial as an acute therapy. Usually this is coupled with zinc maintenance therapy, which also blocks absorption, and is a safe choice in children for chronic treatment (34). As tetrathiomolybdate is available only on an experimental basis, physicians should consider referring severe cases as an emergency to a center specializing in Wilson disease. Liver transplant also successfully reverses neurological manifestations of Wilson disease in about 80% of cases (35). With all forms of treatment, neurological symptomatic improvement normally occurs over a period of 6 months to a year.