Chapter 19. Pediatric Movement Disorders and Infectious Disease

Pediatric movement disorders span a large spectrum of signs and symptoms that occur in a wide range of conditions, some of which may herald the development or sequelae of infectious disease. Accurate diagnosis of these disorders is essential for treatment, prognostication, and counseling. Interest in infectious etiologies of pediatric movement disorders has increased because of recent attention to pathophysiology involving immunologic mechanisms. This chapter will provide an overview of pediatric movement disorders, emphasizing their association with infectious diseases.

Movement disorders are traditionally defined as neurological syndromes in which there is either an excess or paucity of movements unrelated to weakness or spasticity. However, in children spasticity is included in the discussion of movement disorders because it often coexists with other movement disorders, especially in cerebral palsy.1 There are two broad categories of movement disorders: hyperkinetic (excess of movement or tone) and hypokinetic (paucity of movement or tone) (Table 19–1). As we are classifying movement disorders by phenomenology, specific disorders will be defined in the Clinical Presentation section below. The diagnosis and treatment sections will then address each movement disorder separately in the context of infectious disease.

Movement disorders can be the result of dysfunction at any level of the central (brain or spinal cord) or peripheral (anterior horn cell, nerve roots, plexus, peripheral nerve, neuromuscular junction, or muscle) nervous system. Many movement disorders are associated with pathologic alterations in the basal ganglia or their connections. The basal ganglia include the caudate, putamen, pallidum, subthalamic nuclei, and substantia nigra. Table 19–2 summarizes areas of dysfunction associated with specific movement disorders.

Although the precise pathophysiology of many movement disorders is unknown, infectious and immune-mediated pathophysiology in children has garnered considerable attention. Examples include congenital infections (TORCH: Toxoplasma gondii, other microorganisms, rubella virus, cytomegalovirus [CMV], herpes virus, and human immunodeficiency virus [HIV]), Sydenham chorea, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS), and acute cerebellar dysfunction.

Congenital TORCH infections cross the placenta in utero and can cause fetal infection, resulting in significant neurologic sequelae. Approximately half of infants with congenital CMV or toxoplasmosis go on to develop cerebral palsy with the associated movement disorders (Table 19–3) and two thirds of infants with congenital rubella go on to have balance and coordination problems.2

Sydenham chorea is considered the prototype for disorders in which an infectious process, group A β-hemolytic streptococcal infection (GABHS), triggers an autoimmune disorder that in turn causes a variety of neuropsychiatric symptoms. Sydenham chorea occurs in approximately 25% of cases of acute rheumatic fever. Antibodies to cells in the brain are found in some patients. These antibodies are absorbable with cell wall preparations from GABHS, but not group D streptococci. This led to the concept of molecular mimicry, with cross-reactivity between GABHS surface antigens and the brain. Abnormalities in cellular immunity have also been described.3 Swedo and colleagues described a group of 50 children in whom GABHS seemed to either trigger or worsen symptoms of tic disorders and/or obsessive compulsive disorder.3 Amidst controversy, this has since been termed PANDAS (discussed below).

Acute cerebellar dysfunction in the setting of infection is a heterogeneous set of disorders, including acute cerebellitis and acute cerebellar ataxia. In acute cerebellitis, pathological studies show T-cell infiltration within the cerebellar cortex, suggesting direct invasion of an etiologic agent.4 On the other hand, acute cerebellar ataxia is postulated to occur as a result of a postinfectious immune mechanism, as autoantibodies may be associated with this condition. Table 19–4 summarizes infectious etiologies for movement disorders in children.

What follows are clinical descriptions of common pediatric movement disorders. This includes spasticity, dystonia, athetosis, chorea, myoclonus, tics, tremor, ataxia, and rigidity.

Spasticity

Spasticity is a velocity-dependent increased resistance to passive muscle stretch. More specifically, the Task Force on Childhood Motor Disorders defined spasticity as a hypertonia in which one or both of the following signs are present: (1) resistance to externally imposed movement increases with increasing speed of stretch and varies with the direction of joint movement or (2) resistance to externally imposed movement rises rapidly above a threshold speed or joint angle.1 Spasticity is the result of an upper motor neuron lesion and thus often accompanied by weakness, loss of motor control, increased deep tendon reflexes, and clonus. It is much more common in cerebral disorders than spinal cord injuries. Spasticity is a dynamic condition, which changes over time based on emotional state, positions, alertness, and age. Often evident by 1 year of age, it may improve or resolve by early childhood. Although spasticity does not usually worsen during childhood, its effects usually do as the patient grows and matures. Prolonged involuntary muscle contraction may result in fixed contractures or joint dislocation.

Dystonia

Dystonia is involuntary muscle contractions that cause twisting and repetitive movements resulting in abnormal postures. The movement disorder can be sustained or intermittent. Muscle tone can fluctuate from normal or low tone to hypertonia. Dystonia can be precipitated by voluntary movement or vary with emotional state such as stress, pain, fatigue, or startle. It typically diminishes with distraction and sleep. Characteristic features of dystonia that may be present are “sensory tricks” or geste antagoniste, in which proprioceptive or tactile stimulation (such as touching oneself gently on the cheek) can ameliorate dystonic movement. Dystonia tends not to occur as early in life as spasticity, and typically begins in children between the age of 5 and 10 years, though it can begin as early as 2 years or later in life. The delayed onset is thought to be due to neuronal maturation or myelin formation that may be required for dystonia to manifest. Dystonia may worsen as the brain matures.1

Chorea, Ballism, and Athetosis

Chorea (derived from Greek khoreia, meaning dance), is involuntary, random, quick movements that flow from joint to joint. Movements are abrupt, nonrepetitive, arrhythmic, and have variable frequency and intensity. Characteristic of chorea is the inability to sustain muscular contraction, known as motor impersistence. This may manifest as the inability to keep the tongue protruded or maintain a fist resulting in a “milk-maid's” grip when patients are asked to grasp the examiner's fingers. It may affect any part of the body, with the most common causes in childhood being Sydenham chorea and cerebral palsy. Ballism is characterized by violent, involuntary flailing movements of the proximal muscles of the extremities. It has been considered a severe form of chorea, and is associated with damage to subcortical structures, especially the subthalamic nucleus.

Athetosis has been has been considered a slow form of chorea, and often coexists with chorea resulting in the term choreoathetosis. Athetosis is the inability to retain fingers and toes in any position because of their continual motion. This can be seen by having patients outstretch their arms with their hands held in front, demonstrating slowing moving, “piano-playing” fingers.

Myoclonus

Myoclonus presents as a sudden shock-like involuntary muscle jerk the may be focal, unilateral, or generalized. It is the fastest movement disorder, with duration of 50–200 milliseconds. It can be normal, such as hiccups or “sleep-starts” as one falls asleep. Myoclonus may be positive, meaning jerking due to active contraction of muscle groups, or negative, meaning movements due to a lapse in sustained contraction. Perhaps the most well-known form of negative myoclonus is asterixis, in which wrist extensors have a lapse in contraction, resulting in hand flapping when arms are outstretched. This is classically described with hepatic encephalopathy though can been seen with other metabolic derangements. Myoclonus may be stimulus sensitive, being brought about by tactile, postural, action, visual, or auditory stimulation, often as an “exaggerated startle.” It can be due to a lesion in any level of the nervous system.

Tics

Tics are sudden, semivoluntary highly stereotyped repetitive movements. They can be simple, involving only specific muscle groups (such as excessive eye blinks or grimacing) or more complex. Tics can be anywhere in the body, but most commonly occur in the face, head, and neck. Although vocal tics associated with outbursts of profanity (copralalia) have received considerable publicity, this is rare and vocal tics may be phonations such as sorting, sniffing, sneezing, grunting, throat-clearing, or nonsensical utterances. Tics naturally wax and wane in severity, increasing with excitement, boredom, stress, and fatigue.

Tics are often described as having a premonitory urge to move, and while the movement is suppressible, the urge builds until it is unbearable and the movement must be executed, manifesting a tic. Immediately after a tic is done, there is a transient relief of the urge to move, only to be replaced by another premonitory urge, and the tic cycle repeats itself. Tics are perhaps the most common primary movement disorder in childhood, with 5–24% of school children having at least a transient tics. Often tic disorders are associated with obsessive compulsive disorder and/or attention-deficient disorder.

Tremor

Tremor is an involuntary, hyperkinetic, and rhythmic oscillatory movement of part of the body around a fixed point or place. It is important to note if tremors occur with action, rest, posture, or specific tasks, as this will influence the differential diagnosis and treatment. While the incidence of tremor in childhood is unknown, it is 1.5 in 10,000 in the general population, and in a pediatric movement disorder clinic, 19% of children had tremor as the sole or main feature of their condition.1

Ataxia

Ataxia is characterized by problems with muscle coordination. It can affect the trunk (truncal ataxia), walking (gait ataxia), or distal extremities (appendicular ataxia). It is often associated, but not restricted to lesions in the cerebellar pathways.

Rigidity

Rigidity is much more common in adults than children. It is hypertonia in which all of the following are true: (1) the resistance to externally imposed (passive) movement is present at low speeds and does not vary with velocity; (2) contraction of muscle groups may occur, reflected in an immediate resistance to a reversal of the direction of movement about a joint; (3) the limb does not tend to return toward a particular fixed posture or extreme joint angle; and (4) voluntary activity in distant muscle groups does not lead to involuntary movements about the rigid joints, although rigidity may worsen.5 In children, it is most commonly associated with drug-induced side effects or juvenile Parkinsonism.

Any infection in the central nervous system may lead to a movement disorder, depending on which structures are involved. When approaching movement disorders, correct identification may be difficult in children where movement disorders can change in appearance given the context of growth and development. Half of all children with cerebral palsy at 1 year of age no longer have motor signs by the seventh year of life.1 More than one movement disorder may exist within the same child especially in the presence of developmental abnormalities. Other conditions that may mimic movement disorders include epileptic seizures, gastroesophageal reflux (Sandifer's syndrome), and developmentally normal involuntary movements. These include jitteriness in neonates, rapid eye movement sleep myoclonus in young infants, ritualistic behaviors, shivering, self-stimulation, and shuddering. A videotape of the movement in question provided by the caregiver can be quite helpful. Obtaining details of birth history (especially for TORCH infections), family history, medications, as well as any exposure to toxins will help guide the workup. Referral to a pediatric neurologist and/or movement disorder specialist can be quite useful early in the course of evaluation.

During the interview and examination, it is important to be very observant, as many movements may be seen while the child is unaware that he/she is being examined. For example, playing with toys, crawling, or walking is helpful and the child must be observed both during action and at rest. All children with movement disorders should undergo a neurologic examination, and most will need neuroimaging. While computed tomography can be helpful in identifying masses, bleeds, and malformations, magnetic resonance imaging (MRI) is often the modality of choice given its greater detail. If a family history is present, genetic counseling and testing may be considered.

Testing should emphasize both common and treatable etiologies. Thus, virtually every child with no obvious cause of a movement disorder undergoes testing for Wilson disease, a disorder of copper metabolism with progressive neuropsychiatric manifestations including a wide array of movement disorders. If treated with chelating therapy, it may be reversible and further progression is prevented. In Wilson disease, serum ceruloplasmin, a protein bound to copper, is low and serum copper may be high. A 24-hour urine collection looking for copper may also be low, and ophthalmologic examination may reveal copper deposition in the cornea (Keyser–Fleisher rings, see Figure 19–1). While virtually all movement disorders may warrant the evaluation described, specific issues pertinent to each disorder will now be discussed.

Spasticity

Spasticity may be secondary to brain, spinal cord, or peripheral nerve injury from virtually any etiology. Infectious culprits include abscesses within or compressing the central nervous system, encephalitis, meningitis, and postinfectious processes such as transverse myelitis and acute disseminated encephalomyelitis. Also, an infection outside of the central nervous system (e.g., otitis, urinary tact infection, pneumonia) can exacerbate preexisting spasticity. Other treatable etiologies include tethered spinal cord, spinal cord tumor, hydrocephalus and intracranial, epidural or subdural bleed. Spasticity is also present in most children with cerebral palsy, spinal cord injury, traumatic brain injury, or multiple sclerosis. For any child with spasticity, neuroimaging is indicated and joint contractures may develop. If spasticity is fluctuating or no lesion is found on imaging, infection, deep venous thrombosis, bladder distention, bowel impaction, and seizure are possibilities.

Dystonia

Dystonia may be focal or generalized and either primary, secondary, or acquired. Common focal dystonias include writer's cramp and torticollis (also known as abnormal head posture, cervical dystonia, or twisting of the neck). The term dystonia is reserved for neurologic etiologies of abnormal postures, with other causes referred to as pseudodystonia. A rare but serious and potentially infectious cause of pseudodystonia is Grisel syndrome, a nontraumatic rotatory subluxation of C1 or C2 vertebrae (atlantoaxial subluxation) without any prior history of osteopathy. This results in abnormal head and neck posture, and can appear identical to cervical dystonia (torticollis) with limited or no range of motion. It was first described as a consequence of syphilitic ulceration of the pharynx, but has since been recognized as a rare consequence of infectious, inflammatory, and/or postsurgical complications in the head and neck. It has predilection for the pediatric population, with 90% of cases below the age of 21 years. Approximately 23% of cases occur after mastoidectomy, tonsillectomy, and adenoidectomy, in that order. Upper respiration infection in the second most commonly associated syndrome.6 Patients may present with painful torticollis or sudden onset, possibly with a history of fever. Computed tomography of the neck with contrast is necessary to confirm subluxation and look for possible infection, such as retropharyngeal abscess, odontoid osteomyelitis, or deep-space infection (Figure 19–2). Treatment usually includes cervical immobilization, airway preservation, neurosurgical consultation, antibiotics, muscle relaxants, and bed rest.

Abnormal head postures have an incidence of 1.3% in children and may benefit from a multidisciplinary approach. A recent study in 73 children ages 6 months to 8 years with this presentation found etiologies to be orthopedic in 48%, ocular in 34%, neurologic in 7%, and no cause was found in 11%.7 Most cases presenting in the first 2 years of life were orthopedic, with congenital muscular torticollis (caused by tight neck muscles or a fibrous band) most commonly diagnosed. Ocular and neurologic causes manifested later in life. Ocular causes included abnormalities in extraocular muscles, especially superior oblique muscle palsy causing compensatory head tilting to minimize double vision.

The earlier the onset of dystonia, the more likely it will generalize and be disabling. A trial of levodopa is warranted in most cases of cryptogenic dystonia cases to evaluate the possibility of dopa-responsive dystonia (Segawa disease) or biopterin deficiency. Other etiologies of dystonia include hypoxia, trauma, encephalitis, stroke, tumor, or use of dopamine-receptor antagonists. Neuroimaging may show lesions in the basal ganglia, specifically the globus pallidus. Genetic testing may be considered if a family history is present.

Chorea, Ballism, and Athetosis

Chorea, ballism, and athetosis are often found associated with lesions in the basal ganglia. Sydenham chorea is a common cause of chorea in children and a major Jones criterion for rheumatic fever. Given its ramifications, all children presenting with chorea of unknown etiology should be asked about prior streptococcal infection and associated symptoms, such as an untreated sore throat. Sydenham chorea tends to involve the face and extremities and can begin unilaterally. If severe, ballism may be present. Children may also have behavioral abnormalities such as obsessive–compulsive symptoms that can predate chorea by weeks or months. Onset is usually between the ages of 5 and 15 years with a female predominance. The diagnosis is made strictly on clinical grounds as there is no confirmatory test. Symptoms tend to resolve in 1–6 months, though milder chorea can persist, with up to half of patients having chorea after 2 years. Chorea can recur, usually within 1–2 years after the original event.3 If a diagnosis of Sydenham chorea is suspected, a workup for rheumatic heart disease should be done including an electrocardiogram and echocardiography. Carditis is reported in 25–80%, with higher percentages in subjects who underwent echocardiography.3 Valvular heart disease results in antibiotic prophylaxis for medical and dental procedures. Although elevated antistreptococcal titers are found in 80% of patients, there is no consensus regarding antibiotic treatment, immunomodulatory regimens or the monitoring of antistreptococcal antibodies. However, treatments for chorea detailed below may be considered.

Chorea has many other causes, including several infectious etiologies listed in Table 19–4. It can also occur in autoimmune conditions such as sarcoidosis, systemic lupus erythematosis, and antiphospholipid syndrome. The most common causes of chorea besides Sydenham chorea include cerebral palsy and medication side effects. It is thus critical to look for secondary causes of chorea as several are treatable and reversible. If constitutional symptoms such as fever, fatigue, sweats, or lymphadenopathy or rashes are found, then an evaluation for infectious or autoimmune causes should be undertaken, including lumbar puncture. All patients with no clear etiology should also have a thyroid panel, sodium, glucose, magnesium, vitamin deficiency, and kidney function evaluated. In girls who have undergone menarche, a pregnancy test may be considered (Chorea gravidarum). A thorough medication history should also be obtained.

Ballism may be considered a severe form of chorea, and athetosis a milder variant. Thus, both have a similar differential diagnosis as chorea. Ballism is associated with lesions of the subthalamic nucleus, while athetosis is also associated with lesions in the basal ganglia due to infection, hyperbilirubinemia, ischemia, or trauma.

Myoclonus

The etiology of myoclonus is diverse, as it can originate from the cerebral cortex (cortical myoclonus), brainstem (brainstem myoclonus), or spinal cord (spinal myoclonus). Rarely, it may start in the peripheral nervous system. If an infectious or autoimmune process such as encephalitis is suspected, a lumbar puncture looking for pleocytosis and immunoglobulins in addition to neuroimaging and a complete blood count should be done. Medication and toxin exposure may also be assessed.

Cortical myoclonus may be spontaneous, occur with voluntary action or with somatosensory stimulation. Postanoxic myoclonus can be cortical in origin and stimulus sensitive with action myoclonus, which is particularly disabling as it prevents normal voluntary motion. Brainstem myoclonus, such as an exaggerated startle, is usually generalized and often triggered by auditory stimuli. Spinal myoclonus can be segmental, multisegmental, or generalized. Palatal myoclonus is a rhythmic contraction of the soft palate that occurs usually at 2–3 Hz and may persist in sleep. It may be associated with an ear-clicking sound. Some have called this palatal tremor because of its rhythmicity. There are two forms: essential and symptomatic. The essential form is self-limited and mainly occurs in children and a click may be audible. The symptomatic form results from brainstem lesions, specifically the red nucleus, inferior olive and dentate nucleus in the cerebellum, known as the Guillain–Mollaret triangle. Negative myoclonus (or asterixis) may be seen in children with diffuse encephalopathies from renal, hepatic, or pulmonary failure; malabsorption syndromes; and drug toxicity (such as phenytoin).

In virtually all cases, the possibility of epileptic activity should be evaluated. Thus an EEG should be done preferably while myoclonic movements are occurring. Video-EEG, in which a patient is videotaped during EEG recording, can be helpful in distinguishing epileptic from nonepileptic movements. Metabolic causes include kidney failure, liver failure, and hyperglycemia.

Tics

There is a wide spectrum of tic disorders, as defined by the DSM-IV criteria,8 listed in Table 19–5. The differential is categorized by severity, duration, and the presence of motor and/or vocal tics. There is much debate as to whether the pathophysiology of tics is associated with streptococcal infection or autoimmunity, highlighted by the term PANDAS. Criteria for the diagnosis of PANDAS are (1) Presence of obsessive–compulsive disorder and/or a tic disorder, (2) Age of onset after 3 years but before 11 years, (3) Episodic course of symptom severity, (4) Association with GABHS infection, and (5) Association with choreaform signs is optional.3 Much criticism of the PANDAS concept comes from the fact that Tourette syndrome and obsessive–compulsive disorder can have sudden onset or worsening without association with streptococcal infection, and isolated GABHS infection is common in children. It is thus difficult to distinguish a child with Tourette syndrome or OCD who happens to also have GABHS infection and one who may have PANDAS. Another interpretation is that PANDAS may be another form of Sydenham chorea. This controversy makes evaluation and treatment decisions difficult. If a child presents with tics or obsessive compulsive disorder in the context of recent streptococcal infection, what should be done? Certainly, if chorea is also present one should conduct an evaluation for Sydenham chorea and rheumatic fever. However, in children without chorea there is no established treatment protocol. This controversy continues to be intensely researched.

Tics usually occur in absence of any detectable pathology. Neuroimaging is normal. Unfortunately, Tourette syndrome is often misdiagnosed. However, accurate diagnosis is possible if the DSM-IV criteria are strictly followed. Tourette syndrome can only be diagnosed if both motor and vocal tics have been present for sufficient time and severity before the age of 18 years. Also, it is important to assess for and treat the common comorbidities of attention-deficit disorder and obsessive–compulsive disorder.

Tremor

Pathologic tremors can be classified by when they occur as resting, postural, action- or task-specific. Neuroimaging may reveal infection, trauma, or tumors as secondary causes and children with cerebral palsy can have any combination of tremors. Resting tremor usually has a frequency of 4–5 Hz, occurs in the absence of any voluntary movement, and is significantly reduced during volitional movement. It is relatively rare in childhood but is associated with dopa-responsive dystonia (see above), Wilson disease (dysfunction in copper metabolism), juvenile Parkinson disease, juvenile Huntington disease, basal ganglia degeneration with iron accumulation, and brain tumors.

Postural tremor has a frequency of 6–12 Hz, occurring when part of the body is maintained in a posture against gravity (i.e., arms outstretched). Two causes of postural tremor are essential tremor and enhanced physiologic tremor. Essential tremor is postural and sometimes seen during action. There may be a family history or alcohol ingestion may result in marked reduction of tremor. Essential tremor may be evident before the age of 20 years in almost one-fifth of cases, and has been reported as early as 2 years of age. Enhanced physiologic tremor may occur in children during times of stress or as a side effect of medications such as amphetamines (often used for attention-deficit disorder), bronchodilators (used in asthma and other respiratory aliments), and valproate (an antiepileptic medication). Intention, kinetic, or action tremor has a frequency of 2–4 Hz and occurs during voluntary movement and is caused by dysfunction of cerebellar pathways. Task-specific tremors occur during specific motor actions, such as writing or speaking. Psychogenic tremors occur in the context of underlying psychological disturbance, and often disappear when the patient is distracted. In almost all cases of tremor, secondary and treatable etiologies should be investigated. Thus, evaluations for Wilson disease, thyroid disease, blood glucose, electrolytes, and medications side effects should be done. In some cases, blood levels of medications can be assessed (e.g., valproate, cyclosporine, phenytoin).

Ataxia

Ataxia has several causes and like other movement disorders, in virtually all instances neuroimaging is warranted. Reversible or treatable causes include infectious or autoimmune ataxias, neoplasms, vascular etiologies, and medication-induced. In cases where an infectious, autoimmune, or neoplastic cause is suspected, a lumbar puncture for cerebrospinal fluid (CSF) analysis can be helpful. Ataxia can be classified as acute, recurrent, chronic-static, or chronic-progressive.

Infection-related etiologies include acute cerebellitis and acute cerebellar ataxia. Acute cerebellitis can present with nausea, headache, and altered mental status, including loss of consciousness in addition to acute onset of cerebellar symptoms (e.g., tremor, ataxia, dysmetria). The main symptoms of acute cerebellitis are headache, vomiting, and disturbances of consciousness varying from somnolence to coma. Fever and signs of meningeal irritation may be present. All patients show abnormal MRI findings on T2-weighted images in the cerebellar cortex. Hydrocephalus or herniation may develop owing to the obstruction of CSF flow, in which case lumbar puncture is contraindicated. CSF findings are variable, but may show increased white cell counts and/or protein. The causative agent of acute cerebellitis often remains unknown despite extensive testing, however Epstein–Barr virus (EBV) and varicella zoster virus are the most frequently identified pathogens. Associations are also reported with mumps, Lyme disease, rubella, Coxsackie B3, mycoplasma, and Streptococcuspneumoniae.4 Managing acute cerebellitis requires immediate treatment with appropriate antimicrobial therapy. MRI should be done, looking for cerebellar involvement, edema, herniation, and hydrocephalus. If cerebellar swelling is seen, the patient should be treated with corticosteroids and mannitol or glycerol. If obstructive hydrocephalus is a concern, neurosurgical consultation for possible ventriculostomy or other decompressive procedures are indicated.

Acute cerebellar ataxia, unlike acute cerebellitis, is acute onset of gait ataxia without meningismus, seizures, alteration of mental status, or other neurologic abnormalities. Acute cerebellar ataxia is usually a self-limited benign disease showing temporary signs of gait ataxia, which may develop in children after viral infection or vaccination. It may be caused by varicella, mumps, mycoplasma, or EBV.9 CSF in acute cerebellar ataxia may reveal oligoclonal IgG bands, and autoantibodies may be associated with this condition.4 If acute cerebellar ataxia does not resolve or eye movements are abnormal, opsoclonus–myoclonus, which is associated with neuroblastoma, should be considered.10

Rigidity

Rigidity as noted above is relatively uncommon in children but can be seen in Parkinson disease, medication exposure, and infections, which affect the basal ganglia. Thus, neuroimaging is warranted as well as a thorough history of medication intake. Because childhood rigidity is often associated with juvenile Parkinson disease, other Parkinsonian signs may be seen such as bradykinesia, tremor, flexed posture, and unsteady gait. Drug-induced Parkinsonism may also be seen in the context of dopamine-receptor blocking agents such as antipsychotics and antiemetics.

Encephalitic Movement Disorders

Encephalitis has long been associated with a variety of movement disorders—both hyperkinetic and hypokinetic. This includes spasticity, Parkinsonism, dystonia, myoclonus, and ataxia. Although not always present, a distinguishing feature of encephalitic movement disorders can be oculogyric crisis, in which eyes are tonically deviated to one side. Encephalitic movement disorders may occur acutely, subacutely, or chronically. It is important to distinguish such movements from seizures, and thus an EEG is useful. Such movement disorders can be treated empirically, and may or may not be associated with MRI lesions (Figure 19–3). In the setting of HIV infection, a movement disorder may indicate an opportunistic infection or lymphoma of the central nervous system.

Most movement disorders are treatable. Treatment of secondary causes such as infection, autoimmunity, medication side effect, tumor, or metabolic derangement may very well lead to resolution of the movement disorder. If a primary movement disorder is diagnosed, empiric symptomatic treatment can be effective (Table 19–6). Treatment should focus on functional improvement to allow for growth and development, rather than complete resolution of movement disorder per se.

Spasticity may improve with a combination of physical therapy and muscle relaxants such as baclofen, clonidine, tizanidine, or dantroline. Focal treatment of spasticity with botulinum toxin injections can be quite effective, though careful selection of injection sites and dose are essential to avoid excessive weakness. Avoidance of contracture formation is also important. These musculoskeletal changes require surgical lengthening rather than reduction in muscle tone to improve range of motion. Intrathecal baclofen for more widespread spasticity, especially in the lower extremities may be effective.

Almost all cases of dystonia should undergo a trial of carbidopa/levodopa, in case it is a form of dopa-responsive dystonia. If this does not work, trihexyphenidyl initiated at low doses and gradually increased over the course of several weeks to months may be effective. Other muscle relaxants such as those listed above for spasticity may also be effective. Where available, dopamine-depleting medication such as tetrabenazine or reserpine may be effective, especially for tardive dyskinesia. Benzodiazepines may alleviate some dystonic symptoms, and for more focal cases, botulinum toxin injections can be very effective. Deep-brain stimulation of the globus pallidus interna has also been effective in carefully selected cases.

Often chorea, ballismus, and athetosis resolve if the underlying etiology is treated. If it persists or other nontreatable etiologies are suspected, leviteracitam, peracitam, clonazepam, valproate, tetrabenazine or reserpine can be effective. Dopamine-receptor blockers may be effective but should be avoided because of the risk of inducing tardive dyskinesia or Parkinsonism.

Myoclonus can respond to antiepileptics despite not being associated with seizure activity on EEG. Clonazepam, valproate, leviteracitam, and other antiepileptics may be tried. Potential secondary causes such as metabolic derangements and medication side effects should first be addressed.

Tic disorders naturally wax and wane, and thus it is difficult to know definitively if a particular medication is effective. Not all tics are pathologic and only tics, which confer a negative impact in a child's life socially, physically, academically, or psychologically need treatment. A multidisciplinary approach with behavioral therapy such as habit-reversal training may be helpful. Also, addressing comorbidities of attention-deficit disorder and obsessive–compulsive disorder can minimize the impact of tics. Medications that may be effective for tics include clonidine, clonazepam, and pimozide. Because of concerns of tardive dyskinesia, some consider neuroleptics such as pimozide only in severe cases refractory to other treatment. As tics spontaneously fluctuate, it is important to titrate medication based on symptomatology.

Tremor is treated by evaluation for secondary causes or based upon the type of tremor. Action, kinetic, or postural tremor that is seen in essential or familial tremor can be treated with either propranolol or primidone. Second-line treatments include topiramate, gabapentin, and benzodiazepines. Use of wrist or ankle weights may dampen the tremor. If a rest tremor is seen, then dopamine agonists or carbidopa/levodopa may be tried. In severe cases of action or rest tremor, deep-brain stimulation may be quite effective though experience in children is limited.

Ataxia may be treatable if an underlying etiology is found such as infection, autoimmunity, neoplasm, or migraine. Unfortunately, primary ataxias do not have any proven effective treatment, though physical therapy may prevent falls and allow greater independence. Rigidity, like rest tremor, may respond to dopaminergic therapy.