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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Chorea, Ballism, and Athetosis
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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.
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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.
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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.
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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.
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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).
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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.
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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.
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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.
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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.
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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).
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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.
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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.
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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
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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.
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Encephalitic Movement Disorders
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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.
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