Paroxysmal movement disorders are a heterogeneous group of disorders characterized by episodes of abnormal movements involving limb, trunk, and facial muscles that appear different from the pattern of normal motor behavior. The diagnosis of these disorders is dependent on the history detailing its onset, evolution, post-ictal changes, and precipitating factors. These conditions are not associated with alteration in sensorium and are often confused with partial seizures. At times, the distinction can be extremely difficult, even when a reliable description from observers is available. Individual disorders are rare; however, as a group, they occur frequently enough to be considered in the differential diagnosis of a seizure disorder. It is important to make this distinction because seizures can be treated effectively with anticonvulsants. By the same token, misdiagnosing a paroxysmal movement disorder as epilepsy would result in unnecessary treatment with an anticonvulsant and exposure of the patient to its side effects. Most movement disorders can be controlled using medications, and others need no treatment other than reassurance for patients and their parents.
Some chronic movement disorders occur secondary to underlying metabolic, degenerative, or acquired diseases and can present initially as an episodic disorder. Wilson's disease and the syndrome of opsoclonus and myoclonus are particularly important to recognize because a delay in diagnosis and treatment causes serious consequences. Hence, all intermittent movement disorders should be critically evaluated.
The first step in establishing the diagnosis of paroxysmal movement disorder is obtaining a detailed history. In most instances, the diagnosis must be made based on the description provided by witnesses. Less often, the clinician actually witnesses the event. Video recordings of the spell are helpful and are more readily available now than previously. The history is focused on the activity preceding the event and any precipitating factors such as sudden movement, posture change, or sensory stimuli such as touch, light, sound, or joint movement. The duration of the spell and the child's behavior and sensorium after the event should be documented.
The medication history must be reviewed in detail because several drugs can cause intermittent dyskinesias as side effects (Table 1). Repeated use can cause recurrent episodes that would be confused with paroxysmal movement disorder. Discontinuing the medication or changing to another drug is curative. Because some movement disorders are familial, a family history of similar or other movement disorders is very important.
The general physical and neurologic examination results are most often normal. A complete neurologic examination must be performed because a paroxysmal movement disorder can be superimposed on a chronic neurologic disease and because the initiating complaint may be but one facet of the complete problem. When these episodes are seen during the examination, the amount and speed of the movement, the limbs involved, and the pattern of progression and resolution of the movements must be noted. The alertness of the child, the effect of distraction, and the effect of other complex tasks on the severity and pattern of movement should also be documented.
Except for the rare metabolic diseases, most of the disorders discussed here have no diagnostic laboratory studies. Electroencephalography (EEG) and neuroimaging (computed tomography and magnetic resonance imaging) are rarely helpful in making a diagnosis of paroxysmal movement disorders but may exclude other diseases. Hospitalization to witness the spells is usually nonproductive. Video monitoring with simultaneous EEG can be helpful in difficult cases, especially when suspicion of partial seizure disorder is high. Sometimes the outcome of a therapeutic trial is supportive of a diagnosis.
Drugs Associated With Movement Disorders
TIC DISORDERS AND TOURETTE'S SYNDROME
Tics are sudden, brief, repetitive, nonrhythmic and stereotyped movements or vocalizations.1 Tics are common in the general population, and the estimated prevalence is approximately 1 to 10 per 10 000. Tics are seen in all races and affect both genders but are three times more common in male than female patients. The movements are easily recognized when witnessed by medical personnel but can be difficult to describe for lay observers. The motor tic may be simple or complex in pattern. Simple tics are most often manifested as rapid and repetitive eye blinks, shoulder shrugs, and facial grimaces. Complex tics involve more coordinated movements of multiple muscle groups and are manifested as bizarre searching eye movements, shoulder and body gyrations, and even seductive and self-mutilating movements. The vocalizations are varied and consist of sounds (sniffs, snorts, barks, and others) and words. Coprolalia (obsessive or uncontrollable obscene language) and echolalia (repetition or echoing what another has just said) occur but less frequently. Tics are exacerbated when the patient is relaxed or fatigued and can be suppressed by the patient in social settings such as the doctor's office, school, and parties or during activities requiring concentration. Complex tics, especially when associated with vocalizations, can easily be confused with seizures. The normal sensorium, the quasi-purposeful pattern of movements, and the ability of the individual to suppress the movements differentiate the complex tic from a seizure.
Many preschoolers go through a brief period of simple tics for several months that resolve spontaneously. On the other hand, many older children and adults develop a chronic, simple tic that persists lifelong. Gilles de la Tourette syndrome and related disorders are a group of neuropsychiatrie disorders characterized by fluctuating motor and vocal tics. There is a strong familial pattern of dominant transmission affecting male more than female patients. Symptoms usually begin around 7 years of age, and 96% of patients have onset before 1 1 years of age. The tics are infrequent at onset and may not be seen during the examination in a doctor's office. Symptoms progress, with the development of multiple tics, some of which may be complex. Coprolalia is not common and, if present, rarely persists. Children develop a variable combination of motor and vocal tics whose severity waxes and wanes over time. Spontaneous remissions and recurrences can occur, but most children improve with time. About one half of children wirh Tourette 's syndrome experience problems with attention and about one third have an obsessive-compulsive disorder.2 Some predisposed children treated wirh methylphenidate or other stimulants for attention deficit disorder may subsequently develop tics and lead to this diagnosis.
This clinical presentation is often confused with recurrent seizures as cause for school failure. EEG is not indicated if the history is typical for tics and the movements are observed during examination or on video recordings of the spells by parents. If an EEG is performed, the results are generally normal. Neuroimaging and laboratory studies are not indicated for tic disorders.
Treatment of Tic Disorders and Comorbid Conditions
Treatment of tic disorders is individualized for each patient (Table 2). Most children with transient or chronic simple tics need no intervention. Less than one half of children with Tourette 's syndrome need pharmacotherapy, and treatment should be considered only if the tics are disturbing to the child or learning is impaired because of the tics or because the child is ostracized by other children (causing emotional problems). Two groups of medications are useful: alpha-adrenergic agonists (clonidine, guanfacine) and dopamine-depleting agents (haloperidol, pimozide). Alpha-adrenergic compounds have fewer side effects and are usually chosen as first-line agents. Also, clonidine is useful for treating attention disorder, which is a common problem in patients with Tourette's syndrome. Clonidine is started at 0.05 mg once daily and gradually increased weekly until the tics are controlled or the side effects, mainly sedation, become intolerable. The usual maintenance dose is 0.1 to 0.5 mg/day in two divided doses. Haloperidol is started at 0.5 mg/day and gradually increased each week until there is adequate control of tics with the fewest side effects. The typical maintenance dose is 1.0 to 3.0 mg/day in divided doses. Sedation, depression, and interference with concentration are side effects. Dystonia (occulogyric crisis) acutely and akathisia with chronic use are idiosyncratic reactions. Details of management of tic disorders are available in several reviews.3"6
Paroxysmal Kinesigenic Choreathetosis (PKC) and Paroxysmal Dystonie Choreathetosis (PDC)
Patients should be referred when the diagnosis is unclear or when there is a poor response to treatment. Because many children have attention, education, and behavior problems in addition to the tics, a multispecialty team may be needed to treat complicated patients.
Paroxysmal choreoathetosis is characterized by episodes of abnormal muscle movement, mainly dystonia, chorea, or athetosis, with a clear onset and cessation. The disorders are most often familial and are divided into paroxysmal kinesigenic choreoathetosis (PKC), paroxysmal nonkinesigenic dystonic choreoathetosis (PDC), and an intermediate variety (Table 3).7
The attacks of PKC consist of a combination of dystonic posturing of the trunk, with chorea, athetosis, or ballism (swinging, jerking movements) of the limbs, and may be preceded by a sensation of tightness or parasthesias in the affected part. The episodes affect one or both sides and can begin unilaterally and become bilateral. They are precipitated by sudden movement after a period of rest. The episodes are generally brief and last up to 5 minutes, although some can last longer. The frequency of the episodes is variable. As many as 100 spells have been reported in a single day in one individual. There is a brief refractive period following a spell when another one may not occur. These movements can be severe enough to cause the patient to fall. Patients can avoid the spells by not moving or gradually warming up before activity.7 Most cases are inherited in an autosomal-dominant fashion but some are idiopathic.
Differentiation of PKC from seizures is made based on the association of spells with initiation of movement, the absence of altered consciousness or postictal symptoms, and the pattern of movements (dystonia, chorea, and athetosis).8'9 A video recording may be necessary to make the distinction. Imaging studies of the brain and the EEG results are normal. Autopsy studies have not shown any abnormalities in the brain.9 Similar movements occur rarely in patients with multiple sclerosis10 and head injury. PKC responds well to anticonvulsant therapy, especially phenytoin, with nearly complete cessation of the movements.
Patients with PDC also have recurrent episodes of uncontrolled movements involving the limbs in the form of chorea, athetosis, and, at times, dystonic posturing. However, unlike PKC, the attacks are not initiated by movement and they last longer than those of PKC. Patients may experience subjective symptoms of parasthesias, cramps, or a moving sensation prior to the onset of the episode. The abnormal movements can be unilateral or bilateral, and the attack may begin on one side and spread bilaterally. Consumption of caffeine or alcohol, psychological stress, excitement, and excessive fatigue often trigger the attacks. Speech is affected in some from dystonia of the face and tongue, but there is no alteration of sensorium. The spells are relieved by sleep and rest.8
The dominantly inherited, idiopathic form of PDC is the most common type. Sporadic cases occur rarely.11 Symptomatic cases of PDC have resulted from a variety of causes, especially multiple sclerosis. Other causes are hypoglycemia, anoxia, thyrotoxicosis, cystinuria, hypoparathyroidism, brain tumor, and acquired immune deficiency syndrome. PDC, unlike PKC, does not respond to anticonvulsants such as phenytoin or carbamazepine. Benzodiazepines, especially clonazepam, produce amelioration of the symptoms in some patients.12
An intermediate form of paroxysmal choreathetosis is shorter in duration than PDC, lasting a few minutes to 30 minutes. The attacks are often triggered by prolonged physical exertion. Benzodiazepines are useful for controlling symptoms. This disorder is familial and very rare.
BENIGN PAROXYSMAL TORTICOLLIS
Benign paroxysmal torticollis consists of episodes of torticollis in infants lasting minutes to days. The attacks usually occur several times a month without any warning. During the episode, the head tilts to one side and rotates to the opposite side. The child is in no discomfort except when the head is forced to the normal position. The spells in some children are associated with dyskinesias affecting the extremity on the side of the head tilt. Lateral incurvation of the trunk can also occur. The disorder is self-limited and it resolves by the age of 2 years in all patients.13 Some patients later develop paroxysmal vertigo or classic migraine.
The etiology of this disorder is not known, and some researchers believe it to be early presentation of paroxysmal dyskinesias or perhaps a migraine variant. The main differential diagnosis is from Sandifer syndrome (head tilt associated with gastroesophageal reflux) and a posterior fossa mass. Other conditions such as vertebral anomalies, ocular motor paralysis, and mass lesions at the craniocervical junction should be excluded. Infants should be evaluated with a neuroimaging study of the head and cervical radiographs.
Intermittent ataxia can be idiopathic or symptomatic. Symptomatic intermittent ataxia occurs in many metabolic disorders such as maple syrup urine disease, pyruvate dehydrogenase deficiency, and Hartnup's disease, and with disorders of the urea cycle. These episodes are often triggered by fever and intercurrent illness and they are associated with encephalopathy or other neurologic signs. Intermittent ataxia is also a side effect of many drugs, especially anticonvulsants.
Idiopathic intermittent ataxia is a rare familial disorder with an autosomal-dominant pattern of inheritance in most families.14 Mutations in the gene coding for the potassium channel located on chromosome 12 (KCNA 1 gene) and in a gene coding the calcium channel located on chromosome 19 have been discovered.15 The attacks usually last for minutes, although in rare cases they may last hours. Some of the patients experience dysarthria, vertigo, and nystagmus during the attacks14 and others have persistent slow muscle activity referred to as myokynia.16 Older patients with this disorder may develop fixed cerebellar ataxia. The attacks are triggered by fatigue, stress, and occasionally consumption of a carbohydrate meal. A few of these patients have attacks triggered by sudden movement (kinesigenic). Acetazolamide is effective in some patients,17 and clonazepam may be effective in those who do not respond to acetazolamide.
Brief episodes of rapid, tremulous movement of the entire body in young children characterize shuddering (or shivering) attacks. The patients' trunk and limbs are in a flexed posture of their trunk and limbs during these episodes. The individual attacks are brief with no loss of consciousness, and a child may have several to 100 episodes a day. The parents describe the child appearing frightened and as if the infant had "stepped out into the cold." The episodes begin at age 4 to 6 months and patients have almost always completely resolved by 10 years of age. A family history of essential tremor is common, and some physicians consider these episodes as an expression of essential tremor by an immature brain. Treatment is not required in the majority of cases; however, when the episodes are very frequent, propranolol has been used with variable success.18
Gastroesophageal reflux can cause intermittent, severe, and unusual posturing of the neck and trunk. The episodes of torticollis may be sustained or fleeting. When there is severe reflux, it may present as dystonic posturing affecting the entire body. This presentation is seen commonly in children with static encephalopathy, although it may also occur in normal infants. A diagnosis of reflux can be established using barium swallow or esophageal pH probe tests. The movements resolve with the treatment of the reflux.19*20 The latter is diagnostic of Sandifer syndrome; the posturing episodes occur simultaneously with a fall in esophageal pH below 4-0.
Spasmus nutans is a curious movement disorder of infants characterized by head nodding, head tilt, and nystagmus. The onset is generally in the first few months of life and the disorder usually resolves spontaneously after several years. The movements are intermittent and can be subtle and remit during sleep. Most cases are idiopathic, but in rare instances, tumors of the optic nerve or hypothalamus cause similar signs. For this reason, all children with spasmus nutans must have neuroimaging of the brain and orbits.21 The movements require no therapy.
A related disorder is called bobble-head doll syndrome. This a rare sign of hydrocephalus especially associated with a third ventricular cyst and aqueductal stenosis. The abnormal movement may anticipate signs of increased intracranial pressure.
SYNDROME OF OPSOCLONUS AND MYOCLONUS
Opsoclonus (chaotic, irregular, and conjugate movements of the eyes triggered by eye movement) and myoclonus, occurring intermittently or continuously, often follow a viral syndrome. In over 50% of patients, however, it is a paraneoplastic syndrome resulting from neuroblastoma.22 The syndrome evolves over weeks, with most patients experiencing a change in behavior or mood suggesting a more widespread encephalopathy. The patient's gait is abnormal because of ataxia or impairment secondary to widespread myoclonus. Occasionally, acute or intermittent ataxia is the only neurologic expression of neuroblastoma. The course is prolonged and typically waxes and wanes. When the disorder is associated with neuroblastoma, the tumor is often inapparent at the onset of the symptoms. A 24-hour urine collection for catecholamines and imaging studies of the neck, chest, abdomen, and pelvis should be performed and should be repeated periodically if initially unrevealing. These patients frequently respond to oral glucocorticoids. However, the outcome of the opsoclonus and myoclonus is the same whether the disease is associated with neuroblastoma or not; or whether there is a response to glucocorticoids: approximately one half of the children have an incomplete recovery with impaired motor or intellectual abilities. The other half have a full recovery.
Myoclonic movements limited to one or more myotomes occur from local pathology in the spinal cord. These movements affect the muscles innervated by the spinal segments close to the site of pathology. The myoclonus may occur rhythmically or arrhythmically and, at times, episodically. It results from a variety of local pathologies such as tumors, arteriovenous malformations, inflammatory disorders, and traumatic injury to the spinal cord. These movements, when episodic, may be confused with motor tics. Because of the frequent association with pathologic lesions in the cord, patients need prompt imaging studies of the spinal cord and appropriate management. The myoclonus responds to treatment with clonazepam.23
Hyperexplexia, or "startle disease," is an excessive startle reaction to a sudden, unexpected stimulus. Falling is a common symptom. The movement can be either brief or a prolonged, complex motor act. Hyperexplexia can be familial or sporadic. Excessive startle is seen in children with degenerative disorders such as Krabbe 's disease and Tay Sach's disease, and it can also be noted in young children with static encephalopathy and severe spasticity. A rare familial form has been reported in individuals of FrenchCanadian descent referred to as the "Jumping Frenchmen of Maine."
Stereotypy refers to simple or complex motor movements that repeat themselves continually and identically. These patterns of movements may arise intermittently and be derived from normal motor behavior. This pattern of identical repeated motor patterns can be seen episodically in children with mental retardation or autism, and in patients with schizophrenia. The patterns may occur in some healthy children as well and take the form of head banging, body rocking, and hand flapping behavior.
PAROXYSMAL MOVEMENTS DURING SLEEP
Almost all of the paroxysmal movement disorders discussed previously are absent during sleep. There are a few specific syndromes only related to sleep. Benign nocturnal myoclonus is very common, especially in infants and young children. As the child drifts into sleep, there are a few sudden, forceful generalized or localized jerks. Parents of children with epilepsy may confuse this normal phenomenon with seizures.
Sleep myoclonus and the related restless leg syndrome persist throughout the night during sleep and can cause repeated awakenings. As with any sleep disturbance, severe sleep myoclonus can be a cause for daytime somnolence, poor attention, and irritability. The disorder is often familial and often responds to small doses of levodopa before bedtime.
Jacinto capitis nocturna, or head banging, is a curious event in infants and young children. It begins as the child falls asleep and persists for several hours. The child may simply rock the head from side to side or get into a semi-crouched position and rock the entire body front to back while banging the head on the headboard of the bed. The syndrome is benign and remits by 4 years of age. Head banging does not normally require therapy but benzodiazepines before bedtime can ameliorate the movements.
Other sleep disturbances are discussed elsewhere in this issue of Pediatric Annals (see article by Merrill S. Wise, MD, entitled "Parasomnias in Children).
Metabolic disorders can produce movement disorders, some of which are intermittent. Chorea, with or without athetosis, and dystonia are common signs. Disorders of amino acids, organic acids, the urea cycle, and energy metabolism are often associated with intermittent movement disorders and encephalopathy. Hyperthyroidism, hyperparathyroidism, and hypoglycemia can cause episodic chorea and dystonia.25 These conditions need to be excluded by appropriate laboratory tests when suspected.
Wilson's disease is a progressive neurologic disease caused by a disorder of copper metabolism. The clinical manifestations of this condition involve the liver, hematopoetic system, and the nervous system. Neurologic symptoms are rare in children and involve symptoms of extrapyramidal dysfunction in the form of dystonia, chorea, and athetosis. The movement disorder is often intermittent and episodic in the early stages of the condition. All older children, adolescents, or young adults who present with new-onset dystonia, chorea, athetosis, or myoclonus with or without psychiatric symptoms need to be evaluated for Wilson's disease.24 Failure to diagnose the disease early causes a delay in treatment and can result in incomplete recovery from the neurologic complications.
1. Singet HS. Tic disorders. Pediatr Ann. 1993;22:22-29.
2. Comings DE. Tourecte's syndrome: a behavioral spectrum disorder. Adv Neurol. 1995;65:293-303.
3. Comings DE, Comings BG. A controlled study of Tourette syndrome: attention deficit disorder, learning disorders and school problems. Am J Hum Genet. 1987;41:701-741.
4. ErenbergG. Pharmacologic oHerapyoftics in childhood. Pediatr Ann. 1988;17:395404.
5. Riddle MA, Hardin MT, King R, Scahill L, Woolston JL. Fluoxetine treatment of children and adolescents with Tourette syndrome and obsessive compulsive disorders: preliminary clinical experience. J Am Acad CWId Adoiesc Psychiatry. 1990;29:45-48.
6. Flament MF, Rapopon JL, Berg CJ, et al. Clomipramine treatment of childhood obsessive compulsive disorder. A double Mind controlled study. Arch Gen Psychiatry. 1985;42:977-983.
7. Fahn S. The paroxysmal dyskinesias. In: Fahn S, Marsden CD, eds. Movement Disorders. 3rd ed. Boston, Mass: Butcerworth Publishing Co; 1994:311-345.
8. Stevens H. Paroxysmal choreathetosis. A form of reflex epilepsy- Arch Neurol. 1966;44:140-152.
9. Kertesz A, Paroxysmal kinesigenic choreathetosis. An entity within the paroxysmal choreathetosis syndrome. Description of 10 cases including 1 aucopsy. Neurology. 1967;17:680-690.
10. Berger JR, Sheramata WA, Melamed E. Paroxysmal dystonia as the initial manifestation of multiple sclerosis. Arch Neuroi. 1984;41:747-750.
11. Fahn S, Williams DT Psychogenic dystonia. Adv Neurol. 1988; 50:431-455.
12. Lance AE Familial paroxysmal kinesigenic choreathetosis and its differentiation from related syndromes. Ann Neurol. 1977;2:285-293.
13. Snyder CH. Paroxysmal torticollis in infancy. A possible form of labyrinthitis. Am JDisChild. 1969:117:458-460.
14. Hill W, Sherman H. Acute intermittent familial cerebellar ataxia. Arch Neurol. 1986;18:350-357.
15. Lubbers WJ, Brunt ER, Scheffer H, et al. Hereditary myokynia and paroxysmal ataxia linked to chromosome 12 is responsive to acetazolamide. J Neurol Neurosurg Psychiatry. 1995;59:400-405.
16. Brunt ER, van Weerden TW. Familial paroxysmal kinesigenic ataxia and continuous myokynia. Brain. 1990,113:1361-1382.
17. Griggs RC, Moxley RT III, LaFrance RA, McQuillen J. Hereditary paroxysmal ataxia: response to acetazolamide- Neurology. 1978;28:1259-1264.
18. Vannasse M, Bedard P, Andermann F. Shuddering attacks in children: an early expression of essential tremor. Neurology. 1976,26:1027-1030.
19. Kinsboum M. Hiatus hernia with contortions of die neck. Lancet. 1964; 1:10581061.
20. Sutcliffe J. Torsion spasms and abnormal postures in children with hiatus hernia. Sandifer's syndrome. Progress m Pediatrie Radiology. 1969;2:190-197.
21. Albrighc AL, Sclabasst RJ, Salmovits TL, et al. Spasmus nutans associated with optic gliomas in infants, i Pediatr. 1984;105:778-782.
22. Warner RP, Kini R, Besser A, Wiatrak BA, Raju U. Opsoclonus and neuroblastoma. Clin Pediatr. 1985;24:32-35.
23. Marsden CM. Peripheral movement disorders. In: Fahn S1 Marsden CD, eds. Movement Disorders. 3rd ed. Boston, Mass: Butterworth Publishing Co; 1994:407417.
24. Weiner WJ1 Lang AE. Wilson's disease. In: Weiner WJ, Lang AE, eds. Movement Disorders: A Comprehensive Survey. Mt. Kisco, NY: Futura Publishing Cb; 1989:257-291.
Drugs Associated With Movement Disorders
Treatment of Tic Disorders and Comorbid Conditions
Paroxysmal Kinesigenic Choreathetosis (PKC) and Paroxysmal Dystonie Choreathetosis (PDC)