0021-7557/02/78-Supl.1/S73 Jornal de Pediatria - Vol. 78, Supl.1 , 2002 S73 Jornal de Pediatria Copyright © 2002 by Sociedade Brasileira de Pediatria

REVIEW ARTICLE

Paroxysmal non-epileptic events

Márcio A. Sotero de Menezes*

Abstract Objective: this publication aims at reviewing one of the most important problems faced by the pediatrician in the field of child neurology. The paroxistic non-epileptic events are also a frequent reason for pediatric neurology consultations and admission for diagnostic video-eletroencephalogram monitoring. Methods: literature review on the subject was perform on Medline, data was also collected from the main Pediatric Neurology Textbooks, which were found to be important and unique source of information on the subject. Results: many of entities discussed in this paper are very common in the pediatric population like syncope, breath-holding spells and the movement disorders associated with gastroesophageal reflux. Other syndromes are less frequent such as the pararoxymal dystonias and the Segawa Syndrome (dystonia with diurnal variation). Conclusions: the basic knowledge of these syndromes is very important since it may avoid unnecessary procedures and the wrongful diagnosis of epilepsy. Patients who are mistakenly diagnosed as epileptics are exposed to anti-convulsant medications, which are probably not going to be effective and may expose them to the risk of side effects.

J Pediatr (Rio J) 2002; 78 (Supl.1): S73-S88: epilepsy, convulsions, seizures, paroxystic non-epileptic events, syncope, movement disorder, tetany, hyperekplexia, vertigo.

Introduction About 10-30% of the children referred to neurology- least in part epileptic seizures.4 These events show epilepsy clinics have an incorrect diagnosis.1-3 According resemblance with one or many of the aspects of epileptic to Bye and Nunan up to 1/3 of the patients with suspected seizures such as loss of consciousness, behavioral arrest, seizures evaluated with video-EEG have in actuality non- autonomic changes and repetitive motor or psychological epileptic events. A large variety of events may mimic at behavior. This review aims at discussing only some of the most common paroxysmal non-epileptic seen in pediatric neurology practice. The tables are organized alphabetically but not all the diseases mentioned included in the tables are

* Associate Professor, Department of Neurology and Pediatrics, Washington discussed. Table 1 lists alphabetically the most common University. Co-Director of the Pediatric Epilepsy Program, Children’s types of paroxysmal non-epileptic events, which are seen in Hospital and Regional Medical Center. Seattle, Washington, USA. pediatric neurology practice.

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Table 1 - Paroxysmal non-epileptic events

Paroxysmal movement disorders Benign neonatal myoclonus Benign myoclonus of early infancy Benign paroxysmal tonic upgaze Benign paroxysmal torticollis Benign paroxysmal vertigo Dystonia with diurnal variation (a.k.a. Segawa syndrome) Hyperekplexia Paroxysmal ataxia (with or w/o response to acetazolamide) Paroxysmal non-kinesiongenic dystonia-chorea Paroxysmal kinesiongenic dystonia-chorea Shuddering attacks Stereotypies

Others paroxysmal activity Apnea (especially infants) Breath-holding spells Cyclic vomiting Jitteriness of infants and neonates (physiological, hypoglycemic, hypocalcemic) Masturbation Psychogenic seizures (pseudoseizures) Sandifer syndrome SIDS - sudden infant death syndrome Spasmus nutans Syncope

Transient cerebral hypoperfusion-hypoxemia causing hypotonia), followed by complete flattening of the EEG paroxysmal signs and symptoms tracing during the tonic phase. As the hypoxia gets corrected Among the most common seizure imitators are breath- the slow waves re-appear and at the same time that a few holding spells and syncope. We start this review with these jerks of the limbs are seen before resumption of normal 7,8 two entities because they are very common in the general EEG activity. population but also due to their similar physiopathology. The basis of the symptoms of both syncope and breath- holding spells is a decrease in perfusion and delivery of Syncope oxygen delivery to the brain leading to energy metabolism Syncope is a commonly confused with epileptic seizures. failure. Authoritative sources list a few critical values which Syncope accounts for about 1% of pediatric emergency in an adult individuals would lead to CNS dysfunction: room visits.9,10 One study the prevalence of syncope among bradycardia of less than 40 beats per minute, tachycardia of adults was 3% for men and 3.5% for women.11 One third to more than 150 beats per minute, asystole of more than four half of the cases of syncope show when followed up for 5 seconds, systolic pressure of less than 50 mmHg or venous years.12 02 pressure of less than 20 mmHg.5,6 This cortical hypoxia- ischemia leads to a sequence of event including: loss of During a syncope there is a transient cerebral consciousness and of postural tone, increase in tone hypoperfusion, followed by spontaneous recovery which is (decorticate/opisthotonus) followed by a few beats of clonus. associated loss of consciousness and postural tone.7,13-15 This sequence is probably due to liberation of corticoreticular An interruption of cerebral blood flow lasting 8 to 10 inhibition. Cortical hypoxia produce slowing of frequency seconds causes loss of consciousness.13 There are many of the brain electrical activity (loss of consciousness- causes and triggers of syncope (see Table 2). Paroxysmal non-epileptic events - Sotero de Menezes MA Jornal de Pediatria - Vol. 78, Supl.1 , 2002 S75

Table 2 - Causes-precipitators of syncope

Cardio-inhibitory syncope of infants (a.k.a. breath holding spells) Cardiovascular Atrio-ventricular conduction abnormalities (AV heart-block) Cardiac arrhythmias (long QT syndrome) Congenital Heart Disease Rheumatic Heart Disease Congestive Heart failure Drug-induced syncope Hyperventilation syndrome-related syncope Neurocardiogenic Situational-valsalva-parasympathetic activation syncope: cough, defecation, deglutition, diving, hair grooming, micturition, sneezing, trumpet-playing, weight-lifting Suffocation syncope Psychogenic syncope

The diagnosis of syncope rests mainly on clinical postural tone, which in the prolonged events is followed by grounds.16 The syncope is often precipitated by assuming tonic posturing and a brief clonic activity. Less frequently the upright posture (orthostasis), prolonged standing, heat, incontinence may be seen. After the syncope a spontaneous fatigue, hunger, Valsalva maneuver, physical or emotional recovery without persistent neurologic deficits is the rule stress including venipuncture, pain, and fear, are also but nausea, pallor, diaphoresis and fatigue may be seen. The commonly identified.17,18 Several activities which produce recovery takes place in less than an hour.15 Even though a valsalva maneuver and/or parasympathetic activation can most cases syncope in children are benign and self-limited cause syncope including cough, defecation, deglutition, falls may lead to physical injuries. diving, hair grooming, micturition, sneezing, trumpet- Even though syncope is usually can be distinguished playing, weight-lifting.6,19,20 Other stimuli include getting 8,21 22 from epilepsy both by the clinically and EEG picture in into or out of a bath, or stretching. Less commonly some cases both diseases may co-exist. syncope may result from primary cardiac events (see primary cardiac syncope below). Syncope is often preceded by a sensation of lightheadedness, blurred vision, “things going far away” Syncopes of cardiac origin (sometimes described as “tunnel vision”), pallor, nausea, Syncopes of cardiac origin should be considered apart epigastric discomfort or diaphoresis.13,15 In most cases since they require a different focus in their work-up. Syncopes the loss of tone is characterized by a progressive and slow of cardiac are less frequent than reflex vasovagal or slumping to the ground. Less frequently the loss of posture cardioinhibitory attacks.6 The conditions that cause these may be abrupt with a sudden fall which may be associated syncopes are associated with sudden death, which is the with tongue lacerations. The latter the cuts are typically in reason why it is important to recognize them. Both congenital the tip of the tongue and tongue biting with lateral laceration and acquired (rheumatic) aortic stenosis that can produce occurs only exceptionally in syncopes.8,23 Urinary syncopes on effort and the same is true for cardiomyopathies incontinence is not uncommon reflecting cortical inhibition and disturbances of cardiac conduction. Among the and does not indicate an epileptic mechanism. conduction abnormalities associated with syncope are the The loss of consciousness during a syncope usually lasts long Q-T syndromes, Wolff-Parkinson-White syndrome, from a few seconds to a few minutes. During the period of and congenital atrioventricular block.24 Among the cases impairment of consciousness the patient has decreased showing a long Q-T on the EKG there are those with the S76 Jornal de Pediatria - Vol. 78, Supl.1, 2002 Paroxysmal non-epileptic events - Sotero de Menezes MA

Jervell-Lange-Nielsen syndrome features an associated “Breath-holding” spells (Cardio-inhibitory or Pallid neurosensory deafness and is recessively inherited and the syncope and Cyanotic breath holding spells) Ward-Romano syndrome, which is dominantly transmitted. “Breath-holding” spells are frequently confused epileptic Both syndromes can mimic epilepsy and in a few cases seizures. One of the main reason for that are the clonic secondary epileptogenesis may be seen can result in sudden movements which can be seen at times towards the end of 25,26 death in some children. The episodes can occur during these spells. sleep, exercise and may be also precipitated by emotion or stress but since similar precipitants may be seen in epilepsy EKG and EEG confirmation is mandatory in all cases. A family history of sudden death or ‘epilepsy’ or a personal history of chest pains, palpitations or of a surgically repaired Cardio-inhibitory or Pallid syncope heart defect should trigger a full cardiac evaluation. The A better denomination for some these episodes would EKG examination should include Q-Tc interval calculation. be cardio-inhibitory syncope (CIS or pallid “Breath-holding” The Q-T interval is measured from the onset of the first QRS spells) since the main problem is transient cerebral waveform to the end of the T wave on the EKG. The hypoperfusion (syncope) induced by bradycardia leading corrected (QTc) is calculated by dividing the QT interval to facial pallor. Other cases a Valsava maneuver with or value by the square root of the RR interval. QTc values without bradicardia causes a similar syncope during which above 0.44 seconds are abnormally elevated.27 A prolonged the patients are more or less cyanotic (Cyanotic “Breath- EKG recording and an effort test may be indicated when holding” spells). there is a high index of suspicion, especially in association The age onset range is between 6 and 24 months but with history of familial syncope or sudden death is present. cases with onset in the neonatal period and as late as 42 The treatment with pacemaker placement may prevent months have been described.29 About 4.9% of the pediatric sudden death. There are at least three different genetic population is thought to have these episodes.29 The sequence substrates for long Q- T syndromes one linked to the ras-l of events tends to be helpful when the parents are observative. protein gene on chromosome 11p15; another associated to A mild head injury or any type of pain or even extreme a potassium channel mutation on chromosome lq35-q36 emotional upsetting will start the episode. The trigger fever (LQT2), and a third linked to a sodium channel protein 30 28 may be also a trigger for similar events. After that the mutation on chromosome 3 (LQT3). patient will begin to cry and than suddenly stops crying Another type of syncope of cardiac origin are the attacks (giving the impression of “holding the breath”) and turns of hyperventilation and cyanosis seen in congenital cyanotic pale (thus the name pallid syncope), quickly they become cardiopathies such as the Tetralogy of Fallot. These attacks hypotonic and most of the times the episodes will end on this if severe will result in loss of consciousness. One should be phase with gradual recovery of the patient’s color and careful since congenital cyanotic cardiopathies are associated normal activities. Some times the parents will touch the with a high risk of thromboembolic phenomena, which may patient’s chest and will notice the heart rate to be slow or lead to strokes and true epileptic foci. they will not be to feel the heart beating or the pulse (which is usually weak) in the limb arteries so the worried parents Patients with poor cardiac reserve who are in chronic will start doing CPR in the child if they know how to do so. heart failure may also faint when they try to exert themselves In the more prolonged cases after the hypotonic phase the or when their fragile cardiovascular system is overtaxed patients will become rigid (hypertonic) and may even show such is the case during severe infections. a few clonic beats mostly in the upper extremities. These patients will be often labeled as having seizures or epileptics and are treated with anticonvulsants. Phenobarbital, which one of the anticonvulsants most used in this age group may selectively depress the transmission in sympathetic ganglia Treatment of syncope and has a mild effect in the heart rate and blood pressure that The idiopathic syncope is best managed acutely by may be potentially harmful for patients with a tendency to increasing the blood flow (venous return) to the heart by bradycardia. Around 18% of these patients will have episodes placing the child flat with legs at the level of the heart or of syncope as adolescents.31 above it. Patients with situation related syncope should avoid the precipitating environment such as extreme heat. The diagnosis is made mostly by the typical history. In In all cases of repetitive syncope before the diagnosis of the past ocular compression has been done to confirm the 29 “idiopathic syncope” is made it is wise to have a proper diagnosis. Nonetheless this test has fallen out of favor due 32 cardiac evaluation with good history, careful cardiac to some potential ocular side-effects. auscultation and EKG interpreted by someone familiar with Treatment is rarely needed and reassurance as well as pediatric patterns. In selected cases consultation with a proper teaching on how to monitor vital signs (such as it is pediatric cardiologist is strongly advised especially. done in good CPR training) can help convince the parents Paroxysmal non-epileptic events - Sotero de Menezes MA Jornal de Pediatria - Vol. 78, Supl.1 , 2002 S77 that the patient is not dying during the events. Parent Benign neonatal myoclonus education should also mention that putting the patient on a Commonly benign neonatal myoclonus is described as vertical position may worsen the symptoms by decreasing repetitive myoclonic jerks which are seen mostly during cerebral perfusion. Even though this seems to be very non-REM sleep involving mainly the arms.36 In this obvious during the crises the parents may instinctively pick syndrome patients have myoclonus which is often decreased up the child with idea of consoling her/him. Patients with by gentle restrain even simple touch.37 The myoclonus is anemia should be properly treated since a low hemoglobine restricted to sleep periods and and stop abruptly with is associated with an increase in the number of crises. awakening.37 The myoclonus is focal, multifocal or Atropine 0.01mg/kg/day (40-240 microgram/kg/dose) can generalized but in almost every case the focal myoclonic be sometimes helpful in children with frequent episodes. activity will eventually migrate to other sites.37 Repeated jerks lasting for a few seconds often recur every 3-15 The physiopathology of the cyanotic variant of breath minutes but in some cases the cluster may last up to 60 holding spells is probably multifactorial in nature still minutes.37 The movements may be so dramatic that even imperfectly known.31 Among the several factors that have experienceded pediatric neurologists may confuse it with been implicated in the genesis of these crises are epileptic neonatal myoclonic seizures (patient 1 reference hyperventilation (causing alkalosis and pCO reduction), 2 37). The family history may be positive in 10%37 to 25% of apnea, Valsava maneuver (causing an increase in the the cases.38 Treatment with anti-convulsant medications intrathoracic pressure e decreased venous return/cardiac (lorazepam, phenobarbital, phenytoin) may be ineffective.37 output). The latter factors decreased cerebral perfusion and Even though in most cases no autonomic changes are seen, oxygenation. The latter factors are much to slow to explain in 2/10 cases described by Daoust-Roy and Seshia (1992) the quick onset of cyanosis. An imperfect matching of showed 10-30% increases in heart rate.37 Polygraphic studies ventilation to perfusion resulting in intrapulmonaty right- of benign neonatal myoclonus suggest that this movement to-left shunt is one possible explanation.33 pattern is seen mostly during non-REM (quiet) sleep.36,37,39 Cyanotic breath-holding spells are also provoked by Nonetheless as many 22% of the events may actually occur pain and sudden emotional changes such as fright, anger or during in REM (active) sleep or less commonly (3% of the 37 frustration. After the precipitant factors the infant cries, cases) during transitional sleep. The same study found then holds her/his breath in expiration.6 The sequence of that quiet sleep was the predominant state in their tracings events is one of cyanosis, loss of consciousness and and that in any particular infant with benign neonatal limpness.6 In rare cases some brief body stiffening may be myoclonus the events did not occur more frequently or seen before respiration restarts at the end of the attack.6 The exclusively during quiet sleep. The electroencephalogram polygraphic recordings pattern have shown a sequence is normal during these events may show movement artifact. slightly different of from the one seen in the pallid variant In some cases the events may be followed by a decremental 37 with slowing of the EEG tracing with bradycardia such as reaction which is a normal pattern of arousal and/reactivity one would expect in the overshoot phase of a Valsalva in neonatal EEG tracings after 32 weeks of post-conceptional 40 maneuver. Breath-holding spells can have a frightening age. Some tracings may show excessive multifocal sharp appearance but are rarely if ever associated with serious transients but one puzzling finding in one study was the consequences so drug therapy is not indicated.34 presence of positive sharp waves in some patients over the temporal and central regions.37 As the name implies benign neonatal myoclonus is thought to be an entity with a good prognosis with remission of the myoclonus and normal development in almost all the patients.37 In some instances sleep myoclonus may persist Self-induced reflex syncopes through 4 months of age.37 If the diagnosis is correct (infant Gastaut et at. (1987) described a type of syncope that with myoclonus with normal neurological exam and EEG) 35 occurs mostly in retarded and/or psychotic patients. These no treatment is recommended even for the cases in which self-induced reflex syncopes are rare but at times can cause the myoclonus persists for several months. difficult diagnostic problems since they maybe mistaken for absences or drop-attacks. The children stop breathing, perform a Valsalva maneuver and after a few seconds, they become pale, stare and loose postural tone. Sometimes the Benign myoclonus of early infancy loss of postural tone may be limited to the neck or it may Benign myoclonus of early infancy is a syndrome in involve the lower limbs with causing a fall. In some cases which the infants have series of brief tonic or myoclonic flenfluramine may be helpful but currently due to contractions involving the axial muscles and more cardiovascular toxicity this drug is not used very often.16,35 prominently the neck (cephalic myoclonus). Flexion, This pattern may be rarely seen in children with normal extension or abduction of the arms can also be seen.41 Most intelligence.6 of these events occur during wakefulness, the EEG’s are S78 Jornal de Pediatria - Vol. 78, Supl.1, 2002 Paroxysmal non-epileptic events - Sotero de Menezes MA normal and the long term prognosis is excellent so no seizures are often triggered by an unconscious mechanism treatment is recommended.41 may not be obvious on an initial interview but they are commonly precipitated by suggestion. Psychogenic seizures must be distinguished from Shuddering attacks malingering seizures in which the patient will fake the event Shuddering attacks are an uncommon benign disorder 42-45 due to a secondary gain such as medico-legal compensation. of infancy and early childhood. This problem is In malingering seizures there is awareness of both the characterized shivering movements with bilateral fine production of symptoms and the underlying motivation. tremors, at times associated with stiffening of the upper extremities.44,45 The attacks were not associated with Clinically pseudoseizures have being recognized since impairment of consciousness or electroencephalographic the time of Charcot. These events usually occur when other abnormalities.44,45 These attacks last for several seconds, people are around (at home or at school) and are often occur daily and may be very frequent. Neurophysiologic precipitated by emotional factors. Often there is recall of monitoring (electromyography/ electroencephalography) the episodes. During the events there is a combination of of these events shows that the activity has a similar frequency some of the following elements: movements that tend to be to be almost the same as that as of essential tremor.45 A uncoordinated, non-synchronous thrashing of limbs, family history of essential tremor is not unusual.42 quivering, pelvic thrusting, side to side movements of the Shuddering attacks may represent the expression of the head, opsithotonic posturing, screaming or talking, episodes mechanism of essential tremor in the immature brain.42 In are often not stereotyped and the eyes tend to be closed. most patients the shuddering attacks decrease in number or When pseudoseizures resemble generalized tonic-clonic disappeared overtime.45 seizures the tonic phase is rarely seen, the clonic phase is In most cases the patients are otherwise normal but mild associated with wild thrashing movements, there is usually abnormalities on magnetic resonance imaging have been no loss of consciousness and if there is loss of consciousness described.45 it may be accompanied by shouting or obscene utterances. There are some features that are often not helpful since they Children with shuddering spells specially those with a maybe seen in both epileptic and non-epileptic events positive family history of tremor may develop head tremor include pupillary dilatation, depressed corneal reflexes, (“yes-yes” or “no-no” movement) which can be accompanied Babinski response and cardiorespiratory changes. Some 46 by the development of mild dystonia. patients may have event that are almost identical to partial Shuddering attacks are usually self-limited and improve motor (focal) or staring-absence seizures.6 In rare cases overtime becoming less frequent or remitting during the incontinence and even injuries may happen during the latter part of the first decade but the development of events. In some cases post-ictal confusion or abnormal essential tremor has been seen (see above). In the cases that clinical behavior after an attack may be seen. shuddering attacks are very disturbing propranolol therapy During the pseudoseizure the EEG does not show any may be helpful.47 In most cases no treatment is necessary. alteration of the background and no organized seizure activity or postictal slowing is seen. During an electrographic epileptic seizure the EEG shows a disruption of ongoing activity such as suppression of the posterior background Non-epileptic seizures/Pseudoseizures/Psychogenic rhythm, attenuation besides that there is usually the onset of seizures a novel rhythmic electrographic activity. Pseudoseizures have been more recently called psychogenic seizures. These events are involuntary, Making the diagnosis by video-EEG and inducing an intermittent episodes that resemble epileptic seizures, but episode by suggestion is the preferred method of confirming are not associated with epileptic discharges. Psychogenic the non-epileptic nature of psychogenic seizures. seizures can be psychologically induced especially by One has to be careful not to confuse pseudoseizures with suggestion. extratemporal (specially frontal lobe) onset seizures. Patients These events are often a manifestation of psychiatric with frontal lobe seizures have bizzare patterns with pelvic disturbances such as conversion or somatization disorder. thrusting, copulation-like or alternating leg movements.6 Psychogenic seizures have an age of onset 4-70, more often Besides that frontal onset seizures are at times difficult to in teenagers and they are three times more frequent in document by EEG recordings. Video-EEG monitoring will females than in males.6 These types of events are thought to show in frontal lobe seizures a stereotyped pattern of be a consequent of a “deep seated” conflict. A remote behavior whereas consecutive seizures tend to vary more in history of child abuse can be elicited in some cases. the psychogenic events. Patients with frontal lobe epilepsy Nonetheless the psychological origin of the pseudoseizure also tend to have seizures at night, where as pseudoseizures may not found even with proper psychotherapy. Psychogenic are usually daytime events. Paroxysmal non-epileptic events - Sotero de Menezes MA Jornal de Pediatria - Vol. 78, Supl.1 , 2002 S79

Postictal serum prolactin measurements have been Hyperekplexia advocated as a means of differentiating psychogenic from This disease is transmitted by an autosomal dominant epileptic events. Prolactin is elevated in mostly generalized trait is caused by a mutation in the alpha1 subunit of the and tonic-clonic and complex partial seizure types but may glycine receptor. The glycine receptor is encoded in the be normal in simple partial seizures and in some unilateral long arm of the chromosome 5 in the 5q33-q35 chromosomal mesial temporal seizures. locus.50,51 Other helpful tests include neuropsychological testing Familial cases demonstrate point mutations in the alpha- patients with psychogenic seizures are more likely to have l subunit of the inhibitory glycine receptor (GLRA1).52 The high scores on the schizophrenia, hypochondriasis, and glycine receptors have higher density in the brainstem and hysteria scales of the MMPI. spinal cord.53 The disease is characterized by an Even though as many as 50% of the patients with exaggeration of the normal startle reflex. Hyperekplexia is pseudo-seizures may also have genuine epileptic attacks in a term originary from the Greek meaning exaggerated adults this occurrence is not as common in children in our jumping/jerking. experience. In these cases anti-seizure medications often Andermann et al. (1980) described the details of the reach toxic levels because psychogenic seizures continue normal startle reflex which consists of alerting reaction after epileptic seizures are controlled with lower doses of associated with eye blinking, facial grimacing, flexion of these drugs. the head, elevation of the shoulders, and flexion of the 54 One should be careful about making the diagnosis of elbows, trunk, and knees. The authors call attention to the psychogenic seizures since careful follow-up may show a fact that tension, fatigue, will heighten and repeated stimulation will decrease the reaction. The startle reflex relatively high rate of recurrence even with appropriate 55 treatment on long-term follow-up (see reference 6 for appears early in infancy. review of the literature). The treatment of psychogenic This condition is characterized by episodes of excessive seizures includes psychotherapy, behavioral modification, startle after sudden tactile, auditory (loud noises) or visual relaxation, stress management, reassurance. Psychotic stimuli. Stimuli of similar intensity usually fail to produce patients with pseudoseizures need proper antipsychotic a similar response in most normal individuals.6 The attacks medications. are associated with increased muscle tone and spontaneous clonus. In some cases patients may have loss of muscle tone with a subjective sensation of stiffness. Patients with hyperkplexia the exaggerated startle reaction may be Hyperventilation syndrome followed by fall, which may be due to loss of postural This syndrome is defined by symptoms, which are control. reliably reproduced by voluntary hyperventilation.48 These The physiopathology of this disease is thought to be symptoms seen during attacks of hyperventilation include related to an impairment of reciprocal inhibition at the level anxiety, breathlessness, light-headedness, and paresthesias. of the spinal cord.56 Children with hyperventilation syndrome commonly have many chronic symptoms including headaches, irritable bowel The neonatal presentation of hyperekplexia is the period anxiety and depression.49 In the pediatric age group the has been called “major form”, stiff-baby syndrome or stiff- syndrome is more frequent among adolescents, although it man syndrome in the newborn.57-59 The neonatal has been recorded as early as 6 years of age.20 hyperekplexia is characterized by hypertonia starting on the first day of life (especially around the shoulder girdle) and It is not uncommon for the children hyperventilation excessive startle which can be produced by tapping the tip syndrome to have psychiatric problems before the onset of of the or the glabella (glabellar tap) as well as by feeding but hyperventilation attacks. The prognosis of this syndrome is may occur spontaneously.60 A clinically useful maneuver not very good and up to 40% of patients are still having is to tap the tip of the nose or the glabella. The glabellar tap hyperventilation episodes in adulthood.49 will elicit a non-habituating exaggerated startle response in Authoritative sources have pointed out that this diagnosis almost all affected individuals.61 This startle reaction leads is commonly missed and requires a high index of suspicion not only to an increase in muscle tone but may cause apnea as well as reproduction of the symptoms during hyper- in infants. Frequent choking and swallowing difficulties ventilation.20 Voluntary hyperventilation does not reproduce may be seen too. Over time the patients develop these symptoms every time so empirical treatment is hyperreflexia, gait ataxia, rhythmic clonus and are commonly indicated when the diagnosis is being strongly considered. mistaken for cases of spastic cerebral palsy.62 Sudden death Breath-holding, slow breathing, or breathing into a paper may occur in infancy starting from the neonatal period bag may improve the symptoms and it is recommended possibly due fatal apnea.60,63-65 In older patients the startle during the crises. Treatment with reassurance, psychotherapy reaction may cause falls, which are not unlike, drop attacks and psychiatric consultation is necessary in most cases. except for the EEG (see below). Often the patients’ falls are S80 Jornal de Pediatria - Vol. 78, Supl.1, 2002 Paroxysmal non-epileptic events - Sotero de Menezes MA associated with a loss of postural control causing loss of valproic acid, 5-hydroxytryptophan, or piracetam may protective mechanisms or fall “en statue”.6 Hypertonia reduce abnormal startle.74 Valproic acid has been helpful in tends to disappear overtime65,66 and it is absent during cases of late onset.70 Valproic acid is usually started on a sleep. Due to facial muscle involvement the patients may dose of 15-20 mg/kg/day, hematologic and liver toxicity have the appearance of being frightened or tense. Transition can be seen in any patient taking this drug and it is especially from awake to sleep state produces the normalization of the common with polytherapy and below age 2 years. Even baseline tone patients will often have violent and repetitive though one is tempted to say that clonazepam and valproic myoclonic jerks of the limbs especially during quiet sleep in acid exert their effect through their actions in the GABA some cases this pattern is so dramatic that the child is lifted receptor52 another GABAergic drug Vigabatrin was not off the bed.55,67 This dramatic pattern starts often when the effective in controlling the startle reactions.75 patients baseline awake tone starts to decrease, towards the The prognosis is variable and the main concern in end of the first year of life55 but cases with onset in the neonatal hyperekplexia is apnea. Early identification and neonatal period have been described.63,68 Insecure and treatment may help improving the outcome in these cases. hesitating gait may be also present in patients with the major There is a tendency for the neonatal form to improve form of hyperekplexia. spontaneously during the two years of life, although later on A chronic increase in the tone may lead to hip dislocation but delayed motor development is often seen.20,61 In some as well as increased intra-abdominal pressure and subsequent cases hyperekplexia may persist into adult life. Complete umbilical, inguinal and diaphragmatic hernias heart block has also been described in one case of non- formation.6,66,69 familial hyperekplexia.76 A “minor form” which begins in infancy has been described. In these cases as the patients get older emotional stress plays a major role. Exaggerated startle is often isolated and may be inconstant. One patient was reported with onset in adolescence that responded well to valproic Sandifer syndrome 70 acid. In some pedigrees the “major and minor forms” may Children with hiatus hernia, gastroesophageal reflux or coexist in the same family and sporadic cases have also been 71 esophageal dysmotility may have contortions of the neck described. associated abnormal postures.77-79 In spite of the abnormal Neurophysiologic studies demonstrate that neck position and movements the tone of the neck muscles 6 hyperekplexia is not only an exaggerated normal startle is not increased. Some of the head and neck movements response since the EMG latencies are shorter than normal.72 resemble in part those seen in adversive seizures. In some 6 The EEG may show centro-parietal spikes followed by cases head nodding and gurgling sounds may be seen. In slowing and desynchronization during the events.55 The one study of 126 infants and children with gastroesophageal 80 EEG’s changes have been questioned to be due to artifact reflux 7.6% had Sandifer’s syndrome. This pattern of and/or not related to seizure activity. Somatosensory and movements has been named Sandifer syndrome consist of auditory evoked potentials have been described to be sudden extension or torsion spasms of the neck and it is increased or normal in this disease.55,72,73 often assocaited with continuous twisting of the head from side to side.78 This pattern of movements be mistaken by The author agrees with the other authoritative sources dystonia may be made. Less dramatic patterns often go that the relationship of hyperekplexia with other nonepileptic unrecognized and undiagnosed and it is not uncommon for startle disorders, such as jumping (jumping Frenchmen of the patients to carry another diagnosis such as dystonia or Maine), latah (ticklishness associated with echopraxia and epilepsy are entertained before the Sandifer Syndrome is coprolalia in Malaysia), and myriachit (to act foolishly as diagnosed.81,82 reported in Siberia and other parts of Asia), remains speculative at this point.20,55 An exaggerated startle response The presence of hiatus hernia or reflux in association may be a component of reflex epilepsy (startle epilepsy), with such a dyskinesia allows the correct diagnosis to be which is outside of the scope of this review.55 made and appropriate therapy to be given. Medical treatment may not be sufficient and fundoplication is often necessary. Valproate and clonazepam are the treatments of choice for hyperekplexia. Clonazepam is used in relatively high The recognition of Sandifer’s syndrome may lead to doses 0.1 to 0.2 mg/ kg/day but symptoms may only partially effective medical or surgical treatment (fundoplication) of controlled.6 Clonazepam may help prevent neonatal gastroesophageal reflux. Sandifer syndrome should be problems.60 At times the episodes of increased tone may not included thedifferential diagnosis of pediatric patients with respond to benzodiazepines but forced flexion of the legs, presumptive paroxysmal torticollis, paroxysmal dystonia head and trunk may abort them.63,67 It is possible that of the neck without palpable increased tone of the familial cases are more likely to respond to clonazepam.50 corresponding muscle groups, or adversive seizures without In some cases in which clonazepam proved ineffective alteration of the level of consciousness. Paroxysmal non-epileptic events - Sotero de Menezes MA Jornal de Pediatria - Vol. 78, Supl.1 , 2002 S81

Dystonia and hypermotor movement disorders drowsiness etc. In the recent years the recommended initial 89 The typical dystonic reactions are not very hard to treatment for dystonia to be a trial L-DOPA. The rationale differentiate from epileptic seizures nonetheless there is a for using L-DOPA as the first-line therapy is to rule-out an border-zone of symptom overlap between epilepsy and infrequent syndrome named DOPA-sensitive dystonia (a.k.a. 90 dystonia. In dystonia there is co-contraction of agonist and Dystonia with diurnal variation or Segawa Syndrome). antagonist muscle groups often leading to twisting of body Patients with the latter syndrome typically have dystonia parts. Dystonias are not associated with impairment of which gets worse or appears in the afternoon by but many consciousness but may be preceded by a subjective sensation atypical cases can be diagnosed with the empirical treatment over the body part affected. Some cases of frontal lobe with L-DOPA. The onset of dystonia is typically in the epilepsy there is a dystonic-type motor phenomenon and preschool years90 but atypical cases have been described. loss of consciousness is not an obligatory the partial seizure Untreated cases develop parkinsonism in adolescence.89 in that epileptic syndrome. Patients with hemiplegia may The L-DOPA dose is dependent on the patient’s weight and develop dystonia too. One of my personal patients had a it is usually given in association with a peripheral DOPA large congenital infarct in the left internal carotid territory carboxylase inhibitor such as carbidopa to avoid nausea.89 and the cavitation which formed after the stroke made The initial dose in pre-school children in 50 mg of L-DOPA remaining functional cortex three centimeters or more but the dose can be increased to 250 mg if some response is removed from the internal skull surface. The boy had a seen. In most cases the response is obtained with low dose history of partial seizures with dystonic posturing leading to but atypical cases may required up to 750 mg/day.90 secondary generalization but he had also some plain dystonic The second line of treatment of dystonia (for patients posturing without any EEG changes. The lack of EEG who fail L-DOPA trial) is usually one of the anti-cholinergic changes could have been due to the large distance between agents such as trihexyphenidyl on an initial dose of 1-2 mg/ cortical generators and the recording electrodes. It took a day increasing by 1-2 mg/week up to doses of 40-80 mg/day while and some therapeutic trials of antiepileptic medications if tolerated.90 Anti-cholinergic type of side-effects are quite to get to the conclusion that he had two problems partial common specially with the higher doses including dry seizures and dystonia. mouth, difficulty initiating micturition, tachycardia, Clinically dystonia and hypermotor movement disorders precipitation of glaucoma etc. Other alternatives in the may affect only one of a few limbs but trunkal stiffness, treatment of dystonia include baclofen (initial dose 2.5 mg hyperextension of the head, opisthotonus, oculogyric crises tid increase up to 30 mg tid by 2.5 mg/day/week), clonazepan may be seen as well. Oculogyric crises are frequently (initial dose 0.01 mg/ kg/day increase to up to 0.2 mg/ kg/ related to drugs use. Among these drugs are psychotropic day), valproic acid (see Hyperekplexia above) and drugs such as phenothiazines and butyrophenones and carbamazepine on an initial dose of 5 mg/kg/day increased 83,84 metoclopramide. Many other agents have been reported to up to 30 mg/kg/day.89 to induce movement disorders this is especially true of the Chorea and tics are often easily differentiated from drugs with DOPAminergic effects.85,86 Young males are seizures. The exception are cases of simple motor tics more prone to dystonic reaction after exposure to which can be confused with myoclonus, in these cases an psychotropic medications such as haloperidol. Weaning EEG easily differentiate cortical/epileptic myoclonus from patients after treatment with haloperidol or other dopamine tics . Movement disorders do not need to be treated in all agonist drugs may cause emergent withdrawal reactions patients. In many cases the tics a mild and transient and do which include oro-facial dyskinesias, dystonia and akathisia. not need treatment. When the tics are very socially disruptive Akathisia is a sensation of restlessness which accompanied they can be treated initially with alpha-receptor agonist by the need to move incessantly. The diagnosis can be such as guanfacine (0.5 mg bid) or clonidine on an initial confirmed by urine examination for the commonly dose of 0.05 mg/day increased to up to 0.1 mg tid. We responsible drugs. In most acute drug reactions are self- routinely obtain an ECG before initiating treatment with limited and the treatment with intravenous anti-histaminics alpha-agonists. Patients who do not respond to guanfacine such as diphenhydramine (1mg/kg/dose intravenous slowly) or clonidine need treatment with dopamine antagonist which can control dystonic or dyskinetic symptoms and oculogyric are drugs with more complex toxicity including potentially crises, but in some episodes may not respond to high irreversible side-effects such as tardive dyskinesia and doses.87 akathisia that are better prescribed in consultation with a Other causes of dystonia include intracerebral lesions experienced Pediatric Neurologist or Psychiatrist. (tumors, vascular malformations, parasitic cysts) and more rarely the attacks may be caused by a mastocytoma.88 Dystonia which is not related to drug use may respond to anticholinergic drugs. These medications are rather toxic Spasmus nutans and should only be used a trained Pediatric Neurologist Spasmus nutans is characterized by the asymmetric since they are associated with a multitude of side-effects ocular oscillations, head nodding, and anomalous head such as dry mouth, constipation, postural hypotension, positions (tilting) with onset in infancy between ages 1-15 S82 Jornal de Pediatria - Vol. 78, Supl.1, 2002 Paroxysmal non-epileptic events - Sotero de Menezes MA months.20,91-93 Asymmetric nystagmus and head nodding postoperative hypoparathyroidism and pseudohypo- may be missed during the exam and many cases of spasmus parathyroidism are among the most frequent the causes of nutans often do not demonstrate all of the typical diagnostic hypocalcemia.6 features.20,91-93 The nystagmus in spasmus nutans can be conjugate (binocular), monocular or dissociated.94 The The classical tetany symptoms often do not appear nystagmus in these children is enhanced by the presentation before the age 3 months. Carpopedal spasm appears abruptly of a visual target (baby toy or colored books).91 Much of the and affecting mostly the fingers, which become flexed at the pathophysiology of spasmus nutans is unknown but the proximal joint and extended at the distal joints, with the cause of the head nodding is a normal compensatory thumbs adducted and opposed. The feet become tonically oculovestibular reflex.91 This conclusion is secondary to extended. No alterations in consciousness are noted which the fact that infants with spasm nutans. Speculations that is a key differentiating factor in older children. Laryngospasm spasmus nutans results from deprivation of sunlight have may occur with or without carpopedal spasm and it is not been confirmed.20 Even though the typical syndrome of diagnosed when inspiratory stridor is heard due to vocal spasmus nutans is thought to be often benign and self- cord adduction. Latent tetany may be tested with the Chvostek limiting condition but other more serious centities may have sign, which is the presence of facial muscle contraction after some of the symptoms and need to be differentiated before tapping the zygomatic arch region. Chvostek sign may 6 one makes the correct diagnosis.20 Among the “secondary” occur in some normal children. Hypoparathyroidism and causes of spasmus nutans are cases of congenital nystagmus, pseudohypoparathyroidism may be also associated with chiasmatic lesions,94 diencephalic syndrome, porencephalic headaches, extrapyramidal signs and calcification of the 97 cysts, opsoclonus-myoclonus,95 empty sella, ependymoma, basal ganglia. Pseudohypoparathyroidism is associated and retinal disorders.20,91-93 with short metacarpals, moon-shaped facies, enamel defect, decreased olfaction and auditory acuity, besides other One compared the clinical findings in spasmus nutans, nonspecific signs such as mental retardation, cataracts, with spasmus nutans-like disease (CNS lesions and obesity and decreased height.6,98 Epileptic seizures can 96 congenital nystagmus). These authors found that in the occur at any age in patients with hypocalcemia and are more spasmus nutans group the mean onset of nystagmus and commonly observed than the classical muscle spasms of head nodding was 8 months, and the mean onset of head tilt tetany.6 In infants especially in neonates, bona fide was 15 months. Nystagmus was asymmetric, intermittent convulsions that are persistently focal may be seen due to and had a later onset in spasmus nutans compared with the hypocalcemia. The treatment of tetany consists of parenteral other causes of infantile nystagmus. The optokinetic administration of calcium which requires careful nystagmus was frequently present in spasmus nutans and monitoring.99,100 Calcium given by an umbilical vein absent in the majority of cases infantile nystagmus. Head catheter may cause liver necrosis if the tip of the catheter nodding was also more frequent, of larger amplitude, and is not pushed into the inferior vena cava, the infusion site clinically easier to detect in spasmus nutans. Head tilt was should be checked frequently since extravasation of not found to be a useful differentiating criterion. calcium into the subcutaneous tissues may cause severe 99,100 Long-term follow-up is important to confirm the necrosis. Calcium chloride causes more severe diagnosis of spasmus nutans since most patients attain good reactions when extravasation occurs thus calcium gluconate 99,100 visual acuity but subtle nystagmus may persist until to age is the preparation of choice. Calcium should not be 12 years.93 mixed with sodium bicarbonate in the same vial or infusion line since precipitation of calcium carbonate in the solution may occur. Animal experiments suggest that calcium infused quickly through the aorta decreases the intestinal perfusion so slow infusion should be also used with umbilical artery Tetany catheters.99,100 Acute therapy of symptomatic hypocalcemia Tetany is in most cases due to hypocalcaemia or (tetany, seizures and apnea) should be 1-2 ml/kg of 10% hypomagnesemia or both. The term is used to designate calcium gluconate (1 ml of the Calcium gluconate 10% increased muscle tone due to increased excitability of the solution = 100mg = 9mg elemental Ca) by intravenous muscle membrane due to low calcium and magnesium infusion over 5 minutes under cardiorespiratory concentrations. Sometimes the total serum calcium may be monitoring.99,100 The dose may be repeated if there is no normal but ionized calcium level is low a condition which clinical response and the serum calcium remains low. may be due to alkalosis secondary to hyperventilation or Ionised Ca correlates more reliable of neuron membrane repeated vomiting such as in pyloric stenosis.6 In third irritability and should be used whenever possible to world countries babies who are fed cow’s milk improperly guide the beginning and termination of acute therapy diluted may develop hypocalcemia secondary to the excess especially in neonates since in this age group total serum phosphorus in the feedings. Vitamin D deficiency is now a Ca correlates poorly with ionized Ca99,100. Vitamin D rare cause of tetany. In developed countries congenital and magnesium are indicated when low levels are (inborn errors of calcium and vitamin D metabolism) and documented. Paroxysmal non-epileptic events - Sotero de Menezes MA Jornal de Pediatria - Vol. 78, Supl.1 , 2002 S83

Apnea-bradycardia episodes, Sudden Infant Death sudden death109 (see reference 6 for review). The indications Syndrome/Apparently Life-Threatening Events (ALTE) and usefulness of home electronic monitoring for apnea 110 In many instances patients presenting with apnea may be remains unclear. thought to have seizures. Apnea as the sole manifestation of seizures is rare but may occur infants especially full term neonates.101-102 Commonly neonates with seizure related Paroxysmal vertigo apnea eventually show other signs such as tonic eye deviation A syndrome of recurrent brief (one to several minutes) or clonic activity. Apnea of preterm infants is usually due to attacks of vertigo and nystagmus, which come on suddenly respiratory centers immaturity an it is only rarely seizure without known precipitant has been described in children. related. A full discussion of all causes of apnea is beyond The onset of symptoms is between the ages 1- 5 years and the scope of this review (see reference 6 for review). A boys and girls equally affected.111 The usual frequency of partial list of the common causes of apnea is neonates and attacks is low usually one to three per month but in some infants includes: acute presentation of asphyxia, neonatal case several per day have been reported.20,112 Most children seizures (with or without asphyxia), spinal cord and brain cease having attacks before age 7 years and in many cases birth injury, closed-head injury (accidental), non-accidental less than five attacks are recorded in their life. During the trauma (shaken-baby syndrome), acute sepsis, shock- attacks the child appears in pale and frightened but conscious, dehydration, respiratory infection (for example respiratory and may stagger and even fall. The patients will often hold syncicial virus-RSV), mechanical cord compression onto something (usually furniture or someone) at the onset (osteogenesis imperfecta), increased intracranial pressure of the event or she/he will lie down on the floor, refusing to from any cause. Among the CNS malformations associated move for the duration of the symptoms.112 In most cases the with apnea are Chiari type II, Joubert,103 Charge,103 Mohr, 6 patients have normal examinations are negative, but Dandy-Walker and Miller-Dicker syndromes . Metabolic abnormalities in inner ear/labyrinthine function have been diseases associated with infant apnea include fatty acid reported.111 metabolism defects (medium chain acyl-decarboxylase deficiency), nonketotic hyperglycinemia organic acidurias The relationship between childhood migraine and benign hypoglycemia, urea cycle disorders, mitochondrial disorders paroxysmal vertigo remains speculative but a positive family (Leigh syndrome), infantile neuroaxonal dystrophy. Known history of migraine among immediate relatives is not neuromuscular disorders may be associated with sudden uncommon. That possibility that benign paroxysmal vertigo respiratory dysfunction but apnea may also be the presenting represents a “migraine equivalent” is supported by cases of sign of these problems which include congenital and acquired children with the typical syndrome with or without myasthenia gravis, congenital myotonic dystrophy, associated headache that subsequently develop classic or congenital myopathies, spinal muscular atrophy, amyoplasia, vertebrobasilar migraine (reference 20; and several of my Pena-Shokeier Syndrome etc. Miscelania causes of apnea personal cases). include congenital central alveolar hypoventilation (Ondine’s curse), vocal cord paralysis, Moebius syndrome, Pierre Robin sequence, Neonatal form (major) of hyperekplexia (see above), infantile thalamic degeneration. Benign paroxysmal torticollis of infancy In older children obstructive apnea due to hypertrophy of Benign paroxysmal torticollis of infancy is probably amygdalae and adenoids, obesity and Rett syndrome are the closely related to paroxysmal vertigo but it may be have most common causes of apnea but other causes include different etiologies.113,114 The symptoms appear during neuromuscular disorders, CNS diseases, mitochondrial the first year of life and may even be present in the neonatal encephalomyopathy, Familial encephalopathy with period more often between ages 2-8 months.20 The duration permanent periodic breathing and central apnea of unknown 6 of the attacks is usually several hours but they may be short cause. Gastroesophageal reflux and esophageal spasm (10 minutes) and may last for as long as 14 days.20 Clinically may also cause apnea and bradycardia also known as “the 104-107 twisting of the neck (wryneck or torticollis) is seen without awake apnea syndrome”. persistent or obligatory abnormal head positioning and Sudden infant death syndrome (SIDS) is an subsequent spontaneous resolution is the rule in this inhomogeneous entity, which includes a group of diseases syndrome.20 “Spread” of the dystonic posturing to the and can not be fully discussed. Suffice to say that cases of trunk may be seen in some cases.115 Associated symptoms near-miss SIDS cases may be easily mistaken for epileptic include repeated vomiting, discomfort and tilting of the events due to the association of apnea with hypotonia or head to one side (may change with successive attacks) and stiffness and cyanosis or pallor. Severe cases may produce abnormal eye movements. In some cases the attacks may be hypotensive and hypoxic-ischemic injuries and may be heralded by a period of irritability, distress, or vomiting.20 followed by epileptic seizures.108 The majority of the More extreme cases have been describes in which one sees recent publications have found no clear-cut correlation inclination of the trunk to the side sometimes ipsilateral between polygraphic recordings and the later occurrence of stiffness, ataxia veering toward the side to which the head S84 Jornal de Pediatria - Vol. 78, Supl.1, 2002 Paroxysmal non-epileptic events - Sotero de Menezes MA is tilted.6 In these extreme cases a CNS tumor needs to be Paroxysmal kinesigenic dyskinesia in many cases ruled-out unless there is a clear-cut history of previous responds well to anticonvulsant drugs, especially those similar episodes, which subside leaving a completely normal which act by inactivation of the sodium channel such as child free of any neurological anomaly. During the carbamazepine and phenytoin even in low doses.117 Patients assessment of the first episode head imaging is commonly affected by paroxysmal kinesigenic choreoathetosis have necessary. Familial clustering has been reported.116 normal longevity but the attacks in public may lead social embarrassment. Other causes of torticollis must be ruled out including ocular, pain-related, contracture-related, dystonic, This syndrome is usually treated initially with Sandifer’s syndrome. CNS tumors including those located carbamazepine 5 mg/kg/day some patients can respond to in the posterior fossa, third ventricle (colloid cyst) and even lower doses but others may required slight higher spinal cord may also produce intermittent torticollis. doses in the range used for children with seizures (15-25 Syringomyelia may also have similar symptoms. One of my mg/kg/day). In some resistant cases, flunarizine has been personal cases presented with intermittent tonic posturing successful in controlling of the attacks but totally 120 of the neck as a toddler which lead to an investigation for unresponsive cases have been reported. Flunarizine is dystonia and seizures. “Ocular torticollis” resolves with usually started on a dose of 2.5-5mg/day in children and supine position or occlusion of paretic eye and it is present increased as tolerated to up to 0.5-1mg/kg/day. in the sitting position. Trauma and infection-related lymphadenitis may also produce pain and abnormal neck posturing. Paroxysmal torticollis can be differentiated from Paroxysmal non-kinesigenic (dystonic) choreoathetosis contractures since the head can be passively returned to the Attacks similar to the ones described under neutral position but the tilting recurs immediately. Like in “Paroxysmal Kinesigenic Choreoathetosis” (see above) the case of paroxysmal vertigo a relationship to migraine but triggered by stress, coffee or alcohol ingestion have has been suggested for paroxysmal torticollis. Typical been described.117,121 Attacks are usually longer than migraine has been seen in cases of torticollis as the child the ones see in the kinesigenic forms often lasting from 113 grows older. Other etiologies of vertiginous episodes several hours on the other hand they occur less frequently. may occur in children such as drug intoxication or acute This condition is also familial and transmitted by a labyrinthitis of infectious origin need to be taken in dominant trait but is less common. The non-kinesigenic consideration when making the diagnosis of paroxysmal for of paroxysmal choreoathetosis does not usually 6 vertigo. Most cases of Benign Paroxysmal Torticollis of improve with anticonvulsant agents, with the exception Infancy recover before age 2 to 3 years without medical of clonazepam and oxazepam.117,122 One patient who 20 intervention. also had familial ataxia responded positively to acetazolamide.123 The initial clonazepam dose is 0.01 mg/kg/day wihc is increased to 0.1 mg/kg/day over a several weeks, sedation is often one of the most limiting side- Paroxysmal kinesigenic choreoathetosis effects. In this disorder sudden movement precipitates uni or bilateral dystonia and/or chorea spells which may repeat up to 100 times.6 The attacks may be preceded by an aura of tightness or tingling in the affected segment.6 No loss of Other idiopathic paroxysmal dyskinesias consciousness is noted during in the events, which last from Lance described also intermediate cases that did not one to a few minutes.20 The movements may be bizarre, fit either the kinesigenic or the non-kinesigenic writhing dystonia, choreic or even and ballistic in nature paroxysmal choreoathetosis groups.117 These odd cases and sometimes cause falls.117 Other stimuli which have are often induced by sustained exercise with attacks been described to precipitate the attacks include stress, lasting 5-30 minutes but cases of.117,121 Wali reported hyperventilation, excitement and startle.117 Cases also hemidystonia induced by prolonged exercise and precipitated by methylphenidate have been described.118 cold.124 A rare form of autosomal dominant paroxysmal Three-quarters of the cases of this disease are familial and choreoathetosis with spasticity has been described and transmitted by a dominant trait.6 The other ¼ of the cases recently mapped to chromosome 1p near the potassium probably represent denovo mutations. One needs to be gene channels cluster.125 careful with this diagnosis since cases which have been thought to be paroxysmal kinesigenic choreoathetosis undergoing long-term video-EEG monitoring have been shown to have an electroencephalographic seizures Paroxysmal dystonia of infancy originating from the supplementary sensorimotor cortex Angelini et al. described a paroxysmal dystonia in and ipsilateral caudate nucleus.119 infants aged between 1 and 5 months.126 Clinically the Paroxysmal non-epileptic events - Sotero de Menezes MA Jornal de Pediatria - Vol. 78, Supl.1 , 2002 S85 episodes are characterized by brief, frequently and repeated over time and disappear altogether before the end of the episodes of dystonia of the upper limbs (symmetrical or second year of life.126 asymmetrical) and/or opisthotonus. The symptoms abated

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126. Angelini L, Rumi V, Lamperti E, Nardocci N. Transient Corresponding author: paroxysmal dystonia in infancy. Neuropediatrics 1988; Dr. Márcio A. Sotero de Menezes 19:171-4. E-mail: [email protected]