Paroxysmal nonepileptic disorders

key source: Paroxysmal nonepileptic disorders: differential diagnosis of epilepsy [John Stephenson, William P Whitehouse and Sameer Zuberi]

---

Introduction

Nonepileptic events have been arbitrarily divided into the following categories:

• syncopes and anoxic seizures
• psychological disorders
• derangements of the sleep process
• paroxysmal movement disorders
• migraine and possibly related disorders
• miscellaneous neurological events
• Anoxic-epileptic seizures

Syncopes and anoxic seizures

An anoxic seizure is the consequence of a syncope, which occurs usually as a result of a sudden decrease in cerebral perfusion of oxygenated blood, either from a reduction in cerebral blood flow itself or from a drop in the oxygen content, or a combination of these.[1, 2]

Although we have categorized the syncopes, it must be recognized that overlaps occur. Indeed, it seems likely that what we call reflex anoxic seizures or reflex asystolic syncope (RAS), breath-holding spells or prolonged expiratory apnea, vasovagal syncope and neurocardiogenic syncope are all varieties of the same disorder, called by the adult cardiologists neurally mediated syncope. When parents or children are bewildered by these diagnoses, or annoyed when told that 'it's only breath holding' or 'only a simple faint', contact with a family support organization such as [3, 4, 5, 6, 7, 8] may be very helpful.

Reflex anoxic seizures or reflex asystolic syncope (RAS)

Gastaut used the term reflex anoxic cerebral seizure to describe all the various syncopes, sobbing spasms and breath-holding spells which followed noxious stimuli in young children.[9] Since 1978, the term reflex anoxic seizure has been used more specifically to describe a particular type of nonepileptic convulsive event, most commonly induced in young children by an unexpected bump to the head.[10] Although other terminology, such as pallid breath-holding and pallid infantile syncope have been applied to such episodes,[11] the term reflex anoxic seizure is now widely recognized.[12, 13]

The clinical picture has been extensively documented. [1] Previously, almost all the available information came from descriptions by parents who had witnessed their child's attack or from observations of episodes reproduced by ocular compression, and it is only in recent times that home video-recordings of reflex anoxic seizures have become available. The first video-recording of a 'natural' attack obtained by one of the authors occurred when a 4-year-old girl was having capillary blood taken. The accompanving convulsive syncope was more severe than that previously recorded in the same child after ocular compression. Although the duration of postictal stupor was also longer, other mothers who watched the videotape were surprised at how quickly the child recovered.

Until the advent of cardiac loop recorders, there was very little direct evidence of the pathophysiology of natural attacks. In a child who had two episodes while connected to EEG and ECG recorders, cardiac asystole alone appeared to account for the resultant anoxic seizure.[2] At the time of the first edition of this book, only three further recordings had been obtained.[14] Observations of the anoxic seizure induced by ocular compression in one of these children help to explain the confusion between reflex anoxic seizures and breath-holding spells. When this particular girl had ocular compression, asystole was apparent from the moment the thumbs began the ocular pressure, which is the usual finding in such cases. In the first few seconds of the asystolic period, however, there were repeated expiratory grunts at about three grunts per second. The parents recognized these grunts as similar to those noticed in the natural events. Thus, the anoxic seizure in this case was clearly related to the cardiac asystole and the expiratory grunting was an epiphenomenon. In cyanotic breath-holding attacks resulting in syncope or even a convulsive syncope, the amount and duration of expiratory grunting is greater and longer and the latency between the stimulus and the nonepileptic motor seizure is undoubtedly greater. Since prolonged cardiac recording by loop recorders has become feasible in young children, many episodes of prolonged reflex asystole have been recorded and several examples published.[15, 16]

Reflex anoxic seizures or reflex asystolic syncope (RAS)

Gastaut used the term reflex anoxic cerebral seizure to describe all the various syncopes, sobbing spasms and breath-holding spells which followed noxious stimuli in young children.[9] Since 1978, the term reflex anoxic seizure has been used more specifically to describe a particular type of nonepileptic convulsive event, most commonly induced in young children by an unexpected bump to the head.[10] Although other terminology, such as pallid breath-holding and pallid infantile syncope have been applied to such episodes,[11] the term reflex anoxic seizure is now widely recognized.[12, 13]

The clinical picture has been extensively documented. [1] Previously, almost all the available information came from descriptions by parents who had witnessed their child's attack or from observations of episodes reproduced by ocular compression, and it is only in recent times that home video-recordings of reflex anoxic seizures have become available. The first video-recording of a 'natural' attack obtained by one of the authors occurred when a 4-year-old girl was having capillary blood taken. The accompanving convulsive syncope was more severe than that previously recorded in the same child after ocular compression. Although the duration of postictal stupor was also longer, other mothers who watched the videotape were surprised at how quickly the child recovered.

Until the advent of cardiac loop recorders, there was very little direct evidence of the pathophysiology of natural attacks. In a child who had two episodes while connected to EEG and ECG recorders, cardiac asystole alone appeared to account for the resultant a]noxic seizure.[2] At the time of the first edition of this book, only three further recordings had been obtained.[14] Observations of the anoxic seizure induced by ocular compression in one of these children help to explain the confusion between reflex anoxic seizures and breath-holding spells. When this particular girl had ocular compression, asystole was apparent from the moment the thumbs began the ocular pressure, which is the usual finding in such cases. In the first few seconds of the asystolic period, however, there were repeated expiratory grunts at about three grunts per second. The parents recognized these grunts as similar to those noticed in the natural events. Thus, the anoxic seizure in this case was clearly related to the cardiac asystole and the expiratory grunting was an epiphenomenon. In cyanotic breath-holding attacks resulting in syncope or even a convulsive syncope, the amount and duration of expiratory grunting is greater and longer and the latency between the stimulus and the nonepileptic motor seizure is undoubtedly greater. Since prolonged cardiac recording by loop recorders has become feasible in young children, many episodes of prolonged reflex asystole have been recorded and several examples published.[15, 16]

Extracts from a letter from a consultant neurologist may give the reader some idea of the clinical diagnostic difficulties that were experienced before the phenomenon of reflex asystole was well known: Thank you for asking me to see this seven-year-old young man. As a toddler he began to have attacks of loss of awareness, rigidity and eye rolling which would be induced by minor knocks. This has continued and recently an episode occurred in which he had an undoubted tonic/ clonic seizure with incontinence of urine. Curiously, as far as I can tell from mother's account, every attack has been triggered by a minor bump on the head and he has never had an attack out of the blue. He had difficulties at birth. The family history is clear except for a convulsion in the mother when she was tiny, about which there is no further information. It seems to me that this boy is having a form of reflex epileptic seizure and my inclination would have been to start treatment with sodium valproate. In fact mother told me that he is attending the paediatric department at... and that he was started on Epilim just a couple of weeks ago. Even though two EEGs have been normal I do not doubt that he has an epileptic tendency and I am sure that he should be on treatment for at least a couple of years free from attacks.

When this boy was seen he was beginning to become an 'epileptic', his school knew about his 'epilepsy', his mother was in touch with an epilepsy association, and invalidity benefit had been applied for on the basis of epilepsy. Presumably the difficulty here was that neither the pediatrician nor the neurologist knew that this was precisely the description of a reflex anoxic seizure of the vagally mediated cardioinhibitory type, otherwise known as reflex asystolic syncope.

As children grow older reflex anoxic seizures may cease altogether or change to more obvious convulsive or nonconvulsive vasovagal syncope. Beyond the toddler stage, children may report sensory disturbances along with the syncopes. Most dramatic are out-of-body experiences with a dream-like quality,[17] which may include the child feeling as if they have floated up to the ceiling and are watching their body lying on the floor in a seizure.

Although it is often said that breath-holding spells or syncope caused by prolonged expiratory apnea may also occur in children who have reflex anoxic seizures, there are no good recordings that confirm this proposition. Rather, recordings of what may on history or observation be taken as 'breath-holding attacks' turn out to demonstrate primarily asystole. In one such case of a 4-year-old twin in whom the attack was triggered by her brother snatching a toy, the girl started to cry, made a few expiratory grunts, looked cross, and had an end-expiratory apnea and extensor axial spasm. The asystole lasted 25 s and started during the grunting. This child also had similar reflex anoxic seizures triggered by unexpected knocks to the head.

It is important to determine whether a convulsive syncope in a young child is cardiogenic or respiratory in origin. If it is cardiogenic, the main differential diagnosis of a reflex anoxic seizure (reflex asystolic syncope) is convulsive syncope from long QT syndrome or other cardiac cause. In contrast, the differential diagnosis of a respiratory syncope includes breath-holding spells and intentional suffocation.

Vasovagal syncope

Vasovagal syncope is the most familiar and predominant form of neurally mediated syncope. Unlike classical reflex anoxic seizures, which represent a fairly pure vagal attack, vasovagal syncope involves a vasodepressor component with variable vagal accompaniment. Episodes may begin in infancy but are seen at all ages, becoming most dramatic perhaps in old age.[18] Tables in medical textbooks are extremely misleading and tend to perpetuate myths about factors that are useful in distinguishing vasovagal syncope from epileptic seizures. Contrary to what is often stated, vasovagal syncope may sometimes occur in the supine position, particularly in the case of episodes occurring during venepuncture. Similarly, pallor and sweating are not invariable features and the onset of the episode is not always gradual. There is no evidence that injury is less common in convulsive syncope than in a convulsive epileptic seizure. Convulsive jerks are certainlv not rare and occur in perhaps 50 per cent of vasovagal syncopes[19] and more often in experimental syncope.[20] Urinary incontinence is common[21] and occurred in 10 per cent of cases in one experimental study.[2] Although consciousness is regained rapidly in mild syncope, it is often impaired initially and marked postictal confusion can occur.[1] Finally, vasovagal syncope may occur more than once a day in some individuals.

Stimuli maybe very subtle, but some sort of stimulus should be detected for at least some attacks in order to make this diagnosis. Indeed, the most reliable indicators of vasovagal syncope are the setting and stimulus, together with elicitation of the warning symptoms or aura that are often present. A seizure that occurs after a bath, while the child is having her hair blow-dried or brushed, is virtually certain to be a vasovagal nonepileptic convulsive syncope. Premonitory symptoms are usually present in older children, even if only for a second or two, but these may sometimes be forgotten and recalled only when syncope is reproduced by the head-up tilt test.

Dizziness, graying out of vision and tinnitus are well-recognized symptoms of cerebral ischemia, but an important additional symptom is abdominal pain. Abdominal pain may be either a trigger of a vasovagal syncope or an actual intestinal symptom of a strong vagal discharge. The latter is more common than appreciated,[2] and is sometimes confused with the epigastic aura that may occur at the onset of a temporal lobe seizure. Almost all children with vasovagal syncope have an affected first-degree relative, commonly a parent.[22] It is unfortunately not uncommon to find that the patient, who now seems convincingly to have vasovagal convulsive syncope, has become irredeemably'epileptic' and is too habituated (or too frightened of losing a precious driving license) to discontinue years of useless (and perhaps embryopathic) antiepileptic medication (histories are included in ref. [2] ).

Head-up tilt testing of children has now been reported by a number of authors.[23] We have used a technique of 60° head-up tilt with foot-plate support, recording simultaneous EEG and ECG on cassette tape linked to a video-camera through a video-interface processor (VIP). At the same time beat-to-beat blood pressure is measured noninvasively using the Finapres method. A witness to natural events, normally a parent, is always present during this tilt test to confirm that what is reproduced is identical to natural episodes. The child is also able to say whether premonitory symptoms are the same as those experienced cin the field'. We have reproduced convulsive syncope in nine children aged 8-13 years using the head-up tilt test. In contrast to the adult situation,[24, 25] there has been marked cardioinhibition with asystole varying from 4 to 30 s. We have been struck also by the high incidence of behaviors that resemble syncope but do not have the cardiovascular or cerebral features of true syncope. These emotional or psychogenic episodes have been described in adults also[25] and are discussed in the section on conversion disorder below. These events often occur in individuals who also have vasovagal syncope.

Case History A case history illustrates the transition from reflex anoxic seizures in infancy through short latency pain-induced vasovagal syncope to blood-injury phobia in adolescence.[26, 27] The mother gave the history when her affected daughter was aged 13 years. A consultation had been requested as soon as she saw the recording of a finger-prick-induced reflex anoxic seizure on television. Her daughter had been diagnosed previously at different times to have epilepsy, hypoglycemia and hysterical behavior.

The first episode occurred at the age of 10 months after a very slight bump to the infant's head. The appearance of the attacks has been similar from then to now, except that severity has varied and tended to increase with the passage of time. Typically there is a latency of 10-20s during which she may say 'oh mum I've hurt myself. By this time the blood has drained from her face, she goes limp and falls as if dead, then going totally rigid making a noise like a cackle or gurgle, with her hands and feet turned in and her back sometimes forming the shape of an arc. Sometimes her arms and legs jerk, but not violently, as though pedaling her bicycle, but on occasion thrashing wildly like a full seizure (as her mother describes it). Again she looks like death and then wakes up as if coming out of a very deep sleep. She is then very disorientated, does not know what has happened or where she is, but within a couple of minutes she has come to herself and may then want to lie down again and have a proper sleep. Since about the age of 7 or 8 years she has described an aura. She hears a noise like a high-pitched screaming and sometimes hears a voice but cannot describe the voice precisely. Sometimes she sees red, a color she does not like.

More recently she has had strange hallucinations during the warning period, such as seeing a train rushing towards her. The stimuli have modified over the years after the first head hump. All episodes in earlier years followed small pains like her finger being bent back. Then she developed the same reaction to seeing a minor injury such as a scab that had come off a wound, and then inevitable syncope at the sight of blood. Most recently merely the thought of self-injury was sufficient.

On the evening before the intended consultation, she was told (wrongly) that her eyeballs would be pressed down and within 2 minutes she was stiff and snorting. Although a family history of syncope of any kind was denied, the mother later admitted to several faints in adolescence and in pregnancy but did not mention them because she did not have a 'fit'.

The results of a recent study suggest that adults with blood/injury phobia have a 'constitutional autonomic dysregulation' that predisposes them to neurally mediated syncope, even in the absence of any blood or injury stimulus, and that repeated syncopes resulting from such stimuli secondarily lead to the blood/injury phobia.[28]

In contrast to vasovagal syncope, convincing vagovagal syncope is rare. The reflex is usually triggered by swallowing or vomiting and the anoxic seizure occurs if the asystole is sufficiently prolonged. This is probably not a life-threatening disorder, but the symptoms can be trouble-some, particularly if the patient also has migraine with associated vomiting. Pacemaker therapy has been used successfully in this situation.[2]

Hyperventilation syncope

Hyperventilation induces various symptoms in everyone. In certain individuals this may stimulate further hyperventilation and exacerbation of the original symptoms, and a degree of panic may result. Asking the child to hyperventilate (whether by getting them to repeatedly blow out a candle, blow soap bubbles, blow a tissue or to directly hyperventilate) may induce symptoms similar to those of which they complain. Continuation of hyperventilation once the directed hyperventilation has been stopped may be of additional diagnostic value. Hyperventilation may also lead to episodes that resemble absence seizures but are not associated with spike and wave discharges.[29]

Orthostasis

Syncope due to orthostatic hypotension secondary to autonomic failure is rare in childhood. Chronic orthostatic intolerance may be caused by dopamine ß-decarboxylase deficiency.[30] Chronic orthostatic intolerance may also manifest in teenagers and young adults as the postural/ orthostatic tachycardia syndrome (POTS).[31] Patients have symptoms of chronic orthostatic intolerance with significant daily disability, associated with a marked tachycardia on standing: a heart rate increase of >30 beats/min or a heart rate of >120 beats/min within l0min of head-up tilt.[32] Chronic orthostatic intolerance is a treatable disorder and should be considered in the differential diagnosis of idiopathic chronic fatigue syndrome.

in addition to vasovagal syncope, chronic orthostatic intolerance can produce symptoms of light-headedness, dizziness, blurred vision, exercise intolerance, chronic fatigue, migrainous headache, nausea, abdominal discomfort, chest discomfort, palpitations, shortness of breath, hyperventilation, peripheral cyanosis, and sweating and flushing on standing.[32] The simplest way to demonstrate orthostatic intolerance is to stand the child on a foam mat (to avoid injury when falling) for l0min with con-tinuous blood pressure measurement, which is best done using Finapres recording from a finger with the hand secured at heart level. A similar method can also be used to provoke vasovagal syncope in young children, including those too young to tilt.[33]

Long QT disorders

The long QT syndromes are associated with genuinely life-threatening syncopes, which may be hypotonic or convulsive. The mechanism of the syncopes is a ventricular tachyarrhythmia, normally torsades de pointes. As a rule, there is no great difficulty in the diagnosis of the syndrome of Jervell and Lange-Nielsen,[34] in which congenital deafness is associated with an autosomal recessive inheritance. Much more difficult is the Romano-Ward syndrome,[35] which is dominantly inherited but with incomplete penetrance. There is a degree of overlap between the stimuli that induce the neurally mediated syncopes, and those that trigger the ventricular tachyarrhythmias of the long QT syndrome; for instance, head bumps may trigger long QT as well as RAS.[36]However, a history of convulsions triggered by fear or fright, particularly if they occur during exercise (especially when that exercise is emotionally charged) or during sleep is strongly suggestive of the long QT syndrome.

A personal example illustrates some of the diagnostic difficulties:

A 5-year-old girl presented with a history of convulsive syncope since the age of 2 years. At the first consultation the parents said that when she fell, not necessarily hurting herself and not necessarily falling on any particular part of her, she went gray or gray/purple around the mouth, looked faintish as if dead, went very, very rigid as her eyes rolled and her head flopped, she moaned and 'she was dead in my arms'. One of the episodes was said to have occurred as a splinter was being taken out of her finger by her mother. There was a positive family history in that the father had fainted on cutting his finger and the mother had faints in pregnancy. An interictal 24-h ambulatory cassette ECG of the child had been reported as normal. A diagnosis of reflex anoxic seizures (reflex asystolic syn-cope) was made and it was decided that it would not be necessary to do ocular compression as a confirmatory test. Three years later the consultant pediatrician wrote again:

'She had approximately one year without any episodes but has had two close episodes in the last few weeks both of which occurred during physical exertion during play. At least one of these episodes seemed to be associated with an olfactory aura, the child describing strange smells before the event. In both situations she was found unconscious, stiff and mottled gray but recovered fairly promptly. I guess this is still a vagally mediated event but the parents would value further assessment and reassurance'.

Review of the history revealed that although two of the episodes had originally been associated with falling when playing with a ball, other episodes had occurred when chasing a dog, trying to catch the waves at the edge of the sea, playing being chased on her bicycle and during a hopping race. The new historical details prompted immediate measurement of her QT interval, the corrected value of which (QTc) 479 ms (normal value less than 440 ms). A review of the original 24-h ECG from 3 years previously showed that the QTc was prolonged then also, at 470 ms. Her mother had a marginally prolonged QTc of 449 ms, whereas her father and sister had normal QTc measure-ments of 387 and 390 ms respectively.

Long QT disorders are very much less common than reflex anoxic seizures, but should be considered when the precipitants are not typical and particularly when exercise or sleep are triggers.

Other cardiac syncopes

Cardiac syncopes, other than those of the long QT syn-dromes, do not usually pose diagnostic difficulties. However, it is important for the clinician to obtain a sufficiently clear history to determine whether the event is an epileptic seizure or a nonepileptic convulsive syncope. Ventricular tachyarrhythmias may occur with normal QT intervals.[37] In patients with congenital heart disease, exercise can precipitate paroxysmal pulmonary hypertension, which may manifest as an anoxic seizure.[2] We have also seen a 10-year-old boy who presented with recurrent convulsions with pain or stress. A standard 12-lead ECG demonstrated third-degree heart block, for which he was successfully treated.

Breath-holding attacks

Breath-holding spells have been described for centuries[38] but controversy as to what they are remains.[39] The term breath-holding seems to imply some sort of voluntary I'll hold my breath until I get what I want' behavior, and many members of the public and even pediatricians appear to believe that breath-holding spells are a manifestation of a behavior disorder. Indeed, breath-holding attacks are described in the section on psychiatric or psychological disorders in some pediatric textbooks. However, behavioral disorders in those with breath-holding spells are not more common or different from those in control children.[40]

As with many paroxysmal disorders, there are very lew precise detailed descriptions of what happens during an event. Cinematographic registration[41] and video-recordings have been obtained, predominantly of several episodes in a single child.[2, 42] Southall, Samuels and Talbert[43] have made polygraphic recordings of a small number of children. There appears to be a pure respiratory 'breath-holding' spell or prolonged expiratory apnea,[44] which occurs without any change in cardiac rate or rhythm (albeit information on cardiac output is not available) and is associated with cyanosis, the so-called 'blue' breath-holding attack. However, there are also 'mixed' breath-holding episodes that are characterized by both expiratory apnea and also a degree of bradycardia or cardiac asys-tole.[2] Furthermore, we have seen a video with simultaneous ECG of a child with a prolonged expiratory apnea while crying who became unconscious and had an event typical of that seen in reflex asystolic syncopes. However, this child maintained sinus rhythm with a modest tachycardia throughout (personal communication, E Wylie, 2000). This illustrates that the clinical features of reflex anoxic seizures may also occasionally be provoked by crying and occur with pure 'breath-holding' or pro-longed expiratory apnea [2] The difficulty in distinguishing between these by history and video alone without simultaneous ECG emphasizes the importance of obtain-ing an ictal ECG recording if atropine or pacing is to be considered for treatment.[45]

Prolonged expiratory apnea (cyanotic breath-holding) attacks in neurodevelopmentally normal children are benign and have an excellent prognosis.[39, 46] The reports of life-threatening episodes[47] reflect the fact that attacks with similar features may occur in children with other abnor-malities. For example, infants with tracheal anomalies may have similar episodes.[41, 48] In addition, severe cyanotic breath-holding spells resembling prolonged expiratory apnea may be seen in infants with structural malforma-tions of the posterior fossa. We have also seen potentially life-threatening episodes in a variety of Joubert syndrome with supratentorial neuronal migration disorder.

Compulsive Valsalva maneuver

Children with abnormal neurological development, including those with autistic disorders, may compulsively self-induce their atonic or more dramatic syncopal seizures by something akin to a Valsalva or Weber maneuver.[1, 49] Such episodes may be very severe and even have a fatal outcome.[50] If the episodes are very frequent, as is often the case, video-recording with polygraphic regis-tration may be useful.[50] The episodes are characterized by 'breath-holding' for about 10 s in inspiration, reduc-tion of the amplitude of the QRS complexes on ECG, and then a burst of high-voltage slow waves on EEG. Some-times, hyperventilation precedes the Valsalva maneuver,1 as in the experimental syncopes described by Lempert, Bauer and Schmidt.[50] It is likely that many of the reported seizures in Rett syndrome are of this nature.[51]

Gastroesophageal reflux

Much has been written about gastroesophageal reflux in infants, but video-recording or full polygraphic registra-tion of a reflux-associated anoxic episode has not been reported, although a true reflux episode associated with an epileptic seizure has been described[52] Nonetheless, a persuasively recognizable condition, the awake apnea syndrome, has been described[53] The episodes occur within an hour of a feed and usually follow an imposed change of posture. The infant gasps, becomes apneic, stiffens, changes color and may then look startled.[2] What might be called a reflux (sic) anoxic seizure may well be an example of vagovagal syncope, but a respiratory cause such as laryngeal spasm may be responsible. Gastroesophageal reflux may also result in the Sanditer syn-drome, mentioned under 'Miscellaneous neurological events' below. Imposed upper airway obstruction: suffocation

Suffocation of a baby, usually by the mother, [54] is a rare but important cause of 'breath-holding spells'. This is a classic example of fabricated or induced illness.[55] The parent repeatedly suffocates the baby by pressing a hand or some material over the baby's mouth, or else the mother presses the baby's face against her bosom6 with a resultant syncope and anoxic seizure. Unlike the retlex anoxic seizures that occur with reflex asystolic syncope or cyanotic breath-holding spells, the evolution is much longer, with a latency of approximately 2 min[56] The diagnosis may be exceedingly difficult. A cardinal feature is that the episodes only begin in the presence of the mother and other observers see only the conclusion of the episodes.[57] The EEG and ECG demonstrate a particular sequence of abnormalities, including movement and muscle potentials6 and features of hypoxemia. [58] Establishing a definite diagnosis may require covert video-recording. [55, 59] It has been found helpful to involve another experienced pediatrician, a psychiatrist and child protection procedures before discussion of the mechanism of induction of these truly life-threatening anoxic seizures with the family.[2]

Hyperekplexia

Hyperekplexia is a rare disorder (or group of disorders), which may present dramatically in the neonatal period with nonepileptic convulsive syncopes that may prove fatal. [60] This is a treatable disorder and so diagnostic awareness should be high.[61] A major early paper on this topic[62] described a dominantly inherited disorder in which there was hypertonia in the neonatal period with later onset of pathologic startles. A consistent diagnostic sign of hyperekplexia is elicited by tapping the infant's nose.[63] Nose-tapping produces a minimal response in a normal infant, whereas there is an obvious and reproducible startle response including head retraction in affected children. This startle may be induced over and over again. The diagnosis is not too difficult in sporadic cases in which the baby is stiff and tends to startle. The diagnosis is more easily missed in the baby that is not stiff and has neonatal onset convulsions with severe syncope. The ability to precipitate these dramatic nonepileptic seizures using the nose-tap test is particularly helpful. It is very important for the parent (and the examining physician) to know that the episodes, which can be very dramatic and even life-threatening in some infants, can be aborted by neck flexion.[61] The EEG recording during an episode demonstrates characteristically a series of what superficially may appear to be spikes but are actually rapidly recurring muscle potentials from scalp muscle. The frequency of the 'spikes' decreases pari passu with slowing of both EEG and ECG in the resultant severe syncope. The genetic basis in both the dominantly inherited variety of hyperekplexia and the apparently sporadic cases is a defect in either the α(l)63 or ß64 sub-units of the strychnine-sensitive glycine receptor. Clon azepam is the prophylactic treatment of choice.

Familial rectal pain syndrome

The curiously named familial rectal pain syndrome is very rare. However, we have seen three families and made or reviewed ictal video-recordings of three children and one adult, which suggests that this unpleasant disorder is also underdiagnosed.[64] Familial rectal pain syndrome is dominantly inherited, but apparently sporadic cases occur. The presenting feature is neonatal onset of dra matic seizures. These were initially considered to be epileptic seizures, in part because there was a favorable response to carbamazepine.[65] In our patients there were no other features that would suggest epilepsy, and no paroxysmal EEG discharges during many observed seizures. There were two important clues to the diagnosis. First, there were frequent striking harlequin color changes. In particular, one side of the face would turn red while the other side would turn white. Secondly, the precipitating factor for the seizures was some sort of perineal stimulation, such as wiping or cleaning. We believe that the seizures are severe syncopal episodes, similar to those seen in neonatal hyperekplexia. There was brady-cardia and sometimes asystole with slowing and then flattening of the EEG, and generally a life-threatening appearance. These episodes abated eventually, but the adults with a similar neonatal history described continuing attacks of excruciating pain that was maximum in the nether regions and precipitated by stimuli such as passing a constipated stool. Other syncopes and presyncopes

Many varieties of syncope and pre-syncope have cer tainly not yet been described. In a study of 92 infants with apparently life-threatening events, 52 events were recorded in 34 patients. However, the precise mechanism of events could not be identified in 22 of the events, which were characterized by prolonged hypoxemia of entirely unexplained mechanism. [58]

Psychological disorders

Some of the disorders listed in this section may not be fundamentally different from other disorders described above and elsewhere in this chapter. The disorders included in this section are those in which psychological mechanisms seem to play a significant role.

Daydreams

There is a general awareness that episodes referred to as daydreams may be mistaken for absence seizures. These may not differ fundamentally from that described in the next subsection as gratification, but the subsequent conditions are more likely to lead to diagnostic difficulties.

Gratification (including infantile masturbation) and stereotypies

More or less pleasurable behavior, apparently similar to masturbation, may be seen from infancy onwards, perhaps more in preschool girls. [66] Rhythmic hip flexion and adduction may be accompanied by a distant expression and perhaps somnolence thereafter. The relative frequency of events and occurrence in specific circumstances, such as when bored or in a car seat, lends this behavior to home video-recording. [67] Parents understand ably prefer the term gratification (or even benign idio pathic infantile dyskinesia) to infantile masturbation.

It is sometimes more difficult to diagnose a phenomenon that occurs in slightly older children, known as 'tele vision in the sky'. Affected children appear to stare into space or have unvocalized speech with imaginary indi viduals. They sometimes seem to twitch or move one or more limbs for several minutes at a time (ref. [2] , case 14.2, p. 144). When there are repeated jerks or spasms, there may be confusion with epileptic infantile spasms.

Benign nonepileptic infantile spasms (benign myoclonus of early infancy)

This important disorder is harmless only if it is not misdiagnosed as epileptic infantile spasms.[68] Although the original authors[69] and a more recent successor[70] favored the term benign myoclonus of early infancy, we prefer benign nonepileptic infantile spasms[71] because the movements are more sustained than those produced by the shock-like muscle contraction of myoclonus. We consider that this phenomenon is a special type of stereotypy.

Out-of-body experiences

There are several situations in which children may describe experiences in which they appear to lose immediate contact with their bodies and perhaps see themselves from above. Such hallucinations have been described in epileptic seizures, anoxic seizures, migraine and as a 'normal' phenomenon. Some of these perceptual disorders have been described as the Alice in Wonderland phenomenon. Dissociated states have been well described by Mahowald and Schenck.[72]

Panic/anxiety

Panic attacks are well recognized in both adults and children, and criteria for their presence in children have been described.[73] However, it is important to recognize that panic attacks may also be manifestations of epileptic seizures.[74] As the latter authors emphasize, long-term video-EEG monitoring may be necessary to establish the correct diagnosis and prevent inappropriate psychiatric interventions.

Conversion disorder

Whether the term hysteria should be used is debatable, but self-induced nonepileptic and nonsyncopal episodes arc not rare.4 These have been termed pseudo-seizures, pseudo-epileptic seizures, psychogenic nonepileptic seizures and nonepileptic attack disorder, but none of these terms is satisfactory for every case. The psychiatric literature has used different terms over the years from hysteria to conversion hysteria to conversion disorders to dissociative states, without adding precision or clarity to the disorders. We strongly recommend to readers a clear and modern view of hysteria. [75] Whatever the mech anism, it is important to recognize these disorders so that they can be treated appropriately rather than with anti convulsants. It is also important to appreciate that they can also occur in patients who have epilepsy.

The episodes may mimic epileptic seizures, particu larly frontal lobe seizures, and can have prominent sexual and aggressive components. They can often be recognized readily by observation of an event or videotape. Some are characterized by a more or less graceful collapse without injury, often into a recovery position. There may be some rhythmic jerking of the head or one or more limbs, or thrusting of the trunk or pelvis may predominate.

The extent to which professional help is necessary depends on the severity and cause. A socio-medical model is useful for management, in which the illness is accepted as 'real' recognizing that it may be an inevitable response to a particular 'predicament'. [76, 77]This allows the patient to recover while saving face.[78] Reassurance and encouragement, with or without simple behavioral techniques, is often effective. However, post-traumatic stress disorder, and in some cases incest or child sexual abuse, may be the etiology.[79, 80] Psychiatric and or psy chologic consultation is important in patients who do not respond to a more simple approach but, even then, it is often difficult to identify underlying trauma or abuse.

What has been called a psychosomatic syncope has been described in adults who collapse on head-up tilt with normal vital signs.[25] This sort of response (pseudo syncope) can also be seen quite frequently in head-up tilt testing in children. One such child had been expelled from school because of frequent 'fainting'. Collapse occurred on head-up tilt without change in heart rate, blood pressure (continuously recorded by Finapres) or EEG. Simple psychotherapy was followed by prompt recovery. The differential diagnosis here includes hyperventilation syncope (see above).

Depression

Psychogenic pseudo-seizures have been described as a manifestation of depression in adults,[25] and depression is likely to be a factor in some children and adolescents with pseudo-seizures.

Schizophrenia

Alterations of behavior related to hallucinations in childhood may be due to schizophrenia and resemble certain types of epileptic seizure. Psychiatric evaluation may be necessary to clarify the diagnosis.

Fabricated illness or invention

In some families, episodes resembling seizures or syncopes are not induced but are invented.[81] These have been described in the section on suffocation above. This can be considered as a passive form of Meadow syndrome (Munchausen by proxy) and the diagnosis may require considerable professional collaboration. In one of our cases, the affected child was reported to be having daily seizures although these were no longer observed after admission to hospital. However, when adult psychiatrists at another hospital interviewed the mother during this time, she affirmed that the seizures were continuing with the same frequency as previously.

Derangements of the sleep process

Parasomnias and neurological disorders of sleep such as narcolepsy may be confused with epilepsy because of their paroxysmal nature. The difficulty in distinguishing epileptic and nonepileptic events is compounded by the fact that paroxysmal nonepileptic sleep events are more common in children.[82] Sleep disorders in children remain a largely neglected and poorly understood area. With the use of video EEG and nocturnal polysomnography, many of these conditions are being classified and differentiated from epileptic seizures. However, if there are many Tunny turns1 during the day that have not been described, there are even more types of sleep disturbance that fall into this category.

Parasomnias

A detailed history will distinguish most parasomnias from epileptic seizures. Parasomnias typically occur only once or twice a night. If events are occurring more often, they are more likely to be epileptic seizures, often arising from mesial/orbital frontal lobe structures. Epileptic seizures tend to occur more frequently in stage II sleep. In differentiating these events, video polysomnography and/or video-EEG are the most useful investigative tools. Non-REM partial arousal disorders, arousal parasomnias and night terrors

Brief nocturnal arousals are normal in children. They occur typically in stage IV non-REM sleep, 1-2 h after sleep onset. They vary from normal events such as mumbling, chewing, sitting up and staring, to arousals, which can be thought of as abnormal because of the disruption they cause the family. These include calm and agitated sleepwalking, and a spectrum from confusional arousals to night terrors or pavor nocturnus.

The child may exhibit automatic behavior during night terrors, but the events are not truly stereotyped. Affected children appear very agitated and look frightened as if they do not recognize their parents. They look awake and may be partially responsive but in fact are still in deep slow-wave sleep (stage IV). These events typically occur only once a night, usually 1-2 h after falling asleep and nearly always in the first half of sleep. Children have no memory of the event, which typically lasts 10-15 min before the child either wakes or settles back to restful sleep. By contrast, nocturnal frontal lobe epileptic seizures typically last less than 2 min and will often occur in clusters. The distinction between non-REM arousal disorders and benign partial epilepsy with affective symptoms (BPEAS)[83] can be more difficult. In this disorder, children arouse and look similarly wild and combative. However, the epileptic seizures are brief, do not arise particularly from stage IV sleep, are more likely to occur towards the end of sleep, and may occur while awake.

Non-REM arousal disorders likely represent a disordered balance between the drive to wake and the drive to sleep. They are more common in toddlers who sleep very deeply, in children who are overtired because of insufficient sleep, and in those who are unwell or on certain medications. An increased drive to wake occurs if the child has an irregular sleep schedule, is unwell or needs environmental associations to fall asleep normally. These disorders are therefore primarily managed by reassurance, explanation and behavioral measures to establish stable sleep routines and ensure good sleep hygiene.

REM sleep disorders

Nightmares and sleep paralysis are the principal REM sleep disorders. Some 10-20 per cent of individuals will have some experience of sleep paralysis, which may be a frightening experience because it occurs when the person wakes from REM sleep without abolishing the physiological REM atonia that normally prevents us from 'acting out' our dreams. Nightmares are usually easier to distinguish from epileptic seizures than night terrors because the child will have a memory both of waking and of the dream, and will then move rapidly into normal wakefulness. In contrast to these disorders, nocturnal epileptic seizures rarely arise out of REM sleep. Behavioral management and treatment of any co-morbid medical conditions are the appropriate treatment strategies.

Sleep-wake transition disorders

Rhythmic movement disorders such as nocturnal head hanging, body rocking and head rolling typically occur in infants and toddlers as they are trying to fall asleep. They can he present in deep sleep and in wakefulness. They will typically remit by 5 years of age but may persist into adult life. Management relies on good sleep hygiene and padding the headboard so the rest of the house is not woken.

Benign neonatal sleep myoclonus

The major importance of recognizing benign neonatal sleep myoclonus is to prevent the misdiagnosis of neonatal epileptic seizures,[84] which may result in inappropriate treatment that has even included admission to the intensive care unit and ventilation.[2] The baby exhibits repetitive, usually rhythmic, jerks of one or more limbs during sleep. There have been reports of the occasional jerk in the waking state. Slow (1/second) rocking of the infant's crib in a head-to-toe direction will often reproduce the myoclonus, [85] which - in contrast to the situation in jitteriness - does not stop if the limbs are restrained. These episodes are usually diagnosed easily from the history, but an EEG can be helpful if the diagnosis is uncertain.

Sleep starts

Vigevano's group have described the occurrence of repetitive sleep starts in children with epilepsy and cerebral palsy. [86] These jerks occurred repetitively at the onset of sleep in clusters lasting several minutes, with arousal appearance on EEC but no jerk-related spike discharges. These children already have epilepsy and so it is important to differentiate these sleep starts from epileptic seizures in order to avoid inappropriate dosage increases in the antiepileptic medication.

Restless legs syndrome

Although generally thought of as a condition of middle age, this disorder may present in childhood and be misdiagnosed as attention deficit disorder86 or even absence epilepsy. Recognition is important in that it tends to be exquisitely sensitive to dopaminergic therapy. [87]

Narcolepsy-cataplexy syndrome

Narcolepsy is a disorder characterized by excessive day time sleepiness, cataplexy, sleep paralysis, hypnagogic hallucinations and disturbed night-time sleep. The onset of narcolepsy occurs before 16 years of age in 33 per cent, before 10 years in 10 per cent and under 5 years of age in 4 per cent of patients.[88] Deficiency of hypocretin (also known as orexin), a neurotransmitter produced in the hypothalamus, has been demonstrated in narcolepsy. [89] Hypocretins help mediate arousal and project to brain stem structures involved in muscle tone.

Cataplexy is a loss of tone in response to strong emotion, typically laughter. Consciousness is maintained during cataplexy, even though the eyes may be closed. Diagnostic confusion may arise if several attacks of cataplexy occur one after the other and the individual then falls asleep on the floor.[90] Typically the loss of tone spreads from the face down the body. The individual has a degree of control so that they will often collapse in a series of stages rather than a sudden fall. Narcolepsy is often misdiagnosed as epilepsy: four of the six children diagnosed by us between 1997 and 2000 had been given a diagnosis of epilepsy and one child had been treated with multiple antiepileptic medications. REM sleep characteristically occurs shortly after the onset of sleep and the diagnosis can be confirmed by a multiple sleep latency test, provided the child is 8 years or older. [91]

Paroxysmal movement disorders

The major distinguishing features between paroxysmal movement disorders and epileptic seizures are the frequent presence of precipitating factors and the retention of consciousness in the paroxysmal dyskinesias and ataxias. However, they share many symptoms and are frequently confused with each other. Indeed, the boundaries between epilepsy and movement disorders are increasingly difficult to define.[92] Recent reports have emphasized the co-occurrence of movement disorders and epilepsy within the same family, suggesting that they may share the same underlying mechanism. [92, 93, 94, 95, 96] The recognition that dysfunction of ion channels leads to cellular hyperex-citabilty, and that mutations in these channel proteins may be associated with both epilepsy and movement disorders, provides a possible mechanism of action. [97] It is possible that mutant ion channels are expressed in variable degrees in different central nervous system structures, and that this expression may also vary with brain development. Thus the phenotype of a genetic ion chan nelopathy might include partial epileptic seizures in infancy indicating a cortical abnormality, and an episodic ataxia in childhood and adolescence, suggesting cerebellar dysfunction. It may be relevant that many antiepileptic medications are effective in the treatment of paroxysmal movement disorders. The channelopathies affect the cen tral nervous system in many ways and comprise a large group of paroxysmal disorders, including epilepsy, migraine, movement disorders and hyperekplexia. [94]

Various complex classifications have been proposed for the paroxysmal movement disorders (see Fahn [98] for a summary and a history of terminology). The most clinically relevant and simplest is used below. Most reports describe familial cases, which are easier to diagnose when more than one family member is affected, and are possibly more interesting to report than sporadic cases. However, it is our impression that most paroxysmal dyskinesias occur sporadically. Furthermore, many cases do not fit exactly into the classical descriptions outlined below.

Paroxysmal kinesigenic dyskinesia (PKD)

The onset is typically in early childhood or adolescence with episodes of choreoathetosis or dystonia. Attacks last seconds to 5 min and are precipitated by sudden movements, change in position or change in movement velocity." Getting up from a chair and getting out of a car are frequent triggers. Some individuals may have a brief nonspecific warning or aura before an attack, and consciousness is retained. Interictal neurological examination is normal. Attacks tend to become less frequent in adult life or remit completely. Carbamazepine is often highly effective in small doses.

There is a family history of similar events in about a quarter of patients, and the most common pattern of inheritance is autosomal dominant. Linkage to several overlapping but distinct loci around the pericentromeric region of chromosome 16 has been reported but the genes involved have not been identified.[99, 100] In some families the paroxysmal dyskinesia is associated with benign familial infantile convulsions.[93, 95] This has been reported as the infantile convulsions and choreoathetosis syndrome (ICCA). However, the movement disorder may include paroxysmal dystonia and is therefore better classified as a paroxysmal dyskinesia.

Paroxysmal nonkinesigenic dyskinesia (PNKD)

In this disorder, sometimes referred to also as paroxysmal dystonic choreoathetosis (PDC), attacks are often longer than in kinesiogenic dystonia and may last up to several hours or even days. The attacks are often markedly dystonic and may be precipitated by alcohol, caffeine or stress. Treatment involves avoidance of precipitating factors. Antiepileptic medications are not very effective. Inheritance is usually autosomal dominant and linkage to chromosome 2 has been reported.[101, 102]

Paroxysmal exercise-induced dyskinesia (PED)

The events occur usually after 10-15 min of exercise and not at the initiation of movement as in PKD.[103] Typically the part of the body that has been doing most exercise will become dystonic. The abnormal movement resolves gradually over 5-30 min after the exercise is stopped. Antiepileptic medications are not generally helpful, but acetazolamide has been effective in some families.[103]

Paroxysmal nocturnal (hypnogenic) dyskinesia

This condition is almost certainly a form of nocturnal frontal lobe epilepsy, [104, 105] and this term will become obsolete. In a typical episode a child will rouse and exhibit mixed involuntary dyskinetic movements of the limbs often associated with a cry either before the event or after.[106] The events are typically brief, lasting 10 s to 2 min, and may occur multiple times a night. They may be confused with night terrors (see above). Carbamazepine is often effective in very low doses.

Benign paroxysmal torticollis in infancy (BPT)

Infants have attacks of retro-, latero- or torticollis, which may last from minutes to hours.[107] The attacks typically begin in early infancy and remit by 5 years of age. They may be triggered by movement and are heralded by irritability, pallor, vomiting, and in older children by ataxia. BPT is both a movement disorder and a migraine equivalent.[108] Two patients with BPT in a recent series came from a family with familial hemiplegic migraine linked to a mutation in the voltage-gated calcium channel gene CACNA1A on chromosome 19. [109]

Benign paroxysmal tonic upgaze of childhood

Benign paroxysmal tonic upgaze of childhood [110] typically presents in infants less than 3 months with prolonged periods (hours to days) of sustained or intermittent upgaze deviation. Ataxia may appear particularly during intercurrent illness. The episodes remit within a few years but are associated with psychomotor retardation or language delay in up to 80 per cent of cases.[111]

Episodic ataxias

Episodic ataxia type 1 (EA1) is a rare disorder caused b\ mutations in a voltage-gated potassium channel. Affectec individuals have brief episodes of cerebellar ataxia lasting seconds or minutes.[112] Interictal myokymia detected clin ically or by demonstration of continuous motor uni activity on EMG is the principal diagnostic feature. Parox ysmal ataxia may be mistaken as a partial epilepti seizure, but there is also an overrepresentation c epilepsy in families with EA1. [113, 114] The potassium chan nel is expressed throughout the central and periphen nervous system. Whether the phenotype comprises ataxia, myokymia (or neuromyotonia), or epilepsy or a combination of the above seems to relate to the functional consequences of the mutation and its tissue specific developmental expression. [114]

Episodic ataxia type 2 (EA2) is characterized by longer attacks, lasting minutes, and is less frequently mistaken for epilepsy. There may be interictal cerebellar signs including impairment of eye movement control. This disorder is associated with mutations in a voltage gated calcium channel gene CACNA1A located on chromosome 19.[115] It is allelic with familial hemiplegic migraine and spinocerebellar ataxia type 6. In their pure forms these are distinct disorders, but overlap syndromes do occur. Partial seizures have been documented in familial hemiplegic migraine families and there is a case report of a child with a de novo truncating mutation in [CACNA1A] who has EA2 and absence epilepsy. [116, 117]

Migraine and related disorders

Some authors regard migraine with aura as an important differential in the diagnosis of epilepsy.[118] Indeed, the similarity is close but distinct between migraine with visual aura and occipital epilepsy.[119] In this section we discuss disorders which are probably migraine equivalents, but also some that are only possibly related. Familial hemiplegic migraine (FHM)

Insofar as virtually all attacks of FHM are associated with headache and a family history,[120] the differential diagnosis of this true migraine should not normally be difficult.

Benign paroxysmal vertigo of childhood

This is the most common migraine equivalent. [108]Although affected preschool children are often referred with a diagnosis of epilepsy, the characteristic history of anxious arrest of movement without loss of awareness and subjective vertigo or 'drunking' makes the diagnosis easy. A related migraine equivalent, benign paroxysmal torticollis of infancy, is discussed above.

Cyclical vomiting

Cyclical vomiting syndrome is clearly related to migraine, [121]but may be confused with epilepsy (or indeed EA2).

Benign nocturnal alternating hemiplegia of childhood

Benign nocturnal alternating hemiplegia of childhood is even rarer than the better-known alternating hemiplegia (described in the next section). [122] normal young children experience recurrent attacks of hemiplegia arising from sleep and lasting 5-20 min. Attacks begin between 4 months and 3(1/2) years of age and the course is benign. There is often a family history of migraine.

Alternating hemiplegia

Alternating hemiplegia of childhood is fascinating neurologic disorder that is both underdiagnosed and under-reported. [123] The attacks of flaccid hemiplegia affect one or other side, or both, begin at 6-18 months of life and are associated with autonomic phenomena. Nystagmus and strabismus are the earliest manifestation and may even be seen in the neonatal period. The nystagmus is paroxysmal and frequently unilateral. The strabismus may also be paroxysmal and is also associated with signs of transitory internuclear ophthalmoplegia. [124] Tonic and dystonic episodes may also appear early in infancy, well before the first hemiplegic attack. These consist of pre dominantly brief and perhaps clustered tonic attacks which may easily be mistaken for epileptic tonic seizures. These stiffenings are commonly unilateral, with some resemblance to the asymmetric tonic neck reflex. They may also be bilateral, with a degree of opisthotonus and up-deviation of the eyes. Pallor, crying or screaming, and general misery tend to accompany these attacks. The attacks may be unilateral or bilateral. Bilateral hemiplegia is associated particularly with autonomic phenomena and drooling. Some sort of trigger precedes attacks in most affected children. Emotional factors, excitement, bright lights and bathing, particularly in hot baths, have been described. The frequency of bathing as a precipitating factor is probably under-reported. Developmental delay, ataxia and persistent choreoathetosis develop in most of these children, and a few develop migraine with aura (ref. [125] , case 3). [126]

Miscellaneous neurologic events

There are many paroxysmal neurologic disorders that may be mistaken for epileptic seizures. Some well-recognized examples are described briefly. Many disorders have surely yet to be described. Tics, whether simple, complex or as part of Tourette syndrome, do not usually pose diagnostic difficulty. Nonepileptic myoclonus occurs in many situations. Benign nonepileptic infantile spasms have been described above. If there is difficulty in diagnosis of these disorders, ictal EEG will determine whether the event is epileptic.

Cataplexy in other neurological disorders

[Cataplexy] has been described above in the narcolepsy cataplexy syndrome. Cataplexy has also been described in association with acquired brainstem lesions, [Niemann Pick type C disease] , [Norrie disease] , the [Prader-Willi Syndrome] , [127] and as an isolated familial trait. A cataplexy like disorder is also seen in the [Coffin-Lowry syndrome] [128] and many of the early reports of epilepsy in this syndrome are probably describing the cataplexy-like disorder.

Nonepileptic head-drops

Nonepileptic head drops are characterized by repetitive head-nods that are not accompanied by generalized epileptiform discharges on EEG. The initial flexion of the neck and the subsequent extension occur at the similar velocity instead of the rapid head drop and slow recovery characteristic of epileptic head nods.[129]

Functional blinking

Functional blinking[130] should perhaps be included in the psychogenic section. Unlike the epileptic syndrome of eyelid myoclonia with absences, it is not associated with epileptiform EEC discharges. However, if drug treatment abolishes the absence seizures and photoparoxysmal response in patients with eyelid myoclonia and absences, they often continue to have eyelid myoclonia without EEC change, and may not be aware of the blinking. [131]

Jitteriness

Jitteriness[132] is a phenomenon of fullterm neonates and very young infants. In contrast to benign neonatal sleep myoclonus, the movements are suppressed by limb restraint.

Shuddering

Shuddering begins in infancy. [133] We agree with Kanazawa[134] that shuddering and benign myoclonus of early infancy or benign infantile spasms are the same condition. A child with shuddering may develop essential tremor, although this is not invariable.[135]

Craniocervical junction disorders - Chiari type 1

Disorders of the craniocervical junction, particularly congenital disorders such as type 1 Chiari malformation, may be responsible for apparent syncopes which are not associated with EEG or ECG change. Stimuli, such as coughing, which would be expected to increase downward brain herniation, may precipitate attacks. A definitive diagnosis can be established by brain MRI.

Raised intracranial pressure

Decorticate or decerebrate posturing may accompany brain swelling, for instance in Hemophilus influenzac meningitis, and are often misdiagnosed as tonic epileptic seizures and treated with repeated injections of diazepam, with disastrous results (ref. 6, case 15.46). Although immunizatsion should now prevent serious Hemophilus infections, these episodes can be seen with any acute rise in intracranial pressure, such as with intracranial hemorrhage or decompensated hydrocephalus.

Tetany

Aside from metabolic derangements in which the diagnosis is obvious, tetany is most often seen with hyperventilation - see 'Vasovagal syncope', 'Hyperven tilation syncope', 'Panic/anxiety' above. In hypoparathy roidism it is more usual to have some form of epileptic seizure than tetany.

Sandifer syndrome

Intermittent contortions of the neck with marked lateral flexion are occasionally seen with severe gastroesophageal reflux, particularly in children with dyskinetic cerebral palsy.

Anoxic epileptic seizures

This is an important and under-recognized phenomenon in which provoked syncopes themselves trigger epileptic seizures in individuals who rarely have unprovoked epileptic seizures.[2]

It is surprising that although there are many comments in the literature suggesting that it is 'common knowledge' that severe anoxia can cause a tonic-clonic epileptic seizure, there is no published, well-documented report of a generalized tonic-clonic epileptic seizure following acute anoxia either due to asphyxia or ischemia. In contrast, true epileptic seizures as an immediate consequence of syncope have been recorded and described.6,[136] We call this phenomenon of a syncope followed by an epileptic seizure an anoxic-epileptic seizure (AES).

Most anoxic-epileptic seizures have been reported in infants or young children who also had a history of reflex syncopes without an epileptic component. Most of these syncopes were reflex asystolic syncope, reflex expiratory apnea (cyanotic breath-holding spells), or mixed episodes. Compulsive Valsalva maneuvers have also caused AES. [137] The epileptic seizures precipitated by the syncopal episode have been predominantly clonic or absence seizures. Status epilepticus[138] is either common or a stimulus to the medical attendants to write a paper!

Key points

• Many children suspected of having epilepsy, and even those with a definite diagnosis of epilepsy, have never had an epileptic seizure
• Reflex anoxic seizures, breath-holding spells, vasovagal syncope and neurocardiogenic syncope may all be varieties of the same disorder, neurally mediated syncope
• Reflex anoxic seizures are nonepileptic convulsive episodes that are due to cardiac asystole that has been provoked by a noxious stimulus
• The most reliable indicators of vasovagal syncope are the setting of the event, the stimulus, and the warning symptoms or aura that are often present
• The major distinguishing features between paroxysmal movement disorders and epileptic seizures are the frequent presence of precipitating factors and the retention of consciousness in the paroxysmal dyskinesias and ataxias
• Anoxic-epileptic seizures are an important and under-recognized phenomenon in which triggered syncopes themselves provoke epileptic seizures. They usually occur in individuals who do not have epilepsy
• In the diagnosis of all paroxysmal disorders, history is all

References

1. Stephenson JBP. Anoxic seizures: self-terminating syncopes. Epileptic Disorders 2001 ; 3: 3-6.
2. Stephenson JBP. Fits and Faints. Cambridge: Cambridge University Press; New York: Mac Keith Press, 1990.

9. Gastaut H. A physiopathogenic study of reflex anoxic cerebral seizures in children (syncopes, sobbing spasms and breath-holding spells). In: Kellaway P, Petersen I (eds) Clinical Electroencephalography of Children. Stockholm: Almquist & Wiksell, 1968.

10. Stephenson JBP. Two types of febrile seizure - anoxic (syncopal) and epileptic mechanisms differentiated by oculocardiac reflex. British Medical Journal 1978; 2: 726-728.

11. Lombroso CT, Lerman P. Breath-holding spells (cyanotic and pallid infantile syncope). Pediatrics 1967; 39: 563-581.

12. Roddy SM, Ashwal S, Schneider S. Venepuncture fits: a form of reflex anoxic seizure. Pediatrics 1983; 72: 715-718.

13. Appleton RE. Reflex anoxic seizures. British Medical Journal 1993;307:214-215.

14. Wallace SJ. Epilepsy in Children. London: Chapman & Hall, 1996.

15. Sreeram N, Whitehouse W. Permanent cardiac pacing for reflex anoxic seizure. Archives of Disease in Childhood 1996; 75: 462.

16. Kelly AM, Porter CJ, McGoon MDr et al. Breath-holding spells associated with significant bradycardia: successful treatment with permanent pacemaker implantation. Pediatrics 2001; 108:698-702.

17. Stephenson JBP, McLeod KA. Reflex anoxic seizures. In: David TJ (ed.) Recent Advances in Paediatrics 18. Edinburgh: Churchill Livingstone, 2000.

18. Fitzpatrick A, Sutton R. Tilting towards a diagnosis in recurrent unexplained syncope. Lancet 1989; i: 658-660.

19. Ziegler DK, Lin J, Bayer WL. Convulsive syncope: relationship to cerebral ischemia. Transactions of the American Neurological Association 1978; 103: 150-154.

20. Lempert T, Bauer M, Schmidt D. Syncope: a videometric analysis of 56 episodes of transient cerebral hypoxia. Annals of Neurology 1994; 36: 233-237.

21. Lempert T. Recognizing syncope: pitfalls and surprises. Journal of the Royal Society of Medicine 1996; 89, 372-375.

22. Camfield PR, Camfield CS. Syncope in childhood: a case control clinical study of the familial tendency to faint. Canadian Journal of Neurological Science 1990; 17: 306-308.

23. Seifer CM, Kenny RA. Head-up tilt testing in children. European Heart Journal 2001; 22: 1968-1971.

24. Grossi D, Buonomo C, Mirizzi F, et al. Electroencephalographic and electrocardiographic features of vasovagal syncope induced by head-up tilt. Functional Neurology 1990; 5: 257-260.

25. Linzer M, Varia I , Pontinen M, et al. Medically unexplained syncope: relationship to psychiatric illness. American Journal of Medicine 1992; 92(1 A): 18S-25S.

26. Connolly J, Hallam RS, Marks IM. Selective association of fainting with blood-injury-illness fear. Behaviour Therapy 1976; 7: 8-13

27. Marks I. Blood-injury phobia: a review. American Journal of Psychiatry 1988; 145: 1207-1213.

28. Accurso V, Winnicki M, Shamsuzzaman AS, et al. Predisposition to vasovagal syncope in subjects with blood/injury phobia. Circulation 2001; 104: 903-907.

29. North KN, Ouvrier RA, Nugent M. Pseudoseizures caused by hyperventilation resembling absence epilepsy. Journal of Child Neurology 1990; 5: 288-294.

30. Mathias CJ, Bannister R, Cortelli P, et al. Clinical autonomic and therapeutic observations in two siblings with postural hypotension and sympathetic failure due to an inability to synthesize noradrenaline from dopamine because of a deficiency of dopamine betahydroxylase. Quarterly Journal of Medicine 1990; 75: 617-633.

31. Stewart JM, Gewitz MH, Weldon A, Munoz J. Patterns of orthostatic intolerance: the orthostatic tachycardia syndrome and adolescent chronic fatigue. Journal of Pediatrics 1999; 135:218-225.

32. Stewart JM. Orthostatic intolerance in pediatrics. Journal of Pediatrics 2002; 140: 404-411.

33. Oslizlok P, Allen M, Griffin M, Gillette P. Clinical features and management of young patients with cardioinhibitory response during orthostatic testing. American Journal of Cardiology 1992; 69(16): 1363-1365.

34. Jervell A , Lange-Nielsen F. Congenital deaf-mutism, functional heart disease with prolongation of the Q-T interval and sudden death. American Heart Journal 1957; 54: 59-67.

35. Ward OC. A new familial cardiac syndrome in children. Journal of the Irish Medical Association 1964; 54: 103-106.

36. Breningstall GN. Breath-holding spells. Pediatric Neurology 1996; 14:91-97.

37. Shaw TR. Recurrent ventricular fibrillation associated with normal QT intervals. Quarterly Journal of Medicine 1981; 50: 451-462.

38. Culpepper N. A Directory for Midwives; or a Guide for Women in their Conception, Bearing (etc.). London: Bettersworth & Hitch, 1737.

39. Gordon N. Breath-holding spells. Developmental Medicine and Child Neurology 1987; 29: 810-814.

40. DiMario FJ Jr, Burleson JA. Behaviour profile of children with severe breath-holding spells. Journal of Pediatrics 1993; 122:488-491.

41. Gauk EW, Kidd L, Prichard JS. Aglottic breath-holding spells. New England Journal of Medicine 1966; 275: 1361-1362.

42. Stephenson JBP. Blue breath-holding is benign. Archives of Disease in Childhood 1991; 66: 255-257.

43. Southall DP, Samuels MP, Talbert DG. Recurrent cyanotic episodes with severe arterial hypoxaemia and intrapulmonary shunting: a mechanism for sudden death. Archives of Disease in Childhood 1990; 65: 953-961.

44. Southall DP, Johnson P, Morley CJ, et al. Prolonged expiratory apnoea: a disorder resulting in episodes of severe arterial hypoxaemia in infants and young children. Lancet 1985; ii: 571-577.

45. McLeod KA, Wilson N, Hewitt J, Norrie J, Stephenson JB. Cardiac pacing for severe childhood neurally mediated syncope with reflex anoxic seizures. Heart 1999; 82: 721-725.

46. DiMario FJ Jr. Prospective study of children with cyanotic and pallid breath-holding spells. Pediatrics 2001; 107: 265-269.

47. Samuels MP, Talbert DC, Southall DP. Cyanotic breath-holding and sudden death. Archives of Disease in Childhood 1991; 66: 257-258.

48. Filler RM, Rossello PJ, Lebowitz RL Life-threatening hypoxic spells caused by tracheal compression after repair of esophageal atresia: correction by surgery. Journal of Pediatric Surgery 1976; 11: 739-748.

49. Gastaut H, Broughton R, de Leo G. Syncopal attacks compulsively self-induced by the Valsalva manoeuvre in children with mental retardation. Electroencephalography and Clinical Neurophysiology 1982; 35(Suppl): 323-329.

50. Genton P, Dusserre A. Pseudo-absences atoniques par syncopes auto-provoquees (manoeuvre de Valsalva). Epilepsies 1993; 5: 223-227.

51. Glaze DG, Schultz RJ, Frost JD. Rett syndrome: characterization of seizures versus non-seizures. Electroencephalography and Clinical Neurophysiology 1998; 106: 79-83.

52. Navelet Y, Wood C, Robleux C, Tardieu M. Seizures presenting as apnoea. Archives of Disease in Childhood 1989; 64: 357-359.

53. Spitzer AR, Boyle JT, Tuchman DN, Fox WW. Awake apnea associated with gastroesophageal reflux: a specific clinical syndrome. Journal of Pediatrics 1984; 104: 200-205.

54. Meadow R. Suffocation, recurrent apnea, and sudden infant death. Journal of Pediatrics 1990; 117: 351-357.

55. . Royal College of Paediatrics and Child Health. Fabricated or Induced Illness by Carers. London: Royal College of Paediatrics and Child Health, 2002; 78.

56. Rosen CL, Frost JD, Bricker T, et al. Two siblings with recurrent cardiorespiratory arrest: Munchausen syndrome by proxy or child abuse? Pediatrics 1983; 71: 715-720.

57. Rosen CL, Frost JD Jr, Glaze DG. Child abuse and recurrent infant apnea. Journal of Pediatrics 1986; 109: 1065-1067.

58. Poets CF, Samuels MY, Noyes IP, et al. Home event recordings of oxygenation, breathing movements, and heart rate and rhythm in infants with recurrent life-threatening events. Journal of Pediatrics 1993; 123: 693-701.

59. Southall DP, Plunkett MC, Banks MW, et al. Covert video recordings of life-threatening child abuse: lessons for child protection. Pediatrics 1997; 100: 735-760.

60. Pascotto A, Coppola G. Neonatal hyperekplexia: a case report. Epilepsia 1992;33:817-820.

61. Vigevano F, Di Capua M, Dalla Bemardina B. Startle disease: an avoidable cause of sudden infant death. Lancet 1989; i: 216.

62. Suhren 0, Bruyn GW, Tuynman JA. Hyperexplexia: a hereditary startle syndrome. Journal of the Neurological Sciences 1966; 31:577-605.

63. Kurczynski TW. Hyperekplexia. Archives of Neurology 1983; 40: 246-248.

64. Elmslie FV, Wilson J, Rossiter MA. Familial rectal pain: is it under-diagnosed? Journal of the Royal Society of Medicine 1996; 89: 290-291 P.

65. Schubert R, Cracco JB. Familial rectal pain: a type of reflex epilepsy? Annals of Neurology 1992; 32: 824-826.

66. Fleisher DR, Morrison A. Masturbation mimicking abdominal pain or seizures in young girls. Journal of Pediatrics 1990; 116:810-814.

67. Nechay A, Ross LM, Stephenson JBP, O'Regan M. Gratification disorder ("infantile masturbation"): a review. Archives of Disease in Childhood. In press.

68. Maydell BV, Berenson F, Rothner AD, et al. Benign myoclonus of early infancy: an imitator of West's syndrome. Journal of Child Neurology 2001; 16: 109-112.

69. Lombroso CT, Fejerman N. Benign myoclonus of early infancy. Annals of Neurology 1977; 1: 138-143.

70. Pachatz C, Fusco L, Vigevano F. Benign myoclonus of early infancy. Epileptic Disorders 1999; 1: 57-61.

71. Dravet C, Giraud N, Bureau M, et al. Benign myoclonus of early infancy or benign non-epileptic infantile spasms. Neuropediatrics 1986; 17: 33-38.

72. Mahowald MW, Schenck CH. Dissociated states of wakefulness and sleep. Neurology 1992; 42 (Suppl 6): 44-52.

73. Ollendick TH, Mattis SG, King NJ. Panic in children and adolescents: a review. Journal of Child Psychology and Psychiatry 1994; 35: 113-134.

74. Huppertz HJ, Franck P, Korinthenberg R, Schulze-Bonhage A. Recurrent attacks of fear and visual hallucinations in a child. Journal of Child Neurology 2002; 17: 230-233.

75. Jureidini J, Taylor DC. Hysteria. Pretending to be sick. European Child and Adolescent Psychiatry 2002; 11: 123-128.

76. Taylor DC. The components of sickness: diseases, illnesses, and predicaments. Lancet 1979; ii(8150): 1008-1010.

77. Taylor DC. The sick child's predicament. Australian and New Zealand Journal of Psychiatry 1985; 19: 130-137.

78. Gudmundsson 0, Prendergast M, Foreman D, Cowley S. Outcome of pseudoseizures in children and adolescents:a 6-year symptom survival analysis. Developmental Medicine Child Neurology 2001; 43: 547-551.

79. Goodwin DS, Simms M, Bergman R. Hysterical seizures: a sequel to incest. American Journal of Orthopsychiatry 1979; 49: 698-703.

80. Alper K, Devinski 0, Perrine K, et al. Non epileptic seizures and childhood sexual and physical abuse. Neurology 1993; 43: 1950-1953.

81. Meadow R. Fictitious epilepsy. Lancet 1984; ii: 25-28.

82. Bye AM, Kok DJ, Ferenschild FT, Vies JS. Paroxysmal non-epileptic events in children: a retrospective study over a period of 10 years. Journal of Paediatrics and Child Health 2000; 36: 244-248.

83. Dal la Bernardina B, Colamaria V, Chiamenti C, et al. Benign partial epilepsy with affective symptoms (benign psychomotor epilepsy). In: Roger J, Bureau M,Dravet C, et al. (eds) Epileptic Syndromes in Infancy Childhood and Adolescence, 2nd edn. London: John Libbey, 1992; 219-223.

84. Coulter DL, Allen RJ. Benign neonatal sleep myoclonus. Archives of Neurology 1982; 39: 191-192.

85. Alfonso I, Papazian 0, Aicardi J , Jeffries HE. A simple maneuver to provoke benign neonatal sleep myoclonus. Pediatrics 1995; 96: 1161-1163.

86. Fusco L, Pachatz C, Cusmai R, Vigevano F. Repetitive sleep starts in neurologically impaired children: an unusual non-epileptic manifestation in otherwise epileptic subjects. Epileptic Disorders 1999; 1: 63-67.

87. Walters AS, Mandelbaum DE and Lewin DS, et al. Dopaminergic therapy in children with restless legs/periodic limb movements in sleep and ADHD. Dopaminergic Therapy Study Group. Pediatric Neurology 2000; 22: 182-186.

88. Challamel MJ, Mazzola ME, Nevsmalova S, et al. Narcolepsy in children. Sleep 1994; 17(Suppl 8): S 17-20.

89. Nishino S, Ripley B, Overeem S, et al. Hypocretin (orexin) deficiency in human narcolepsy. Lancet 2000; 355: 39-40.

90. Zeman A, Douglas N, Aylward R. Lesson of the week: Narcolepsy mistaken for epilepsy. British Medical Journal 2000; 322: 216-218.

91. Guilleminault C, Pelayo R. Narcolepsy in children: a practical guide to its diagnosis, treatment and follow-up. Paediatric Drugs 2000; 2: 1-9.

92. Guerrini R, Aicardi J, Andermann F, Hallett M (eds). Epilepsy and Movement Disorders. Cambridge: Cambridge University Press, 2002.

93. Szepotowski P, Rochette R, Berquin P et al. Familial infantile convulsions and paroxysmal choreoathetosis: A new neurological syndrome linked to the pericentromeric region of chromosome 16. American Journal of Human Genetics 1997; 61:889-898.

94. Zuberi SM, Hanna MG. Ion channels and neurology. Archives of Disease in Childhood 2001; 84: 277-280.

95. Thiriaux A, de St Martin A , Vercueil L, et al. Co-occurrence of infantile epileptic seizures and childhood paroxysmal choreoathetosis in one family: clinical, EEG, and SPECT characterization of episodic events. Movement Disorders 2002; 17:98-104.

96. Guerrini R, Sanchez-Carpentiro R, Deonna T, et al. Early-onset absence epilepsy and paroxysmal dyskinesias. Epilepsia 2002; 43: 1224-1229.

97. Singh R, Macdonnel RA, Scheffer IE, et al. Epilepsy and paroxysmal movement disorders in families: evidence for shared mechanisms. Epileptic Disorders 1999; 1: 93-99.

98. Fahn S. The paroxysmal dyskinesias. In: Marsden CD, Fahn S (eds) Movement Disorders 3. Oxford: Butterworth-Heineman, 1994; 310-345.

99. Bennett LB, Roach ES, Bowcock AM. A locus for paroxysmal kinesigenic dyskinesia maps to human chromosome 16. Neurology 2000; 54: 125-130.

100. Tomita H, Nagamitsu S, Wakui K, et al. A gene for paroxysmal kinesigenic choreoathetosis mapped to 16p11.2-q12.1. American Journal of Human Genetics 1999; 65: 1688-1697.

101. Fink JK, Hedera P, Mathay JG, Albin R. Paroxysmal dystonic choreoathetosis linked to chromosome 2q: clinical analysis and proposed physiology. Neurology 1997; 49: 177-183.

102. Fouad GT, Servidei S, Durcan S, Bertini E, Ptacek LJ. A gene for familial dyskinesia (FPDI) maps to chromosome 2q. American Journal of Human Genetics 1996; 59: 135-139.

103. Bhatia KPr Soland VL, Bhatt MH, Quinn NP, Marsden CD. Paroxysmal exercise induced dystonia: eight new sporadic cases and a review of the literature. Movement Disorders 1997; 12:1007-1012.

104. Scheffer IE, Bhatia KP, Lopes-Cendes I, et al. Autosomal dominant nocturnal frontal lobe epilepsy diagnosed as sleep disorder. Lancet 1994; 343: 515-517.

105. Steinlein 0, Mulley JC, Propping P, et al. A missense mutation in the neuronal nicotinic acetylcholine receptor α4 subunit is associated with autosomal dominant nocturnal frontal lobe epilepsy. Nature Genetics 1995; 11: 201-203.

106. Lugaresi F, Cirignotta F. Hypnogenic paroxysmal dystonia: epileptic seizure or a new syndrome? Sleep 1981; 4: 129-138.

107. Fernandez-Alvarez E. Transient movement disorders in children. Journal of Neurology 1998; 245: 1-5.

108. Al-Twaijri WA, Shevell Ml. Pediatric migraine equivalents: occurrence and clinical features in practice. Pediatric Neurology 2002; 26: 365-368.

109. Giffin NJ, Benton S, Goadsby PJ. Benign paroxysmal torticollis of infancy: four new cases and linkage to CACNA1A mutation. Developmental Medicine and Child Neurology 2002; 44: 490-493.

110. Ouvrier RA, Billson MD. Benign paroxysmal tonic upgaze of childhood. Journal of Child Neurology 1988; 3: 177-180.

111. Hayman M, Harvey A, Hopkins U, et al. Paroxysmal tonic upgaze: a reappraisal of outcome. Annals of Neurology 1998; 43: 514-520.

112. Browne DL, Gancher ST, Smith EA, et al. Episodic ataxia/ myokymia syndrome is associated with point mutations in the human potassium channel gene KCNA1. Nature Genetics 1994;8:136-140.

113. Zuberi SM, Eunson LH, Spauschus A, et al. A novel mutation in the human voltage gated potassium channel gene (Kv1.1) associates with episodic ataxia and sometimes with partial epilepsy. Brain 1999; 122: 817-825.

114. Eunson LH, Rea R, Zuberi SM, et al. Clinical, genetic, and expression studies of mutations in the human voltage-gated potassium channel KCNA1 reveal new phenotypic variability. Annals of Neurology 2000; 48: 647-656.

115. Ophoff RA, Terwindt GM, Vergouwe MN, et al. Familial hemiplegic migraine and episodic ataxia type 2 are caused by mutations in the Ca2+ channel gene CACNL1A4. Cell 199G; 87:543-552.

116. Terwindt GM, Ophoff RA, Lindhout D, et al. Partial cosegregation of familial hemiplegic migraine and a benign familial epileptic syndrome. Epilepsia 1997; 38: 915-921.

117. Jouvenceau A, Eunson LH, Spauschus A, et al. Human epilepsy associated with dysfunction of the brain P/Q-type calcium channel. Lancet 2001; 358: 801-807.

118. Gibbs J, Appleton RE. False diagnosis of epilepsy in children. Seizure 1992; 1: 15-18.

119. Panayiotopoulos CP. Visual phenomena and headache in occipital epilepsy: a review, a systematic study and differentiation from migraine. Epileptic Disorders 1999; 1: 205-216.

120. Thomsen LL, Eriksen MK, Roemer SF, et al. A population-based study of familial hemiplegic migraine suggests revised diagnostic criteria. Brain 2002 ; 125: 1389-1391.

121. Dignan F, Symon DNK, AbuArafeh I, Russell G. The prognosis of cyclical vomiting syndrome. Archives of Disease in Childhood 2001; 84: 55-57.

122. Chaves-Vischer V, Picard F, Andermann E, et al. Benign nocturnal alternating hemiplegia of childhood: six patients and long-term follow-up. Neurology 2001; 57: 1491-1493.

124. Bursztyn J, Mikaeloff Y, Kaminska A, et al. Hemiplegies alternantes de I'enfant et leurs anomalies oculo-motrices Alternating hemiplegia of childhood and oculomotor anomalies. Journal Erancais d'Ophthalmologie 2000; 23: 161-164.

125. Casaer P. Flunarizine in alternating hemiplegia in childhood. An international study in 12 children. Neuropediatrics 1987; 18: 191-195.

126. Silver K, Andermann F. Alternating hemiplegia of childhood: a study of 10 patients and results of flunarizine treatment. Neurology 1993; 43: 36-41.

127. Tobias ES, Tolmie JL, Stephenson JBP. Cataplexy in the Prader-Willi syndrome. Archives of Disease in Childhood 2002; 87: 170.

128. Crow YJ, Zuberi SM, McWilliam R, et al. "Cataplexy" and muscle ultrasound abnormalities in Coffin-Lowry syndrome. Journal of Medical Genetics 1998; 35: 94-98.

129. Brunquell P, McKeever M, Russman BS. Differentiation of epileptic from non-epileptic head drops in children. Epilepsia 1990;31:401-405.

130. VrabecTR, Levin AV, Nelson LB. Functional blinking in childhood. Pediatrics 1989; 83: 967-970.

131. Kent L, Blake A, Whitehouse W. Eyelid myoclonus and absences: phenomenology in children. Seizure 1987; 7: 193-199.

132. Parker S, Zuckerman B, Bauchner H, et al. Jitteriness in full-term neonates: prevalence and correlates. Pediatrics 1990 ; 85:17-23.

133. Holmes GL, Russman BS. Shuddering attacks. American Journal of Diseases of Children 1986; 140: 72-74.

134. Kanazawa 0. Shuddering attacks - report of four children. Pediatric Neurology 2000; 23: 421-424.

135. Vanasse M, Bedard P, Andermann F. Shuddering attacks in children: an early clinical manifestation of essential tremor. Neurology 1976; 26: 1027-1030.

136. Battaglia A, Guerrini R, Gastaut H. Epileptic seizures induced by syncopal attacks. Journal of Epilepsy 1989; 2: 137-146.

137. Aicardi J, Gastaut H, Mises J. Syncopal attacks compulsively self-induced by Valsalva's manoeuvre associated with typical absence seizures. Archives of Neurology 1988; 45: 923-925.

138. Kuhle S, Tiefenthaler M, Seidl R, Hauser E. Prolonged generalized epileptic seizures triggered by breath-holding spells. Pediatric Neurology 2000; 23: 271-273.

139. Gomes MMM, Kropf LA, Beeck E, Eda S, Figueira, IL. Inferences from a community study about non-epileptic events. Arquivos de Neuropsiquiatria 2002; 60#3-B): 712-716.

140. Kotagal P, Costa M, Wyllie E, Wolgamuth B. Paroxysmal nonepileptic events in children and adolescence. Pediatrics 2002; 110: E4-6.

141. Smith PE, Myson V, Gibbon F. A teenager epilepsy clinic: observational study. European Journal of Neurology 2002; 9:373-376.

142. Leenhardt A, Lucet V, Denjoy I, Grau F, Ngoc DD, Coumel P. Catecholaminergic polymorphic ventricular tachycardia in children. A 7-year follow-up of 21 patients. Circulation 1995; 91: 1512-1519.

143. Rees Ml, Lewis TM, Vafa B, et al. Compound heterozygosity and nonsense mutations in the alpha(l)-subunit of the inhibitory glycine receptor in hyperekplexia. Human Genetics 2001; 109:267-270.

144. Rees ML, Lewis TM, Kwok JB, et al. Hyperekplexia associated with compound heterozygote mutations in the beta-subunit of the human inhibitory glycine receptor (GLRB). Human Molecular Genetics 2002; 11: 853-860.

145. Walters AS, Picchietti DL, Ehrenberg BL, Wagner ML. Restless legs syndrome in childhood and adolescence. Pediatric Neurology 1994; 11:241-245.

146. Houser MK, Soland VL, Bhatia KP, Quinn MP, Marsden CD. Paroxysmal kinesigenic choreoathetosis: a report of 26 cases. Journal of Neurology 1999; 246: 120-126.

147. Scheffer IE, Bhatia KP, Lopes-Cendes I et al. Autosomal dominant nocturnal frontal lobe epilepsy. A distinctive clinical disorder. Brain 1995; 118: 61-73.

148. Verret S, Steele JC. Alternating hemiplegia in childhood: a report of eight patients with complicated migraine beginning in infancy. Pediatrics 1971 ; 47: 675-680.

149. Bourgeois M, Aicardi J, Goutieres F. Alternating hemiplegia of childhood. Journal of Pediatrics 1993; 122: 673-679.

150. Mikati MA, Kramer U, Zupanc ML, Shanahan RJ. Alternating hemiplegia of childhood: clinical manifestations and long-term outcome. Pediatric Neurology 2000; 23: 134-141.

Key Source:[151]

151. edited by Sheila J. Wallace and Kevin Farrell. Epilepsy in children. London: Arnold, 2004. isbn:0340808144.

     Chapter 2. Paroxysmal nonepileptic disorders: differential diagnosis of epilepsy John Stephenson, William P Whitehouse and Sameer Zuberi

Contributors to this page

Admin, Junaid