Nonepileptic paroxysmal disorders in children

INTRODUCTION — Epilepsy is a condition characterized by recurrent seizures. The term seizure refers to a transient occurrence of signs and/or symptoms due to abnormally excessive neuronal activity of the brain. Many pediatric epilepsy centers find that least 20 percent of referrals do not have epileptic seizures [1-4]. Many of these children are referred for evaluation of spells that are later determined to be temper tantrums, oppositional defiant behavior, and attention deficit disorder/attention deficit hyperactivity disorder (ADD/ADHD). Others have stereotyped paroxysmal disorders that may look like seizures and may even have loss of consciousness and unusual motor phenomena. A few children have behavior that initially sounds like true seizures but on video-electroencephalogram (EEG) monitoring proves to be nonepileptic. Nonepileptic paroxysmal events are not rare in children and can lead to multiple trials of anticonvulsant medications before the correct diagnosis is recognized.

The common nonepileptic disorders that can mimic seizures in children will be reviewed here. A more detailed discussion of the clinical and historical phenomena that help distinguish true seizures from nonepileptic events and the urgent evaluation of children and adolescents with syncope is discussed separately. Nonepileptic paroxysmal events more common in infancy and in adolescents are presented separately. (See "Seizures and epilepsy in children: Classification, etiology, and clinical features" and "Emergency evaluation of syncope in children and adolescents" and "Nonepileptic paroxysmal disorders in infancy" and "Nonepileptic paroxysmal disorders in adolescents and adults".)

MIGRAINE SYNDROME — Recurrent headaches with a family history of migraine rarely present a diagnostic dilemma. However, acute neurologic events without significant headache, particularly those with loss or alteration of consciousness, can be misdiagnosed as seizures. A migraine attack may be dominated by neurologic symptoms, including visual hallucinations, confusion, stupor and coma, total blindness, hemiparesis, or brainstem signs including diplopia, vertigo, and ataxia (so-called basilar-type migraine). (See "Types of migraine and related syndromes in children" and "Pathophysiology, clinical features, and diagnosis of migraine in children" and "Migraine with brainstem aura".)

Post-traumatic migraine is a well-defined syndrome characterized by predominantly neurologic signs occurring after relatively minor head trauma. Some children given the diagnosis of cerebral concussion in reality have suffered an attack of migraine.

True epileptic seizures are rarely triggered by a migraine, and it is unusual for a headache to precede an epileptic seizure. More commonly, a migraine-like headache follows a seizure. This latter association is particularly common with generalized tonic-clonic seizures and after partial seizures arising in the occipital regions. Migraine should be suspected if the child has vomiting with the episode, a history of severe headaches without neurologic symptoms exists, or the family has a strong history of headaches [5-9].

Migraine may be associated with epilepsy in children. A population-based case control study found an association between incident epilepsy and migraine with aura (OR = 8.1, 95 percent CI, 2.7-24.3) but not migraine without aura [10].

BENIGN PAROXYSMAL VERTIGO — Benign paroxysmal vertigo (BPV) is a disorder of early childhood manifested by recurrent episodes of brief disequilibrium. It is classified as an episodic syndrome that may be associated with migraine [11]. During the attacks, the child appears frightened and off balance, often reaching out to steady himself. The events may be associated with nystagmus, diaphoresis, nausea, and vomiting. Older children will grab nearby persons or furniture for support to prevent falling and may complain of vertigo or dizziness. Episodes usually last less than a minute and are not associated with an altered consciousness. They usually recur in clusters, occurring daily for several days in a row, then remitting for several weeks, and recurring again.

The disorder is typically benign and may resolve without treatment, but some children have attacks may persist into adolescence [12,13]. Many patients will subsequently develop typical migraine [14,15]. A family history of migraine is also often noted [10]. The pathophysiology of BPV of childhood is unknown.

There are no laboratory tests that have been useful in establishing the diagnosis of BPV.

BPV remains a diagnosis of exclusion. The main role of the clinician is to differentiate these episodes from seizures, particularly in young children who cannot describe the attacks and whose level of consciousness can be difficult to determine. (See "Types of migraine and related syndromes in children", section on 'Episodic syndromes that may be associated with pediatric migraine'.)

NONEPILEPTIC STARING SPELLS — Staring spells or pseudoabsences occur in children with intellectual disability, attention deficit disorder/attention deficit hyperactivity disorder (ADD/ADHD), autism, and in some otherwise normal children [2,16]. In one series, these nonepileptic staring spells made up one-third of nonepileptic events in children referred for video-electroencephalography (EEG) monitoring [4].

Pseudoabsences must be distinguished from true absence seizures, particularly in the child with ADHD and staring spells. Nonepileptic staring spells usually occur when the child is either bored or inactive, such as when watching television or sitting in a classroom [4]. The staring episodes can be interrupted by tactile or vocal stimulation (but usually not hand-waving). They rarely occur during physical activity, and are never associated with automatisms, myoclonus, or the other motor signs that typify true absence seizures.

Hyperventilation is an effective trigger of typical absence seizures and can be a useful tool in the primary care office setting. However, both true and pseudoabsence seizures may be precipitated by hyperventilation. The child is asked to deeply overbreathe for at least three minutes. Younger children can be asked to blow out imaginary candles or blow objects out of the examiner's hand.

●An absence seizure is usually obvious; there is a sudden cessation of overbreathing, a stare often with slow upward deviation of the eyes; low-amplitude myoclonic jerks (three per second) of the facial musculature, head, and upper extremities; and in most children, automatisms (eg, chewing, swallowing, lip-smacking, fussing with clothing). The seizure usually lasts a few seconds but can continue for 15 to 20 seconds. The child is amnestic for the absence and cannot recall nonsense words presented by the examiner during the seizure. Occasionally, the child will have increased extensor tone of the trunk characterized by a slow backward lean when sitting on the examining table. The examiner should sit next to the patient in the unlikely event that hyperventilation precipitates a generalized tonic-clonic seizure. A concurrent EEG is abnormal, with bursts of generalized, three hertz spike and wave activity.

●A small percentage of children may have benign nonepileptic staring spells during hyperventilation that result from altered consciousness caused by the alkalosis and decreased cerebral blood flow [17]. A concurrent EEG will show generalized high-voltage slow activity, the expected EEG changes in the hyperventilating healthy child, but no epileptiform activity. An inexperienced electroencephalographer may confuse this striking slow activity, called a "build-up," with the paroxysmal activity of an absence seizure.

Video-EEG monitoring is a useful tool for distinguishing epileptic and nonepileptic staring spells. (See "Childhood absence epilepsy", section on 'Electroencephalography'.)

PSYCHOGENIC NONEPILEPTIC SEIZURES — Psychogenic nonepileptic seizures (PNES) are reviewed here briefly and discussed in detail separately. (See "Psychogenic nonepileptic seizures: Etiology, clinical features, and diagnosis".)

PNES are dramatic behavioral events in a conscious individual that are often misdiagnosed as epileptic seizures and may lead to treatment with antiseizure medications. PNES most commonly present in the third decade of life; however, all age groups can be affected. In children, the events typically occur in teenage patients with affective and anxiety disorders and are less common in younger children [18,19]. Comorbid epilepsy is common, particularly in children. A family history of seizures or a friend or acquaintance with seizures is a risk factor.

PNES often present as a prolonged episode with generalized, atypical-appearing motor activity and a prompt return of consciousness. One study found that younger children (<13 years) were more likely to have more subtle motor manifestations as compared to teenagers and adults [18]. During psychogenic nonepileptic seizures, patients often close their eyes tightly and resist their opening. In contrast, patients having a generalized epileptic convulsion typically have their eyes open.

Nonepileptic seizures are best distinguished from true seizures by capture of an event on video-electroencephalogram (EEG) monitoring. (See "Psychogenic nonepileptic seizures: Etiology, clinical features, and diagnosis", section on 'Video-EEG monitoring'.)

SYNCOPE — Syncope is an abrupt loss of consciousness due to an interruption of energy sources to the brain, usually because of a sudden reduction of cerebral perfusion.

In children, most cases of syncope are vasovagal in origin. They are distinguished from seizures by the situation in which they occur (emotional stress, prolonged upright posture, pain) accompanying pallor, prodromal lightheadedness and visual changes, and lack of postictal state. (See "Causes of syncope in children and adolescents", section on 'Vasovagal syncope'.)

Rare, but potentially life-threatening cardiac conditions (eg, long QT syndrome) can also present with syncope in children [20]. These events often present without provocation or prodrome and may mimic a seizure, although pallor is common and postictal confusion is rare. These patients usually have an abnormal cardiac examination (table 1) and/or electrocardiogram (ECG). (See "Causes of syncope in children and adolescents", section on 'Life-threatening conditions'.)

Breath-holding spells often persist into childhood, but usually present during infancy. (See "Nonepileptic paroxysmal disorders in infancy", section on 'Breath-holding spells'.)

Syncope in children is discussed separately. (See "Causes of syncope in children and adolescents" and "Emergency evaluation of syncope in children and adolescents".)

MOVEMENT DISORDERS — Hyperkinetic movement disorders or dyskinesias include chorea, dystonia, athetosis, tics, tremors, and ballism. These are described separately. (See "Hyperkinetic movement disorders in children".)

Movement disorders are rarely confused with seizures when the motor activity is classic in appearance and is sustained rather than episodic. Also, impaired consciousness does not occur with movement disorders, and when present, strongly suggests seizures. However, the diagnosis can be confusing when movement disorders present with episodic symptoms and when focal epileptic seizures are characterized by isolated dystonic posturing.

Patients with dystonia and other movement disorders may obtain symptomatic relief from sensory tricks, such as lightly touching their face in cervical dystonia. This phenomenon is known as geste antagoniste and may be a useful feature distinguishing these from epilepsy.

In children with cognitive impairment, differentiating nonepileptic movements from seizures can be especially challenging. Seizures and nonepileptic motor events often coexist in these patients. In these and other situations, video-electroencephalography (EEG) monitoring can be extremely helpful [21].

Tics and stereotypies — Tics are relatively brief, sudden, rapid, and intermittent movements (motor tics) or sounds (vocal tics). They may be repetitive and stereotypic. Tics are usually abrupt in onset and brief (clonic tics) but may be slow and sustained (dystonic tics). Tics are associated with a premonitory feeling that is relieved by performing the tics. In contrast to other hyperkinetic dyskinesias or epileptic seizures, children with tics are distractible, and the tics may be temporarily suppressed [4]. Tics also differ from epilepsy by the variability of the movement and the urge to perform tics. The myoclonic jerks of juvenile myoclonic epilepsy can be mistaken for tics [22]. Tics can occur in Tourette syndrome but may also be an isolated phenomenon or accompany other disorders, as outlined in the table (table 2). (See "Juvenile myoclonic epilepsy", section on 'Clinical features' and "Tourette syndrome: Pathogenesis, clinical features, and diagnosis".)

Stereotypies are repetitive, purposeless actions such as head banging, head rolling, body rocking, and hand flapping. Similar to tics, stereotypies also may be consciously suppressed and decreased by distraction. Unlike tics, stereotypies are not preceded by a progressive urge or relief following the activities. Often, they manifest as self-stimulating behaviors in response to tension and anxiety and may comfort the patient.

Stereotypies may occur alone or may be secondary to trauma, drugs (eg, chronic amphetamine abuse), or toxic-metabolic insult. These movements can be seen in normal children, but are more common in children with schizophrenia, intellectual disability, and autism, and are characteristic of Rett syndrome. (See "Hyperkinetic movement disorders in children" and "Rett syndrome: Genetics, clinical features, and diagnosis".)

Paroxysmal dyskinesia — These paroxysmal movement disorders are classified according to the setting in which they occur and can include a variety of movements including dystonia, ballism, and chorea. These disorders can present in childhood, adolescence, or early adulthood. These are briefly described below and are discussed in more detail separately. (See "Hyperkinetic movement disorders in children", section on 'Other causes' and "Nonepileptic paroxysmal disorders in adolescents and adults", section on 'Paroxysmal dyskinesia'.)

●Paroxysmal hypnogenic dyskinesia consists of dystonic or dyskinetic episodes during or immediately after arousal from non-rapid eye movement (REM) sleep or, more rarely, during wakefulness. These may, in fact be epileptic in origin. (See "Nonepileptic paroxysmal disorders in adolescents and adults", section on 'Nocturnal paroxysmal dystonia'.)

●Paroxysmal kinesigenic dyskinesia (PKD) consists of brief (less than one minute) attacks of choreoathetosis, dystonia, or both that are precipitated by sudden changes in movement [23-25]. Movements may be unilateral or bilateral. Consciousness is retained. Many individuals have a brief, nonspecific warning or aura prior to an attack. The interictal examination is normal. PKD may be associated with pathogenic variants in the PRRT2 gene), sporadic/idiopathic, or secondary condition (due to multiple sclerosis, stroke, traumatic brain injury), and is more common in boys than girls. Carbamazepine or phenytoin is often effective [23,26].

●Paroxysmal nonkinesigenic dyskinesia consists of attacks of spontaneous, severe dystonia that may be precipitated by alcohol, caffeine, and stress [25,26]. The duration of these episodes may be two minutes or several hours, occasionally a day or two. Causes include pathogenic variants in the PNKD gene [25]. Antiseizure medications may be efficacious, but less consistently than with PKD. Familial, sporadic, and secondary forms have been described.

●Paroxysmal exercise-induced dyskinesia consists of brief episodes of dystonia that occur after several minutes of exercise, not at initiation of movement, as in kinesigenic dyskinesia [25,26]. Typically, the part of the body that has been doing the most exercise becomes dystonic. The abnormal movement resolves gradually with cessation of the exercise. This may be sporadic or a hereditary condition, associated with pathogenic variants in the SLC2A1 gene [25]. Antiseizure medications are not generally helpful. Acetazolamide has been effective in some individuals.

SLEEP DISORDERS — Episodes arising out of sleep disturbances are a common cause of nonepileptic events in children referred for video-electroencephalography (EEG) monitoring [4].

Rhythmic movement disorders — Rhythmic movements such as nocturnal head banging, body rocking, and head rolling typically occur in children younger than one year of age as they try to fall asleep, but can first appear at any age [27-29]. They also can be present in deep sleep and in wakefulness. They are somewhat more common in children with learning disabilities, but occur in developmentally normal children as well. They can remit within a few years of onset or persist into adulthood. The characteristic nature of the movements is not typical for epilepsy, and patients can often be directed to stop the movements, which is not true for an epileptic seizure. (See "Sleep-related movement disorders in childhood", section on 'Rhythmic movement disorder'.)

Sleep walking, night terrors, and confusional arousals — These non-rapid eye movement (REM) sleep arousal disorders are common, occurring in 15 to 20 percent of preadolescent children [29]. The diagnosis and treatment of these disorders are discussed separately. (See "Parasomnias of childhood, including sleepwalking", section on 'Disorders of arousal from non-rapid eye movement sleep'.)

●Sleep walking or somnambulism occurs in up to 15 percent of children between the ages of 5 and 12 years with a peak prevalence between 4 and 6 years [30]. While eyes are often open, patients demonstrate a low level of awareness with a blank facial expression and reduced responsiveness to stimulation. Movements are usually slow, clumsy, and purposeless; but more complex and directed activity, as well as agitated behaviors, are also described. (See "Parasomnias of childhood, including sleepwalking", section on 'Sleepwalking'.)

Postictal wandering after a night-time seizure may be difficult to differentiate from sleep walking. Such patients are usually confused and disoriented, not just less responsive as with sleep walking. Signs indicating a prior seizure might include incontinence or a bitten tongue.

●Sleep terrors are characterized by a sudden, often dramatic arousal with facial expression, vocalization, and other behaviors that express agitation and fear [31]. Tachycardia, diaphoresis, mydriasis, and other autonomic features are prominent. Patients are difficult to arouse and will fall back to sleep spontaneously after a few to several minutes. These episodes can first manifest at a young age, around 18 months, have a peak prevalence at age 5 to 7 years, and typically resolve prior to adolescence. Triggers include acute stress and sleep deprivation, as well as certain medications including stimulants, neuroleptics, sedatives, and antihistamines. (See "Parasomnias of childhood, including sleepwalking", section on 'Sleep terrors'.)

●Confusional arousals are characterized by sudden arousal with disorientation, confusion, agitation, and some semipurposeful motor activity. Vocalization with coherent speech is common, but autonomic activation typical of a night terror is not. Episodes last a few to several minutes. (See "Parasomnias of childhood, including sleepwalking", section on 'Confusional arousals'.)

These disorders overlap and have a typical duration of a few to 30 minutes. Episodes arise out of sleep stages 3 and 4, typically within the first half of sleep, but after the first 30 to 90 minutes. In an intermediate stage between waking and sleep, patients may not respond normally to questions or other stimuli. Amnesia is common, but some children report brief dream-like images. It is common for an individual and a family to manifest more than one of these disturbances.

These episodes can usually be distinguished from nocturnal seizures, which are usually briefer (a few minutes or less), stereotyped, and more frequent, often occurring in clusters [29,31]. In contrast, it is rare for these sleep disturbances to recur in the same night and their average frequency is one to three times a month. Case reports of night terrors that were determined to be epileptic in origin were atypical for sleep terrors because of their short duration, frequency, and occurrence in the second rather than first half of sleep [32,33]. Recording episodes on video-EEG and polysomnography is necessary when the diagnosis is unclear.

Sleep starts — Sleep starts or hypnic myoclonus refers to a sudden jerking movement upon falling asleep, often accompanied by a subjective sensation of falling [3,4]. These can occur at almost any age and are usually easily recognized. Rarely, hypnic myoclonus can become unusually violent, very frequent, or repetitive and confused for myoclonic seizures or even tonic-clonic seizures. The myoclonic jerks are restricted to sleep, usually in the transition between sleep and wakefulness, and are not associated with other clinical phenomena. (See "Nocturnal leg cramps".)

OTHERS — This topic reviews those imitators of epilepsy that are most common in children. Disorders more typical of infancy or adolescence can occasionally present in this age group as well (table 3). (See "Nonepileptic paroxysmal disorders in infancy" and "Nonepileptic paroxysmal disorders in adolescents and adults".)

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Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Sleepwalking in children (The Basics)")

SUMMARY

●The differential diagnosis of epileptic seizures in children includes a variety of benign, physiologic phenomena as well as pathologic conditions (table 3). Some of these conditions can persist into childhood and longer.

●Clinical features of these events help distinguish these from epileptic seizures (see descriptions of individual disorders, above). In difficult cases, electroencephalography (EEG), particularly video-EEG monitoring, is useful. (See "Seizures and epilepsy in children: Clinical and laboratory diagnosis".)