Chapter 567. Other Paroxysmal Disorders

Many childhood disorders have paroxysmal features. It is therefore not uncommon that these episodes are interpreted as seizures. In this section, common disorders that may mimic epilepsy are emphasized.

Breath-holding spells (BHS) occur most often between the ages of 6 months and 6 years, with a prevalence rate of 4% to 27%1. There may be a familial predisposition to BHS in 20% to 35% of cases.2 The predisposing setting is frustration, anger, fear, or reaction to pain, which leads to crying or a tantrum. The child then holds his or her breath in expiration, often resulting in pallor, cyanosis, or a mixture of both.3 When the spell resolves without loss of consciousness, it is called simple. The child may appear dazed and ultimately lose consciousness and may even have a few convulsive movements or tonic stiffening. Convulsive activity has been seen in up to 55% of children with BHS. The entire episode lasts less than a few minutes, and the child is not impaired for a prolonged period after the attack. Lambroso and Lerman classified the spells in 1960 as pallid, cyanotic, and mixed, in an attempt to separate them into different pathophysiological mechanisms. The etiology is unclear but data suggest excessive centrally mediated sympathetic reflex activity in cyanotic breath-holders, and excessive centrally mediated parasympathetic reflex activity in pallid breath-holders. EEGs during the event fail to show any electrographic seizures; diffuse background slowing of the EEG in the theta-delta range accompanied with slowing of the heart rate is often seen. Conditions besides seizures that can mimic BHS include central apnea due to an Arnold-Chiari malformation, gastroesophageal reflux (GER), prolonged QT syndrome with syncope, brain stem lesions, rage, panic attacks, and Munchausen-en-proxy. Treatment is directed at reassuring the parents of the benign nature of BHS and its ultimate natural remission. Oral iron therapy at 5 to 6 mg/kg/day of elemental iron has been found to be beneficial in some cases.4 The exact mechanism of iron in improving the spells is unclear, but it may act via its effect on serotonin, its degrading enzyme aldehyde oxidase, sympathomimetic neurotransmitter norepinephrine, or its degrading enzyme monoamine oxidase. Use of atropine or scopolamine in refractory pallid breath-holding spells, tetrabenazine or clonidine in refractory cyanotic breath-holding spells, and cardiac pacing in refractory spells accompanied with prolonged asystole have been tried with some success.5 Medications that have been tried on an experimental basis include theophylline, piracetam, naltrexone, acetazolamide, and madroxyprogesterone, but none have definite clinical utility. Educating the parent about intervention during the event including placing in the lateral position to prevent aspiration and applying a gentle thrust on the back to reinitiate respiration is important. Issues regarding the disruptive effects on the parents and extended family and difficulty in obtaining child care and baby-sitting need to be addressed. Seventeen percent go on to develop syncope by teenage years.

Gastroesophageal reflux (GER) signifies the retrograde movement of gastric contents across the lower esophageal sphincter into the esophagus. GER is a common physiological event in infants and children which only becomes pathologic, gastroesophageal reflux disease (GERD), when complications occur. These include esophagitis or esophageal symptoms and respiratory sequelae.6 Children with neurological impairment are more at risk for GERD. A rare symptom complex described most frequently in infancy and childhood, but occasionally in adults, is Sandifer syndrome. Named after the neurologist Paul Sandifer, Kinsbourne first reported Sandifer syndrome in 1962. The syndrome is characterized by gastroesophageal reflux disease (GERD) presenting with spastic torticollis and paroxysmal dystonic head and neck movements, head/eyes version, irritability, crying, vomiting, and abdominal pain, with or without hiatus hernia.7 It is postulated that the abnormal movements during the reflux are the result of a mechanism to protect the air passages from reflux, or to relieve the pain caused by acid reflux. It has been frequently mistaken for seizures including infantile spasms.8,9 A normal EEG, especially during the event, rules out seizures. It is important to be cognizant of this condition because delay in diagnosis can lead to significant morbidity, including aspiration of the stomach acid into the lungs, anemia, and esophageal ulcers. The diagnosis is confirmed with a 24-hour pH probe study, ideally combined with multiple impedance monitoring to correlate reflux events with occurrence of symptoms. The symptoms of Sandifer syndrome respond very well to medical management with use of proton pump inhibitors.

Parasomnias are defined as undesirable events or experience that occur predominantly during sleep. They are subclassified into disorders of arousal from Non-REM sleep, or those associated with REM sleep. They include disorders such as confusional arousal, sleep terrors, sleepwalking and nightmares. The diagnosis and approach to these disorders is further described in Chapter 509.

According to the international classification of sleep disorders, second edition (ICSD-2), parasomnias are defined as undesirable physical events or experiences that occur during entry into sleep, during sleep, or during arousals from sleep. They are classified as (1) disorders of arousals from nonrapid eye movement (NREM) sleep, (2) parasomnias associated with rapid eye movement (REM) sleep, and (3) other parasomnias.10

Disorders of Arousal from NREM Sleep11,12

Most disorders of arousals occur during slow wave sleep (SWS) as incomplete transitions into wakefulness and are characterized by automatic behavior, altered perception of the environment, and a variable degree of amnesia for the event. They tend to occur in the first third of the night when SWS is more prominent. The EEG during the episodes demonstrates an admixture of theta, delta, and alpha frequencies. They are thought to be due to a faulty switch that prevents normal sleep cycle progression. They are brought out by sleep deprivation, medications, noisy or stimulating environments, stress, fever, and sleep fragmentation due to obstructive sleep apnea (OSA) or periodic limb movements of sleep (PLMS). Several studies suggest a genetic predisposition to some of the arousal parasomnias.

The clinical history in a child with any parasomnia should include a complete description of the event, time of night when they happen, frequency of episodes, recollection of the event by the child, and presence during daytime naps.13 Information regarding whether the movements are rhythmic and stereotypical and are associated with eye deviation and focal tonic clonic activity may support an epileptic origin to the events. A home video often proves useful for identifying and classifying parasomnias and differentiating them from seizures.14 Examination should focus on looking for evidence of upper airway obstruction such as adenotonsillar hypertrophy, midfacial hypoplasia, and retrognathia.15 In appropriate cases, a video-EEG may be indicated to rule out seizures.16 Overnight polysomnography is indicated when there is concern for an intrinsic sleep disorder like obstructive sleep apnea (OSA) or periodic limb movements of sleep (PLMS), rather than to document the parasomnia, per se.17

Management usually includes reassuring parents that parasomnias are common in childhood and that they are benign and self-remitting. Parents should be counseled where appropriate on instituting important safety measures including securing windows, staircases, and doors to prevent injuries. They should be educated about avoiding sleep deprivation, maintaining regular sleeping hours, avoiding caffeinated drinks, and avoiding any attempts of restraining or awakening the child during the episode which may actually be counterproductive. Scheduled or anticipatory awakenings several minutes beforehand have been attempted to abort such events when they happen consistently at particular times, but in general have not been well accepted by families. Treatment of the underlying intrinsic sleep disorder like OSA with tonsillectomy and adenoidectomy, and oral iron supplementation for PLMS has shown disappearance of these events. Medications should be reserved for those rare, protracted cases with no associated sleep disorders, with frequent parasomnias, or with a threat for injury. Low-dose clonazepam or tricyclic antidepressants for a short duration have been used with good success in such cases.

Sleepwalking

Sleepwalking occurs in up to 17% of children, highest at 12 to 13 years of age, and with equal frequencies among males and females. It is further classified as calm or agitated subtype, with the former more common in children. The major concern during these benign behaviors is risk for injury.

Confusional Arousals

Confusional arousals occur mainly in infants and toddlers, in up to 17.3% of the population. A typical event begins with moaning, evolving to confused and agitated behavior lasting 5 to 15 minutes. Attempts to wake up the child fully are unsuccessful.

Sleep Terrors

Sleep terrors occur in 1% to 6% of children with peak frequency between 4 and 8 years of age. The child may sit up suddenly and scream with a blood-curdling battle-cry. There is an expression of intense fear on the face, accompanied by autonomic activation including mydriasis, tachycardia, and diaphoresis. Some children may report indistinct recollections of threat such as monsters, spiders, and snakes from which they have to defend themselves, but this is unusual. The event may last from a few minutes up to 20 minutes. Most cases go into a natural remission by adolescence.

Parasomnias classified as disorders of arousal from NREM sleep need to be differentiated from nocturnal seizures. Frontal lobe seizures are especially important because they occur predominantly in sleep, sometimes on many occasions per night, and are characterized by stereotypical movements, thrashing of the entire body, vocalizations, and dystonic posturing, lasting 20 seconds to a few minutes; there is minimal postictal drowsiness or confusion. Paroxysmal nocturnal dystonia, which is now considered to be a frontal lobe seizure, is characterized by an arousal from NREM sleep, accompanied by dystonic posturing, bizarre movements of the extremities, and vocalization, with minimal EEG correlation, because the focus of seizure onset is deep seated in the mesial frontal region. Inpatient video-EEG monitoring is useful in confirming the diagnosis, and differentiating such events from nocturnal panic attacks, fugue states, conversion reactions, and parasomnias like night terrors, confusional arousals, and sleepwalking.

Parasomnias Associated with REM Sleep

Nightmares

These are characterized by vivid dreams in the second half of the night with intense feelings of terror or dread that typically awaken the child from sleep. The child can be easily aroused, with good recollection of the event. They are frequently seen between the ages of 3 and 6 years of age. Prevalence ranges from 30% to 90% for occasional and 5% to 30% for frequent episodes. In children, psychiatric disorders are seen more often in those experiencing nightmares than those without nightmares. They may also be a marker for a history of sexual abuse in children and adolescents.

REM Sleep Behavior Disorders

These are characterized by enacting unpleasant and combative dreams with complex movements that can be vigorous and violent due to lack of REM sleep atonia. They occur more often in the sixth or seventh decade in males and may precede onset of Parkinson’s disease, or progressive supranuclear palsy. They are uncommon in children but may be seen in association with use of selective serotonin reuptake inhibitors such as fluoxetine, or accompanying narcolepsy, and Tourette syndrome. They respond very well to small doses of clonazepam given at bedtime.

Recurrent Isolated Sleep Paralysis

This is characterized by a generalized inability to speak, or to move the trunk, head, and limbs that occur during the transitional period between sleep and wakefulness. The episodes are brief and transient but may be accompanied by vivid hallucinations that make them very distressing. Usually seen with narcolepsy, they may be seen as an isolated form in otherwise healthy individuals, with a strong family history in some cases.

Sleep-Related Hallucinations

These are characterized as vivid dreams, or perceptions not based in reality, that occur at sleep onset (hypnagogic hallucinations) or on awakening (hypnopompic hallucinations) that occur in otherwise healthy individuals but are frequently seen as part of the symptoms of narcolepsy. They may be visual, tactile, auditory, or kinetic in nature. They probably represent brief intrusion of REM sleep into NREM sleep or wakefulness.

Other Parasomnias

Enuresis

Nocturnal enuresis (bedwetting) (see Chapter 468) refers to involuntary passage of urine while asleep. It occurs in almost 15% to 25% of children at 5 years of age, more often in boys, and in almost 1% to 3% of adolescents. It may be classified as primary (when present from birth) or secondary (with periods of at least 6 months of dryness prior to recurrence of enuresis), nocturnal or diurnal. Three major pathological factors have been considered as possible etiologies: Group 1, volume dependent with polyuria; Group 2, detrussor dependent, with involuntary detrussor contractions, and small urinary bladder; Group 3, with decreased arousability. There are strong associations of enuresis with genetic and familial factors, and high prevalence of secondary enuresis in children with OSA. Treatment involves removal of inciting factors, reassurance, behavioral programs, and use of nasal desmopressin, or oral tricyclics like imipramine.

Exploding Head Syndrome

It is a harmless but potentially terrifying situation usually occurring while a patient is falling asleep, and it is characterized by a terrifying loud noise, accompanied by myoclonic jerks, or the perception of a flash of light. They are very brief but lead to intense anxiety. There is no headache or pain accompanying these episodes, and they can begin in childhood. No treatment is needed.

Sleep-Related Eating Disorder

Usually seen accompanying sleepwalking and daytime eating disorder, it is characterized by out-of-control eating binges, predominantly of carbohydrate-containing diets, 2 to 3 hours after sleep-onset, with no recall of the event subsequently. They can be seen to begin in childhood but are more often seen in teenage years and adulthood. These behaviors have recently been described in association with use of hypnotics like zolpidem.

Catathrenia

Also called nocturnal groaning, this can occur in REM or NREM sleep during expiration in clusters of 2 minutes to an hour, ending with a snort, and accompanied with changes in heart rate. The onset may begin during childhood or adolescence. The exact etiology is unknown, and no specific therapy has been found to be effective.

Sleep Starts

Also called hypnic jerks, these are sudden whole-body jerks experienced by individuals during sleep-wake transition. Variations include sensory, auditory including exploding tinnitus, and visual sensations, which may occur without the motor jerks. No treatment other than reassurance is necessary.

Sleep-Sex Disorders

Inappropriate sexual behavior occurring during sleep without conscious awareness has been reported in adults, with onset around adolescence in some cases.

Sleeptalking

Sleeptalking is very common in the general population and can occur in REM or NREM sleep with a strong familial and genetic propensity.

Hypnic Headaches

This is characterized by diffuse headache occurring 4 to 6 hours after sleep onset at a consistent time, lasting 30 to 60 minutes, seen in older adults, and accompanied with nausea but no other autonomic features.

Head Banging

Also called jactatio capitis nocturna, head banging is now classified as a rhythmic movement disorder of sleep, and is characterized by rhythmic movements of head and body at sleep onset in infants and toddlers. It is seen more often in children with developmental disability or autism, but may be seen in normal children. No specific treatment other than reassurance is indicated.

Benign paroxysmal torticollis (BPT) of infancy is a self-limiting condition that appears in early infancy and disappears spontaneously by school age. There are recurrent episodes of torticollis, usually alternating from side to side. Episodes usually continue for several hours to a few days.18 The etiology remains unknown. Various mechanisms have been postulated to explain its pathogenesis, including vestibular, vestibulocerebellar dysfunction, or migraine. Recent reports demonstrated excess EMG activity within the sternomastoid muscle belly on the side of the head/neck tilt during the episode, thus indicating that it may be a form of focal dystonia.19 Accordingly, this condition has been interchangeably called BPT or paroxysmal dystonia. Usually no specific treatment is necessary.

Conversion reaction is defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, as a physical (sensory, motor, or autonomic) symptom that occurs after stress or conflict, is not intentionally produced, and is without evident somatic cause, resulting in significant impairment.20 Primary gain is achieved via the symptom that symbolizes the unconscious conflict, and secondary gain by the gratification the patient receives from the sympathy and attention from the family and friends. The overall prevalence of this condition is about 1% to 3% in childhood and adolescence. It is commonly seen in children ages 10 to 15 years, being twice as common in girls than boys. Predisposing factors include rigid obsessive personality trait, anxiety, depression, previous sexual abuse, domestic stress, feelings of parental rejection, poor intrafamilial communication, unresolved grief, unhappiness at school, illness, and disability.

The symptoms can be varied, but in general, younger children present with unresponsiveness, whereas older children present with agitated behaviors. Psychogenic seizures, a form of a conversion reaction, are commonly misdiagnosed as seizures. It is preferable to consider these events as nonepileptic seizures (NES) rather than pseudoseizures or psychogenic seizures.In adult epilepsy monitoring units, 25% to 35% of patients referred because of uncontrolled seizures have nonepileptic events. In children, such events account for 12% to 43% of admissions to the epilepsy monitoring units to rule out true seizures.21 Unresponsiveness without motor manifestations is the most common feature of psychogenic seizures, seen more often in younger children, while motor manifestations are more common in teenage girls. These include irregular movements that switch from one extremity to another with preserved consciousness, side-to-side head movements, pelvic thrusting, violent asynchronous features without self-injury or urinary incontinence, suggestibility, happening in the presence of company, and during wakefulness, forced eye closure, and prolonged duration of the event in spite of intervention.

History alone is usually not sufficient to make the diagnosis, and even close observation by an experienced clinician is diagnostically accurate only 75% of the time.22 Inpatient video- NES monitoring is therefore required for definitive diagnosis. In addition, many children with NES have concurrent epilepsy, making the diagnosis very challenging. Frontal lobe epilepsy can present with bizarre semiology, and every effort must be made to rule out true seizures before the diagnosis of NES can be made in a given case. Besides seizures, other physiological and organic conditions such as behavioral phenomenon including staring spells, stereotypy, gastroesophageal reflux, shuddering attacks, tics, other paroxysmal movement disorders, Munchausen-en-proxy, and factitious disorders need also to be ruled out.23

Intervention strategies may need involvement of multiple specialists including a psychologist, psychiatrist, social worker, neurologist, and the primary care physician.24 Every effort must be made to not put the blame on either the patient or family members. Unnecessary antiepileptic drugs must be withdrawn when seizures have been conclusively ruled out. The literature contains therapeutic approaches such as dynamic therapy, behavioral therapy, suggestion, removal of secondary gains, hypnosis, and combination therapy. Follow-up at 3 months has shown that 75% to 90% of patients recovered completely; less than 10% showed no improvement. Poor outcome has been correlated with longer duration of the condition before diagnosis, history of sexual abuse, and the premorbid personality of the patient.25