Chapter 64 Breath-Holding Spells and Reflex Anoxic Seizures
Possibly the earliest report of breath-holding spells was published in 1737 by Nicholas Culpepper, who gave the following description: “There is a disease … in children from anger or grief, when the spirits are much stirred and run from the heart to the diaphragms forceably, and hinder or stop the breath … but when the passion ceaseth, this symptom ceaseth.”
Breath-Holding Spells
Clinical Features
The term breath holding is a misnomer and implies that the child is voluntarily holding his or her breath in a prolonged inspiration. Breath-holding episodes actually occur during expiration and are involuntary. Breath-holding spells are not uncommon, with an incidence of 4.6–4.7 percent [Linder, 1968; Lombroso and Lerman, 1967]. The typical age of onset is between 6 and 18 months, although occasionally the onset may occur in the first few weeks of life [Breukels et al., 2002]. Fewer than 10 percent have onset after 2 years of age [DiMario, 1992]. The frequency of episodes ranges from several times daily to once yearly. The spells are often spaced weeks to months apart at onset, and increase in frequency to as many as several per day during the second year of life [Laxdal et al., 1969; DiMario, 2001]. Breath-holding spells are classified by the color change manifested in the child during an event. Cyanotic episodes are more common than pallid episodes. In some instances, there are features of both cyanosis and pallor, and these are termed mixed episodes.
An association between behavior problems, emotional factors, and breath-holding spells has been discussed by many investigators. Breath-holding spells were described by Abt [1918] as occurring in “neuropathic children of neuropathic parents.” Bridge et al. [1943] stated that children susceptible to breath holding are usually of the active, energetic type, who react vigorously to situations, and that episodes were precipitated by “spoiled child reactions.” Breath-holding spells were felt to be a sign of a disturbed parent–child relationship by Kanner [1935]. Laxdal et al. [1969] reported that 30 percent of the children with breath-holding spells had abnormal behavior, including temper tantrums, hyperactivity, and stubbornness. To investigate the role of behavior and breath holding further, DiMario and Burleson [1993b] studied behavior in children with breath-holding spells compared with controls and found no differences in the behavioral profiles, suggesting that breath-holding spells are nonvolitional and cannot be equated with a temperamentally difficult child.
Breath-holding spells generally decrease in frequency during the second year of life. By 4 years of age, 50 percent of children will no longer have episodes. Almost all will have stopped having episodes by age 7–8 years [DiMario, 1992; Goraya and Virdi, 2001]. Syncopal episodes occur in late childhood or adolescence in as many as 17 percent of patients with breath-holding spells [Lombroso and Lerman, 1967].
Serious complications with breath-holding spells are rare. Taiwo and Hamilton [1993] reported a prolonged cardiac arrest in a patient with breath-holding spells. The few reported deaths may have been precipitated by aspiration or occurred in children who were at the severe end of the spectrum of breath-holders, often with structural abnormalities of the respiratory tract or complicated medical histories [Paulson, 1963; Southall et al., 1987, 1990].
Clinical Laboratory Tests
A detailed history of the event, including the precipitating circumstances, is essential in making the diagnosis of breath-holding spells. If the event was not witnessed from onset, important details may not be available. A video recording by the parents may be helpful in confirming the diagnosis. Usually, no laboratory tests are needed to make the diagnosis. An electroencephalogram (EEG) is usually not indicated, unless the convulsive activity is prolonged or the clinical description is incomplete and epileptic seizures cannot be ruled out. If ocular compression is performed in patients with pallid breath-holding spells, there may be asystole on cardiac monitoring, and slowing or suppression of voltage on EEG [Lombroso and Lerman, 1967; Stephenson, 1978]. Long QT syndrome is rare but should be considered as part of the differential diagnosis in a child with breath-holding spells. Patients with long QT syndrome have episodes of loss of consciousness that may be induced by injury, fright, or excitement. An electrocardiogram should be considered in any patient with breath-holding spells [Breningstall, 1996; Franklin and Hickey, 1995].
Pathophysiology
Cyanotic Spells
The pathophysiology of cyanotic breath-holding spells is complex and not completely understood. Cyanosis occurs early in the episode, which is unusual during voluntary breath holding. In breath-holding spells, the breath is held in full expiration, which also is not typical with voluntary breath holding [Livingston, 1970]. Gauk et al. [1963] studied a child during a cyanotic breath-holding episode with cinefluorography and noted the diaphragm to be high, as would be seen in full expiration, and motionless during the period of apnea. Spasm of the glottis and respiratory muscles, with increased intrathoracic pressure, occurs during expiration. Increased intrathoracic pressure reduces cardiac output, causing a decrease in cerebral perfusion. Lombroso and Lerman [1967] suggested that violent crying could lead to hypocapnia, which would also impair cerebral circulation.
Southall et al. [1985] further evaluated the prolonged expiratory mechanism in nine infants with cyanotic episodes that were usually triggered by noxious stimuli. Arterial oxygen saturation fell below 20 mm Hg within 20 seconds. Loss of consciousness occurred after 30 seconds. Measurements of respiratory movements, airflow, and esophageal pressure, and, in some patients, microlaryngoscopy and chest fluoroscopy were obtained. They documented no inspiratory flow during the period of apnea but continued expiratory muscle activity at low lung volumes with partial or complete glottic closure. No intracardiac shunt could be demonstrated. The rapid fall in arterial oxygen saturation was attributed to lack of ventilation at a maximum expiratory position in the presence of a rapid circulation time. The researchers hypothesized that central and peripheral neural respiratory control was functioning normally but was interfered with by a mechanical defect involving lung-volume maintenance. This defect could occur because of an excessively compliant rib cage, allowing alveolar collapse. This collapse, in turn, could lead to stretching of the airways and their stretch receptors, inappropriately simulating maximum lung volumes and thereby inhibiting inspiration. Southall et al. [1990] did further evaluations of prolonged expiratory apnea with krypton infusion scans and demonstrated krypton outside the lung fields, without evidence of an intracardiac shunt. They felt there was intrapulmonary shunting that contributed to the rapid onset and severity of the hypoxemia.
The relation between breath holding and chemosensitivity has also been investigated. Anas et al. [1985] hypothesized that persons with cyanotic breath-holding episodes have blunted ventilatory chemosensitivity. Because of the difficulty of measuring chemosensitivity in toddlers, they measured ventilatory responses to progressive hypercapnia and to progressive hypoxia in subjects aged 11–50 who had a history of cyanotic breath-holding spells and compared the results with a control group. Contrary to their hypothesis, the majority of persons with a history of cyanotic breath-holding spells had normal ventilatory responses. However, no one with a history of breath-holding spells had high normal responses to hypercapnia or hypoxia, as did some individuals in the control group. They postulated that the difference between the groups might represent the vestige of a disorder of ventilatory chemosensitivity that resolved with maturation.
Kahn et al. [1990] also investigated the relation between breath holding and cardiorespiratory control. The study included 71 infants with a history of breath-holding spells and age- and gender-matched controls. The median age of infants in the study was 14 weeks, which is younger than the typical age for onset of breath-holding episodes. The infants with breath-holding spells were significantly more often covered with sweat during sleep and wakefulness compared with control infants. One-night sleep studies were obtained in each infant. The infants with breath-holding spells had significantly less non-rapid eye movement (REM) stage III sleep, more indeterminate sleep, more arousals, and more sleep-stage changes than the control infants. Airway obstructions during sleep occurred in 41 infants with a history of breath holding, compared with 6 in the control group. The obstructions were generally short and not accompanied by significant bradycardia or oxygen desaturation. The researchers concluded that there was a common underlying mechanism resulting in airway obstruction during breath-holding spells and sleep, which possibly involved the autonomic nervous system because the autonomic nervous system controls the patency of the upper airways. Guilleminault et al. [2007] performed polysomnography in 14 children with cyanotic breath-holding spells and found an abnormal respiratory index in all 14. Examination showed upper airway narrowing, and adenotonsillectomy was performed in 13 with marked improvement in sleep-disordered breathing and resolution of their breath-holding spells.
Kohyama et al. [2000] did polysomnography to evaluate REM sleep in seven children with breath-holding spells and nine normal age-matched controls. The children with breath-holding spells had a significant decrease in ocular activity during REM sleep, especially during the last third of the night, compared with the controls. Relative elevation of cholinergic tone, compared with monoaminergic tone, is considered to be involved in the physiologic increase of REM sleep in the later cycles of the night. The vestibular nucleus and the medioventral caudal pons are believed to be involved in bursts of eye movements during REM sleep. They hypothesized that there was a functional disturbance in the pons of children with breath-holding spells. The study also suggests that the autonomic nervous system is involved because of the more pronounced decrease in eye movement in the later cycles of the night, which are regulated by the autonomic nervous system.
