This phenomenon is characterized by episodes of cyanosis, dyspnea, and unconsciousness and can present during the first several years. The repertoire of events occurs in 10% to 20% of children with congenital heart disease and may result in seizures. Anoxia-induced seizures occur in such individuals who suffer chronic and significant hypoxemia. Such episodes are labeled “tet spells” because young children with the especially cyanotic congenital heart lesions (such as tetralogy of Fallot) usually present in this manner. The pathogenesis for “tet spells” is the sudden increase in right-to-left shunting of blood through the heart with sudden oxygen desaturation. On careful history taking, attacks of hyperpnea and cyanosis are seldom misinterpreted as epileptic seizures. Loss of consciousness may result from anoxia or hypoxia, however, which then may precipitate seizures in certain children and, therefore, may be confusing to the clinician. For those children old enough to be ambulatory, taking a squatting position and then remaining nearly motionless is a maneuver for recovering cardiac reserve.⁴⁹

Children with recurrent episodes of loss of consciousness or alterations in arousal may suffer from cardiac arrhythmias. Disturbances of cardiac conduction of either intracardiac or extracardiac origin include sick sinus syndrome,⁶⁰ Jervell-Lange-Nelson syndrome, which is genetically determined and includes an associated deafness,²⁹ and Ward-Romano syndrome.⁵¹ Therefore, careful history taking and examination may reveal characteristic features such as hair hypopigmentation, hearing loss, or dysmorphea. Syncope may frequently include convulsive movements similar to an Adams-Stokes attack. The prolonged-QT syndrome should be suspected in children particularly with underlying cardiac disease on a genetic basis such as the velocardiofacial syndrome (i.e., chromosomal 22q 11.2 deletion).³¹ Prolonged-QT syndrome may be benign and transient or prolonged with risk for sudden death.⁶⁷ Prognosis is guarded because sudden unexpected death may occur at any time. True epileptic seizures may ensue in affected children as a result of asphyxia-induced brain injury incurred during prolonged episodes of hypoxemia during cardiac arrest. A cardiologic evaluation, including a prolonged electrocardiographic (ECG) recording and/or ECG during exercise may be required.

In a recent study of adults, 20% of patients referred to a neurologic department with possible idiopathic epilepsy were subsequently found to have cardiac arrhythmias that caused or significantly contributed to their symptoms.⁶⁰ Pediatric populations referred to neurology or epilepsy clinics may reflect comparable percentages, but few studies are available for comparisons with older populations. A report of sudden death in the young presenting with presumed cardiac arrhythmias was the most common cause of mortality in people 5 to 35 years of age. The two most common noncardiac causes of sudden death were epilepsy (23.8%) and intracerebral hemorrhage (23.8%).⁵⁵ In another study of adult epileptic patients, one third showed ictal bradycardia, with greater than one half experiencing serious cardiac events meriting pacemaker placement.⁵⁸ In general, sinus tachycardia accompanies approximately 90% and bradycardia or asystole 0.5% of all seizures.⁷²

Hypoglycemia may occasionally challenge the clinician because of its association with unusual symptomatology. Both seizures and nonepileptic behaviors occur with hypoglycemia at any age, including the neonatal period. Neonates with hypoglycemia may present with tremulous behavior. Rare metabolic disorders can present early in life with hypoglycemia associated with, for example, hyperammonemic states, leucine intolerance, and hereditary fructose intolerance. Particularly after 1 year of age, unusual episodes of unconsciousness, stupor, or even seizures may occur during the early morning hours after an all-night fast. Postevent confusion or stupor can be prolonged after hypoglycemia-induced seizures. Such events may occur after episodes of vomiting, diarrhea, or transient reduced food intake, sometimes in the setting of a transient illness. The combination of symptoms associated with the condition of ketotic hypoglycemia⁸ accounts for approximately 50% of cases of hypoglycemia that occur during early childhood. The child appears grossly ketotic during the attack and may exhibit marked hyperventilation. Acetonuria is an essential feature, which is rapidly corrected by administration of glucose. Hospitalization with carefully controlled provocation tests are suggested to induce hypoglycemia, such as with the administration of a ketogenic diet. Treatment consists primarily in preventing ketosis by adhering to regular mealtimes, particularly during times of illness, together with glucose supplementation. Of course, hypoglycemia and seizures may coexist; children may have epileptiform discharges on electroencephalogram (EEG), which may support a seizure diagnosis but not be interpreted in the context of the patient’s clinical history. For example, neonatal hypoglycemia can result in injury to parietal-occipital cortical regions, which may later present as one form of focal epilepsy, involving posterior pathways.

Hypocalcemic stress usually results in seizures and can be secondary to primary or secondary hypoparathyroidism (with or without genetic cardiac syndromes). Severe nutritional deficiencies may be associated with poor feeding practices, starvation, or chronic diseases such as malabsorption syndromes or rickets.² A rare genetic disease of familial hypomagnesemia may be associated with hypocalcemia.⁶⁸ Rarely, profound hypocalcemia can result in nonepileptic tetanic spells,
including generalized clonic activity, jaw rigors, and tremulousness.

Infants may demonstrate episodic extension and lateral flexion of the head, usually in association with feeding. This syndrome was first described by Kinsbourne³⁴ and is sometimes termed “Sandifer syndrome” because the first patient described by Kinsbourne was under the care of Dr. Paul Sandifer. Although these seizure-like episodes suggest epilepsy, gastroesophageal reflux disorder (GERD) should be suspected after a careful history is obtained. In a retrospective review of 342 infants presenting with symptoms suggestive of GERD, all were <1 year of age; they presented with regurgitation, choking, irritability, failure to thrive, an apparent life-threatening event (ALTE), or wheezing.⁶⁴ In a study of 69 infants with ALTE, GERD was diagnosed in 38 cases and gastric volvulus in 21.⁴⁵

Gastrointestinal radiographs, such as barium swallow study, document reflux with or without hiatal hernia or other morphologic abnormalities of the upper airway or gastrointestinal tract. Surgical correction is sometimes required to correct such attacks. The age range for these events is wide, beginning during the neonatal period and extending into adolescence. For infants, choking, apnea, laryngospasm, and opisthotonos also commonly occur,²⁵ whereas other gastrointestinal complaints, weight loss, or sleep disturbances are noted for older children.

Syncope is a common occurrence for adults and older children and is usually distinguished from true epileptic seizures by the historical description of a witness (see Chapter 271).⁵ Patients describe warning signs of lightheadedness, dizziness, or visual dimming, such as graying out or browning out. Nausea may also be described after the event. Subjective feelings of temperature change and profuse sweating are also described. Sometimes a specific stimulus such as the sight of blood, minor trauma, or enclosure in a confined space may precipitate an attack. Orthostatic syncope may follow after prolonged standing or sudden change in posture. A careful review of a family history may document similar events in other relatives.⁶

Reflex syncope may also be described with certain physiologic maneuvers such as coughing, swallowing, or micturition.³² Table 2 lists some causes of syncope, some of which are described elsewhere in this chapter, such as cardiac arrhythmias.

Syncopal events in the neonate, infant, or preverbal children have unique diagnostic challenges. Events may occur precipitously following surprise, pain, or prolonged crying. Breath-holding spells are discussed later, given the prominent respiratory component to this event. Underlying illnesses such as cardiorespiratory or metabolic-genetic causes may suggest a pathophysiologic mechanism. Neurocardiogenic syncope and neurologic disorders (80% and 9%, respectively) are the most common diagnoses for pediatric patients presenting to an emergency department.⁴¹ Cardiogenic studies such as prolonged ECG monitoring, ultrasonography of the heart, or a tilt-table test may help to document associated abnormalities or capture events. Serum studies during an attack may document metabolic disturbances, such as hypoglycemia. Rarely, syncope triggers epileptic seizures, requiring both cardiologic treatment such as antiarrhythmic medication or cardiac pacing, as well as antiepileptic medications.²⁸ Patients with syncope, however, may have a few clonic jerks or even incontinence during or following the syncopal event⁵² without evolving to seizures.

The physical examination of syncopal patients yields normal results. Blood pressure changes from supine to standing positions, however, may demonstrate a substantial drop in the diastolic component, supporting the diagnosis of orthostatic syncope. A tilt-table test may also be helpful. If one documents a blood pressure reduction of more than 15 points or the presence of a sinus bradycardia on standing, orthostatic hypotension should be suspected. A cardiologic evaluation including investigation for a heart murmur or dysrhythmia should be considered. Exceptional cases of congenital heart block have been associated in children with chronic myopathy, ophthalmoplegia, deafness, and ataxia, termed the Kearne-Sayne syndrome.³

If an attack is prolonged, a tonic motor seizure may occur. In a review of 77 patients appearing in an emergency room, 40 had syncope, 17 had near-syncope, and 20 did not have a syncopal episode. Vasovagal (50%) and orthostatic hypertension (20%) were the most common causes of syncope. Near-syncopal episodes occurred with lightheadedness (29%), seizures (18%), tension headaches (12%), and migraine (6%).⁵² Adolescents, particularly those who lift weights or perform gymnastics, may induce syncope by stretching or straining the musculature, including inducing a neck-hyperextended position.

Children with recurrent symptoms should be evaluated by a cardiologist. Autonomic functioning of patients with beta-adrenergic hypersensitivity should be tested. A tilt-table test is particularly useful, sometimes with administration of isoprotosenol infusion as a provocative agent to induce blood pressure changes.²³