Syncope

Abstract

Syncope, defined as the temporary loss of consciousness and postural tone resulting from an abrupt, transient decrease in cerebral blood flow, has emerged over the last decade as one of the most common reasons for a pediatric cardiology referral. Other widely used synonyms are vasovagal syncope or “simple fainting.” Although many individuals will experience syncope at least once during their lifetime (estimated 30 % lifetime risk), it is usually self-limited and benign. Rarely, it may be the first warning sign of a serious condition including arrhythmia, structural heart disease, or noncardiac disease. Patients with recurrent syncopal episodes, syncope during exercise, emotion/stress-induced syncope, syncope resulting in injury, syncope in the driving-age pediatric patient, syncope in those with a family history of hypertrophic cardiomyopathy or a channelopathy, or syncope in patients with congenital heart disease require investigation. Recurrent syncope may cause a major impact on lifestyle, interfering with school and/or sports. Many states impose driving restrictions following syncope. This chapter presents a differential diagnosis of syncope in children, outlines in detail neurocardiogenic or neurally mediated syncope (NCS, NMS), and reviews different evaluation and treatment strategies.

Introduction

Syncope, defined as the temporary loss of consciousness and postural tone resulting from an abrupt, transient decrease in cerebral blood flow, has emerged over the last decade as one of the most common reasons for a pediatric cardiology referral. Other widely used synonyms are vasovagal syncope or “simple fainting.” Although many individuals will experience syncope at least once during their lifetime (estimated 30 % lifetime risk), it is usually self-limited and benign. Rarely, it may be the first warning sign of a serious condition including arrhythmia, structural heart disease, or noncardiac disease (Table 17.1). Patients with recurrent syncopal episodes, syncope during exercise, emotion/stress-induced syncope, syncope resulting in injury, syncope in the driving-age pediatric patient, syncope in those with a family history of hypertrophic cardiomyopathy or a channelopathy, or syncope in patients with congenital heart disease require investigation. Recurrent syncope may cause a major impact on lifestyle, interfering with school and/or sports. Many states impose driving restrictions following syncope. This chapter presents a differential diagnosis (Table 17.1) of syncope in children, outlines in detail neurocardiogenic or neurally mediated syncope (NCS, NMS), and reviews different evaluation and treatment strategies.

Table 17.1 Differential diagnosis of syncope

Diagnostic Evaluation

Given the many possible causes of syncope, the diagnostic evaluation can be quite involved and expensive and the specific etiology may never be determined. Therefore, a carefully planned approach rather than a “shotgun” diagnostic strategy is important. The patient history, family history, physical examination, and an electrocardiogram are fundamental and direct the remainder of the evaluation. Table 17.2 details the components of a comprehensive syncope evaluation. The patient history is the cornerstone on which the syncope evaluation is constructed and the diagnosis depends; it is often, along with the physical examination and an ECG, all that is necessary. Important historical details from the patient include: the age of the patient (syncope is rare before 10 years of age except for breath-holding spells in the toddler), time of day of the event (early morning is typical), the state of hydration and nutrition at the time of the event (when last had fluid or food intake), the environmental conditions (i.e., ambient temperature), the patient’s activity or body position immediately prior to the syncopal episode, the frequency and duration of the episodes, and any aura, prodrome, or specific symptoms and signs prior to the episode. Witnesses, if available, should provide details regarding the patient’s condition prior to the syncope, duration of loss of consciousness, any injuries or seizure-like movements, heart rate during episode (rarely available), and duration and nature of recovery (often patients are sleepy after neurocardiogenic syncope (NCS)). Medications (prescriptions and/or over-the-counter) used by the patient are critical historical points particularly regarding proarrhythmic agents such as QT prolonging medications. Information regarding prior diagnostic reports and/or consultations can prevent duplicate testing.

Table 17.2 Syncope evaluation

Family history is vital in the evaluation of syncope. It is not uncommon to find a history of multiple family members who experienced syncope during adolescence. Many of the older family members may also report a history of low blood pressure, and many families limit salt due to a hypertensive family member who is on a salt-restricted diet. However, if the family history is positive for recurrent syncope, it is also important to consider other familial disorders by specific questioning about the presence of hypertrophic or dilated cardiomyopathy, long QT syndrome (and other ion channelopathies), primary pulmonary hypertension, or arrhythmogenic right ventricular dysplasia. Families should be queried regarding sudden unexplained death in children or young adults (i.e., drownings, sudden cardiac death, sudden infant death syndrome, and car accidents), seizures, or familial congenital deafness (Table 17.2). Noting the person or source providing the family history and an estimate of its reliability can be of future use; it may be helpful to request further details from additional family members, particularly if a genetic disorder is suspected. A genetic counselor can be invaluable in helping to sort out the family history.

During the patient examination, orthostatic vital signs (magnitude of decrease in blood pressure relative to change from supine to erect position and heart rate changes) should be obtained. Many patients will manifest a mild (up to a 30 mmHg drop in blood pressure) but asymptomatic orthostatic change with upright positioning. An ECG should be obtained on every patient who experiences syncope, particularly if it is recurrent, occurs with exercise, and is not associated with the characteristic symptoms of NCS. The ECG should be evaluated for heart rate, corrected QT interval (gender-related), T-wave morphologic changes (persistent so-called juvenile T waves in the older adolescent), T-wave alternans, or any ventricular arrhythmia. The ECG should also be evaluated for ventricular preexcitation syndromes, atrioventricular (AV) conduction, or features of Brugada syndrome (see Chaps. 4, 13–15, 18).

For the infrequent patient whose evaluation lacks internal consistency, other studies may be advisable, such as echocardiography to examine for cardiomyopathy, myocarditis, anomalous coronary arteries, pulmonary arterial hypertension, or arrhythmogenic right ventricular dysplasia. A rare patient may warrant cardiac catheterization, including hemodynamic, angiographic, and electrophysiologic evaluation, along with right ventricular endomyocardial biopsy, to exclude potential structural, functional, and arrhythmic abnormalities, particularly before clearance to resume activities.

NCS: Simple Fainting, Vasovagal Syncope

Pathophysiology

The pathophysiologic mechanisms underlying NCS are complex, likely heterogeneous, and not completely understood. However, one major hypothesis invokes a cardiac-central nervous system reflex (Fig. 17.1). The most common initiating event is prolonged (or the abrupt assumption of) upright position (sitting or standing), which subjects the patient to gravitationally mediated venous pooling in the lower extremities and pelvis. This causes an abrupt central hypovolemia (compared to the immediate preexisting state), leading to a decrease in venous return and stroke volume. In addition, an emotional or physical stress (e.g., pain or fright) or a reflex mechanism related to hair grooming, glutition (swallowing), or micturation may initiate this sequence by stimulating a reflex increase in sympathetic output manifested as tachycardia and vasoconstriction along with an increase in ventricular contractility. Activation of C-fiber mechanoreceptors increases afferent neural traffic to the central nervous system (medulla), stimulating the brain-stem motor center and causing several and often combined possible responses, such as the following: (1) an increase in parasympathetic activity, causing profound bradycardia or asystole; (2) a sympathetic withdrawal resulting in peripheral vasodilatation (venous and arterial), a decrease in systemic blood pressure, and decrease in heart rate; and (3) an increase in serotonin concentration, also resulting in peripheral vasodilatation and marked decrease in the systemic blood pressure. This sequence of events is one hypothesis, but it does not account for all the observed complex and integrated interaction between the neurohumoral traffic and the cardiovascular responses, additionally confounded by age and comorbidity.

Fig. 17.1

Algorithm of one possible mechanism for neurocardiac syncope [Reprinted from Strieper MJ. Distinguishing benign syncope from life threatening cardiac causes of syncope. Semin Pediatr Neurol 2005;12:32–38. With permission from Elsevier]

As a result of the loss of consciousness, postural tone and the upright state, the patient falls to a supine position restoring venous return and the central circulating blood volume (i.e., heart and lungs) followed by rapid normalization of blood pressure and heart rate. The loss of consciousness is usually short (generally ≤1–2 min). Excretory incontinence is uncommon. Seizures rarely occur as a result of the sudden prolonged decrease in cerebral perfusion. During recovery, return to sentience is rapid but post-event fatigue is common.

Clinical Presentation: NCS–NMS and Other Considerations

A prodrome lasting from several seconds to 1–2 min and consisting of nausea, epigastric discomfort, a clammy and cold sweat, pallor, dizziness, lightheadedness, tunnel vision, headache, and weakness is highly characteristic and strongly suggests simple fainting, vasovagal or neurocardiogenic syncope. If the prodrome is of sufficient duration, patients may learn to recognize their symptoms and lie down to relieve the symptoms and prevent syncope. Some patients with profound bradycardia or asystole may have little or no prodrome, causing a sudden loss of consciousness that may result in injury. Absence of a significant prodrome also raises the possibility of structural, functional, or arrhythmic causes for syncope. On the other hand, palpitations, chest discomfort, and a sudden loss of consciousness as well as a prompt recovery are more compatible with an isolated cardiac event. Other symptoms such as atypical precordial chest pain or tightness in the chest, breathlessness, acrocyanosis, tingling in the hands or feet, and a sense of alarm or anxiety are compatible with hyperventilation and a “panic attack.”

If “seizures” (tonic-clonic movements) occur as a result of cerebral hypoperfusion and anoxia, the patient can be confused as having a primary neurologic abnormality. Formal neurologic consultation and neurologic testing should be considered if seizures are part of the presentation. Interestingly, longstanding complaints of intermittent abdominal pain and nausea, most likely due to a profound increase in vagal tone, constitute an unusual and rarely suspected presentation of NCS. This symptom complex, as a manifestation of NCS, may be associated with a positive head-up tilt (HUT) evaluation, and may respond favorably to NCS treatment. In addition, there may be a link between NCS and chronic fatigue syndrome, which also has findings of hypotension, headaches, and postexertional fatigue. However, it is unlikely that an otherwise healthy preadolescent child or adolescent would exhibit the chronic fatigue syndrome.

Patients who present with syncope during exercise are also a challenge. Gradual loss of consciousness, associated with a pre-syncopal prodrome and occurring as the exercise is reaching its completion and the exerciser is in an exhausted state at the finish after maximal effort suggests the possibility of exercise-induced NCS, provoked by preexisting unrecognized dehydration, exercise-induced catecholamine-enhanced ventricular contractility, a sudden decrease at the end of exercise in the peripheral blood flow from the vasodilated skeletal muscle vasculature and cerebral vasoconstriction (induced by the respiratory alkalosis of the exercise-related hyperventilation) producing a decrease in cerebral blood flow at that critical moment and syncope. On the other hand, sudden syncope during exercise and without prodrome raises the suspicion for a more serious underlying cardiac structural or functional cause, including arrhythmias, and warrants further investigation.

Postural orthostatic tachycardia syndrome (POTS) has been described as a specific variation of NCS, usually in older adolescents and adults but may occur in children as well. Most of these patients present with symptoms of rapid palpitations suggesting a primary tachycardia, but on further questioning, also have associated symptoms suggesting low blood pressure (BP) including dizziness and lightheadedness. Hyperthyroidism can present in this manner. When this clinical situation presents, ECG and BP monitoring should be performed to evaluate for primary tachycardia. Sinus tachycardia (130–160 bpm) during a symptomatic hypotensive phase strongly supports the diagnosis of POTS and helps to exclude primary tachycardia. Treatment is directed towards prevention of venous pooling and intravascular volume depletion.

Breath-holding spells most likely represent a variation of NCS in the small child. These spells generally occur in young children between the ages of 12 months and 4 years of age. As a result of painful stimuli or emotional upset, these episodes usually begin with crying which escalates. Breath holding generally occurs during expiration which can cause hypoxemia (inducing hypoxemic syncope) and a decrease in venous return (provoking the NCS reflex). Evaluation with continuous ECG monitoring generally reveals significant bradycardia or prolonged asystole (10–15 s) (Fig. 17.2). With loss of consciousness, spontaneous respirations resume and the patient generally shows a rapid return to full consciousness with normalization of heart rate. Although there is no proven treatment for breath-holding spells, which generally resolve spontaneously with age, a trial of anticholinergic agents (belladonna) along with parental counseling may reduce their recurrence.

Fig. 17.2

Breath-holding spell in 11-month-old boy. Note tachycardia followed by abrupt asystole

Another clinical entity, usually occurring in the toddler, is the reflex anoxic seizures, caused by sudden asystole, without breath holding. Detection is difficult because of the abrupt onset and immediate recovery; the event may be limited to a sudden “face plant” followed by prompt recovery. An implanted loop recorder can be diagnostic. These patients may respond to permanent pacing or vagolytic therapy.

Vocal cord dysfunction, often associated with and mistaken for asthma attack, can present with shortness of breath dyspnea, wheezing, coughing, tightness in the throat, skin discoloration due to oxygen deprivation, noise during inhalation stridor, and in severe cases, loss of consciousness. Due to the difficulty and delay in diagnosis, considerable anxiety often accompanies the patient’s symptom complex further confounding the origin of the syncope. Diagnosis is dependent upon laryngoscopic exam during an episode.

Other clinical triggers highly consistent with NCS are syncope during hair combing, micturition, deglutition, Valsalva maneuvers, hot morning showers, or blood drawing or donation (even if lying horizontal). Even a cough and laughter have been identified as triggers for NCS.

A “stressful” milieu is often in the background of 20–25 % patients with recurrent syncope. It is often prudent to introduce the notion of stress-related factors early in the patient evaluation, thereby introducing the possibility that psychiatric issues may be involved. Several findings may suggest the presence of a psychiatric role in the genesis of “syncope.” First, patients who experience the onset of syncope in the supine position [excluding a strong physical provocative stress (phlebotomy, donating blood, dental tooth extraction, or simple suturing of a laceration) or an arrhythmia] may have a psychiatric cause. Second, patients with psychiatric issues do not often rapidly recover from their loss of consciousness even after resuming the supine position. Third, the syncope is frequently prolonged with waxing and waning levels of consciousness and by witnessed accounts often up to several hours. Finally, there is a marked indifference to syncope and its ramifications. These patients often experience a conversion reaction, “lose consciousness” but maintain blood pressure and heart rate during the HUT table test. This HUT finding is important, since the patient-specific diagnosis directs the appropriate recommendations.

A variant of NCS may result in an extensive multisystem (presumably mediated through the autonomic nervous system) symptom complex of repeated vague, “blacking out” episodes (often brief and not associated with a total loss of consciousness), nausea (even vomiting), alarm, profound fatigue, and clinical depression. The patient, usually an adolescent, is often described as a high achiever in school, athletics, or the arts who suddenly becomes dysfunctional with the full spectrum of profound dysautonomia. This broad array of symptoms suggests the possibility of a generalized “autonomic instability” in some patients expressed through a number of organ systems and may benefit from consultation with a mental health provider. It may be related to the chronic fatigue syndrome.

HUT Table Test: Indications

Current indications for a HUT table test include: (1) recurrent unexplained syncope with no evidence by exam, or ECG, for a structural or arrhythmia abnormality; (2) syncope resulting in injury; (3) exercise-induced syncope if atypical; (4) syncope in the driving-age patient; (5) recurrent troublesome pre-syncope causing severe patient incapacitation that interferes with the events of daily living; or (6) failed empiric treatment for NCS. Syncope that is characterized by a typical history, is infrequent, and is not associated with injury or a potentially adverse event (driving a car, exercise) does not require confirmation by a HUT test.

HUT Protocol

A number of HUT protocols have been advanced. The basic principle in HUT is a passive head-up tilt at an angle of 60–80° for 20–60 min or until hypotension, bradycardia, pre-syncope, syncope, or clinical symptoms are reproduced or the time has ended (Fig. 17.3). A continuous noninvasive digital arterial pulse waveform is useful to allow uninterrupted recording of noninvasive beat-to-beat representation of the arterial pressure during the HUT test (Fig. 17.3a). The use of automated or manual blood pressure recordings is less optimal during the presence of HUT-induced hypotension.

Fig. 17.3

(a) Finapres monitor for continuous heart rate and noninvasive blood pressure measurement. (b) The patient positioned supine on the tilt table with EKG and blood pressure monitor. (c) Tilt to 80° upright position, with “seat belt” restraint

If this baseline HUT is negative (no symptoms, no hypotension or bradycardia), various medications including isoproterenol, sublingual nitrates, or intravenous clomipramine can be used to induce an end point during a repeat HUT. Once medication is administered the patient is again tilted for the defined time or until a positive HUT response occurs.

There are three positive HUT NCS clinical responses (Fig. 17.4). The first clinical response is the patients with a mixed hypotensive and bradycardic response, defined as a ≥50 % decrease in mean arterial pressure and a ≥50 % decrease from the maximum heart rate during HUT testing. This represents approximately 50 % of the positive HUT responses. Second, a cardioinhibitory response is defined as sudden severe bradycardia or asystole, which occurs in approximately 5–10 % of HUT positive patients; a widely used classification system divides this group into two forms, based on length of impulse pause (Figs. 17.4 and 17.5). Finally, vasodepressor response, defined as a ≥50 % decrease in mean arterial blood pressure, often with preservation of the heart rate or only a mild increase in heart rate. This represents approximately 40 % of positive tilt table responses.

Fig. 17.4

Classification of positive responses to title-test [Reprinted from Nowak L, et.al. Investigation of various types of neurocardiogenic response to head-up tilting by extended hemodynamic and neurohumoral monitoring. Pacing and Clinical Electrophysiology 2007;30(5):623–630. With permission from John Wiley & Sons]

Fig. 17.5

Cardioinhibitory response in 15-year-old girl after 4 min of HUT—13 s asystole. Note the slowing of the heart rate before asystole (paper speed 12.5 mm/s)

These clinical responses are not necessarily patient specific nor are they necessarily reproducible; there could be considerable variation day-to-day and HUT-to-HUT, with different responses expressed at different times.

Although the HUT test is regarded in some quarters as the “gold standard” for NCS diagnosis, it should be noted that it is only a supportive test, confirming the clinical history. HUT engages a complex physiologic neural-humoral-cardiovascular reflex response with a highly provocative and exaggerated physiologic stress in individuals who may or may not be particularly vulnerable to this stress. HUT is most useful when clinical symptoms and significant hypotension and/or bradycardia are reproduced during the episode. Only then can this test be interpreted as truly positive. False positive HUT responses can occur, when patients experience hypotension or bradycardia but the clinical symptoms are not exactly reproduced. Negative HUT responses may represent either a true negative (patient does not suffer from NCS) or a false negative (patient is NCS positive, but HUT negative). It is not possible at this time to distinguish clinically false negative results from true negative HUT results. There is no widely accepted standard HUT protocol. Considerable variation in tilt angle, duration of tilt, and monitoring exists between centers. This lack of a standard protocol confounds the interpretation of HUT responses between centers. Sensitivity and specificity for HUT test parameters is by report variable and limited data regarding sensitivity and specificity in pediatric patients are available.

Implantable Loop Recorders

Patients that present a diagnostic dilemma with infrequent episodes may benefit from having an implantable loop recorder (ILR) placed. The ILR can correlate EKG findings with the symptoms. ILRs have not been studied systematically in the pediatric population; however, the adult literature reports that after 2 years there was a probability of diagnosis in about 50 % of adults that had ILRs implanted with most diagnoses being bradycardia. Newer (2014) ILRs have increased miniaturization and longer implanted life (3 years) and thus increase their usefulness in ambiguous cases. However, because of the required surgery and resultant permanent scar, placement of an ILR in a child should be limited to patients in whom a life-threatening outcome is a valid possibility.

NCS Treatment

The purpose of treatment for NCS is to prevent recurrent syncope. Additionally, pre-syncopal symptoms may also be eliminated. However efforts to eliminate all pre-syncopal symptoms are often associated with drug side effects and the use of multiple medications. There are only limited randomized treatment trials for pediatric patients. The opinion that any treatment for pediatric syncope patients is better than no treatment has not been established. Additionally, NCS in the young almost always resolves spontaneously within several months to years after onset. Apparent therapeutic drug efficacy may simply represent spontaneous resolution of NCS. Occurrences of syncopal episodes are unpredictable and some patients may be event free for months to years or longer. Therefore, duration of treatment and assessment of drug effect is further confounded. A daily diary to record syncope and pre-syncopal episodes may help when evaluating symptoms both before and after treatment.

Volume Expansion

Maintaining adequate intravascular volume is the foundation for the treatment of NCS. Patients are instructed to avoid caffeinated beverages (due to the renal diuretic effect), but any and all other fluids are encouraged. Specially, liquid such as “sport drinks” with additional sodium are preferable for maintaining hydration. Up to 60–120 oz a day are recommended for adolescents. Reusable plastic 16 oz. bottles should be part of the young person’s backpack; he or she be allowed access to it at all times including school. Frequent “swigs” each hour from the bottle are encouraged. Salt tablets may be prescribed, but they are relatively large, difficult to swallow, and will frequently cause nausea. Alternatively, patients are encouraged to liberally use salt with meals and eat nonfatty salted snacks (i.e., pretzels, salted nuts, and salted popcorn without butter).

Although fluid administration alone helps to alleviate symptoms, it may not alone be adequate to prevent most patient symptoms or recurrent syncope. However, drug therapy alone, in the absence of adequate of intravascular volume, is rarely as effective as when combined with good hydration.

Counter Maneuvers

Some simple patient physical maneuvers may help to ameliorate or abort pre-syncopal symptoms or syncope. These maneuvers generally involve exercising the muscles of the leg (leg pumping and tensioning, leg crossing, squatting, elevation of the legs above the level of the heart). A recent study demonstrated a therapeutic effect with isometric handgrip to abort impending NCS by increasing systemic blood pressure. These simple maneuvers can be taught to even young children. However, it is important that these patients have an adequate prodrome to allow them time to perform the maneuvers prior to the onset of true syncope. The possible beneficial effects of conditioning by using prolonged exposure to the upright position in pediatric NCS patients are often stymied by lack of patient compliance due to the time required for appropriate conditioning.

Medications

Fludrocortisone

Florinef (fludrocortisone) has several effects. It increases intravascular volume and sodium, often at the expense of an increased urinary loss of potassium. It also may augment the peripheral effects of catecholamines, leading to both venous and/or arterial vasoconstriction. Together with adequate intravascular volume through the use of oral hydration, significant decrease in venous return may not occur and NCS may be prevented. Florinef has been demonstrated to produce a positive therapeutic response in a non-blinded pediatric population, and fludrocortisone acetate and beta-blocker treatment (for pediatric NCS) have been found to be equally effective. Florinef is generally well tolerated with a low incidence of side effects. Monitoring for hypokalemia, as a result of increased urinary loss, is important. When receiving Florinef and alpha agonist medications, patients must be monitored for the onset of hypertension, due to the combined vasoconstrictive effects.

Alpha Agonist Agents

Alpha agonist agents work through their vasoconstrictor effects; venoconstriction helps to maintain ventricular volume, while arterial constriction offsets the hypotensive response. Acute intravenous phenylephrine hydrochloride is effective in pediatric patients for blocking NCS responses on follow-up HUT, after an initial positive HUT. Midodrine stimulates the alpha-1-adrenergic receptors and together with adequate hydration strategies, is often an effective treatment for NCS. Up to 75–80 % of HUT positive patients may respond to this treatment, with complete elimination of recurrent syncope and either improvement in or elimination of pre-syncopal symptoms. Patients who fail with this treatment are treated concomitantly with Florinef. Together these two medications may provide up to 85–90 % control for tilt positive pediatric patients. Patients on Midodrine should be monitored for supine hypertension. The medication is usually given three times during the day at q 6 h intervals; it should be taken in the early morning, noon, and early evening to prevent the occurrence of supine hypertension. Compliance is an issue with a medication needing frequent dosing.

Beta-Blockers

Beta-blockers were one of the first drug treatment options described for NCS. These medications operate through several mechanisms, including block of sympathetically mediated increase in ventricular contractility and activation of the C-fibers, and also by prevention of sympathetically mediated arterial vasodilatation. Some patients may manifest side effects, which may mask the therapeutic benefits or aggravate the pre-syncopal symptoms. Care should be taken when using this agent with patients who suffer from POTS, since block of the compensatory sinus tachycardia may actually worsen the patient’s clinical status, causing syncope. They should be prescribed in low doses and titrated to an effective dose as necessary.

Disopyramide

Disopyramide, an antiarrhythmic agent, has been employed as a third-line NCS treatment. Data suggest several mechanistic actions, including peripheral anticholinergic effect (to combat bradycardia), negative inotropic properties (preventing activation of the C-fibers), and smooth muscle vasoconstriction, preventing both venous and arterial vasodilatation. Despite the concern for possible drug side effects, specifically pro-arrhythmia, this drug is generally tolerated quite well by pediatric patients and may prove effective when other agents fail.

Anticholinergic Agents

This drug group may be most effective for patients who manifest profound parasympathetic-driven bradycardia or asystole or a parasympathetic component to peripheral arterial vasodilatation leading to hypotension. Even when effective, pronounced drug side effects including dry mouth, urinary retention, constipation, and visual blurring often make long-term treatment with these drugs intolerable. A recent study has demonstrated a possible therapeutic benefit with the use of glycopyrrolate for breath-holding spells in young infants.

Serotonin Reuptake Inhibitors

Because serotonin may lead to vasodilatation, promoting a vasodepressor or mixed NCS clinical response, serotonin reuptake inhibitors (SSRIs) have been advocated by some for the treatment of drug refractory NCS. The mechanism of action is still uncertain, although it has been speculated that these agents may desensitize central serotonin receptors or decrease serotonin release to the peripheral circulation. These drugs may also be applicable for patient subsets when anxiety or emotional upset triggers the NCS episode or in whom the emotional response to recurrent syncope is also problematic clinically. They also may be useful for the individual who expresses the severe form with profound fatigue and clinical depression. Patients with this degree of disability are best managed in consultation with a physician (psychiatrist) with experience with these medications.

Pacemaker Therapy

While initially thought to be an ideal therapy for patients with predominant bradycardia or asystole, many centers have learned that pacing alone is often ineffective in preventing all episodes of NCS. Many patients, although adequately paced, will still be symptomatic as a result of vasodepression and hypotension. Patients with asystolic HUT responses can often be managed effectively with medications, obviating the need for pacemaker therapy. Since medical therapy generally will prevent recurrent syncope, and NCS is often self-limited, the decision to implant a permanent pacemaker should be the last resort, especially in a young person.

Prognosis

Most patients have spontaneous resolution of their NCS syncope and pre-syncope in 6–12 months following onset of episodes. Based on our experience, 5–10 % of NCS patients will have symptoms over an extended period of time, often 3–5 years. The reasons for these differing clinical courses are unknown.

A special concern with NCS is the driving-age patient. Even following diagnosis of NCS as the definite cause of the patient’s syncope, and the institution of effective therapy, these patients should be restricted from driving for at least 2–4 months. Different states have guidelines about restrictions from driving for patients with different medical issues, including seizure disorders, life-threatening arrhythmias, and syncope. It is important to be certain that a definite diagnosis has been made and that treatment has proven effective before the patient can safely return to driving. Physicians involved in care of these patients should give written instructions regarding driving restrictions, and specifically document these restrictions in detail in the patient’s chart.

Conclusion

Syncope is a common clinical event. An organized, detailed approach to diagnosis, with particularly close attention paid to the details of the history, is most likely to result in a time and cost-effective evaluation. To optimally define treatment, restrictions, and prognosis, patient-specific diagnosis is important. Although NCS is the most common cause of pediatric syncope, potentially life-threatening etiologies must not be overlooked.