Clinical Approach to Syncope in Children

Manikum Moodley, MBChB, FRCP

Pediatric syncope is one of the most common neurological problems in the pediatric population in both the ofce setting and in the emergency department. The abrupt brief loss of consciousness is usually dramatic and alarming to patients, family, onlookers, and providers. The differential diagnosis of syncope is wide but most cases are benign. A comprehensive but focused history and a thorough clinical examination are usually the cornerstones in the diagnosis of high-risk patients. It should be noted that the evaluation of syncope in children is costly and testing provides a low diagnostic yield. This chapter reviews the various types of syncope and provides a succinct clinical approach to the diagnosis, investigation, and management of syncope in children. Semin Pediatr Neurol 20:12-17 C 2013 Elsevier Inc. All rights reserved.

Introduction
Syncope is dened as the abrupt loss of consciousness and postural tone resulting from transient global cerebral hypoperfusion followed by spontaneous complete recovery.1 Presyncope is the feeling that one is about to pass out but remains conscious with a transient loss of postural tone.2 In the young patient, syncope often results from a fall in systolic pressure below 70 mmHg or a mean arterial pressure of 30-40 mmHg.3,4 The syncopal event is typically preceded by a prodrome lasting from several seconds to 1-2 minutes characterized by distinctive premonitory features such as nausea, epigastric discomfort, blurred or tunnel vision, mufed hearing, dizziness, light-headedness, diaphoresis, hyperventilation, palpitations, pallor, cold and clammy skin, or weakness.4 These symptoms may occur in any combination or be variably present in any given patient from 1 episode to the next.4 Most cases of pediatric syncope are benign but an evaluation must exclude a rare life-threatening cardiac or noncardiac disorder. Furthermore, the term syncope may have different meanings to different people, therefore specic questions should be asked to help differentiate cardiac from neurologic, psychogenic, and metabolic conditions.

Epidemiology
Syncope is a common pediatric problem, affecting 15%25% of the children and adolescents.4 The incidence peaks between the ages of 15 and 19 years for both sexes but there appears to be a female predominance.5 Before age 6, syncope is unusual except in the setting of seizures, breathholding spells, and cardiac arrythmias.1 In contrast to adults, neurocardiogenic syncope or vasovagal syncope or vasodepressor syncope is the most frequent cause of pediatric syncope (61%-80%).6 Syncope secondary to orthostatic hypotension is frequent in the very old but rare in individuals less than 40 years of age.7 The recurrence rate of syncope ranges from 33%-51% when patients are followed for up to 5 years.4

Etiology
A detailed history of the event followed by a comprehensive physical examination will help in categorizing syncope into the 3 major categories: (a) Neurally mediated syncope (b) Cardiovascular mediated syncope (c) Noncardiovascular syncope. Neurally mediated syncope and cardiovascularmediated syncope, each accounts for about 50% of the cases of syncope in adults but in children cardiovascular-mediated syncope is less frequent than it is in adults.8 The differential diagnosis of syncope is given in Table 1.

From the Center for Pediatric Neurology, Neurological Institute, Cleveland Clinic Foundation, Cleveland, OH. Address reprint requests to Manikum Moodley, MBChB, FRCP, Center for Pediatric Neurology, Neurological Institute, Cleveland Clinic Foundation, 9500 Euclid Ave/ S60, Cleveland, OH 44195. E-mail: moodlem@ccf.org

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1071-9091/11/$-see front matter & 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.spen.2012.12.003

Clinical approach to syncope in children

Table 1 Differential Diagnosis of Pediatric Syncope*
       

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Table 3 Cardiovascular Causes of Syncope*
K

Cardiovascular mediated syncope Neurocardiogenic syncope (vasodepressor vasovagal) Orthostatic hypotension Postural orthostatic tachycardia syndrome (POTS) Convulsive syncope Reex syncope Psychogenic syncope/ panic attacks/ hyperventilation Situational syncope J Coughing J Sneezing J Micturition J Defecation J Deglutition (cold liquids) J Hair grooming J Trumpet playing J Suffocation J Weight lifting J Diving J Stretching  Drug and toxin induced  Metabolic J Hypoglycemia J Electrolyte disorder J Endocrine disorder
*Modied and reprinted with permission.4

Arrhythmias Complete heart block Sick sinus syndrome Tachyarrhythmias: J Supraventricular (Wolff-Parkinson-Whitesyndrome) J Ventricular Ion channel abnormalities J Long QT syndrome (congenital or drug induced) J Brugada syndrome Arrhythmogenic right ventricular disease Cardiacstructural Valvular aortic stenosis Hypertrophic obstructive cardiomyopathy Coronary artery anomalies Primary pulmonary hypertension Eisenmenger syndrome Mitral valve prolapse Neuromuscular disorders Cardiac tumors

*Modied and reprinted with permission.4

Clinical Features
The diagnosis of syncope rests mainly on clinical grounds but the lack of objective ndings in pediatric syncope often poses a challenge to caregivers. A thorough history with a detailed physical examination and electrocardiography (EKG) have a combined diagnostic yield of about 50%.3 A detailed history should include the time of day, time of last meal, activities leading up to the event, and associated symptoms such as light-headedness, dizziness, palpitations, chest pain, headache, shortness of breath, nausea, pallor, diaphoresis, visual changes, and auditory changes. When these clinical features are present, they help to differentiate syncope from epilepsy.4 A detailed history usually reveals contributory environmental factors before the syncopal events (upright posture, prolonged standing, change in posture, crowding, heat, fatigue, hunger, or a concurrent illness).9 The loss of consciousness is usually brief, lasting from a few seconds to 1-2 minutes, followed by rapid spontaneous recovery without neurologic decits.4 During the episode the patient may have tonic posturing or a brief clonic seizure, rarely associated with urinary incontinence. In addition to the pertinent medical history, a family history of familial heart disease, congenital heart disease, metabolic disease, medication history, pregnancy, and psychiatric history should be gathered. Distinguishing between neurocardiogenic syncope and seizures is the most common clinical dilemma faced by care providers, whereas, in distinguishing patients with syncope due to cardiac causes a history and physical examination can be 95% sensitive for a cardiac etiology.10 Patients with pseudosyncope and pseudoseizures typically use the events consciously or unconsciously to avoid an unpleasant emotional situation.11 Most of these patients are females with a very high number of events, orid symptomatology, and

Cardiovascular-mediated syncope Cardiovascular-mediated syncope has a higher mortality and higher incidence of sudden death than neurally mediated syncope.4 A detailed cardiac history is, therefore, of paramount importance and red ags in the history that signal a need for an urgent pediatric cardiology referral are given in Table 2. Cardiovascular causes of syncope in children are given in Table 3. Neurocardiogenic syncope Neurocardiogenic syncope, previously known as vasodepressor, vasovagal, or neurally mediated syncope, is the most common cause of syncope. The history that suggests this type of benign syncope includes triggers such as postural changes, prolonged standing or sitting, obnoxious stimuli (anger, pain, sight of blood), and a positive family history is often elicited.

Table 2 History of Red Flags Requiring Urgent Referral to Pediatric Cardiology

 History of heart murmur or congenital heart disease  Acute attacks associated with hyperpnea or cyanosis  Syncope during exercise, including swimming or with

exertion
 Family history of early sudden cardiac death, long QT

syndrome, sensorineural hearing loss, familial heart disease  Medications that can result in long QT syndrome, arrhythmias  Absence of usual premonitory symptoms or precipitating factors associated with neurally mediated syncope  Unusual syncope triggers such as loud noises, fright, or extreme emotional stress

14 episodes without injury. Hyperventilation and conversion syncope commonly occur in adolescents, usually in a highly emotional setting. Both these conditions are rare in children younger than 10 years of age. Unlike typical syncopal episodes, conversion syncope is not posture dependent and the recovery is often prolonged lasting up to an hour.12 In true syncope, consciousness returns within 1 minute of lying down, and unconsciousness for more than 5 minutes is rare.11 In general, a detailed physical examination of patients with syncope is normal. However, the physical examination should be focused to rule out serious cardiac and neurologic causes of syncope, and should also include orthostatic vital signs, search for neurocutaneous lesions, and physical features associated with cardiac disease (dysmorphic facial features, Marfan syndrome, and Ehlers-Danlos phenotype, deafness etc).12

M. Moodley
Table 4 Key Elements in the History of Pediatric Syncope* Patient  Hydration status  Environmental conditions  Activity immediately before syncopal event  Frequency and duration of the episode  Historical data from witnesses  Complete drug history  Exercise induced syncope  Menstrual history Family  History of syncope or cardiac disease  Sudden unexplained death in children or young adults  Family history of seizures  Familial deafness  Pacemaker placement
*Modied and reprinted with permission.4

Diagnostic Evaluation
A detailed history, a comprehensive yet focused clinical examination and an EKG have a combined diagnostic yield of 50%.3 The patient history is the cornerstone on which the diagnosis of syncope is made.4 The key historical elements to be elicited from patients presenting with syncope are given in Table 4. Diagnostic evaluation should include an EKG on all patients with syncope, especially if it occurs with exercise or is recurrent. All patients with risk factors for cardiac disease should be referred to cardiology for further evaluation. These may include performing echocardiography or usage of Holter or event monitor. Rarely cardiac catheterization with right ventricular endomyocardial biopsy may be necessary before a patient can resume activities.13 Electroencephalography, neuroimaging studies, and autonomic function testing (Tilt table, quantitative sudomotor axon reex test) may be indicated with specic neurologic ndings. See Table 5 for a simple diagnostic evaluation of pediatric syncope. The history and physical examination will guide practitioners in choosing the diagnostic studies that apply to a given patient. Details on the laboratory evaluation of syncope are discussed elsewhere in this issue by Drs Kuntz and Patwari. Figure 1 gives a user-friendly emergency department approach to pediatric syncope.

who had recurrent syncope, tilt table testing at 801 for 30 minutes was superior to other studies, such as EKG, echocardiogram, electroencephalography, or neuroimaging in arriving at a diagnosis of neurocardiogenic syncope.4,16 The tilt table test has been used in children as young as 3 years of age.17 However, tilt table testing for neurocardiogenic syncope in children is relatively new. More controlled studies and standardization of degree and duration of tilting are necessary to validate the tilt table test as a safe, practical, and useful diagnostic tool for neurocardiogenic syncope in children.18-21 As syncope is a relatively common presentation in children and the etiology is diverse including seizures, pseudosyncope, and metabolic disorders, the evaluation may result in unnecessary and costly investigations.22 Despite exhaustive testing, more than 40% of the patients with recurrent syncope do not receive a specic diagnosis.17,23
Table 5 Diagnostic Evaluation of Pediatric Syncope
1. Hematologicalbiochemical  CBC  Serum iron, TIBC, ferritin  CMP 2. Cardiac evaluation  EKG  Echocardiography  Holter or event monitor. 3. Autonomic evaluation  Neurocardio autonomic reex testing with and with-

Tilt Table Testing

The head-up tilt table test as a potential diagnostic tool for neurocardiogenic syncope was only introduced in 1986 after the ground breaking report by Kenny et al.14 Since then several reports have emerged attesting to the utility of this test in reproducing syncopal episodes in patients who are predisposed to neurocardiogenic syncope. The test is done by positioning the head of the patient upright at an angle of 601-801 for 15-60 minutes on a tilt table with a supporting footboard. A tilt table test result is positive when the symptoms of syncope or presyncope are reproduced.4,15 Experience with tilt table testing among pediatric populations is limited. Among 54 pediatric patients

out tilt table testing Quantitative sudomotor axon reex test (QSART) Thermoregulatory sweat test (TST). 4. Miscellaneous  Urine specic gravity  Urinary sodium levels  Pregnancy test in all menstruating females.
 
EEG, CT, and MRI of the brain are not recommended unless the loss of consciousness is suspected not to be syncope. CBC, complete blood count; CMP, complete metabolic panel; TIBC, total iron binding capacity

Clinical approach to syncope in children

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Figure 1

Treatment
The objective of treatment for neurocardiogenic syncope is to prevent recurrent syncope which leads to impaired quality of life, psychological distress, and substantial morbidity including frequent absence from school. The mainstay of treatment of neurocardiogenic syncope is education and counseling of the patient and his or her parents.4 The benign nature of these events should be explained to the patient and the parents and they should be reassured that these episodes would not result in epilepsy or sudden death. Neurocardiogenic syncope almost always resolves within months to about 5 years after onset.4,13 Patients should be encouraged to maintain adequate

hydration and enhance dietary salt intake. Patients should learn to recognize and avoid triggers and situations inducing syncope. If the patients are on hypotensive medication, then they should be modied or discontinued. Table 6 outlines the nonpharmacologic treatment of neurocardiogenic syncope. If despite these conservative measures the syncopal episodes become refractory, pharmacologic therapy may be tried. A wide variety of pharmacologic agents are currently used for the prevention of recurrent neurocardiogenic syncope in children and adolescents. At the present time, b-adrenergic antagonists, udrocortisone, and midodrine, an alpha adrenergic receptor agonist, are often prescribed in children.24 None of these agents, however,

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Table 6 Nonpharmacologic Treatment of Neurocardiogenic Syncope*
 Education, counseling and reassurance  Avoid precipitating or triggering factors  Increase water and salt intake  1.5-2.5 L of water daily  At least 2-5 g of salt daily  Isometric counter pressure maneuvers  Leg crossing  Buttock tensing  Squatting  Head-up sleeping  Abdominal binders, thigh-high or below knee elastic

M. Moodley
within the rst year after onset; 5%-10% would, however, continue to show symptoms over an extended period of time, often up to 5 years.4,13

Other Types of Syncope

Convulsive Syncope Occasionally a brief tonic or rarely a clonic, tonic-clonic, or myoclonic seizure may accompany a syncopal episode (convulsive syncope).28 These convulsions recover rapidly and spontaneously with no postictal period or postneurologic sequalae. Convulsive syncope results from transient cerebral ischemia and is not indicative of an epileptic predisposition but is a common reason for misdiagnosis of pediatric epilepsy. Situational Syncope Situational syncope occurs in close proximity to a specic trigger like cough, defecation, micturition, diving, sneezing, trumpet playing, weight lifting, and the Valsalva maneuver.29 A common denominator in situational syncope is the fact that most of the triggering factors are accompanied by a Valsalva maneuver. Hyperventilation Syncope Hyperventilation syncope is preceded by symptoms of paresthesias, lip tingling, and anxiety or panic attacks. The syncopal episode is thought to be secondary to cerebral vasoconstriction triggered by hypocarbia.4 This type of syncope commonly occurs in the adolescent age group and is rare in children younger than 10 years of age.2 Psychogenic Syncope Patients with pseudosyncope and pseudoseizures typically use the event to consciously or unconsciously avoid an unpleasant emotional situation.30 Psychogenic syncope is one of the most important causes of syncope in pediatric patients especially in young females. Several features help distinguish psychogenic syncope from neurocardiogenic syncope4,31,32: 1. Episodes are extremely frequent (sometimes several episodes per day). 2. The episodes are usually not associated with injury and lack any of the usual precipitating or triggering factors. 3. Patients experience onset of syncope in the supine posture. 4. Patients fail to regain consciousness rapidly after a syncopal event (occasionally taking as long as several hours), during which time there are no cardiovascular or neurologic abnormalities and resumption of the supine posture does not terminate the event. 5. Finally, these patients show remarkable indifference to their syncope. During tilt table testing, these patients may suddenly faint without any changes in their heart rate and blood pressure.

compression stockings (2030 mm Hg pressure)

 Psychological counseling.
*Modied and reprinted with permission.4

has shown a consistent therapeutic benet in clinical trials.25,26 Low-dose midodrine is promising and is currently recommended as rst-line therapy for neurocardiogenic syncope in children by some authorities.27 When using udrocortisone it is always advisable to combine it with increased salt intake for optimal effect. Table 7 outlines the currently recommended medications for treatment of neurocardiogenic syncope.

Prognosis of Neurocardiogenic Syncope

The actual loss of consciousness in neurocardiogenic syncope lasts between 5 and 20 seconds, rarely extending to minutes.2 The recovery phase lasts 5-30 minutes associated with fatigue, dizziness, weakness, headaches, and nausea.2 Fortunately the prognosis for recovery is excellent in neurocardiogenic syncope. Most patients show spontaneous recovery of their syncope and presyncope
Table 7 Pharmacologic Treatment of Neurocardiogenic Syncope*

b-Adrenergic antagonists  Atenolol 1-2 mg/kg/d  Esmolol  Metoprolol 1-2 mg/kg/d  Nadolol  Propranolol 0.5-4 mg/kg/d a- Adrenergic agonists  Ephedrine  Methylphenidate 5-10 mg tid  Midodrine 2.510 mg tid  Pseudoephedrine 60 mg bid Anticholinergics  Disopyramide 10-15 mg/kg/d  Hyoscine  Propantheline  Scopolamine Selective serotonin receptor reuptake inhibitors  Fluoxetine 10-20 mg/d  Sertraline 25-50 mg/d Mineralocorticoids Fludrocortisone 0.1-0.3 mg/d.
*Modied and reprinted with permission.4

Clinical approach to syncope in children

A detailed psychosocial history may provide clues about the possible mechanisms involved.4 Many of these individuals turn out to have conversion reactions, most frequently secondary to sexual abuse. A useful clinical clue to the diagnosis is that during pseudosyncope, the eyes are usually tightly closed with a lid utter, whereas during syncope the eyes are lightly closed or open and deviated.30 Many of these patients have syncopal episodes during tilt testing without falls in blood pressure or heart rate. These patients will benet from a referral to a pediatric psychiatrist or behavioral specialist.

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7. Sutton R, Brignole M, Benditt D: The diagnosis and management of syncope. Curr Hypertens Rep 12:316-322, 2010 8. Kapoor WN: Syncope. N Engl J Med 343:1856-1862, 2000 9. Sutton R: Vasovagal syncope: Clinical features, epidemiology, and natural history In: in Blanc JJ, Benditt D, Sutto R (eds.), Neurally Mediated Syncope: Pathophysiology, Investigations, and Treatment. Armonk, NY, Futura, 1996 10. Crompton DE, Berkovic SF: The borderland of epilepsy: Clinical and molecular features of phenomena that mimic epileptic seizures. Lancet Neurol 8:370-381, 2009 11. Wieling W, Shen WK: Syncope: Approach to management. In: Low PA, Benarroch EE (eds): Clinical Autonomic Disorders, ed 3, Baltimore, MD, Lippincott, Williams and Wilkins, 2008. 12. Prodinger RJ, Reisdorff EJ: Syncope in children. Emerg Med Clin North Am 16:617-626, 1998 13. Strieper MJ: Distinguishing benign syncope from life-threatening cardiac causes of syncope. Semin Pediatr Neurol 12:32-38, 2005 14. Kenny RA, Ingram A, Bayliss J, et al: Head-up tile: A useful test for investigation unexplained syncope. Lancet 1:1352-1355, 1986 15. Sra JS, Anderson AJ, Sheikh SH, et al: Unexplained syncope evaluated by electrophysiologic studies and head-up tilt testing. Ann Intern Med 114:1013-1019, 1991 16. Strieper MJ, Auld DO, Hulse JE, et al: Evaluation of recurrent pediatric syncope: Role of tilt table testing. Pediatrics 93:660-662, 1994 17. Grubb BR, Orecchio E, Kurczynski TW: Head upright tilt table testing in evaluation of recurrent, unexplained syncope. Pediatr Neurol 8:423-427, 1992 18. Benditt DG, Lurie KG, Adker SW, et al: Pathophysiology of vasovagal syncope In: in Blanc JJ, Benditt D, Sutto R (eds.), Neurally Mediated Syncope: Pathophysiology, Investigations, and Treatment. Armonk, NY, Futura, 1996 19. Mansourati J, Blanc JJ: Tilt test procedure: Angle, duration, positive criteria In: in Blanc JJ, Benditt D, Sutton R (eds.), Neurally Mediated Syncope: Pathophysiology, Investigations, and Treatment. Armonk, NY, Futura, 1996 20. Moya A, Permanyer-Miralda G, Sagrista J, et al: Is there a role for tilt testing in the evaluation of treatment of vasovagal syncope? And Isoproterenol and tilt test: Protocol, importance, containdications, Neurally Mediated Syncope: Pathophysiology, Investigations, and Treatment. Armonk, NY, Futura, 1996 21. Victor J: Tile test. Environment, material, patient preparation In: in Blanc JJ, Benditt D, Sutto R (eds.), Neurally Mediated Syncope: Pathophysiology, Investigations, and Treatment. Armonk, NY, Futura, 1996 22. Landau WM, Nelson DA: Clinical neuromythology XV. Feinting science: Neurocardiogenic syncope and collateral vasovagal confusion. Neurology 46:609-618, 1996 23. Kapoor WN: Diagnostic evaluation of syncope. Am J Med 90:91-106, 1991 24. Massin M: Neurocardiogenic syncope in children: Current concepts in diagnosis and management. Pediatr Drugs 5:327-334, 2003 25. Kaufman H., Freeman R., Pharmacological treatment of reex syncope, Clin Auton Res 2004;14:71-74[Abstract]. 26. Freeman R: A treatment for neurally mediated syncope? (Dont) hold your breath. Ann Neurol 37:265-267, 2008 27. Stewart JM: Midodrine for the treatment of vasovagal syncope (simple faint). J Pediatr 149:740-742, 2006 28. Lin JT, Ziegler DK, Lai CW, et al: Convulsive syncope in blood donors. Ann Neurol 11:525-528, 1982 29. Hannon DW, Knilans TK: Syncope in children and adolescents. Curr Probl Pediatr 23:358-384, 1993 30. Low PA, Benarvoch EE. Clinical Autonomic Disorders. 3rd edition. Baltimore, MD, Lippincott William and Wilkins; 2008. pp 490491. 31. Benbadis SR, Chichkova R: Psychogenic pseudosyncope: An underestimated and provable diagnosis. Epilepsy Behav 1:106-110, 2006 32. Thijs RD, Bloem BR, van Dijk JG: Falls, faints, ts and funny turns. J Neurol 256:155-167, 2009

Conclusion
Syncope is a common presenting problem in children with a wide differential diagnosis. Most causes of syncope are benign but rarely may be the rst warning sign of a serious underlying cardiac or noncardiac disease. The key to identifying high-risk patients is a detailed history and a comprehensive physical examination. This approach will guide practitioners in choosing the diagnostic tests that are appropriate for a given patient. Key features in the history and physical examination that would prompt a cardiac evaluation include a family history of early sudden cardiac death, familial heart disease, known or suspected heart disease, exercise induced syncope, syncope triggered by loud noises, fright, extreme emotional stress, or an abnormal EKG. Syncope must also be differentiated from epilepsy and psychogenic pseudosyncope, which are uncommon but important causes of transient alterations in the level of consciousness. Signicant advances in the understanding of syncope in infants, children and adolescents have occurred in the last decade. The management of syncope may be substantially enhanced by establishment of a multidisciplinary syncope evaluation unit or team. This unit should set standards of excellence for the comprehensive care of the pediatric patient with syncope and keep abreast of scientic advances in the eld so that our contributions to patient care, education, and research would always be innovative and appropriate to their needs.

References
1. Feit LR: Syncope in the pediatric patient: Diagnosis, pathophysiology, and treatment. Adv Pediatr 43:469-494, 1996 2. Fischer JWJ, Cho CS: Pediatric syncope: Cases from the emergency department. Emerg Med Clin North Am 28:501-516, 2010 3. Kaufman H: Evaluation of the patient with syncope In: in Robertons D, Biaggioni I, Burnstock G, et al.(eds.), Primer on the Autonomic Nervous System, (ed 2) San Diego, CA, Elsevier Academic Press, 2004 4. Friedman NR, Ghosh D, Moodley M: Syncope and paroxysmal disorders other than epilepsy In: in Swaiman K, Ashwal S, Ferriero D, Schor N (eds.), Swaimans Textbook of Pediatric Neurology, ed 5 China; Elsevier, Inc, 2012, pp 905-925 5. Driscoll Dj, Jacobson SJ, Porter CJ, et al: Syncope in children and adolescents. J Am Coll Cardiol 29:1039-1045, 1997 6. Massin MM, Bourguignont A, Coremans C, et al: Syncope in pediatric patients presenting to an emergency department. J Pediatr 145:223-228, 2004