Clinical Approach to SyncopManikum Moodley, MBChB, FRCP

mmo riche em ssala nd

ncopthoratienprovpro

of syevier Inc. All rights reserved.

such as nausea, epigastric discomfort, blurred or tunnel

vision, muffled hearing, dizziness, light-headedness, dia-

clammy skin, or w

any combination

from 1 episodesyncope are beni

life-threatening c

more, the term sdifferent people,

asked to help di

chogenic, and me

rate of syncope ranges from 33%-51% when patients are

followed for up to 5 years.4

a comprehensiveing syncope intocardiovascular-mediated syncope is less frequent thanit is in adults.8 The differential diagnosis of syncope is

given in Table 1.

12 1071-9091/11/$-see front matter & 2013 Elsevier Inc. All rights reserved.

Address reprint requests to Manikum Moodley, MBChB, FRCP, Center for

Pediatric Neurology, Neurological Institute, Cleveland Clinic Founda-

tion, 9500 Euclid Ave/ S60, Cleveland, OH 44195. E-mail:

moodlem@ccf.orgthe cases of syncope in adults but in children(c) Noncardiovascular syncope.

Neurally mediated syncope and cardiovascular-mediated syncope, each accounts for about 50% ofFrom the Center for Pediatric Neurology, Neurological Institute, Cleveland

Clinic Foundation, Cleveland, OH.http://dx.doi.oeakness.4 These symptoms may occur in

or be variably present in any given patient

to the next.4 Most cases of pediatricgn but an evaluation must exclude a rare

ardiac or noncardiac disorder. Further-

yncope may have different meanings totherefore specific questions should be

fferentiate cardiac from neurologic, psy-

tabolic conditions.

EtiologyA detailed history of the event followed byphysical examination will help in categoriz

the 3 major categories:

(a) Neurally mediated syncope(b) Cardiovascular mediated syncopephoresis, hyperventilation, palpitations, pallor, cold andPediatric syncope is one of the most copopulation in both the office setting and in tof consciousness is usually dramatic andproviders. The differential diagnosis of sycomprehensive but focused history and acornerstones in the diagnosis of high-risk psyncope in children is costly and testingreviews the various types of syncope anddiagnosis, investigation, and managementSemin Pediatr Neurol 20:12-17 C 2013 Els

IntroductionSyncope is defined as the abrupt loss of consciousness and

postural tone resulting from transient global cerebralhypoperfusion followed by spontaneous complete recov-

ery.1 Presyncope is the feeling that one is about to pass out

but remains conscious with a transient loss of posturaltone.2

In the young patient, syncope often results from a fall in

systolic pressure below 70 mmHg or a mean arterialpressure 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 featuresrg/10.1016/j.spen.2012.12.003EpidemiologySyncope is a common pediatric problem, affecting 15%-

25% of the children and adolescents.4 The incidence peaksbetween 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, breath-holding spells, and cardiac arrythmias.1 In contrast to

adults, neurocardiogenic syncope or vasovagal syncope or

vasodepressor syncope is the most frequent cause ofpediatric 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 recurrencee is wide but most cases are benign. Aough clinical examination are usually thets. It should be noted that the evaluation ofides a low diagnostic yield. This chaptervides a succinct clinical approach to thencope in children.ergrminency department. The abrupt brief log to patients, family, onlookers, an neurological problems in the pediate in Children

Table 1 Differential Diagnosis of Pediatric Syncope*

Cardiovascular mediated syncope Neurocardiogenic syncope (vasodepressor vasovagal) Orthostatic hypotension Postural orthostatic tachycardia syndrome (POTS) Convulsive syncope Reflex syncope Psychogenic syncope/ panic attacks/ hyperventilation Situational syncope

J CoughingJ SneezingJ MicturitionJ DefecationJ Deglutition (cold liquids)

*

Clinical approach to syncope in children

TabPe

Cardiovascular-mediated syncopeCardiovascular-mediated syncope has a higher mor-

tality and higher incidence of sudden death than

neurally mediated syncope.4 A detailed cardiac his-tory is, therefore, of paramount importance and red

HypoglycemiaJ Electrolyte disorderJ Endocrine disorder

Modified and reprinted with permission.4J Hair groomingJ Trumpet playingJ SuffocationJ Weight liftingJ DivingJ Stretching

Drug and toxin inducedMetabolicJflags 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 syncopeNeurocardiogenic syncope, previously known as vaso-

depressor, vasovagal, or neurally mediated syncope, is

the most common cause of syncope. The history thatsuggests this type of benign syncope includes triggers

such as postural changes, prolonged standing or

sitting, obnoxious stimuli (anger, pain, sight ofblood), and a positive family history is often elicited.

le 2 History of Red Flags Requiring Urgent Referral todiatric Cardiology

History of heart murmur or congenital heart diseaseAcute attacks associated with hyperpnea or cyanosisSyncope during exercise, including swimming or withexertionFamily history of early sudden cardiac death, long QTsyndrome, sensorineural hearing loss, familial heartdiseaseMedications that can result in long QT syndrome,arrhythmiasAbsence of usual premonitory symptoms or precipitatingfactors associated with neurally mediated syncopeUnusual syncope triggers such as loud noises, fright, orextreme emotional stressClinical FeaturesThe diagnosis of syncope rests mainly on clinical grounds

but the lack of objective findings in pediatric syncope often

poses a challenge to caregivers. A thorough history with adetailed physical examination and electrocardiography

(EKG) have a combined diagnostic yield of about 50%.3

A detailed history should include the time of day, time oflast meal, activities leading up to the event, and associated

symptoms such as light-headedness, dizziness, palpitations,

Table 3 Cardiovascular Causes of Syncope*

K ArrhythmiasComplete heart blockSick sinus syndromeTachyarrhythmias:J Supraventricular (Wolff-Parkinson-White-

syndrome)J Ventricular

Ion channel abnormalitiesJ Long QT syndrome (congenital or drug

induced)J Brugada syndrome

Arrhythmogenic right ventricular diseaseK Cardiacstructural

Valvular aortic stenosisHypertrophic obstructive cardiomyopathyCoronary artery anomaliesPrimary pulmonary hypertensionEisenmenger syndromeMitral valve prolapseNeuromuscular disorders

K Cardiac tumors

*Modified and reprinted with permission.4

13chest 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 revealscontributory environmental factors before the syncopal

events (upright posture, prolonged standing, change in

posture, crowding, heat, fatigue, hunger, or a concurrentillness).9 The loss of consciousness is usually brief, lasting

from a few seconds to 1-2 minutes, followed by rapid

spontaneous recovery without neurologic deficits.4 Duringthe 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 historyof 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 syncopedue 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 eventsconsciously or unconsciously to avoid an unpleasant emo-

tional situation.11 Most of these patients are females with a

very high number of events, florid symptomatology, and

logic causes of syncope, and should also include orthostatic

will guide practitioners in choosing the diagnostic studies

who had recurrent syncope, tilt table testing at 801 for 30

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*Modified and reprinted with permission.4

1. Hematologicalbiochemical CBC Serum iron, TIBC, ferritin CMP

2. Cardiac evaluation EKG Echocardiography Holter or event monitor.

3. Autonomic evaluation Neurocardio autonomic reflex testing with and with-

out tilt table testing Quantitative sudomotor axon reflex test (QSART) Thermoregulatory sweat test (TST).

4. Miscellaneous Urine specific gravity Urinary sodium levels Pregnancy test in all menstruating females.

EEG, CT, and MRI of the brain are not recommended unless the lossof consciousness is suspected not to be syncope.

M. Moodleythat 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-friendlyemergency department approach to pediatric syncope.

Tilt Table TestingThe head-up tilt table test as a potential diagnostic tool for

neurocardiogenic syncope was only introduced in 1986after 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 whoare 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 asupporting footboard. A tilt table test result is positive

when the symptoms of syncope or presyncope are repro-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

Diagnostic EvaluationA detailed history, a comprehensive yet focused clinical

examination and an EKG have a combined diagnostic yieldof 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 withsyncope are given in Table 4.

Diagnostic evaluation should include an EKG on all

patients with syncope, especially if it occurs with exerciseor is recurrent. All patients with risk factors for cardiac

disease should be referred to cardiology for further evalua-

tion. These may include performing echocardiography orusage of Holter or event monitor. Rarely cardiac catheter-

ization with right ventricular endomyocardial biopsy may

be necessary before a patient can resume activities.13

Electroencephalography, neuroimaging studies, and auto-

nomic function testing (Tilt table, quantitative sudomotor

axon reflex test) may be indicated with specific neurologicfindings. See Table 5 for a simple diagnostic evaluation of

pediatric syncope. The history and physical examinationepisodes without injury. Hyperventilation and conversion

syncope commonly occur in adolescents, usually in a highly

emotional setting. Both these conditions are rare in childrenyounger 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 Intrue 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 patientswith syncope is normal. However, the physical examination

should be focused to rule out serious cardiac and neuro-

14duced.4,15 Experience with tilt table testing among pedia-tric populations is limited. Among 54 pediatric patientsminutes was superior to other studies, such as EKG,

echocardiogram, electroencephalography, or neuroimagingin 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 neurocar-diogenic syncope in children is relatively new. More

controlled studies and standardization of degree and

duration of tilting are necessary to validate the tilt tabletest as a safe, practical, and useful diagnostic tool for

neurocardiogenic syncope in children.18-21

As syncope is a relatively common presentation inchildren 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 specific

diagnosis.17,23

Table 5 Diagnostic Evaluation of Pediatric SyncopeCBC, complete blood count; CMP, complete metabolic panel; TIBC,total iron binding capacity

Clinical approach to syncope in childrenTreatmentThe objective of treatment for neurocardiogenic syncope is

to prevent recurrent syncope which leads to impairedquality of life, psychological distress, and substantial

morbidity including frequent absence from school. The

mainstay of treatment of neurocardiogenic syncope iseducation 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 bereassured 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

Figure15hydration and enhance dietary salt intake. Patients shouldlearn to recognize and avoid triggers and situations indu-

cing syncope. If the patients are on hypotensive medica-

tion, then they should be modified or discontinued. Table 6outlines the nonpharmacologic treatment of neurocardio-

genic syncope.

If despite these conservative measures the syncopalepisodes become refractory, pharmacologic therapy may

be tried. A wide variety of pharmacologic agents are

currently used for the prevention of recurrent neurocardio-genic syncope in children and adolescents. At the present

time, b-adrenergic antagonists, fludrocortisone, and mido-drine, an alpha adrenergic receptor agonist, are oftenprescribed in children.24 None of these agents, however,

1

has shown a consistent therapeutic benefit in clinicaltrials.25,26 Low-dose midodrine is promising and is cur-

rently recommended as first-line therapy for neurocardio-27

syncope lasts between 5 and 20 seconds, rarely extending2

tim

O

fact that most of the triggering factors are accompanied by a

age group and is rare in children younger than 10 years2

Table 6 Nonpharmacologic Treatment of NeurocardiogenicSyncope*

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 elasticcompression stockings (2030 mm Hg pressure)

Psychological counseling.*Modified and reprinted with permission.4

16to minutes. The recovery phase lasts 5-30 minutesassociated with fatigue, dizziness, weakness, headaches,

and nausea.2 Fortunately the prognosis for recovery is

excellent in neurocardiogenic syncope. Most patients showspontaneous recovery of their syncope and presyncope

Table 7 Pharmacologic Treatment of Neurocardiogenic Syncope*

b-Adrenergic antagonists Atenolol 1-2 mg/kg/dgenic syncope in children by some authorities. Whenusing fludrocortisone it is always advisable to combine it

with increased salt intake for optimal effect. Table 7 out-

lines the currently recommended medications for treatmentof neurocardiogenic syncope.

Prognosis of Neurocardiogenic SyncopeThe actual loss of consciousness in neurocardiogenicpatients especially in young females. Several features help

hours), during which time there are no cardiovascular or

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

MineralocorticoidsFludrocortisone 0.1-0.3 mg/d.

*Modified and reprinted with permission.4neurologic 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 patientsdistinguish 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 supineposture.

4. Patients fail to regain consciousness rapidly after a

syncopal event (occasionally taking as long as severalof age.

Psychogenic SyncopePatients with pseudosyncope and pseudoseizures typically

use the event to consciously or unconsciously avoid an

unpleasant emotional situation.30 Psychogenic syncope isone of the most important causes of syncope in pediatricValsalva maneuver.

Hyperventilation SyncopeHyperventilation syncope is preceded by symptoms of

paresthesias, lip tingling, and anxiety or panic attacks.

The syncopal episode is thought to be secondary tocerebral vasoconstriction triggered by hypocarbia.4

This type of syncope commonly occurs in the adolescentpredisposition but is a common reason for misdiagnosis of

pediatric epilepsy.

Situational SyncopeSituational syncope occurs in close proximity to a specific

trigger like cough, defecation, micturition, diving, sneezing,trumpet playing, weight lifting, and the Valsalva maneu-

ver.29 A common denominator in situational syncope is theolo

cerd spontaneously with no postictal period or postneur-

gic sequalae. Convulsive syncope results from transient

ebral ischemia and is not indicative of an epileptic(coanoclonic seizure may accompany a syncopal episode

nvulsive syncope).28 These convulsions recover rapidlyOc

mynvulsive Syncopecasionally a brief tonic or rarely a clonic, tonic-clonic, orContinue to show symptoms over an extended period of

e, often up to 5 years.4,13

ther Types of Syncopewit

cohin the first year after onset; 5%-10% would, however,

M. Moodleymay suddenly faint without any changes in their heartrate and blood pressure.

1. Feit LR: Syncope in the pediatric patient: Diagnosis, pathophysiology,adolescents. J Am Coll Cardiol 29:1039-1045, 1997and 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

6. Massin MM, Bourguignont A, Coremans C, et al: Syncope in pediatric

patients presenting to an emergency department. J PediatrA detailed psychosocial history may provide clues about

the possible mechanisms involved.4 Many of these indivi-

duals turn out to have conversion reactions, most fre-quently secondary to sexual abuse. A useful clinical clue to

the diagnosis is that during pseudosyncope, the eyes are

usually tightly closed with a lid flutter, whereas duringsyncope 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. Thesepatients will benefit from a referral to a pediatric psychia-

trist or behavioral specialist.

ConclusionSyncope is a common presenting problem in children witha wide differential diagnosis. Most causes of syncope are

benign but rarely may be the first warning sign of a serious

underlying cardiac or noncardiac disease. The key toidentifying high-risk patients is a detailed history and a

comprehensive physical examination. This approach willguide 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 cardiacevaluation include a family history of early sudden cardiac

death, familial heart disease, known or suspected heart

disease, exercise induced syncope, syncope triggered byloud noises, fright, extreme emotional stress, or an abnor-

mal EKG. Syncope must also be differentiated from

epilepsy and psychogenic pseudosyncope, which areuncommon but important causes of transient alterations

in the level of consciousness.

Significant advances in the understanding of syncope ininfants, children and adolescents have occurred in the last

decade. The management of syncope may be substantially

enhanced by establishment of a multidisciplinary syncopeevaluation unit or team.

This unit should set standards of excellence for the

comprehensive care of the pediatric patient with syncopeand keep abreast of scientific advances in the field so that

our contributions to patient care, education, and research

would always be innovative and appropriate to their needs.

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Clinical Approach to Syncope in ChildrenIntroductionEpidemiologyEtiologyClinical FeaturesDiagnostic EvaluationTilt Table Testing

TreatmentPrognosis of Neurocardiogenic SyncopeOther Types of SyncopeConvulsive SyncopeSituational SyncopeHyperventilation SyncopePsychogenic Syncope

ConclusionReferences