Dizziness and syncope in adolescence

Heart 2001;86:350–354
CONGENITAL HEART DISEASE
Classification of syncope in adolescence
x Neurally mediated syncopes
Dizziness and syncope in adolescence
–reflex syncopes
–postural orthostatic tachycardia
syndrome (POTS)
Karen A McLeod
–pure autonomic failure
350
Department of Cardiology, Royal Hospital for Sick Children, Glasgow,
–multiple system atrophy
UK
x Cardiovascular causes
–arrhythmic
“The only diVerence between syncope
–structural
and sudden death is that in syncope you
–vascular
wake up”—G L Engels 1
Syncope is a common problem in adoles- x Noncardiovascular
cence, with up to one in five experiencing
–epileptic
an episode of syncope before adulthood.2
–psychogenic
Whereas the vast majority of syncope is benign,
a minority is caused by something potentially
more serious or even life threatening. For this
reason and also because syncope has such a
be a period of retrograde amnesia and, despite
death-like quality, it often generates extreme
a prodrome, the child might claim “I went
anxiety and is often extensively, inappropri-
straight down without warning”. Depending
ately, and unfruitfully investigated.
on the duration and severity of cerebral
hypoxia secondary to hypotension or profound
Classification
bradycardia, or both, the child may have an
anoxic seizure and may be incontinent. An
anoxic seizure is often mistaken for an epileptic
There are many causes of syncope and
seizure but in reality is quite diVerent. During
therefore it can be helpful to categorise them.
an anoxic seizure the electroencephalogram
One way of categorising syncope is to divide
(EEG) is flat and rather than tonic-clonic
the causes into three main groups.2 Neurally
movements, there tends to be stiVening,
mediated syncopes occur when there is a
opisthotonos, and fine twitching.4 On recovery
disturbance in the autonomic nervous system’s
the child will often complain of feeling tired
control of heart rate and blood pressure. Gen-
and “washed out” for some time afterwards.
erally they can be considered as benign.
The mechanism of neurocardiogenic syn-
Cardiovascular causes of syncope are rare in
cope is not entirely understood. It has been
adolescence, but it is important to be aware of
proposed that in response to being in the
them, as they are potential causes of sudden
upright position, there is peripheral pooling of
death.
Non-cardiovascular
syncopes
can
blood.2 This results in reduced venous return
broadly be divided into the epilepsies and the
and an empty heart. The empty heart contracts
psychogenic causes. In the latter the child
overvigorously, stimulating so called “C fi-
actually fakes the syncope. It is beyond the
bres”. The brain interprets this as hypertension,
scope of this article to discuss all the causes of
resulting in sympathetic withdrawal. There is
syncope and the aim will be to concentrate on
initially pallor, sweating, often with hyperventi-
the most common form of syncope, the
lation and tachycardia, followed by relative
neurally mediated syncopes.
bradycardia, hypotension, and loss of con-
sciousness.
A type of reflex syncope that has only been
Neurally mediated syncopes
recognised relatively recently is cerebral vaso-
constrictive syncope.5 In this condition syn-
Although neurally mediated syncope can occur
cope occurs as a result of cerebral vasoconstric-
at any age in childhood, the peak age groups are
tion in the absence of hypotension and
in toddlers and in adolescents. Neurally medi-
bradycardia. The diagnosis is made by showing
ated syncopes are a heterogeneous group of
that cerebral vasoconstriction occurs during
autonomic disorders, which result in orthos-
symptoms. This can be done by measuring
tatic intolerance. Grubb suggests dividing
cerebral blood flow with techniques such as
them
into
four
main
groups: the
reflex
transcranial Doppler or near infrared cerebral
syncopes, postural orthostatic tachycardia syn-
spectrophotometry.3 5 Cerebral vasoconstric-
drome, pure autonomic failure. and multiple
tive syncope is probably uncommon in adoles-
system atrophy.3
cence, but probably also underdiagnosed. As
Neurocardiogenic syncope is a form of reflex
blood pressure and heart rate are not signifi-
Correspondence to:
syncope and also the most common type of
cantly altered during symptoms, it can be mis-
Dr Karen A McLeod,
Department of
syncope in adolescence. A typical history is of
taken for psychogenic pseudosyncope. This
Cardiology, Royal
syncope that occurs when the child is upright,
mistake can usually be avoided by recording an
Hospital for Sick
either sitting or standing. Characteristically the
EEG or measuring cerebral blood flow during
Children, Yorkhill
child will experience a prodrome such as dizzi-
tilt testing in individuals who have symptoms
NHS Trust, Glasgow,
ness, nausea and pallor, before loss of tone and
despite normal blood pressure and heart rate.
UK
consciousness. It is important to remember
Postural orthostatic tachycardia syndrome
karen.mcleod@
yorkhill.scot.nhs.uk
that following loss of consciousness there may
(POTS) probably is a heterogeneous group of
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Diagnosis of syncope—history, history,
Syncope “warning bells”
history!
x Syncope in response to loud noise, fright or
x Eye witness?
extreme emotional stress
x Onset and frequency?
x Syncope during exercise
x
351
Circumstances: relation to exercise?
x Syncope while supine
posture? precipitating factor?
x Syncope associated with tonic clonic or
x Prodrome: dizziness? nausea? pallor? aura?
abnormal movements
x Altered consciousness: complete loss?
x Family history of sudden death in young
partial impairment? duration?
person < 30 years old
x Abnormal movements: tonic-clonic?
x Syncope with an “odd” history
anoxic? fine repetitive?
x Incontinence, injury?
as this would be very unusual for neurally
mediated syncope. A family history of sudden
x Recovery: tired? “washed out”? post-ictal?
death in a young person raises the possibility of
rapid return to normal?
a hereditary cardiovascular cause such as long
QT syndrome or hypertrophic cardiomyopa-
x Family history: fits? faints? sudden death in
thy. Tonic-clonic or fine repetitive movements
young person?
suggest a possible epileptic cause. One caveat is
that in some susceptible individuals, an anoxic
conditions.3 Although not common in adoles-
seizure can result in a secondary epileptic
cence, it is almost certainly underdiagnosed.
seizure, leading to an incorrect diagnosis of
POTS is defined as an excessive tachycardia,
primary epilepsy.8 A careful history should help
either a rise of > 30 beats per minute (bpm) or
prevent this mistake.
an increase to > 120 bpm, in response to being
upright.6 In some, the heart rate may be
persistently greater than 160 bpm. Symptoms
Investigation of recurrent syncope
include fatigue, dizziness, and exercise intoler-
ance.7 POTS is probably a mild form of chronic
Investigations for syncope in adolescents will
autonomic failure, such that there is failure of
almost always be normal. The most important
the peripheral vasculature to vasoconstrict
investigation is a 12 lead ECG, primarily to
adequately in response to upright posture. This
exclude a long QT interval. Pre-excitation,
results in a compensatory tachycardia. There is
heart block or ventricular hypertrophy can also
a danger of misdiagnosing POTS as inappro-
be diagnosed from an ECG. If symptoms are
priate
sinus
tachycardia.
Radiofrequency
related to exercise, an exercise test should be
modification of the sinus node will usually
performed in the hope of inducing symptoms.
make symptoms worse.
In reality, they rarely occur during the test.
Pure autonomic failure and multiple system
Holter monitoring is usually unhelpful, as
atrophy are very rare in adolescence and are
symptoms almost never occur in the 24–48
accompanied by other signs of autonomic fail-
hour period while the monitor is worn. This
ure, including loss of sweating, thermoregula-
also tends to be true for cardiac event monitor-
tory problems, and bladder and bowel dysfunc-
ing. Unless the child has other cardiac signs or
tion.
symptoms, or any of the warning bells from the
history, an echo will almost certainly be
normal. Although an EEG is often performed
Diagnosis of syncope
on children with syncope to “exclude epi-
lepsy”, this is rarely helpful for even in children
History, history, history!
with epilepsy the EEG will usually be normal
The key to the diagnosis of syncope is to take a
between attacks. Intracerebral causes of syn-
careful and detailed history. If a good history is
cope are very rare in childhood and would usu-
taken, the physician will obtain a very good
ally be associated with other neurological signs
idea which of the three categories the syncope
or symptoms; thus magnetic resonance imag-
is likely to fall into. It is important be on the
ing (MRI) or computed tomographic (CT)
alert for any “warning bells” from the history
scan is usually an expensive waste of time.
that would point towards a potentially more
It is our practise to perform a 12 lead ECG in
serious or life threatening cause of syncope.
all adolescents referred with recurrent syncope.
Neurally mediated syncope can occur before or
If there are any of the “warning bells” from the
following exercise, but syncope that occurs
history or if there are any other cardiac or
during exercise raises the possibility of a
neurological signs or symptoms, appropriate
cardiac structural or arrhythmic cause of
cardiac or neurological investigations are un-
syncope. Syncope that occurs secondary to a
dertaken. If there is a good history for neurally
loud noise, fright or extreme emotional stress
mediated syncope and the ECG is normal,
raises the possibility of the long QT syndrome.
usually no further investigation is required. For
Syncope that occurs when supine is of concern
those who have very severe or frequent attacks,
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Education in Heart
who are in need of reassurance or where the
history is not entirely clear, tilt testing is prob-
ably the most productive investigation.9 Unfor-
tunately there is no standardised protocol for
tilt testing in either children or adults, and pro-
tocols vary in terms of duration of tilt, degree of
tilt, and whether or not drugs, including
352
isoprenaline or glyceryl trinitrate, are given.10
The specificity or sensitivity of any given
protocol will therefore vary. Our own protocol
at The Royal Hospital for Sick Children in
Glasgow is very simple and tolerated by most
children, as it does not involve any intravenous
cannulae or drugs. We rest the child supine for
15 minutes. The child is then tilted to 60°
head-up for a maximum of 45 minutes. During
this time the blood pressure is continuously but
non-invasively monitored using the Finapres
system, and a three lead ECG continuously
recorded. We always warn the children (and
those supervising) that the test is likely to be
one of the most boring things they have ever
done! Using this protocol, approximately 50%
of children with a good history for neurally
mediated syncope will have a positive tilt test.
The use of drugs increases the sensitivity of the
test but reduces its specificity and makes the
test more unpleasant for the child. Whatever
Figure 1. The Reveal Plus monitor (A) is easy to
tilt test protocol is chosen it seems important to
implant and tends to be more acceptable to
have a period of supine rest before tilting, to tilt
adolescents than the more traditional non-invasive
cardiac event monitors. The Reveal Plus can be
to between 60–80° to reduce false positive and
activated using an external activator or programmed
negative responses, and to tilt for at least 40
to recognise and record significant bradycardias,
minutes of drug-free period.
tachycardias or pauses. The quality of ECG
recording is usually very good (B). Although there
The most common positive tilt test response
may be some artefact from muscle activity, it is rarely
is a combination of hypotension and brady-
sufficient to affect ECG interpretation.
cardia before syncope. Hypotension with no
significant change in heart rate is the next most
activity, we have not found this to be enough to
common positive response. The least common
impair ECG interpretation (fig 1). The new
positive response is asystole before syncope.
Reveal Plus monitors have automatic functions
In children with suspected psychogenic
and can be programmed to recognise and
pseudosyncope it is important to include EEG
record significant pauses, bradycardias, and
monitoring or measurement of cerebral blood
tachycardias even if the patient does not
flow during tilt in order not to miss the diagno-
activate the monitor with the external activator.
sis of cerebral vasoconstrictive syncope. In
This is a distinct advantage in the adolescent
situations where it is claimed that syncope is
population where there are the inevitable
occurring several times a day every day, admis-
excuses of forgetting the activator or forgetting
sion to hospital for observation with continu-
to use it to record an event.
ous ambulatory ECG and EEG monitoring is
usually the best approach. With this history the
Management of neurally mediated
ECG, EEG, and measured blood pressure will
syncope
almost always be normal during the “synco-
pes” and a diagnosis of psychogenic pseudo-
syncope can be confirmed.
The mainstay of treatment is reassurance, spe-
In situations where the distinction between
cifically that the episodes are not caused by
neurally mediated syncope and potentially
epilepsy or a cardiac problem.11 Advice should
serious arrhythmia remains unclear—for exam-
be given to drink plenty (with the exception of
ple, in a child with a borderline QT interval or
caVeine containing drinks as they tend to
slightly worrying history—our approach is now
dehydrate) such that the urine always looks
to implant a Reveal monitor (Medtronic Inc,
clear. Many families now restrict the amount of
USA). The monitors are extremely easy and
salt in the diet because of concerns about
quick to implant. Most adolescents find them
future hypertension. We advise an increase in
considerably more acceptable than the non-
dietary salt to what might be termed a
invasive monitors in that they are less conspicu-
“normal” salt diet. Advice on posture when
ous and do not restrict activities. The manufac-
prodromal symptoms are experienced can be
turer
recommends
that
the
monitors
be
helpful. Manoeuvres such as crossing the legs
implanted in the left parasternal region to
and folding the arms especially when standing
reduce artefact from muscle activity. We have
help to maintain blood pressure. Often with the
found that a pocket made medial to the left
above simple measures of reassurance, fluid,
axilla is better cosmetically, and although there
posture and salt, symptoms will improve
can be some artefact on the ECG from muscle
significantly.
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Education in Heart
any great degree hypotension caused by
Management of neurally mediated syncope
vasodilation .
An excellent review examining the role of
x Reassurance
pacing in the treatment of neurocardiogenic
syncope is provided by Sheldon.17 In his
x Fluid, posture, salt
summary of clinical studies evaluating the role
of permanent pacing for neurocardiogenic syn-
x Drugs: fludrocortisone, blocker, others
cope, all studies showed a benefit from pacing
353
but only one study successfully addressed the
x Biofeedback techniques
issue of placebo.
x Pacemaker
The recently published North American
vasovagal pacemaker study tested whether dual
chamber pacing would reduce frequency of
The likelihood of further syncopal attacks
neurocardiogenic syncope.18 Patients were ran-
depends on the number of episodes of syncope
domised to pacing or to medical treatment.
before presentation.12 For those who present
Pacing did reduce recurrence of syncope by
with frequent syncope or continue to have syn-
91% compared with medical treatment, but the
cope despite the above simple measures, drug
important issue of placebo was not addressed.
treatment should be considered. There are
The only completed study to date that has
many pharmacological agents available, which
successfully addressed the problem of placebo
no doubt testifies to our lack of understanding
was a three way, double blind, randomised,
of the mechanisms of neurally mediated
crossover study of dual chamber pacing in 12
syncope and probably also reflects a likely pla-
children.19 The children had frequent, severe
cebo eVect of drugs. No drug has been
neurocardiogenic syncopes and a demon-
adequately evaluated by randomised clinical
strated asystole of > 4 seconds during a typical
trials, but fludrocortisone and
blockers are
attack. The pacemakers were programmed to
the most favoured first line drugs, with
no pacing, ventricular pacing with hysteresis,
relatively few side eVects.13 My own preference
and dual chamber pacing with the rate drop
is for fludrocortisone at a dosage of 100 µg
algorithm. Each treatment arm lasted four
daily in the first instance. This seems to be
months. Both ventricular pacing and dual
eVective in most adolescents in reducing
chamber pacing with rate drop algorithm were
frequency and severity of syncope. Occasion-
equally eVective in preventing syncope, but
ally the drug is not tolerated because of
dual chamber pacing with the rate drop
problems of fluid retention and weight gain. If
algorithm was more eVective in preventing
symptoms continue despite fludrocortisone,
pre-syncope.20
then the addition of a
blocker can be helpful.
It would appear that pacing can be a very
Serotonin reuptake inhibitors such as fluoxet-
eVective treatment for children who have
ine hydrochloride and vasoconstrictors such as
severe neurocardiogenic syncope and who have
midodrine are currently under clinical review.
a demonstrated asystole during a typical
Initial studies suggest they might prove benefi-
episode. The question remains as to whether
cial for some forms of neurally mediated
pacing would be eVective for the majority of
syncope, but the use and safety of the drugs in
children who have neurocardiogenic syncope
children has not been established. It would be
but who do not demonstrate prolonged asys-
wise, therefore, to reserve them for those who
tole during an event. The vasovagal pacemaker
continue to have symptoms despite first line
study II might help to answer this question.
treatments. Serotonin reuptake inhibitors are
This study will evaluate adult patients who
thought to act by inhibiting sympathetic neural
have had six or more syncopal episodes and
outflow and reducing susceptibility to certain
who have a positive tilt test with or without
neurally mediated events.14 Midodrine is an 1
bradycardia. All patients will receive a pace-
agonist which causes peripheral vasoconstric-
maker and will be randomised to either pacing
tion but with minimal cardiac and neurological
with the rate drop algorithm, pacing with an
eVects.15
escape rate of 45 bpm, or to no pacing. It is
An alternative or adjunct to drugs is biofeed-
expected that the study will be completed by
back therapy. Techniques include tilt training
the year 2002.
and active tension.16 The latter is best under-
As cardiac pacing is a significant commit-
taken with the help and supervision of a clinical
ment in a young person it should be reserved
psychologist.
for those who have severe, frequent attacks and
in whom drug treatment has failed or is
declined. Although ventricular pacing with
Cardiac pacing
hysteresis should suYce for the younger child,
for adolescents who are likely to be more aware
The use of cardiac pacing for neurocardiogenic
of and distressed by symptoms of presyncope, a
syncope remains controversial. The rationale is
dual chamber pacemaker with the rate drop
that pacing should eliminate any contribution
algorithm is recommended. Until the question
of bradycardia to the hypotension that results
is answered as to whether patients with neuro-
in syncope. There is little direct evidence, how-
cardiogenic syncope but without demonstrable
ever, that significant bradycardia commonly
asystole will benefit from pacing, it seems sen-
occurs in spontaneous neurocardiogenic syn-
sible to reserve pacing for children who have a
cope even if it is demonstrated during tilt test-
recorded asystole or profound bradycardia
ing. Pacing would not be expected to aVect to
during a typical attack. It is now our practise to
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Education in Heart
• It is increasingly recognised that neurally mediated
syncope is a heterogeneous group of disorders. This
Syncope in adolescence: key points
excellent overview provides a new classification of the
disorders together with a discussion of the
pathophysiology and diagnosis.
x Common
7. Karas B, Grubb BP, Boehm K, et al. The postural
orthostatic tachycardia syndrome: a potentially treatable
x Usually benign
cause of chronic fatigue, exercise intolerance, and cognitive
impairment in adolescents. Pacing Clin Electrophysiol
2000;23:344–51.
x Most common cause is neurally mediated
354
8. Stephenson JBP. Nonepileptic seizures, anoxic-epileptic
syncope
seizures and epileptic-anoxic seizures. In: Wallace S, ed.
Epilepsy in children. London: Chapman and Hall, 1996:5–26.
x Diagnosis primarily from history
9. Sutton R, Bloomfield D. Indications, methodology, and
classification of tilt table testing. Am J Cardiol
1999;84:10Q–19Q.
x 12 lead ECG is most important
10. Kenny RA, O’Shea D, Parry SW. The Newcastle
investigation
protocols for head-up tilt table testing in the diagnosis of
vasovagal syncope and related disorders. Heart
x Investigations usually normal
2000;83:564–9.
• Wide variation in tilt test protocols affects sensitivity,
specificity, and reproducibility. The authors suggest a
x Mainstay of treatment for neurally
practical and standardised approach to tilt testing, based
on their considerable experience.
mediated syncope is reassurance
11. Bloomfield DM, Sheldon R, Grubb BP, et al. Putting it
together: a new treatment algorithm for vasovagal syncope
x BEWARE OF “WARNING BELLS” FROM HISTORY
and related disorders. Am J Cardiol 1999;84:33Q–39Q.
• A comprehensive algorithm is given to help guide the
diagnosis and subsequent management of patients with
neurally mediated syncope.
implant a Reveal Plus monitor in any young
12. Grimm W, Degenhardt M, Hoffman J, et al. Syncope
person with frequent neurally mediated syn-
recurrence can be better predicted by history than by
cope in whom we are considering a pacemaker.
head-up tilt testing in untreated patients with suspected
neurocardiogenic syncope. Eur Heart J 1997;18:1465–9.
The Reveal allows us to determine accurately
13. Benditt D, Fahy G, Lurie K, et al. Pharmacotherapy of
both the frequency of events and whether asys-
neurocardiogenic syncope. Circulation 1999;100:1242–8.
tole or profound bradycardia occurs during a
• This paper gives an excellent overview of the use of drugs
in the management of neurally mediated syncope. It
spontaneous syncope. It has been our experi-
includes discussion of relatively new agents such as
ence that implantation of the Reveal can have
serotonin reuptake inhibitors and midodrine.
14. Di Girolamo E, Di Iorio C, Sabatini P, et al. Effects of
an astonishingly curative eVect. Perhaps it
paroxetine hydrochloride, a selective serotonin reuptake
works as a placebo or perhaps the awareness of
inhibitor, on refractory vasovagal syncope: a randomized
double-blind, placebo-controlled study. J Am Coll Cardiol
the monitor and activator works as a form of
1999;33:1227–30.
biofeedback. Certainly we been impressed
15. Ward C, Gray J, Gilroy J, et al. Midodrine: a role in the
enough to wonder whether the manufacturer
management of neurocardiogenic syncope. Heart
1998;79:45–9.
should recommend it as a treatment for neuro-
16. Reybrouck T, Heidbuchel H, Van de Werf F, et al. Tilt
cardiogenic syncope!
training: a treatment for malignant and recurrent
neurocardiogenic syncope. Pacing Clin Electrophysiol
2000;23:493–8.
1. Engel GL. Psychological stress, vasodepressor syncope
and sudden death. Ann Intern Med 1978;89:403–12.
17. Sheldon R. Role of pacing in the treatment of
vasovagal syncope. Am J Cardiol 1999;84:26Q–32Q.
2. Ross B, Grubb B. Syncope in the child and adolescent.
• An excellent and comprehensive review of clinical studies
In: Grubb B, Oshlansky B, eds. Syncope: mechanisms and
evaluating the efficacy of pacing for vasovagal syncope.
management, New York: Futura, 1998:305–16.
18. Connolly SJ, Sheldon RS, Roberts RS, et al. The
• This book is well worth reading for anyone interested in
North American vasovagal pacemaker study: a randomized
syncope. It includes a well written chapter that summarises
trial of permanent cardiac pacing for the prevention of
the mechanisms and management of syncope in the
vasovagal syncope. J Am Coll Cardiol 1999;33:16–20.
paediatric and adolescent population.
• The paper publishes the findings of the North American
3. Grubb BP, Karas B. Clinical disorders of the autonomic
vasovagal pacemaker study. Patients were randomised to
nervous system associated with orthostatic intolerance: an
pacing with the rate drop algorithm or to medical
overview of classification, clinical evaluation, and
treatment. Pacing reduced recurrence of syncope by 91%
management. PACE 1999;22:789–810.
compared with medical treatment but the issue of placebo
• A helpful overview of the classification, evaluation, and
was not addressed.
management of neurally mediated syncope and related
19. McLeod K, Wilson N, Hewitt J, et al. Double-blind trial
disorders. It includes discussion on postural orthostatic
of cardiac pacing for severe childhood neurally mediated
tachycardia (POTS) and cerebral vasoconstrictive
syncope with reflex anoxic seizures. Heart 1999;82:721–6.
syncope.
• This study was a three way, double blind, randomised,
4. Stephenson J, McLeod K. Reflex anoxic seizures. In:
crossover study of dual chamber pacing in 12 children with
David TJ, ed. Recent advances in paediatrics. Edinburgh:
frequent, severe neurocardiogenic syncope and
Churchill Livingstone, 2000:1–19.
demonstrated asystole (median age 2.9 years). The
• This chapter provides a detailed overview of the
pacemakers were programmed to no pacing, ventricular
pathophysiology, diagnosis, and management of reflex
pacing with hysteresis, and dual chamber pacing with the
anoxic syncope in childhood.
rate drop algorithm for four month periods. Ventricular
pacing and dual chamber pacing were equally effective in
5. Grubb B. Cerebral syncope: new insights into an
preventing syncope but dual chamber pacing was more
emerging entity. J Pediatr 2000;136:431–2.
effective in preventing presyncope.
6. Grubb BP. Pathophysiology and differential diagnosis of
20. Gammage MD. Rate-drop response programming.
neurocardiogenic syncope. Am J Cardiol 1999;84:3Q–9Q.
PACE 1997;20:841–3.
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