Syncope in Adults - Epidemiology, Pathogenesis, and Etiologies

2/8/22, 12:54 Syncope in adults: Epidemiology, pathogenesis, and etiologies - UpToDate
Official reprint from UpToDate®

www.uptodate.com © 2022 UpToDate, Inc. and/or its affiliates. All Rights Reserved.
Syncope in adults: Epidemiology, pathogenesis, and

etiologies
Author: David Benditt, MD
Section Editor: Peter Kowey, MD, FACC, FAHA, FHRS
Deputy Editor: Susan B Yeon, MD, JD, FACC
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jul 2022. | This topic last updated: Jun 30, 2022.
INTRODUCTION
Syncope is a clinical syndrome in which transient loss of consciousness (TLOC) is caused by a

period of inadequate cerebral nutrient flow, most often the result of an abrupt drop of systemic
blood pressure. Typically, the inadequate cerebral nutrient flow is of relatively brief duration (8
to 10 seconds) and, in syncope, is by definition spontaneously self-limited.
Loss of postural tone is inevitable with loss of consciousness, and consequently syncope usually
is associated with collapse, which may trigger injury due to a fall (such as may occur if the
person is standing) or other type of accident (eg, if syncope occurs while driving). Recovery
from true syncope is usually complete and rapid, with episodes rarely lasting more than a
minute or two. Longer periods of real or apparent loss of consciousness suggest that the event
is not syncope or is not syncope alone (eg, syncope resulting in a head injury, thereby
prolonging the event).
True syncope itself has many possible causes ( table 1). Syncope, however, is only one of the
many potential causes of TLOC. Examples of nonsyncopal causes of TLOC, or apparent TLOC,
include seizure disorders, traumatic brain injury (eg, concussion), intoxications, metabolic
disturbances, and conversion disorders (eg, psychogenic "pseudosyncope" or
"pseudoseizures"). Distinguishing these conditions from true syncope may be challenging, but
it is crucial in order to determine appropriate management. Until relatively recently (eg, 2010
and beyond), in much of the published literature, it is not possible to distinguish true syncope
from other TLOC events.
https://www.uptodate.com/contents/syncope-in-adults-epidemiology-pathogenesis-and-etiologies/print?search=sincope&source=search_result&selec… 1/28
The epidemiology, pathogenesis, and etiologies of syncope will be reviewed here. The clinical
manifestations, diagnostic evaluation, and management of syncope is discussed in detail
separately. (See "Syncope in adults: Clinical manifestations and initial diagnostic evaluation" and
"Syncope in adults: Management and prognosis".)
EPIDEMIOLOGY
Syncope/collapse is a common clinical problem, with a lifetime prevalence in the population as

a whole of approximately 20 percent [1,2].
In the Framingham Heart study, 822 of 7814 individuals (11 percent) who were followed for an
average of 17 years reported an apparent syncopal episode [3]. However, given advances in the
evaluation of patients with suspected syncope, the applicability of the Framingham data
requires reevaluation given the manner in which syncope and the causal "diagnosis" was
established. The study did not limit the diagnosis to the current definition of syncope (ie, self-
limited inadequate cerebral perfusion). As a result, the report inevitably combined syncope and
nonsyncopal collapse, and some seizures may also have been included. Also, the cause of
syncope in the Framingham population was, at best, inferential. As an example, a diagnosis of
"cardiac syncope" was based on the presence of cardiac disease, not a documented connection
to the symptoms as currently required. Despite these limitations, the Framingham data provide
a useful population estimate of syncope/collapse, and are largely consistent with a later study
[1].
In a retrospective community-based study of more than 1900 adults from Olmsted county,
Minnesota, aged ≥45 years (47 percent male, mean age 62 years), 364 individuals (19 percent)
reported having experienced syncope [1]. Nearly 50 percent of these individuals had
subsequent recurrences of syncope, which may have been related to their mean age of 62.
The occurrence of syncope versus age has been reported as roughly bimodal, with a peak in
late adolescence to early adulthood (mostly vasovagal in origin) and a second peak later in
older age, with a sharp rise after age 70 years ( figure 1). The increased risk of syncope in
older adult patients appears to be due to age- and disease-related abnormalities that impair
the ability to respond to physiologic stresses that would ordinarily not cause syncope [4].
Syncope/collapse appears to be slightly more common among females depending upon the
population studied [1,3]. Variation in the reported rates of syncope in different studies is due to
varying study populations, definitions of syncope, and diagnostic methods and criteria. Males,
however, are more likely than females to have a cardiac cause of syncope, presumably due to
greater risk of cardiovascular disease in males [3,5].
Syncope/collapse is also a common clinical complaint of patients treated in the emergency

department and is the source for a significant number of hospital admissions. Between 1 and 3
percent of all emergency department visits, and 1 percent of all hospital admissions, are related
to syncope [6-8]. In general, approximately 35 percent of patients who present to the
emergency department with syncope/collapse are admitted to hospital. This later proportion is
substantially greater than is essential, and efforts have been directed to reducing admission
rates. In regard to the latter, a 2018 report shows a trend reduction of hospital admission for
syncope in the United States, possibly due to greater use of short-term observation or
outpatient care; nonetheless, the overall cost of care continues to rise [9]. Among 282,311
United States patients (54 percent female; median age 72 years) with a primary diagnosis of
syncope identified from the 2013 to 2014 Nationwide Readmissions Database, 9.3 percent were
re-admitted within 30 days; predictors of readmission primarily centered around medical co-
morbidities (eg, heart failure [HF], atrial fibrillation, COPD, diabetes) and longer initial hospital
stays (>3 days) [10]. (See "Approach to the adult patient with syncope in the emergency
department".)
Determining the cause of syncope is important for both prognostic and therapeutic reasons.
Several large studies have assessed the causes for syncope [3,11-14]. In general, vasovagal
attacks are the most common cause of syncope in all age groups, followed by orthostatic
syncope and then cardiac arrhythmias.
● Vasovagal syncope (also known as the "common" or "innocent" faint), a type of reflex
(neurally-mediated) syncope, is a common cause of transient loss of consciousness,
particularly in patients without apparent cardiac or neurologic disease. In contrast to
vasovagal syncope, carotid sinus hypersensitivity is much more common in older patients,
especially those with atherosclerotic vascular disease.
● A pooled analysis of five population-based studies including 1002 patients with presumed
syncope between 1984 and 1990 found that arrhythmias were responsible for 14 percent
of syncope cases (range 4 to 38 percent in different studies) [13].
● Orthostatic hypotension accounted for 8.6 and 9.9 percent of syncope cases among
individuals in the Framingham cohort, respectively, and for 8 percent of cases in the five
pooled cohort studies ( table 2 and table 3) [3,13]. However, the frequency of
orthostatic hypotension increases substantially in older populations in whom treatment
with antihypertensive drugs and diuretics is common.
● The cause is unknown in approximately one-fifth to one-third of cases ( table 2 and

table 3), although arrhythmias may also be the etiology of a significant proportion of
unexplained syncopal events [15]. (See 'Causes of syncope' below.)
Cardiovascular disease is a major risk factor for syncope. The age-adjusted incidence rate for
apparent syncope among participants with cardiovascular disease was almost twice that of
participants without cardiovascular disease in the Framingham cohort (10.6 versus 6.4 per 1000
person-years) [3]. Nonetheless, reflex syncope (particularly vasovagal syncope) is the most
common cause of syncope overall. (See 'Reflex syncope' below.)
CAUSES OF SYNCOPE
In the evaluation of a patient with transient loss of consciousness (TLOC) in whom syncope is
suspected, the clinician must necessarily consider and exclude conditions that mimic
TLOC/syncope but are not true syncope. The most common of these conditions are seizures,
sleep disturbances, accidental falls, and some psychiatric conditions (eg, conversion reactions
resulting in psychogenic pseudo-syncope, or as preferred by many neurologists, nonepileptic
seizures, also called psychogenic pseudoseizures). These conditions are discussed in detail
separately. (See "Classification of sleep disorders" and "Psychogenic nonepileptic seizures:
Etiology, clinical features, and diagnosis" and "Evaluation and management of the first seizure
in adults".)
The possible causes of TLOC resulting in true syncope are generally grouped into several major
categories ( table 1):
● Reflex syncope (neurally-mediated)

● Orthostatic syncope
● Cardiac (arrhythmias and structural cardiopulmonary disease)
Reflex syncope accounts for the vast majority of cases in younger individuals, and
approximately 50 percent of cases in older patients. As individuals age, orthostatic and cardiac
causes increase in frequency.
Reflex syncope — Reflex syncope comprises a number of related conditions in which neural
reflexes modify heart rate and blood pressure inappropriately, resulting in syncope or near-
syncope. The most well-known of these conditions is vasovagal syncope, otherwise known as
the common faint. Other types of neurally-mediated reflex syncope include carotid sinus
syncope as well as syncope triggered by micturition, defecation, swallowing, or coughing. (See
"Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation",
section on 'Types of reflex syncope' and "Carotid sinus hypersensitivity and carotid sinus
syndrome".)
Orthostatic (postural) hypotension — Orthostatic (postural) hypotension, defined as a

decrease in systolic blood pressure of at least 20 mmHg, or in diastolic blood pressure of at
least 10 mmHg upon assuming upright posture, is another common cause of near-syncope and
syncope. Orthostatic syncope occurs most often following movement from lying or sitting to a
standing position. Orthostatic (postural) hypotension is often considered as being either
immediate or delayed.
● Immediate orthostatic hypotension – Many healthy individuals experience a minor form

of orthostatic change in blood pressure when rising abruptly from a supine or seated
position, and need to support themselves momentarily, a condition referred to as
immediate orthostatic hypotension (OH). Immediate OH usually is fully resolved with 10 to
20 seconds of the change of posture.
● Delayed orthostatic hypotension – Episodes of near-syncope or syncope that occur a

few moments (usually one to several minutes) after standing are generally more
worrisome as the patient may be unprepared to protect themselves from the hazards of a
fall. This so-called delayed or "classic" orthostatic hypotension can be particularly
hazardous if the affected individual has walked a short distance and is unable to
adequately avoid falling and the associated risk of injury.
The major causes of orthostatic hypotension associated with syncope include (see
"Mechanisms, causes, and evaluation of orthostatic hypotension"):
● Decreased intravascular volume, as may occur with inadequate fluid intake or the result of
diuretics or as a consequence of losses associated with certain gastrointestinal disorders.
● Drug effects, especially antidepressants (tricyclics, phenothiazine) and antihypertensive

agents (beta and alpha blockers, hydralazine, angiotensin converting enzyme inhibitors,
ganglionic blockers), particularly vasodilators, including calcium channel blockers and
nitrates (more commonly observed in older adults). Other drugs that may cause
orthostatic hypotension include opiates and bromocriptine.
● Primary autonomic insufficiency or failure (including pure autonomic failure, multiple

system atrophy, Parkinson disease, and others).
● Secondary autonomic insufficiency (eg, diabetes mellitus and amyloidosis).
● Alcohol consumption which impairs vasoconstriction [16].

● Aging is associated with an increased prevalence of orthostatic hypotension [17]. One

contributory mechanism may be attenuation of the vestibulo-sympathetic reflex [18].
The greatest risk of orthostatic hypotension resulting in syncope is in older frail individuals,
patients on multiple vasodilating and/or diuretic drugs, those who have underlying medical
problems causing autonomic failure (eg, diabetes, certain nervous system diseases), and
persons who are dehydrated (eg, hot environments, inadequate fluid intake). (See
"Mechanisms, causes, and evaluation of orthostatic hypotension".)
Cardiac arrhythmias — Cardiac arrhythmias may cause syncope or near-syncope if the heart
rate is either too slow or too fast to permit maintenance of an adequate cardiac output and
systemic arterial pressure. Bradycardia resulting from prolonged sinus pauses, high grade
atrioventricular (AV) block, or at the termination of an atrial tachyarrhythmia may cause
syncope and near-syncope. Similarly, syncope or near-syncope may occur at the onset of an
episode of tachycardia in which a fall in cardiac output cannot be adequately compensated for
by vascular constriction. Although an arrhythmic etiology for syncope is often suspected
clinically, the culprit arrhythmia frequently may be difficult to diagnose since most are
paroxysmal and infrequent. Long-term ambulatory ECG monitoring is often essential. (See
"Syncope in adults: Clinical manifestations and initial diagnostic evaluation" and "Ambulatory
ECG monitoring".)
The most common arrhythmic causes of syncope include:
● AV block – High grade (ie, complete or Mobitz type II second degree) AV block may trigger
syncope (an event previously termed a Stokes-Adams attack). Conversely, Mobitz type I
(Wenckebach) second degree AV block is usually benign and not associated with syncope.
When Mobitz type II second degree or third degree AV block is present in conjunction with
syncope, a permanent pacemaker is indicated. (See "Syncope in adults: Management and
prognosis", section on 'Arrhythmias' and "Second-degree atrioventricular block: Mobitz
type II" and "Third-degree (complete) atrioventricular block".)
● Cardiac pauses – Due to sinus node disease or prolonged recovery times after
spontaneous termination of an episode of atrial fibrillation or flutter. (See "Sinus node
dysfunction: Clinical manifestations, diagnosis, and evaluation".)
● Ventricular tachyarrhythmias – Syncope resulting from ventricular tachycardia (VT)

occurs most commonly in the setting of structural heart disease, particularly coronary
heart disease. Patients with dilated cardiomyopathy and some congenital myopathic
processes (eg, hypertrophic cardiomyopathy [HCM], arrhythmogenic right ventricular
cardiomyopathy) are also prone to have VT presenting with syncope. In addition, an
unusual form of VT, torsades de pointes, may cause syncope in patients with either the
congenital or acquired form of the long QT syndrome. In addition, there has been
substantial expansion of knowledge into other genetic cardiac ion channel diseases. While
relatively rare, conditions such as Brugada syndrome, catecholaminergic polymorphic VT
(CPVT), and others need to be considered as part of the syncope/collapse differential
diagnosis. Finally, ventricular fibrillation is not often a cause of syncope as it only rarely is
self-terminating [19]. In nearly all cases, this rhythm disturbance causes cardiac arrest and
death. (See "Ventricular arrhythmias: Overview in patients with heart failure and
cardiomyopathy" and "Congenital long QT syndrome: Epidemiology and clinical
manifestations" and "Acquired long QT syndrome: Definitions, pathophysiology, and
causes".)
● Ventricular bigeminy – Ventricular bigeminy, with ventricular premature beats occurring

every other beat, may occasionally be associated with hypotension, bradycardia, and near
syncope, though full syncope with loss of consciousness is exceedingly rare. Syncope
occurs primarily in patients with an underlying sinus bradycardia or those with advanced
heart disease and significant left ventricular dysfunction. Ventricular bigeminy typically is
associated with in ineffective cardiac output of the premature beats, thereby diminishing
overall cardiac output.
● Supraventricular tachyarrhythmias – Supraventricular tachyarrhythmias are only rarely

associated with syncope [20]. Syncope may occur at the onset of the arrhythmia as
impaired vasomotor function may be responsible for syncope due to delayed vascular
compensation. In some cases the cause may be due to neurally-mediated
(neurocardiogenic) responses rather than a direct result of the tachycardia [21-23].
Individuals with underlying heart disease (eg, previous myocardial infarction [MI], valvular heart
disease), a channelopathy (eg, long QT syndrome, Brugada syndrome), HCM, congenital heart
disease, or significant vascular disease are at greatest risk for syncope due to a
tachyarrhythmia (usually VT). In contrast to patients who have vasovagal or other causes of
syncope, an arrhythmic cause of syncope often occurs without warning. This is particularly true
of the bradyarrhythmias and, in addition to reporting no warning symptoms, the patient may
also suffer an injury with the event. Patients with a tachyarrhythmia may report having
palpitations but may also have syncope without warning symptoms.
An abrupt change in heart rate, as occurs during the initiation of many arrhythmias, can cause
TLOC. The blood pressure may precipitously decline, especially in an upright position, causing
TLOC if a prompt compensatory vasopressor response (which may be blunted by
antihypertensive or HF medications) does not occur. Then, over time, with augmentation in
sympathetic nervous system activation and elevation of catecholamine levels, vasoconstriction

and increased ventricular contractility can help regulate and normalize cerebral blood flow.
The hemodynamic stability resulting from any arrhythmia is also influenced by other factors
including rate, ventricular function or presence of coronary or valvular heart disease, body
position, medications, and baroreceptor sensitivity [24,25].
Structural cardiac or cardiopulmonary disease — The presence of heart disease has been
shown to be an independent predictor of cardiac cause of syncope, with a sensitivity of 95
percent and a specificity of 45 percent; by contrast, the absence of heart disease excludes a
cardiac cause of syncope in 97 percent of patients [26].
Structural cardiac or cardiopulmonary diseases that may lead to syncope due to inadequate
cardiac output include cardiac valvular disease (particularly aortic stenosis), HCM, atrial
myxoma, pulmonary embolus, pulmonary hypertension, pericardial tamponade, acute
MI/ischemia, and acute aortic dissection. Channelopathies such as long QT syndrome, Brugada
syndrome, CPVT, and others that are less frequent should also be included here, although the
"structural" disease is at the cellular level.
Patients with an underlying cardiovascular cause of syncope have higher rates of sudden
cardiac death (SCD) and all-cause mortality than those with a noncardiovascular cause of
syncope. The mortality rate in patients with cardiovascular disease after five years of follow-up
has been reported to approach 50 percent, with a 30 percent incidence of death in the first year
( figure 2) [3,6,27,28]. Mortality in these patients is in large part due to the severity of the
underlying cardiovascular disease.
Syncope may be caused by obstruction to blood flow due to cardiovascular abnormalities, the
most frequent being aortic stenosis and HCM. Less common conditions include pulmonic
stenosis, idiopathic pulmonary arterial hypertension, atrial myxomas, and pulmonary
embolism.
● Aortic stenosis – Aortic stenosis rarely presents with syncope unless the valve is critically
stenotic. Syncope in patients with aortic stenosis is often associated with exertion. In most
such cases, syncope results from an inability to produce a compensatory increase in
cardiac output (due to the obstruction), which normally occurs in response to exercise-
induced peripheral vasodilation [29]. Patients with syncope and severe aortic stenosis
have a high mortality if untreated; aortic valve replacement is generally indicated in such
patients. (See "Clinical manifestations and diagnosis of aortic stenosis in adults", section
on 'Dizziness and syncope' and "Natural history, epidemiology, and prognosis of aortic
stenosis" and "Indications for valve replacement for high gradient aortic stenosis in
adults".)
● Hypertrophic cardiomyopathy – Syncope may occur in up to 25 percent of patients who

have HCM and may be due to dynamic left ventricular outflow tract (LVOT) obstruction or
other causes. LVOT obstruction can intensify with postural changes, hypovolemia, or
drugs. Multiple mechanisms may lead to syncope in patients with HCM and LVOT
obstruction, notably including the LVOT obstruction itself (leading to reduced cardiac
output) and VT. Syncope in patients with HCM is discussed in detail separately. (See
"Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation", section
on 'Syncope'.)
● Myocardial ischemia – VT and bradyarrhythmias secondary to myocardial ischemia are

infrequent causes of syncope, accounting for only 1 percent of cases [30]. Although
patients who are admitted to the hospital with syncope are commonly evaluated for acute
coronary syndrome (myocardial infarction or unstable angina), generally, only a limited
evaluation for acute coronary syndrome is required, as discussed separately. (See
"Syncope in adults: Clinical manifestations and initial diagnostic evaluation", section on
'Approach to initial evaluation'.)
● Other causes – Pulmonary embolism, severe pulmonic stenosis, idiopathic pulmonary

arterial hypertension, and atrial myxomas are all rare causes of syncope due to
obstruction of blood flow [31]. (See "Clinical presentation, evaluation, and diagnosis of the
nonpregnant adult with suspected acute pulmonary embolism", section on 'History and
examination'.)
Cerebrovascular disease — Atherosclerotic disease of the cerebral arteries is almost never the
cause of true syncopal symptoms, as the brain has a very redundant blood supply. Instead,
stroke and transient ischemia attacks cause focal neurologic deficits that do not recover rapidly
or, in most cases, completely. As examples:
● If the posterior cerebral circulation is impaired (vertebrobasilar artery insufficiency),

symptoms such as dizziness are more apt to occur than syncope. Other causes of syncope
should be excluded in patients with syncope and suspected vertebrobasilar ischemia.
● If the anterior circulation is compromised, a focal neurologic deficit and not a global
decrease in consciousness will occur.
The rare exception in which syncope can occur is with severe obstructive four vessel
cerebrovascular disease; however, other neurologic findings are likely to occur prior to the loss
of consciousness in these patients. (See "Vertebral artery revascularization".)
A vascular steal syndrome occurs when the arterial circulation to the arm is blocked, resulting in
a shunt of blood through the cerebrovascular system that supplies both parts of the brain and
the arm. Impairment in brain perfusion during arm exercise may cause loss of consciousness.
Vertebrobasilar steal is typically associated with vertigo, diplopia, blurred vision, cranial nerve
dysfunction, drop attacks (sudden fall without loss of consciousness), and syncope. (See
"Subclavian steal syndrome", section on 'Upper extremity ischemia' and "Subclavian steal
syndrome", section on 'Clinical presentations' and "Overview of upper extremity peripheral
artery disease".)
SYNCOPE OF UNKNOWN ORIGIN
When the initial evaluation, including history, physical examination, and electrocardiogram
(ECG) are completely nondiagnostic, the patient is considered to have syncope/collapse of
unknown origin/cause. Importantly, as was noted above, in many instances, apart from not
knowing the cause, it may not be clear that the patient has experienced true syncope. The
published literature often misses this point and syncope and nonsyncope collapse are, as a
result, inappropriately combined; lumping these conditions together complicates our
understanding of the epidemiology and prognosis associated with such patients. (See
'Epidemiology' above.)
Leaving aside the uncertainty regarding combining true syncope and nonsyncopal causes of
collapse (eg, accidents, seizures), approximately one-fifth to one-third of cases in the literature
have been identified as having syncope from "unknown causes." However, identification of this
group is problematic given limitations in diagnostic discrimination of causes. As an example, in
the Framingham Heart Study cited above, the group identified as having syncope of "unknown"
origin likely included individuals with a mixed group of conditions in which benign and not-so-
benign diagnoses could not be sorted out, given the limited diagnostic data available to
Framingham investigators [3]. In more contemporary practice, however, with the increasingly
broader availability of specialized syncope/collapse clinics, the frequency of "unexplained"
transient loss of consciousness is diminishing and may be closer to 10 percent [32,33].
CAUSES OF NONSYNCOPAL ATTACKS
Episodes that may be confused with syncope include disorders without impairment of
consciousness and disorders with partial or complete loss of consciousness ( table 4). These
https://www.uptodate.com/contents/syncope-in-adults-epidemiology-pathogenesis-and-etiologies/print?search=sincope&source=search_result&sele… 10/28
disorders should be considered and excluded as part of the initial evaluation of the transient
loss of consciousness (TLOC)/collapse patient (which includes a thorough history, physical
examination, ECG, and selected additional testing on a case by case basis) ( algorithm 1).
● Seizures – Seizures are the probable cause in 5 to 15 percent of apparent TLOC/collapse

episodes [3,13,30,34]. They can mimic syncope, especially when the seizure is atypical and
not associated with tonic-clonic movements, the seizure is not observed, or a complete
history cannot be obtained ( table 5). Another potentially confounding factor is that loss
of cerebral blood flow due to any cause of syncope can result in a myoclonic jerking that
non-expert witnesses may conclude is an epileptic state. As an example, the initiation of a
rapid ventricular tachycardia may be associated with impaired cerebral blood flow,
followed within seconds by movements that might (although only rarely) appear to the lay
bystander or inexperienced medical practitioner to be tonic-clonic activity. This apparent
seizure activity is associated with brain wave slowing, not epileptiform spikes, on the
electroencephalogram. One distinguishing feature is that patients with seizures rarely
have an abrupt complete recovery. Instead, the postictal state is characterized by a slow
complete recovery. Other important clues, if present, are evidence of soft tissue injury at
multiple sites due to tonic-clonic movements during the seizure. (See "Evaluation and
management of the first seizure in adults".)
● Psychogenic pseudo-syncope and nonepileptic "seizures" – Conversion disorders can

mimic syncope or seizures and have been termed in some literature as psychogenic
nonepileptic seizures (but are better called psychogenic pseudosyncope or psychogenic
pseudoseizures, the distinction being whether the patient manifests jerky movements
suggesting a seizure to untrained bystanders). These conditions, diagnosed in
approximately 1 percent of patients referred to a syncope/collapse clinic, are usually
distinguished by having multiple recurrences of apparent collapse, prolonged duration of
apparent TLOC (often many minutes), absence of physical injury, and absence of evidence
pointing toward a cause for syncope or evidence of seizure activity [35-37]. (See
"Psychogenic nonepileptic seizures: Etiology, clinical features, and diagnosis".)
● Metabolic and/or toxic abnormalities – Metabolic or toxic abnormalities are rarely

associated with an abrupt onset or complete brisk recovery; syncope is therefore rare in
this setting. Hypoglycemia and encephalitis can cause coma, stupor, and confusion, but
rarely the transient loss of consciousness characteristic of syncope. Although metabolic
abnormalities (such as hypoglycemia or hypoxia) infrequently cause syncope, they can
cause impaired consciousness that may be difficult to distinguish from syncope. Metabolic
abnormalities, anemia, and hypovolemia can be effectively managed by specific therapy to

correct these abnormalities.
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Syncope".)
INFORMATION FOR PATIENTS
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the
Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade
reading level, and they answer the four or five key questions a patient might have about a given
condition. These articles are best for patients who want a general overview and who prefer
short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more
sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading
level and are best for patients who want in-depth information and are comfortable with some
medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print
or e-mail these topics to your patients. (You can also locate patient education articles on a
variety of subjects by searching on "patient info" and the keyword[s] of interest.)
● Basics topic (see "Patient education: Syncope (fainting) (The Basics)")
● Beyond the Basics topic (see "Patient education: Syncope (fainting) (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
● Epidemiology – Syncope is a common clinical problem, which is one of the many causes
of transient loss of consciousness (TLOC). Syncope has a lifetime prevalence in the
population as a whole of approximately 20 percent. Syncope is responsible for between 1
and 3 percent of all emergency department visits and 1 percent of all hospital admissions.
(See 'Epidemiology' above.)
● Causes – The possible causes of TLOC resulting in true syncope are generally grouped into
four major categories ( table 1): reflex syncope (neurally-mediated), orthostatic syncope,
cardiac arrhythmias, and structural cardiopulmonary disease. (See 'Causes of syncope'

above.)
● Causes of nonsyncopal attacks – In the evaluation of a patient with TLOC in whom

syncope is suspected, the clinician must necessarily consider and exclude conditions that
mimic TLOC/syncope but are not true syncope ( algorithm 1). The most common of
these conditions are seizures, sleep disturbances, accidental falls, and some psychiatric
conditions (eg, conversion reactions resulting in psychogenic nonepileptic seizures,
previously called psychogenic pseudoseizures). (See 'Causes of nonsyncopal attacks' above
and "Evaluation and management of the first seizure in adults" and "Classification of sleep
disorders" and "Psychogenic nonepileptic seizures: Etiology, clinical features, and
diagnosis".)
Atherosclerotic disease of the cerebral arteries is almost never the cause of true syncopal
symptoms, as the brain has a very redundant blood supply. Instead, stroke and transient
ischemia attacks cause focal neurologic deficits that do not recover rapidly or completely.
(See 'Cerebrovascular disease' above.)
● Syncope of unknown origin – When the initial evaluation, including history, physical
examination, and ECG, is nondiagnostic in a patient with suspected syncope, the patient is
considered to have syncope with an unexplained diagnosis (ie, syncope of unknown
origin). The frequency of an "unknown" cause was previously approximately one-third of
cases, but is now closer to 10 percent as syncope experts and specialized syncope
diagnostic clinics have become more widely available. As a rule, syncope of unknown
cause is generally associated with a good prognosis, suggesting that most are likely
"reflex" in origin. (See 'Syncope of unknown origin' above.)
Use of UpToDate is subject to the Terms of Use.
REFERENCES
1. Chen LY, Shen WK, Mahoney DW, et al. Prevalence of syncope in a population aged more
than 45 years. Am J Med 2006; 119:1088.e1.
2. Shen WK, Sheldon RS, Benditt DG, et al. 2017 ACC/AHA/HRS Guideline for the Evaluation
and Management of Patients With Syncope: A Report of the American College of
Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, and the
Heart Rhythm Society. J Am Coll Cardiol 2017.
3. Soteriades ES, Evans JC, Larson MG, et al. Incidence and prognosis of syncope. N Engl J Med
2002; 347:878.
4. Lipsitz LA. Syncope in the elderly. Ann Intern Med 1983; 99:92.
5. Freed LA, Eagle KA, Mahjoub ZA, et al. Gender differences in presentation, management,
and cardiac event-free survival in patients with syncope. Am J Cardiol 1997; 80:1183.
6. Kapoor WN. Evaluation and outcome of patients with syncope. Medicine (Baltimore) 1990;
69:160.
7. Manolis AS, Linzer M, Salem D, Estes NA 3rd. Syncope: current diagnostic evaluation and
management. Ann Intern Med 1990; 112:850.
8. Costantino G, Sun BC, Barbic F, et al. Syncope clinical management in the emergency
department: a consensus from the first international workshop on syncope risk
stratification in the emergency department. Eur Heart J 2016; 37:1493.
9. Anand V, Benditt DG, Adkisson WO, et al. Trends of hospitalizations for syncope/collapse in
the United States from 2004 to 2013-An analysis of national inpatient sample. J Cardiovasc
Electrophysiol 2018; 29:916.
10. Kadri AN, Abuamsha H, Nusairat L, et al. Causes and Predictors of 30-Day Readmission in
Patients With Syncope/Collapse: A Nationwide Cohort Study. J Am Heart Assoc 2018;
7:e009746.
11. Alboni P, Brignole M, Menozzi C, et al. Diagnostic value of history in patients with syncope
with or without heart disease. J Am Coll Cardiol 2001; 37:1921.
12. Mathias CJ, Deguchi K, Schatz I. Observations on recurrent syncope and presyncope in 641
patients. Lancet 2001; 357:348.
13. Linzer M, Yang EH, Estes NA 3rd, et al. Diagnosing syncope. Part 1: Value of history, physical
examination, and electrocardiography. Clinical Efficacy Assessment Project of the American
College of Physicians. Ann Intern Med 1997; 126:989.
14. Linzer M, Yang EH, Estes NA 3rd, et al. Diagnosing syncope. Part 2: Unexplained syncope.
Clinical Efficacy Assessment Project of the American College of Physicians. Ann Intern Med
1997; 127:76.
15. Olshansky B, Mazuz M, Martins JB. Significance of inducible tachycardia in patients with
syncope of unknown origin: a long-term follow-up. J Am Coll Cardiol 1985; 5:216.
16. Narkiewicz K, Cooley RL, Somers VK. Alcohol potentiates orthostatic hypotension :
implications for alcohol-related syncope. Circulation 2000; 101:398.
17. Rutan GH, Hermanson B, Bild DE, et al. Orthostatic hypotension in older adults. The
Cardiovascular Health Study. CHS Collaborative Research Group. Hypertension 1992;
19:508.
18. Ray CA, Monahan KD. Aging attenuates the vestibulosympathetic reflex in humans.
Circulation 2002; 105:956.
19. Kontny F, Dale J. Self-terminating idiopathic ventricular fibrillation presenting as syncope: a
40-year follow-up report. J Intern Med 1990; 227:211.
20. Benditt DG. Syncope risk assessment in the emergency department and clinic. Prog
Cardiovasc Dis 2013; 55:376.
21. Leitch JW, Klein GJ, Yee R, et al. Syncope associated with supraventricular tachycardia. An
expression of tachycardia rate or vasomotor response? Circulation 1992; 85:1064.
22. Doi A, Miyamoto K, Uno K, et al. Studies on hemodynamic instability in paroxysmal
supraventricular tachycardia: noninvasive evaluations by head-up tilt testing and power
spectrum analysis on electrocardiographic RR variation. Pacing Clin Electrophysiol 2000;
23:1623.
23. Brembilla-Perrot B, Beurrier D, Houriez P, et al. Incidence and mechanism of presyncope
and/or syncope associated with paroxysmal junctional tachycardia. Am J Cardiol 2001;
88:134.
24. Hamer AW, Rubin SA, Peter T, Mandel WJ. Factors that predict syncope during ventricular
tachycardia in patients. Am Heart J 1984; 107:997.
25. Landolina M, Mantica M, Pessano P, et al. Impaired baroreflex sensitivity is correlated with
hemodynamic deterioration of sustained ventricular tachycardia. J Am Coll Cardiol 1997;
29:568.
26. Menozzi C, Brignole M, Garcia-Civera R, et al. Mechanism of syncope in patients with heart
disease and negative electrophysiologic test. Circulation 2002; 105:2741.
27. Kapoor W, Karpf M, Levey GS. Issues in evaluating patients with syncope. Ann Intern Med
1984; 100:755.
28. Krahn AD, Andrade JG, Deyell MW. Selecting appropriate diagnostic tools for evaluating the
patient with syncope/collapse. Prog Cardiovasc Dis 2013; 55:402.
29. Grech ED, Ramsdale DR. Exertional syncope in aortic stenosis: evidence to support
inappropriate left ventricular baroreceptor response. Am Heart J 1991; 121:603.
30. WAYNE HH. Syncope. Physiological considerations and an analysis of the clinical
characteristics in 510 patients. Am J Med 1961; 30:418.
31. Badertscher P, du Fay de Lavallaz J, Hammerer-Lercher A, et al. Prevalence of Pulmonary
Embolism in Patients With Syncope. J Am Coll Cardiol 2019; 74:744.
32. Kenny RA, Brignole M, Dan GA, et al. Syncope Unit: rationale and requirement--the
European Heart Rhythm Association position statement endorsed by the Heart Rhythm
Society. Europace 2015; 17:1325.
33. Brignole M, Moya A, de Lange FJ, et al. 2018 ESC Guidelines for the diagnosis and
management of syncope. Eur Heart J 2018; 39:1883.
34. Sheldon R, Rose S, Ritchie D, et al. Historical criteria that distinguish syncope from seizures.
J Am Coll Cardiol 2002; 40:142.
35. Heyer GL, Harvey RA, Islam MP. Comparison of Specific Fainting Characteristics Between
Youth With Tilt-Induced Psychogenic Nonsyncopal Collapse Versus Reflex Syncope. Am J
Cardiol 2017; 119:1116.
36. Walsh KE, Baneck T, Page RL, et al. Psychogenic pseudosyncope: Not always a diagnosis of
exclusion. Pacing Clin Electrophysiol 2018; 41:480.
37. Tannemaat MR, van Niekerk J, Reijntjes RH, et al. The semiology of tilt-induced psychogenic
pseudosyncope. Neurology 2013; 81:752.
Topic 1049 Version 35.0
GRAPHICS
Major cardiovascular causes of syncope
Reflex-mediated*
Vasovagal
Orthostatic vasovagal syncope: usually after prolonged standing, frequently in a warm
environment, etc
Emotional vasovagal syncope: secondary to fear, pain, medical procedure, etc
Unknown trigger
Situational
Micturition, defecation
Swallowing
Coughing/sneezing
Carotid sinus syndrome
Orthostatic hypotension*
Medication-related
Diuretics (eg, thiazide or loop diuretics)
Vasodilators (eg, dihydropyridine calcium channel blockers, nitrates, alpha blockers, etc)
Antidepressants (eg, tricyclic drugs, SSRIs, etc)
Volume depletion
Hemorrhage
Gastrointestinal losses (ie, vomiting or diarrhea)
Diminished thirst drive (primarily in older patients)
Autonomic failure
Primary: pure autonomic failure, Parkinson disease, multiple system atrophy, Lewy body
dementia
Secondary: diabetes mellitus, amyloidosis, spinal cord injuries, autoimmune neuropathy
(eg, Guillain-Barré), paraneoplastic neuropathy
Cardiac
Tachyarrhythmias
Ventricular tachycardia
Supraventricular tachycardias
Bradyarrhythmias (with inadequate ventricular response)

Sinus node dysfunction
Atrioventricular block
Structural disease
Severe aortic stenosis
Hypertrophic cardiomyopathy
Cardiac tamponade
Prosthetic valve dysfunction
Congenital coronary anomalies
Cardiac masses and tumors (eg, atrial myxoma)
Cardiopulmonary/vascular
Pulmonary embolus
Severe pulmonary hypertension
Aortic dissection
SSRI: selective serotonin reuptake inhibitor.
* Reflex-mediated syncope and syncope due to orthostatic hypotension are more likely to occur, or
are more severe, when other factors may also be contributing, such as medication(s) causing low
blood pressure, volume depletion, pulmonary diseases causing reduction in brain oxygen supply,
alcohol use, and/or environmental factors (excessive heat or humidity).
Adapted from: Brignole M, Moya A, de Lange FJ, et al. 2018 ESC Guidelines for the diagnosis and management of syncope.
Eur Heart J 2018; 39:1883.
Graphic 118175 Version 4.0
Incidence rates of syncope according to age and sex
The incidence rates of syncope per 1000 person-years of follow-up

increased with age among both men and women. The increase in
the incidence rate was steeper starting at the age of 70 years.
Syncope rates were similar among men and women.
Soteriades ES, Evans JC, Larson MG, et al. Incidence and prognosis of syncope. N Engl
J Med 2002; 347:878.
Causes of syncope in pooled data from five population-based studies
Cause Mean prevalence, percent
Neurally mediated
Vasovagal 18
Situational (eg, cough, micturition, defecation, swallow) 5
Carotid sinus syncope 1
Orthostatic hypotension 8
Medications 3
Psychiatric 2
Neurologic 10
Cardiac
Organic heart disease 4
Arrhythmia 14
Unknown 34
Data from Linzer M, Yang EH, Estes M, et al. Ann Intern Med 1997; 126:989. Includes 1002 unselected patients with syncope,
including those from hospital-based referrals, emergency departements, and outpatient clinics between 1984 and 1990.
Causes of syncope in Framingham cohort
Prevalence, percent
Cause
Men Women
Cardiac 13.2 6.7
Stroke or transient ischemic attack 4.3 4.0
Seizure disorder 7.2 3.2
Vasovagal 19.8 22.2
Orthostatic hypotension 8.6 9.9
Medication 6.3 7.2
Other 9.5 6.1
Unknown 31.0 40.7
Includes data from 727 patients.
Data from Soteriades ES, Evans JC, Larson MG, et al. N Engl J Med 2002; 347:878.
Overall survival of patients with syncope
Survival was worst for patients with a cardiovascular cause of syncope. p<0.001 for the comparison
between participants with and those without syncope. The category "Vasovagal and other causes"
includes vasovagal, orthostatic, medication-induced, and other, infrequent cause of syncope.
Sorteriades ES, Evans JC, Larson MG, et al. Incidence and prognosis of syncope. N Engl J Med 2002; 347:878.
Conditions incorrectly diagnosed as syncope
Disorders with partial or complete LOC but without global cerebral hypoperfusion
Epilepsy
Metabolic disorders including hypoglycaemia, hypoxia, hyperventilation with hypocapnia
Intoxication
Vertebrobasilar TIA
Disorders without impairment of consciousness
Cataplexy
Drop attacks
Falls
Functional (psychogenic pseudosyncope)
TIA or carotid origin
LOC: loss of consciousness; TIA: transient ischaemic attack.
Reproduced with permission from: European Heart Rhythm Association (EHRA), Heart Failure Association (HFA), Heart
Rhythm Society (HRS), et al. Guidelines for the diagnosis and management of syncope (version 2009): the Task Force for the
Diagnosis and Management of Syncope of the European Society of Cardiology (ESC). Eur Heart J 2009; 30:2631. Copyright ©
2009 Oxford University Press.
Algorithm for syncope/collapse
This algorithm poses key questions about a collapse episode, including whether and
when LOC occurred. However, in the absence of a credible witness, information
about such episodes is often limited, as the affected individual may not have
accurate recall of the event. Some causes have more than one possible type of
presentation.
LOC: loss of consciousness; BLS: basic life support; ACLS: advanced cardiac life
support; SAH: subarachnoid hemorrhage; TIA: transient ischemic attack.
* This includes actual LOC as well as apparent LOC.
¶ Accidental falls without LOC often have multiple causes, including gait, posture, or
balance impairment, environmental hazard, vertigo, focal seizure, TIA, stroke, and
presyncope.
Δ These conditions result in apparent transient LOC, although consciousness may be

preserved.
◊ Other causes of collapse may cause secondary head trauma.
§ Most TIAs and strokes are not associated with LOC. An SAH may cause transient or
prolonged LOC. A rare cause of LOC is a brainstem stroke.
Differentiation of generalized tonic-clonic seizures from pseudoseizures and

syncope
Generalized
Characteristic seizure tonic- Pseudoseizure Syncope
clonic
Circumstances
Situation Awake or sleep Awake Usually upright; any position if

cardiogenic
Precipitating Sleep loss, alcohol Emotion Emotion, injury, heat, crowds;

factors withdrawal, none if cardiogenic
flashing lights
Presence of Variable Usual Variable

others
Motor phenomena
Vocalization At onset, if any During course None
Location of Proximal limb Proximal limb None

motor
component (if
present)
Generalized Tonic, then clonic Tonic; flailing; struggling Usually atonic; if syncope lasts
motor or thrashing, or both >20 seconds: tonic, then clonic
Tonic posture Partial flexion or Opisthotonic -

straight
Head To one side or Side to side -

movements none
Clonus/limb Bilaterally Asynchronous Bilaterally synchronous

jerks synchronous
Purposeful Absent Occasional, including Absent

movements avoidance
Biting Tongue, inside Lips, arms, other people Tongue biting rare
mouth
Babinski's sign Present Absent Absent
Autonomic features
Micturition Frequent Rare Occasional
Eyes Open Closed Open
Pupils Dilated or hippus Normal Dilated

during attacks
Colour Cyanotic or grey Rubor or normal Pale
Pulse Rapid, strong Normal Slow if vasovagal, weak if

vasodepressor; that of
arrhythmias if cardiogenic
Timing
Usual duration 1 to 5 min 5 to 60 min 1 to 2 min
Onset Sudden Gradual Gradual; possibly sudden if

cardiogenic
Sequence of Stereotyped Variable Stereotyped

symptoms
Termination Spontaneous Spontaneous or induced Rapid

by supraorbital pressure,
suggestion
Sequelae
Injury Frequent, mild; Rare, but multiple bruises If sudden onset

scalp, face, possible; scalp, face, rare
common
Postictal Tired, confused, Alert, emotional outburst Regains consciousness in 2 to 3

sleepy min; alert but tired
Reproduced with permission from: Blume WT. Diagnosis and management of epilepsy. CMAJ 2003; 168:441. Copyright ©
2003 Canadian Medical Association.
Contributor Disclosures
David Benditt, MD Equity Ownership/Stock Options: Medtronic [Pacemakers/event recorders and
defibrillators]. Grant/Research/Clinical Trial Support: Medtronic [Pacemakers/event recorders and
defibrillators]; St Jude Medical. Consultant/Advisory Boards: Medtronic [Pacemakers/event recorders and
defibrillators]; Zoll [Pacemakers/event recorders and defibrillators]. Other Financial Interest: Advanced
CPR Solutions [Outside director]. All of the relevant financial relationships listed have been
mitigated. Peter Kowey, MD, FACC, FAHA, FHRS Equity Ownership/Stock Options: VuMedi [Arrhythmias].
Consultant/Advisory Boards: Acesion Pharma [Arrhythmias];Allergan [Arrhythmias, cardiac safety of non-
cardiac drugs];Boehringer-Ingelheim [Arrhythmias];Bristol-Meyers-Squibb [Arrhythmias];Daiichi Sankyo
[Arrhythmias];Gilead [Arrhythmias];InCarda Therapeutics [Arrhythmias];INSTA [Arrhythmias];Johnson &
Johnson [Arrhythmias];Medtronic [Arrhythmias];Milestone [Arrhythmias];Novartis [Arrhythmias, cardiac
safety of non-cardiac drugs];Pfizer [Arrhythmias];Sanofi [Arrhythmias]. All of the relevant financial
relationships listed have been mitigated. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s)
with ineligible companies to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must
conform to UpToDate standards of evidence.
Conflict of interest policy

Syncope in Adults - Epidemiology, Pathogenesis, and Etiologies

Uploaded by

Copyright:

Available Formats

You might also like

Syncope in Adults - Epidemiology, Pathogenesis, and Etiologies

Uploaded by

Document Information

Original Description:

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Syncope in Adults - Epidemiology, Pathogenesis, and Etiologies

Uploaded by

Copyright:

Available Formats

2/8/22, 12:54 Syncope in adults: Epidemiology, pathogenesis, and etiologies - UpToDate

Official reprint from UpToDate®

Syncope in adults: Epidemiology, pathogenesis, and

Syncope is a clinical syndrome in which transient loss of consciousness (TLOC) is caused by a

Syncope/collapse is a common clinical problem, with a lifetime prevalence in the population as

Syncope/collapse is also a common clinical complaint of patients treated in the emergency

● The cause is unknown in approximately one-fifth to one-third of cases ( table 2 and

● Reflex syncope (neurally-mediated)

Orthostatic (postural) hypotension — Orthostatic (postural) hypotension, defined as a

● Immediate orthostatic hypotension – Many healthy individuals experience a minor form

● Delayed orthostatic hypotension – Episodes of near-syncope or syncope that occur a

● Drug effects, especially antidepressants (tricyclics, phenothiazine) and antihypertensive

● Primary autonomic insufficiency or failure (including pure autonomic failure, multiple

● Secondary autonomic insufficiency (eg, diabetes mellitus and amyloidosis).

● Alcohol consumption which impairs vasoconstriction [16].

● Aging is associated with an increased prevalence of orthostatic hypotension [17]. One

The most common arrhythmic causes of syncope include:

● Ventricular tachyarrhythmias – Syncope resulting from ventricular tachycardia (VT)

● Ventricular bigeminy – Ventricular bigeminy, with ventricular premature beats occurring

● Supraventricular tachyarrhythmias – Supraventricular tachyarrhythmias are only rarely

sympathetic nervous system activation and elevation of catecholamine levels, vasoconstriction

● Hypertrophic cardiomyopathy – Syncope may occur in up to 25 percent of patients who

● Myocardial ischemia – VT and bradyarrhythmias secondary to myocardial ischemia are

● Other causes – Pulmonary embolism, severe pulmonic stenosis, idiopathic pulmonary

● If the posterior cerebral circulation is impaired (vertebrobasilar artery insufficiency),

of consciousness in these patients. (See "Vertebral artery revascularization".)

SYNCOPE OF UNKNOWN ORIGIN

CAUSES OF NONSYNCOPAL ATTACKS

● Seizures – Seizures are the probable cause in 5 to 15 percent of apparent TLOC/collapse

● Psychogenic pseudo-syncope and nonepileptic "seizures" – Conversion disorders can

● Metabolic and/or toxic abnormalities – Metabolic or toxic abnormalities are rarely

abnormalities, anemia, and hypovolemia can be effectively managed by specific therapy to

SOCIETY GUIDELINE LINKS

INFORMATION FOR PATIENTS

● Basics topic (see "Patient education: Syncope (fainting) (The Basics)")

SUMMARY AND RECOMMENDATIONS

cardiac arrhythmias, and structural cardiopulmonary disease. (See 'Causes of syncope'

● Causes of nonsyncopal attacks – In the evaluation of a patient with TLOC in whom

Use of UpToDate is subject to the Terms of Use.

Major cardiovascular causes of syncope

Carotid sinus syndrome

Bradyarrhythmias (with inadequate ventricular response)

SSRI: selective serotonin reuptake inhibitor.

Graphic 118175 Version 4.0

Incidence rates of syncope according to age and sex

The incidence rates of syncope per 1000 person-years of follow-up

Graphic 82449 Version 2.0

Causes of syncope in pooled data from five population-based studies

Cause Mean prevalence, percent

Situational (eg, cough, micturition, defecation, swallow) 5

Carotid sinus syncope 1

Organic heart disease 4

Graphic 55289 Version 2.0

Causes of syncope in Framingham cohort

Cardiac 13.2 6.7

Stroke or transient ischemic attack 4.3 4.0

Seizure disorder 7.2 3.2