CASE 24

A 67-year-old right-handed woman is seen for evaluation after suffering a fall. She
recalls that she felt light-headed while standing at a supermarket checkout on a busy
day. A few minutes later her discomfort intensified, resulting in dizziness, body warmth,
palpitations, and tremors. She last recalls visual dimming before finding herself on the
ground, and had mild urinary incontinence during the episode. Her daughter was
present throughout the event, and noted her mother appeared pale and diaphoretic prior
to collapsing. As she fell, her body stiffened and her arms were shaking for a few
seconds on the ground. She was unconscious for <30 seconds and appeared dazed
upon awakening, but she recognized her daughter and was able to stand with
assistance. Upon further questioning, you learn that your patient frequently feels light-
headed when first arising from bed in the morning. She also has complaint of urinary
frequency and chronic constipation. She frequently feels a sensation of pins and
needles in the feet at bedtime. The review of systems is otherwise negative. Her history
is significant for diabetes, for which she was recently started on metformin, and
hypertension (HTN), which is controlled with a thiazide diuretic and ACE-inhibitor. She
is overweight, but otherwise the general examination was normal. Blood pressure while
seated is 120/80 mm Hg, and heart rate is 75 beats/min (bpm). On neurological
examination she is alert and speaks fluently. Cranial nerve testing shows no deficit.
There is slight difficulty performing a tandem gait, but her coordination on finger-to-nose
and heel-to-shin testing is normal. She sways mildly when closing her eyes on stance
testing. Muscle strength and tone are normal throughout. Muscle stretch reflexes are 2+
at the upper limbs and knees and 1+ at the ankles. Plantar responses are flexor.
Sensory examination reveals decreased perception of vibration at the toes and
decreased pinprick and temperature sensation in a stocking distribution.

What is your most likely diagnosis?

What is your next diagnostic step?

What is the next step in therapy?

ANSWERS TO CASE 24:

Syncope
Summary: A 67-year-old woman is seen for witnessed syncopal episode of brief
duration and without a postictal period. She felt light-headed while standing at a
supermarket checkout on a busy day. She developed dizziness, body warmth,
palpitations, and tremors. Your patient frequently feels light-headed when first arising in
the morning. Past medical history is remarkable for diabetes and HTN. Vital signs were
normal, and neurological examination was nonfocal.

Most likely diagnosis: Syncope secondary to orthostatic hypotension (OH).

Next diagnostic step: Assess orthostatic blood pressure and pulse. Consider
performing tilt table testing. Obtain a basic metabolic panel, CBC, and an ECG.
Next step in therapy: Ensure that adequate intravascular volume is maintained.

ANALYSIS
Objectives
1. To know the differential diagnosis of syncope.
2. To know the diagnostic criteria for OH.
3. To be familiar with autonomic testing.
4. To be familiar with the treatment options for OH as well as other types of syncope.
Considerations
Falls are a very common problem in the elderly, and frequently is related to syncope.
Syncope is defined as a transient loss of consciousness and postural tone caused by
impaired global cerebral perfusion. This patient is presenting with dizziness, light-
headedness, warmth with associated pallor, and diaphoresis prior to her recent
syncopal event. These are prodromal symptoms commonly seen with reflexive or
orthostatic syncope. Obtaining a good history can give you clues for making the
appropriate conclusion as to cause of syncope. In this patient’s case, her history of
diabetes and peripheral neuropathy points to possible autonomic dysfunction
involvement. Also, this patient describes multiple symptomatic episodes of light-
headedness when moving from a lying to standing position—a classic presentation of
orthostatic hypotension. The autonomic nervous system modulates cardiovascular
function, and its dysfunction is often associated with orthostatic intolerance and
syncope. OH resulting from sympathetic adrenergic failure is prevalent in the elderly. Tilt
table testing, carotid sinus massage, and orthostatic challenge are all warranted. OH is
defined as a fall in blood pressure of at least 20 mm Hg systolic or 10 mm Hg diastolic
within 3 minutes of assuming the upright posture.
Other etiologies to be excluded include seizures, neurodegenerative central nervous
system disorders such as Parkinson disease, stroke or TIA, pulmonary embolus and
cardiac etiologies such as structural disease, arrhythmias, or aortic dissection. Also, this
patient is on antihypertensive medications which could be a contributing factor
especially since patient is being treated with an ACE inhibitor and a thiazide diuretic,
which are infamous for their electrolyte effects. Blood work is necessary to assess for
anemia and electrolyte imbalances, since disruption in these parameters can lead to
syncopal events.
An ECG should be a part of all initial syncope workups because they are a cheap and
effective means of assessing arrhythmias or signs of hypertrophy or heart strain that
could indicate more serious cardiac etiology, such as heart failure or aortic stenosis.
Cardiac causes of syncope are more common in the elderly than in the general
population. The decision on whether to pursue echocardiography should be based on
results of baseline blood work, other diagnostic testing, and thorough cardiac history.
Often, syncope secondary to a cardiac event lacks the prodromal symptoms classically
associated with reflex or vasovagal syncope. Many patients will describe waking up on
the floor without any warning signs prior to passing out. Chest pain and increasing
shortness of breath with activity would also make you more suspicious that this was
more likely cardiac related. Seizures should be on your differential as well. Seizures
may be heralded by an aura and often result in a longer period of loss of consciousness
and postictal confusion. In this case, an EEG is not warranted even though patient
experienced some urinary incontinence post event, as this can occur secondary to
syncope alone.

APPROACH TO:
The Patient with Syncope

DEFINITIONS
SYNCOPE: Transient loss of consciousness and postural tone caused by impaired
global cerebral perfusion
PRESYNCOPE: Prodromal symptoms of light-headedness, warmth, diaphoresis,
nausea, and blurry vision prior to fainting or near fainting
ORTHOSTATIC HYPOTENSION: A fall in systolic blood pressure of at least 20 mm Hg
and diastolic blood pressure of at least 10 mm Hg when a person assumes a standing
position
REFLEX SYNCOPE: Also known as vasovagal syncope is a reflex medicated by the
vagus nerve that results in fainting in response to a trigger such as stress, seeing blood,
violent coughing, or heat, for example. Activation of the sympathetic and
parasympathetic reflexes initiates the hypotension

CLINICAL APPROACH
Etiologies
Noncardiogenic syncope results from various disorders that ultimately share decreased
preload as a common underlying pathophysiology. Firstly, neurally mediated syncope
(NMS), also known as vasovagal or reflex syncope, is due to an exacerbation of an
innate reflex-mediated vasodepressor-bradycardic response. It is a benign condition
that does not increase mortality. Any person can be affected in the proper situational
context, although some individuals are particularly susceptible. Loss of consciousness
occurs from decreased cerebral perfusion when significant bradycardia occurs
concomitantly with markedly decreased venous return to the heart. It can be provoked
by various stimuli, such as fear, carotid sinus stimulation, micturition, defecation, and
coughing. A good test for this disorder is the Valsalva maneuver, in which the patient is
asked to blow into a mouthpiece for 15 seconds while maintaining an expiratory
pressure of 40 mm Hg. The Valsalva ratio is calculated as the proportion of the highest
heart rate achieved during the maneuver to the lowest heart rate within 30 seconds of
cessation. These conditions are treated primarily by trigger avoidance, recognizing
prodrome symptoms, and sitting or lying down to avoid syncopal event. Medications
such as fludrocortisone, midodrine, and paroxetine have been studied and used when
avoidance treatment alone fails. β-Blockers such as metoprolol have been very
popularly used; however, these agents are not recommended for treatment of
vasovagal syncope.
Clinical Presentation
OH is another important cause of syncope in the elderly as noted in the above scenario.
The patient will describe symptoms of presyncope, such as a “veil being pulled over the
eyes.” The patient may feel weak, may transiently appear pale, may drop objects or the
hands may fall to the sides, the eyes may fall back in an opisthotonic appearance, and
there may be a moment prior to falling of awareness. The patient may possibly move
from side to side, and may catch him- or herself, without syncope per se.
The autonomic nervous system modulates cardiovascular function, and its higher
dysfunction prevalence in the elderly is often associated with orthostatic intolerance and
syncope. We have a compensatory mechanism that is mediated by sympathetic
noradrenergic activation, which results in vasoconstriction and increased venous return
to the heart. When this compensatory system is malfunctioning, cardiac preload
reduction results in decreased cardiac output. Ultimately, this results in decreased brain
perfusion, and cerebral function is curtailed due to diminished availability of oxygen and
glucose. Our bodies respond with “fainting” which allows them to theoretically lay
horizontal, allowing ease of blood flow to the brain with less gravitation input.
Hypovolemia is a common etiology or aggravating factor leading to OH in elderly
patients, as daily fluid intake is commonly decreased. Tests include the tilt test or a
variation test, the head-up tilt test, to assess for orthostasis. Treatment of OH typically
includes preventive therapy, which focuses on keeping intravascular volume high by
encouraging fluid intake, compression stocking to aid with venous return to the heart,
and increased salt intake even in patients with associated HTN. Medications such as
fludrocortisone, midodrine, and paroxetine can be used in this condition as well if
preventative treatment alone fails.
There are some neurodegenerative central nervous system disorders that can result
in syncope as well. Of these, Parkinson disease is the most common. The most
frequent etiology of autonomic peripheral neuropathy is diabetes mellitus, which is
associated with syncope secondary to the effect of uncontrolled blood glucose on
nervous system. OH occurs with long-term, uncontrolled diabetes because of efferent
sympathetic vasomotor denervation, causing reduced vasoconstriction of the splanchnic
and other peripheral vascular beds. Tests such as the thermoregulatory sweat test
which allows for analysis of sympathetic cholinergic dysfunction, as well as the
quantitative sudomotor axon reflex test (QSART) which studies postganglionic function
can aid in the assessment of peripheral autonomic neuropathies. Other less common
neuropathic causes of syncope include Guillain-Barre syndrome (acute inflammatory
demyelinating polyradiculoneuropathy), primary amyloidosis, toxic neuropathies, and
Sjogren syndrome. Here it becomes important to treat the underlying condition as well
as symptomatic and preventative treatment as noted with the causes discussed earlier.
In cardiogenic syncope there is decreased cardiac output or outflow obstruction.
Causes of decreased cardiac output include bradyarrhythmias, tachyarrhythmias, and
cardiomyopathies, while outflow obstruction may result from aortic or subaortic stenosis.
Many times these patients will describe a sensation of skipped heartbeats, pause,
tachycardia, or palpitations, and it is common for syncope to occur while supine.
Exertional syncope suggests cardiac outflow obstruction, and should be considered if
patient presents with chest pain and or worsening shortness of breath with normal
activities of daily living. All of these presentations will require further cardiac evaluation
and workup for arrhythmias, cardiomyopathies, or stenosis as etiology of patient’s
syncope.
Other causes that should be considered are medication-induced syncope, TIA, or
cerebral tumor. The elderly are often taking multiple medications that can cause or
aggravate OH. The prevalence of OH is proportional to the number of medications
taken with a higher risk with the use of antihypertensives and antidepressants. A
thorough review of medications and analysis for polypharmacy should be included.
Imaging of the head may be necessary to rule out intracranial hematoma, especially if
patient experienced an unwitnessed fall. Further imaging such as MRI of the head and
neck maybe warranted with suspicion for blood flow restriction as a cause.
Treatment
Treatment is supportive until the underlying cause can be identified and addressed.
Unpredictable syncope is associated with significant risk of morbidity or mortality. If
vasovagal, it is required that the stimuli be avoided, or recognized if exposure is
occurring. If OH is diagnosed, pharmacologic interventions may improve the function
and quality of life; side effects of agents such as midodrine or fludrocortisone should be
monitored. If cardiogenic causes are identified, electrophysiologic manipulation may
potentially provide definitive response. If neurologic, antiepileptic medication may render
protection against ictal events leading to syncope. Narcolepsy or other sleep disorders
can often be pharmacologically managed. Vascular etiologies (eg, cerebrovascular,
carotid, or peripheral vascular disease) need to be medically managed and/or surgically
treated. Endocrine causes such as diabetes mellitus (hypoglycemia, hyperglycemia,
and peripheral neuropathy should be managed. In cases of adrenal insufficiency,
lifelong medications are warranted.
In all cases, proper nutritional intake, physical activities (eg, graded pressure
stockings), and fluid balance (and electrolyte management, as in the case of OH)
strategies are mainstays to general supportive care of the patient with a history of
syncope. Restriction of activities wherein the possibility of syncope could have
catastrophic results (eg, commercial vehicle operator or pilot, etc) are also required. It is
possible that these activities are recreational hobbies for a retired older adult patient.

CLINICAL CASE CORRELATION

See also Case 20 (Osteoarthritis), Case 21 (Falls in the Elderly), Case 22 (Fragility
Fracture/Osteoporosis), Case 23 (Geriatric Trauma), Case 25 (Cerebrovascular
Accident (CVA)), and Case 26 (Complex Partial Seizure).

COMPREHENSION QUESTIONS
24.1 Which of the following is the most common cause of syncope?
A. Vasovagal syncope
B. Orthostatic syncope
C. Cardiac etiologies
D. Seizures
E. Transient ischemic attack

24.2 An 87-year-old woman is brought into the ED by Emergency Medical Services

Authority (EMSA) who reports that the patient was found lying down on the
floor at her nursing home after an unknown period of time. Her only medical
history is positive for hypothyroidism and HTN. Initial vital signs are within
normal limits and the patient is breathing and resting comfortably now. She is
pleasant but confused. Which of the following evaluative strategies are the
LEAST important initially?
A. A thorough history and physical
B. An appropriate blood work including CBC, BMP, TSH
C. An ECG
D. A head CT without contrast
E. A Holter monitor

24.3 A 78-year-old man with known history of HTN, extensive history of CAD with a
CABG 6 years prior presents to the ER with a witnessed presyncopal event
during physical therapy. The event was preceded by paleness, diaphoresis,
and nausea and chest pain. It resolved after he lay down for about 15 minutes.
The patient had 2 stents placed after CABG but is noncompliant with his
antiplatelet therapy. He also had a below-knee amputation (BKA) of his right
lower extremity 6 months prior. What test would be the most important of
those listed for this patient’s presentation?
A. Echocardiogram
B. Carotid ultrasound
C. CBC
D. Head CT

24.4 In your clinic you are seeing an 89-year-old female patient who has a past
medical history of HTN, diabetes mellitus, and hyperlipidemia but otherwise is
in good health. She has been experiencing vasovagal syncopal episodes over
the past 2 years despite lying down when initial symptoms appear, avoiding hot
environments, prolonged standing, and increasing her fluid intake. Which below
is least supported medication treatment option by literature?
A. Fludrocortisone
B. Midodrine
C. Paroxetine
D. Metoprolol
ANSWERS

24.1 A. Vasovagal syncope is the most common etiology of syncope. In a study of

833 patients with syncope, the most common causes were vasovagal or
neurocardiogenic syncope at 28.7%. There is a higher occurrence of
cardiogenic etiologies in the elderly versus the general population; however, it
is not higher than vasovagal responses. Since cardiac causes are more likely
to produce significant morbidity and mortality, this cause is generally thoroughly
investigated. While seizures are common and TIA more frequent in the elderly,
they are not the most common cause of syncope.

24.2 E. A thorough history and physical examination is most helpful to lead to a

diagnosis. Even with a patient is confused, a review of medications, discussion
with nursing home care takers, and examination are important. While the CBC,
ECG, and head CT imaging are important, they are not as helpful as the history
and physical. The Holter monitor is not a first-line assessment for syncope.
Holter monitor maybe used to assess for an arrhythmia that is highly suspected
but cannot be detected with 12-lead ECGs alone. An initial ECG is sufficient on
admission if cardiac cause is low on the differential. A thorough physical and
history is always warranted, as this is the source of majority of information
necessary to make the diagnosis. Initial blood work to assess for anemia and
electrolyte imbalance is important as they show correctable causes. Any
unwitnessed fall especially with loss of consciousness warrants a head CT for
evaluation of hematoma or hemorrhagic stroke.

24.3 A. Patient does have extensive coronary artery disease and peripheral artery
disease history, which does make a vascular etiology very likely and should be
investigated thoroughly. However, in this case, this patient is an elderly
experiencing exertional syncope, which is highly suspicious for aortic stenosis.
Of the choices provided, an echocardiogram of the heart to determine function
and valvular abnormalities would be the most important test. Carotid ultrasound
would not be appropriate, as carotid artery narrowing from PVD is not a
common cause of syncope. Patient does not present with any symptoms or
history that would warrant imaging of the brain. While a CBC is always a good
initial assessment for anemia, it is not the most important test listed to be
ordered for this patient.

24.4 C. Serotonin reuptake inhibitors such as paroxetine, are thought to reduce

central sympathetic activity and recurrent vasovagal syncope. Beta-blockers
are thought to reduce sympathetic activity to avoid vagal reactions. However,
long-term studies do not show benefit despite their long-term use as first-line
therapy. In fact, studies show they reduce blood pressure, which could
exacerbate symptoms. Midodrine is an alpha-agonist and vasoconstrictor.
Patients treated with this showed more symptom-free days and higher quality
of life. Fludrocortisone is a mineralocorticoid that acts on distal tubules to retain
sodium and water, and expand blood volume. Though it is not a well-studied
drug, the studies carried out so far show modest evidence of efficacy.
CLINICAL PEARLS

The etiology of OH in the elderly is often multifactorial.

Neurological disorders, often severe, can be associated with OH.

Autonomic neuropathy and Parkinson disease are common neurological causes of

OH.

Diabetes is a common cause of autonomic neuropathy. Syncope may be the first

manifestation of diabetes.

The management of concomitant OH and HTN represents a conundrum due to

conflicting objectives. Oftentimes, some degree of supine hypertension must be
accepted in order to allow for functional capacity in the upright position.

REFERENCES
Aydin MA, Salukhe TV, Wilke I, Willems S. Management and therapy of vasovagal
syncope: a review. World J Cardiol. Oct 2010,2(10):308-315.
Forman DE, Lipsitz LA. Syncope in the elderly. Cardiol Clin. May 1997;15(2):295-
311.
Low PA. Prevalence of orthostatic hypotension. Clin Auton Res. Mar 2008;18(suppl
1):8-13.
Robertson D. The pathophysiology and diagnosis of orthostatic hypotension. Clin
Auton Res. Mar 2008;18 (suppl 1):2-7.
Soteriades ES, Evans JC, Larson MG, et al. Incidence and prognosis of syncope. N
Engl J Med. 2002;347: 878-885.