152 PART 2 Cardinal Manifestations and Presentation of Diseases

■ FURTHER READING

Bleeker-Rovers CP et al: A prospective multicenter study on fever

of unknown origin: The yield of a structured diagnostic protocol.

Medicine (Baltimore) 86:26, 2007.

Kouijzer IJE et al: Fever of unknown origin: The value of FDG-PET/

CT. Semin Nucl Med 48:100, 2018.

Mulders-Manders C et al: Fever of unknown origin. Clin Med

15:280, 2015.

Mulders-Manders C et al: Long-term prognosis, treatment, and outcome of patients with fever of unknown origin in whom no diagnosis

was made despite extensive investigation: A questionnaire based

study. Medicine (Baltimore) 97:e11241, 2018.

Vanderschueren S et al: Inflammation of unknown origin versus

fever of unknown origin: Two of a kind. Eur J Intern Med 20:4, 2009.

Vanderschueren S et al: Mortality in patients presenting with fever of

unknown origin. Acta Clin Belg 69:12, 2014.

Section 3 Nervous System Dysfunction

21 Syncope

Roy Freeman

Syncope is a transient, self-limited loss of consciousness due to acute

global impairment of cerebral blood flow. The onset is rapid, duration

brief, and recovery spontaneous and complete. Other causes of transient loss of consciousness need to be distinguished from syncope;

these include seizures, vertebrobasilar ischemia, hypoxemia, and hypoglycemia. A syncopal prodrome (presyncope) is common, although loss

of consciousness may occur without any warning symptoms. Typical

presyncopal symptoms include lightheadedness or faintness, dizziness,

weakness, fatigue, and visual and auditory disturbances. The causes of

syncope can be divided into three general categories: (1) neurally mediated syncope (also called reflex or vasovagal syncope), (2) orthostatic

hypotension, and (3) cardiac syncope.

Neurally mediated syncope comprises a heterogeneous group of

functional disorders that are characterized by a transient change in

the reflexes responsible for maintaining cardiovascular homeostasis.

Episodic vasodilation (or loss of vasoconstrictor tone), decreased cardiac output, and bradycardia occur in varying combinations, resulting

in temporary failure of blood pressure control. In contrast, in patients

with orthostatic hypotension due to autonomic failure, these cardiovascular homeostatic reflexes are chronically impaired. Cardiac syncope

may be due to arrhythmias or structural cardiac diseases that cause

a decrease in cardiac output. The clinical features, underlying pathophysiologic mechanisms, therapeutic interventions, and prognoses

differ markedly among these three causes.

■ EPIDEMIOLOGY AND NATURAL HISTORY

Syncope is a common presenting problem, accounting for ~3% of all

emergency department (ED) visits and 1% of all hospital admissions.

The annual cost for syncope-related hospitalization in the United States

is ~$2.4 billion. Syncope has a lifetime cumulative incidence of up to

35% in the general population. The peak incidence in the young occurs

between ages 10 and 30 years, with a median peak around 15 years.

Neurally mediated syncope is the etiology in the vast majority of these

cases. In older adults, there is a sharp rise in the incidence of syncope

after 70 years of age.

In population-based studies, neurally mediated syncope is the most

common cause of syncope. The incidence is higher in women than

men. In young subjects, there is often a family history in first-degree

relatives. Cardiovascular disease due to structural disease or arrhythmias is the next most common cause in most series, particularly in ED

TABLE 21-1 High-Risk Features Indicating Hospitalization or Intensive

Evaluation of Syncope

Chest pain suggesting coronary ischemia

Features of congestive heart failure

Moderate or severe valvular disease

Moderate or severe structural cardiac disease

Electrocardiographic features of ischemia

History of ventricular arrhythmias

Prolonged QT interval (>500 ms)

Repetitive sinoatrial block or sinus pauses

Persistent sinus bradycardia

Bi- or trifascicular block or intraventricular conduction delay with QRS duration

≥120 ms

Atrial fibrillation

Nonsustained ventricular tachycardia

Family history of sudden death

Preexcitation syndromes

Brugada pattern on ECG

Palpitations at time of syncope

Syncope at rest or during exercise

settings and in older patients. Orthostatic hypotension also increases in

prevalence with age because of the reduced baroreflex responsiveness,

decreased cardiac compliance, and attenuation of the vestibulosympathetic reflex associated with aging. Other contributors are reduced fluid

intake and vasoactive medications, also more likely in this age group.

In the elderly, orthostatic hypotension is more common in institutionalized than community-dwelling individuals, most likely explained by

a greater prevalence of predisposing neurologic disorders, physiologic

impairment, and vasoactive medication use among institutionalized

patients.

Syncope of noncardiac and unexplained origin in younger individuals has an excellent prognosis; life expectancy is unaffected. By

contrast, syncope due to a cardiac cause, either structural heart disease

or a primary arrhythmic disorder, is associated with an increased risk

of sudden cardiac death and mortality from other causes. Similarly, the

mortality rate is increased in individuals with syncope due to orthostatic hypotension related to age and the associated comorbid conditions (Table 21-1). The likelihood of hospitalization and mortality risk

are higher in older adults.

■ PATHOPHYSIOLOGY

The upright posture imposes a unique physiologic stress upon humans;

most, although not all, syncopal episodes occur from a standing

position. Standing results in pooling of 500–1000 mL of blood in the

lower extremities, buttocks, and splanchnic circulation. The dependent

pooling leads to a decrease in venous return to the heart and reduced

ventricular filling that result in diminished cardiac output and blood

pressure. These hemodynamic changes provoke a compensatory reflex

response, initiated by the baroreceptors in the carotid sinus and aortic

arch, resulting in increased sympathetic outflow and decreased vagal

nerve activity (Fig. 21-1). The reflex increases peripheral resistance,

venous return to the heart, and cardiac output and thus limits the fall

in blood pressure. If this response fails, as is the case chronically in

orthostatic hypotension and transiently in neurally mediated syncope,

hypotension and cerebral hypoperfusion occur.

Syncope is a consequence of global cerebral hypoperfusion and thus

represents a failure of cerebral blood flow autoregulatory mechanisms.

Myogenic factors, local metabolites, and to a lesser extent autonomic

neurovascular control are responsible for the autoregulation of cerebral

blood flow (Chap. 307). The latency of the autoregulatory response is

5–10 s. Typically, cerebral blood flow ranges from 50–60 mL/min per

100 g brain tissue and remains relatively constant over perfusion pressures ranging from 50–150 mmHg. Cessation of blood flow for 6–8 s

153 Syncope CHAPTER 21

CLASSIFICATION

■ NEURALLY MEDIATED SYNCOPE

Neurally mediated (reflex; vasovagal) syncope is the final pathway

of a complex central and peripheral nervous system reflex arc. There

is a transient change in autonomic efferent activity with increased

parasympathetic outflow, plus sympathoinhibition, resulting in bradycardia, vasodilation, and/or reduced vasoconstrictor tone (the vasodepressor response) and reduced cardiac output. The resulting fall in

systemic blood pressure can then reduce cerebral blood flow to below

the compensatory limits of autoregulation (Fig. 21-3). In order to

develop neurally mediated syncope, a functioning autonomic nervous

system is necessary, in contrast to syncope resulting from autonomic

failure (discussed below).

Multiple triggers of the afferent limb of the reflex arc can result in

neurally mediated syncope. In some situations, these can be clearly

defined, e.g., orthostatic stress and stimulus of the carotid sinus, the

gastrointestinal tract, or the bladder. Often, however, the trigger is

less easily recognized and the cause is multifactorial. Under these

circumstances, it is likely that different afferent pathways converge on

the central autonomic network within the medulla that integrates the

neural impulses and mediates the vasodepressor-bradycardic response.

Classification of Neurally Mediated Syncope Neurally mediated syncope may be subdivided based on the afferent pathway and

provocative trigger. Vasovagal syncope (the common faint) is provoked

FIGURE 21-1 The baroreflex. A decrease in arterial pressure unloads the baroreceptors—the terminals of afferent fibers of the glossopharyngeal and vagus nerves—that are

situated in the carotid sinus and aortic arch. This leads to a reduction in the afferent impulses that are relayed from these mechanoreceptors through the glossopharyngeal

and vagus nerves to the nucleus of the tractus solitarius (NTS) in the dorsomedial medulla. The reduced baroreceptor afferent activity produces a decrease in vagal nerve

input to the sinus node that is mediated via connections of the NTS to the nucleus ambiguus (NA). There is an increase in sympathetic efferent activity that is mediated by

the NTS projections to the caudal ventrolateral medulla (CVLM) (an excitatory pathway) and from there to the rostral ventrolateral medulla (RVLM) (an inhibitory pathway).

The activation of RVLM presympathetic neurons in response to hypotension is thus predominantly due to disinhibition. In response to a sustained fall in blood pressure,

vasopressin release is mediated by projections from the A1 noradrenergic cell group in the ventrolateral medulla. This projection activates vasopressin-synthesizing

neurons in the magnocellular portion of the paraventricular nucleus (PVN) and the supraoptic nucleus (SON) of the hypothalamus. Blue denotes sympathetic neurons, and

green denotes parasympathetic neurons. (From R Freeman: Neurogenic orthostatic hypotension. N Engl J Med 358:615, 2008. Copyright © 2008 Massachusetts Medical

Society. Reprinted with permission.)

will result in loss of consciousness, while impairment of consciousness

ensues when blood flow decreases to 25 mL/min per 100 g brain tissue.

From the clinical standpoint, a fall in systemic systolic blood

pressure to ~50 mmHg or lower will result in syncope. A decrease in

cardiac output and/or systemic vascular resistance—the determinants

of blood pressure—thus underlies the pathophysiology of syncope.

Common causes of impaired cardiac output include decreased effective circulating blood volume, increased thoracic pressure, massive

pulmonary embolus, cardiac brady- and tachyarrhythmias, valvular

heart disease, and myocardial dysfunction. Systemic vascular resistance may be decreased by central and peripheral autonomic nervous

system diseases, sympatholytic medications, and transiently during

neurally mediated syncope. Increased cerebral vascular resistance,

most frequently due to hypocarbia induced by hyperventilation, may

also contribute to the pathophysiology of syncope.

Two patterns of electroencephalographic (EEG) changes occur in

syncopal subjects. The first is a “slow-flat-slow” pattern (Fig. 21-2)

in which normal background activity is replaced with high-amplitude

slow delta waves. This is followed by sudden flattening of the EEG—a

cessation or attenuation of cortical activity—followed by the return of

slow waves, and then normal activity. A second pattern, the “slow pattern,” is characterized by increasing and decreasing slow wave activity

only. The EEG flattening that occurs in the slow-flat-slow pattern is a

marker of more severe cerebral hypoperfusion. Despite the presence of

myoclonic movements and other motor activity during some syncopal

events, EEG seizure discharges are not detected.

154 PART 2 Cardinal Manifestations and Presentation of Diseases

88 bpm 45 bpm

X2-X1ECG

Cz-C3

C4-Cz

C3-O1

C4-O2

T4-C4

0 mm Hg

50

75

100

ECG

EEG

Blood pressure

Asystole 10 s

Slow

Jerks Jerks

Unresponsive

Flat Slow

FIGURE 21-2 The electroencephalogram (EEG) in vasovagal syncope. A 1-min segment of a tilt-table test with typical vasovagal syncope demonstrating the “slow-flatslow” EEG pattern. Finger beat-to-beat blood pressure, electrocardiogram (ECG), and selected EEG channels are shown. EEG slowing starts when systolic blood pressure

drops to ~50 mmHg; heart rate is then ~45 beats/min (bpm). Asystole occurred, lasting about 8 s. The EEG flattens for a similar period, but with a delay. A transient loss of

consciousness, lasting 14 s, was observed. There were muscle jerks just before and just after the flat period of the EEG. (From W Wieling et al: Symptoms and signs of

syncope: a review of the link between physiology and clinical clues. Brain 132:2630, 2009. Reprinted (and translated) by permission of Oxford University Press on behalf of

the Guarantors of Brain.)

Time (s)

60 120 180 240 300 360

BP (mm Hg)

0

25

50

75

100

125

150

HR (bpm)

25

50

75

100

125

HR (bpm)

20

40

60

80

100

120

Time (s)

120 140 160 180 200

BP (mm Hg)

20

40

60

80

100

120

A B

FIGURE 21-3 A. The paroxysmal hypotensive-bradycardic response that is characteristic of neurally mediated syncope. Noninvasive beat-to-beat blood pressure and heart

rate are shown >5 min (from 60 to 360 s) of an upright tilt on a tilt table. B. The same tracing expanded to show 80 s of the episode (from 80 to 200 s). BP, blood pressure; bpm,

beats per minute; HR, heart rate.

by intense emotion, pain, and/or orthostatic stress, whereas the situational reflex syncopes have specific localized stimuli that provoke the

reflex vasodilation and bradycardia that leads to syncope. The underlying mechanisms have been identified and pathophysiology delineated

for most of these situational reflex syncopes. The afferent trigger may

originate in the pulmonary system, gastrointestinal system, urogenital

system, heart, and carotid sinus in the carotid artery (Table 21-2).

Hyperventilation leading to hypocarbia and cerebral vasoconstriction,

and raised intrathoracic pressure that impairs venous return to the

heart, play a central role in many of the situational reflex syncopes.

The afferent pathway of the reflex arc differs among these disorders,

but the efferent response via the vagus and sympathetic pathways is

similar.

Alternately, neurally mediated syncope may be subdivided based on

the predominant efferent pathway. Vasodepressor syncope describes

syncope predominantly due to efferent, sympathetic, vasoconstrictor

failure; cardioinhibitory syncope describes syncope predominantly

associated with bradycardia or asystole due to increased vagal outflow;

155 Syncope CHAPTER 21

and mixed syncope describes syncope in which there are both vagal

and sympathetic reflex changes.

Features of Neurally Mediated Syncope In addition to symptoms of orthostatic intolerance such as dizziness, lightheadedness, and

fatigue, premonitory features of autonomic activation may be present

in patients with neurally mediated syncope. These include diaphoresis,

pallor, palpitations, nausea, hyperventilation, and yawning. During the

syncopal event, proximal and distal myoclonus (typically arrhythmic

and multifocal) may occur, raising the possibility of a seizure. The eyes

typically remain open and usually deviate upward. Pupils are usually

dilated. Roving eye movements may occur. Grunting, moaning, snorting, and stertorous breathing may be present. Urinary incontinence

may occur. Fecal incontinence is very rare, however. Postictal confusion is also rare, although visual and auditory hallucinations and neardeath and out-of-body experiences are sometimes reported.

Although some predisposing factors and provocative stimuli are

well established (for example, motionless upright posture, warm ambient temperature, intravascular volume depletion, alcohol ingestion,

hypoxemia, anemia, pain, the sight of blood, venipuncture, and intense

emotion), the underlying basis for the widely different thresholds for

syncope among individuals exposed to the same provocative stimulus

is not known. A genetic basis for neurally mediated syncope may

exist; several studies have reported an increased incidence of syncope

in first-degree relatives of fainters, but no gene or genetic marker has

been identified, and environmental, social, and cultural factors have

not been excluded by these studies.

TREATMENT

Neurally Mediated Syncope

Reassurance, education, avoidance of provocative stimuli, and

plasma volume expansion with fluid and salt are the cornerstones

of the management of neurally mediated syncope. Isometric counterpressure maneuvers of the limbs (tensing of the abdominal and

leg muscles, handgrip and arm tensing, and leg crossing) may raise

blood pressure by increasing central blood volume and cardiac

output. Of these, abdominal muscle tensing is the most effective. By

maintaining pressure in the autoregulatory zone, these maneuvers,

which may be particularly helpful in patients with a long prodrome,

avoid or delay the onset of syncope. Randomized controlled trials

support this intervention.

Fludrocortisone, vasoconstricting agents, and β-adrenoreceptor

antagonists are widely used by experts to treat refractory patients,

although there is no consistent evidence from randomized controlled trials for any pharmacotherapy to treat neurally mediated

syncope. Because vasodilation, decreased central blood volume,

decreased stroke volume and cardiac output are the dominant

pathophysiologic syncopal mechanisms in most patients, use of a

cardiac pacemaker is rarely beneficial. A systematic review of the

literature examining whether cardiac pacing reduces risk of recurrent syncope and relevant clinical outcomes in adults with neurally

mediated syncope, concluded that the existing evidence does not

support the use of routine cardiac pacing. Possible exceptions are

(1) older patients (>40 years), with at least three prior episodes

associated with asystole (of at least 3 s associated with syncope or at

least 6 s associated with presyncope) documented by an implantable

loop recorder; and (2) patients with prominent cardioinhibition due

to carotid sinus syndrome. In these patients, dual-chamber pacing

may be helpful, although this continues to be an area of uncertainty.

■ ORTHOSTATIC HYPOTENSION

Orthostatic hypotension, defined as a reduction in systolic blood

pressure of at least 20 mmHg or diastolic blood pressure of at least

10 mmHg after 3 min of standing or head-up tilt on a tilt table, is

a manifestation of sympathetic vasoconstrictor (autonomic) failure

(Fig. 21-4). In many (but not all) cases, there is no compensatory

TABLE 21-2 Causes of Syncope

A. Neurally Mediated Syncope

Vasovagal syncope

 Provoked fear, pain, anxiety, intense emotion, sight of blood, unpleasant

sights and odors, orthostatic stress

Situational reflex syncope

 Pulmonary

 Cough syncope, wind instrument player’s syncope, weightlifter’s

syncope, “mess trick”a

 and “fainting lark,”b

 sneeze syncope, airway

instrumentation

 Urogenital

 Postmicturition syncope, urogenital tract instrumentation, prostatic

massage

 Gastrointestinal

 Swallow syncope, glossopharyngeal neuralgia, esophageal stimulation,

gastrointestinal tract instrumentation, rectal examination, defecation

syncope

 Cardiac

 Bezold-Jarisch reflex, cardiac outflow obstruction

 Carotid sinus

 Carotid sinus sensitivity, carotid sinus massage

 Ocular

 Ocular pressure, ocular examination, ocular surgery

B. Orthostatic Hypotension

 Primary autonomic failure due to idiopathic central and peripheral

neurodegenerative diseases—the “synucleinopathies”

 Lewy body diseases

 Parkinson’s disease

 Lewy body dementia

 Pure autonomic failure

 Multiple system atrophy (Shy-Drager syndrome)

Secondary autonomic failure due to autonomic peripheral neuropathies

 Diabetes

 Hereditary amyloidosis (familial amyloid polyneuropathy)

 Primary amyloidosis (AL amyloidosis; immunoglobulin light chain

associated)

 Hereditary sensory and autonomic neuropathies (HSAN) (especially

type III—familial dysautonomia)

 Idiopathic immune-mediated autonomic neuropathy

 Autoimmune autonomic ganglionopathy

 Sjögren’s syndrome

 Paraneoplastic autonomic neuropathy

 HIV neuropathy

Postprandial hypotension

Iatrogenic (drug-induced)

Volume depletion

C. Cardiac Syncope

Arrhythmias

 Sinus node dysfunction

 Atrioventricular dysfunction

 Supraventricular tachycardias

 Ventricular tachycardias

 Inherited channelopathies

Cardiac structural disease

 Valvular disease

 Myocardial ischemia

 Obstructive and other cardiomyopathies

 Atrial myxoma

 Pericardial effusions and tamponade

a

Hyperventilation for ~1 min, followed by sudden chest compression. b

Hyperventilation

(~20 breaths) in a squatting position, rapid rise to standing, then Valsalva maneuver.

156 PART 2 Cardinal Manifestations and Presentation of Diseases

Time (s)

60 120 180 240 300 360

BP (mm Hg)

0

50

100

150

200

HR (bpm)

65

70

75

HR (bpm)

68

70

72

74

Time (s)

180 190 200 210 220

BP (mm Hg)

60

90

120

150

180

A B

FIGURE 21-4 A. The gradual fall in blood pressure without a compensatory heart rate increase that is characteristic

of orthostatic hypotension due to autonomic failure. Blood pressure and heart rate are shown >5 min (from 60

to 360 s) of an upright tilt on a tilt table. B. The same tracing expanded to show 40 s of the episode (from 180 to

220 s). BP, blood pressure; bpm, beats per minute; HR, heart rate.

increase in heart rate despite hypotension; with partial autonomic failure, heart rate may increase to some degree but is insufficient to maintain cardiac output. A variant of orthostatic hypotension is “delayed”

orthostatic hypotension, which occurs beyond 3 min of standing; this

may reflect a mild or early form of sympathetic adrenergic dysfunction.

In some cases, orthostatic hypotension occurs within 15 s of standing

(so-called initial orthostatic hypotension), a finding that may reflect

a transient mismatch between cardiac output and peripheral vascular

resistance and does not represent autonomic failure.

Characteristic symptoms of orthostatic hypotension include

light-headedness, dizziness, and presyncope (near-faintness) occurring in response to sudden postural change. However, symptoms may

be absent or nonspecific, such as generalized weakness, fatigue, cognitive slowing, leg buckling, or headache. Visual blurring may occur,

likely due to retinal or occipital lobe ischemia. Neck pain, typically

in the suboccipital, posterior cervical, and shoulder region (the “coathanger headache”), most likely due to neck muscle ischemia, may be

the only symptom. Patients may report orthostatic dyspnea (thought

to reflect ventilation-perfusion mismatch due to inadequate perfusion

of ventilated lung apices) or angina (attributed to impaired myocardial

perfusion even with normal coronary arteries). Symptoms may be

exacerbated by exertion, prolonged standing, increased ambient temperature, or meals. Syncope is usually preceded by warning symptoms,

but may occur suddenly, suggesting the possibility of a seizure or cardiac cause. Some patients have profound decreases in blood pressure,

sometimes without symptoms but placing them at risk for falls and

injuries if the autoregulatory threshold is crossed with ensuing cerebral

hypoperfusion.

Supine hypertension is common in patients with orthostatic

hypotension due to autonomic failure, affecting >50% of patients in

some series. Orthostatic hypotension may present after initiation

of therapy for hypertension, and supine hypertension may follow

treatment of orthostatic hypotension. However, in other cases, the

association of the two conditions is unrelated to therapy; it may in

part be explained by baroreflex dysfunction in the presence of residual

sympathetic outflow, particularly in patients with central autonomic

degeneration.

Causes of Neurogenic Orthostatic Hypotension Causes of

neurogenic orthostatic hypotension include central and peripheral

autonomic nervous system dysfunction

(Chap. 440). Autonomic dysfunction of

other organ systems (including the bladder, bowels, sexual organs, and sudomotor system) of varying severity frequently

accompanies orthostatic hypotension in

these disorders (Table 21-2).

The primary autonomic degenerative

disorders are multiple system atrophy

(Shy-Drager syndrome; Chap. 440), Parkinson’s disease (Chap. 435), dementia

with Lewy bodies (Chap. 434), and pure

autonomic failure (Chap. 440). These are

often grouped together as “synucleinopathies” due to the presence of α-synuclein,

a protein that aggregates predominantly

in the cytoplasm of neurons in the Lewy

body disorders (Parkinson’s disease,

dementia with Lewy bodies, and pure

autonomic failure) and in the glia in multiple system atrophy.

Peripheral autonomic dysfunction may

also accompany small-fiber peripheral

neuropathies such as those associated with

diabetes mellitus, acquired and hereditary

amyloidosis, immune-mediated neuropathies, and hereditary sensory and autonomic neuropathies (HSAN; particularly

HSAN type III, familial dysautonomia)

(Chaps. 446 and 447). Less frequently, orthostatic hypotension is

associated with the peripheral neuropathies that accompany vitamin

B12 deficiency, neurotoxin exposure, HIV and other infections, and

porphyria.

Patients with autonomic failure and the elderly are susceptible to

falls in blood pressure associated with meals. The magnitude of the

blood pressure fall is exacerbated by large meals, meals high in carbohydrate, and alcohol intake. The mechanism of postprandial syncope

is not fully elucidated.

Orthostatic hypotension is often iatrogenic. Drugs from several

classes may lower peripheral resistance (e.g., α-adrenoreceptor antagonists used to treat hypertension and prostatic hypertrophy; antihypertensive agents of several classes; nitrates and other vasodilators;

tricyclic agents and phenothiazines). Iatrogenic volume depletion

due to diuresis and volume depletion due to medical causes (hemorrhage, vomiting, diarrhea, or decreased fluid intake) may also result in

decreased effective circulatory volume, orthostatic hypotension, and

syncope.

TREATMENT

Orthostatic Hypotension

The first step is to remove reversible causes—usually vasoactive

medications (see Table 440-6). Next, nonpharmacologic interventions should be introduced. These include patient education

regarding staged moves from supine to upright; warnings about the

hypotensive effects of large meals; instructions about the isometric

counterpressure maneuvers that increase intravascular pressure

(see above); and raising the head of the bed to reduce supine hypertension and nocturnal diuresis. Intravascular volume should be

expanded by increasing dietary fluid and salt. If these nonpharmacologic measures fail, pharmacologic intervention with fludrocortisone acetate and vasoconstricting agents such as midodrine and

l-dihydroxyphenylserine should be introduced. Some patients with

intractable symptoms require additional therapy with supplementary agents that include pyridostigmine, atomoxetine, yohimbine,

octreotide, desmopressin acetate (DDAVP), and erythropoietin

(Chap. 440).

157 Syncope CHAPTER 21

APPROACH TO THE PATIENT

Syncope

DIFFERENTIAL DIAGNOSIS

Syncope is easily diagnosed when the characteristic features are

present; however, several disorders with transient real or apparent

loss of consciousness may create diagnostic confusion.

Generalized and partial seizures may be confused with syncope;

however, there are a number of differentiating features. Whereas

tonic-clonic movements are the hallmark of a generalized seizure,

myoclonic and other movements also may occur in up to 90% of

syncopal episodes. Myoclonic jerks associated with syncope may

be multifocal or generalized. They are typically arrhythmic and of

short duration (<30 s). Mild flexor and extensor posturing also may

occur. Partial or partial-complex seizures with secondary generalization are usually preceded by an aura, commonly an unpleasant

smell; fear; anxiety; abdominal discomfort; or other visceral sensations. These phenomena should be differentiated from the premonitory features of syncope.

Autonomic manifestations of seizures (autonomic epilepsy)

may provide a more difficult diagnostic challenge. Autonomic seizures have cardiovascular, gastrointestinal, pulmonary, urogenital,

pupillary, and cutaneous manifestations that are similar to the

premonitory features of syncope. Furthermore, the cardiovascular

manifestations of autonomic epilepsy include clinically significant

tachycardias and bradycardias that may be of sufficient magnitude

to cause loss of consciousness. The presence of accompanying nonautonomic auras may help differentiate these episodes from syncope.

Loss of consciousness associated with a seizure usually lasts

>5 min and is associated with prolonged postictal drowsiness and

disorientation, whereas reorientation occurs almost immediately

after a syncopal event. Muscle aches may occur after both syncope

and seizures, although they tend to last longer and be more severe

following a seizure. Seizures, unlike syncope, are rarely provoked by

emotions or pain. Incontinence of urine may occur with both seizures and syncope; however, fecal incontinence occurs very rarely

with syncope.

Hypoglycemia may cause transient loss of consciousness, typically in individuals with type 1 or type 2 diabetes (Chap. 403)

treated with insulin. The clinical features associated with impending or actual hypoglycemia include tremor, palpitations, anxiety,

diaphoresis, hunger, and paresthesias. These symptoms are due to

autonomic activation to counter the falling blood glucose. Hunger,

in particular, is not a typical premonitory feature of syncope. Hypoglycemia also impairs neuronal function, leading to fatigue, weakness, dizziness, and cognitive and behavioral symptoms. Diagnostic

difficulties may occur in individuals in strict glycemic control;

repeated hypoglycemia impairs the counterregulatory response and

leads to a loss of the characteristic warning symptoms that are the

hallmark of hypoglycemia.

Patients with cataplexy (Chap. 31) experience an abrupt partial

or complete loss of muscular tone triggered by strong emotions,

typically anger or laughter. Unlike syncope, consciousness is maintained throughout the attacks, which typically last between 30 s and

2 min. There are no premonitory symptoms. Cataplexy occurs in

60%–75% of patients with narcolepsy.

The clinical interview and interrogation of eyewitnesses usually

allow differentiation of syncope from falls due to vestibular dysfunction, cerebellar disease, extrapyramidal system dysfunction,

and other gait disorders. A diagnosis of syncope can be particularly

challenging in patients with dementia who experience repeated falls

and are unable to provide a clear history of the episodes. If the fall is

accompanied by head trauma, a postconcussive syndrome, amnesia

for the precipitating events, and/or a loss or alteration of consciousness, this may also contribute to diagnostic difficulty.

Apparent loss of consciousness can be a manifestation of psychiatric disorders such as generalized anxiety, panic disorders, major

■ CARDIAC SYNCOPE

Cardiac (or cardiovascular) syncope is caused by arrhythmias and

structural heart disease. These may occur in combination because

structural disease renders the heart more vulnerable to abnormal electrical activity.

Arrhythmias Bradyarrhythmias that cause syncope include those

due to severe sinus node dysfunction (e.g., sinus arrest or sinoatrial

block) and atrioventricular (AV) block (e.g., Mobitz type II, highgrade, and complete AV block). The bradyarrhythmias due to sinus

node dysfunction are often associated with an atrial tachyarrhythmia,

a disorder known as the tachycardia-bradycardia syndrome. A prolonged pause following the termination of a tachycardic episode is a

frequent cause of syncope in patients with the tachycardia-bradycardia

syndrome. Medications of several classes may also cause bradyarrhythmias of sufficient severity to cause syncope. Syncope due to bradycardia or asystole has been referred to as a Stokes-Adams attack.

Ventricular tachyarrhythmias frequently cause syncope. The likelihood of syncope with ventricular tachycardia is in part dependent

on the ventricular rate; rates <200 beats/min are less likely to cause

syncope. The compromised hemodynamic function during ventricular

tachycardia is caused by ineffective ventricular contraction, reduced

diastolic filling due to abbreviated filling periods, loss of AV synchrony,

and concurrent myocardial ischemia.

Several disorders associated with cardiac electrophysiologic instability and arrhythmogenesis are due to mutations in ion channel subunit

genes. These include the long QT syndrome, Brugada syndrome, and

catecholaminergic polymorphic ventricular tachycardia. The long

QT syndrome is a genetically heterogeneous disorder associated with

prolonged cardiac repolarization and a predisposition to ventricular

arrhythmias. Syncope and sudden death in patients with long QT

syndrome result from a unique polymorphic ventricular tachycardia

called torsades des pointes that degenerates into ventricular fibrillation.

The long QT syndrome has been linked to genes encoding K+ channel

α-subunits, K+ channel β-subunits, voltage-gated Na+ channel, and a

scaffolding protein, ankyrin B (ANK2). Brugada syndrome is characterized by idiopathic ventricular fibrillation in association with right

ventricular electrocardiogram (ECG) abnormalities without structural

heart disease. This disorder is also genetically heterogeneous, although

it is most frequently linked to mutations in the Na+ channel α-subunit,

SCN5A. Catecholaminergic polymorphic tachycardia is an inherited, genetically heterogeneous disorder associated with exercise- or

stress-induced ventricular arrhythmias, syncope, or sudden death.

Acquired QT interval prolongation, most commonly due to drugs, may

also result in ventricular arrhythmias and syncope. These disorders

are discussed in detail in Chap. 255.

Structural Disease Structural heart disease (e.g., valvular disease,

myocardial ischemia, hypertrophic and other cardiomyopathies, cardiac masses such as atrial myxoma, and pericardial effusions) may lead

to syncope by compromising cardiac output. Structural disease may

also contribute to other pathophysiologic mechanisms of syncope. For

example, cardiac structural disease may predispose to arrhythmogenesis; aggressive treatment of cardiac failure with diuretics and/or vasodilators may lead to orthostatic hypotension; and inappropriate reflex

vasodilation may occur with structural disorders such as aortic stenosis

and hypertrophic cardiomyopathy, possibly provoked by increased

ventricular contractility.

TREATMENT

Cardiac Syncope

Treatment of cardiac disease depends on the underlying disorder.

Therapies for arrhythmias include cardiac pacing for sinus node

disease and AV block, and ablation, antiarrhythmic drugs, and

cardioverter-defibrillators for atrial and ventricular tachyarrhythmias. These disorders are best managed by physicians with specialized skills in this area.

158 PART 2 Cardinal Manifestations and Presentation of Diseases

depression, and somatization disorder. These possibilities should be

considered in individuals who faint frequently without prodromal

symptoms. Such patients are rarely injured despite numerous falls.

There are no clinically significant hemodynamic changes concurrent with these episodes. In contrast, transient loss of consciousness

due to vasovagal syncope precipitated by fear, stress, anxiety, and

emotional distress is accompanied by hypotension, bradycardia,

or both.

INITIAL EVALUATION

The goals of the initial evaluation are to determine whether the transient loss of consciousness was due to syncope; to identify the cause;

and to assess risk for future episodes and serious harm (Table 21-1).

The initial evaluation should include a detailed history, thorough

questioning of eyewitnesses, and a complete physical and neurologic examination. Blood pressure and heart rate should be

measured in the supine position and after 3 min of standing to

determine whether orthostatic hypotension is present. High-risk

features on history include: the new onset of chest discomfort,

abdominal pain, shortness of breath or headache; syncope during

exertion or while supine; sudden onset of palpitations followed by

syncope; severe coronary artery or structural heart disease.

High-risk features on examination include an unexplained systolic BP of <90 mmHg; suggestion of gastrointestinal hemorrhage;

persistent bradycardia (<40 beats/min); and an undiagnosed systolic murmur.

An ECG should be performed if there is suspicion of syncope

due to an arrhythmia or underlying cardiac disease. Relevant

electrocardiographic abnormalities include bradyarrhythmias or

tachyarrhythmias, AV block, acute myocardial ischemia, old myocardial infarction, long QTc

, and bundle branch block. This initial

assessment will lead to the identification of a cause of syncope in

~50% of patients and also allows stratification of patients at risk for

cardiac mortality.

Laboratory Tests Baseline laboratory blood tests are rarely helpful

in identifying the cause of syncope. Blood tests should be performed when specific disorders, e.g., myocardial infarction, anemia,

and secondary autonomic failure, are suspected (Table 21-2).

Autonomic Nervous System Testing (Chap. 440) Autonomic testing, including tilt-table testing, can be performed in specialized

centers. Autonomic testing is helpful to uncover objective evidence

of autonomic failure and also to demonstrate a predisposition to

neurally mediated syncope. Autonomic testing includes assessments of parasympathetic autonomic nervous system function (e.g.,

heart rate variability to deep respiration and a Valsalva maneuver),

sympathetic cholinergic function (e.g., thermoregulatory sweat

response and quantitative sudomotor axon reflex test), and sympathetic adrenergic function (e.g., blood pressure response to a

Valsalva maneuver and a tilt-table test with beat-to-beat blood

pressure measurement). The hemodynamic abnormalities demonstrated on the tilt-table test (Figs. 21-3 and 21-4) may be useful in

distinguishing orthostatic hypotension due to autonomic failure

from the hypotensive bradycardic response of neurally mediated

syncope. Similarly, the tilt-table test may help identify patients with

syncope due to immediate or delayed orthostatic hypotension.

Carotid sinus massage should be considered in patients with

symptoms suggestive of carotid sinus syncope and in patients

>40 years with recurrent syncope of unknown etiology. This test

should only be carried out under continuous ECG and blood pressure monitoring and should be avoided in patients with carotid

bruits, possible or known plaques, or stenosis.

Cardiac Evaluation ECG monitoring is indicated for patients with

a high pretest probability of arrhythmia causing syncope. Patients

should be monitored in the hospital if the likelihood of a lifethreatening arrhythmia is high, e.g., patients with severe coronary artery or structural heart disease, nonsustained ventricular

tachycardia, supraventricular tachycardia, paroxysmal atrial fibrillation, trifascicular heart block, prolonged QT interval, Brugada syndrome ECG pattern, syncope during exertion, syncope while seated

or supine, and family history of sudden cardiac death (Table 21-1).

Outpatient Holter monitoring is recommended for patients who

experience frequent syncopal episodes (e.g., one or more per week),

whereas loop recorders, which continually record and erase cardiac

rhythm, are indicated for patients with suspected arrhythmias with

low risk of sudden cardiac death. Loop recorders may be external

(e.g., for evaluation of episodes that occur at a frequency of >1 per

month) or implantable (e.g., if syncope occurs less frequently).

Echocardiography should be performed in patients with a history of cardiac disease or if abnormalities are found on physical

examination or the ECG. Echocardiographic diagnoses that may

be responsible for syncope include aortic stenosis, hypertrophic

cardiomyopathy, cardiac tumors, aortic dissection, and pericardial

tamponade. Echocardiography also has a role in risk stratification

based on the left ventricular ejection fraction.

Treadmill exercise testing with ECG and blood pressure monitoring should be performed in patients who have experienced

syncope during or shortly after exercise. Treadmill testing may help

identify exercise-induced arrhythmias (e.g., tachycardia-related AV

block) and exercise-induced exaggerated vasodilation.

Electrophysiologic studies are indicated in patients with structural heart disease and ECG abnormalities in whom noninvasive

investigations have failed to yield a diagnosis. Electrophysiologic

studies have low sensitivity and specificity and should only be performed when a high pretest probability exists. Currently, these tests

are rarely performed to evaluate patients with syncope.

Psychiatric Evaluation Screening for psychiatric disorders may

be appropriate in patients with recurrent unexplained syncope

episodes. Tilt-table testing, with demonstration of symptoms in the

absence of hemodynamic change, may be useful in reproducing

syncope in patients with suspected psychogenic syncope.

■ FURTHER READING

Brignole M et al: 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart J 39:1883, 2018.

Cheshire WP et al: Electrodiagnostic assessment of the autonomic

nervous system: a consensus statement endorsed by the American

Autonomic Society, American Academy of Neurology, and the International Federation of Clinical Neurophysiology. Clin Neurophysiol

132:666, 2021.

Freeman R et al: Consensus statement on the definition of orthostatic

hypotension, neurally mediated syncope and the postural tachycardia

syndrome. Auton Neurosci 161:46, 2011.

Freeman R et al: Orthostatic Hypotension: JACC State-of-the-Art

Review. J Am Coll Cardiol 72:1294, 2018.

Gibbons CH et al: The recommendations of a consensus panel for

the screening, diagnosis, and treatment of neurogenic orthostatic

hypotension and associated supine hypertension. J Neurol 264:1567,

2017.

Sheldon RS, Raj SR: Pacing and vasovagal syncope: back to our physiologic roots. Clin Auton Res 27:213, 2017.

Shen WK 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. Circulation 136:e60, 2017.

Varosy PD et al: Pacing as a treatment for reflex-mediated (vasovagal,

situational, or carotid sinus hypersensitivity) syncope: a systematic

review for the 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 70:664, 2017.

159 Dizziness and Vertigo CHAPTER 22

Dizziness is an imprecise symptom used to describe a variety of

common sensations that include vertigo, light-headedness, faintness,

and imbalance. Vertigo refers to a sense of spinning or other motion

that may be physiological, occurring during or after a sustained head

rotation, or pathological, due to vestibular dysfunction. The term

light-headedness is classically applied to presyncopal sensations resulting from brain hypoperfusion but as used by patients has little specificity, as it may also refer to other symptoms such as disequilibrium

and imbalance. A challenge to diagnosis is that patients often have difficulty distinguishing among these various symptoms, and the words

they choose do not reliably indicate the underlying etiology.

There are many causes of dizziness. Vestibular dizziness (vertigo

or imbalance) may be due to peripheral disorders that affect the labyrinths or vestibular nerves, or it may result from disruption of central

vestibular pathways. It may be paroxysmal or due to a fixed unilateral

or bilateral vestibular deficit. Acute unilateral lesions cause vertigo due

to a sudden imbalance in vestibular inputs from the two labyrinths.

Bilateral lesions cause imbalance and instability of vision when the

head moves (oscillopsia) due to loss of normal vestibular reflexes.

Presyncopal dizziness occurs when cardiac dysrhythmia, orthostatic hypotension, medication effects, or another cause leads to brain

hypoperfusion. Such presyncopal sensations vary in duration; they

may increase in severity until loss of consciousness occurs, or they

may resolve before loss of consciousness if the cerebral ischemia is

corrected. Faintness and syncope, which are discussed in detail in

Chap. 21, should always be considered when one is evaluating patients

with brief episodes of dizziness or dizziness that occurs with upright

posture. Other causes of dizziness include nonvestibular imbalance,

gait disorders (e.g., loss of proprioception from sensory neuropathy,

parkinsonism), and anxiety.

When evaluating patients with dizziness, questions to consider

include the following: (1) Is it dangerous (e.g., arrhythmia, transient

ischemic attack/stroke)? (2) Is it vestibular? (3) If vestibular, is it

peripheral or central? A careful history and examination often provide sufficient information to answer these questions and determine

whether additional studies or referral to a specialist is necessary.

APPROACH TO THE PATIENT

Dizziness

HISTORY

When a patient presents with dizziness, the first step is to delineate

more precisely the nature of the symptom. In the case of vestibular disorders, the physical symptoms depend on whether the

lesion is unilateral or bilateral, and whether it is acute or chronic.

Vertigo, an illusion of self or environmental motion, implies an

acute asymmetry of vestibular inputs from the two labyrinths or

in their central pathways. Symmetric bilateral vestibular hypofunction causes imbalance but no vertigo. Because of the ambiguity in

patients’ descriptions of their symptoms, diagnosis based simply

on symptom characteristics is typically unreliable. Thus the history

should focus closely on other features, including whether this is the

first attack, the duration of this and any prior episodes, provoking

factors, and accompanying symptoms.

Dizziness can be divided into episodes that last for seconds,

minutes, hours, or days. Common causes of brief dizziness (seconds) include benign paroxysmal positional vertigo (BPPV) and

orthostatic hypotension, both of which typically are provoked by

changes in head and/or body position relative to gravity. Attacks of

vestibular migraine and Ménière’s disease often last hours. When

episodes are of intermediate duration (minutes), transient ischemic

22 Dizziness and Vertigo

Mark F. Walker, Robert B. Daroff

attacks of the posterior circulation should be considered, although

migraine and other causes are also possible.

Symptoms that accompany vertigo may be helpful in distinguishing peripheral vestibular lesions from central causes. Unilateral

hearing loss and other acute aural symptoms (ear pain, pressure,

fullness, new tinnitus) typically point to a peripheral cause. Because

the auditory pathways quickly become bilateral upon entering the

brainstem, central lesions are unlikely to cause unilateral hearing

loss unless the lesion lies near the root entry zone of the auditory

nerve. Symptoms such as double vision, numbness, and limb ataxia

suggest a brainstem or cerebellar lesion.

EXAMINATION

Because dizziness and imbalance can be a manifestation of a variety

of neurologic disorders, the neurologic examination is important in the evaluation of these patients. Focus should be given to

assessment of eye movements, vestibular function, and hearing.

The range of eye movements and whether they are equal in each

eye should be observed. Peripheral eye movement disorders (e.g.,

cranial neuropathies, eye muscle weakness) are usually disconjugate

(different in the two eyes). One should check pursuit (the ability to

follow a smoothly moving target) and saccades (the ability to look

back and forth accurately between two targets). Poor pursuit or

inaccurate (dysmetric) saccades usually indicate central pathology,

often involving the cerebellum. Alignment of the two eyes can be

checked with a cover test: while the patient is looking at a target,

alternately cover the eyes and observe for corrective saccades. A

vertical misalignment may indicate a brainstem or cerebellar lesion.

Finally, one should look for spontaneous nystagmus, an involuntary

back-and-forth movement of the eyes. Nystagmus is most often of

the jerk type, in which a slow drift (slow phase) in one direction

alternates with a rapid saccadic movement (quick phase or fast

phase) in the opposite direction that resets the position of the eyes

in the orbits. Except in the case of acute vestibulopathy (e.g., vestibular neuritis), if primary position nystagmus is easily seen in the

light, it is probably due to a central cause. Two forms of nystagmus

that are characteristic of lesions of the cerebellar pathways are vertical nystagmus with downward fast phases (downbeat nystagmus)

and horizontal nystagmus that changes direction with gaze (gazeevoked nystagmus). By contrast, peripheral lesions typically cause

unidirectional horizontal nystagmus. Use of Frenzel eyeglasses

(self-illuminated goggles with convex lenses that blur the patient’s

vision but allow the examiner to see the eyes greatly magnified) or

infrared video goggles can aid in the detection of peripheral vestibular nystagmus, because they reduce the patient’s ability to use

visual fixation to suppress nystagmus. Table 22-1 outlines key findings that help distinguish peripheral from central causes of vertigo.

The most useful bedside test of peripheral vestibular function is

the head impulse test, in which the vestibulo-ocular reflex (VOR) is

assessed with small-amplitude (~20 degrees) rapid head rotations.

While the patient fixates on a target, the head is rotated quickly to

the left or right. If the VOR is deficient, the rotation is followed by a

catch-up saccade in the opposite direction (e.g., a leftward saccade

TABLE 22-1 Features of Peripheral and Central Vertigo

• Nystagmus from an acute peripheral lesion is unidirectional, with fast phases

beating away from the ear with the lesion. Nystagmus that changes direction

with gaze is due to a central lesion.

• Transient mixed vertical-torsional nystagmus occurs in benign paroxysmal

positional vertigo (BPPV), but pure vertical or pure torsional nystagmus is a

central sign.

• Nystagmus from a peripheral lesion may be inhibited by visual fixation,

whereas central nystagmus is not suppressed.

• Absence of a head impulse sign in a patient with acute prolonged vertigo

should suggest a central cause.

• Unilateral hearing loss suggests peripheral vertigo. Findings such as diplopia,

dysarthria, and limb ataxia suggest a central disorder.

160 PART 2 Cardinal Manifestations and Presentation of Diseases

after a rightward rotation). The head impulse test can identify both

unilateral (catch-up saccades after rotations toward the weak side)

and bilateral (catch-up saccades after rotations in both directions)

vestibular hypofunction.

All patients with episodic dizziness, especially if provoked by

positional change, should be tested with the Dix-Hallpike maneuver. The patient begins in a sitting position with the head turned 45

degrees; holding the back of the head, the examiner then lowers the

patient into a supine position with the head extended backward by

about 20 degrees while watching the eyes. Posterior canal BPPV can

be diagnosed confidently if transient upbeating-torsional nystagmus is seen. If no nystagmus is observed after 15–20 s, the patient is

raised to the sitting position, and the procedure is repeated with the

head turned to the other side. Again, Frenzel goggles may improve

the sensitivity of the test.

Dynamic visual acuity is a functional test that can be useful in

assessing vestibular function. Visual acuity is measured with the

head still and when the head is rotated back and forth by the examiner (about 1–2 Hz). A drop in visual acuity during head motion of

more than one line on a near card or Snellen chart is abnormal and

indicates vestibular dysfunction.

ANCILLARY TESTING

The choice of ancillary tests should be guided by the history and

examination findings. Audiometry should be performed whenever

a vestibular disorder is suspected. Unilateral sensorineural hearing loss supports a peripheral disorder (e.g., vestibular schwannoma). Predominantly low-frequency hearing loss is characteristic

of Ménière’s disease. Videonystagmography includes recordings of

spontaneous nystagmus (if present) and measurement of positional

nystagmus. Caloric testing compares the responses of the two

horizontal semicircular canals, while video head-impulse testing

measures the integrity of each of the six semicircular canals. Vestibular evoked potentials assess otolith reflexes. The test battery

often includes recording of saccades and pursuit to evaluate central

ocular motor function. Neuroimaging is important if a central vestibular disorder is suspected. In addition, patients with unexplained

unilateral hearing loss or vestibular hypofunction should undergo

MRI of the internal auditory canals, including administration of

gadolinium, to rule out a schwannoma.

■ DIFFERENTIAL DIAGNOSIS AND TREATMENT

Treatment of vestibular symptoms should be driven by the underlying

diagnosis. Simply treating dizziness with vestibular suppressant medications is often not helpful and may make the symptoms worse and

prolong recovery. The diagnostic and specific treatment approaches

for the most commonly encountered vestibular disorders are discussed

below.

■ ACUTE PROLONGED VERTIGO (VESTIBULAR NEURITIS)

An acute unilateral vestibular lesion causes constant vertigo, nausea,

vomiting, oscillopsia (motion of the visual scene), and imbalance.

These symptoms are due to a sudden asymmetry of inputs from the

two labyrinths or in their central connections, simulating a continuous

rotation of the head. Unlike BPPV, continuous vertigo persists even

when the head remains still.

When a patient presents with an acute vestibular syndrome, the most

important question is whether the lesion is central (e.g., a cerebellar or

brainstem infarct or hemorrhage), which may be life-threatening, or

peripheral, affecting the vestibular nerve or labyrinth (vestibular neuritis). Attention should be given to any symptoms or signs that point

to central dysfunction (diplopia, weakness or numbness, dysarthria).

The pattern of spontaneous nystagmus, if present, may be helpful

(Table 22-1). If the head impulse test is normal, an acute peripheral

vestibular lesion is unlikely. A central lesion cannot always be excluded

with certainty based on symptoms and examination alone; thus older

patients with vascular risk factors who present with an acute vestibular

syndrome should be evaluated for the possibility of stroke even when

there are no specific findings that indicate a central lesion.

Most patients with vestibular neuritis recover spontaneously,

although chronic dizziness, motion sensitivity, and disequilibrium may

persist. The role of early glucocorticoid therapy is uncertain, as studies

have yielded disparate results. Antiviral medications are of no proven

benefit and are not typically given unless there is evidence to suggest

herpes zoster oticus (Ramsay Hunt syndrome). Vestibular suppressant

medications may reduce acute symptoms but should be avoided after

the first several days because they may impede central compensation

and recovery. Patients should be encouraged to resume a normal level

of activity as soon as possible, and directed vestibular rehabilitation

therapy may accelerate improvement.

■ BENIGN PAROXYSMAL POSITIONAL VERTIGO

BPPV is a common cause of recurrent vertigo. Episodes are brief (<1 min

and typically 15–20 s) and are always provoked by changes in head

position relative to gravity, such as lying down, rising from a supine

position, and extending the head to look upward. Rolling over in bed is

a common trigger that may help to distinguish BPPV from orthostatic

hypotension. The attacks are caused by free-floating otoconia (calcium

carbonate crystals) that have been dislodged from the utricular macula

and have moved into one of the semicircular canals, usually the posterior canal. When head position changes, gravity causes the otoconia

to move within the canal, producing vertigo and nystagmus. With

posterior canal BPPV, the nystagmus beats upward and torsionally (the

upper poles of the eyes beat toward the affected lower ear). Less commonly, the otoconia enter the horizontal canal, resulting in a horizontal

nystagmus when the patient is lying with either ear down. Superior

(also called anterior) canal involvement is rare. BPPV is treated with

repositioning maneuvers that use gravity to remove the otoconia from

the semicircular canal. For posterior canal BPPV, the Epley maneuver

(Fig. 22-1) is the most commonly used procedure. For more refractory cases of BPPV, patients can be taught a variant of this maneuver

that they can perform alone at home. A demonstration of the Epley

maneuver is available online (http://www.dizziness-and-balance.com/

disorders/bppv/bppv.html).

■ VESTIBULAR MIGRAINE

Vestibular migraine is a common yet underdiagnosed cause of episodic

vertigo. Vertigo sometimes precedes a typical migraine headache but

more often occurs without headache or with only a mild headache.

Some patients who have had frequent migraine headaches in the past

present later in life with vestibular migraine as the predominant problem. In vestibular migraine, the duration of vertigo may be from minutes to hours, and some migraineurs also experience more prolonged

periods of disequilibrium (lasting days to weeks). Motion sensitivity

and sensitivity to visual motion (e.g., movies) are common. Even in

the absence of headache, other migraine features may be present, such

as photophobia, phonophobia, or a visual aura. Although data from

controlled studies are generally lacking, vestibular migraine typically

is treated with medications that are used for prophylaxis of migraine

headaches (Chap. 430). Antiemetics may be helpful to relieve symptoms at the time of an attack.

■ MÉNIÈRE’S DISEASE

Attacks of Ménière’s disease consist of vertigo and hearing loss, as well

as pain, pressure, and/or fullness in the affected ear. Low-frequency

hearing loss and aural symptoms are key features that distinguish

Ménière’s disease from other peripheral vestibulopathies and from

vestibular migraine. Audiometry at the time of an attack shows a characteristic asymmetric low-frequency hearing loss; hearing commonly

improves between attacks, although permanent hearing loss may

eventually occur. Ménière’s disease is associated with excess endolymph

fluid in the inner ear; hence the term endolymphatic hydrops. The exact

pathophysiological mechanism, however, remains unclear. Patients

suspected of having Ménière’s disease should be referred to an otolaryngologist for further evaluation. Diuretics and sodium restriction

are typically the initial treatments. If attacks persist, injections of