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CHAPTER 23: SYNCOPE

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DEFINITION

• Presyncope (syncopal prodrome): lightheadedness, faintness, dizziness, weakness, fatigue, visual and auditory disturbances.
• Must be distinguished from: seizures, vertebrobasilar ischemia, hypoxemia, hypoglycemia.

1. Neurally mediated syncope (reflex/vasovagal syncope)
2. Orthostatic hypotension
3. Cardiac syncope

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EPIDEMIOLOGY AND NATURAL HISTORY

• Accounts for ~3% of all ED visits and 1% of all hospital admissions.
• Annual cost of syncope-related hospitalization in the US: ~$2.4 billion.
• Lifetime cumulative incidence: up to 40% of the general population.
• Bimodal age distribution:
  • Young peak: ages 10-30 years (median ~15 years) - mostly neurally mediated
  • Elderly peak: sharp rise after age 70 years
• Neurally mediated syncope: more common in women than men; family history in first-degree relatives common in young.
• Prognosis:
  • Noncardiac/unexplained syncope in young: excellent prognosis, life expectancy unaffected.
  • Cardiac syncope (structural disease or arrhythmia): increased risk of sudden cardiac death and all-cause mortality.
  • Orthostatic hypotension syncope: increased mortality (due to associated comorbidities).

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PATHOPHYSIOLOGY

• Cerebral blood flow is normally ~50-60 mL/100g brain/min.
• Global cessation of cerebral blood flow for as little as 6-8 seconds is sufficient to cause loss of consciousness.
• Common final pathway: a reduction in systemic blood pressure results in global cerebral hypoperfusion.
• The primary determinants of blood pressure are cardiac output and peripheral vascular resistance.
• The baroreflex is the key homeostatic mechanism:

Figure 23-1: The Baroreflex - Easy Explanation

1. Sensors (baroreceptors) are located in the carotid sinus and aortic arch. They continuously monitor blood pressure.
2. When BP drops (e.g., on standing up):
   • Baroreceptors send fewer signals to the brainstem (nucleus tractus solitarius)
   • Brainstem reduces vagal (parasympathetic) outflow to the heart → heart rate increases
   • Brainstem increases sympathetic outflow:
     • To the heart → increased contractility
     • To blood vessels → vasoconstriction (raises peripheral resistance)
3. Net result: BP is restored
4. When BP rises, the opposite happens - more vagal tone, less sympathetic = BP lowered.

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TABLE 23-1: EVALUATION OF SYNCOPE

Risk Stratification Features

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CLASSIFICATION

A. NEURALLY MEDIATED SYNCOPE (Reflex/Vasovagal Syncope)

• Episodic vasodilation (loss of vasoconstrictor tone)
• Decreased cardiac output
• Bradycardia

Classification of Neurally Mediated Syncope

1. Vasovagal syncope - triggered by emotional stress, pain, fear, prolonged standing; the most common form
2. Situational reflex syncope - specific triggers:
   • Cough syncope, sneeze syncope
   • Swallow syncope, defecation syncope
   • Micturition syncope
   • Post-exercise syncope
   • Postprandial syncope
3. Carotid sinus hypersensitivity - triggered by head rotation, tight collar, shaving over carotid sinus
4. Glossopharyngeal neuralgia - triggered by swallowing

• Cardioinhibitory - predominant bradycardia
• Vasodepressor - predominant vasodilation/hypotension
• Mixed - combination of both

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TABLE 23-2: FEATURES OF NEURALLY MEDIATED SYNCOPE

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TREATMENT: Neurally Mediated Syncope

• Patient education and reassurance
• Physical counterpressure maneuvers (PCMs): leg crossing, squatting, arm tensing, lower limb muscle tensing - activates muscle pump, raises venous return; abort impending syncope.
• Increased salt and fluid intake (2-3 L/day, 6-9 g NaCl/day)
• Avoid triggers (prolonged standing, dehydration, alcohol, heat)
• Elevation of head of bed (10-30 cm) to expand blood volume over time
• Tilt training (for recurrent syncope)
• Compression stockings or abdominal binders

• Midodrine (alpha-1 agonist, peripheral vasoconstrictor): most evidence-based drug; taken before activities likely to precipitate syncope
• Fludrocortisone (mineralocorticoid): expands plasma volume
• Beta-blockers: generally not effective; may paradoxically worsen
• SSRIs (e.g., paroxetine, fluoxetine): may help in selected patients
• Pyridostigmine: acetylcholinesterase inhibitor, used in some cases

• Cardiac pacing (dual-chamber): for patients with dominant cardioinhibitory response (severe bradycardia/asystole) on tilt-table or implantable loop recorder; NOT effective for vasodepressor type.

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B. ORTHOSTATIC HYPOTENSION

• Classical orthostatic hypotension: BP drop within 3 min of standing
• Immediate orthostatic hypotension: BP drop within 15 seconds of standing; usually benign
• Delayed orthostatic hypotension: BP drop after >3 min of standing; often early autonomic failure

Causes of Neurogenic Orthostatic Hypotension

• Multiple system atrophy (MSA)
• Pure autonomic failure (PAF)
• Parkinson disease with autonomic failure
• Spinal cord lesions (above T6)

• Diabetes mellitus (most common worldwide)
• Amyloidosis (primary or familial)
• Autoimmune autonomic neuropathy (anti-ganglionic AChR antibodies)
• Hereditary sensory and autonomic neuropathies
• Sjögren syndrome
• HIV autonomic neuropathy
• Paraneoplastic autonomic neuropathy

Treatment: Orthostatic Hypotension

• Liberal salt and fluid intake (2-3 L/day, 6-9 g NaCl/day)
• Head-of-bed elevation (10-30 cm) - reduces overnight diuresis and supine hypertension
• Avoid precipitants: prolonged standing, large carbohydrate meals, alcohol, heat exposure
• Compression stockings and abdominal binders (raise venous return)
• Physical counterpressure maneuvers
• Small frequent meals (reduces postprandial hypotension)
• Bolus water drinking (500 mL cold water) - pressor effect via sympathetic reflex

• Midodrine (alpha-1 agonist): first-line drug; 2.5-10 mg TID; avoid at bedtime (supine hypertension)
• Droxidopa (norepinephrine prodrug): FDA-approved for neurogenic OH; 100-600 mg TID
• Fludrocortisone (mineralocorticoid): 0.1-0.3 mg/day; expands plasma volume; side effects: supine hypertension, hypokalemia, edema
• Pyridostigmine (acetylcholinesterase inhibitor): modestly effective; minimal supine hypertension
• Octreotide (somatostatin analog): for postprandial hypotension
• Caffeine: helpful for postprandial hypotension
• Desmopressin (DDAVP): nocturnal use reduces overnight polyuria and morning orthostatic hypotension
• EPO (erythropoietin): for refractory cases with associated anemia

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C. CARDIAC SYNCOPE

Structural Disease

• Sick sinus syndrome / sinoatrial disease
• AV block (Mobitz II, complete heart block)
• Ventricular tachycardia / ventricular fibrillation
• Supraventricular tachycardia (rapid rate)
• Long QT syndrome (drug-induced or congenital) → Torsades de Pointes
• Brugada syndrome
• Arrhythmogenic right ventricular cardiomyopathy (ARVC)
• WPW syndrome with rapid conduction
• Pacemaker malfunction

Treatment: Cardiac Syncope

• Arrhythmia-based: pacemaker implantation (for bradyarrhythmias), ICD (for VT/VF, Brugada, ARVC, LQTS), catheter ablation (for SVT, WPW), antiarrhythmic drugs.
• Structural disease: treat the underlying condition - aortic valve replacement for AS, surgical/alcohol septal ablation or myectomy for HOCM, anticoagulation for PE, surgical repair for aortic dissection.

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APPROACH TO THE PATIENT: SYNCOPE

Differential Diagnosis

• Neurally mediated (vasovagal, situational, carotid sinus)
• Orthostatic hypotension
• Cardiac (arrhythmia, structural)

• Seizures - tonic-clonic activity, postictal confusion, tongue biting, incontinence, prolonged recovery
• Psychogenic pseudosyncope (functional neurological symptom disorder) - prolonged, no BP/HR change, eyes closed, resists eye opening
• Hypoglycemia - slow onset, slow recovery, hunger, sweating, low glucose
• Hypoxia - cyanosis, respiratory cause
• Vertebrobasilar TIA - associated with diplopia, dysarthria, ataxia; loss of consciousness is rare without other brainstem symptoms
• Drop attacks - fall without loss of consciousness
• Cataplexy - sudden muscle weakness with preserved consciousness

Initial Evaluation

1. Detailed history: circumstances (position, activity, environment), prodrome, witness account (appearance, duration, movements), post-event state (confusion? rapid recovery?), prior episodes, medications, medical history
2. Physical and neurologic examination
3. Vital signs: supine and standing BP/HR (check for orthostatic hypotension)
4. High-risk history features: syncope on exertion/supine, chest pain/dyspnea preceding syncope, sudden palpitations then syncope, structural heart disease
5. High-risk exam features: systolic BP <90 mmHg, signs of GI bleed, bradycardia <40 bpm, undiagnosed systolic murmur
6. ECG: should be performed whenever arrhythmia or cardiac disease is suspected

Laboratory Tests and Testing

• Basic labs: rarely diagnostic but useful when specific disorders suspected (myocardial infarction, anemia, autonomic failure, Addison's)
• CBC, electrolytes, glucose, renal function, cardiac biomarkers (troponin when ischemia suspected)
• Autonomic testing (specialized centers):
  • Heart rate variability (deep breathing, Valsalva) - assesses parasympathetic function
  • Thermoregulatory sweat response / QSART - sympathetic cholinergic
  • Tilt-table test with beat-to-beat BP - distinguishes orthostatic hypotension (autonomic failure) from neurally mediated syncope
  • Useful for diagnosing immediate and delayed orthostatic hypotension
• Carotid sinus massage: consider in >40 years with unexplained recurrent syncope; requires continuous ECG and BP monitoring; avoid with bruits/plaques

Cardiac Evaluation

• ECG monitoring:
  • In-hospital telemetry: for high-risk (severe structural disease, nonsustained VT, SVT, AF, trifascicular block, prolonged QT, Brugada, exertional/supine syncope)
  • Holter monitor (24-48 hr): frequent episodes (daily or almost daily)
  • External loop recorder: episodes >1/month
  • Implantable loop recorder (ILR): episodes occurring rarely; records continuously for up to 3 years; preferred for unexplained syncope with suspected arrhythmia
• Echocardiography: when structural heart disease suspected (murmur, exertional syncope)
• Exercise stress test: for syncope during or immediately after exercise
• Electrophysiology (EP) study: for suspected arrhythmic syncope not captured on monitoring; evaluates sinus node function, AV conduction, and inducibility of VT

Psychiatric Evaluation

• Important when syncope is recurrent, no cause identified, multiple somatic complaints, young patient, high episode frequency without injury.
• Psychiatric conditions associated with syncope/pseudo-syncope:
  • Generalized anxiety disorder and panic disorder (hyperventilation → cerebral vasoconstriction)
  • Major depression
  • Somatization disorder
  • Psychogenic pseudosyncope (functional neurological symptom disorder) - eyes closed, resists eye opening during episode, long duration, aware of surroundings later
• Psychiatric co-morbidity is common even in patients with "organic" syncope; address both.

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CHAPTER 24: DIZZINESS AND VERTIGO

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APPROACH TO THE PATIENT

History

• "What exactly do you feel?" - Ask the patient to describe without leading
• Vertigo = illusion of motion (room spinning or self-spinning) - indicates vestibular disorder
• Lightheadedness/presyncope = feeling faint, "head rush" - indicates cardiovascular/hemodynamic
• Disequilibrium = imbalance without head sensation - suggests cerebellar, proprioceptive, or visual cause
• Non-specific dizziness = vague/floating/rocking sensation - multisensory or functional

Associated Symptoms

• Hearing loss + tinnitus + aural fullness: Meniere's disease
• Hearing loss without tinnitus: bilateral vestibular hypofunction (aminoglycoside toxicity)
• Headache: vestibular migraine
• Diplopia, dysarthria, dysphagia, ataxia: brainstem/cerebellar lesion (central cause)
• Ear pain/discharge: labyrinthitis
• Facial numbness: brainstem lesion
• Tinnitus alone (no hearing loss): may be Meniere's, acoustic neuroma, or functional
• Photophobia/phonophobia, personal/family history of migraine: vestibular migraine

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EXAMINATION

Ocular Motility

• Test smooth pursuit, saccades, and nystagmus in all gaze directions.
• Spontaneous nystagmus direction:
  • Peripheral nystagmus: unidirectional (beats away from the lesion side), horizontal or horizontal-torsional, suppressed by visual fixation, associated with severe vertigo
  • Central nystagmus: may be direction-changing, purely vertical (up- or downbeat), or purely torsional; not suppressed by fixation; may occur with mild or no vertigo
• Skew deviation (vertical misalignment of eyes): indicates brainstem/cerebellar lesion (central)
• Gaze-evoked nystagmus (nystagmus beats in direction of gaze): suggests cerebellar or drug toxicity

Head Impulse Test (HIT)

• Purpose: tests VOR (vestibuloocular reflex) function in the horizontal canal
• Technique: patient fixates on examiner's nose; examiner rapidly turns the head 10-15° to one side; normal VOR keeps eyes on target
• Positive (abnormal) HIT = corrective saccade seen after head turn toward affected side → indicates peripheral vestibular lesion (hypofunction on that side)
• Negative (normal) HIT in a patient with acute vertigo and nystagmus: suggests central cause (stroke!) - this is a red flag
• The HINTS exam (Head Impulse, Nystagmus direction, Test of Skew) helps distinguish peripheral from central acute vertigo:
  • Central pattern = DANGER: Normal HIT + Direction-changing nystagmus + Skew deviation → cerebellar/brainstem stroke

Positioning Maneuvers

• Dix-Hallpike maneuver: test for posterior canal BPPV
  • Position patient from sitting to supine with head turned 45° to one side and neck extended
  • Positive: latency of 1-5 seconds then upbeat-torsional nystagmus lasting <1 minute, with fatigability on repeat
  • Direction of nystagmus indicates which ear is affected (upper pole of torsional component beats toward the affected ear)
• Supine roll test (Pagnini-McClure): for horizontal canal BPPV
  • Patient supine, head turned to each side; horizontal nystagmus that geotropic (beats toward ground) = canalith in that canal

Dynamic Visual Acuity (DVA)

• Tests VOR function during head movement
• Compare visual acuity with head still vs. while shaking head at 2 Hz
• Decline of >2-3 lines on Snellen chart during head movement = abnormal VOR (oscillopsia) = bilateral or severe unilateral vestibular hypofunction

Ancillary Testing

• Audiometry: for all patients with hearing symptoms; asymmetric sensorineural hearing loss → rule out vestibular schwannoma
• MRI brain (with gadolinium, posterior fossa): when central cause suspected; to rule out cerebellopontine angle (CPA) mass; DWI for acute infarct
• Vestibular function tests:
  • Videonystagmography (VNG): caloric testing - warm/cool water stimulates each horizontal canal separately; canal paresis on one side = reduced response
  • Video head impulse test (vHIT): quantitative HIT; can test all 6 canals
  • Vestibular evoked myogenic potentials (VEMP): cervical (cVEMP) tests saccule/inferior vestibular nerve; ocular (oVEMP) tests utricle/superior vestibular nerve
  • Rotary chair testing: for bilateral vestibular hypofunction
• Electrocochleography (ECoG): elevated SP:AP ratio supports endolymphatic hydrops (Meniere's)

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DIFFERENTIAL DIAGNOSIS

Acute Prolonged Vertigo

History and Examination Features

Treatment: Acute Prolonged Vertigo (Vestibular Neuritis)

• Symptomatic (acute phase, first 1-3 days only):
  • Antihistamines: meclizine 25 mg TID, dimenhydrinate
  • Benzodiazepines: lorazepam 0.5-1 mg, diazepam (use sparingly - impairs central compensation)
  • Antiemetics: ondansetron, prochlorperazine, metoclopramide
  • Caution: Vestibular suppressants should NOT be used long-term - they impair vestibular compensation
• Disease-modifying:
  • Glucocorticoids (methylprednisolone): improve recovery of vestibular function; start within 72 hours; taper over 3 weeks
  • Antivirals (valacyclovir): no proven benefit
• Rehabilitation:
  • Vestibular rehabilitation therapy (VRT): mainstay of long-term recovery; gaze stabilization exercises, balance training, habituation exercises; accelerates central compensation

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BPPV (Benign Paroxysmal Positional Vertigo)

• Most common cause of vertigo in all age groups.
• Mechanism: Canalith (otoconia/calcium carbonate crystals) displaced from the utricle into the semicircular canals (usually posterior canal = 90%).
• Clinical features: Brief (seconds, <1 minute) episodes of vertigo triggered by head position changes (rolling in bed, looking up, bending forward); no hearing loss; no tinnitus.
• Diagnosis: Dix-Hallpike (posterior canal BPPV) - upbeat-torsional nystagmus with latency and fatigability.
• Treatment:
  • Epley maneuver (canalith repositioning procedure): highly effective (80-90% single treatment); gravity moves the canalith out of the canal back into the utricle.
  • Semont maneuver: alternative repositioning maneuver.
  • For horizontal canal BPPV: Barbeque roll (Lempert maneuver)
  • Vestibular suppressants are NOT effective for BPPV.
  • Surgical (posterior canal occlusion): for refractory intractable cases.
  • Recurrence rate ~50% over 5 years.

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Vestibular Migraine

• Second most common cause of episodic vertigo (after BPPV).
• Clinical features:
  • Episodic vertigo lasting minutes to 72 hours
  • Associated with headache (not necessarily simultaneous), photophobia, phonophobia
  • Personal or family history of migraine
  • May have positional component
  • No consistent hearing loss (differentiates from Meniere's)
• Diagnosis: Criteria require ≥5 episodes of moderate-severe vestibular symptoms + current/past migraine + at least 50% episodes with migrainous features (headache, photophobia, phonophobia, visual aura).
• Treatment:
  • Acute: Triptans, NSAIDs, vestibular suppressants (meclizine), antiemetics
  • Prophylactic (for frequent episodes):
    • Beta-blockers: propranolol, metoprolol
    • Tricyclic antidepressants: nortriptyline, amitriptyline
    • Calcium channel blockers: verapamil
    • Valproate, topiramate
    • CGRP monoclonal antibodies (erenumab, fremanezumab): newer option
  • Lifestyle: avoid migraine triggers (stress, sleep deprivation, certain foods, bright lights)

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Meniere's Disease

• Pathology: Endolymphatic hydrops (excess endolymph in membranous labyrinth).
• Classic tetrad:
  1. Episodic vertigo - attacks lasting 20 minutes to 12 hours (unlike BPPV = seconds, unlike neuritis = days)
  2. Fluctuating sensorineural hearing loss - low-frequency initially
  3. Tinnitus - low-pitched roaring
  4. Aural fullness/pressure
• Attacks may cluster, then remit; hearing loss and tinnitus may persist between attacks.
• Diagnosis: Audiometry (low-frequency SNHL), ECoG (elevated SP:AP ratio), gadolinium-enhanced MRI (endolymphatic hydrops protocol).
• Treatment:
  • Dietary: Low-sodium diet (<1500 mg/day), caffeine restriction, alcohol avoidance
  • Diuretics: Hydrochlorothiazide-triamterene (acetazolamide or amiloride): reduce endolymph production
  • Betahistine: increases cochlear blood flow; widely used in Europe; evidence variable
  • Acute attacks: Vestibular suppressants (meclizine, lorazepam), antiemetics
  • Intratympanic steroids: for hearing preservation
  • Intratympanic gentamicin: chemical labyrinthectomy; controls vertigo in ~90% but risks further hearing loss; used when hearing is already severely compromised
  • Surgery: Endolymphatic sac decompression, vestibular nerve section (for hearing preservation with refractory vertigo), labyrinthectomy (last resort - sacrifices hearing)

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Vestibular Schwannoma (Acoustic Neuroma)

• Benign tumor of Schwann cells of the vestibular portion of CN VIII, arising in the internal auditory canal (IAC) or at the CPA.
• Usually sporadic (unilateral); bilateral = Neurofibromatosis type 2 (NF2).
• Clinical features:
  • Asymmetric progressive sensorineural hearing loss (high-frequency) - hallmark
  • Tinnitus (unilateral, high-pitched)
  • Slowly progressive unilateral vestibular loss - rarely acute vertigo (gradual - brain compensates)
  • Facial numbness (CN V compression) and facial weakness (CN VII) in larger tumors
  • Diplopia, ataxia (cerebellar compression) in very large tumors
• Diagnosis: Gadolinium-enhanced MRI (test of choice); audiometry (asymmetric SNHL); ABR (abnormal wave V latency).
• Treatment:
  • Observation (watch and wait): for small, slow-growing tumors in elderly/poor surgical candidates; serial MRI.
  • Stereotactic radiosurgery (Gamma Knife): for tumors <3 cm; good tumor control; hearing preservation possible.
  • Microsurgical resection: for larger tumors or growth; approaches: retrosigmoid, translabyrinthine, middle fossa.

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Bilateral Vestibular Hypofunction (BVH)

• Definition: Bilateral loss or severe reduction of vestibular function.
• Causes:
  • Gentamicin/aminoglycoside ototoxicity (most common cause)
  • Meningitis
  • Bilateral vestibular neuritis (rare)
  • Bilateral vestibular schwannoma (NF2)
  • Autoimmune inner ear disease
  • Idiopathic
• Clinical features:
  • Oscillopsia (visual blurring with head movement) - due to failed VOR
  • Chronic disequilibrium and imbalance, worse in dark or on uneven surfaces
  • Gait ataxia - worse without visual cues
  • No vertigo (bilateral loss = no asymmetry to cause spinning)
  • Cognitive impairment may occur over time (hippocampal atrophy)
• Diagnosis:
  • Abnormal DVA (>2-3 Snellen lines lost during head movement)
  • Abnormal bilateral HIT (corrective saccades bilaterally)
  • Caloric testing: bilateral canal paresis
  • vHIT: reduced VOR gain bilaterally
• Treatment:
  • Vestibular rehabilitation therapy (VRT): primary treatment; substitution strategies, gaze stabilization
  • Avoid vestibulotoxic drugs
  • For gentamicin-induced: stop drug immediately

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Central Vestibular Disorders

• Direction-changing or purely vertical nystagmus (pure upbeat or downbeat nystagmus)
• Negative HIT in acute severe vertigo
• Skew deviation
• Additional cranial nerve signs or long tract signs
• Cannot walk or severe truncal ataxia
• Headache or neck pain onset with vertigo
• Age/vascular risk factors

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Functional Dizziness

• Definition: Persistent (>3 months) non-vertiginous dizziness and/or unsteadiness provoked by upright posture, active/passive motion, complex visual environments.
• Often triggered by an initial vestibular or other precipitating event that has since resolved.
• Clinical features:
  • Worse with standing/walking, complex visual environments (stores, crowds, screens)
  • Fluctuates with anxiety, stress
  • Not explained by active organic vestibular/neurologic disorder
  • No objective nystagmus or balance test abnormality (or out of proportion to any finding)
  • Co-morbid anxiety disorder very common
• Diagnosis: Clinical - requires excluding organic causes; supportive = typical history.
• Treatment:
  • Vestibular rehabilitation therapy (VRT): desensitization and habituation
  • Cognitive Behavioral Therapy (CBT): highly effective; addresses catastrophizing, avoidance
  • SSRIs / SNRIs (sertraline, venlafaxine): pharmacological first line for PPPD
  • Education and reassurance
  • Avoid: vestibular suppressants (meclizine, benzodiazepines) - do not help PPPD and may worsen anxiety/dependence

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TABLE 24-1: CAUSES OF DIZZINESS AND VERTIGO

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TABLE 24-2: PERIPHERAL VS. CENTRAL VESTIBULAR SYNDROME

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