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Syncope is episodic loss of consciousness associated with loss of postural tone. The pathophysiology, involving global hypoperfusion of the brain or brainstem, is distinct from that of seizures. The most common causes of syncope are given in Table 12-10.
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VASOVAGAL SYNCOPE (SIMPLE FAINTS)
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Vasovagal syncope occurs in all age groups. Genetic factors may be relevant. Precipitating factors include emotional stimulation, pain, the sight of blood, fatigue, medical instrumentation, blood loss, or prolonged motionless standing. Vagally mediated decreases in arterial blood pressure and heart rate combine to produce CNS hypoperfusion and subsequent syncope. Cerebral ischemia resulting in brief tonic–clonic movements can occur.
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Vasovagal episodes generally begin while the patient is in a standing or seated position and only rarely in a horizontal position (eg, with phlebotomy or intrauterine device insertion). A prodrome lasting 30 to 60 seconds usually precedes syncope and can include marked facial pallor, lassitude, yawning, light-headedness, nausea, diaphoresis, salivation, blurred vision, and tachycardia.
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The patient, who then loses consciousness and falls to the ground, is pale and diaphoretic and has dilated pupils. Breathing continues. The eyes remain open and there is an upward turning of the globes. Bradycardia replaces tachycardia as consciousness is lost. During unconsciousness, abnormal movements may occur, particularly if the patient remains relatively vertical; these are mainly tonic or opisthotonic, but seizure-like tonic–clonic activity is occasionally seen, which can lead to a misdiagnosis of epilepsy. Urinary incontinence may also occur.
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The patient recovers consciousness very rapidly (20-30 seconds) after assuming the horizontal position, but residual nervousness, dizziness, headache, nausea, pallor, diaphoresis, and an urge to defecate may be noted. A postictal confusional state, characteristic of seizures, with disorientation and agitation either does not occur or is very brief (<30 seconds). Syncope may recur, especially if the patient stands within the next 30 minutes.
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Reassurance and a recommendation to avoid precipitating factors are usually the only treatment necessary.
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Recurrent vasovagal syncope (also termed neurally mediated or neurocardiogenic syncope) can be diagnosed by inducing syncope during head-up tilt-testing. The bradycardia and hypotension of syncope can be ameliorated by the alpha-agonist midodrine (2.5 to 10 mg three times daily) or with the alpha-beta adrenergic agonist droxidopa (100 mg three times daily initially). Tilt-training may have benefit. Artificial pacing is ineffective.
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CARDIOVASCULAR SYNCOPE
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A cardiovascular cause is suggested when syncope occurs in a recumbent position, during or after physical exertion, or in a patient with known heart disease. Loss of consciousness related to cardiac disease is most often due to an abrupt decrease in cardiac output with resultant cerebral hypoperfusion. Such cardiac dysfunction can result from cardiac arrest, rhythm disturbances (either brady- or tachyarrhythmias), cardiac inflow or outflow obstruction, intracardiac right-to-left shunts, leaking or dissecting aortic aneurysms, or acute pulmonary embolism (Table 12-11). The diagnosis is established by electrophysiologic study and/or long-term event recording. Event monitors triggered by the patient at the onset of symptoms may be helpful; implantable loop recorders, providing continuous EKG recording for up to 3 years, have a high diagnostic yield in unexplained syncope.
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Cardiac arrest (ventricular fibrillation or asystole) from any cause will result in loss of consciousness in 3 to 5 seconds if the patient is standing or within 15 seconds if the patient is recumbent. Seizure like activity and urinary and fecal incontinence may be seen as the duration of cerebral hypoperfusion increases.
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Supraventricular Tachyarrhythmias
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Supraventricular tachyarrhythmias (atrial or junctional tachycardia, atrial flutter, or atrial fibrillation) may be paroxysmal or chronic. Syncope is preceded most often by sudden brief palpitations or less often by dizziness or dyspnea.
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Heart rates faster than 160 to 200/min reduce cardiac output by decreasing the ventricular filling period or inducing myocardial ischemia. Prolonged tachycardia of 180 to 200 beats or more per minute will produce syncope in 50% of normal persons in the upright posture; in patients with underlying heart disease, a heart rate of 135/min may impair cardiac output enough to induce loss of consciousness. Patients with sinus node dysfunction may develop profound bradycardia or even asystole on termination of their tachyarrhythmias. The diagnosis is established when arrhythmias are demonstrated during a symptomatic episode.
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The postural tachycardia syndrome (POTS) is a systemic disorder that occurs predominantly in women 15-45 years old. Its major symptom is an orthostatic increase in heart rate of 30 or more beats per minute, generally without significant change in blood pressure, occurring on standing from a supine position. Associated symptoms include palpitation, tremulousness, gastrointestinal symptoms, fatigue, sleep disturbances, and migraine. Symptoms are accentuated by dehydration, alcohol, and exercise. The induced heart rate increase diminishes with age.
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Ventricular Tachyarrhythmias
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Ventricular tachyarrhythmias (idiopathic ventricular tachycardia or multiform, frequent, or paired premature ventricular contractions) are found on prolonged ECG monitoring in some patients with syncope. The syncope associated with ventricular tachycardia is characterized by a very brief prodrome (<5 seconds). The duration of syncope and of the arrhythmia are closely linked. Frequent or repetitive premature ventricular contractions alone do not often coincide with syncopal symptoms but are predictive of sudden death. Elevation of the ST segment in the right precordium of young adults, without structural heart disease (Brugada syndrome), predisposes to ventricular arrhythmias and sudden death. Multiple genes, particularly involving sodium channels, have been implicated.
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Mitral Valve Prolapse
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Mitral valve prolapse (click-murmur syndrome) is a common disorder that can be associated with ventricular tachyarrhythmias and resultant syncope in a small number of patients. Other symptoms include nonexertional chest pain, dyspnea, and fatigue. The ECG may be normal or show nonspecific ST-T wave changes or frequent premature ventricular contractions. Diagnosis is by echocardiography.
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Prolonged QT Syndrome
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The congenital prolonged QT-interval syndrome consists of paroxysmal ventricular arrhythmias (often torsades de pointes), syncope (usually during exercise), and sudden death. It is inherited as an autosomal recessive condition associated with deafness or as an autosomal dominant form without deafness. Cardiac events are most common during the early teenage years to the mid-twenties. Genes implicated in prolonged QT syndrome include potassium channels (KCNE1, KCNE2, KCNH2, KCNJ2, KCNJ5, KCNQ1), sodium channels (SCN4B, SCN5A), calcium channels (CACNA13), A kinase anchor protein 9 (AKAP9), ankyrin 2 (ANK2), caveolin 3 (CAV3), and α-1 syntrophin (SNTA1). Sporadic cases also occur. Antiarrhythmic drugs and electrolyte disorders (hypomagnesemia, hypocalcemia, hypokalemia) can also produce QT prolongation. Hereditary cases may respond to β-blockers.
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Sinoatrial Node Disease
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Sinoatrial node disease (ie, sick sinus syndrome), a disorder of older adults, is commonly associated with syncope caused by profound sinus bradycardia, prolonged sinus pauses, or sinus arrest with a slow atrial, junctional, or idioventricular escape rhythm. The diagnosis is by electrocardiographic rhythm identification. Sick sinus syndrome may be inherited as an autosomal recessive or dominant disorder, caused by mutations in the type V voltage-gated sodium channel alpha subunit (SCN5A) or hyperpolarization-activated cyclic nucleotide-gated potassium channel 4 (HCN4) genes, respectively. Patients should be evaluated promptly by a cardiologist, as a permanent pacemaker is necessary in many cases. In tachycardia-bradycardia syndrome, a form of sick sinus syndrome, both types of arrhythmias occur.
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Complete heart block (third-degree atrioventricular block) is a common cause of bradyarrhythmia producing recurrent syncope without prodrome. Permanent atrioventricular conduction abnormalities are easily noted on a routine ECG, but intermittent (paroxysmal) conduction abnormalities may not be present on a random tracing. A normal PR interval on an ECG obtained after the episode does not exclude the diagnosis of transient complete heart block.
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Patients with syncope and documented or suspected complete heart block should be hospitalized promptly. Patients with acute inferior myocardial infarctions are at high risk for atrioventricular block.
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CARDIAC INFLOW OBSTRUCTION
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Atrial or ventricular myxomas and atrial thrombi usually present with embolic events, but they may also produce a left ventricular inflow or outflow obstruction that results in a sudden decrease in cardiac output, followed by syncope. A history of syncope occurring with change in position is classic but uncommon. Echocardiography can confirm the diagnosis. Surgical removal of the myxoma is indicated.
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Constrictive pericarditis or pericardial tamponade presents with dyspnea, thoracic pain, and signs of cardiac failure. Here, any maneuver or drug that decreases heart rate or venous return can result in suddenly inadequate cardiac output and syncope.
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CARDIAC OUTFLOW OBSTRUCTION
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Loss of consciousness from congenital or acquired severe aortic stenosis usually occurs after exercise and is often associated with dyspnea, angina, and diaphoresis. The pathophysiology may involve acute left ventricular failure resulting in coronary hypoperfusion and subsequent ventricular fibrillation, or abrupt increases in left ventricular pressure that stimulate baroreceptors, leading to peripheral vasodilation. Echocardiography can help confirm the diagnosis.
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Symptomatic aortic stenosis requires valve replacement; without treatment, survival after syncope from aortic stenosis is 18 months to 3 years.
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Most pulmonic valve disorders are congenital. Severe pulmonary stenosis can produce syncope, associated with dyspnea and angina, especially after exertion. A hemodynamic process similar to that occurring in aortic stenosis is responsible. Diagnosis is by echocardiology.
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HYPERTROPHIC CARDIOMYOPATHY
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Hypertrophic cardiomyopathy comprises a group of congenital cardiomyopathies inherited as autosomal dominant disorders of variable severity. Many different genes have been implicated. Symptoms usually begin between the second and fourth decades. Dyspnea is the most common presenting complaint and can be associated with chest pain and palpitations. Syncope occurs in 30% of patients, is the presenting complaint in 10% of patients, and characteristically develops during or after exercise, but orthostatic and posttussive episodes also occur. Syncope may be due to left ventricular outflow obstruction, inflow obstruction, or transient arrhythmias. The diagnosis can be confirmed by echocardiography. Propranolol may control symptoms; an implantable cardioverter defibrillator may terminate potentially fatal ventricular arrhythmias.
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DISSECTING AORTIC ANEURYSM
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Although acute onset of severe chest or back pain is the most common presenting symptom, approximately 5% to 10% of patients with acute aortic dissections (usually proximal dissection) present with isolated syncope. In 15% of patients, the dissection is painless. Other neurologic abnormalities (stroke, coma, spinal cord ischemia) may or may not be present. Cardiac tamponade is present and may be etiologic in the majority of patients presenting with syncope. A transthoracic echocardiogram is diagnostic.
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PULMONARY HYPERTENSION & PULMONARY EMBOLUS
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Syncope, often exertional, may be the presenting symptom of pulmonary hypertension. A history of exertional dyspnea is usual, and blood gas analysis shows hypoxemia, even at rest. Syncope is the presenting symptom in approximately 20% of patients experiencing massive pulmonary embolism. The mechanism of syncope is pulmonary vascular occlusion with attenuated cardiac output resulting in reduced cerebral perfusion. Tachy- and bradyarrhythmias may be associated. Upon recovery, such patients are hypotensive, often complain of pleuritic chest pain, dyspnea, and apprehension. Hypotension, tachycardia, tachypnea, hemoptysis, and arterial hypoxemia (O2 saturations are an inadequate screen) frequently accompany these large emboli. Venous thrombosis is a common embolic source; in some cases, embolization may be induced by defecation.
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CEREBROVASCULAR SYNCOPE
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Cerebrovascular disease (Chapter 13, Stroke) is an often suspected but actually uncommon cause of episodic unconsciousness.
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BASILAR ARTERY INSUFFICIENCY
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Basilar artery transient ischemic attacks usually occur after the sixth decade; males with ischemic heart disease and hypertension are most commonly affected. Syncopal attacks occur in about 10% and occur among other symptoms of brainstem ischemia: diplopia, vertigo, ataxia, dysphagia, dysarthria, paresthesias, and drop attacks. Syncopal episodes are typically sudden in onset and brief in duration (seconds to minutes), but when consciousness is lost, recovery is frequently prolonged (30-60 minutes or longer). Isolated unconsciousness without other symptoms of brainstem ischemia is rarely due to basilar artery insufficiency. Two-thirds of patients have recurrent attacks, and strokes eventually occur in approximately one-fifth of all cases. Basilar artery symptoms can also be due to associated subclavian steal. Treatment is discussed in Chapter 13, Stroke.
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SUBCLAVIAN STEAL SYNDROME
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The subclavian steal syndrome results from subclavian or innominate artery stenosis that causes retrograde blood flow in the vertebral artery, diverting flow from the brainstem and producing hypoperfusion. Sudden turning of the head in the direction of the affected side can induce symptoms of vertigo, syncope, and intermittent claudication of the upper extremity. The degree of subclavian artery stenosis that produces symptoms is variable, but even minor (~40%) stenosis may sometimes do so. A difference between blood pressures measured in the two arms is nearly always found, the average difference being a 45 mm Hg decrease in systolic pressure in the arm supplied by the stenotic vessel. Cerebrovascular risk factors should be modified; stroke is rare. Arteriography and revascularization procedures may be considered.
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In ~10% of patients with migraine, syncope occurs during the headache, often on rapid rising to a standing position, suggesting that loss of consciousness is due to orthostatic hypotension; autonomic neuropathy may coexist. The headache can precede or follow the syncopal spell. Migraine without syncope occurs in the majority. Syncopal migraine has both more prolonged unconsciousness and more prolonged recovery than syncope alone. A familial association between migraine and syncope occurs. In some patients, basilar migraine produces symptoms similar to those of basilar artery transient ischemic attacks. Antimigraine prophylactic agents (see Chapter 6, Headache & Facial Pain) are often effective in preventing attacks.
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Takayasu disease, sometimes referred to as pulseless arteritis, is a panarteritis of the aorta and its major branches that is most prevalent in young Asian women. Symptoms of claudication are most common, followed by fatigue, headache, visual disturbances, and dyspnea. Syncope occurs in 10%; precipitating factors include exercise, standing, or head movement. Vascular examination shows an absent or diminished pulse, a blood pressure difference between extremities, bruits, hypertension, stroke, heart failure, and aortic regurgitation. The erythrocyte sedimentation rate and C reactive protein may be elevated. Angioplasty is the treatment of choice although medical approaches include corticosteroids or methotrexate.
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CAROTID SINUS SYNCOPE
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Carotid sinus syncope is uncommon. Men are affected twice as often as women, and most affected individuals are more than 60 years old. Drugs known to predispose to carotid sinus syncope include propranolol, digitalis, and methyldopa. Carotid sinus syncope is diagnosed when carotid sinus massage for 10 seconds (on either side and in supine and upright postures) results in a mixture of bradycardia/hypotension (carotid sinus hypersensitivity) and reproduces spontaneous syncope. Carotid sinus hypersensitivity without syncope is common in older men. Treatment for symptomatic patients is with pacing.
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Carotid sinus syncope may be mistakenly diagnosed when symptoms result from compression of a normal carotid artery contralateral to an occluded internal carotid artery. Carotid sinus massage should not be performed in patients with recent TIA or stroke or with carotid bruit.
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ORTHOSTATIC HYPOTENSION
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Orthostatic hypotension patients represent approximately 15% of syncope patients. Symptomatic orthostasis occurs more often in men than in women, is most common in the sixth and seventh decades, but may appear even in teenagers. Loss of consciousness usually occurs upon rapidly rising to a standing position, standing motionless for a prolonged period (especially after exercise), or standing after prolonged recumbency (especially in the elderly).
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Numerous conditions can produce orthostatic hypotension (Table 12-12), which generally results from either hypovolemia or autonomic dysfunction. The latter may be due to drugs, autonomic neuropathy, or CNS disorders affecting sympathetic pathways in the hypothalamus, brainstem, or spinal cord.
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Orthostatic hypotension may also be a feature of neurodegenerative disorders. Idiopathic orthostatic hypotension is associated with isolated degeneration of postganglionic sympathetic neurons. In multisystem atrophy (Shy-Drager syndrome), degeneration of preganglionic sympathetic neurons occurs in combination with parkinsonian, pyramidal, cerebellar, or lower motor neuron signs. These disorders are discussed in Chapter 11, Movement Disorders.
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The diagnosis of classic orthostatic hypotension is established by demonstrating a decline in blood pressure of at least 20 mm Hg systolic or 10 mm Hg diastolic within 3 minutes of the patient standing from a lying position. Severe orthostatic intolerance associated with heart rate increases (>120/min) without significant hypotension or syncope is termed postural orthostatic tachycardia syndrome (POTS) and is most common in young women (see above).
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A detailed general physical and neurologic examination and laboratory studies (hematocrit, stool occult blood, serum glucose and electrolytes, FTA-ABS, nerve conduction studies) should be directed toward establishing the cause of the disorder. Any medication (particularly diuretics, venodilators such as nitrates, and vasodilators such as α-agonists) that might be responsible for orthostatic hypotension should be discontinued if possible. The patient should be instructed to stand up gradually, to elevate the head of the bed on blocks, and to use waist-high elasticized support hosiery. Rapid ingestion of 500 mL of water on awakening prior to getting out of bed increases blood pressure for an hour. Other therapy is dictated by the specific cause of hypotension.
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After discontinuing hypotension-inducing medications, enhancing hydration, and adding dietary salt, patients with continued symptoms can be treated with regimens that include midodrine (starting at 2.5 mg two or three times daily increasing to 10 mg tid as needed) and droxidopa as blood pressure enhancers. Pyridostigmine and fludrocortisone are next-line agents, and low-dose atomoxetine may be effective with central autonomic failure.
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MISCELLANEOUS CAUSES OF SYNCOPE
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Cough (tussive) syncope occurs chiefly in middle-aged men with chronic obstructive pulmonary disease but has also been reported in children. Coughing, which need not be prolonged, immediately precedes unconsciousness. Cough syncope may occur while the patient is supine. Prodromal symptoms are absent, and the duration of unconsciousness is brief—often only a few seconds. Full recovery of consciousness occurs promptly. A history of similar episodes is common, and symptoms may be reproduced by having the patient cough on request. The cause may be a decrease in cerebral blood flow from increased intracranial pressure, which results from the transmission of cough-induced, markedly increased intrathoracic pressure to the intracranial compartment via the spinal fluid or venous connections. Other data support a baroreflex-mediated fall in total peripheral resistance induced by coughing.
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The condition is usually benign, and there is no specific treatment except for antitussive drugs such as dextromethorphan. Syncopal spells with a pathophysiology similar to that of coughing include laughter-induced syncope and syncope induced by sneezing or weightlifting.
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MICTURITION & DEFECATION SYNCOPE
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Micturition syncope is a cerebral hypoperfusion event occurring almost exclusively in men, probably because of the standing position for urination, and is due to peripheral pooling of blood plus vagally induced bradycardia. Episodes can occur immediately before, during, or after micturition. They are more likely to occur at night after the prolonged recumbency of sleep. Urination in a sitting position usually eliminates the symptoms. Syncope during defecation occurs most often in older women and at night, but it can occur throughout the day. The etiology is speculative, but vasodilation and bradycardia following distension of the rectum has been suggested. Border-zone cerebral ischemia has been reported.
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GLOSSOPHARYNGEAL NEURALGIA
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Glossopharyngeal neuralgia (see Chapter 6, Headache & Facial Pain) is a rare syndrome characterized by intermittent, agonizing, paroxysmal pain localized to the tonsillar pillar or occasionally to the external auditory meatus. The pain is triggered by contact with or movement of the tonsillar pillars, especially during swallowing or talking. Syncope results from activation of a glossopharyngeal-vagal reflex arc, producing transient bradyarrhythmia leading to cerebral hypoperfusion. Carbamazepine 400 to 1000 mg/d orally will prevent pain and bradycardia in most patients. Microvascular decompression of cranial nerve IX or X has been suggested.
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Psychogenic syncope is a diagnosis of exclusion and is often made erroneously. Recording an episode with an implantable loop recorder may be required. Suggestive clinical features are lack of any prodrome, possible secondary gain, bizarre postures and movements, lack of pallor, frequent spells, and a prolonged period of apparent unresponsiveness. Eyes are closed during episodes. Psychogenic spells rarely occur when the patient is alone and are rarely associated with incontinence or injury. Most patients are young or have a well-documented history of conversion disorder. Without such a history, diagnosis after the third decade is suspect.
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The EEG during psychogenic unconsciousness is normal, without the slowing that typically occurs with cerebral hypoperfusion and follows unconsciousness from a seizure. Caloric testing (see Chapter 3, Coma), which produces nystagmus in conscious patients and tonic eye deviation in unconscious patients, can distinguish psychogenic unresponsiveness from coma caused by a metabolic or structural lesion. Establishing a diagnosis of psychogenic pseudosyncope has been associated with a decrease in frequency of episodes.
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Severe episodes of daytime sleepiness, occurring in the setting of adequate nighttime sleep, can mimic syncope. In narcolepsy, a sporadic disorder with an onset between ages 10 and 20, induced sleep episodes are brief and follow a fixed pattern in a given patient. REM sleep is disordered, and REM elements occur during wakefulness. These elements include sleep paralysis and hypnogogic hallucinations-described as dreaming while awake (both occurring at the transition between sleep and waking), as well as motor paralysis of cataplexy (evolving over many seconds, lasting 1-2 minutes, affecting the face and neck before trunk and limbs, and induced by emotion, usually laughing). A decrease in hypocretin neurons of the lateral hypothalamus and a decrease in CSF hypocretin are found in most narcolepsy and all cataplectic patients. A narcolepsy diagnosis is made by history and nocturnal polysomnography to exclude nocturnal sleep disorders, document two or more sleep onset REM periods, and show brief sleep latencies (less than eight minutes). Narcolepsy treatment begins with brief naps in the morning and afternoon. Modafinil (100-400 mg each morning or 200 mg bid) is the first-line pharmacologic therapy. Cataplexy can be attenuated by tricyclic antidepressants (clomipramine 10-150 mg/d). Sleep paralysis and hypnogogic hallucinations are usually addressed by education.