This article includes discussion of ulnar neuropathies, Guyon canal neuropathy, ulnar neuropathy at the wrist, and flexor carpi ulnaris exit compression.
Jun. 07, 2021
At vero eos et accusamus et iusto odio dignissimos ducimus qui blanditiis praesentium voluptatum deleniti atque corrupti quos dolores et quas.
Syncope is a specific category of transient loss of consciousness that is “due to transient global cerebral hypoperfusion [and is] characterized by rapid onset, short duration, and spontaneous complete recovery” (111). Narrowing of the field of vision and loss of color vision (graying out) occur, followed by complete loss of vision, loss of consciousness, turning up of the eyeballs, and, possibly, myoclonic jerks. Although the treatment of neurologic or cardiac syncope aims at the underlying cause, the primary treatment of neurovascular syncope consists of patient education and instruction in reasonable precautions.
• Syncope is a specific category of transient loss of consciousness that is “due to transient global cerebral hypoperfusion [and is] characterized by rapid onset, short duration, and spontaneous complete recovery” (111).
• Syncope is a prevalent disorder, accounting for 3% to 5% of emergency department visits and 1% to 3% of hospital admissions.
• Syncope may be confused with seizure, cryptogenic drop attacks, migraine, basilar thrombosis, or metabolic disturbances.
• Unlike true episodes of syncope, episodes of pseudosyncope are not associated with compromised cerebral circulation.
Transient loss of consciousness. Transient loss of consciousness (TLOC) is an umbrella term that encompasses “all disorders that are characterized by self-limited loss of consciousness” (111). The 2018 Task Force for the Diagnosis and Management of Syncope of the European Society of Cardiology operationally defines transient loss of consciousness as “a state of real or apparent [loss of consciousness] with loss of awareness, characterized by amnesia for the period of unconsciousness, abnormal motor control, loss of responsiveness, and a short duration” (28). Unfortunately, many papers inappropriately equate transient loss of consciousness with syncope, distorting estimates of frequency, and generating confusing conclusions and misleading or incorrect recommendations for assessment and management. Categories of nontraumatic transient loss of consciousness include syncope, epileptic seizures, psychogenic pseudosyncope, and psychogenic nonepileptic seizures (111; 28).
Syncope. Syncope is a specific category of transient loss of consciousness that is “due to transient global cerebral hypoperfusion [and is] characterized by rapid onset, short duration, and spontaneous complete recovery” (111; 28). The 2018 Task Force for the Diagnosis and Management of Syncope of the European Society of Cardiology noted that low blood pressure and global cerebral hypoperfusion are “the central final common pathway of syncope” (28). Loss of consciousness will be produced by a sudden cessation of cerebral blood flow for as short as 6 to 8 seconds, or a systolic blood pressure of 50 to 60 mm Hg at the heart level (corresponding to 30 to 45 mm Hg at the brain level in the upright position) (28).
Presyncope. Presyncope and near syncope are terms used “to describe a state that resembles the prodrome of syncope but which is not followed by [loss of consciousness]” although whether the mechanisms involved are the same as in syncope is not entirely clear (111).
Classification and pathophysiology of syncope. Syncope may be classified as reflex (neurally mediated), secondary to orthostatic hypotension, or cardiac (cardiovascular) (111; 28).
Blood pressure is the product of cardiac output and total peripheral vascular resistance. Causes of low total peripheral resistance include: (1) decreased reflex activity causing vasodilatation through withdrawal of sympathetic vasoconstriction as in the vasodepressive type of reflex syncope; (2) a functional impairment of the autonomic nervous system as may occur with various drugs; and (3) a structural impairment of the autonomic nervous system from primary or secondary autonomic failure (28). Causes of low cardiac output include: (1) reflex bradycardia, known as cardioinhibitory reflex syncope; (2) cardiovascular causes, eg, arrhythmia, structural disease including pulmonary embolism, and pulmonary hypertension; (3) inadequate venous return due to volume depletion or venous pooling; and (4) chronotropic and inotropic incompetence through autonomic failure (28).
Reflex syncope. Reflex syncopes are a heterogeneous group of disorders mediated by cardiovascular reflexes that are inappropriately triggered, producing vasodilation and/or bradycardia, with a resultant fall in both blood pressure and cerebral perfusion. Reflex syncopes can be classified as vasovagal, situational, carotid sinus, and atypical (111; 28). Vasovagal syncopes are the most common reflex syncopes and include the common faint; they are often triggered by emotional distress, fear, pain, and instrumentation (eg, blood draw) (111; 28). Atypical vasovagal syncope may be associated with a short or absent prodrome and amnesia for loss of consciousness, thus increasing the possibility of misdiagnosis with nonsyncopal falls (62). Situational syncopes are triggered by specific circumstances such as coughing/sneezing, swallowing, defecation, visceral pain, micturition (or immediately postmicturition), postexercise, postprandial, and weightlifting; they are often forms of reflex syncope, but may not be, or can be multifactorial in causation (111; 28).
Orthostatic hypotension. Syncope due to orthostatic hypotension may result from primary autonomic failure (eg, pure autonomic failure, multisystem atrophy, Parkinson disease, Lewy body dementia), secondary autonomic failure (eg, alcoholism, diabetes mellitus, spinal cord injury), drugs (eg, alcohol, vasodilators, alpha-blockers, beta-blockers, diuretics, phenothiazines, antidepressants), and volume depletion (eg, dehydration, hemorrhage, diarrhea, vomiting) (111; 28; 84).
Cardiac syncope. Cardiac (cardiovascular) syncope may result from bradycardia (eg, sinus node dysfunction including bradycardia/tachycardia syndrome, atrioventricular conduction system disease, and implanted device malfunction), tachycardia (supraventricular or ventricular), structural heart disease (eg, aortic stenosis, acute myocardial ischemia or infarction, hypertrophic cardiomyopathy, atrial myxoma, pericardial tamponade), and cardiopulmonary conditions and disorders of the great vessels, (eg, pulmonary embolism, acute aortic dissection, and pulmonary hypertension) (111; 28). The cardiac subtype is also likely to yield the highest rate of electrocardiographic abnormality. A cardiac cause of syncope is an independent predictor of sudden death, and mortality rates are higher in patients with cardiac syncope compared with those of noncardiac or unknown origin (59).
• In some forms of syncope there may be a prodrome with various symptoms (eg, lightheadedness, nausea, diaphoresis, weakness, and disturbed vision), but in other cases loss of consciousness occurs without warning.
• Neurologic symptoms, when present, are brief and often progress in a stereotyped manner, culminating in loss of consciousness.
• Eye deviation and myoclonus occur frequently ("convulsive syncope"), which may lead to an incorrect diagnosis of epilepsy.
• Loss of consciousness generally lasts 20 seconds at most in cases of reflex syncope, but it can rarely be longer.
• Rarely, epileptic seizures can occur in association with syncope as a result of ictal bradycardia or ictal asystole.
• Cognitive impairment is common in elderly patients with syncope.
In some forms of syncope there may be a prodrome with various symptoms (eg, lightheadedness, nausea, diaphoresis, weakness, and disturbed vision), but in other cases loss of consciousness occurs without warning (111). Stereotyped presyncopal symptoms may be absent in some elderly patients for unclear reasons, but other deviations from this clinical presentation should alert the examiner to consider other entities in the differential diagnosis.
Neurologic symptoms, when present, are brief and often progress in a stereotyped manner, culminating in loss of consciousness (116). The patient initially experiences a sense of "dizziness" or disequilibrium, nausea, and unclear thinking. This is followed by fixation of the eyes in the midline and a “frozen” appearance. Vision narrows followed by graying out of vision. This may progress to complete loss of vision (blacking out), with or without hearing loss. Complete loss of consciousness is associated with the “turning up” of the eyeballs. There is a loss of postural tone, usually with enough time to brace oneself to prevent injury. This process may take as little as 7 seconds in cases of sudden circulatory arrest, viz. abrupt asystole, but in other circumstances it depends on the rate and depth of cerebral hypoperfusion.
Eye deviation and myoclonus occur frequently ("convulsive syncope"), which may lead to an incorrect diagnosis of epilepsy (63; 06; 76). The myoclonic movements may be prolonged if the patient is unable to assume a recumbent position.
Loss of consciousness generally lasts at most 20 seconds in cases of reflex syncope, but it can rarely be longer (111). Rapid restoration of consciousness and orientation follows, with post-return-of-consciousness symptoms caused by mixed vagal and sympathetic outflow (eg, nausea, diaphoresis, and tremor). Postictal confusion is not observed but fatigue may be present during the post-recovery period (111). Focal neurologic symptoms are absent before and following syncope unless the patient has some preexisting neurologic deficit that may become more pronounced during the spell.
Rarely, epileptic seizures can occur in association with syncope as a result of ictal bradycardia or ictal asystole (75). Ictal bradycardia or ictal asystole occur predominantly with partial complex seizures, particularly with left-lateralized temporal lobe seizures. Ictal syncope is associated with EEG signs of brain ischemia and the duration of the cardiac arrhythmia.
Cognitive impairment is common in elderly patients with syncope, with a reported overall prevalence of 58%, comparative to the frequency of cognitive impairment among elderly patients with unexplained falls (36).
In a systematic review and meta-analysis of prognosis after an acute-care evaluation for syncope, the clinical findings most predictive of a short-term, serious event were (1) an elevated blood urea nitrogen level; (2) history of congestive heart failure; (3) initial low blood pressure in the emergency department; (4) history of arrhythmia; and (5) an abnormal troponin value (42). An abnormal electrocardiogram was also mildly predictive of increased risk. Younger age was associated with lower risk.
Significant morbidity results from falls or accidents resulting from syncope. After analyzing 1114 patients with syncope and 139 individuals with a non-syncopal transient loss of consciousness, Bartoletti and colleagues reported that 365 of those with transient loss of consciousness presented with a history of trauma, which was classified as severe in 59 cases (20). Carotid sinus syndrome and vasovagal syncope, both neurally mediated categories of syncope, have been increasingly recognized as important causes for unexplained falls and syncope in the elderly, though still likely to be underdiagnosed (11). In older patients with unexplained falls and syncope, 20% demonstrate an arrhythmia as the attributable cause for their falls and such patients are at a significantly increased risk of further falls (24). In a nationwide Danish cohort, syncope was associated with a 1.4-fold higher risk of occupational accidents and a 2-fold higher risk of termination of employment compared with the employed general population (83).
Near-syncope confers risks similar to that of syncope for the composite outcome of 30-day death or serious clinical event (21).
Although patients may harm themselves with falls, neurocardiogenic syncope generally has an excellent prognosis and tends to cease with advancing age. However, it may have a poor prognosis and may be refractory to treatment in patients with left ventricular dysfunction (119).
Autonomic insufficiency secondary to medications may be alleviated by medication change; however, neurodegenerative causes for autonomic insufficiency are more serious and refractory.
The prognosis for various cardiac causes depends on the specific condition. A patient with a normal ECG and echocardiogram has an excellent long-term prognosis, but a patient with heart disease or cardiac dysrhythmia has a more serious prognosis (71). Structural heart disease and electrical dysfunction (eg, long QT syndrome, Brugada syndrome, short QT syndrome) are major risk factors for sudden cardiac death and overall mortality in syncopal patients (111). Patients with aortic stenosis who develop syncope have a smaller aortic valve area, smaller cardiac cavities, and lower stroke volumes than those without syncope, and the syncopal patients also had an increased risk of mortality after aortic valve replacement (43). Implanted automatic defibrillators also improve the prognosis for patients with ventricular fibrillation and non-sustained ventricular tachycardia (13). New-onset syncope of unknown etiology is not an independent predictor of mortality in elderly patients (95).
Cardiac syncope has significantly higher mortality compared with syncope due to noncardiac causes or idiopathic syncope. Nevertheless, among older, diabetic, or hypertensive individuals, a history of either noncardiac or unexplained syncope, even in the absence of an obvious cardiac etiology, is associated with significantly higher all-cause mortality (94).
Although the overall in-hospital mortality rate in patients with syncope is relatively low (< 2%), patients with syncope coexistent with pulmonary embolism, pneumonia, myocardial infarction, or stroke have a mortality rate exceeding 8%, whereas syncope coexistent with atrial fibrillation has no independent impact on in-hospital mortality (61). Syncope as a manifestation of acute pulmonary embolism is associated with a higher prevalence of hemodynamic instability and right ventricular dysfunction at presentation, a higher risk of all-cause early death (ie, death either in-hospital or within 30 days), and an elevated risk for early pulmonary embolism-related adverse outcomes (17).
Multiple approaches to risk stratification have been developed for the initial evaluation of syncope (73; 32; 99; 91; 34; 111; 28). According to the San Francisco Syncope Rule, the presence of any of the following is predictive of a serious event within 1 week with 98% sensitivity and 56% specificity: abnormal ECG, congestive heart failure, dyspnea, hematocrit of less than 30%, or systolic blood pressure of less than 90 mm Hg (99). According to a study by Martin and colleagues, which I will refer to as the Martin Rule, predictors of severe arrhythmia or arrhythmic death by 1 year include an abnormal ECG, history of ventricular arrhythmia, history of congestive heart failure, and age over 45 years; with each of these factors accorded a score of 1 point, the risk of severe arrhythmia or arrhythmic death by 1 year was 0% with a total score of 0, 5% with a score of 1, 16% with a score of 2, and 27% with a score of 3 or 4 (73). According to the OESIL Rule, predictors of 1-year mortality include an abnormal ECG, history of cardiovascular disease, lack of a prodrome, and age over 65 years; with each of these factors accorded a score of 1 point, the risk of 1-year mortality was 0% with a total score of 0, 0.6% with a score of 1, 14% with a score of 2, 29% with a score of 3, and 53% with a score of 4 (32). According to the EGSYS Rule, there are positive and negative predictors that carry different weights for cardiac syncope and 2-year mortality: (1) palpitations before syncope (4 points); (2) abnormal ECG and/or heart disease (3 points); (3) syncope during effort (3 points); (4) syncope while supine (2 points); (5) autonomic prodrome with nausea/vomiting (-1 point); and (6) the presence of predisposing and/or precipitating factors (eg, warm crowded place, prolonged standing, fear, pain, intense emotion) (-1 point) (34). By the EGSYS Rule, 2-year mortality is 2% when the total score is less than 3 and 21% for scores of 3 or more (34).
Syncope among drivers has significant implications for personal and public safety, so consequently syncope should be carefully considered in assessments of driving fitness (46; 82). The incidence of motor vehicle crashes among patients with syncope is almost double that of the general population (20.6 per 1000 person-years vs. 12.1 per 1000 person-years), with a rate ratio of 1.83 after adjustment for age, sex, socioeconomic position, relevant comorbidities, and pharmacotherapy (82). The 5-year crash risk following syncope is 8% among the population aged 18 to 69 years compared with 5% in the general population (82). Prior hospitalization for syncope is associated with a persistent increased risk of motor vehicle crashes (82). Those with structural heart disease are at an especially high risk of further syncope. Driving recommendations “should not differ, whether or not the syncopal spell occurred while driving” (46).
According to the Task Force for the Diagnosis and Management of Syncope, about a third of syncopal patients have recurrent syncope within 3 years of follow-up (111). Another study reported that the risk of syncope recurrence following an initial emergency department visit for syncope was 9% at 6 months, 12% at 1 year, and 23% at 5 years (16).
The strongest predictor of recurrence is the prior number of syncopal episodes (111). Recurrent syncope is associated with fractures and soft tissue injury in 12% of cases (111). Other significant predictors of syncope recurrence include diabetes mellitus and anemia (16).
A 38-year-old man had experienced several episodes of graying of vision and feeling of faintness after weightlifting. He was referred for new-onset seizures because he reported that after lifting a heavy weight, he was observed to fall to the floor and to have jerking movements of his limbs. He rapidly awoke with no confusion but was sweating and nauseous. He was otherwise healthy, and family history was negative for seizures or syncope. His examination showed no postural blood pressure changes. On cardiac auscultation he had a systolic ejection murmur heard best over the left upper sternal border; the murmur increased with Valsalva maneuver. Neurologic examination was normal. The EEG was normal, but his ECG showed left ventricular hypertrophy. A cardiology consultant found idiopathic hypertrophic subaortic stenosis and arranged an electrophysiological study. The myoclonus was interpreted as secondary to cerebral hypoperfusion (ie, convulsive syncope), and antiepileptic drugs were not initiated.
• Cerebral perfusion is maintained relatively constant by an intricate and complex feedback system involving cardiac output, systemic vascular resistance, arterial pressure, intravascular volume status, cerebrovascular resistance with intrinsic autoregulation, and metabolic regulation.
• Cardiac output can be diminished secondary to medications (eg, beta blockers), mechanical outflow obstruction, pump failure, hemodynamically significant arrhythmias, or conduction defects.
• The baroreflex, one of the body’s homeostatic mechanisms, maintains blood pressure through a negative feedback loop: an elevated blood pressure reflexively causes a decrease in heart rate and, thus, blood pressure, whereas a decreased blood pressure activates the baroreflex, causing an increase in heart rate and, thus, a rise in blood pressure.
• Hyperventilation may cause syncope by reduction in cerebral blood flow from cerebral vasoconstriction.
• Fear and anxiety both may precipitate neurocardiogenic syncope, but both may stimulate central hyperventilation as well.
• Patients with conversion disorders or malingering may complain of transient loss of consciousness that may be misdiagnosed as syncope.
Cerebral perfusion is maintained relatively constant by an intricate and complex feedback system involving cardiac output, systemic vascular resistance, arterial pressure, intravascular volume status, cerebrovascular resistance with intrinsic autoregulation, and metabolic regulation. A clinically significant defect in any 1 of these systems or subclinical defects in several of these systems may cause reflex syncope.
Cardiac output can be diminished secondary to medications (eg, beta blockers), mechanical outflow obstruction, pump failure, hemodynamically significant arrhythmias, or conduction defects. Systemic vascular resistance can drop secondary to medication-induced vasodilation, vasomotor instability, autonomic failure, or vasodepressor/vasovagal response. Mean arterial pressure decreases with all causes of hypovolemia.
The baroreflex, 1 of the body’s homeostatic mechanisms, maintains blood pressure through a negative feedback loop: an elevated blood pressure reflexively causes a decrease in heart rate and, thus, blood pressure, whereas a decreased blood pressure activates the baroreflex, causing an increase in heart rate and thus a rise in blood pressure. Baroreceptors are located predominantly in the auricles of the heart, the vena cava, the aortic arch, and the carotid sinuses. They monitor the changes in blood pressure and relay them to the nucleus of solitary tract in the brainstem via glossopharyngeal and vagus nerves. Subsequent changes in blood pressure are mediated by the autonomic nervous system (sympathetic and parasympathetic). The stretch sensitive baroreceptors (mechanoreceptors) become active when the blood pressure rises, resulting in the distention of the aorta and the carotid sinuses. Subsequent activation of the nucleus of solitary tract in turn inhibits the vasomotor center and stimulates the vagal nuclei. The result is inhibition of the sympathetic nervous system and activation of parasympathetic system.
Hyperventilation may cause syncope by reduction in cerebral blood flow from cerebral vasoconstriction. Fear and anxiety both may precipitate neurocardiogenic syncope, but both may stimulate central hyperventilation as well. Additionally, patients with conversion disorders or malingering may complain of transient loss of consciousness that may be misdiagnosed as syncope.
Syncope that occurs in the passive phase of the head-up tilt test depends on the cardioinhibitory reaction (123). The cardioinhibitory reaction is associated with a decrease in heart rate, whereas the vasodepressive reaction is associated with a decrease in arterial pressure. Some patients may have a mixed type.
An uncommon but important cause of reflex syncope is glossopharyngeal neuralgia, which may occur, for example, with esophageal carcinoma (78). Patients may have recurrent episodes of syncope associated with prolonged cardiac standstill and arterial hypotension, which, in most affected patients, can be prevented by atropine or cardiac pacing (15). However, in one well-studied case, a 55-year-old man was admitted with recurrent attacks of left glossopharyngeal neuralgia accompanied by syncope; despite cardiac pacing, he still developed profound hypotension (with systolic blood pressure readings below 40 mm Hg) and lost consciousness during attacks (15). In addition, although atropine eliminated bradycardia with triggered attacks, systolic arterial blood pressure still declined from 120 to 60 mmHg. Blockade of the right and then left vagus nerves with lidocaine failed to eliminate cardiac arrest, but blockade of the left glossopharyngeal and vagus nerves prevented neuralgic attacks and eliminated autonomic and EKG changes associated with stimulation of the trigger point. From the results in this case and others, it is evident that 2 cardiovascular manifestations occur in glossopharyngeal neuralgia: the afferent glossopharyngeal stimulus activates (1) brainstem mechanisms involved in cardiovascular regulation with bilateral efferent responses mediated via vagal discharge and producing cardiac standstill and prolonged delayed ventricular escape, and (2) inhibition of vasomotor centers while producing peripheral vasodilation and pronounced drops in blood pressure, even with cardiac pacing (15).
Commonly, cardiac syncope is caused by coronary artery disease that may induce ventricular dysrhythmias from transient ischemia or lead to foci of automaticity within the myocardial scar. Therefore, the risk factors for coronary artery disease and atherosclerosis (eg, hypertension, diabetes, smoking, hyperlipidemia, male gender, and advancing age) all are associated with cardiac syncope. Young athletes may also develop syncope from ventricular dysrhythmia. Familial prolonged QT syndrome may present with syncope or sudden death.
Short QT syndrome is an autosomal dominant genetic disorder affecting infants, children, and young adults that is characterized by a short QT interval between 210 and 340 milliseconds. Normally, QT interval lengthens when the heart rate is slow and shortens during fast heart rates. In short QT syndrome, the QT interval changes very little as the heart rate changes. Short QT syndrome is a risk factor for paroxysmal atrial fibrillation, life-threatening ventricular arrhythmias, syncope, and sudden death. Mutations in several genes encoding K+ channels have been identified, explaining the abbreviated repolarization seen in this condition. An intracardiac device is recommended for symptomatic patients, but the therapeutic strategy for asymptomatic patients, especially children, remains uncertain. Quinidine has shown to prolong QT and reduce the inducibility of ventricular arrhythmias.
Brugada syndrome was first described in 1992 as a unique set of electrocardiographic abnormalities associated with sudden death in otherwise healthy adults without structural heart disease (29). Brugada syndrome signs include right bundle branch block or J wave, ST-segment elevation in the right precordial leads (V1, V2, and V3) at least 0.1 mV, and normal QT interval. Brugada syndrome is responsible for a large portion of patients with “idiopathic ventricular fibrillation” (05). In a study of 203 patients with Bragada syndrome, syncope occurred in 28% of patients (97). In 30% of patients the etiology of syncope was questionable. Because pharmacological treatment does not protect against recurrent events, implantable cardioverter defibrillator implantation is the only effective therapy to prevent sudden death in these patients (05). Lead failures often cause serious secondary complications such as implantable cardioverter defibrillator shocks or asystole (01).
In patients with acute pulmonary emboli, syncope is associated with a hypotension, tachycardia, right ventricular dysfunction, and reduced cardiac output (60). Syncope is positively correlated with the severity of pulmonary emboli (86). Central pulmonary emboli, blood troponin I level, unprovoked pulmonary emboli, and female sex are clinical factors related with syncope in patients with pulmonary emboli (68).
• Syncope is a prevalent disorder, accounting for 3% to 5% of emergency department visits and 1% to 3% of hospital admissions.
• Neurologic causes account for approximately 40% of syncope cases.
• Syncope due to orthostatic hypotension represents approximately a tenth of cases in the general population and up to a quarter of cases presenting to emergency rooms.
• Pulmonary emboli represent a surprisingly common cause among patients hospitalized for syncope.
• Approximately one third of syncope remains unexplained.
Syncope is a prevalent disorder, accounting for 3% to 5% of emergency department visits and 1% to 3% of hospital admissions (106). The age of a first syncopal event shows a sharp peak between the ages of 10 and 30 years before falling to a nadir around age 50 years and then again rising progressively with age, but only 5% of adults have a first syncopal event over age 40 years (111). Vasovagal syncope is more common in women; compared to men with vasovagal syncope, women with vasovagal syncope are younger at the time of their first syncopal event, experience more post-syncope fatigue, and are more likely to experience recurrent syncope (37).
Neurologic causes account for approximately 40% of syncope cases (70). Neurologic causes follow a bimodal distribution and occur primarily in the younger patients, with autonomic insufficiency developing in the later decades of life. Reflex syncopes are generally the most common form of syncope, representing approximately one fifth of cases (21%) in the general population (based on the Framingham Study results), and a third to half of cases presenting to emergency rooms (111).
Syncope due to orthostatic hypotension represents approximately a tenth of cases (9.4%) in the general population (based on the Framingham Study results) and up to a quarter of cases presenting to emergency rooms (111). It is much more common in the elderly and in those on multiple medications.
Cardiac causes represent 10% to 30% of syncope cases (74). In older adults with syncope presenting to the emergency department, approximately 3% receive a diagnosis of a serious cardiac arrhythmia that is not recognized on initial emergency department evaluation (80). Cardiac causes of syncope most commonly appear after the seventh decade, when coronary disease is most common. However, familial prolonged QT syndrome may cause symptoms at any age, typically in the second and third decades.
Pulmonary emboli represent a surprisingly common cause among patients hospitalized for syncope: indeed, in 1 study, pulmonary emboli were present in nearly 1 of every 6 patients (17%) hospitalized with a first episode of syncope: 13% among those with an alternative explanation for syncope and 25% among those who did not (90). The estimates from this study, though, are significantly higher than other studies in the literature, suggesting a possible site effect, accrual bias, or investigation strategy (85; 07). In most studies, the estimated prevalence of pulmonary embolism in patients presenting with syncope is low (85), particularly among patients presenting to the emergency department (generally 2% or less) (14, 88; 92), but various other studies have reported that 2% to 11% of hospitalized patients with syncope have pulmonary emboli as a cause (07; 14; 88). In addition, the low prevalence of diagnosed venous thromboembolism in patients with syncope and the extremely low 30-day readmission rate with venous thromboembolism suggests that missed diagnoses of venous thromboembolism are uncommon in admissions for syncope (104). Among patients with pulmonary embolism, the presence of syncope at presentation is associated with a more complicated in-hospital course (79).
In a Korean study, 2.2% of patients with influenza experienced syncope (81). None of the affected patients had severe cough, hypotension, or dehydration. Patients experienced frequent episodes of dizziness before syncope. A long duration of loss of consciousness occurred more commonly among those with a high fever or orthostatic hypotension.
Approximately one third of syncope remains unexplained (70; 71; 110). The frequency of residual idiopathic syncope after evaluation has not changed much over the past 20 years.
Some patients have an incorrect diagnosis for more than 10 years, and such misdiagnosed patients are often excessively investigated, inappropriately treated, and have unnecessary restrictions placed on driving and employment (55).
Syncope is likely when loss of consciousness is complete and of rapid onset and short duration, associated with loss of postural tone, and spontaneous and complete recovery without sequelae (111). If some of these features are not present, other forms of transient loss of consciousness should be considered and excluded (111).
Syncope must be distinguished from disorders with transient loss of consciousness but without global cerebral hypoperfusion, including seizures, metabolic disorders (eg, hypoglycemia, hypoxia), vertebrobasilar transient ischemic attacks, and intoxication. Syncope must also be distinguished from disorders that may be associated with falls but that occur without impairment of consciousness, including cataplexy, drop attacks, psychogenic pseudosyncope, and anterior circulation transient ischemic attacks (111; 28).
A stereotyped prodrome followed by loss of consciousness and rapid return of sensorium supports the diagnosis of syncope. Reflex syncope can be commonly mistaken for a seizure. If the patient is unable to recall events just moments prior to postural collapse, syncope may still be the correct diagnosis, but one must consider seizure. The presence of postictal confusion and reports of convulsion from observers would support a diagnosis of seizure, but one must be careful not to misattribute the myoclonus of convulsive syncope to an epileptic convulsion.
Ischemia in the distribution of the posterior circulation may cause transient loss of consciousness; there is a selective decrease in perfusion to the posterior circulation rather than a global decrease, and return of consciousness is slow. Transient loss of consciousness associated with transient posterior circulation hypoperfusion often produces visual field impairments, diplopia, ataxia, and dysarthria prior to collapse. Following reperfusion, the patient may manifest transient disconjugate gaze, hemiataxia, hemianopsia, and dysarthria with or without good recall of the event.
Variants of migraine, particularly basilar migraine, may produce transient loss of consciousness with or without head pain. Basilar migraine is more frequent in children but may rarely present in adulthood. The presence of migrating sensory symptoms before or after the event suggests migraine. Other forms of migraine may also have an association with syncope, but in such cases migraine and syncope do not occur simultaneously or in close temporal succession (111).
Metabolic causes of transient loss of consciousness may include hypoglycemia and hypoxemia, but the mechanism of loss of consciousness is not a decrease in global cerebral perfusion, and the alteration in consciousness is rarely of sudden onset and offset.
Unlike syncope, episodes of pseudosyncope (or “psychogenic nonsyncopal collapse”) are not associated with compromised cerebral circulation (49). Pseudosyncope is usually a manifestation of conversion disorder and, as such, shares many features with pseudoseizure (23). Psychiatric disease and age of less than 45 years are risk factors for pseudosyncope (111). Some patients may have a combination of tilt-induced vasovagal syncope and psychogenic pseudosyncope (26): such individuals are more likely to have a high attack frequency (including multiple attacks in a single day), delayed recovery following apparent transient loss of consciousness, episodes without prodromes, lacking or atypical triggers, eye closure and especially forced eye closure with attempted passive eye opening by the examiner (the eyes are typically not closed during epileptic seizures and syncope), apparent loss of consciousness lasting longer than 1 minute (affected patient may lie on the floor for 15 minutes or longer), and tearfulness associated with fainting (111; 26; 49). It is important to note that physical injury does not exclude pseudosyncope (111).
The most common cause of syncope in paced patients is cardiovascular autonomic dysfunction (120). In a study of 39 paced patients with syncope, orthostatic hypotension (41%) and vasovagal syncope (31%) were the most common diagnoses; there were no cases of pacemaker dysfunction (120a). Predictors of syncope recurrence and fall-related injury after pacemaker implantation include treated hypertension, renal failure, and atrial fibrillation (120b). Recurrent syncope after pacemaker implantation is associated with increased mortality risk (120b).
• Syncope is a common and a typically benign clinical problem in children and adolescents.
• The majority of tests ordered in otherwise healthy pediatric patients presenting with syncope have low diagnostic yield.
• Current evaluation strategies in common use for syncope in adults are expensive and lack diagnostic value.
• When considering clinical evaluation and diagnostic studies, history, physical examination, and electrocardiography have the greatest utility in evaluating syncope and should be the key components of an initial evaluation for syncope.
• Physical examination should include blood pressure measurement in each arm, orthostatic blood pressure measurement (3 sets of pulse and blood pressure: after supine for 5 minutes, on standing, and after standing for 3 minutes), neck auscultation, cardiac examination, examination of the extremities for swelling, and examination of cranial nerves and motor function.
• Tongue biting, particularly if it is along the lateral aspect of the tongue, is highly specific to generalized tonic-clonic seizures.
• Diagnosis of reflex syncope is supported by a long history of recurrent syncope (with onset before the age of 40 years); evidence of typical triggers; occurrence in crowded or hot places; occurrence during a meal; occurrence with head rotation or when pressure is placed on the carotid sinus from tumors, shaving, or tight collars; or evidence of autonomic activation prior to syncope, absent of heart disease.
• A prodrome duration of 5 seconds or less suggests arrhythmic syncope, whereas a prodrome duration of more than 10 seconds in the absence of structural heart disease suggests reflex syncope.
• Vasovagal syncope is diagnosed if syncope is precipitated by emotional or orthostatic stress and is associated with a typical prodrome.
• Situational syncope is diagnosed if it occurs during or immediately after specific triggers such as coughing/sneezing, swallowing, defecation, visceral pain, micturition, exertion, or after eating.
• Orthostatic hypotension is the likely basis for syncope if syncope and presyncope are present during standing, absent while lying, and less severe or absent while sitting.
• Orthostatic hypertension is defined as a sustained fall in systolic blood pressure of at least 20 mm Hg (at least 30 mm Hg in those with supine hypertension), or diastolic blood pressure of 10 mm Hg, or a decrease in systolic blood pressure to less than 90 mm Hg within 3 minutes of standing or head-up tilt to at least 60 degrees on tilt table testing.
• Diagnosis of syncope due to orthostatic hypotension is supported by the following (1) an appropriate triggering situation; (2) a temporal association with starting or changing dosage of medications known to cause orthostatic hypotension; and (3) a history of autonomic neuropathy or parkinsonism.
• Diagnosis of cardiovascular syncope is supported by the presence of structural heart disease, a family history of unexplained sudden death or channelopathy, occurrence during exertion or while supine, occurrence of syncope following palpitations, and specific ECG findings suggesting arrhythmic syncope.
• The clinical examination, plus electrocardiography, as part of multivariable scores, can accurately identify patients with and without cardiac syncope.
• Pulmonary embolus as a cause of syncope should be suspected in patients with elevated troponin levels or a dilated right ventricle on echocardiogram.
Children and adolescents. Syncope is a common and a typically benign clinical problem in children and adolescents (93). The majority of tests ordered in otherwise healthy pediatric patients presenting with syncope have low diagnostic yield. Nevertheless, children with syncope often undergo expensive and unnecessary cardiac and neurologic testing (93).
A diagnostic approach to vasovagal syncope in children that is more cost effective than the traditional approach has been proposed (69; 100). In the new diagnostic approach, the first steps are the history, physical examination, supine and upright blood pressure, and a standard ECG (69). Echocardiography and electrocardiogram monitoring are recommended only when necessary to exclude other diseases. The head-up tilt test is recommended only in patients with frequent and severe episodes of unexplained syncope after the other studies mentioned above. Other authors have since questioned even the utility of performing blood glucose determinations and an electrocardiogram in the outpatient evaluation of previously healthy children who present to an emergency department with a clinical diagnosis of benign syncope (45).
Initial evaluation of adults. Current evaluation strategies in common use for syncope in adults are expensive and lack diagnostic value (56). The syncope work-up should be tailored to the patient's presentation. When considering clinical evaluation and diagnostic studies, history, physical examination, and electrocardiography have the greatest utility in evaluating syncope and should be the key components of an initial evaluation for syncope (04; 28). Additional testing should be guided by history and physical examination. Evaluation results indicating a need for further work-up include a history of cardiac or valvular disease (ie, ventricular dysrhythmia, congestive heart failure), abnormal EKG, anemia or severe volume depletion (eg, from a gastrointestinal bleed), syncope while supine or with effort, report of palpitations or chest pain, persistent abnormal vital signs, or family history of sudden death (04). Note, though, that in children with syncope the diagnosis is primarily clinical; laboratory investigations add little to the diagnosis in children, especially in those with neurocardiogenic syncope (105).
A detailed history with careful review of medications and family history is often diagnostic. Physical examination should include blood pressure measurement in each arm, orthostatic blood pressure measurement (3 sets of pulse and blood pressure: after supine for 5 minutes, upon standing, and after standing for 3 minutes), neck auscultation, cardiac examination, examination of the extremities for swelling, and examination of cranial nerves and motor function (08; 09; 10). Overall, a diagnosis can be established in 25% to 50% of patients with history and examination alone (71; 111).
In the elderly, it is often difficult to distinguish syncope from unexplained or accidental falls (87). Valvulopathy and the number of antihypertensive drugs are significantly related to syncope in this group.
Syncopal events with high-risk features suggesting a serious underlying condition include: (1) new-onset chest discomfort, breathlessness, abdominal pain, or headache; (2) syncope during exertion or while supine; (3) sudden onset of palpitations, immediately followed by syncope; (4) severe structural heart disease or coronary artery disease (ie, heart failure, low left ventricular ejection fraction, or previous myocardial infarction); (5) unexplained hypotension with systolic blood pressure of less than 90 mm Hg; (6) evidence of gastrointestinal bleeding (eg, on rectal examination); (7) persistent bradycardia (40 bpm or lower) while awake in the absence of physical training; and (8) an unexplained systolic murmur (28). In those with structural heart disease or an abnormal ECG, the following are also high-risk features: (1) absence of warning symptoms prior to syncope, or a short prodrome (lasting less than 10 seconds); (2) a family history of sudden cardiac death at a young age; and (3) syncope occurring in the sitting position (28).
The occurrence of tongue biting in seizure has a sensitivity of 24% and a specificity of 99% for the diagnosis of generalized tonic-clonic seizures (22). Tongue biting, particularly if it is along the lateral aspect of the tongue, is highly specific to generalized tonic-clonic seizures. Among the 45 patients with syncope, in only 1 was the tongue lacerated, and this was at the tip. Lateral tongue biting was specific to generalized tonic-clonic seizures.
Hyperventilation syndrome can be diagnosed by having the patient hyperventilate voluntarily to see if symptoms are reproduced (50; 64). This often requires strong and persistent encouragement by the examiner.
Reflex syncope. Diagnosis of reflex syncope is supported by a long history of recurrent syncope (with onset before the age of 40 years), evidence of typical triggers (eg, after prolonged standing or an unpleasant sight, sound, smell, or pain); occurring in crowded or hot places; occurring during a meal; occurring with head rotation or when pressure is placed on the carotid sinus from tumors, shaving, or tight collars; or evidence of autonomic activation prior to syncope (eg, pallor, sweating, or nausea/vomiting), absence of heart disease (111; 28). A clear history consistent with reflex syncope with an appropriate stimulus and a typical progressive prodrome (ie, pallor, sweating, and/or nausea) requires no further workup; all other patients should receive an electrocardiogram (70).
Prodrome duration can be helpful in distinguishing arrhythmic and reflex syncope. A prodrome duration of 5 seconds or less suggests arrhythmic syncope, whereas a prodrome duration of more than 10 seconds in the absence of structural heart disease suggests reflex syncope (03; 28).
Vasovagal syncope is diagnosed if syncope is precipitated by emotional or orthostatic stress and is associated with a typical prodrome (111; 28).
Situational syncope is diagnosed if it occurs during or immediately after specific triggers such a coughing/sneezing, swallowing, defecation, visceral pain, micturition, exertion, or after eating (111; 28).
Orthostatic hypotension. Orthostatic hypotension is the likely basis for syncope if syncope and presyncope are present during standing, absent while lying, and less severe or absent while sitting. Sitting or lying down must alleviate the symptoms of presyncope. Orthostatic hypotension is often most symptomatic upon arising in the morning and may be aggravated immediately after exercise, after meals, or in high ambient temperatures.
Although orthostatic hypotension is a very common cause of syncope, it is often overlooked, and orthostatic blood pressure measurements are often overlooked during the initial evaluation of syncope in the emergency department (48). Nevertheless, it should be emphasized that demonstration of orthostatic hypotension does not, by itself, indicate the reason for syncope. In particular, orthostatic blood pressure measurements do not, in isolation, reliably diagnose or exclude orthostatic syncope, nor do they rule out life-threatening causes of syncope (eg, cardiac syncope) (102).
Orthostatic hypertension is defined as a sustained fall in systolic blood pressure of at least 20 mm Hg (at least 30 mm Hg in those with supine hypertension), or diastolic blood pressure of 10 mm Hg, or a decrease in systolic blood pressure to less than 90 mm Hg within 3 minutes of standing or head-up tilt to at least 60 degrees on tilt table testing (39; 40; 28). The 90 mm Hg threshold for orthostatic hypotension was added with the 2018 guidelines from the Task Force for the Diagnosis and Management of Syncope (28). An isolated diastolic blood pressure drop is rare, the diastolic criterion is seldom used, and in any case its clinical relevance is doubtful.
Orthostatic hypotension is not defined or determined by the heart rate response to standing. With neurogenic orthostatic hypotension, the increase in heart rate with standing is blunted or absent, whereas with anemia or hypovolemia the orthostatic heart rate response is increased or exaggerated (28). An orthostatic heart rate increase of more than 30 bpm, or to a rate of more than 120 bpm, within 10 minutes of active standing, without a drop in blood pressure, is indicative of postural orthostatic tachycardia syndrome (or POTS) and should not be labeled as orthostatic hypotension.
Diagnosis of syncope due to orthostatic hypotension is supported by the following (1) an appropriate triggering situation (eg, a history of syncope upon or shortly after standing, with prolonged standing, with standing shortly after exertion, or after meals); (2) a temporal association with starting or changing dosage of medications known to cause orthostatic hypotension; and (3) a history of autonomic neuropathy or parkinsonism (111; 28).
In a prospective cohort study of patients with suspected (pre)syncope presenting to the emergency department of a tertiary care teaching hospital, orthostatic blood pressure was measured during the active lying-to-standing test with a continuous noninvasive finger arterial pressure measurement device, and then orthostatic blood pressure recovery patterns were assessed (112). Classic orthostatic hypotension was the most prevalent abnormal blood pressure pattern (19%), but only half of the patients received a final diagnosis of orthostatic hypotension. Initial orthostatic hypotension and delayed blood pressure recovery were present in 20% of the patients with (pre)syncope, of whom 45% were diagnosed as unexplained syncope.
Cardiovascular syncope. Diagnosis of cardiovascular syncope is supported by the presence of structural heart disease, a family history of unexplained sudden death or channelopathy, occurrence during exertion or while supine, occurrence of syncope following palpitations, and specific ECG findings suggesting arrhythmic syncope (111; 28).
The clinical examination, plus electrocardiography, as part of multivariable scores, can accurately identify patients with and without cardiac syncope (02).
According to the EGSYS Rule, there are positive and negative predictors that carry different weights for cardiac syncope and 2-year mortality: (1) palpitations before syncope (4 points); (2) abnormal ECG and/or heart disease (3 points); (3) syncope during effort (3 points); (4) syncope while supine (2 points); (5) autonomic prodrome with nausea/vomiting (-1 point); and (6) the presence of predisposing and/or precipitating factors (eg, warm crowded place, prolonged standing, fear, pain, intense emotion) (-1 point) (34). An EGSYS score of less than 3 is associated with lower likelihood of cardiac syncope: the probability of cardiac syncope is 2% with a total score of less than 3, 13% with a score of 3, 33% with a score of 4, and 77% with a score of more than 4 (34).
Clinical predictors of cardiac syncope include the following, based on a systematic reviews (02; 72): (1) age at first syncope of at least 35 years; (2) history of atrial fibrillation or flutter; (3) known severe structural heart disease; and (4) cyanosis witnessed during the episode. Negative predicators of cardiac syncope include the following: (1) age at first syncope younger than 35 years; (2) certain prodromal symptoms prior to syncope, including mood change, preoccupation with details, feeling cold, or headache; (3) mood changes after syncope; and (4) inability to remember behavior prior to syncope (02).
The Task Force for the Diagnosis and Management of Syncope of the European Society of Cardiology has identified specific ECG findings suggestive of an arrhythmic basis for syncope, which were modified somewhat from 2009 to 2018: (1) bifascicular block (ie, left or right bundle branch block combined with left anterior or left posterior fascicular block); (2) other intraventricular conduction abnormalities with QRS duration of at least 0.12 seconds; (3) Mobitz I second-degree atrioventricular block and first degree AV block with a markedly prolonged PR interval; (4) asymptomatic inappropriate sinus bradycardia (40 to 50 bpm) or slow atrial fibrillation (40 to 50 bpm) in the absence of negative chronotropic medications or athletic physical training; (5) nonsustained ventricular tachycardia; (6) pre-excited QRS complexes; (7) long (greater than 460 ms) or short (less than 340 ms) QT intervals; (8) early repolarization; (9) a right bundle branch block pattern with ST elevation in leads V1 to V3 (Brugada syndrome); (10) negative T waves in the right precordial leads (epsilon waves) suggestive of arrhythmogenic right-ventricular cardiomyopathy; and (11) left ventricular hypertrophy suggesting hypertrophic cardiomyopathy (111; 28).
Arrhythmic syncope is considered highly probable when the ECG shows any of the following: (1) persistent sinus bradycardia or slow atrial fibrillation of less than 40 bpm or repetitive sinoatrial block or pauses of at least 3 seconds; (2) Mobitz II second- or third-degree atrioventricular block; (3) alternating right and left bundle branch block; (4) ventricular tachycardia or rapid paroxysmal supraventricular tachycardia; (5) episodes of polymorphic ventricular tachycardia with either a long or short QT interval; or (6) malfunction of a pacemaker or implanted cardiac defibrillator with resulting cardiac pauses (111; 28).
Cardiac ischemia-related syncope is confirmed when syncope presents with evidence of acute myocardial ischemia (with or without myocardial infarction) (28).
Syncope due to structural cardiopulmonary disorders is highly probable when syncope presents in patients with any of the following: prolapsing atrial myxoma, left atrial ball thrombus, severe aortic stenosis, pulmonary embolus, or acute aortic dissection (28).
Pulmonary embolus as a cause of syncope should be suspected in patients with elevated troponin levels or a dilated right ventricle on echocardiogram (07).
Immediate ECG monitoring. Immediate ECG monitoring is indicated when there is suspicion for arrhythmic syncope (111; 28).
Echocardiography. Although echocardiography is considered to be useful for diagnosis and risk stratification, the yield of echocardiography for syncope evaluation is low (28). Given the lack of any favorable impact on mortality and the increased costs, echocardiography in patients presenting with syncope should be limited to evidence-based use (101).
Echocardiography should be performed if there is previously known heart disease, data suggestive of structural heart disease, or syncope secondary to cardiovascular cause (28). More specifically, a transthoracic echocardiogram should be done in patients with syncope who are older than 60 years or have known heart disease or evidence suggestive of structural heart disease or syncope due to a cardiovascular cause (including an abnormal electrocardiogram or an elevated brain natriuretic peptide level) (70; 111; 47).
Two-dimensional and Doppler echocardiography during exercise in the standing, sitting, or semi-supine position is useful to detect provocable left ventricular outflow tract obstruction in patients with hypertrophic cardiomyopathy, a history of syncope, and a resting or provoked peak instantaneous left ventricular outflow tract gradient of less than 50 mm Hg (28).
Carotid sinus massage. Carotid sinus massage may be diagnostic, and traditional recommendations suggest that it should generally be performed in patients over age 40 with syncope of unknown etiology after initial evaluation, although it should be avoided in patients with a history of ventricular tachycardia, recent myocardial infarction, transient ischemic attack, stroke within the previous 3 months, or anterior cervical bruit (unless significant plaque and stenosis have been excluded by carotid Doppler (70; 111; 28). Carotid sinus hypersensitivity is defined as asystole of more than 3 seconds and/or a drop in systolic blood pressure of more than 50 mm Hg with carotid sinus massage (28). Carotid sinus hypersensitivity is common in older men without syncope (low specificity), but the specificity increases if spontaneous syncope is reproduced during carotid sinus massage (28). Because the response to carotid sinus massage was similar in patients with and without syncope, the utility of carotid sinus massage has been questioned as a “nonspecific and dubious diagnostic method” (118). It is precisely for this reason that a diagnosis of carotid sinus syndrome requires that carotid sinus massage precipitates bradycardia, asystole, and/or hypotension that reproduces spontaneous symptoms in patients with syncope of unknown origin that is compatible with a reflex mechanism (28). The main complications of carotid sinus massage are neurologic, with transient ischemic attacks or strokes occurring in 0.24% of patients who undergo the procedure (28).
Head-up tilt testing. Head-up tilt testing is recommended when there is suspicion reflex syncope and, in some cases, where syncope is thought consistent with POTS, psychogenic pseudosyncope, or orthostatic hypotension (particularly when orthostatic hypotension is suspected based on history, but when initial evaluation does not disclose orthostatic hypotension) (28). Tilt table testing may confirm the diagnosis of vasovagal or neurocardiogenic syncope and may be useful for a positive cardioinhibitory response to tilt testing predicts, with high probability, asystolic spontaneous syncope, a finding with therapeutic implications when cardiac pacing is considered (44; 70; 28). Tilt table testing may be of further value when establishing a diagnosis of syncope of unknown cause (71; 53). In a retrospective study on presyncope and single and multiple episodes of syncope, tilt table testing was very useful in making the correct diagnosis, especially when there was a well-taken, detailed clinical history (98). There are multiple potential hemodynamic patterns to tilt table testing: among 400 pediatric cases with unexplained syncope, the responses included vasovagal syncope (10%); postural orthostatic tachycardia syndrome, either symptomatic (6%) or asymptomatic (7%); orthostatic intolerance (7%); orthostatic hypotension (2%); and negative response (69%) (122). Tilt table testing has an important role in the evaluation of patients with unexplained syncope and in the differential diagnosis of vasovagal syncope (53).
Tilt table testing can sometimes be useful in correcting misdiagnoses of epilepsy in those with convulsive syncope, and in identifying rare cases of ictal asystole. Inducing syncope with tilt table testing is helpful in distinguishing convulsive syncope from seizures (103). In 1 study, 3 patients with normal electroencephalograms who were being treated for epilepsy with anticonvulsants developed bradycardia and prolonged asystole and then typical convulsions during tilt table testing; implantation of permanent pacemakers (atrial/ventricular stimulation, heart rate control) allowed withdrawal of anticonvulsants and prevented further syncope over 2 years of follow-up (53). In another report, a 53-year-old woman presented with episodes of expressive aphasia that were treated with antiepileptic drugs, but then while on therapy she developed episodes of syncope (65). During a 24-hour EEG monitoring, she had a seizure followed by sinus bradycardia and an 18-second sinus pause, causing syncope and a slowing of cerebral activity that was restored 10 seconds after the return of cardiac activity. This prompted insertion of a dual-chamber pacemaker.
It is worth emphasizing that “seizure-like activities” are commonly precipitated by head-up tilt testing (54). In a study of head-up tilt testing for suspected vasovagal syncope, 47 of 71 patients (66%) showed “seizure-like activities” at the time of syncope during head-up tilt testing: 14 with eyeball deviation but without abnormal limb movements, and 33 with eyeball deviation and abnormal limb movements (eg, myoclonic or tonic-clonic activities) (54). Patients with “seizure-like activities” had a significantly lower heart rate at the time of syncope, and patients with eyeball deviation and abnormal limb movements had a significantly lower systolic blood pressure and cardiac output at the time of syncope.
Tilt table testing can also help establish a diagnosis of pseudosyncope by the constellation of apparent loss of consciousness with loss of motor control, normal blood pressure, heart rate, and electroencephalography (111).
Cardiac stress test. A cardiac stress test should be done if syncope is related to exertion (70).
Holter monitoring. Although Holter monitoring may rarely reveal transient bradyarrhythmias or tachyarrhythmias in patients with syncope (71), in most patients with syncope symptoms do not recur during monitoring (28). Holter monitoring for syncope evaluation is expensive in terms of cost per diagnosis and has a true yield as low as 1% to 2% (28). Holter monitoring can be considered in patients with frequent syncope or presyncope (at least 1 episode per week) (28).
Event recorders. External event recorders are applied by the patient when symptoms occur; they can be useful for evaluation of palpitations but are not useful for evaluation of syncope (28). Patients with recurrent but infrequent syncope can wear a loop event recorder that records their cardiogram just prior to and following a clinical event (31). External loop recorders have a higher diagnostic yield than Holter monitoring and can be useful for patients with relatively frequent syncope (28). An implantable loop recorder registers a 1-channel ECG and stores arrhythmic episodes for up to 36 months. These data can be uploaded over standard phone lines and scrutinized for alteration in the cardiac rhythm. Patients with suspected myocardial ischemia should be referred for cardiology evaluation immediately. Based on a systematic Cochrane review of all randomized controlled trials of adult participants (ie, ≥ 18 years) with a diagnosis of unexplained syncope, an implantable loop recorder-based diagnostic strategy increases the frequency of etiologic diagnosis of syncope, although it is not clear that an implantable loop recorder-based diagnostic strategy reduces long-term mortality compared with the standard diagnostic assessment (107). Implanted loop recording is indicated in an early phase of evaluation of patients with recurrent syncope of unknown etiology, who do not meet high-risk criteria for a likely serious underlying problem, and who have a high likelihood of a recurrent event within the battery life of the device (28). Other studies have confirmed that an implantable loop recorder is useful for detecting syncope-correlated arrhythmias in patients with unexplained syncope (67). Atrial fibrillation and bradycardia are common diagnostic rhythms identified in older adults with implantable loop recorders for unexplained syncope (12; 51).
Pacemaker or defibrillator interrogation. For patients admitted with permanent pacemakers or implantable cardiac defibrillators, device interrogation is rarely useful for elucidating a cause of syncope without concerning physical exam, telemetry, or EKG findings (33). Interrogation may occasionally document paroxysmal arrhythmias responsible for a syncopal episode, but this rarely alters clinical outcomes (33). Interrogation may be more useful in patients with syncope after recent device placement.
Electrophysiological testing. Electrophysiological testing to determine the threshold for induction of atrial and ventricular dysrhythmias may be diagnostic and potentially therapeutic with radioablation or placement of a permanent automatic implanted defibrillator (77; 25). A positive electrophysiologic study suggests that the likely mechanism of syncope is paroxysmal AV block (28).
Neurologic investigations. Neurologic investigations for assessment of patients deemed to have syncope are used widely but are typically of no utility (89; 28). This applies to brain imaging with CT or MRI, ultrasound of neck arteries, and electroencephalography. The Task Force for the Diagnosis and Management of Syncope of the European Society of Cardiology concluded bluntly that “EEG, ultrasound of neck arteries, and computed tomography or magnetic resonance imaging of the brain are not indicated in patients with syncope” (28).
Indeed, CT or MRI brain imaging are of little value in patients with syncope if the neurologic examination is normal, even if the patient experienced mild head trauma due to syncope (52).
Also, electroencephalography is of little diagnostic value in unselected cases (50; 70). Routine electroencephalography has the implicit danger of false-positive abnormalities, especially in children (108). Although electroencephalography is not generally needed in the assessment of syncope, it is appropriate when there is diagnostic uncertainty between syncope and seizures. Electroencephalography during a syncopal spell shows initial slowing followed by generalized large amplitude delta activity, and absence of epileptiform discharges despite clinical convulsion (06; 27).
Screening for paraneoplastic antibodies and antiganglionic acetylcholine receptor antibodies is recommended in cases of multidomain autonomic failure with an acute or subacute onset (28).
Autonomic testing. Struhal and colleagues applied quantitative sweat testing to assess differences in sudomotor sympathetic activity in relation to the type of reflex syncope (109). They found that in cardioinhibitory type, sweating started in 7 of 9 patients after syncope, whereas in contrast in vasodepressor type, sweating started in 11 of 12 patients before syncope. In mixed type, sweating started before syncope in 20 patients and after syncope in 10 patients. They also noted that the onset of sweating correlated significantly with the onset of syncope symptoms.
• High-risk patients with syncope require acute hospitalization and urgent, intensive evaluation.
• Features that warrant evaluation as a high-risk case of syncope include severe cardiovascular or structural heart disease, a family history of sudden cardiac death, palpitations at the time of syncope, abnormal ECG findings suggesting arrhythmic syncope, or severe comorbidities.
• Treatment of reflex syncope is generally conservative and consists of reassurance, patient education, and instruction in reasonable precautions, avoidance of triggers, isometric counter-pressure maneuvers, and modification or discontinuation of hypotensive drug regimens, if possible.
• Treatment of syncope related to orthostatic hypotension includes education and lifestyle measures, ensuring adequate hydration and salt intake, discontinuation or reduction of vasoactive drugs, application of isometric physical counter-pressure maneuvers, application of abdominal binders and thigh-high moderate-to-high compression support stockings to reduce venous pooling, and head-up tilt sleeping.
• Hyperventilation syndrome may respond to rebreathing into a paper bag to normalize arterial pCO2.
• Recurrent syncope, especially without injury, should prompt consideration of a psychogenic pseudosyncope and possibly psychiatric referral.
Management of patients with syncope requires careful assessment and appropriate adjustment of medications. Inappropriate prescribing is extremely common for older patients with falls and syncope and is typically persistent and unexplained in medical records (35). The most frequent inappropriate prescribing concerned medications that increased the risk of falls or syncope, specifically vasodilator drugs and benzodiazepines (35).
High-risk patients with syncope require acute hospitalization and urgent, intensive evaluation (111). Features which warrant such evaluation include severe cardiovascular or structural heart disease (eg heart failure, low ventricular ejection fraction, previous myocardial infarction), a family history of sudden cardiac death, palpitations at the time of syncope, abnormal ECG findings suggesting arrhythmic syncope (see below), or severe comorbidities (eg, severe anemia or electrolyte abnormalities, particularly hypo- and hyperkalemia) (111; 96;28).
Reflex syncope. Treatment of reflex syncope is generally conservative and consists of reassurance, patient education and instruction in reasonable precautions, avoidance of triggers, isometric counter-pressure maneuvers, and modification or discontinuation of hypotensive drug regimens if possible (Mehlsen 2008; 62; 66; 96;28).
Physical counter-pressure maneuvers are very helpful in reducing syncopal recurrences, particularly in patients less than 60 years old who have longstanding, recognizable prodromal symptoms and who are physically able to do them (28; 38). Such maneuvers include forcefully squeezing a rubber ball in the dominant hand, arm tensing in the manner of the Jendrassik maneuver, forceful leg crossing (ie, crossing one leg over the other and squeeze the muscles in the legs, abdomen, and buttocks), and squatting. These maneuvers can transiently increase systolic blood pressure, diastolic blood pressure, and mean arterial pressure, thereby averting syncope (38).
Fludrocortisone can improve venous volume and may reduce syncopal recurrences in young patients with low-normal blood pressures and without comorbidities (117;28). Alpha adrenergic agonists such as midodrine may help patients with the orthostatic form of vasovagal syncope (117;28). Beta blocking drugs are not indicated; beta blockers had previously been thought to decrease the degree of ventricular mechanoreceptor activation, which might lessen the frequency or severity of reflex syncope, but they were found to be ineffective in randomized double-blind controlled trials in patients with vasovagal syncope.
Based on the 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients with Syncope from the American College of Cardiology, the American Heart Association Task Force on Clinical Practice Guidelines, and the Heart Rhythm Society, available evidence does not support the use of pacing for reflex-mediated syncope beyond patients with recurrent vasovagal syncope and asystole documented by implantable loop recorder (113; 114). However, for patients with cardioinhibitory vasovagal syncope aged at least 40 years, with a high burden of syncope (greater than or equal to 5 episodes, greater than or equal to 2 episodes in the past year) and a cardioinhibitory head-up tilt test (bradycardia less than 40 beats/min for 10 seconds or asystole greater than 3 seconds), dual-chamber pacing with closed loop stimulation significantly reduced syncope burden and time to first recurrence by 7-fold (19; 18).
The Task Force for the Diagnosis and Management of Syncope of the European Society of Cardiology now promotes a broader use of pacing for reflex syncope, noting that the recurrent unpredictable events may be disabling (28). These guidelines now recommend consideration of dual-chamber cardiac pacing to reduce recurrence of reflex syncope when the correlation between symptoms and ECG is established in patients 40 years of age or older who have appropriate clinical features (ie, documentation, by means of an implanted loop recorder, of spontaneous syncope with at least 3 seconds of asystole, or at least 6 seconds of asystole without syncope due to sinus arrest, AV block, or a combination of the 2) (28). These guidelines also now recommend consideration of dual-chamber cardiac pacing to reduce syncopal recurrences in patients affected by dominant cardioinhibitory carotid sinus syndrome with recurrent, frequent, unpredictable syncope (28). The evidence is much less clear for tilt-induced vasovagal syncope with divergent opinions among investigators for patients with cardioinhibitory responses, but pacing was clearly ineffective in patients without an asystolic tilt response (28). Thus, a strong consensus pacing is not indicated in patients without a documented cardioinhibitory reflex, such as patients with noncardioinhibitory tilt-positive responses (28).
Orthostatic hypotension. Treatment of syncope related to orthostatic hypotension includes education and lifestyle measures, ensuring adequate hydration and salt intake, discontinuation or reduction of vasoactive drugs, application of isometric physical counter-pressure maneuvers (see the section above on the management of reflex syncope for a elaboration of physical counter-pressure maneuvers), application of abdominal binders and thigh-high moderate-to-high compression support stockings to reduce venous pooling, and head-up tilt sleeping (with the head of the bed elevated more than 10 degrees) (28). Increasing salt intake and oral intake of fluids may be helpful to alleviate orthostatic symptoms. Medication adjustments may alleviate autonomic insufficiency even if caused by an underlying neurodegenerative disorder.
Fludrocortisone (0.05 to 0.3 mg once daily) can stimulate renal sodium retention and expand fluid volume and may reduce syncopal recurrences in young patients with low normal blood pressures and without comorbidities (117;28). Alpha adrenergic agonists, such as midodrine, may also help patients with postural syncope and the orthostatic form of vasovagal syncope (117;28), but this may be complicated by problematic nocturnal hypertension.
Cardiac syncope. Cardiac syncope treatment is varied depending on exact diagnosis. Dysrhythmias secondary to myocardial ischemia may respond to endovascular procedures and coronary artery bypass.
Cardiac pacing is indicated for selected patients with syncope due to intrinsic cardiac sinus node dysfunction: (1) with sinus node dysfunction (sick sinus syndrome) and an established relationship between sinus bradycardia and syncope; (2) with intrinsic second and third degree heart block (persistent AV block, paroxysmal AV block (narrow QRS and bundle branch block), or with atrial fibrillation with a slow heart rate); and (3) with bifascicular bundle branch block with documentation of paroxysmal AV block during prolonged ECG monitoring with an implanted loop recorder or with a with a positive electrophysiologic study (57;28).
In patients with unexplained syncope and signs of sinus node dysfunction or impaired atrioventricular conduction on invasive electrophysiologic testing, pacemaker implantation is associated with longer syncope-free survival (41).
In Brugada syndrome an implanted defibrillator is safe, and programming a single, high-rate VF zone is recommended to reduce inappropriate defibrillator discharges, especially supraventricular tachyarrhythmias (115).
Catheter ablation is indicated in patients with syncope due to supraventricular tachycardia or ventricular tachycardia to prevent syncope recurrence.
An implantable cardioverter defibrillator (ICD) is indicated in patients with (1) syncope due to ventricular tachycardia and an ejection fraction of 35% or less; (2) patients with syncope and previous myocardial infarction who have ventricular tachycardia induced during an electrophysiological study; or (3) unexplained syncope and left ventricular systolic function (28). ICD therapy can reduce sudden cardiac death in patients with symptomatic heart failure (NYHA class II–III) and a left ventricular ejection fraction of 35% or less after at least 3 months of optimal medical therapy, who are expected to survive at least 1 year with good functional status (28).
Recurrent ventricular fibrillation responds poorly to medications, and treatment needs to be tailored with electrophysiological studies. Implantation of an automatic defibrillator has been shown to enhance survival and is well tolerated (13).
Hyperventilation syndrome. Hyperventilation syndrome may respond to rebreathing into a paper bag to normalize arterial pCO2.
Psychogenic pseudosyncope. Recurrent syncope, especially without injury, should prompt consideration of a psychogenic pseudosyncope and possibly psychiatric referral. In population-based series of syncope, psychiatric causes (eg, anxiety disorders, panic attacks, and depression) are found in 35% of transient loss of consciousness patients (58).
Pregnant women typically have a systolic blood pressure in the 90 to 110 mm Hg range, and despite increased plasma and red-cell volume, they may be predisposed to neurocardiogenic syncope. Simple supportive treatment is warranted, and rarely are medications necessary or desired. Impaired venous return by uterine compression of the inferior vena cava may produce syncope in the supine position. Detailed physical examination is mandatory in pregnant patients, especially if they have prior heart disease, dysrhythmias, exertional syncope, or palpitations (70). Recurrent syncope coupled with peripheral edema should raise suspicion for dilated cardiomyopathy.
Syncope occurs in approximately 1% of pregnancies (30). From 2005 to 2014 in the province of Alberta, Canada, 32% of the syncope episodes among pregnant women occurred in the first trimester, 44% in the second trimester, and 24% in the third trimester; 8% of pregnancies had more than 1 episode of syncope (30).
Pregnant women with syncope, especially with first-trimester syncope, may be at a higher risk of adverse pregnancy outcomes (including preterm birth) as well as cardiac arrhythmia and syncope postpartum (30). The incidence of congenital anomalies among children born to women with multiple syncope episodes during pregnancy is significantly higher (4.9%) compared with children born to women without syncope during pregnancy (30).
Patients with recurrent neurocardiogenic syncope may be prone to syncope when exposed to blood drawing and anesthetic procedures, as fear and the site of blood may trigger a spell. The anesthesiologist should be aware of the patient's volume status and the presence of autonomic neuropathy because blood pressure swings may be exaggerated with general or spinal anesthesia. Cardiac status is critical to patient tolerance to general or spinal anesthesia, so careful cardiac examination is essential in a preoperative evaluation.
Douglas J Lanska MD FAAN MS MSPH
Dr. Lanska of the University of Wisconsin School of Medicine and Public Health, the Medical College of Wisconsin, and IM Sechenov First Moscow State Medical University has no relevant financial relationships to disclose.See Profile
Nearly 3,000 illustrations, including video clips of neurologic disorders.
Every article is reviewed by our esteemed Editorial Board for accuracy and currency.
Full spectrum of neurology in 1,200 comprehensive articles.
This article includes discussion of ulnar neuropathies, Guyon canal neuropathy, ulnar neuropathy at the wrist, and flexor carpi ulnaris exit compression.
Jun. 07, 2021
May. 26, 2021
May. 04, 2021
Epilepsy & Seizures
Apr. 09, 2021
Apr. 03, 2021
Apr. 03, 2021
Apr. 01, 2021
Acute traumatic spinal cord injury (TSCI) is a global epidemic in modern society. Yearly, there are over 12,000 new cases of acute spinal cord injury
Mar. 31, 2021