of the many causes of TLOC or apparent TLOC, including seizure disorders, traumatic brain injury (ie, concussion), intoxications, metabolic disturbances, mechanical falls, and conversion disorders (ie, psychogenic "pseudosyncope" or "pseudoseizures") [9-12]. Distinguishing these conditions from true syncope can be challenging, but is crucial to appropriate management and assessment of prognosis. When caring for patients who present with TLOC/collapse, it is also important to consider causes that are not syncope ( algorithm 1). Examples of nonsyncopal causes of TLOC or apparent TLOC include: Seizures. (See "Evaluation and management of the first seizure in adults".) Cardiac arrest, which requires resuscitation. (See "Overview of sudden cardiac arrest and sudden cardiac death" and "Adult basic life support (BLS) for health care providers" and https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 13/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate "Advanced cardiac life support (ACLS) in adults".) Sleep disturbances, including narcolepsy and cataplexy. (See "Clinical features and diagnosis of narcolepsy in adults".) Accidental falls or other incidents resulting in traumatic brain injury (ie, concussion). Intoxications and metabolic disturbances (including hypoglycemia). Some psychiatric conditions (eg, conversion reactions resulting in psychogenic pseudosyncope or pseudoseizures, with the latter termed "nonepileptic seizures" by some neurologists). (See "Nonepileptic paroxysmal disorders in adolescents and adults".) ADDITIONAL EVALUATION Additional diagnostic evaluation is individualized based on the suspected etiology of syncope ( table 4 and table 2) [2]. The major causes of syncope and their evaluation are discussed separately. (See "Syncope in adults: Epidemiology, pathogenesis, and etiologies" and "Syncope in adults: Risk assessment and additional diagnostic evaluation".) Of note, many patients have multiple comorbidities that can contribute to TLOC, and, consequently, there may be multiple plausible causes of syncope that require careful assessment. An observed abnormality should not be assumed to be the cause of collapse without first giving careful consideration to alternative diagnoses and interactions among various coexisting conditions. For example, orthostatic hypotension is common among older patients, but susceptibility to syncope may be the result of medications that the patient has been prescribed, an intercurrent illness, a previously unrecognized neurologic disease (eg, Parkinson disease), or even a previously unsuspected arrhythmia that undermines the individual's hemodynamic stability. Similarly, carotid sinus hypersensitivity (CSH) is a common finding in older patients, but only infrequently is CSH the cause of syncope (in which case the condition is termed carotid sinus syndrome). (See "Mechanisms, causes, and evaluation of orthostatic hypotension" and "Carotid sinus hypersensitivity and carotid sinus syndrome".) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Syncope".) https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 14/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topic (see "Patient education: Syncope (fainting) (The Basics)") Beyond the Basics topic (see "Patient education: Syncope (fainting) (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS Definition Syncope is a transient, self-limited loss of consciousness caused by transient, self-terminating, inadequate nutrient flow to the brain; episodes may or may not be preceded by prodromal symptoms. Presyncope (or near-syncope) is a manifestation of prodromal symptoms reflecting the same conditions that might lead to syncope in the same individual at other times. (See 'Definitions' above.) Initial evaluation The initial evaluation of patients with transient loss of consciousness (TLOC) and suspected syncope should focus on differentiation of true syncope from other events ( algorithm 1), risk stratification ( table 1), and assessment of potential causes ( table 2). The evaluation should generally include a comprehensive history (including information about events, preexisting conditions, medications, and family history), witness observations if available, a physical examination (which may include careful carotid sinus massage in older patients), and review of ECGs. Documentation of medications that the patient is taking is an important element of the initial evaluation. A transthoracic echocardiogram is useful to evaluate for structural heart disease if this is suspected. (See 'Approach to initial evaluation' above.) https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 15/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate Clinical features The clinical features associated with a syncopal event may be diagnostic ( table 1 and table 2). Key features of events include the frequency and duration of events, triggers and circumstances, presence and types of prodromal symptoms, witnessed signs during episodes, and features of recovery. (See 'Clinical features' above.) Classic prodromal symptoms associated with syncope and presyncope, particularly the vasovagal form of reflex syncope, include lightheadedness, a feeling of being warm or cold, sweating, palpitations, pallor, nausea, visual blurring, and diminution of hearing and/or occurrence of unusual (often "whooshing") sounds. (See 'Onset/prodrome' above.) Physical examination A number of findings on physical examination can aid in the identification of some of the common causes of syncope, including abnormalities in the vital signs, orthostatic blood pressure changes, cardiovascular abnormalities, and, less frequently, neurologic signs. (See 'Physical examination' above.) Electrocardiogram A 12-lead ECG should be obtained in all patients with suspected syncope, and an ambulatory ECG is warranted in many cases. The 12-lead ECG only rarely identifies a specific arrhythmic cause of syncope, although certain findings (eg, persistent bradycardia <40 beats per minute, high-grade atrioventricular (AV) block, ventricular or supraventricular tachycardia with rapid ventricular rate, pacemaker malfunction, etc) are considered diagnostic. (See 'Electrocardiogram' above.) Differential diagnosis Distinguishing syncope from other conditions with or without TLOC requires careful diagnostic assessment ( algorithm 1). Nonsyncopal causes of TLOC or apparent TLOC include accidental falls, cardiac arrest, seizures, sleep disturbances, intoxications, metabolic disorders, and some psychiatric conditions. (See 'Differential diagnosis' above.) Additional testing Additional diagnostic evaluation is individualized based on the suspected etiology of syncope ( table 2 and table 4). Many patients have multiple comorbidities that can contribute to TLOC, and thus multiple plausible causes of syncope may require careful assessment. (See 'Additional evaluation' above and "Syncope in adults: Epidemiology, pathogenesis, and etiologies" and "Syncope in adults: Risk assessment and additional diagnostic evaluation".) Use of UpToDate is subject to the Terms of Use. REFERENCES https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 16/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate 1. Thijs RD, Benditt DG, Mathias CJ, et al. Unconscious confusion a literature search for definitions of syncope and related disorders. Clin Auton Res 2005; 15:35. 2. Shen WK, Sheldon RS, Benditt DG, et al. 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, and the Heart Rhythm Society. J Am Coll Cardiol 2017. 3. Brignole M, Moya A, de Lange FJ, et al. 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart J 2018; 39:1883. 4. Albassam OT, Redelmeier RJ, Shadowitz S, et al. Did This Patient Have Cardiac Syncope?: The Rational Clinical Examination Systematic Review. JAMA 2019; 321:2448. 5. Furlan R, Alciati A. Psychogenic pseudosyncope and pseudoseizure: Approach and treatmen t. In: Syncope: An Evidence-Based Approach, 2nd ed, Brignole M, Benditt DG (Eds), Springer Nature 2020. p.135. 6. Fedorowski A, Pirouzifard M, Sundquist J, et al. Risk Factors for Syncope Associated With Multigenerational Relatives With a History of Syncope. JAMA Netw Open 2021; 4:e212521. 7. Altinsoy M, Sutton R, Kohno R, et al. Ambulatory ECG monitoring for syncope and collapse in United States, Europe, and Japan: The patients' viewpoint. J Arrhythm 2021; 37:1023. 8. Sarasin FP, Junod AF, Carballo D, et al. Role of echocardiography in the evaluation of syncope: a prospective study. Heart 2002; 88:363. 9. van Dijk JG, Thijs RD, Benditt DG, Wieling W. A guide to disorders causing transient loss of consciousness: focus on syncope. Nat Rev Neurol 2009; 5:438. 10. Kapoor WN. Evaluation and outcome of patients with syncope. Medicine (Baltimore) 1990; 69:160. 11. Blanc JJ, L'Her C, Touiza A, et al. Prospective evaluation and outcome of patients admitted for syncope over a 1 year period. Eur Heart J 2002; 23:815. 12. Ungar A, Morrione A, Rafanelli M, et al. The management of syncope in older adults. Minerva Med 2009; 100:247. Topic 969 Version 46.0 https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 17/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate GRAPHICS Algorithm for syncope/collapse This algorithm poses key questions about a collapse episode, including whether and when LOC occurred. However, in the absence of a credible witness, information about such episodes is often limited, as the affected individual may not have accurate recall of the event. Some causes have more than one possible type of presentation. LOC: loss of consciousness; BLS: basic life support; ACLS: advanced cardiac life support; SAH: subarachnoid hemorrhage; TIA: transient ischemic attack. This includes actual LOC as well as apparent LOC. Accidental falls without LOC often have multiple causes, including gait, posture, or balance impairment, environmental hazard, vertigo, focal seizure, TIA, stroke, and presyncope. https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 18/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate These conditions result in apparent transient LOC, although consciousness may be preserved. Other causes of collapse may cause secondary head trauma. Most TIAs and strokes are not associated with LOC. An SAH may cause transient or prolonged LOC. A rare cause of LOC is a brainstem stroke. Graphic 131146 Version 1.0 https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 19/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate Clinical and electrocardiographic (ECG) features of patients with syncope at high risk of an arrhythmic cause Significant structural heart disease or CAD (including reduced LVEF, heart failure, CAD with prior MI, severe aortic or mitral stenosis, hypertrophic cardiomyopathy) Persistent sinus bradycardia <40 beats per minute or sinus pauses >3 seconds in an awake patient Third-degree (complete) AV block Mobitz II second-degree AV block Preexcited QRS complexes, suggesting Wolff-Parkinson-White syndrome Alternating left and right bundle branch block VT or paroxysmal supraventricular tachycardia with rapid ventricular rate Nonsustained polymorphic VT with long or short QT interval Long or short QT intervals Right bundle branch block pattern with ST elevation in leads V1 to V3 (Brugada syndrome) Negative T waves in right precordial leads and epsilon waves suggestive of arrhythmogenic right ventricular cardiomyopathy Pacemaker or implantable cardioverter-defibrillator malfunction with cardiac pauses CAD: coronary artery disease; LVEF: left ventricular ejection fraction; MI: myocardial infarction; AV: atrioventricular; VT: ventricular tachycardia. Adapted from: Brignole M, Moya A, de Lange FJ, et al. 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart J 2018; 39:1883. Graphic 118883 Version 3.0 https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 20/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate Clinical features of syncope that suggest a cause Neurally mediated syncope: Absence of heart disease Long history of recurrent syncope After sudden unexpected unpleasant sight, sound, smell, or pain Prolonged standing or crowded, hot places Nausea, vomiting associated with syncope During a meal or postprandial With head rotation or pressure on carotid sinus (as in tumors, shaving, tight collars) After exertion Syncope due to OH: After standing up Temporal relationship with start or changes of dose of vasodepressive drugs leading to hypotension Prolonged standing, especially in crowded, hot places Presence of autonomic neuropathy or Parkinsonism Standing after exertion Cardiovascular syncope: Presence of definite structural heart disease Family history of unexplained sudden death or channelopathy During exertion or supine Abnormal ECG Sudden onset palpitation immediately followed by syncope ECG findings suggesting arrhythmic syncope: Bifascicular block (defined as either LBBB or RBBB combined with left anterior or left posterior fascicular block) Other intraventricluar conduction abnormalities (QRS duration 0.12 s) Mobitz I second-degree AV block Asymptomatic inappropriate sinus bradycardia (<50 bpm), sinoatrial block or sinus pause 3 s in the absence of negatively chronotropic medications Nonsustained VT https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 21/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate Preexcited QRS complexes Long or short QT intervals Early repolarization RBBB pattern with ST elevation in leads V1 to V3 (Brugada syndrome) Negative T waves in right precordial leads, epsilon waves and ventricular late potentials suggestive of ARVC Q waves suggesting myocardial infarction OH: orthostatic hypotension; ECG: electrocardiogram; LBBB: left bundle branch block; RBBB: right bundle branch block; AV: atrioventricular; bpm: beats per minute; VT: ventricular tachycardia; ARVC: arrhythmogenic right ventricular cardiomyopathy. Reproduced with permission from: European Heart Rhythm Association (EHRA), Heart Failure Association (HFA), Heart Rhythm Society (HRS), et al. Guidelines for the diagnosis and management of syncope (version 2009): the Task Force for the Diagnosis and Management of Syncope of the European Society of Cardiology (ESC). Eur Heart J 2009; 30:2631. Copyright 2009 Oxford University Press. Graphic 66884 Version 10.0 https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 22/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate Causes of bradycardia Intrinsic Extrinsic Idiopathic degenerative disorder Drugs Ischemic heart disease Antiarrhythmic agents Chronic ischemia Class IA - quinidine, procainamide Acute myocardial infarction Class IC - propafenone, flecainide Hypertensive heart disease Class II - -blockers Cardiomyopathy Class III - sotalol, amiodarone, dronedarone Trauma Class IV - diltiazem, verapamil Surgery for congenital heart disease Cardiac glycosides Heart transplant Antihypertensive agents Inflammation Clonidine, reserpine, methyldopa Collagen vascular disease Antipsychotic agents Rheumatic fever Lithium, phenothiazines, amitriptyline Pericarditis Autonomically mediated Infection Vasovagal syncope (cardioinhibitory) Viral myocarditis Carotid sinus hypersensitivity Lyme disease (Borrelia burgdorfer I) Hypothyroidism Neuromuscular disorder Intracranial hypertension Friedreich ataxia Hypothermia X-linked muscular dystrophy Hyperkalemia Familial disorder Hypoxia Anorexia nervosa Reproduced with permission from: Fuster V, Walsh R, Harrington R. Hurst's the Heart, 13th ed, McGraw-Hill Professional, New York 2010. Copyright 2010 The McGraw-Hill Companies, Inc. Graphic 65521 Version 11.0 https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 23/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate Major cardiovascular causes of syncope Reflex-mediated* Vasovagal Orthostatic vasovagal syncope: usually after prolonged standing, frequently in a warm environment, etc Emotional vasovagal syncope: secondary to fear, pain, medical procedure, etc Unknown trigger Situational Micturition, defecation Swallowing Coughing/sneezing Carotid sinus syndrome Orthostatic hypotension* Medication-related Diuretics (eg, thiazide or loop diuretics) Vasodilators (eg, dihydropyridine calcium channel blockers, nitrates, alpha blockers, etc) Antidepressants (eg, tricyclic drugs, SSRIs, etc) Volume depletion Hemorrhage Gastrointestinal losses (ie, vomiting or diarrhea) Diminished thirst drive (primarily in older patients) Autonomic failure Primary: pure autonomic failure, Parkinson disease, multiple system atrophy, Lewy body dementia Secondary: diabetes mellitus, amyloidosis, spinal cord injuries, autoimmune neuropathy (eg, Guillain-Barr ), paraneoplastic neuropathy Cardiac Tachyarrhythmias Ventricular tachycardia Supraventricular tachycardias Bradyarrhythmias (with inadequate ventricular response) Sinus node dysfunction Atrioventricular block Structural disease https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 24/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate Severe aortic stenosis Hypertrophic cardiomyopathy Cardiac tamponade Prosthetic valve dysfunction Congenital coronary anomalies Cardiac masses and tumors (eg, atrial myxoma) Cardiopulmonary/vascular Pulmonary embolus Severe pulmonary hypertension Aortic dissection SSRI: selective serotonin reuptake inhibitor. Reflex-mediated syncope and syncope due to orthostatic hypotension are more likely to occur, or are more severe, when other factors may also be contributing, such as medication(s) causing low blood pressure, volume depletion, pulmonary diseases causing reduction in brain oxygen supply, alcohol use, and/or environmental factors (excessive heat or humidity). Adapted from: Brignole M, Moya A, de Lange FJ, et al. 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart J 2018; 39:1883. Graphic 118175 Version 4.0 https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 25/26 7/6/23, 2:38 PM Syncope in adults: Clinical manifestations and initial diagnostic evaluation - UpToDate Contributor Disclosures David Benditt, MD Equity Ownership/Stock Options: Medtronic [Pacemakers/event recorders and defibrillators]. Grant/Research/Clinical Trial Support: Medtronic [Pacemakers/event recorders and defibrillators]; St Jude Medical [Pacemakers/event recorders and defibrillators]. Consultant/Advisory Boards: Medtronic [Pacemakers/event recorders and defibrillators]; Zoll [Pacemakers/event recorders and defibrillators]. Other Financial Interest: Advanced CPR Solutions [Outside director]. All of the relevant financial relationships listed have been mitigated. Peter Kowey, MD, FACC, FAHA, FHRS Equity Ownership/Stock Options: VuMedi [Arrhythmias]. Consultant/Advisory Boards: Abbvie [Arrhythmias]; Acesion Pharma [Arrhythmias]; Allergan [Arrhythmias, cardiac safety of non-cardiac drugs]; Anthos [Anticoagulants]; Boehringer-Ingelheim [Arrhythmias]; Bristol-Meyers-Squibb [Arrhythmias]; Daiichi Sankyo [Arrhythmias]; Gilead [Arrhythmias]; Huya [Arrhythmias]; InCarda Therapeutics [Arrhythmias]; INSTA [Arrhythmias]; Johnson & Johnson [Arrhythmias]; Medtronic [Arrhythmias]; Milestone [Arrhythmias]; Novartis [Arrhythmias, cardiac safety of non-cardiac drugs]; Pfizer [Arrhythmias]; Sanofi [Arrhythmias]; Takeda [Arrhythmias]. All of the relevant financial relationships listed have been mitigated. Korilyn S Zachrison, MD, MSc Grant/Research/Clinical Trial Support: American College of Emergency Physicians [Stroke quality improvement]; CRICO [Headache management]; National Institutes of Health/National Institute of Neurological Disorders and Stroke [Telestroke, telehealth, prehospital stroke care, COVID and thromboembolic risk]. Speaker's Bureau: Efficient CME [Honorarium]. Other Financial Interest: Journal of the American Heart Association [Associate Editor]. All of the relevant financial relationships listed have been mitigated. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-initial-diagnostic-evaluation/print 26/26