Achieving the correct final diagnosis with the presenting symptom of transient loss of consciousness can challenge even the most seasoned clinician. Syncope and epileptic seizures reign high on the list of differential diagnoses, followed by narcolepsy, cataplexy, pseudoseizures, and pseudosyncope (Sheldon, 2015). Distinguishing between these top two contenders can be difficult and often the investigation is inconclusive or incorrect. Research suggests that between 20-40% of patients diagnosed with epilepsy have been misdiagnosed, and syncope is the most common misdiagnosis in epilepsy (Hackethal, 2017). Let’s take a closer look into this medical diagnosis conundrum.
Syncope is defined as a symptom that presents with an abrupt, transient, complete loss of consciousness, associated with inability to maintain postural tone, with rapid and spontaneous recovery, and that is caused by cerebral hypoperfusion. Studies of syncope report prevalence rates as high as 41%, with recurrent syncope occurring in 13.5% and the prevalence of syncope as a presenting symptom to the ED ranged from 0.8% to 2.4% (Shen, et al., 2017). The most common causes of syncope include reflex syncope (blood/injury exposure), orthostatic syncope, cardiac arrythmias, and structural cardiopulmonary disease (Benditt, 2018). Often syncope is preceded by a prodrome or period of presyncope that may include a constellation of symptoms including lightheadedness, feeling warm or cold, diaphoresis, palpitations, nausea/abdominal discomfort, visual blurring, pallor, or changes in hearing (Benditt, 2018).
Seizures fall into two categories: epileptic and non-epileptic. Epileptic seizures occur spontaneously or unprovoked and are recurrent. They are further classified as generalized tonic-clonic seizure and the more common, partial complex seizure (Sheldon, 2015). Causes of epileptic seizures include brain injury, stroke, brain tumors, and neurological disorders. Diagnosis is made by abnormal brain activity on an electroencephalogram (EEG). Non-epileptic seizure causes can include fever, infection, electrolyte imbalance, drug/alcohol withdrawal, psychological conditions, and hypoglycemia. You will expect to find normal brain wave activity on EEG testing in a patient with a non-epileptic seizure.
Many syncopal events include loss of consciousness as the only symptom. The diagnostic problem occurs when a patient with syncope also has myoclonic jerks or convulsions. These events are sometimes referred to as seizure-like syncope or convulsive syncope. Myoclonic jerks and tonic spasms are the most misleading symptoms in the differential diagnosis between syncope and seizures (Bergfeldt, 2003). The underlying pathophysiology of convulsive syncope is as follows: the cardiac syncope causes a variable amount of hemodynamic instability resulting in cerebral hypoperfusion, which triggers the medullary reticular formation and results in myoclonic activity that mimics seizure activity (Patel and Cohen, 2013). The gold standard to differentiate between the two would require videotelemetry with simultaneous EEG and electrocardiographic (ECG) recording with scalp and chest electrodes – a clinical scenario that is rarely fulfilled (Bergfeldt, 2003). One of the most important clues usually comes from an observant bystander who witnesses the event and is able to report if the person went limp then convulsed (syncope) or if the episode began with convulsions (seizure). Be alert for other clues, as well. Identifiable triggers are associated with syncope and seizures tend to have a longer duration than syncope and are followed by postictal confusion and significant fatigue, although brief periods of confusion have been reported with convulsive syncope. Other common features of convulsive syncope that are not common in seizures include a period of presyncope with prodrome, pallor, duration less than one minute, and fixed or upward eye deviation. Conversely, common features of a seizure, that are not common in syncope, can include tongue biting, prodromal cry, incontinence, duration often a few minutes, and lateral eye deviation (Sheldon, 2015). Accurate diagnosis is often challenged by the patient’s amnesia of the events, lack of bystander presence/account, and discordance among clinician opinions (McKeon, Vaughan, and Delanty, 2006).
Evaluation of a patient that presents with transient loss of consciousness can be extensive and often include cardiology and neurology consultations. All patients must have a comprehensive history and physical examination. The detailed history must include:
- Detailed past medical history
- Number, frequency, and duration of episodes
- Time of onset
- Body position when the event occurred
- Provocative factors or associated symptoms preceding the event
- Symptoms following the event
- Witness account, if available
- Family history
The physical exam must include:
- Pulse and blood pressure measurements while the patient is lying, sitting, and standing to assess for orthostatic hypotension
- Blood pressure in each arm. Inequality suggests aortic dissection or aortic coarctation
- Respiration rate to assess for hyperventilation as seen with pulmonary and/or psychiatric causes
- Careful auscultation of heart sounds to assess for cardiac murmurs
- Consider careful carotid massage in an older patient
- Neurological exam
Initial evaluation should also include ECG, echocardiogram, and basic laboratory testing to exclude anemia, infection, electrolyte imbalances, or renal and liver dysfunction. The ECG is a powerful tool in the setting of evaluation of a patient with transient loss of consciousness. The ECG can help with the assessment for arrythmias (sinus bradycardia, sinus pauses, atrioventricular heart blocks, ventricular tachycardia, bundle branch blocks), intraventricular conduction delays, pre-excited QRS complexes, left ventricular hypertrophy, and pacemaker or implantable cardioverter-defibrillator malfunction, as well as others. An echocardiogram helps assess for structural heart disease including left ventricular dysfunction, hypertrophic cardiomyopathy, significant aortic stenosis, intracardiac tumors, and right ventricular enlargement (suggestive of pulmonary embolism). This initial evaluation yields a relative certain diagnosis approximately 50% of the time (Benditt, 2018).
Based on the yield from the initial investigation, further testing may be warranted depending on results and clinical suspicion. When the suspicion of epilepsy is high with the first unprovoked seizure or focal neurologic deficits, a 30-minute interictal EEG and neuroimaging including CT or MRI. Head-up tilt table testing (HUT), with or without the use of intravenous isoproterenol or sublingual nitroglycerin, is useful in identifying neurocardiogenic syncope, orthostatic hypotension, and autonomic dysfunction. A positive HUT is demonstrated by loss of consciousness with hypotension with or without bradycardia. More specifically, bradycardia followed by hypotension is seen in neurocardiogenic syncope, a gradual decrease in heart rate and mean arterial pressure indicate autonomic dysfunction, and a decrease in blood pressure followed by reflex tachycardia indicates orthostatic hypotension. If a HUT is negative and arrhythmia is strongly suspected, an electrophysiology study (EPS), implantable loop recorder, or ambulatory heart monitor may also be considered.
When a patient presents with transient loss of consciousness, identifying the accurate underlying diagnosis can be daunting. This task is manageable, however, by first documenting an excellent history and physical, then performing the above standard tests, and finally, collaborating with your colleague consultations from cardiology and neurology.
Benditt, D. (2018). Syncope in adults: Clinical manifestation and diagnostic evaluation. In B.C. Downey (Ed.), UpToDate. Retrieved July 31, 2019, from www.uptodate.com/contents/syncope-in-adults-clinical-manifestations-and-diagnostic-evaluation
Bergfeldt, L. (2003). Differential diagnosis of cardiogenic syncope and seizure disorders. Heart, 89, 353-358. doi: 10.1136/heart.89.3.353
Hackethal, V. (2017). Epilepsy, syncope, or both? Retrieved July 11, 2019, from https://www.neurologytimes.com/epilepsy-and-seizure/epilepsy-syncope-or-both
McKeon, A., Vaughan, C., and Delanty, N. (2006). Seizure versus syncope. Lancet Neurology, 5, 171-180. doi: 10.1016/S1474-4422(06)70350-7
Patel, D.P. and Cohen, T.J. (2013). Cardiac syncope versus seizure: The value of the EP consult. EP Lab Digest, 13(2). Retrieved July 11, 2019, from https://www.eplabdigest.com/articles/Cardiac-Syncope-Versus-Seizure-Value-EP-Consult
Sheldon, R. (2015). How to differentiate syncope from seizure. Cardiology Clinics, 33 (3), 377-385. doi: 10.1016/j.ccl.2015.04.006
Shen, W.K., Shledon, R.S., Benditt, D.G., Cohen, M. I., Forman, D. E., Goldberger., Z. D.,...Yancy, C.W. (2017). 2017 ACC/AHA/HRS guideline for the evaluation and management of patients with syncope. Heart Rhythm, 14(9), e155-e217. doi: 10.1016/j.hrthm.2017.03.004