Cardiac Syncope Versus Seizure: The Value of the EP Consult

Dhimesh P. Patel, MD and Todd J. Cohen, MD* Acting Research Coordinator, Department of Electrophysiology, Research Assistant, Department of Electrophysiology; *Director of Electrophysiology, Director of the Pacemaker Arrhythmia Center, Director of Advanced EP Technologies and Innovations Winthrop-University Hospital Mineola, New York

Dhimesh P. Patel, MD and Todd J. Cohen, MD* Acting Research Coordinator, Department of Electrophysiology, Research Assistant, Department of Electrophysiology; *Director of Electrophysiology, Director of the Pacemaker Arrhythmia Center, Director of Advanced EP Technologies and Innovations Winthrop-University Hospital Mineola, New York

Syncope is the loss of consciousness associated with absence of postural tone, followed by complete recovery. It accounts for approximately 5% of all emergency room visits and hospital admissions. Most causes of syncope are not neurologic in nature. Cardiac etiology and seizure disorder are also twice as likely in men, while women are more likely to suffer syncope due to a vasovagal or orthostatic etiology. Vasovagal syncope accounts for 20% of all syncope cases in both genders, and is the most commonly identified etiology of syncope. Table 1 further shows the etiology of syncope based on gender.1 

It is common to confuse syncope with seizure disorder.2,3 One study showed that combined electroencephalogram (EEG)/electrocardiogram (ECG) monitoring in a patient with prolonged asystole exhibited both tonic-clonic movements and an EEG with slow diffuse waves distinct from typical spikes seen in a true seizure disorder.4 Another study demonstrated in 10 of 22 episodes of induced ventricular tachycardia or fibrillation, stereotypical tonic-clonic movements with varied EEG changes but no EEG-defined seizure.5

Cardiac syncope can result in cerebral hypoperfusion, which can mimic a generalized tonic-clonic seizure. Epileptiform movements may be delayed in patients suffering from syncope in contrast to a true seizure disorder, in which there will be loss of consciousness concurrent with epileptiform activity. The mechanism in which cardiac syncope produces tonic-clonic movements is believed to be as follows: with cardiac syncope a variable amount of hemodynamic instability results in cerebral hypoperfusion, which triggers the medullary reticular formation and results in myotonic activity similar to that witnessed during a seizure. This region has multiple inputs responsible for controlling or regulating posture, tone, balance, and auditory and visual signals to the cerebellum.6 

Cardiac causes of syncope carry an increased risk for mortality, but are very treatable when identified early.1 An electrophysiology consult should be considered in any patient suspected of having a seizure, especially when history points to a cardiac condition such as coronary artery disease or left bundle branch block. Other findings not common in typical epilepsy include findings such as hypertension, smoking, chronic obstructive pulmonary disease, seizure less than two minutes, or nonresponsiveness to anti-epileptic drugs (Table 2).6,7 In these cases, a ruling out of cardiac syncope is essential. 

It is not unusual to describe a prodrome of presyncopal symptoms such as dizziness, nausea, or palpitations; however, these findings may be absent when syncope is caused by an arrhythmia and should not rule out a cardiac etiology. The main cardiac etiologies include cardiac arrhythmia (bradycardia or tachycardia), structural heart disease, and outflow tract obstruction (aortic stenosis, pulmonary stenosis, and hypertrophic obstructive cardiomyopathy). 

The initial workup of recurrent syncope of unknown origin (without any cardiac clues such as arrhythmia, cardiac history, or abnormal ECG) should begin with a head-up tilt table test (HUT). This test is useful in identifying neurocardiogenic syncope, but can also diagnose orthostatic hypotension and autonomic dysfunction. A baseline HUT is first conducted with the patient strapped to a table upright between 60 to 80 degrees for a minimum of 10 minutes and up to 45 minutes. The most commonly used protocol uses intravenous isoproterenol to provoke a neurocardiogenic response; however, this drug is contraindicated in coronary artery disease. Sublingual nitroglycerin could alternatively be used.7 

A positive HUT is demonstrated by loss of consciousness with hypotension with or without bradycardia. In neurocardiogenic syncope, there typically is hypotension preceded by bradycardia. Gradual decreases in heart rate and mean arterial pressure indicate autonomic dysfunction, and a drop in blood pressure followed by reflex tachycardia indicates orthostatic hypotension. HUT is limited in that it has a moderately high sensitivity of 80% that is offset by a low specificity (higher number of false positive results). A case control study and a comprehensive literature review demonstrated that use of isoproterenol decreases specificity with false positive results ranging from 20%–60% in some studies.8,9 Patients with neurocardiogenic syncope may be treated with beta blocker therapy. A previous study by this author has shown that drugs with intrinsic sympathomimetic activity such as pindolol are safe and effective as initial therapy and better tolerated over drugs without intrinsic sympathomimetic activity such as atenolol.10,11 Alternative treatment may include hydration, support stockings, alpha agonists such as midodrine, fludrocortisones, and leg training (movement/crossing legs). 

Following a negative HUT, an electrophysiology study (EPS) should be considered when arrhythmia is suspected. The EPS is well suited to candidates with negative HUT. If patients have signs and symptoms of cardiac disease and/or cardiac syncope, EPS can be considered as the initial diagnostic test. The EPS is useful for identifying the presence and location of conduction disease, and determining the presence or absence of tachycardia (supraventricular tachycardia/ventricular tachycardia). It may also be helpful with other therapies such as catheter ablation and implantable devices (pacemakers or implantable-cardioverter defibrillators).12 

Current diagnostic criteria indicative of syncope on EPS are sinus bradycardia with prolonged corrected sinus node recovery time greater than 525 msec, induction of sustained monomorphic ventricular tachycardia in the setting of previous myocardial infarction, induction of rapid supraventricular tachycardia with hypotension, and bundle branch block with either a baseline HV interval of greater than 100 msec or second- or third-degree His-Purkinje block during incremental atrial pacing or pharmacologic challenge (Table 3).7

If both tests (HUT and EPS) are negative, an implantable loop recorder (ILR) should be considered. An ILR is a thin implantable device roughly the size of a USB memory stick. The ILR is implanted subcutaneously over the left pectoral region (similar to a pacemaker) without the leads and can monitor the rhythm for up to 36 months. This device can be programmed to record events based on preset criteria. The device can also be manually activated to record concurrent arrhythmia symptoms during an event (presyncope or syncope). When an arrhythmic cause for syncope is suspected, HUT is not typically useful in predicting the underlying mechanism of syncope.13 In unexplained and recurrent syncope, the ILR has been demonstrated to provide enhanced diagnostic clues over conventional HUT and EP testing.14,15 It has been useful in demonstrating clinically significant arrhythmias in patients with negative conventional testing.16,17 This author previously reported on an experience with ILR in 100 patients which demonstrated a 48% yield in identifying arrhythmia as the underlying cause of syncope after a negative conventional workup.18 Two additional studies have demonstrated the overall cost effectiveness of the ILR as compared to conventional testing.15,19 

In closing, this paper briefly summarizes the confusion between syncope and seizure disorder. It is important to remember that cardiac syncope has the highest mortality; therefore, when in doubt, a thorough and complete cardiac workup including EPS is warranted. The ILR plays an important part in diagnosing the cause of recurrent syncope of unknown etiology. The neurologist should work hand-in-hand with the cardiac consultant/electrophysiologist in managing the patient with a question of syncope versus seizure. 

Disclosures: Dr. Cohen and Dr. Patel have no conflicts of interest to report.

References

  1. Soteriades E, Evans J, Larson M, et al. Incidence and prognosis of syncope. N Engl J Med. 2002;347:878-885.
  2. Sheldon R, Rose S, Ritchie D, et al. Historical criteria that distinguish syncope from seizures. J Am Coll Cardiol. 2002;40(1):142.
  3. Zaidi A, Clough P, Cooper P, et al. Misdiagnosis of epilepsy: many seizure-like attacks have a cardiovascular cause. J Am Coll Cardiol. 2000;36(1):181. Ozkara C, Metin B, Kucukoglu S. Convulsive syncope: a condition to be differentiated from epilepsy. Epileptic Disord. 2009;11(4):315-319.
  4. Aminoff MJ, Scheinman MM, Griffin JC, et al. Electrocerebral accompaniments of syncope associated with malignant ventricular arrhythmias. Ann Intern Med. 1988;108(6):791-796.
  5. Bergfeldt L. Differential diagnosis of cardiogenic syncope and seizure disorders. Heart. 2003;89:353-358.
  6. The Task Force for the Diagnosis and Management of Syncope of the European Society of Cardiology (ESC). Guidelines for the diagnosis and management of syncope (version 2009). Eur Heart J. 2009;30:2631-2671.
  7. Kapoor WN, Brant N. Evaluation of syncope by upright tilt testing with isoproterenol. A nonspecific test. Ann Intern Med. 1992;116(5):358-363.
  8. Kapoor WN, Smith MA, Miller NL. Upright tilt testing in evaluating syncope: a comprehensive literature review. Am J Med. 1994;97(1):78-88. Review.
  9. Cohen TJ. Cohen MB, Snow JS, et al. Efficacy of pindolol for treatment of vasovagal syncope. Am Heart J. 1995;130(4):786-790.
  10. Cohen TJ, Cayenne S, Black M, et al. The effects of intrinsic sympathomimetic activity on beta-blocker efficacy for treatment of neurocardiogenic syncope. J Invasive Cardiol. 1999;11(7):457-460.
  11. Hess DS, Morady F, Scheinman MM. Electrophysiologic testing in the evaluation of patients with syncope of undetermined origin. Am J Cardiol. 1982;50:1309-1315.
  12. García-Civera R, Ruiz-Granell R, Morell-Cabedo S, et al. Significance of tilt table testing in patients with suspected arrhythmic syncope and negative electrophysiologic study. J Cardiovasc Electrophysiol. 2005;16(9):938-942.
  13. Krahn AD, Klein GJ, Yee R, et al. Randomized assessment of syncope trial: conventional diagnostic testing versus a prolonged monitoring strategy. Circulation. 2001;104(1):46.
  14. Farwell DJ, Freemantle N, Sulke AN. Use of implantable loop recorders in the diagnosis and management of syncope. Eur Heart J. 2004;25(14):1257.
  15. Paisey JR, Yue AM, Treacher K et al. Implantable loop recorders detect tachyarrhythmias in symptomatic patients with negative electrophysiological studies. Int J Cardiol. 2005;98(1):35-38.
  16. Boersma L, Mont L, Sionis A, et al. Value of the implantable loop recorder for the management of patients with unexplained syncope. Europace. 2004;6(1):70-76.
  17. Inamdar V, Mehta S, Juang G, Cohen T. The utility of implantable loop recorders for diagnosing unexplained syncope in 100 consecutive patients. J Invasive Cardiol. 2006;18(7):313-315.
  18. Krahn AD, Klein GJ, Yee R, Manda V. The high cost of syncope: cost implications of a new insertable loop recorder in the investigation of recurrent syncope. Am Heart J. 1999;137(5):870.