Both atrial and ventricular arrhythmias can produce transient neurologic symptoms by disrupting cerebral perfusion, but ventricular arrhythmias rarely result in seizures. In the absence of evidence of infarction, however, arrhythmia-induced convulsive syncope can be difficult to distinguish clinically from seizure.

Nonvalvular atrial fibrillation increases the risk of stroke five- to sevenfold. Multivariate analysis has found additional risk factors for embolic strokes in patients with nonvalvular atrial fibrillation:28

• hypertension
• age over 75
• previous transient ischemic attack (TIA)
• diabetes mellitus

In the Copenhagen Stroke Study, 4.2% of patients had seizures within 2 weeks of embolic stroke.29 Early seizures were associated with worse stroke severity at presentation but predicted better clinical outcome, suggesting that they may be characteristic of strokes with a large reversible ischemic penumbra.

Current recommendations by the Sixth Consensus Conference on antithrombotic therapy30 strongly recommends chronic warfarin therapy (INR 2.0–3.0) for patients with AF with any high-risk factor:

• prior stroke/ TIA or systemic embolus
• history of hypertension
• poor left ventricular systolic function
• rheumatic mitral disease
• prosthetic heart valves
• age over 75 years or with multiple moderate-risk factors:
• age 65 to 75 years
• diabetes mellitus
• coronary artery disease with preserved left ventricular systolic function

For these and patients in whom warfarin is contraindicated, 325 mg of aspirin daily should be used.

Antiepileptic drugs with potential interactions with warfarin or aspirin should be avoided, not only to optimize seizure prophylaxis but also to minimize stroke risk. Valproic acid can produce a serum-level-dependent thrombocytopenia, and may cause abnormal platelet function by inhibiting the second phase of platelet aggregation. These effects are reversible with decreasing dose. The clinical risk of bleeding diatheses is minimal, but may be more significant in patients with other risks of hemorrhage. Such risks include therapeutic use of agents such as aspirin or warfarin.

Clinically important interactions of aspirin or warfarin with antiepileptic drugs

Antiepileptic drug	Antiplatelet/Anticoagulant	Potential clinical effect
Phenytoin	Warfarin	Increases INR
Phenytoin	Aspirin	Increases free phenytoin
Carbamazepine	Warfarin	Decreases INR
Phenobarbital	Warfarin	Decreases INR
Primidone	Warfarin	Decreases INR
Valproic acid	Warfari	Slight decrease in INR
Valproic acid	Aspirin	Increases free valproic acid

INR = international normalized ratio

Patients with sick sinus syndrome, especially those in whom bradycardia alternates with tachycardia, are also at risk for cerebral embolism. These arrhythmias may result in misdiagnosis of epilepsy, especially in children.

Long QT syndromes (LQTS) are rare congenital ion channel disorders that produce episodic ventricular arrhythmias with resultant seizures, syncope, and potentially sudden death:

• Romano-Ward syndrome is characterized by prolonged QT interval and autosomal-dominant inheritance, with 6 identifiable genetic variants (LQT1-6).
• Jervell and Lange-Nielsen syndrome has marked prolongation of QT interval and sensorineural deafness. It is much rarer.

Three LQTS genes have been identified: SCN5A on 3p21-24, HERG on 7q35-36, and KVLQT1 on 11p15.5. Genetic tests are available.31 Mutations of various cardiac voltage-dependent sodium channels and potassium-current mechanisms occur, although some cases are sporadic.32

Clinically there is an imbalance in sympathetic influences on the heart, and symptoms often appear with exercise or stress. Although EEGs may be abnormal, measurement of the corrected QT interval obtained in one EEG channel can document the cardiac abnormality.33

Adapted from: Boggs J. Cardiac disorders. In: Ettinger AB and Devinsky O, eds. . Managing epilepsy and co-existing disorders. Boston: Butterworth-Heinemann; 2002;39-47.
With permission from Elsevier (www.elsevier.com).
Reviewed and revised June 2004 by Jane Boggs, MD, University of South Alabama College of Medicine.

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