How do epileptic seizures cause death?

Sudden unexpected death in epilepsy (SUDEP) accounts for up to 18% of deaths among epileptic patients. Tachyarrhythmias and respiratory pattern disturbances accompany many seizures and evidence points to seizures preceding death in SUDEP cases, but details of the underlying SUDEP mechanism(s) are unclear. We have used a rat model to demonstrate that seizures can cause profound increases in parasympathetic and sympathetic outflow, that bradycardia precedes death, and that a respiratory obstruction is necessary for death to occur. We sought to address several critical cardiac and respiratory questions. First, what determines cardiac rhythm when both divisions of the ANS are strongly activated, and can ventricular fibrillation (VF) be the result? Are epileptic animals more susceptible to fatal cardiac arrhythmias? Second, what are the effects of seizure activity on laryngeal muscle activity and airway patency? Recordings from autonomic nerves showed that arrhythmias were associated with specific patterns of increased autonomic activity in both divisions. Combinations of autonomic activity and hypoxia could result in VF, but only within a narrow range; transient mild arrhythmias or malignant bradycardia were more common alternatives. Rats with chronic seizures were less likely to enter VF, even though they showed echocardiographic, EKG, and histological evidence of eccentric cardiac hypertrophy. During laryngeal EMG, recurrent laryngeal neurograms, and/or video laryngoscopy, hypopnea occurring during seizures was associated with opening and twitching of vocal folds, indicating that a neurally-mediated obstructive apnea was not present. We conclude that a terminal arrhythmia such as VF is an uncommon cause of SUDEP. Repeated seizures may actually contribute to an increased resistance to VF either via cardiac structural changes or by inducing ischemic preconditioning. Further, whereas respiratory pattern disturbances and laryngospasm can occur during seizures, vocal folds tended toward the open position, leaving the airway intact, and suggesting the importance of an external obstruction.