Laryngospasm, central and obstructive apnea during seizures: Defining pathophysiology for sudden death in a rat model

•Seizure activity spreads to laryngeal motor neurons to cause laryngospasm.•Laryngospasm results in partial or complete airway occlusion.•Seizure activity changes breathing frequency, amplitude, variability, and can cause central apnea.•Only obstructive apnea was associated with rapid, severe arterial oxygen desaturation, bradycardia, and death.•Sudden death is the result of respiratory arrest during airway obstruction and nearly simultaneous LV dilatation and asystole.

Seizure spread into the autonomic nervous system can result in life-threatening cardiovascular and respiratory dysfunction. Here we report on a less-studied consequence of such autonomic derangements-the possibility of laryngospasm and upper-airway occlusion.We used parenteral kainic acid to induce recurring seizures in urethane-anesthetized Sprague Dawley rats. EEG recordings and combinations of cardiopulmonary monitoring, including video laryngoscopy, were performed during multi-unit recordings of recurrent laryngeal nerve (RLN) activity or head-out plethysmography with or without endotracheal intubation. Controlled occlusions of a tracheal tube were used to study the kinetics of cardiac and respiratory changes after sudden obstruction.Seizure activity caused significant firing increases in the RLN that were associated with abnormal, high-frequency movements of the vocal folds. Partial airway obstruction from laryngospasm was evident in plethysmograms and was prevented by intubation. Complete glottic closure (confirmed by laryngoscopy) occurred in a subset of non-intubated animals in association with the largest increases in RLN activity, and cessation of airflow was followed in all obstructed animals within tens of seconds by ST-segment elevation, bradycardia, and death. Periods of central apnea occurred in both intubated and non-intubated rats during seizures for periods up to 33 s and were associated with modestly increased RLN activity, minimal cardiac derangements, and an open airway on laryngoscopy. In controlled complete airway occlusions, respiratory effort to inspire progressively increased, then ceased, usually in less than 1 min. Respiratory arrest was associated with left ventricular dilatation and eventual asystole, an elevation of systemic blood pressure, and complete glottic closure.Severe laryngospasm contributed to the seizure- and hypoxemia-induced conditions that resulted in sudden death in our rat model, and we suggest that this mechanism could contribute to sudden death in epilepsy.