Seizure-Induced Laryngospams in Mice

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Abstract Sudden unexpected death in epilepsy (SUDEP) accounts for up to 17% of deaths in epileptic patients. These unexplained deaths may be precipitated by laryngospasm, tight closure of the laryngeal inlet that causes airway obstruction. Seizures cause a wide range of respiratory changes, and laryngospasm has been observed in patients with ictal respiratory distress. Moreover, using a model of anesthetized rats treated with urethane and kainate, we recently demonstrated that seizure-induced laryngospasm initiates a sequence of obstructive apnea, arterial oxygen desaturation, bradycardia, respiratory arrest, and, without intervention, death. Here, we propose to test the hypothesis that laryngospasm is the proximal cause of death in SUDEP cases by using a model of AWAKE, UNANESTHETIZED mice that are prone to dying from audiogenic seizures. Our study population will comprise two cohorts of mice with custom-made T-shaped tubes implanted in the trachea while preserving recurrent-laryngeal-nerve function. In the experimental group, the tube's percutaneous side arm will be left open to provide an alternative airway; in the control group, the side arm will be closed to limit airflow to the normal airway. We predict that the experimental mice will survive audiogenic seizures because the alternative airway will allow air to bypass laryngospasm; the control mice, in contrast, will die from the seizures. The results of this study will provide additional evidence for the contribution of ictal laryngospasm to death. In particular, this animal model more closely resembles typical patients because of the absence of anesthetic and epileptogenic drugs. In addition, this study has direct application to the clinical arena in which skilled upper-airway management during seizures may be a key component to preventing patient deaths. Finally, the results will guide the development of resuscitative and preventative strategies that can be translated to patients at risk for sudden death in epilepsy.