Objective: Recent research suggests that obstructive laryngospasm and consequent respiratory arrest may be a mechanism in sudden unexpected death in epilepsy. We sought to test a new hypothesis that this laryngospasm is caused by seizures driving reflux of stomach acid into the larynx, rather than spontaneous pathological activity in the recurrent laryngeal nerve. Approach: We used an acute kainic acid model under urethane anesthesia to observe seizure activity in Long-Evans rats. We measured the pH in the esophagus and respiratory activity. In a subset of experiments, we blocked acid movement up the esophagus with a balloon catheter. Main Results: In all cases of sudden death, terminal apnea was preceded by a large pH drop from 7 to 2 in the esophagus. In several animals we observed acidic fluid exiting the mouth, sometimes in large quantities. In animals where acid movement was blocked, sudden deaths did not occur. No acid was detected in controls. Significance: The results suggest that acid movement up the esophagus is a trigger for sudden death in KA induced seizures. The fact that blocking acid also eliminates sudden death implies causation. These results may provide insight to the mechanism of SUDEP in humans.

Objective: Recent animal work and limited clinical data have suggested that laryngospasm may be involved in the cardiorespiratory collapse seen in sudden unexpected death in epilepsy (SUDEP). In previous work we demonstrated in an animal model of seizures that laryngospasm and sudden death were always preceded by acid reflux into the esophagus. Here, we expand on that work by testing several techniques to prevent the acid reflux or the subsequent laryngospasm. Methods:In urethane anesthetized Long Evans rats we used systemic kainic acid to acutely induce seizure activity. We recorded pH in the esophagus, respiration, electrocorticography activity, and measured the liquid volume in the stomach postmortem. We performed three interventions to attempt to prevent acid reflux or laryngospasm and gain insights into mechanisms: fasting animals for 12 hours, severing the gastric nerve, and electrical stimulation of either the gastric nerve or the recurrent laryngeal nerve.Results: Seizing animals had significantly more liquid in their stomach. Severing the gastric nerve and fasting animals significantly reduced stomach liquid volume, subsequent acid reflux, and sudden death. Laryngeal nerve stimulation can reverse laryngospasm on demand. Seizing animals are more susceptible to death from stomach-acid induced laryngospasm than non-seizing animals are to artificial-acid induced laryngospasm.

Implantable closed-loop neuromodulation devices for use in long-term chronic studies in a lab or clinical trial are expensive to acquire and difficult to modify for specific use cases. This article documents the design and fabrication of a wireless implantable device using only commercially available off-the-shelf (COTS) components. This device, called the Bionode, can record and transmit up to four channels of biopotential data while simultaneously providing biphasic constant-current stimulation. The Bionode is a viable, low-cost, reusable, and easily modifiable research tool with clinical implications that has gained widespread use in various research projects at Purdue University. CCS Concepts: • Hardware → Bio-embedded electronics; Wireless devices; • Computer systems organization → Firmware;

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