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• Oxygen-conserving reflex (OCR) activation in rats after carotid body (CB) denervation reliably induces sudden death. • Oxygen-conserving reflex in rat models of epilepsy induces death, but electrical CB stimulation prevents death. • Oxygen-conserving reflex-mediated death shares multiple physiological parallels with human SUDEP. • Oxygen-conserving reflex activation in non-seizing rats with intact CB never leads to sudden death. • The CB plays a vital role in restoring respiratory drive following OCR activation. To investigate carotid body (CB) mechanisms related to sudden death during seizure. Ictal activation of oxygen-conserving reflexes (OCRs) can trigger fatal cardiorespiratory collapse in seizing rats, which presents like human sudden unexpected death in epilepsy (SUDEP). The CB is strongly implicated in OCR pathways; we hypothesize that modulating CB activity will provide insight into these mechanisms of death. Long-Evans rats were anesthetized with urethane. Recordings included: electrocorticography, electrocardiography, respiration via nasal thermocouple, and blood pressure (BP). The mammalian diving reflex (MDR) was activated by cold water delivered through a nasal cannula. Reflex and stimulation trials were repeated up to 16 times (4 pre-intervention, 12 post-intervention) or until death. In some animals, one or both carotid bodies were denervated. In some animals, the CB was electrically stimulated, both with and without MDR. Seizures were induced with kainic acid (KA). Animals without seizure and with no CB modulation survived all reflexes. Non-seizing animals with CB denervation survived 7.1 ± 5.4 reflexes before death, and only 1 of 7 survived past the 12-trial threshold. Electrical CB stimulation without seizure and without reflex caused significant tachypnea and hypotension. Electrical CB stimulation with seizure and without reflex required higher amplitudes to replicate the physiological responses seen outside seizure. Seizing animals without CB intervention survived 3.2 ± 3.6 trials (per-reflex survival rate 42.0% ± 44.4%), and 0 of 7 survived past the 12-trial threshold. Seizing animals with electrical CB stimulation survived 10.5 ± 4.7 ictal trials (per-reflex survival rate 86.3% ± 35.0%), and 6 of 8 survived past the 12-trial threshold. These results suggest that, during seizure, the ability of the CB to stimulate a restart of respiration is impaired. The CB and its afferents may be relevant to fatal ictal apnea and SUDEP in humans, and CB stimulation may be a relevant intervention technique in these deaths. [ABSTRACT FROM AUTHOR]

Abstract: Closed-loop neurostimulation devices that stimulate the brain to treat epileptic seizures have shown great promise in treating more than a third of the 2 million people with epilepsy in the United States alone whose seizures are currently nonresponsive to pharmaceutical treatment. Seizure detection algorithms facilitate responsive therapeutic intervention that is believed to increase the efficacy of neurostimulation by improving on its spatial and temporal specificity. Translating these signal processing algorithms into battery-powered, implantable devices poses a number of challenges that severely limit the computational power of the chosen algorithm. We propose a cascaded two-stage seizure detection algorithm that is computationally efficient (resulting in a low-power hardware implementation) without compromising on detection efficacy. Unlike traditional detection algorithms, the proposed technique does not explicitly require a “training” phase from individual to individual and, instead, relies on using features that result in distinct “patterns” at the electrographic seizure onset. We tested the algorithm on spontaneous clinical seizures recorded using depth electrodes from patients with focal intractable epilepsy and annotated by epileptologists at the University of Freiburg Medical Center, via the Freiburg database. The algorithm performs with a specificity and sensitivity of 99.82 and 87.5%, detecting seizures in less than 9.08% of their duration after onset. The proposed technique is also shown to be computationally efficient, facilitating low-power hardware implementation. This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction. [Copyright &y& Elsevier]

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. 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 the following three interventions to attempt to prevent acid reflux or laryngospasm and gain insights into mechanisms: fasting animals for 12 h, severing the gastric nerve, and electrical stimulation of either the gastric nerve or the recurrent laryngeal nerve. 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 nonseizing animals are to artificial acid-induced laryngospasm. These results provide insight into the mechanism of acid production and sudden obstructive apnea in this model. These techniques may have clinical relevance if this model is shown to be similar to human SUDEP. • Animals in the acute KA model have more liquid in their stomach. • The gastric nerve is necessary for acid overproduction, reflux, and sudden death. • Seizing animals die more easily from laryngospasm than nonseizing animals. [ABSTRACT FROM AUTHOR]