Authors :
Presenting Author: Chengsan Sun, PhD – University of Virginia
Suchitra Joshi, PhD – University of Virginia
Rachel Jane Spera, BS – University of Virginia
John M Williamson, BS – University of Virginia
Bhavya Guduru, Undergraduate – University of Virginia
Harini Ganabady, Undergraduate – University of Virginia
Jaideep Kapur, MD, PhD – University of Virginia
Rationale:
Status epilepticus (SE) is second only to sudden unexpected death in epilepsy as a leading cause of seizure-related mortality. In patients, respiratory compromise during generalized convulsive status epilepticus often necessitates intubation; however, the progression of respiratory dysfunction during experimental SE remains poorly characterized. We investigated how pilocarpine-induced SE affects respiration in a mouse model.
Methods:
We performed simultaneous plethysmography, electroencephalography, and electrocardiography recordings in mice administered pilocarpine at 200, 240, or 280 mg/kg. Respiratory rate, ventilation, inspiratory/expiratory timing, seizure progression, and survival outcomes were analyzed.
Results:
The highest administered dose (280 mg/kg) resulted in the shortest latencies to early SE, established SE, and death, with mortality increasing dose-dependently. Across all dose groups, respiratory frequency increased in early and established SE compared to pre-seizure, while ventilation only rose from pre-seizure to established SE. Abnormal respiratory patterns, including apneustic breathing and pathological sighs—both marked by prolonged inspiratory and expiratory phases—were observed during SE. These abnormalities occurred with similar frequency in both fatal and non-fatal cases. In the two minutes preceding terminal apnea, a stereotypical sequence of events was observed: seizures intensified, leading to wild running and jumping, whole-body tonic extension, and followed by terminal apnea. Seizure activity, and repeated spike wave discharges interspersed with suppression persisted for 33.8 ± 4.8 (Mean ± SEM) seconds after apnea onset. This was followed by electrocerebral silence. Cardiac rhythm persisted beyond the cessation of brain activity, with heart rate gradually slowing before terminal arrest 7.5 minutes after apnea onset. In summary the sequence of events leading to death was apnea, electrocerebral silence, and then cardiac arrest.
Conclusions: Pilocarpine-induced SE results in progressive, dose-dependent respiratory disturbances culminating in terminal apnea. These findings highlight the pivotal role of respiratory failure in SE-related mortality and underscore the need for continuous respiratory monitoring and early intervention during SE.
Funding: NIH R01NS120945, R37N119012 and UVA Brain Institute