Acid reflux induced laryngospasm as a potential mechanism of sudden death in epilepsy

• Published in: Epilepsy research 2018-12, Vol.148, p.23-31
• Main Authors: Budde, Ryan B., Arafat, Muhammad A., Pederson, Daniel J., Lovick, Thelma A., Jefferys, John G.R., Irazoqui, Pedro P.
• Format: Article
• Language: English
• Subjects: Animals; Death, Sudden - etiology; Disease Models, Animal; Epilepsy - complications; Epilepsy - physiopathology; Esophagus - metabolism; Female; Gastroesophageal Reflux - complications; Gastroesophageal Reflux - physiopathology; Hydrogen-Ion Concentration; Kainic Acid; Laryngismus - etiology; Laryngismus - physiopathology; Rats, Long-Evans; Respiration; Seizures - complications; Seizures - physiopathology
• ISSN: 0920-1211; 1872-6844
• DOI: 10.1016/j.eplepsyres.2018.10.003

•Sudden deaths in the acute KA model are preceded by a pH change in the esophagus.•When the esophagus is blocked sudden deaths are no longer observed.•Acid induced laryngospasm may cause some deaths in epilepsy. 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. 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. 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. 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.