Suppression of phrenic nerve activity as a potential predictor of imminent sudden unexpected death in epilepsy (SUDEP)

NEUROPHARMACOLOGY

卷:184

Article

Ashraf, Omar¹  Trong Huynh¹  Purnell, Benton S.^1,2  Murugan, Madhuvika¹  Fedele, Denise E.¹  Chitravanshi, Vineet¹  Boison, Detlev^1,3,4 

[1] Rutgers State Univ, Robert Wood Johnson & New Jersey Med Sch, Dept Neurosurg, Piscataway, NJ 08854 USA

[2] Univ Iowa, Dept Neurol, Iowa City, IA 52242 USA

[3] Rutgers State Univ, Brain Hlth Inst, Piscataway, NJ 08854 USA

[4] Rutgers State Univ, Dept Neurosurg, Rutgers Neurosurg HOPE Ctr, New Brunswick, NJ 08901 USA

关键词: Sudden unexpected death in epilepsy;    Seizures;    Epilepsy;    Phrenic nerve activity;    Adenosine;   

DOI  :  10.1016/j.neuropharm.2020.108405

来源: Elsevier

【 摘 要 】

Sudden unexpected death in epilepsy (SUDEP) is a leading cause of death in patients with refractory epilepsy. Centrally-mediated respiratory dysfunction has been identified as one of the principal mechanisms responsible for SUDEP. Seizures generate a surge in adenosine release. Elevated adenosine levels suppress breathing. Insufficient metabolic clearance of a seizure-induced adenosine surge might be a precipitating factor in SUDEP. In order to deliver targeted therapies to prevent SUDEP, reliable biomarkers must be identified to enable prompt intervention. Because of the integral role of the phrenic nerve in breathing, we hypothesized that suppression of phrenic nerve activity could be utilized as predictive biomarker for imminent SUDEP. We used a rat model of kainic acid-induced seizures in combination with pharmacological suppression of metabolic adenosine clearance to trigger seizure-induced death in tracheostomized rats. Recordings of EEG, blood pressure, and phrenic nerve activity were made concomitant to the seizure. We found suppression of phrenic nerve burst frequency to 58.9% of baseline (p < 0.001, one-way ANOVA) which preceded seizure-induced death; importantly, irregularities of phrenic nerve activity were partly reversible by the adenosine receptor antagonist caffeine. Suppression of phrenic nerve activity may be a useful biomarker for imminent SUDEP. The ability to reliably detect the onset of SUDEP may be instrumental in the timely administration of potentially lifesaving interventions.

【 授权许可】

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