Abstracts

Rationale:
Catecholamine levels are known to rise after epileptic seizures. Extreme post-ictal catecholamine responses are thought to be responsible for potentially fatal, acute/subacute phenomena such as Takatsubo cardiomyopathy. However, the role of catecholamines in sudden unexpected death in epilepsy (SUDEP) phenomena is unknown. Hypotheses include catecholaminergic excess as well as insufficient catecholaminergic drive, impacting blood pressure and a failure of post-seizure homeostasis. We aimed to investigate interictal and post-ictal catecholamine levels in relation to various electroclinical seizure figures.
Method:
We prospectively evaluated 170 seizures in 164 patients enrolled in a multicenter study of SUDEP using surface video electro-encephalogram (VEEG). Post-ictal venous blood samples were collected at the earliest after the end of seizure and interictal samples were collected at rest and always at least 12 hours after the last recorded clinical seizure. All samples were processed within 30 minutes of collection. Frozen plasma was shipped to reference laboratory for measurement of plasma catecholamines (epinephrine, norepinephrine and dopamine). A correction for half-life of catecholamines was applied to the post-ictal values to estimate the levels at the end of seizure. The seizures were classified into 2 major groups: generalized convulsive seizures (including generalized tonic-clonic seizures and focal to bilateral tonic-clonic seizures (n = 70) and non-convulsive seizures (n = 100).
Results:
Post-ictal levels of plasma epinephrine, norepinephrine and dopamine increased compared to interictal levels after convulsive and non-convulsive seizures (p < 0.0001). The mean increase for epinephrine was 5 -fold and norepinephrine was 2 -fold after convulsive seizures compared to non-convulsive seizures (p < 0.0001). A  4 -fold increase in the levels of epinephrine and a 3 -fold increase in norepinephrine after seizure was associated with post-ictal generalized EEG suppression (PGES) in patients with convulsive seizures (p = 0.013; p = 0.007). Multivariate regression analysis in convulsive seizures revealed increased epinephrine and dopamine was associated with longer duration of epilepsy (p = 0.006; p = 0.004) and increased heart rate respectively (p = 0.023; p = 0.004). In non-convulsive seizures, epinephrine increase was associated with increased heart rate at seizure onset (p = 0.002). Decreased levels of plasma dopamine was seen in patients with ictal central apnea (p = 0.047).
Conclusion:
The greatest autonomic perturbations were associated with generalized convulsive seizures. Our study revealed that in patients with generalized convulsive seizures, an increased catecholaminergic response was associated with seizure severity risk factors, including PGES and longer duration of epilepsy. We conclude that seizure severity likely drives catecholamine responses.
Funding:
:The study is funded by the Center for SUDEP Research: NIH/NINDS U01-NS090405, NIH/NINDS U01-NS090407 and NIH/NINDS U01-NS090414.