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Postconvulsive central apnea as a biomarker for sudden unexpected death in epilepsy (SUDEP)

Laura Vilella¹, Nuria Lacuey², Johnson P Hampson²

¹From the NINDS Center for SUDEP Research (L.V., M.R.S.R., R.K.S., D.F., M.N., C.S., B.K.G., B.Z., A.Z., S.S., J.O., R.M.H., B.D., L.B., O.D., G.B.R., P.R., S.D.L.); Epilepsy Center (L.V., N.L., J.P.H., N.J.H., N.S., X.Z., V.R.-M., S.D.L.) and Division of Pulmonary, Critical Care and Sleep Medicine (K.S.), University Hospitals Cleveland Medical Center, OH; University of Iowa School of Medicine (R.K.S., B.K.G., G.B.R.), Iowa City; NYU Langone School of Medicine (D.F., O.D.), New York; Sidney Kimmel Medical College (M.N.), Thomas Jefferson University, Philadelphia, PA; Institute of Neurology (C.S., B.D.), University College London, UK; Feinberg School of Medicine (S.S.), Northwestern University, Chicago, IL; Department of Neurobiology and Brain Research Institute (J.O., R.M.H.), University of California, Los Angeles (UCLA); Department of Neurology (L.B.), Columbia University, New York, NY; and Department of Clinical Neuroscience (P.R.), Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. Lvilellabertran@gmail.com.

|December 21, 2018

Abstract

Objective:

To characterize peri-ictal apnea and postictal asystole in generalized convulsive seizures (GCS) of intractable epilepsy.

Methods:

This was a prospective, multicenter epilepsy monitoring study of autonomic and breathing biomarkers of sudden unexpected death in epilepsy (SUDEP) in patients ≥18 years old with intractable epilepsy and monitored GCS. Video-EEG, thoracoabdominal excursions, nasal airflow, capillary oxygen saturation, and ECG were analyzed.

Results:

We studied 148 GCS in 87 patients. Nineteen patients had generalized epilepsy; 65 had focal epilepsy; 1 had both; and the epileptogenic zone was unknown in 2. Ictal central apnea (ICA) preceded GCS in 49 of 121 (40.4%) seizures in 23 patients, all with focal epilepsy. Postconvulsive central apnea (PCCA) occurred in 31 of 140 (22.1%) seizures in 22 patients, with generalized, focal, or unknown epileptogenic zones. In 2 patients, PCCA occurred concurrently with asystole (near-SUDEP), with an incidence rate of 10.2 per 1,000 patient-years. One patient with PCCA died of probable SUDEP during follow-up, suggesting a SUDEP incidence rate 5.1 per 1,000 patient-years. No cases of laryngospasm were detected. Rhythmic muscle artifact synchronous with breathing was present in 75 of 147 seizures and related to stertorous breathing (odds ratio 3.856, 95% confidence interval 1.395-10.663, p = 0.009).

Conclusions:

PCCA occurred in both focal and generalized epilepsies, suggesting a different pathophysiology from ICA, which occurred only in focal epilepsy. PCCA was seen in 2 near-SUDEP cases and 1 probable SUDEP case, suggesting that this phenomenon may serve as a clinical biomarker of SUDEP. Larger studies are needed to validate this observation. Rhythmic postictal muscle artifact is suggestive of post-GCS breathing effort rather than a specific biomarker of laryngospasm.

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