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

Abstract

ObjectiveTo characterize peri-ictal apnea and postictal asystole in generalized convulsive seizures (GCS) of intractable epilepsy. MethodsThis 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. ResultsWe 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). ConclusionsPCCA 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.

Ventilatory response to CO2 in patients with epilepsy

“…This indicates that individuals with low CO 2 chemosensitivity not only have a reduced ventilatory response to CO 2 , but they also have less dyspnea when hypercapnic. Although postictal apnea occurs after convulsive seizures, 34 our findings suggest that GCSs can also provoke a more subtle form of hypoventilation: namely, ventilation that is not frankly apneic or bradypneic, but is insufficient to meet the metabolic demands of a convulsive seizure. 26,32 In other circumstances, however, a low chemosensitivity contributes to disease, as in the obesity hypoventilation syndrome, or may even be lifethreatening, as in congenital central hypoventilation syndrome.…”

“…33 TcCO 2 rose by at least 10% after GCSs in all cases for which these data were available. Although postictal apnea occurs after convulsive seizures, 34 our findings suggest that GCSs can also provoke a more subtle form of hypoventilation: namely, ventilation that is not frankly apneic or bradypneic, but is insufficient to meet the metabolic demands of a convulsive seizure. 14 We did not find any significant association between either the duration or magnitude of postictal tcCO 2 rise and the duration of convulsive phase of the seizure, similar to the findings of Seyal et al 15 Despite a limited number of GCSs available for analysis, our findings clearly suggest that the severity of postictal respiratory depression following GCSs is strongly influenced by baseline CO 2 chemosensitivity, as indicated by the inverse correlation between HCVR slope and the duration and magnitude of postictal tcCO 2 rise.…”

Neuropeptide depletion in the amygdala in sudden unexpected death in epilepsy: A postmortem study

“…Postictal central apnea is regarded as a clinical biomarker for sudden unexpected death in epilepsy (SUDEP) risk . In the MORTEMUS study of witnessed and monitored SUDEP, postictal respiratory depression was recorded, but the physiological basis for the respiratory depression is as yet unclear.…”

“…Postictal central apnea is regarded as a clinical biomarker for sudden unexpected death in epilepsy (SUDEP) risk. 1 In the MORTEMUS study of witnessed and monitored SUDEP, postictal respiratory depression was recorded, 2 but the physiological basis for the respiratory depression is as yet unclear. There is a growing body of evidence, however, for altered and abnormal connectivity of higher central autonomic centers, including the amygdala, regulating autonomic and voluntary respiratory dysfunction during a seizure.…”

The yield of long‐term electrocardiographic recordings in refractory focal epilepsy

“…We currently do not know whom to target and ultimately whom to treat with potential future preventative therapies. 23 Postictal generalized EEG suppression (PGES) is another potential biomarker that has been linked to SUDEP. Other, more sensitive biomarkers are thus needed.…”