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

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.

Figure 1. Postconvulsive central apnea

Generalized convulsive seizure end and subsequent postictal phase are shown in a 20-second page: EEG sensitivity 7 μV, time constant 0.1, high frequency filter 70 Hz. After seizure end, 2 noticeable breaths are followed by postconvulsive central apnea of 6 seconds, with pulse artifact identifiable in the plethysmography signal during this period. Oxygen desaturation and subsequent ongoing recovery are seen as the patient resumes breathing. ABD = abdominal; THOR = thoracic.

Figure 2. Sequence of EEG, ECG, and breathing changes in the near-SUDEP event of patient 1

(A–C) Clinical seizure end and onset of the postictal convulsive phase are shown in 3 consecutive 60-second pages. Two channels of the EEG recording are displayed, along with 2 ECG channels and thoracic (THOR) and abdominal (ABD) belts. (A) After clinical seizure end, apnea is noted, accompanied by bradytachycardia that progresses into asystole. Three apneic periods are seen. The first QRS complex is seen at the end of the page. (B) Apnea and asystole continue from panel A until a second QRS complex and 2 breaths, followed by further apnea and asystole. Regular cardiac rhythm is progressively restored, although apnea persists until several seconds later. (C) Cardiac rhythm is re-established, and breathing excursions become more regular and increase in amplitude. Rhythmic muscle artifact becomes more evident on EEG. SUDEP = sudden unexpected death in epilepsy.

Figure 3. Sequence of EEG, ECG, and breathing changes in the near-SUDEP event of patient 2

Seizure end and onset of the postconvulsive phase are shown in 2 consecutive 60-second pages. Two channels of the EEG recording are displayed, along with 2 ECG channels and thoracic (THOR) and abdominal (ABD) excursions. (A) After clinical end, progressive bradycardia is noted progressing to asystole after EEG end. After the first QRS complex, a brief period of apnea is noted. There are some isolated breaths followed by a longer period of apnea, even as cardiac activity is re-established, although in an arrhythmic fashion. Toward the end of the page, apnea ends and 2 breaths are noted. (B) A bradytachyarrhythmic pattern on the ECG is still present at the beginning of the page. Breathing excursions increase and become more regular accompanied by prominent rhythmic muscle artifact on EEG. SUDEP = sudden unexpected death in epilepsy.

Figure 4. Types of muscle artifact

(A) Rhythmic muscle artifact in a 60-second page. Note the one-to-one correspondence with thoraco (THOR)-abdominal (ABD) excursions and nasal flow assessed by nasal pressure transducer (NPT) (sensitivity 7 μV, time constant 0.03, high frequency filter 70). (B) Continuous muscle artifact in a 60-second page (sensitivity 7 μV, time constant 0.03, high frequency filter 70).