Incidence, Recurrence, and Risk Factors for Peri-ictal Central Apnea and Sudden Unexpected Death in Epilepsy
2019
Introduction: Peri-ictal breathing dysfunction was proposed as a potential mechanism
for SUDEP. We examined the incidence and risk factors for both ictal (ICA) and
post-convulsive central apnea (PCCA) and their relationship with potential seizure severity
biomarkers (i. e., post-ictal generalized EEG suppression (PGES) and recurrence.
Methods: Prospective, multi-center seizure monitoring study of autonomic, and
breathing biomarkers of SUDEP in adults with intractable epilepsy and monitored
seizures. Video EEG, thoraco-abdominal excursions, capillary oxygen saturation, and
electrocardiography were analyzed. A subgroup analysis determined the incidences
of recurrent ICA and PCCA in patients with ≥2 recorded seizures. We excluded
status epilepticus and obscured/unavailable video. Central apnea (absence of
thoracic-abdominal breathing movements) was defined as ≥1 missed breath, and ≥5 s.
ICA referred to apnea preceding or occurring along with non-convulsive seizures (NCS)
or apnea before generalized convulsive seizures (GCS).
Results: We analyzed 558 seizures in 218 patients (130 female); 321 seizures were
NCS and 237 were GCS. ICA occurred in 180/487 (36.9%) seizures in 83/192 (43.2%)
patients, all with focal epilepsy. Sleep state was related to presence of ICA [RR 1.33,
CI 95% (1.08–1.64), p = 0.008] whereas extratemporal epilepsy was related to lower
incidence of ICA [RR 0.58, CI 95% (0.37–0.90), p = 0.015]. ICA recurred in 45/60
(75%) patients. PCCA occurred in 41/228 (18%) of GCS in 30/134 (22.4%) patients,
regardless of epilepsy type. Female sex [RR 11.30, CI 95% (4.50–28.34), p < 0.001] and ICA duration [RR 1.14 CI 95% (1.05–1.25), p = 0.001] were related to PCCA presence,
whereas absence of PGES was related to absence of PCCA [0.27, CI 95%(0.16–0.47), p
< 0.001]. PCCA duration was longer in males [HR 1.84, CI 95% (1.06–3.19), p = 0.003].
In 9/17 (52.9%) patients, PCCA was recurrent.
Conclusion: ICA incidence is almost twice the incidence of PCCA and is only seen
in focal epilepsies, as opposed to PCCA, suggesting different pathophysiologies. ICA is
likely to be a recurrent semiological phenomenon of cortical seizure discharge, whereas
PCCA may be a reflection of brainstem dysfunction after GCS. Prolonged ICA or PCCA
may, respectively, contribute to SUDEP, as evidenced by two cases we report. Further
prospective cohort studies are needed to validate these hypotheses.
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