TY - JOUR
T1 - Incidence, Recurrence, and Risk Factors for Peri-ictal Central Apnea and Sudden Unexpected Death in Epilepsy
AU - Vilella, Laura
AU - Lacuey, Nuria
AU - Hampson, Johnson P.
AU - Rani, M. R.Sandhya
AU - Loparo, Kenneth
AU - Sainju, Rup K.
AU - Friedman, Daniel
AU - Nei, Maromi
AU - Strohl, Kingman
AU - Allen, Luke
AU - Scott, Catherine
AU - Gehlbach, Brian K.
AU - Zonjy, Bilal
AU - Hupp, Norma J.
AU - Zaremba, Anita
AU - Shafiabadi, Nassim
AU - Zhao, Xiuhe
AU - Reick-Mitrisin, Victoria
AU - Schuele, Stephan
AU - Ogren, Jennifer
AU - Harper, Ronald M.
AU - Diehl, Beate
AU - Bateman, Lisa M.
AU - Devinsky, Orrin
AU - Richerson, George B.
AU - Tanner, Adriana
AU - Tatsuoka, Curtis
AU - Lhatoo, Samden D.
N1 - Funding Information:
We would like to thank patients and personnel from the different monitoring units for their invaluable contribution to understanding epilepsy and SUDEP pathophysiology. Funding. LB, DF, MN, RH, BD, LV, MR, BG, NH, AZ, RS, JO, LA, and OD are funded by the Center for SUDEP Research: NIH/NINDS U01-NS090407. SS is on the speaker's bureau for Sunovion and Eisai. He receives grant support from NINDS (RFA-NS-14-004), NIH/NINDS U01-NS090407, and the Danny Did Foundation. SL is funded by the Center for SUDEP Research: NIH/NINDS U01-NS090405 and NIH/NINDS U01-NS090407. GR is funded by the Center for SUDEP Research: NIH/NINDS U01-NS090414 and NIH/NINDS U01-NS090407.
Publisher Copyright:
© Copyright © 2019 Vilella, Lacuey, Hampson, Rani, Loparo, Sainju, Friedman, Nei, Strohl, Allen, Scott, Gehlbach, Zonjy, Hupp, Zaremba, Shafiabadi, Zhao, Reick-Mitrisin, Schuele, Ogren, Harper, Diehl, Bateman, Devinsky, Richerson, Tanner, Tatsuoka and Lhatoo.
PY - 2019/3/1
Y1 - 2019/3/1
N2 - 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.
AB - 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.
KW - apnea
KW - breathing
KW - epilepsy
KW - ictal central apnea (ICA)
KW - post-convulsive central apnea (PCCA)
KW - seizures
KW - sudden unexpected death in epilepsy (SUDEP)
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U2 - 10.3389/fneur.2019.00166
DO - 10.3389/fneur.2019.00166
M3 - Article
C2 - 30890997
AN - SCOPUS:85117687568
VL - 10
JO - Frontiers in Neurology
JF - Frontiers in Neurology
SN - 1664-2295
M1 - 166
ER -