Incidence, Recurrence, and Risk Factors for Peri-ictal Central Apnea and Sudden Unexpected Death in Epilepsy

Laura Vilella; Nuria Lacuey; Johnson P. Hampson; M. R.Sandhya Rani; Kenneth Loparo; Rup K. Sainju; Daniel Friedman; Maromi Nei; Kingman Strohl; Luke Allen; Catherine Scott; Brian K. Gehlbach; Bilal Zonjy; Norma J. Hupp; Anita Zaremba; Nassim Shafiabadi; Xiuhe Zhao; Victoria Reick-Mitrisin; Stephan Schuele; Jennifer Ogren; Ronald M. Harper; Beate Diehl; Lisa M. Bateman; Orrin Devinsky; George B. Richerson; Adriana Tanner; Curtis Tatsuoka; Samden D. Lhatoo

doi:10.3389/fneur.2019.00166

Incidence, Recurrence, and Risk Factors for Peri-ictal Central Apnea and Sudden Unexpected Death in Epilepsy

Laura Vilella^*, Nuria Lacuey, Johnson P. Hampson, M. R.Sandhya Rani, Kenneth Loparo, Rup K. Sainju, Daniel Friedman, Maromi Nei, Kingman Strohl, Luke Allen, Catherine Scott, Brian K. Gehlbach, Bilal Zonjy, Norma J. Hupp, Anita Zaremba, Nassim Shafiabadi, Xiuhe Zhao, Victoria Reick-Mitrisin, Stephan Schuele, Jennifer OgrenRonald M. Harper, Beate Diehl, Lisa M. Bateman, Orrin Devinsky, George B. Richerson, Adriana Tanner, Curtis Tatsuoka, Samden D. Lhatoo

^*Corresponding author for this work

Neurology

Research output: Contribution to journal › Article › peer-review

72 Scopus citations

Abstract

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.

Original language	English (US)
Article number	166
Journal	Frontiers in Neurology
Volume	10
DOIs	https://doi.org/10.3389/fneur.2019.00166
State	Published - Mar 1 2019

Funding

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.

Keywords

apnea
breathing
epilepsy
ictal central apnea (ICA)
post-convulsive central apnea (PCCA)
seizures
sudden unexpected death in epilepsy (SUDEP)

ASJC Scopus subject areas

Neurology
Clinical Neurology

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Vilella, L., Lacuey, N., Hampson, J. P., Rani, M. R. S., Loparo, K., Sainju, R. K., Friedman, D., Nei, M., Strohl, K., Allen, L., Scott, C., Gehlbach, B. K., Zonjy, B., Hupp, N. J., Zaremba, A., Shafiabadi, N., Zhao, X., Reick-Mitrisin, V., Schuele, S., ... Lhatoo, S. D. (2019). Incidence, Recurrence, and Risk Factors for Peri-ictal Central Apnea and Sudden Unexpected Death in Epilepsy. Frontiers in Neurology, 10, Article 166. https://doi.org/10.3389/fneur.2019.00166

@article{539cc0d2ee1d45aab71a80a12fa42242,

title = "Incidence, Recurrence, and Risk Factors for Peri-ictal Central Apnea and Sudden Unexpected Death in Epilepsy",

abstract = "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.",

keywords = "apnea, breathing, epilepsy, ictal central apnea (ICA), post-convulsive central apnea (PCCA), seizures, sudden unexpected death in epilepsy (SUDEP)",

author = "Laura Vilella and Nuria Lacuey and Hampson, {Johnson P.} and Rani, {M. R.Sandhya} and Kenneth Loparo and Sainju, {Rup K.} and Daniel Friedman and Maromi Nei and Kingman Strohl and Luke Allen and Catherine Scott and Gehlbach, {Brian K.} and Bilal Zonjy and Hupp, {Norma J.} and Anita Zaremba and Nassim Shafiabadi and Xiuhe Zhao and Victoria Reick-Mitrisin and Stephan Schuele and Jennifer Ogren and Harper, {Ronald M.} and Beate Diehl and Bateman, {Lisa M.} and Orrin Devinsky and Richerson, {George B.} and Adriana Tanner and Curtis Tatsuoka and Lhatoo, {Samden D.}",

note = "Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 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.",

year = "2019",

month = mar,

day = "1",

doi = "10.3389/fneur.2019.00166",

language = "English (US)",

volume = "10",

journal = "Frontiers in Neurology",

issn = "1664-2295",

publisher = "Frontiers Media SA",

}

Vilella, L, Lacuey, N, Hampson, JP, Rani, MRS, Loparo, K, Sainju, RK, Friedman, D, Nei, M, Strohl, K, Allen, L, Scott, C, Gehlbach, BK, Zonjy, B, Hupp, NJ, Zaremba, A, Shafiabadi, N, Zhao, X, Reick-Mitrisin, V, Schuele, S, Ogren, J, Harper, RM, Diehl, B, Bateman, LM, Devinsky, O, Richerson, GB, Tanner, A, Tatsuoka, C & Lhatoo, SD 2019, 'Incidence, Recurrence, and Risk Factors for Peri-ictal Central Apnea and Sudden Unexpected Death in Epilepsy', Frontiers in Neurology, vol. 10, 166. https://doi.org/10.3389/fneur.2019.00166

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 - 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)

UR - http://www.scopus.com/inward/record.url?scp=85117687568&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85117687568&partnerID=8YFLogxK

U2 - 10.3389/fneur.2019.00166

DO - 10.3389/fneur.2019.00166

M3 - Article

C2 - 30890997

AN - SCOPUS:85117687568

SN - 1664-2295

VL - 10

JO - Frontiers in Neurology

JF - Frontiers in Neurology

M1 - 166

ER -

Incidence, Recurrence, and Risk Factors for Peri-ictal Central Apnea and Sudden Unexpected Death in Epilepsy

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