Journal article
Association of Interictal Respiratory Variability and Severity of Postictal Hypoxemia After Generalized Convulsive Seizures
Neurology, Vol.106(7), e214749
04/14/2026
DOI: 10.1212/WNL.0000000000214749
PMCID: PMC13034677
PMID: 41805401
Abstract
Severe hypoxemia after generalized convulsive seizures (GCSs) can trigger neural injury and is a potential biomarker for sudden unexpected death in epilepsy (SUDEP). Some degree of variability in interbreath interval is normal, but increased variability may suggest dysfunctional breathing control and may be associated with severe postictal hypoxemia. We evaluated the relationship between interictal breathing variability and severity and duration of hypoxemia after GCS.
We prospectively collected video-EEG, respiratory flow and effort, pulse oximetry (SpO
), and ECG from people with epilepsy (PWE). Measures of interictal interbreath interval variability (coefficient of variation, root mean square of successive differences [RMSSD], and long-term [SD-2] variability from Poincaré plots) from interictal asleep and awake periods and other relevant variables were evaluated as covariates for primary outcomes: (1) hypoxemia duration (length of time SpO
<90%) and (2) severity of hypoxemia (SpO
nadir), and secondary outcome: occurrence of combined prolonged and pronounced hypoxemia. Univariable and multivariable models were created for primary outcomes, but only univariable analyses were performed for the secondary outcome.
Of 2,506 participants enrolled, 257 (141 [∼54%] female; mean age = 37.9 years) had ≥1 GCS, but only 152 GCS in 123 had evaluable respiratory data. Multivariable model for hypoxemia duration showed that SpO
nadir (mean ratio [MR] = 0.88, 95% CI 0.81-0.96,
= 0.002) and SD-2 of the awake interbreath interval (MR = 1.06, 95% CI 1.01-1.13,
= 0.04) were significantly associated. RMSSD of the non-REM interbreath interval (mean difference = -5.01, 95% CI -8.10 to -1.93,
= 0.002) was the only variable significantly associated with hypoxemia severity after controlling for duration of postictal generalized EEG suppression, SD-2 of the awake interbreath interval, and body mass index. Univariable analyses for combined prolonged and pronounced hypoxemia showed SD-2 of the awake interbreath interval, temporal lobe epilepsy, ictal central apnea, and a shorter tonic phase duration were significantly associated.
Measures of interictal respiratory variability are associated with severe and prolonged hypoxemia after GCS. Increased interictal respiratory variability suggests baseline respiratory dysregulation in some PWE and may be a surrogate for SUDEP risk.
Details
- Title: Subtitle
- Association of Interictal Respiratory Variability and Severity of Postictal Hypoxemia After Generalized Convulsive Seizures
- Creators
- Jack Caplan - University of IowaLaura Vilella - Hospital Del MarPaula Lee - University of IowaRoshni Nair - University of IowaDeidre Dragon - University of IowaLinder H Wendt - University of IowaPatrick Ten Eyck - University of IowaJennifer A Ogren - Allen Institute for Brain ScienceNuria Lecumberri - The University of Texas Health Science Center at HoustonJohnson P Hampson - The University of Texas Health Science Center at HoustonM R Sandhya Rani - The University of Texas Health Science Center at HoustonBeate Diehl - University College LondonDaniel Friedman - NYU Langone HealthOrrin Devinsky - NYU Langone HealthLisa M Bateman - Cedars-Sinai Medical CenterRonald M Harper - Allen Institute for Brain ScienceShiqiang Tao - The University of Texas Health Science Center at HoustonGuo-Qiang Zhang - The University of Texas Health Science Center at HoustonMaromi Nei - Thomas Jefferson UniversityStephan U Schuele - Northwestern UniversitySamden Lhatoo - The University of Texas Health Science Center at HoustonGeorge B Richerson - University of IowaBrian Gehlbach - University of IowaRup K Sainju - University of IowaCenter for SUDEP Research (CSR)
- Resource Type
- Journal article
- Publication Details
- Neurology, Vol.106(7), e214749
- DOI
- 10.1212/WNL.0000000000214749
- PMID
- 41805401
- PMCID
- PMC13034677
- NLM abbreviation
- Neurology
- ISSN
- 0028-3878
- eISSN
- 1526-632X
- Publisher
- Lippincott Williams & Wilkins
- Grant note
- R01 NS113764 / NINDS NIH HHS
- Language
- English
- Date published
- 04/14/2026
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Iowa Neuroscience Institute; Biostatistics; Neurosurgery; Internal Medicine; Design Biostat and Ethics
- Record Identifier
- 9985147208802771
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