Abstract
Objective
Severe respiratory dysfunction induced by generalized convulsive seizures (GCS) is now thought to be a common mechanism for sudden unexpected death in epilepsy (SUDEP). In a mouse model of seizure-induced death, increased interictal respiratory variability was reported in mice that later die of respiratory arrest after GCS. We studied respiratory variability in epilepsy patients as a predictive tool for severity of postictal hypoxemia, a potential biomarker for SUDEP risk. We then explored the relationship between respiratory variability and central CO2 drive, measured by the hypercapnic ventilatory response (HCVR).
Methods
We reviewed clinical, video-EEG and respiratory (belts, airflow, pulse oximeter, and HCVR) data of epilepsy patients.
Mean, standard deviation (SD), and coefficient of variation (CV) of inter-breath-interval (IBI) were calculated. Primary outcomes were: a) nadir of capillary oxygen saturation (SpO2) and, b) duration of oxygen desaturation. Poincaré plots of IBI were created. Covariates were evaluated in univariate models, then based on Akaike Information Criteria (AIC) multivariate regression models were created.
Results
Of 66 GCS recorded in 131 subjects 30 had interpretable respiratory data. In the multivariate model with the lowest AIC value, duration of epilepsy was a significant predictor of duration of oxygen desaturation. Duration of tonic phase and CV of IBI during the 3rd minute postictal correlated with SpO2 nadir while CV of IBI during NREM sleep had a negative correlation. Poincaré plots showed that long-term variability was significantly greater in subjects with > 200 seconds of postictal oxygen desaturation after GCS compared to those with < 200 seconds desaturation. Finally, HCVR slope showed a negative correlation with measures of respiratory variability.
Significance:
These results indicate that interictal respiratory variability predicts severity of postictal oxygen desaturation, suggesting its utility as a potential biomarker. They also suggest that interictal respiratory control may be abnormal in some patients with epilepsy.
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