Dataset Information

Postconvulsive central apnea as a biomarker for sudden unexpected death in epilepsy (SUDEP).

ABSTRACT:

Objective

To characterize peri-ictal apnea and postictal asystole in generalized convulsive seizures (GCS) of intractable epilepsy.

Methods

This was a prospective, multicenter epilepsy monitoring study of autonomic and breathing biomarkers of sudden unexpected death in epilepsy (SUDEP) in patients ≥18 years old with intractable epilepsy and monitored GCS. Video-EEG, thoracoabdominal excursions, nasal airflow, capillary oxygen saturation, and ECG were analyzed.

Results

We studied 148 GCS in 87 patients. Nineteen patients had generalized epilepsy; 65 had focal epilepsy; 1 had both; and the epileptogenic zone was unknown in 2. Ictal central apnea (ICA) preceded GCS in 49 of 121 (40.4%) seizures in 23 patients, all with focal epilepsy. Postconvulsive central apnea (PCCA) occurred in 31 of 140 (22.1%) seizures in 22 patients, with generalized, focal, or unknown epileptogenic zones. In 2 patients, PCCA occurred concurrently with asystole (near-SUDEP), with an incidence rate of 10.2 per 1,000 patient-years. One patient with PCCA died of probable SUDEP during follow-up, suggesting a SUDEP incidence rate 5.1 per 1,000 patient-years. No cases of laryngospasm were detected. Rhythmic muscle artifact synchronous with breathing was present in 75 of 147 seizures and related to stertorous breathing (odds ratio 3.856, 95% confidence interval 1.395-10.663, p = 0.009).

Conclusions

PCCA occurred in both focal and generalized epilepsies, suggesting a different pathophysiology from ICA, which occurred only in focal epilepsy. PCCA was seen in 2 near-SUDEP cases and 1 probable SUDEP case, suggesting that this phenomenon may serve as a clinical biomarker of SUDEP. Larger studies are needed to validate this observation. Rhythmic postictal muscle artifact is suggestive of post-GCS breathing effort rather than a specific biomarker of laryngospasm.

SUBMITTER: Vilella L

PROVIDER: S-EPMC6340388 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Sudden unexpected death in epilepsy (SUDEP) is a major cause of death in those with drug-resistant epilepsy (DRE). There is a need for inventories and biomarkers associated with the risk for SUDEP. OBJECTIVE:To explore the revised SUDEP Risk Inventory (SUDEP-7) in a cohort with DRE and determine the association with Heart Rate and other covariates. METHODS:Twenty-five subjects with severe DRE were enrolled in a clinical trial for epilepsy. Baseline demographics, duration of epilepsy, seizure types, seizure frequency, seizure severity, AEDs, and vital signs were collected. Heart rate variability (HRV) was calculated from 1-h recordings of ECG. A SUDEP Risk Inventory (SUDEP-7) was administered, which included seven validated and weighted risk factors initially identified by Walczak et al. as factors associated with SUDEP risk. RESULTS:The total score on the revised SUDEP-7 ranged from 1 to 7, mean?=?3.4 (SD 1.8). The SUDEP Risk Inventory score was inversely correlated with RMSSD (Pearson r?=?-0.45, p?=?0.027). The following variables were significantly associated with RMSSD: epilepsy duration (p?=?0.02), age (p?=?0.03), and developmental intellectual disability (p?<?0.001). The correlation between RMSSD and SUDEP-7 tended to persist also after the adjustment for patient age (r?=?-0.40, p?=?0.05). Two subjects died of SUDEP: their SUDEP-7 scores were above average and in the upper twenty-fifth and fiftieth percentiles, respectively (6 and 4, mean?=?3.4). CONCLUSION:RMSSD, a measure of low frequency HRV, was significantly associated with SUDEP Risk Inventory (SUDEP-7) scores. Using a multivariate model, the covariates of developmental intellectual disability, age, and duration of epilepsy were also significantly associated with decreased HRV. The correlation between decreased HRV and a higher SUDEP-7 score remained unchanged even after the adjustment for patient age. The results suggest that older age, greater duration of epilepsy, and the presence of developmental intellectual disability may increase the risk of SUDEP through their direct influence on decreasing the vagus nerve-mediated HRV. Further validation of the SUDEP-7 inventory is indicated. TRIAL REGISTRATION:ClinicalTrials.gov, NCT00871377.