Abstract
Rationale: Seizure clusters may be related to Sudden Unexpected Death in Epilepsy (SUDEP). Two or more generalized convulsive seizures (GCS) were captured during video electroencephalography in 7/11 (64%) patients with monitored SUDEP in the MORTEMUS study. It follows that seizure clusters may be associated with epilepsy severity and possibly with SUDEP risk. We aimed to determine if electroclinical seizure features worsen from seizure to seizure within a cluster and possible associations between GCS clusters, markers of seizure severity, and SUDEP risk.Methods: Patients were consecutive, prospectively consented participants with drug-resistant epilepsy from a multi-center study. Seizure clusters were defined as two or more GCS in a 24-h period during the recording of prolonged video-electroencephalography in the Epilepsy monitoring unit (EMU). We measured heart rate variability (HRV), pulse oximetry, plethysmography, postictal generalized electroencephalographic suppression (PGES), and electroencephalography (EEG) recovery duration. A linear mixed effects model was used to study the difference between the first and subsequent seizures, with a level of significance set at p < 0.05.Results: We identified 112 GCS clusters in 105 patients with 285 seizures. GCS lasted on average 48.7 ± 19 s (mean 49, range 2–137). PGES emerged in 184 (64.6%) seizures and postconvulsive central apnea (PCCA) was present in 38 (13.3%) seizures. Changes in seizure features from seizure to seizure such as seizure and convulsive phase durations appeared random. In grouped analysis, some seizure features underwent significant deterioration, whereas others improved. Clonic phase and postconvulsive central apnea (PCCA) were significantly shorter in the fourth seizure compared to the first. By contrast, duration of decerebrate posturing and ictal central apnea were longer. Four SUDEP cases in the cluster cohort were reported on follow-up.Conclusion: Seizure clusters show variable changes from seizure to seizure. Although clusters may reflect epilepsy severity, they alone may be unrelated to SUDEP risk. We suggest a stochastic nature to SUDEP occurrence, where seizure clusters may be more likely to contribute to SUDEP if an underlying progressive tendency toward SUDEP has matured toward a critical SUDEP threshold.
Highlights
Seizure clusters occur frequently in patients with epilepsy (PWE)
We found no significant effect of duration of epilepsy and age of onset of epilepsy on tendency to worsening of electroclinical markers of seizure severity
If there is no evidence of convincing, progressive deterioration of seizure severity parameters with subsequent seizures, is there a role for clusters in SUDEP? The findings of this study suggest that the occurrence of clusters alone does not set the stage for SUDEP with each successive seizure, in quantifiable terms
Summary
Seizure clusters occur frequently in patients with epilepsy (PWE). Their frequency ranges from 22–43% in an outpatient setting [1, 2] and occurs in up to 83% in inpatient settings [3]. Seizure clusters are usually defined as repetitive and closely grouped seizures whose pattern of occurrence deviates from an expected distribution [5, 6]. Seizure clusters are associated with an increased risk of status epilepticus and hospitalizations, and are deleterious for quality of life of PWE [7, 16]. Seizure clusters are associated with increased mortality and are seen as an adverse event in the epilepsy monitoring unit (EMU) [2, 17, 18]
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