Progressive slowing of clonic phase predicts postictal generalized EEG suppression

Abstract

Objective: Postictal generalized electroencephalography (EEG) suppression (PGES) is a surrogate marker of sudden unexpected death in epilepsy (SUDEP). It is still unclear which ictal phenomena lead to prolonged PGES and increased risk of SUDEP. Semiology features of generalized convulsive seizure (GCS type 1) have been reported as a predictor of prolonged PGES. Progressive slowing of clonic phase (PSCP) has been observed in GCSs, with gradually increasing inhibitory periods interrupting the tonic contractions. We hypothesized that PSCP is associated with prolonged PGES.

Methods: We analyzed 90 bilateral convulsive seizures in 50 consecutive patients (21 female; age: 11-62 years, median: 31 years) recruited to video-EEG monitoring. Five raters, blinded to all other data, independently assessed the presence of PSCP. PGES and seizure semiology were evaluated independently. We determined inter-rater agreement (IRA) for the presence of PSCP, and we evaluated its association, as well as that of other ictal features, with the occurrence of PGES, prolonged PGES (≥20 s) and very prolonged PGES (≥50 s) using multivariate logistic regression analysis.

Results: We found substantial IRA for the presence of PSCP (percent agreement: 80%; beyond-chance agreement coefficient: .655). PSCP was an independent predictor of the occurrence of PGES and prolonged PGES (p < .001). All seizures with very prolonged PGES had PSCP. GCS type 1 was an independent predictor of occurrence of PGES (p = .02) and prolonged PGES (p = .03) but not of very prolonged PGES. Only half of the seizures with very prolonged PGES were GCS type 1.

Significance: PSCP predicts prolonged PGES, emphasizing the importance of gradually increasing inhibitory phenomena at the end of the seizures. Our findings shed more light on the ictal phenomena leading to increased risk of SUDEP. These phenomena may provide basis for algorithms implemented into wearable devices for identifying GCS with increased risk of SUDEP.

FIGURE 1

Dynamics of the clonic phase in generalized clonic seizures (GCSs). (A) Progressive slowing of clonic phase in a GCS. Please note the electromyography signals in the electroencephalography (EEG) and electrocardiography (ECG) channels. The tonic muscle activity is interrupted for longer and longer periods, resulting in a deceleration of the clonic jerks, until the seizure stops. The bar at the bottom of the figure illustrates the silent periods, with gradually increasing duration, interrupting the tonic muscle activity, generating the typical dynamic evolution of GCSs. (B) Quasi‐rhythmic clonic phase, without progressive slowing. In contrast to the seizure shown in Figure 1A, the clonic phase shown in Figure 1B has a quasi‐rhythmic frequency, without progressive slowing.