Ictal Bradycardia and Asystole in Sleep-Related Hypermotor Epilepsy: A Study of 200 Patients

Abstract

Background: Ictal bradycardia (IB) and asystole (IA) represent a rare but potentially harmful feature of epileptic seizures. The aim of this study was to study IB/IA in patients with sleep-related hypermotor epilepsy (SHE). Methods: We retrospectively included cases with video-EEG-confirmed SHE who attended our Institute up to January 2021. We reviewed the ictal polysomnography recordings focusing on ECG and identified cases with IB (R-R interval ≥ 2 s or a ≥10% decrease of baseline heart rate) and IA (R-R interval ≥ 4 s). Results: We included 200 patients (123 males, 61.5%), with a mean age of 42 ± 16 years. Twenty patients (20%) had focal cortical dysplasia (FCD) on brain MRI. Eighteen (out of 104 tested, 17.3%) carried pathogenic variants (mTOR pathway, n = 10, nAchR subunits, n = 4, KCNT1, n = 4). We identified IB/IA in four cases (2%): three had IA (mean 10 s) and one had IB. Three patients had FCD (left fronto-insular region, left amygdala, right mid-temporal gyrus) and two had pathogenic variants in DEPDC5; both features were more prevalent in patients with IB/IA than those without (p = 0.003 and p = 0.037, respectively). Conclusions: We identified IB/IA in 2% of patients with SHE and showed that this subgroup more frequently had FCD on brain MRI and pathogenic variants in genes related to the mTOR pathway.

Keywords: DEPDC5; GATOR1; MRI; SUDEP; arrhythmia; focal cortical dysplasia (FCD); genetics; heart; polygraphy; seizure.

Figure 1

Neuroradiological and neurophysiological features of case 2. Brain MRI ((A) axial, FLAIR; (B), sagittal, T1; (C), coronal, FLAIR) showing an area consistent with focal cortical dysplasia in the left fronto-insular region (yellow circle). Ictal EEG-polygraphy: (D) EEG shows a diffuse slow wave, then it is covered by muscle artifacts; ECG shows bradycardia followed by asystole, lasting 13.3 s.