Nonseizure SUDEP: Sudden unexpected death in epilepsy without preceding epileptic seizures

Abstract

Summary Objective To describe the phenomenology of monitored Sudden Unexpected Death in Epilepsy (SUDEP) occurring in the inter-ictal period where death occurs without a seizure preceding it. Methods We report a case series of monitored definite and probable SUDEP where no electroclinical evidence of underlying seizures was found preceding death. Results Three patients (2 definite and 1 probable) suffered SUDEP. They had a typical high SUDEP-risk profile with longstanding intractable epilepsy and frequent generalized tonic-clonic seizures (GTCS). All patients had varying patterns of respiratory and bradyarrhythmic cardiac dysfunction with profound EEG suppression. In two patients, patterns of cardio-respiratory failure were similar to those seen in some patients in the Mortality in Epilepsy Monitoring Units Study (MORTEMUS). Significance Sudden Unexpected Deaths in Epilepsy (SUDEP) almost always occur postictally, after GTCS and less commonly after a partial seizure. Monitored SUDEP or near-SUDEP cases without a seizure have not yet been reported in literature. When non-monitored SUDEP occurs in an ambulatory setting without an overt seizure, the absence of EEG information prevents the exclusion of a subtle seizure. These cases confirm the existence of non-seizure SUDEP; such deaths may not be prevented by seizure detection based devices. SUDEP risk in epilepsy patients may constitute a spectrum of susceptibility wherein some are relatively immune, death occurs in others with frequent GTCS with one ultimately proving fatal, while in others still, death may occur even in the absence of a seizure. We emphasize the heterogeneity of SUDEP phenomena.

Antiepileptic Drugs Impair Shortening of Isolated Cardiomyocytes

“…Given the large spectrum of epilepsy-related cardiorespiratory alterations, however, SUDEP is likely to be a heterogeneous phenomenon and to have multiple causes (4). For instance, SUDEP may also occur in the absence of epileptic seizures with a similar pattern as described in the MORTEMUS study (5). It is also plausible that, in some cases, SUDEP is due to fatal cardiac arrhythmias such as bradyarrhythmias or ventricular tachyarrhythmias that are not directly related to epileptic seizures.…”

“…In view of the large spectrum of epilepsy-related cardiorespiratory alterations, SUDEP is likely to be a heterogeneous phenomenon and to have multiple etiologies (4, 5). Therefore, it appears plausible that in some cases, SUDEP is caused by fatal cardiac dysfunction due to myocardial failure, bradyarrhythmias, or ventricular tachyarrhythmias.…”

Multicenter clinical assessment of improved wearable multimodal convulsive seizure detectors

“…The measure of the autonomic impact of each seizure has previously been found to correlate with the duration of PGES after FTCb and GTC seizures 23,34 , which has been proposed as a biomarker for SUDEP 5 . While no device has been shown to reduce the risk of SUDEP, which would require very large studies, incorporating EDA analysis in a home seizure detector may help to identify, characterize and alert caregivers to potentially dangerous seizures.…”

“…SUDEP is more likely to occur in patients who have at least one (primary or secondarily) generalized tonic-clonic (GTC) seizure a year, and when a patient is unattended after a seizure [2][3] . While SUDEP's general cause remains unknown, SUDEP can occur after prolonged post-ictal generalized EEG suppression (PGES), and is associated with autonomic dysfunction such as terminal apnea preceding terminal asystole 4,5,6 .…”

Sudden unexpected death in epilepsy in patients treated with brain‐responsive neurostimulation

“…Age-adjusted standardized mortality ratios (SMRs) were calculated based on expected death rates per 10-year age group for the United States using 2007 estimates. 9 3 | RESULTS Demographic data were available for patients studied in the clinical trials (N = 256) and were presented previously. There were 14 deaths across the 707 patients with a total of 2208 years of postimplantation follow-up (data cutoff 5/5/2016).…”