Causes and Effects Contributing to Sudden Death in Epilepsy and the Rationale for Prevention and Intervention

Sudden unexpected death in epilepsy (SUDEP) can affect individuals of any age, but is most common in younger adults (aged 20-45 years). Generalised tonic-clonic seizures are the greatest risk factor for SUDEP; most often, SUDEP occurs after this type of seizure in bed during sleep hours and the person is found in a prone position. SUDEP excludes other forms of seizure-related sudden death that might be mechanistically related (eg, death after single febrile, unprovoked seizures, or status epilepticus). Typically, postictal apnoea and bradycardia progress to asystole and death. A crucial element of SUDEP is brainstem dysfunction, for which postictal generalised EEG suppression might be a biomarker. Dysfunction in serotonin and adenosine signalling systems, as well as genetic disorders affecting cardiac conduction and neuronal excitability, might also contribute. Because generalised tonic-clonic seizures precede most cases of SUDEP, patients must be better educated about prevention. The value of nocturnal monitoring to detect seizures and postictal stimulation is unproven but warrants further study.

The goal of this study was to determine if specific measures of heart rate variability (HRV) are associated with the total score on a new seven-item inventory for sudden unexplained death in epilepsy (SUDEP). Nineteen subjects with intractable partial seizures, at least three per month, were enrolled in a randomized clinical trial of omega-3 fatty acids in epilepsy. At study entry, subjects underwent a 1-hour ECG recording for the determination of HRV. To estimate the risk of SUDEP, we assembled a seven-item inventory (the SUDEP-7 Inventory) from risk factors prospectively validated by T.S. Walczak, I.E. Leppik, M. D'Amelio M, et al. (Neurology 2001;56:519-25). The SUDEP-7 score was then correlated with measures of HRV using the Pearson correlation and other parametric and nonparametric methods. Subjects had highly drug-resistant seizures, with a mean seizure frequency of 22.8 seizures per month. Scores on the SUDEP-7 inventory ranged from 1 to 7 of a maximum possible score of 12. RMSSD, a measure of high-frequency HRV, was inversely correlated with the SUDEP-7 score, r=-0.64, P=0.004. Subjects with higher SUDEP-7 scores had reduced levels of HRV (RMSSD). Other time-dependent measures of HRV (SDNN, SDANN) were not significantly correlated with SUDEP risk scores. RMSSD, a measure of HRV, which reflects the integrity of vagus nerve-mediated autonomic control of the heart, is highly associated with the total score on a new seven-item SUDEP risk inventory. Lower RMSSD values were associated with higher risk scores on the new SUDEP risk inventory. This provides new evidence that HRV (specifically RMSSD) is a marker of SUDEP risk. Copyright © 2010 Elsevier Inc. All rights reserved.

Parial and generalized seizures often affect autonomic function during seizures as well as during the interictal and postictal periods. Activation or inhibition of areas in the central autonomic network can cause cardiovascular, gastrointestinal, cutaneous, pupillary, urinary, and genital manifestations. Autonomic dysfunction during or after seizures may cause cardiac and pulmonary changes that contribute to sudden unexplained death in epilepsy.