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Decreased Heart Rate Variability: A Cause for Sudden Unexpected Death in Epilepsy (SUDEP)?
Abstract & Commentary
By Padmaja Kandula, MD, Assistant Professor of Neurology and Neuroscience, Comprehensive Epilepsy Center, Weill Medical College of Cornell University. Dr. Kandula reports no financial relationships relevant to this field of study.
Synopsis: The authors hypothesize that postictal autonomic dysregulation, as measured by decreased heart rate variability, is a key factor in sudden death in epileptics.
Sources: Toth V, et al. Periictal heart rate variability analysis suggests long-term postictal autonomic disturbance in epilepsy. Eur J Neurol 2010 doi:10.1111/j.1468-1331.2009. 02939.x.
Definitive criteria for sudden unexpected death in epilepsy (SUDEP) exclude death due to trauma, drowning, and status epilepticus. Death can occur with or without evidence of a seizure, can be witnessed or unwitnessed, and occurs without evidence of toxicological or structural abnormality on subsequent postmortem examination. The main risk factor for SUDEP has been poor seizure control, suggesting that in many cases SUDEP is indeed a seizure-related event. Due to the inherent difficulty of formally studying a relatively rare and oftentimes unwitnessed phenomenon, the pathophysiology of SUDEP has not been fully elucidated. The prevailing theory is that seizure-related cardio-respiratory autonomic dysfunction contributes to SUDEP. Heart rate variability indicates the heart's ability to respond to various environmental and physiologic stimuli. Decreased heart rate variability (HRV) has been postulated as a mechanism involved in autonomic dysfunction leading to SUDEP.
The authors of this study analyzed whether decreased HRV exists in early and late postictal states. Thirty-one patients and 31 seizures (one seizure per patient) were included in this retrospective study after fulfilling criteria for medication-resistant partial epilepsy (failure of greater than two anti-epileptic agents). Nine generalized tonic-clonic seizures (GTCS), 15 complex partial seizures (CPS), and seven simple focal motor seizures were included in the study.
All included patients had a normal baseline EKG and prior evaluation with long-term EEG with synchronized six-lead continuous EKG monitoring. In a blinded fashion, one investigator reviewed seizure onsets and offsets while the second investigator analyzed four separate, 300-second EKG epochs (baseline epoch 30 minutes before seizure onset, preictal epoch five minutes before seizure onset, postictal epoch 10 minutes after seizure offset, late postictal epoch defined as six hours after seizure onset). Measured heart rate variability indices include the following: RRI (mean interbeat interval of normal beats in milliseconds and mean heart rate (HR) on the entire 300-second-long epoch), SDNN (standard deviation of normal-to-normal RRI), coefficient of variation (CV) (SDNN divided by the RR expressed in percent), RMSSD (root mean square of successive RR differences).
To minimize the influence of HR on the HRV, CV was used. The RMSSD index represents the parasympathetic activity found from the analysis of adjacent RR intervals.
The results of the study showed elevation in HR both immediately after seizures and return to baseline six hours postictally. Early postictal HR elevation was higher after GTCS compared to both CPS and simple focal seizures. The authors found a long-lasting, decreased postictal HRV up to six hours after the seizures.
The HRV describes the oscillations in the interval between consecutive heart beats (RR interval). Over the years, there has been renewed interest in the clinical application of HRV in various disease states. Low HRV has been associated with poor autonomic nervous system adaptation and is an independent predictor of all causes of death.1
Although retrospective in design, this study suggests that patients may be at risk for sudden cardiac death not just in the immediate post-ictus phase, but up to six hours later.
This potentially prolonged high-risk period raises a very practical concern in the inpatient hospital setting. Perhaps all epilepsy patients undergoing continuously monitored video EEG studies for characterization of seizures (including anti-epileptic medication wean) be monitored by continuous cardiac telemetry with greater attention to heart rate variability. Although SUDEP likely is caused by the periictal existence of several precipitating factors, this study highlights one potential mechanism of SUDEP and emphasizes the need for further rigorous study of this black-box phenomenon.
1. Dekker JM, et al. Heart rate variability from short electrocardiographic recordings predicts mortality from all causes in middle-aged and elderly men. Am J Epidemiol 1997;145:899-908.