Decreased heart rate and enhanced sinus arrhythmia during interictal sleep demonstrate autonomic imbalance in generalized epilepsy

Abstract

Sivakumar SS, Namath AG, Tuxhorn IE, Lewis SJ, Galán RF. Decreased heart rate and enhanced sinus arrhythmia during interictal sleep demonstrate autonomic imbalance in generalized epilepsy. J Neurophysiol 115: 1988 -1999. First published February 17, 2016 doi:10.1152/jn.01120.2015.-We hypothesized that epilepsy affects the activity of the autonomic nervous system even in the absence of seizures, which should manifest as differences in heart rate variability (HRV) and cardiac cycle. To test this hypothesis, we investigated ECG traces of 91 children and adolescents with generalized epilepsy and 25 neurologically normal controls during 30 min of stage 2 sleep with interictal or normal EEG. Mean heart rate (HR) and high-frequency HRV corresponding to respiratory sinus arrhythmia (RSA) were quantified and compared. Blood pressure (BP) measurements from physical exams of all subjects were also collected and analyzed. RSA was on average significantly stronger in patients with epilepsy, whereas their mean HR was significantly lower after adjusting for age, body mass index, and sex, consistent with increased parasympathetic tone in these patients. In contrast, diastolic (and systolic) BP at rest was not significantly different, indicating that the sympathetic tone is similar. Remarkably, five additional subjects, initially diagnosed as neurologically normal but with enhanced RSA and lower HR, eventually developed epilepsy, suggesting that increased parasympathetic tone precedes the onset of epilepsy in children. ECG waveforms in epilepsy also displayed significantly longer TP intervals (ventricular diastole) relative to the RR interval. The relative TP interval correlated positively with RSA and negatively with HR, suggesting that these parameters are linked through a common mechanism, which we discuss. Altogether, our results provide evidence for imbalanced autonomic function in generalized epilepsy, which may be a key contributing factor to sudden unexpected death in epilepsy.SUDEP; heart rate variability; cardiac cycle; parasympathetic tone; children EPILEPTIC SEIZURES ARE KNOWN to have profound effects on autonomic function (Wyllie 2015). To quantify these effects, many studies have focused on heart rate (HR) (Behbahani et al.

Heart rate variability in epilepsy: A potential biomarker of sudden unexpected death in epilepsy risk

“…Analyzing HRV, we found that awake HRV was lower, and sleep:awake HRV ratio was outside of the normal range, in those who later suffered SUDEP. Our findings emphasize the importance of considering arousal state when interpreting HRV data, an issue that has only been looked at previously in a cohort with generalized epilepsy . This has important implications for our understanding of the pathophysiology of SUDEP, as well as the clinical management of patients with drug‐resistant epilepsy.…”

“…Hypothetical model of autonomic “second hit” sudden unexpected death in epilepsy (SUDEP) mechanism. Diurnal variation in heart rate variability (HRV) is based on data from this study as well as previous studies . HRV is lower in patients with epilepsy (blue line) than healthy controls (orange line) during the waking hours and then increases well above the healthy control level at nighttime.…”

“…Our findings emphasize the importance of considering arousal state when interpreting HRV data, an issue that has only been looked at previously in a cohort with generalized epilepsy. 17 This has important implications for our understanding of the pathophysiology of SUDEP, as well as the clinical management of patients with drug-resistant epilepsy. We note, however, that in a retrospective study such as this, certain biases are inevitable, and these should be taken into account when evaluating the data; due to study design, complete observer blinding was not possible.…”

“…Diurnal variation in heart rate variability (HRV) is based on data from this study as well as previous studies. 15,17,38 HRV is lower in patients with epilepsy (blue line) than healthy controls (orange line) during the waking hours and then increases well above the healthy control level at nighttime. This same pattern is seen in patients who go on to have SUDEP (red line) but is more extreme.…”

“…However, the pattern of dysregulation is not as simple as a uniform decrease across sleep and wakefulness. A recent study found that people with generalized epilepsy had enhanced increase in HRV, reflecting parasympathetic tone, in sleep compared to healthy controls . Unfortunately, the data on sleep:wake HRV differences are limited, primarily because many studies have evaluated HRV using cardiac monitoring devices such as Holter monitors, which do not allow for a distinction between sleep and awake states.…”