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

Sivakumar, Siddharth S.; Namath, Amalia; Tuxhorn, Ingrid; Lewis, Stephen J.; Galán, Roberto F.

doi:10.1152/jn.01120.2015

Cited by 25 publications

(22 citation statements)

References 70 publications

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“…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.…”

Section: Discussionmentioning

confidence: 70%

“…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.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Sudep Pathophysiologymentioning

confidence: 98%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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These findings suggest that autonomic dysfunction is associated with SUDEP risk in patients with epilepsy due to sodium channel mutations. The relationship of HRV to SUDEP merits further study; HRV may eventually have potential as a biomarker of SUDEP risk, which would allow for more informed counseling of patients and families, and also serve as a useful outcome measure for research aimed at developing therapies and interventions to reduce SUDEP risk.

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Section: Discussionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Sudep Pathophysiologymentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

et al. 2018

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Epilepsy duration is an independent factor for electrocardiographic changes in pediatric epilepsy

et al. 2021

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Objective Cardiac alterations represent a potential epilepsy‐associated comorbidity. Whether cardiac changes occur as a function of epilepsy duration is not well understood. We sought to evaluate whether cardiac alterations represented a time‐dependent phenomenon in pediatric epilepsy. Methods We retrospectively followed pediatric epilepsy patients without preexisting cardiac conditions or ion channelopathies who had history of pediatric intensive care unit admission for convulsive seizures or status epilepticus between 4/2014 and 7/2017. All available 12‐lead electrocardiograms (ECGs) from these patients between 1/2006 and 5/2019 were included. We examined ECG studies for changes in rhythm; PR, QRS, or corrected QT intervals; QRS axis or morphology; ST segment; or T wave. Data were analyzed using multivariable models containing covariates associated with ECG changes or epilepsy duration from the univariate analyses. Results 127 children with 323 ECGs were included in the analyses. The median epilepsy duration was 3.9 years (IQR 1.3‐8.4 years) at the time of an ECG study and a median of 2 ECGs (IQR 1‐3) per subject. The clinical encounters associated with ECGs ranged from well‐child visits to status epilepticus. We observed changes in 171 ECGs (53%), with 83 children (65%) had at least 1 ECG with alterations. In a multivariable logistic regression model adjusting for potentially confounding variables and accounting for clustering by patient, epilepsy duration was independently associated with altered ECGs for each year of epilepsy (OR: 1.1, 95% CI: 1.0‐1.2, P = .002). Extrapolating from this model, children with epilepsy durations of 10 and 15 years had 2.9 and 4.9 times the odds of having ECG changes, respectively. Significance Cardiac alterations may become more common with increasing epilepsy duration in select pediatric epilepsy patients. Future studies are needed to determine the potential clinical implications and the generalizability of these observations.

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Cardiorespiratory findings in epilepsy: A recent review on outcomes and pathophysiology

Akyüz

Uner

Köklü

et al. 2021

J of Neuroscience Research

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Epilepsy is a debilitating disorder of uncontrollable recurrent seizures that occurs as a result of imbalances in the brain excitatory and inhibitory neuronal signals, that could stem from a range of functional and structural neuronal impairments. Globally, nearly 70 million people are negatively impacted by epilepsy and its comorbidities. One such comorbidity is the effect epilepsy has on the autonomic nervous system (ANS), which plays a role in the control of blood circulation, respiration and gastrointestinal function. These epilepsy‐induced impairments in the circulatory and respiratory systems may contribute toward sudden unexpected death in epilepsy (SUDEP). Although, various hypotheses have been proposed regarding the role of epilepsy on ANS, the linking pathological mechanism still remains unclear. Channelopathies and seizure‐induced damages in ANS‐control brain structures were some of the causal/pathological candidates of cardiorespiratory comorbidities in epilepsy patients, especially in those who were drug resistant. However, emerging preclinical research suggest that neurotransmitter/receptor dysfunction and synaptic changes in the ANS may also contribute to the epilepsy‐related autonomic disorders. Thus, pathological mechanisms of cardiorespiratory dysfunction should be elucidated by considering the modifications in anatomy and physiology of the autonomic system caused by seizures. In this regard, we present a comprehensive review of the current literature, both clinical and preclinical animal studies, on the cardiorespiratory findings in epilepsy and elucidate the possible pathological mechanisms of these findings, in hopes to prevent SUDEP especially in patients who are drug resistant.

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

Cited by 25 publications

References 70 publications

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

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

Epilepsy duration is an independent factor for electrocardiographic changes in pediatric epilepsy

Cardiorespiratory findings in epilepsy: A recent review on outcomes and pathophysiology

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