The brain–heart interaction in epilepsy: implications for diagnosis, therapy, and SUDEP prevention

Abstract

The influence of the central nervous system and autonomic system on cardiac activity is being intensively studied, as it contributes to the high rate of cardiologic comorbidities observed in people with epilepsy. Indeed, neuroanatomic connections between the brain and the heart provide links that allow cardiac arrhythmias to occur in response to brain activation, have been shown to produce arrhythmia both experimentally and clinically. Moreover, seizures may induce a variety of transient cardiac effects, which include changes in heart rate, heart rate variability, arrhythmias, asystole, and other ECG abnormalities, and can trigger the development of Takotsubo syndrome. People with epilepsy are at a higher risk of death than the general population, and sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. Although the cause of SUDEP is still unknown, cardiac abnormalities during and between seizures could play a significant role in its pathogenesis, as highlighted by studies on animal models of SUDEP and registration of SUDEP events. Recently, genetic mutations in genes co-expressed in the heart and brain, which may result in epilepsy and cardiac comorbidity/increased risk for SUDEP, have been described. Recognition and a better understanding of brainheart interactions, together with new advances in sequencing techniques, may provide new insights into future novel therapies and help in the prevention of cardiac dysfunction and sudden death in epileptic individuals.

Impaired brain-heart axis in focal epilepsy: Alterations in information flow and implications for seizure dynamics

“…It is widely recognized that HF frequencies play a crucial role in regulating various physiological processes, such as respiration and vagal tone modulation ( Rajendra Acharya, Paul Joseph, Kannathal, Lim, & Suri, 2006 ; Shaffer & Ginsberg, 2017 ). These results, in line with previous findings in Costagliola et al (2021) , further support the notion that seizures can disrupt this regulatory behavior shortly after the ictal event. Within the framework of the epileptic brain network, the identified BHI differences concerning brain waves may indeed be associated with specific functional roles attributed to these waves.…”

“…In Figure 3 , a constant increase in interactions can be observed for the HtB LF → δ case, while the case θ → HF demonstrates that the preictal interaction values are generally higher than the postictal values, across all the 1-min windows considered. These findings partially align with previous studies ( Costagliola et al, 2021 ; Schiecke et al, 2016 ), which have underscored the functional link between the brain and the heart during seizures, along with the specific alterations occurring in both physiological systems during preictal and postictal periods. In their study, Schiecke et al (2016) utilized the convergent cross mapping approach and identified directed interactions between HRV and delta-related EEG activity in children with TLE.…”

“…In this study, because of movement artifacts and unreliable ECG or EEG recordings during the ictal phase, it was not possible to conduct such analysis for several subjects. However, based on the promising results obtained, it can be inferred that a difference between the preictal and postictal phases occurs, as already suggested in the literature ( Costagliola et al, 2021 ; Verrier et al, 2020 ). Furthermore, the proposed methods provide a quantitative estimation of the interactions between the CNS and ANS, as well as how these connections vary over time, showing an interesting decrease after the seizure event.…”

Synchronous heart rate reduction with suppression‐burst pattern in KCNT1‐related developmental and epileptic encephalopathies

“…Epileptic seizures are known to be associated with HR changes, HR variability (HRV), arrhythmias, and other ECG abnormalities. 11 However, this is the first study revealing that interictal SB might influence HR regulation in patients with KCNT1-DEE.…”

“…Furthermore, a significant correlation was found between the duration of suppression and the extent of HR reduction in one patient with KCNT1 ‐DEE. Epileptic seizures are known to be associated with HR changes, HR variability (HRV), arrhythmias, and other ECG abnormalities 11 . However, this is the first study revealing that interictal SB might influence HR regulation in patients with KCNT1 ‐DEE.…”