Electrocardiographic patterns in children with epilepsy seen at a tertiary Hospital in Benin city, Nigerian: a descriptive cross-sectional study

¹Institute of Child Health, University of Benin, Benin City, Lagos, Nigeria, ²Department of Child Health, University of Benin, Benin City, Lagos, Nigeria

^&Corresponding author
Paul Ikhurionan, Institute of Child Health, University of Benin, Benin City, Lagos, Nigeria

Introduction    

Children with epilepsy are at significantly higher risk of cardiac morbidity and complications compared to their non-epileptic peers [1,2]. Cardiac alterations include interictal and periictal rhythm disturbances, corrected QT interval (QTc) changes, and ventricular conduction and repolarization abnormalities [2,3]. These cardiac alterations can be detrimental, supported by the increased arrhythmogenic potential under conditions of periictal hypoxemia, and seizure?associated fatal and near-fatal arrhythmias [4]. The interplay between epilepsy and myocardial dysfunction is not well understood. These cardiovascular disturbances can be a direct consequence of the seizure activity itself or the pharmacological treatments used to manage the disorder [5]. Approximately 40% of children with epilepsy exhibit abnormalities in their heart rhythms, including benign idiopathic sinus arrhythmia, irregular rhythms, and QT interval changes [6,7]. While some of these irregularities may be transient, there is substantial evidence linking epilepsy to more persistent and potentially life-threatening cardiovascular alterations [8]. Notably, prolonged QT intervals have been associated with an elevated risk of severe arrhythmias, such as ventricular tachycardia and fibrillation, which can result in sudden cardiac events [9]. Several mechanisms contribute to rhythm abnormalities in children with epilepsy, each linked to the physiological disruptions caused by seizures. One such factor is the alteration in respiratory dynamics during the ictal phase, including hypoxia and hypercapnia, which can significantly affect the heart's electrical activity [10].

Seizure-induced sympathetic stimulation further exacerbates these effects, increasing the risk of arrhythmias [11]. Additionally, seizures may induce rapid repolarizations in the Purkinje system and trigger molecular changes within the ventricular myocardium, particularly in ionic channels such as sodium channels [10]. Excessive sodium channel expression can lead to prolonged cardiac depolarization, contributing to a longer QT interval and potentially initiating arrhythmic events [11]. Emerging evidence indicates that certain electrographic changes, including QT prolongation, may persist well beyond the acute phase, with some alterations remaining detectable for over two years following the last seizure event [1,3]. This extended persistence of electrocardiographic (ECG) changes highlights the need for continued monitoring of cardiac function in children with epilepsy, even long after the resolution of seizure activity. Despite growing awareness of the neurological burden of epilepsy in sub-Saharan Africa, there is a notable lack of research on the cardiac impact of epilepsy in children, particularly in Nigeria. This knowledge gap is a cause for concern, given the high prevalence of pediatric epilepsy in the region and the challenges posed by limited healthcare access and specialized services. In resource-limited settings, cardiovascular complications related to epilepsy may be overlooked, as diagnostic tools like electrocardiograms are often underutilized and healthcare providers may lack awareness of the associated risks. Furthermore, while antiepileptic drugs, commonly used in the management of epilepsy, are known to affect cardiac function, there is limited data on their specific impact on the hearts of Nigerian children. This study aims to address this gap by investigating ECG changes in Nigerian children with epilepsy, and to identify associated and predicting factors in children with rhythm abnormalities.

Methods     

Study design: this was a descriptive cross-sectional study of children with epilepsy.

Place of study: this study was conducted at the Pediatric Neurology Clinic of the University of Benin Teaching Hospital (UBTH), a major referral center for pediatric neurological care in Benin City, Nigeria, and neighboring states. The clinic serves over 1000 children with neurological conditions from infancy to the age of 18 years. Neurological conditions such as epilepsy and epileptic encephalopathies, cerebral palsies, developmental disorders, movement disorders, autistic spectrum disorders, attention deficit hyperactivity disorders, neurocutaneous syndromes, and the muscle dystrophies, as well as mixed disorders, are seen in the clinic. Services offered include diagnostic workup, pharmacologic treatment, monitoring/follow-up, and specialized care. The clinic is held twice weekly and is run by two attending consultant pediatricians specialized in pediatric neurology, supported by four pediatric trainee doctors, six pediatric nurses, an electrophysiology laboratory, and pharmacy staff on clinic days.

Study population and inclusion/exclusion criteria: the study population consisted of children aged 6 to 17 years attending the Pediatric Neurology Clinic at UBTH who were diagnosed with epilepsy. The participants were recruited for the study if they had a confirmed diagnosis of epilepsy (based on clinical assessment and electroencephalogram (EEG) results). Exclusion criteria included children with known congenital or acquired heart diseases unrelated to epilepsy; children with active infections or other medical conditions that could interfere with ECG recording.

Sample size determination: the sample size was determined using a formula for estimating proportions with a 95% confidence level and a margin of error of 5%. Based on an estimated proportion of 47% [12] the calculated sample size was 106 children. This sample size is adequate to detect significant ECG changes in the study population, while allowing for a reasonable degree of precision in the findings.

Sample selection and sampling procedure including ECG recording: a consecutive sampling approach was used to select the study participants. All eligible children attending the Pediatric Neurology Clinic at UBTH during the study period who met the inclusion criteria were invited to participate. The recruitment process was carried out over a period of ten months from January 2024 to October 2024. Upon obtaining informed consent from the parents or guardians, children were evaluated for the study. Each child underwent a detailed clinical examination, including a review of their medical history, seizure type, frequency, and duration of epilepsy. Following this, the children were prepared for an electrocardiogram (ECG) recording and rested for about 10 minutes before the ECG recording. The ECG was performed using a standard 12-lead ECG machine (Agilent PageWriter 300pi - Agilent Technologies, Inc., Andover, MA 01810 USA), with the child in a resting, quiet state. Electrodes were placed on the skin according to standard protocols for pediatric ECGs, ensuring optimal contact and minimal discomfort. The ECG was recorded for at least 5 minutes, and the results were analyzed for common abnormalities associated with epilepsy, such as prolonged QT interval, arrhythmias, and other rhythm disturbances.

Study variables: the dependent variables of the study were electrocardiographic abnormalities like PR, QRS, and QTc intervals, rhythm abnormalities, PR interval shortening or prolongation, QRS axis abnormalities, QRS morphologic or interval abnormalities, QTc interval shortening or prolongation, ST segment abnormalities, and T-wave abnormalities. The QT interval was measured as the distance from the beginning of the Q wave to the end of the T wave at least eight leads from the standard ECG. In each lead, the duration from the beginning of the Q wave to the end of the T wave was calculated in milliseconds, and the average was obtained (QT average) for three consecutive beats. The average QTc was calculated using the same QT interval measured using the Bazett formula (QTc =QT/√ RR). An ECG is considered abnormal is there is any abnormality in any of the parameters assessed. Independent variables included socioeconomic and demographic characteristics like age of child, gender, family socio-economic class, as well as epilepsy-related characteristics like age at seizure onset, duration of epilepsy, type of seizure, and names and number of anti-epileptic drugs treatment. The socio-economic class shall be determined using the method described by Oyedeji et al. [13].

Statistical analysis: the collected data were organised, tabulated, and statistically analysed using the International Business Machines Corporation (IBM) Statistical Package for the Social Sciences (SPSS) version 26.0 (SPSS for Windows Inc.; Chicago, LL, USA) Statistical Software. Descriptive characteristics were presented as Frequencies and percentages. The electrocardiographic information was dichotomised into those with and those without pathological findings. Bivariate analysis was done using the chi-squared test. Multivariate logistic regression analysis was also performed to identify potential risk factors for the development of ECG abnormalities in children with epilepsy. The level of statistical significance shall be set at p<0.05.

Ethical consideration: ethical approval for this study was obtained from the Health Research Ethics Committee of the University of Benin Teaching Hospital (UBTH), Benin City, Nigeria (ADM/E22/A/VOL.VII/14830199). Informed written consent was obtained from the caregivers of all participants after providing a clear explanation of the study objectives, procedures, potential risks, and benefits. Participation was entirely voluntary, and caregivers were informed of their right to withdraw from the study at any time without any consequences to their child´s care.

Results     

Demographic and clinical characteristics of participants: the age of the study participants ranged from six years to 15 years, with a mean age of 12 years and 7 months. Of the 100 participants, 56 were male with a male-to-female ratio of 1.27:1. The participants were mainly from the upper (38%) and middle (38%) socioeconomic classes. Generalized seizures (84. 84%) were the most common seizure type, 37 children had seizure onset between 6 years and 10 years, and 44 had had epilepsy duration longer than 5 years. Sixty-nine CWEs were on one AED, mainly valproate, levetiracetam, and carbamazepine, while only 2 were on more than two AEDs. The demographic and clinical characteristics of the study participants are summarized in Table 1.

Electrocardiographic findings in children with epilepsy: the median QTc interval was 0.393 (IQR = 0.384 - 0.414), and the mean heart rate was 84 (SD - 15.7). A total of 46 children with epilepsy had at least one ECG abnormality, giving a prevalence of 46%. The most common ECG abnormality recorded was premature atrial contraction (15, 15%) in children, and ST-segment abnormalities (11, 11%). The patterns and distribution of ECG abnormalities are shown in Table 2.

Association between abnormal electrocardiographic findings and sociodemographic/seizure characteristics: sex (χ²- 6.321, p - 0.012) and Duration of Epilepsy (χ²- 5.421, p - 0.020) were significantly associated with ECG abnormalities in the study participants. The association between ECG abnormalities and Sociodemographic characteristics is summarized in Table 3.

Independent predictor of abnormal electroencephalogram in children with epilepsy: a binary logistic regression was conducted to determine the independent predictors ECG abnormality in children with epilepsy. The model was statistically significant, χ² = 21.000, p= 0.013, indicating that the predictors reliable distinguished between children with abnormal ECG and those without abnormal ECG. Being a male was significant predictor (β = 1.128, p = 0.019, OR = 3.090, 95% CI: 1.202-7.942). Duration of epilepsy was also significant (β= -1.125, p = 0.026, OR = 0.325, 95% CI: 0.121-0.872). Children with epilepsy duration less than 5years were less likely to have abnormal ECG as those with longer disease duration (Table 4).

Discussion     

This study investigated the occurrence of electrocardiographic (ECG) changes in children with epilepsy and the predictors of ECG abnormalities in children with epilepsy. Our results indicate that more than two-fifths of children with epilepsy exhibit at least one abnormality on electrocardiography. Among these, premature atrial contractions and ST-segment abnormalities were the most frequently observed. We found that being a male and prolonged duration of epilepsy were independent risk factors for ECG abnormalities in these children with epilepsy. These findings underscore the potential clinical significance of ECG monitoring in children with epilepsy, particularly in relation to disease duration. The prevalence of electrocardiographic abnormalities observed in our study cohort aligns with findings from previous research. For instance, Chan et al. [14] reported that approximately 53% of American children with epilepsy without preexisting cardiac conditions or ion channelopathies who had history of paediatric intensive care unit admission for convulsive seizures or status epilepticus demonstrated at least one or more ECG abnormality, highlighting the relatively common occurrence of cardiac electrical disturbances in this population. This indicates that ECG abnormalities are not uncommon in pediatric epilepsy. However, the prevalence reported in our study is lower than that described by Ali et al.[15] who found ECG abnormalities in 71% of children admitted to the intensive care unit (ICU) for convulsive status epilepticus. This variance may be because of the differences in the timing of ECG recording. In our study, the participants were not experiencing active seizures at the time of ECG recording, which may have reduced the likelihood of capturing transient seizure-related ECG changes.

Previous studies have shown that acute seizure activity and the periictal period can be associated with various ECG alterations, such as tachycardia, QT interval changes, or ST-segment deviations-many of which tend to resolve postictal and may not pose long-term risks in clinically stable patients [16,17]. The most frequently observed ECG abnormalities in our cohort were premature atrial contractions (PACs) and ST-segment abnormalities, with prevalences of approximately 15% and 11%, respectively. Other repolarization disturbances included tall T waves (8%), inverted T waves (1%), and premature ventricular contractions (PVCs) (8%). These findings are consistent with previous reports in pediatric and adult epilepsy populations, where nonspecific ST–T changes and ectopic beats are common, even in the absence of structural heart disease [18]. Although these ECG abnormalities often resolve postictally, some studies suggest that frequent or persistent abnormalities-particularly those involving ventricular repolarization-could reflect increased electrical instability and may be relevant to the pathophysiology of sudden unexpected death in epilepsy (SUDEP) [2]. Some authors have hypothesized that specific ECG features, including frequent PACs, ST-segment shifts, or QT dispersion, may constitute risk biomarkers for SUDEP. However, direct evidence linking these abnormalities to SUDEP in pediatric epilepsy is absent in the current literature [19].

Male participants were more likely to exhibit ECG abnormalities than females, a finding that aligns with previous research on sex-related differences in cardiac electrophysiology among people with epilepsy. Studies have shown that males may be at greater risk for repolarization abnormalities, including prolonged QTc intervals, ST-segment changes, and ectopic beats, particularly in the context of chronic epilepsy or seizure activity [18]. For example, Surges et al. reported that male sex was associated with greater QTc variability and reduced heart rate variability, both of which are considered markers of autonomic dysfunction and cardiac electrical instability in epilepsy patients [17]. Similarly, Nei et al. found that men with epilepsy demonstrated a higher prevalence of interictal ECG abnormalities, particularly T-wave and ST-segment changes, when compared to females [16]. These sex-based differences may be due to a combination of factors, including hormonal influences on cardiac ion channel function. Testosterone has been implicated in modulating cardiac excitability and may contribute to an increased susceptibility to arrhythmogenic changes in males [20]. Other possible explanations include differences in seizure types or frequency between sexes, and variable sensitivity to antiepileptic drugs.

Another important finding from this study is the association between epilepsy duration and the presence of ECG abnormalities. Specifically, we observed that children with epilepsy for less than 5 years were significantly less likely to have ECG abnormalities compared to those with longer disease duration. This observation agrees with findings from previous studies that have demonstrated a cumulative impact of chronic epilepsy on cardiac electrophysiology [14,21]. In adults with long-standing epilepsy, interictal and postictal T-wave alternans-a marker of repolarization instability and a known predictor of sudden cardiac death-have been consistently reported, particularly among those with treatment-resistant epilepsy [22]. In the pediatric population, similar associations have been identified. For example, children with Dravet syndrome and a disease duration of five years or more were found to have significantly longer corrected QT intervals (QTc) and greater spatial and temporal dispersion of ventricular repolarization, indicating increased cardiac electrical instability [23]. The pathophysiology behind this may involve cumulative effects of seizures, long-term autonomic imbalance, and prolonged exposure to antiepileptic drugs (AEDs) that alter cardiac ion channel function [2,5,24]. The implications of these findings for clinical practice are substantial. Given the high prevalence of ECG abnormalities in children with epilepsy, particularly those with longer disease duration, it may be beneficial to incorporate routine ECG screening into the management of these children. While ECG abnormalities may not always be symptomatic, their presence could indicate underlying pathophysiological changes that may require closer monitoring or adjustment of treatment strategies [5]. Moreover, clinicians should be cautious when prescribing AEDs known to have cardiac side effects, especially in children who are on long-term therapy [25]. Additionally, the finding that rhythm abnormalities are most common in our cohort highlights the need for further studies to investigate the potential long-term risks of these changes, including the risk of sudden cardiac death or other serious cardiovascular events, which are known to be increased in adults with epilepsy [26].

Limitation of study: our study has a few limitations that should be acknowledged. First, the absence of a comparison group limits our ability to draw definitive conclusions about the significance or specificity of the ECG abnormalities observed. Additionally, we used a convenience sampling method, which may introduce selection bias and limit the generalizability of our findings. We also did not examine the influence of specific epilepsy syndromes, comorbidity, or medication use, any of which could have impacted the prevalence and nature of the ECG abnormalities identified. Despite these limitations, the strength of our study lies in its focus on a general pediatric epilepsy population outside of the ICU or ictal phase-making it one of the few studies to explore ECG abnormalities in this clinical context.

Conclusion     

Our study highlights the relatively high occurrence of ECG abnormalities, particularly rhythm disturbances, in children with epilepsy. The sex and duration of disease were found to be significant factors associated with these abnormalities, emphasizing the need for careful monitoring of children with epilepsy, especially those with chronic conditions. These findings suggest that ECG screening could become an essential part of routine care for children with epilepsy, aiding in the early detection of potentially significant cardiovascular changes. Further research is needed to elucidate the mechanisms behind these ECG abnormalities and to evaluate their long-term implications for cardiovascular health in this population.

Competing interests     

All authors declare no competing interests.

Authors' contributions     

Paul Ikhurionan: conceptualization, study design, data collection, and interpretation of data, writing of initial manuscript. Olusola Okunola: study design, data collection, and revision of article for important intellectual content. Nandom Benjamin: study design, data interpretation, and revision of article for important intellectual content. Wilson Sadoh: conceptualization, study design, data interpretation, and writing of initial manuscript. All authors take responsibility for all information provided as correct. All the authors have read and approved the final version of this manuscript.

Tables     

Table 1: sociodemographic and clinical characteristics of study participants

Table 2: patterns and distribution of electrocardiographic abnormalities in children with epilepsy

Table 3: factors associated with electrocardiographic abnormalities in children with epilepsy

Table 4: multivariate analysis of factors associated with electrocardiographic abnormalities in children with epilepsy

References