Interictal cardiac autonomic dysfunction in temporal lobe epilepsy demonstrated by [123I]metaiodobenzylguanidine-SPECT
Abstract and Figures
We studied the post-ganglionic cardiac sympathetic innervation in patients with chronic temporal lobe epilepsy (TLE) by means of [(123)I]metaiodobenzylguanidine-single photon computed tomography (MIBG-SPECT) and evaluated the effects of carbamazepine on cardiac sympathetic innervation. TLE is frequently associated with dysfunction of the autonomic nervous system. Autonomic dysregulation might contribute to unexplained sudden death in epilepsy. Anticonvulsive medication, particularly with carbamazepine, might also influence autonomic cardiovascular modulation. MIBG-SPECT allows the quantification of post-ganglionic cardiac sympathetic innervation, whereas measuring the variability of the heart rate provides only functional parameters of autonomic modulation. Antiepileptic drugs, especially carbamazepine (CBZ), can affect cardiovascular modulation. We determined the index of cardiac MIBG uptake (heart/mediastinum ratio) and heart rate variability (HRV) using time and frequency domain parameters of sympathetic and parasympathetic modulation in 12 women and 10 men (median age 34.5 years) with a history of TLE for 7-41 years (median 20 years). Myocardial perfusion scintigrams were examined to rule out deficiencies of MIBG uptake due to myocardial ischaemia. To assess the possible effects of CBZ on autonomic function, we compared MIBG uptake and HRV in 11 patients who had taken CBZ and 11 patients who had not taken CBZ, and in 16 healthy controls. In order to identify MIBG uptake defects due to myocardial ischaemia, all patients had a perfusion scintigram. Cardiac MIBG uptake was significantly less in the TLE patients (1.75) than in the controls (2.14; P = 0.001), but did not differ between subgroups with and without CBZ treatment. The perfusion scintigram was normal in all patients. Time domain analysis of HRV parameters suggested the predominance of parasympathetic cardiac activity in the TLE patients, but less parasympathetic modulation in the patients treated with CBZ than in those not treated with CBZ (P < 0.05), whereas frequency domain parameters showed no significant difference between the subgroups of patients or between patients and controls. MIBG-SPECT demonstrates altered post-ganglionic cardiac sympathetic innervation. This dysfunction might carry an increased risk of cardiac abnormalities.
![MIBG-SPECT demonstrating non-homogeneous [ 123 I]MIBG accumulation in the heart in a 30-year-old man with a 29-year history of TLE.](https://www.researchgate.net/profile/Torsten-Kuwert/publication/11652289/figure/fig2/AS:276977115254797@1443047898817/MIBG-SPECT-demonstrating-non-homogeneous-123-IMIBG-accumulation-in-the-heart-in-a_Q320.jpg)
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... Many studies have investigated the underlying complexity of the connection between the brain and the heart in patients with epilepsy [3]. Cardiovascular autonomic regulation is impaired in patients with epilepsy, as manifested by impaired heart-rate variability (HRV) in response to various stimuli or reduced uptake of 123I-metaiodobenzylguanidine, a marker of postganglionic sympathetic dysfunction [4][5][6][7]. ...
Epilepsy’s impact on cardiovascular function and autonomic regulation, including heart-rate variability, is complex and may contribute to sudden unexpected death in epilepsy (SUDEP). Lateralization of autonomic control in the brain remains the subject of debate; nevertheless, ultra-short-term heart-rate variability (HRV) analysis is a useful tool for understanding the pathophysiology of autonomic dysfunction in epilepsy patients. A retrospective study reviewed medical records of patients with temporal lobe epilepsy who underwent presurgical evaluations. Data from 75 patients were analyzed and HRV indices were extracted from electrocardiogram recordings of preictal, ictal, and postictal intervals. Various HRV indices were calculated, including time domain, frequency domain, and nonlinear indices, to assess autonomic function during different seizure intervals. The study found significant differences in HRV indices based on hemispheric laterality, language dominancy, hippocampal atrophy, amygdala enlargement, sustained theta activity, and seizure frequency. HRV indices such as the root mean square of successive differences between heartbeats, pNN50, normalized low-frequency, normalized high-frequency, and the low-frequency/high-frequency ratio exhibited significant differences during the ictal period. Language dominancy, hippocampal atrophy, amygdala enlargement, and sustained theta activity were also found to affect HRV. Seizure frequency was correlated with HRV indices, suggesting a potential relationship with the risk of SUDEP.
... Of note, cardiac manifestations often precede the onset of seizure. Both cardiac autonomic impairment and conduction system dysfunction are well reported in patients with epilepsy [33,34]. Changes in vagus nerve activity (which have a great influence on the heart) could predict seizure onset [3]. ...
Background:
The brain and heart are strictly linked and the electrical physiologies of these organs share common pathways and genes. Epilepsy patients have a higher prevalence of electrocardiogram (ECG) abnormalities compared to healthy people. Furthermore, the relationship between epilepsy, genetic arrhythmic diseases and sudden death is well known. The association between epilepsy and myocardial channelopathies, although already proposed, has not yet been fully demonstrated. The aim of this prospective observational study is to assess the role of the ECG after a seizure.
Materials and methods:
From September 2018 to August 2019, all patients admitted to the emergency department of San Raffaele Hospital with a seizure were enrolled in the study; for each patient, neurological, cardiological and ECG data were collected. The ECG was performed at the time of the admission (post-ictal ECG) and 48 h later (basal ECG) and analyzed by two blinded expert cardiologists looking for abnormalities known to indicate channelopathies or arrhythmic cardiomyopathies. In all patients with abnormal post-ictal ECG, next generation sequencing (NGS) analysis was performed.
Results:
One hundred and seventeen patients were enrolled (females: 45, median age: 48 ± 12 years). There were 52 abnormal post-ictal ECGs and 28 abnormal basal ECGs. All patients with an abnormal basal ECG also had an abnormal post-ictal ECG. In abnormal post-ictal ECG, a Brugada ECG pattern (BEP) was found in eight patients (of which two had BEP type I) and confirmed in two basal ECGs (of which zero had BEP type I). An abnormal QTc interval was identified in 20 patients (17%), an early repolarization pattern was found in 4 patients (3%) and right precordial abnormalities were found in 5 patients (4%). Any kind modification of post-ictal ECG was significantly more pronounced in comparison with an ECG recorded far from the seizure (p = 0.003). A 10:1 higher prevalence of a BEP of any type (particularly in post-ictal ECG, p = 0.04) was found in our population compared to general population. In three patients with post-ictal ECG alterations diagnostic for myocardial channelopathy (BrS and ERP), not confirmed at basal ECG, a pathogenic gene variant was identified (KCNJ8, PKP2 and TRMP4).
Conclusion:
The 12-lead ECG after an epileptic seizure may show disease-related alterations otherwise concealed in a population at a higher incidence of sudden death and channelopathies. Post-ictal BEP incidence was higher in cases of nocturnal seizure.
... 13 Sometimes, the focus of seizure may also be on cortical areas that directly control autonomic nervous system, and firing of these areas cause undesired stimulation of autonomic nerves which affect the heart. 43 The effect of AEDs could also be responsible for the ECG abnormality by blocking ion channels of the heart. 44 Furthermore, congenital or acquired channelopathies that are found both in the heart and brain may be responsible for the mutual occurrence of epilepsy and ECG abnormality. ...
Background: Epilepsy is a brain disease that is associated with electrocardiographic (ECG) abnormalities. However, this evidence is limited in Ethiopia. Studying ECG abnormality in epileptic patients could help minimize the cardiac problems and death of epileptic patients by early screening. This study was aimed to assess electrocardiogram abnormalities and associated factors among people with and without epilepsy at referral hospitals in Amhara Regional State (ARS), northern Ethiopia, 2022. Methods: Institutional-based comparative cross-sectional study was conducted from April 20 to June 20, 2022. Three referral hospitals in ARS were selected by simple random sampling. Epileptic patients were selected by systematic random sampling, and 403 age-and sex-matched participants were selected from attendants of patients in the outpatient department. Interviewer-administered questionnaire and digital electrocardiograph were used for data collection. Data were entered to EpiData version 4.6 and exported to stata version 14 for analysis. Variables with P value <0.25 in bivariable analysis were entered to multivariable binary logistic regression. Strength of association was determined by adjusted odds ratio with a 95% confidence interval (CI). Results: The prevalence of ECG abnormality was 40.0% (95% CI = 34.7-46.8) and 29.0% (95% CI = 23.2-34.3) in epileptic and non-epileptic subjects, respectively. The odds of ECG abnormality was 58% higher among epileptic patients. Divorce, duration of epilepsy, uncontrolled epilepsy, former/current smoker, adequate physical activity, hypertension, and overweight/obesity were associated with ECG abnormality among epileptic patients. Conclusion and Recommendations: The proportion of ECG abnormality was higher among the epileptic than the non-epileptic group. This should be a wake-up call for stakeholders to establish appropriate measurements to reduce cardiac issues of epileptic patients.
... 13 Sometimes, the focus of seizure may also be on cortical areas that directly control autonomic nervous system, and firing of these areas cause undesired stimulation of autonomic nerves which affect the heart. 43 The effect of AEDs could also be responsible for the ECG abnormality by blocking ion channels of the heart. 44 Furthermore, congenital or acquired channelopathies that are found both in the heart and brain may be responsible for the mutual occurrence of epilepsy and ECG abnormality. ...
Background:
Epilepsy is a brain disease that is associated with electrocardiographic (ECG) abnormalities. However, this evidence is limited in Ethiopia. Studying ECG abnormality in epileptic patients could help minimize the cardiac problems and death of epileptic patients by early screening. This study was aimed to assess electrocardiogram abnormalities and associated factors among people with and without epilepsy at referral hospitals in Amhara Regional State (ARS), northern Ethiopia, 2022.
Methods:
Institutional-based comparative cross-sectional study was conducted from April 20 to June 20, 2022. Three referral hospitals in ARS were selected by simple random sampling. Epileptic patients were selected by systematic random sampling, and 403 age- and sex-matched participants were selected from attendants of patients in the outpatient department. Interviewer-administered questionnaire and digital electrocardiograph were used for data collection. Data were entered to EpiData version 4.6 and exported to stata version 14 for analysis. Variables with P value <0.25 in bivariable analysis were entered to multivariable binary logistic regression. Strength of association was determined by adjusted odds ratio with a 95% confidence interval (CI).
Results:
The prevalence of ECG abnormality was 40.0% (95% CI = 34.7-46.8) and 29.0% (95% CI = 23.2-34.3) in epileptic and non-epileptic subjects, respectively. The odds of ECG abnormality was 58% higher among epileptic patients. Divorce, duration of epilepsy, uncontrolled epilepsy, former/current smoker, adequate physical activity, hypertension, and overweight/obesity were associated with ECG abnormality among epileptic patients.
Conclusion and recommendations:
The proportion of ECG abnormality was higher among the epileptic than the non-epileptic group. This should be a wake-up call for stakeholders to establish appropriate measurements to reduce cardiac issues of epileptic patients.
... Current medications used for TLE only offer symptomatic relief and typically induce adverse drug reactions. Carbamazepine, a commonly used drug for the treatment of TLE, is reported to reduce atrioventricular conduction, thereby increasing the risk of arrhythmias, especially in patients with interictal cardiac autonomic dysfunction [14][15][16][17][18]. Moreover, carbamazepine treatment has shown neurotoxic effects, such as dysphasia [19,20]. ...
Glutamate excitotoxicity induces neuronal cell death during epileptic seizures. Death-associated protein kinase 1 (DAPK1) expression is highly increased in the brains of epilepsy patients; however, the underlying mechanisms by which DAPK1 influences neuronal injury and its therapeutic effect on glutamate excitotoxicity have not been determined. We assessed multiple electroencephalograms and seizure grades and performed biochemical and cell death analyses with cellular and animal models. We applied small molecules and peptides and knocked out and mutated genes to evaluate the therapeutic efficacy of kainic acid (KA), an analog of glutamate-induced neuronal damage. KA administration increased DAPK1 activity by promoting its phosphorylation by activated extracellular signal-regulated kinase (ERK). DAPK1 activation increased seizure severity and neuronal cell death in mice. Selective ERK antagonist treatment, DAPK1 gene ablation, and uncoupling of DAPK1 and ERK peptides led to potent anti-seizure and anti-apoptotic effects in vitro and in vivo. Moreover, a DAPK1 phosphorylation-deficient mutant alleviated glutamate-induced neuronal apoptosis. These results provide novel insight into the pathogenesis of epilepsy and indicate that targeting DAPK1 may be a potential therapeutic strategy for treating epilepsy.
Background:
Heart rate variability (HRV) reduction is a potential biomarker for sudden cardiac death. This study aimed to study the effects of anti-seizure medications (ASMs), adjusted with reported factors associated with sudden unexpected death in epilepsy (SUDEP) on HRV parameters.
Methods:
We recruited patients who were admitted in our epilepsy monitoring unit between January 2013 and December 2021. Two 5-min electrocardiogram epochs during wakefulness and sleep were selected in each patient. HRV analysis with Python® software was performed. The imputed datasets were used for linear regression analysis to assess association between each ASM item and all HRV parameters. The effects of ASM on HRV parameters were subsequently adjusted with the significant clinical characteristics and the concomitant use of other ASMs, respectively.
Results:
Carbamazepine (CBZ), levetiracetam (LEV), lamotrigine (LTG), and clonazepam (CZP) were statistically significantly associated with changes of sleep HRV parameters. Only CBZ showed negative effects with reduction in HRV, evidenced as lower standard deviation of RR interval (SDNN), even when adjusted with concomitant use of other ASMs (p = 0.045) and had a trend of significance when adjusted with significant clinical characteristics of concurrent taking of beta-blocker drug (p = 0.052). LEV and CZP showed opposite effects with increased HRV even when adjusted with significant clinical characteristics and the concomitant use of other ASMs.
Conclusions:
CBZ showed negative effects on HRV. We proposed that CBZ should be cautiously used in patients with known risks for SUDEP. In addition, HRV assessment should be performed prior to commencing CBZ and re-performed in follow-up in cases of prolonged use.
Objective: Recent animal work, reviews, and retrospective analysis have identified oxygen conserving reflexes as potentially implicated in types of sudden death, namely sudden unexpected death in epilepsy (SUDEP) and sudden infant death syndrome (SIDS). Here we present a summary of current thinking on the topic, supported by our primary research results. Methods: We present an abbreviated review of the literature on autonomic instability in sudden death, on the reflexes in question, and on how the two may dangerously interact. Specifically, we explore the functions of the mammalian diving reflex, the laryngeal chemoreflex, and the carotid body. We include current theory on feedback, control, and hyperactivation of these reflexes. We include recent animal work in rats which explores reflex activity during seizure, resulting in sudden deaths. We conclude with potential mechanism and therapies which may be able to stop fatal reflex responses. Results: Significant historical data has suggested autonomic instability is related to SIDS and SUDEP. Autonomic instability can be dangerous when both branches of the autonomic nervous system are strongly co-activated, which occurs during certain oxygen conserving reflexes. Human and animal research has suggested for decades that these reflexes may cause sudden deaths. Mammalian diving reflex and laryngeal chemoreflex responses are stronger in infants, and the reflex strength peaks with SIDS risk. Carotid body resection, a now uncommon procedure, caused significant impairments to reflex and respiratory control in both animals and humans, and resulted in a high sudden death mortality. The carotid body is strongly implicated in mammalian diving reflex control. Conclusions: Recent and historical data suggest oxygen conserving reflexes may be causative of some sudden deaths. These mechanisms appear to coalesce around a strong terminal central apnea, a result of a failure of feedback control. Fatal apnea appears to be controlled by the mammalian diving reflex and the carotid body. Methods of feedback control on these pathways may be able to prevent some sudden deaths.
Objective: Recent animal work, reviews, and retrospective analysis have identified oxygen conserving reflexes as potentially implicated in types of sudden death, namely sudden unexpected death in epilepsy (SUDEP) and sudden infant death syndrome (SIDS). Here we present a summary of current thinking on the topic, supported by our primary research results. Methods: We present an abbreviated review of the literature on autonomic instability in sudden death, on the reflexes in question, and on how the two may dangerously interact. Specifically, we explore the functions of the mammalian diving reflex, the laryngeal chemoreflex, and the carotid body. We include current theory on feedback, control, and hyperactivation of these reflexes. We include recent animal work in rats which explores reflex activity during seizure, resulting in sudden deaths. We conclude with potential mechanism and therapies which may be able to stop fatal reflex responses. Results: Significant historical data has suggested autonomic instability is related to SIDS and SUDEP. Autonomic instability can be dangerous when both branches of the autonomic nervous system are strongly co-activated, which occurs during certain oxygen conserving reflexes. Human and animal research has suggested for decades that these reflexes may cause sudden deaths. Mammalian diving reflex and laryngeal chemoreflex responses are stronger in infants, and the reflex strength peaks with SIDS risk. Carotid body resection, a now uncommon procedure, caused significant impairments to reflex and respiratory control in both animals and humans, and resulted in a high sudden death mortality. The carotid body is strongly implicated in mammalian diving reflex control. Conclusions: Recent and historical data suggest oxygen conserving reflexes may be causative of some sudden deaths. These mechanisms appear to coalesce around a strong terminal central apnea, a result of a failure of feedback control. Fatal apnea appears to be controlled by the mammalian diving reflex and the carotid body. Methods of feedback control on these pathways may be able to prevent some sudden deaths.
Background:
Epilepsy is one of the most common neurological diseases and has high morbidity and mortality. Multiple methods for assessing dysautonomia have been reported; however, the patient characteristics and epilepsy features that drive any method selection are unclear. People with epilepsy (PWE) can experience sudden unexpected death in epilepsy (SUDEP) and one reason can be dysautonomia. If dysautonomia can be detected in PWE before a severe event, then it could complement and redirect patient treatment and monitoring.
Objective:
To map the available literature on dysautonomia in PWE and describe patients' characteristics and methods used to evaluate dysautonomia.
Methods:
We performed a scoping literature review. We searched PubMed, Scopus, Embase, and hand searched starting from the first registry in the literature until August 2019. Studies were independently assessed by three authors and two epileptologists. We present data in tables and summarize information according to the following structure: population, concepts, and context.
Results:
Thirty-five studies were included in the analysis with epidemiological designs including case reports (23), cross-sectional studies (4), case‒controls (7), and cohort studies (1). A total of 618 patients were enrolled. Heart rate variability, arrhythmia, blood pressure, the tilt-table test, polysomnography, respiratory function, and magnetic resonance imaging were the methods most commonly used to assess dysautonomia in PWE. A detailed description of the heart rate variability assessment is presented.
Conclusions:
This review provides a broad description of the available literature identifying clinical findings, the most frequently reported assessment measurements of dysautonomia, in temporal lobe epilepsy and extratemporal epilepsies.
Autonomic dysfunction is frequently observed in people with epilepsy. Ictal and postictal dysautonomia is not only manifestation of autonomic seizures, but could be a life threatening condition in some cases and contribute to sudden unexpected death (SUDEP). Interictal decrease of autonomic activity is associated with duration and severity of epilepsy, it is the most prominent in focal and drug-resistant epilepsy. Progress in our understanding of the underlying mechanisms, development of the autonomic assessment methods, and its integration in novel technical solutions for seizure detection will improve the quality of care for people with epilepsy.
Amygdalotegmental projections were studied in 26 cats after injections of horseradish peroxidase (HRP) in the diencephalon, midbrain and lower brain stem and in 6 cats after injection of 3H-leucine in the amygdala. Following HRP injections in the posterior hypothalamus, periaqueductal gray (PAG) and tegmentum many retrogradely labeled neurons were present in the central nucleus (CE) of the amygdala, primarily ipsilaterally. Injections of HRP in the posterior hypothalamus and mesencephalon also resulted in the labeling of neurons in the basal nucleus, pars magnocellularis. Following 3H-leucine injections in CE and adjacent structures autoradiographically labeled fibers were present in the stria terminalis and ventral amygdalofugal pathways. In the mesencephalon heavily labeled fiber bundles were located lateral to the red nucleus. Labeled fibers and terminals were distributed to the mesencephalic reticular formation, substantia nigra, ventral tegmental area and PAG. In the pontine and medullary tegmentum the bulk of passing fibers was located laterally in the reticular formation. Many labeled fibers and terminals were distributed to the parabrachial nuclei, locus coeruleus, nucleus subcoeruleus and lateral tegmental fields. Many terminals were also present in the solitary nucleus and dorsal motor nucleus of the vagus nerve. The location of the cells of origin and the distribution of the terminals of the amygdalotegmental projection suggest that this pathway plays an important role in the integration of somatic and autonomic responses associated with affective defense.
After a brief historical résumé, definitions and classifications of epilepsy are considered. The concept of epilepsy as an entity is false, and the term is a misnomer since there are multiple known (symptomatic epilepsy) and unknown (cryptogenic epilepsy) causes. In terms of mechanism an epileptic seizure is defined as "a state produced by an abnormal excessive neuronal discharge within the central nervous system." The seizure may originate in any part of the brain and may or may not spread to other areas. The book is organized around 10 years of experience at the Montreal Neurological Institute. The broader aspects of "the epilepsies," including methods of examination, diagnosis, treatment and prevention, are considered from practical and theoretical standpoints. In the course of treatment by craniotomy involving neurosurgical exploration and removal of cerebral tissue a wealth of information has been gained through physiological, psychological, and patho-histo-anatomical studies. Of particular interest to the psychologist, in addition to what may be learned concerning cerebral functions from a consideration of the physiological mechanisms of epilepsy, are chapters on EEG (by H. H. Jasper) and on the intelligence and personality of epileptics (by M. R. Harrower-Erickson). (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Iodine-123 metaiodobenzylguanidine (MIBG) myocardial imaging is considered to reflect cardiac sympathetic function. We performed myocardial MIBG scintigraphy and echocardiography in 27 patients with essential hypertension (EHT), 7 patients with renovascular hypertension (RVHT), and 8 normotensive subjects (NT) to investigate alterations in MIBG myocardial imaging in the presence of hypertension and left ventricular hypertrophy (LVH). EHT were divided into two groups based on LV wall thickness; EHT with LVH group (≥13 mm, n = 15) and EHT without LVH group (<13 mm, n = 12). The delayed uptake of MIBG was decreased, and the washout rate of MIBG was greater in the EHT with LVH group than EHT without LVH group or NT group. The washout rate was correlated with LV mass and LV diastolic function (as assessed by mitral flow). In RVHT group, the MIBG washout rate increased even without LVH, compared with NT and EHT without LVH groups. In summary, the washout rate of MIBG increased in parallel with the development of LVH in EHT and increased independently of the LV mass in RVHT. Cardiac sympathetic function could be altered in hypertensive LVH and in renovascular hypertension.
Purpose: This study assessed the frequency and character of ictal cardiac rhythm and conduction abnormalities in intractable epilepsy. Sudden unexpected death in epilepsy (SUDEP) is a major cause of excess mortality in people with refractory epilepsy, and cardiac arrhythmias during seizures may be responsible. The frequency of cardiac abnormalities during seizures in patients with refractory epilepsy must be determined.
Methods: Fifty-one seizures in 43 patients with intractable partial epilepsy were analyzed prospectively from CCTV-EEG monitoring with one ECG channel. Arrhythmias, repolarization abnormalities, and PR and QTC intervals were determined for preictal (3 min), ictal, and postictal (3 min) periods for one or more seizures per patient. Parametric statistics were used for continuous variables, and nonparametric statistics were used for categoric variables.
Results: Of the patients, 39% had one or more abnormalities of rhythm and/or repolarization during or immediately after seizures. Abnormalities included asystole (one), atrial fibrillation (one), marked or moderate sinus arrhythmia (six), supraventricular tachycardia (one), atrial premature depolarizations (APDs; eight), ventricular premature depolarizations (VPDs; two), and bundle-branch block (three). Mean seizure duration was longer in patients with abnormalities than in those without (204 vs. 71 s; p < 0.001). Generalized tonic–clonic seizures were also associated with increased occurrence of ictal ECG abnormalities (p = 0.006) as compared with complex partial seizures. There were no clinically significant differences in mean preictal and ictal/postictal PR and QTC intervals.
Conclusions: Cardiac rhythm and conduction abnormalities are common during seizures, particularly if they are prolonged or generalized, in intractable epilepsy. These abnormalities may contribute to SUDEP.
We studied 24 patients with partial seizures receiving carbamazepine (CBZ) monotherapy and 40 normal controls, 17 of whom were tested with and without CBZ therapy. Autonomic nervous system assessment included baseline heart rate (HR) and blood pressure (BP); BP and HR changes during orthostasis and cold pressor test (CPT); and HR changes during sinus arrhythmia, Valsalva maneuver, and cold face test with apnea (CFTA). Our study demonstrated normal interictal autonomic function in patients with epilepsy, but, variations in BP and HR during orthostasis and CPT were significantly (p CBZ. Epilepsy patients had higher initial increases in BP and greater subsequent decreases in BP than did nonmedicated controls during CPT. Controls with CBZ had higher HR during orthostasis and CFTA than did those without CBZ. CBZ levels correlated with baseline and orthostatic BP and HR during deep breathing (sinus arrhythmia). Our results showed that patients with epilepsy have greater BP and HR variability and reactivity than controls, attributable in part to CBZ levels.
Purpose: To measure interictal cardiovascular autonomic functions in patients with either refractory or well-controlled temporal lobe epilepsy (TLE).
Methods: For autonomic assessment, heart rate variation during normal and deep breathing, Valsalva maneuver, and tilting were measured in 19 patients with chronic refractory TLE, 19 patients with well-controlled TLE, and 38 age- and sex-matched healthy control subjects. Blood pressure responses to tilting and isometric work also were evaluated.
Results: Heart-rate (HR) variation during normal breathing (p = 0.006) and tilting (p = 0.043) was lower in patients with refractory TLE than in control subjects. Heart-rate response to tilting (p = 0.036) was also lower in patients with well-controlled TLE than in control subjects. Blood-pressure responses showed no differences between the patients and the control subjects. Patients taking carbamazepine (CBZ) medication had decreased HR responses to deep breathing (p = 0.046) and to tilting (p = 0.014) compared with the control subjects.
Conclusions: Refractory TLE seems to be associated with dysfunction of the cardiovascular autonomic regulation, manifesting as impaired HR responses to certain stimuli. Interictal autonomic dysfunction is seen in patients with well-controlled TLE as well, but it may be more evident in patients with refractory epilepsy. CBZ medication may also be associated with altered autonomic cardiac control.
Autonomic function was studied by the use of spectral analysis of heart-rate variability in patients with epilepsy in relation to type of epilepsy and anti-epileptic drug therapy. A total of 21 patients with juvenile myoclonic epilepsy (JME) and 21 with temporal lobe epilepsy (TLE) were included; 18 patients were treated with carbamazepine (CBZ), 16 with valproate (VPA) and seven with phenytoin (PHT). One healthy drug free control, matched for age and sex, was selected for each patient. Patients and controls underwent an ambulatory 24 h EKG. Heart-rate variability was analyzed in time and frequency domains. Patients with TLE had significantly lower S.D. of the RR-intervals, lower low frequency power and a lower low frequency/high frequency power ratio than their controls. A lower low frequency/high frequency power ratio was the only significant difference between the JME patient group and their controls. Treatment, however, may have had a considerable influence on the heart rate variability in the epilepsy patients. Patients on CBZ had significantly lower S.D. of RR-intervals, low frequency power and a low frequency/ high frequency power ratio than did their matched healthy drug free controls. The ratio of low frequency/high frequency power was also lower in patients on VPA compared with their controls, but apart from that no differences could be demonstrated between this treatment group and the controls. In conclusion, patients with epilepsy appear to have an altered autonomic control of the heart, with a reduction in some heart-rate variability measures, suggesting a decreased sympathetic tone, which may be related to the drug therapy or the epilepsy as such. Further studies are warranted to explore these changes and their possible relevance for sudden death in epilepsy.
