Brain, Vol. 124, No. 12, 2361-2371,
December 2001
© 2001 Oxford University Press
Ictal bradycardia in partial epileptic seizures
Autonomic investigation in three cases and literature review
1 Neurological Institute, University of Bologna and 2 Neurological Section, University of Modena and Reggio Emilia, Italy
Correspondence to:
Paolo Tinuper, MD, Neurological Institute. University of Bologna, Via Ugo Foscolo 7, 40123 Bologna, Italy E-mail: tinuper{at}neuro.unibo.it
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Abstract |
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Ictal bradycardia is a rare, probably underestimated, manifestation of epileptic seizures whose pathophysiology is still debated. Autonomic modifications may result either from a sympathetic inhibition or from a parasympathetic activation probably due to the ictal discharge arising from or spreading to the structures of the central autonomic network. We review 60 cases of ictal bradycardia from the available literature and present three additional cases associated with left temporal lobe seizures studied by autonomic polygraphic ictal monitoring. Only 47 of the 63 reported cases were documented by simultaneous EEG and ECG recordings during an attack. About 76% of patients in whom well-localized ictal discharges were recorded had temporal or frontotemporal lobe seizures. Forty-five cases included information allowing confident localization of the side of ictal onset, and a 26 : 19 ratio of the left versus right side was evident. Simultaneous monitoring of ECG and other autonomic parameters during EEG recording in partial seizures should be performed to gain more insight into ictal semiology. Correlation of the symptoms referred to by patients with changes in autonomic parameters could avoid erroneous diagnosis of non-epileptic attacks and disclose a potentially lethal condition. Our cases confirm the preferential role of the left hemisphere in the genesis of ictal bradycardia and shed light on the relationship between suprabulbar control of autonomic function and partial epileptic seizures.
partial seizures; arrhythmogenic seizures; bradycardia; vegetative ictal symptoms; autonomic system
BP = blood pressure; HR = heart rate
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Introduction |
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Ictal epileptic discharges can often cause changes in cardiac rhythm. Increased heart rate is the most frequent finding: ictal tachycardia occurs in 64–100% of temporal lobe seizures (Marshall et al., 1983
; Blumhardt et al., 1986; Smith et al., 1989).
Almost a century ago, decades before the introduction of EEG or polygraphic monitoring, Russell clinically observed the cessation of the pulse during a seizure in a young man (Russell et al., 1906). Since then, 60 anecdotal cases have been reported in which ictal episodes were accompanied by slowing of the heart rate or asystole. Bradycardia during complex partial seizures has been labelled ictal bradycardia syndrome (Reeves et al., 1996). The true incidence of this rare, potentially life-threatening, condition is probably underestimated. Diagnosis of ictal bradycardia is based on documentation of bradycardia/asystole clearly produced by a concomitant ictal discharge documented on EEG. Misdiagnosis is common because patients with paroxysmal bradyarrhythmias are usually admitted to coronary care units or to cardiology services where simultaneous EEG–ECG monitoring is not routine, and cardiologists consider abnormal heart rhythm only from a cardiac perspective (Jacome and Serropian, 1995; Van Rijckevorsel et al., 1995). On the other hand, neurologists rarely include polygraphic recordings in patients undergoing intensive monitoring for partial seizures, and ictal autonomic modifications are therefore missed. Also for these reasons, ictal bradycardia has been reported in <6% of complex partial seizures (Smith et al., 1989; Schernthaner et al., 1999; Nei et al., 2000). Approximately one-quarter of patients with ictal bradycardia for whom age is reported were at least 60 years old. This is precisely the age group in which the incidence of partial epilepsy rises significantly. Therefore, we would expect the prevalence of ictal bradycardia to increase either due to the rapid expansion of the elderly portion of our population, or as a result of increased recognition (Reeves et al., 1996).
Getting the diagnosis right is essential because appropriate treatment could prevent sudden unexpected death in epileptic patients, which, on the evidence of many experimental and clinical studies, is thought to be related to potentially lethal arrhythmias, such as asystole, induced by epileptic seizures (Lathers and Schraeder 1982; Schraeder and Lathers 1989; Oppenheimer et al., 1990; Mameli et al., 1993).
We describe three patients with temporal lobe epilepsy in whom a left temporal lobe seizure was associated with ictal bradycardia. In addition, we review the available literature for similar cases.
Patients and methods
Electrophysiology
In the last 3 years we have studied three patients presenting with partial seizures in which video-polygraphic recordings revealed bradycardia during focal epileptic seizures. Video-EEG documents were reviewed to define seizure semiology and the topographic localization of the ictal discharges. Electrodes were placed according to the 10–20 International System. Bipolar montage and zygomatic leads were used in Case 2 with electrodes placed over the zygomatic notch in the posterior portion of the cheek, 2 cm beyond the tragus (Sindrup et al., 1981). In a separate session we explored the autonomic nervous system changes associated with the seizures. Together with EEG we monitored ECG, plethysmogram, oronasal and abdominal breathing, blood pressure (BP) continuously and non-invasively by means of Portapress-model II (TNO, Biomedical Instrumentation, Amsterdam, The Netherlands). An algorithm (finger to brachial level correct), utilized by the Beatfast computer program, was applied to correct the mean pressure to avoid erroneous estimation of absolute values. We also performed interictal autonomic investigations: patients were studied in a temperature controlled (23 ± 1°C) room with continuous monitoring of systemic BP, heart rate (HR) and respiratory rate. After 30 min of supine rest, head-up tilt, Valsalva manoeuvre and deep breathing were performed using standard procedures (Matthias and Bannister, 1999). The results of testing procedures during the interictal period were compared with the reference range obtained in our control subjects (mean ± 2 SD). The control group consisted of 18 healthy volunteers. Each patient underwent MRI of the brain and cardiological investigations.
We carried out a retrospective analysis of previously reported cases of ictal bradycardia with respect to age, sex, site of ictal onset, ictal recording, neuroradiological features and possible supporting data. Other reported cases, mentioned in abstract form with scant clinical and electrophysiological data were not included in our analysis (Radtke, 1989; Volpi et al., 1995). Moreover, we excluded cases in which bradycardia appeared during apnoeic seizures in children (Coulter, 1984; Hewertson et al., 1996), or followed a precocious phase of tachycardia (Nousiainen et al., 1989). Finally, we excluded reports of bradycardia, thought to be epileptic but in which the electrophysiological data did not support such a hypothesis, in particular, the case described by Ossentjuk (Ossentjuk et al., 1966) and previously reported in another review (Constantin et al., 1990) in which the relationship between bradycardia and ictal discharge was not certain.
Results
Case 1
A 30-year-old left-handed man with an unremarkable family and personal history, presented at 17 years of age with seizures characterized by loss of contact without warning, pallor, staring, gestural automatisms and sometimes unintelligible speech. Seizure duration was ~5–15 s, without post-ictal confusion or aphasia. At our first observation, seizure frequency was one every 2–3 months, despite antiepileptic drug treatment with carbamazepine 1200 mg/day. We tapered carbamazepine adding lamotrigine 200 mg/day, which failed to reduce the frequency of seizures in 18 months of follow-up.
Neurological examination was normal. Interictal EEG showed left frontotemporal theta activity and diffuse sharp waves, prevalent over the left temporo-parieto-occipital region. Interictal autonomic investigations and 24-h ECG monitoring were normal (Table 1). MRI of the brain was normal. Ictal EEG showed, after a diffuse desynchronization of background rhythm, paroxysmal rhythmic theta activity more evident in the left region, followed by paroxysmal sharp waves in both hemispheres with anterior prevalence. During the ictal discharge, a progressive bradycardia occurred without significant modification of the respirogram.
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During supine polygraphic autonomic monitoring another identical seizure was recorded. Ten seconds after the clinical onset of the seizure, the patient's BP decreased progressively to a minimum of 60/40 mmHg and sudden bradycardia (46 beats/min) occurred. A plethysmogram showed a signal of increased amplitude. The respiratory rate did not change significantly (Fig. 1
).
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Case 2
A 42-year-old right-handed woman, suffering from migraine without aura, and with an unremarkable family history, began having seizures at 38 years of age, characterized by a gastric aura and a warm feeling in the chest, rising to her face, with facial flushing followed sometimes by oro-alimentary automatisms. After this she would lose consciousness and, if standing up, fall to the ground. Enuresis sometimes occurred. Seizures lasted <1 min and occurred in peri-menstrual clusters. Antiepileptic drug treatment with phenytoin 350 mg/day progressively reduced seizure frequency in three years of follow-up. Neurological examination and 24-h ECG monitoring showed normal results. Interictal EEG showed focal spikes over the left temporal region. Interictal autonomic investigations showed a higher HR at rest and a hyper-sympathetic response to the Valsalva manoeuvre and tilt test with respect to the reference range obtained from our control subjects (Table 1
). MRI of the brain disclosed a left mesiotemporal lesion, not enhanced by gadolinium contrast, with a diameter of 5 mm causing a minimal dislocation of the left temporal horn.
Ictal EEG showed disappearance of the interictal abnormalities on the left temporal region followed by a slow amplitude fast activity, subsequently replaced by a prolonged sharp wave discharge that remained confined to the left temporal area (Fig. 2). From the beginning of the discharge there was a progressive slowing of HR and peak bradycardia that coincided with the patient's facial flushing. Normal HR was regained at the end of the seizure.
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). Thor.Resp. = thoracic respiration.During polygraphic autonomic recording in the supine condition, another identical seizure was recorded. Eight seconds after seizure onset, a sudden bradycardia (30 beats/min) occurred and persisted for 30 s. BP concomitantly decreased to a minimum of 75/44 mmHg 39 s after seizure onset. BP normalized 3 min after seizure onset. A plethysmogram showed a signal of increased amplitude. The respiratory rate did not show significant changes (Fig. 3
).
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Case 3
An 81-year-old right-handed man with an unremarkable family history had long-standing hypertension and chronic liver disease after HCV (hepatitis C virus) infection. At 78 years of age, episodes with loss of consciousness began, which were first diagnosed as syncopes. He underwent prolonged ECG monitoring (Holter ECG) that gave normal results. Afterwards, a tonic–clonic seizure diagnosis of epilepsy was made and antiepileptic treatment started. According to our observations 2 years after seizure onset, attacks were characterized by loss of contact, swallowing and pallor without warning. If standing up, he fell down unconscious, staring and unresponsive; in addition some right hand movements might occur. Seizure duration was <1 min, followed by confusion with amnesia and tiredness for 10 min. He had five seizures in 3 years. Phenytoin at a dose of 300 mg completely controlled the seizures.
Neurological examination showed slight extrapyramidal signs in the upper limbs. Interictal autonomic investigations (Table 1) and EEG were normal. Brain CT and MRI scans revealed a mild cortical and subcortical cerebral atrophy and small ischaemic lesions in the periventricular white matter and basal nuclei. Ultrasonography of blood flow in the cerebral vessels showed 35–40% left internal carotid stenosis at the origin, and mild external and internal left carotid and left subclavian artery stenosis. An electrophysiological intracavitary heart study showed normal functioning of the sinoatrial node and normal conduction under the bundle of His. Twenty-four hour ECG monitoring was normal. Ictal EEG and ECG recording, with the patient lying down, showed, at seizure onset, a rhythmic theta activity on the left frontotemporal region after muscle artefacts had been observed (Fig. 4). At the same time, HR progressively decreased until the end of the seizures (from 63 to 36 beats/min). Coincident with the start of the EEG discharge the patient turned pale, lost consciousness and started swallowing and then remained unresponsive for 1 min. At the end of the seizures he could not remember objects shown to him during the attack. No other episode recurred during autonomic recording.
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Literature cases
Tables 2 and 3
list the clinical features of the cases previously described in the literature in chronological order. Table 2 lists those cases (Katz et al., 1983; Gilchrist, 1985; Blumhardt et al., 1986; Rabending and Fisher, 1986; Bertholds et al., 1988; Jacome and Serropian, 1988; Howell and Blumhardt, 1989; Tamara et al., 1989; Lucas et al., 1991; Fincham et al., 1992; Liedholm and Gudjonsson, 1992; Wilder-Smith, 1992; Munari et al., 1995; Van Rijckevorsel et al., 1995; Nashef et al., 1996; Reeves et al., 1996; Devinsky et al., 1997; Jallon, 1997b; Iani et al., 1997; Kowalik et al., 1998; Manitius-Robeck et al., 1998; Saussu et al., 1998; Kahane et al., 1999; Nei et al., 2000) in which simultaneous ictal EEG–ECG recording was available, including our cases. Table 3 lists those observations in which only EEG or ECG (Phizackerley et al., 1954; Pritchett et al., 1980; Devinsky et al., 1986; Kiok et al., 1986; Smaje et al., 1987; Constantin et al., 1990; Joske and Davis, 1991; Jallon, 1997a), or neither (Constantin et al., 1990; Smaje et al., 1987) were available during the seizures. Data reported by the authors to support the diagnosis of ictal bradycardia are added.
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Discussion
A number of studies have been performed both in man and different animal models to identify the components of the central autonomic network involved in the functional relationships between cortical and subcortical centres in cardiovascular control (Lathers et al., 1987
; Bennaroch, 1997).
Early studies on simultaneous recording of autonomic functions during spontaneous and pentylenetetrazole-induced temporal lobe seizures described a stereotyped response consisting of hypertension, tachycardia, decreased skin resistance and plethysmogram, swallowing, inhibition of respiration and gastric motility (Van Buren, 1958; Van Buren and Ajmone-Marsan, 1960; Van Buren et al., 1961).
Since then, both stimulation and ablation experiments have demonstrated that limbic structures modulate hypothalamic functions (Van Buren et al., 1961; Gloor, 1975; Wannamaker, 1985). Electrical stimulation of limbic structures (especially the amygdala and periamygdaloid pyriform cortex) can produce autonomic changes, including cardiovascular responses, mediated by either sympathetic or parasympathetic pathways, which change the excitatory state at lower levels of the central representation of the autonomic system (Gloor, 1975). Electrical stimulation of the cingulate gyrus and orbitofrontal cortex has also produced changes in HR (Pool and Ransohoff, 1949; Kaada, 1951; Wall and Davis, 1951; Van Buren et al., 1961; Oppenheimer et al., 1990) and cases of ictal bradycardia related to orbitofrontal lobe seizures have been reported (Munari et al., 1995). The insular cortex, the central nucleus of the amygdala and some structures of the hypothalamus (paraventricular nucleus, lateral hypothalamic area and dorsomedial nucleus) belong to the central autonomic network (Benarroch, 1997), which controls pre-ganglionic sympathetic and parasympathetic visceromotor outputs. Mesial temporal and frontal areas are interconnected to the central autonomic network so that ictal discharges arising from or spreading to these regions are more likely to induce autonomic changes. Within the temporal lobe, the insula might be the cortical area involved in the genesis of changes in cardiac rhythm during partial seizures.
A left/right asymmetry in suprabulbar control of autonomic function is supported by experimental studies (Critchley et al., 2000, 2001). Intraoperative stimulation of the left insular cortex produces bradycardia and hypotension, while stimulation of the same structures on the right side produces tachycardia and hypertension (Oppenheimer et al., 1992). On the other hand, unilateral hemispheric inactivation with intracarotid amobarbital infusion produces tachycardia when performed on the left side and bradychardia when applied on the right side (Zamrini et al., 1990). It seems, therefore, that a cerebral lesion or a focal seizure may disrupt the hemispheric influence on autonomic centres of the brainstem. Recent PET studies have described significant changes in regional blood flow of different cerebral areas during peripheral sympathetic or parasympathetic activities: the right anterior cingulate gyrus, right insula, cerebellum and brainstem were activated during peripheral cardiovascular arousal, whereas the amygdala, hippocampus, prefrontal cortex, left insula and regions of the cingulate gyrus, cerebellum and brainstem showed decreased cardiovascular arousal, corresponding perhaps to parasympathetic autonomic activity (Critchley et al., 2000). In contrast, the cardiac effects of the amytal test in a larger population of patients with complex partial epilepsy have suggested that the right hemisphere may have preferential access to vagal systems affecting HR (Ahern et al., 2001). Eleven cases of ictal bradycardia with intracranial monitoring have been described (Munari et al., 1995; Devinsky et al., 1997; Manitius-Robeck et al., 1998; Kahane et al., 1999; Altenmüller et al., 2000), but only two of them reported ictal EEG and its correlation with the onset of bradycardia. In the first case (Devinsky et al., 1997), that of a right-handed man, the seizure onset was localized in the left temporal lobe, but the cardiac changes occurred after the seizure had spread to the right mesial temporal lobe. However, the authors did not record directly from the insula and the sinus arrest may have resulted from the seizure spread to the left insula. In the second case, that of a left-handed woman, bradycardia occurred during seizures originating in the right frontocentral and temporal neocortical areas (Kahane et al., 1999).
Reviewing the cases of ictal bradycardia described in the literature and our personal observations, only 47 (for references, see Table 2) out of the 63 reported cases were documented by simultaneous EEG and ECG recordings during an attack, and 46 out of 63 cases (Katz et al., 1983; Gilchrist, 1985; Blumhardt et al., 1986; Kiok et al., 1986; Rabending and Fisher, 1986; Bertholds et al., 1988; Jacome and Serropian, 1988; Howell and Blumhardt, 1989; DiLuzio and Rutecki, 1989; Lucas et al., 1991; Fincham et al., 1992; Liedholm and Gudjonsson, 1992; Wilder-Smith, 1992; Munari et al., 1995; Van Rijckevorsel et al., 1995; Reeves et al., 1996; Devinsky et al., 1997; Iani et al., 1997; Jallon, 1997a, b; Kowalik et al., 1998; Manitius-Robeck et al., 1998; Saussu et al., 1998; Kahane et al., 1999; Nei et al., 2000) included information that allowed confident localization of ictal onset.
The majority (31 out of 46) of these patients had seizures originating from the temporal lobes. The frontal lobe was involved in 13 cases, and in four of these cases the temporal lobe was involved as well. A seizure onset from the orbital portion has been documented in six patients. In one case, EEG recording montages were limited to two channels that did not allow an exact localization, although the visual aura suggested an initial involvement of the occipital lobe (Fincham et al., 1992). In another case, the lateralization of the discharge was determined without a precise localization (Howell and Blumhardt, 1989). Other reported cases either had specific EEG data omitted (Russell et al., 1906; Joske and Davis, 1991), or had no recordings of any ictal disharges (Phizackerley et al., 1954; Pritchett et al., 1980; Devinsky et al., 1986; Smaje et al., 1987; Constantin et al., 1990). Among the 47 cases documented by simultaneous EEG–ECG monitoring, the side of ictal onset discharge was only clearly evident in 32: left in 20 patients and right in 12. Considering also those cases of ictal bradycardia in which ictal onset was assumed solely on the basis of interictal EEG, a 26 : 19 ratio of the left versus right side was evident. In our three cases we recorded a paroxysmal discharge clearly confined to the left temporal areas concomitant with the beginning of the bradycardia.
Therefore, our data and the literature cases weigh against the idea that the right hemisphere has a preferential role in producing the ictal bradycardia, even if we cannot rule out that the left focal discharge, inhibiting the left tachyarrhythmogenic hemisphere, releases the bradycardic influence of the contralateral hemisphere. However, this is speculation and the preferential role of the left hemisphere seems the most likely explanation of ictal bradycardia in agreement with the above experimental and clinical studies. Another hypothesis is that there is a relationship between dominancy and lateralization of seizures producing bradycardia but, as hand preference has been reported in few patients with ictal bradycardia (nine out of 63), this hypothesis remains speculative.
Nashef described four cases in which transient bradycardia or sinus arrest always occurred with a change in respiratory pattern and suggested that bradycardia may be enhanced by cardiorespiratory reflexes, with apnoea playing a central part and hypoxia providing an additional contributory factor (Nashef et al., 1996). He concluded that the interpretation of bradyarrhythmias is incomplete without simultaneous recording of respiration, which has been reported in the literature in only one case (Van Rijckevorsel et al., 1995). We only monitored the respiratory rate in Cases 1 and 2. They presented minor breathing changes during the seizures, affecting amplitude but not frequency, and no apnoeic or anoxic events were recorded. Therefore, we believe that, in our cases, the possibility that bradycardia was enhanced by cardiorespiratory reflexes is unlikely. A more likely interpretation of the breathing changes associated with ictal bradycardia is that the ictal discharge could activate central regions, causing both bradycardia and apnoea; in fact, the electrical stimulation of the frontotemporal lobe in man gave results that seem to support this hypothesis (Bailey and Sweet, 1940; Van Buren et al., 1960).
Documenting ictal bradyarrhythmias during epileptic seizures is relevant in patient management for two main reasons: to avoid undesirable cardiac side-effects of antiepileptic treatment and to prevent potentially life-threatening events such as sudden unexpected death in epileptic patients. Ictal bradycardia per se is not a particular concern, but it could reflect more dangerous events such as heart block and asystole. These life-threatening situations have been disclosed in studies on cat models of ictal bradyarrhythmias leading to complete heart block in cats (Lathers and Schraeder, 1982). The preferential choice of a specific antiepileptic drug in patients with ictal arrhythmia has not been studied (Devinsky et al., 1986). Carbamazepine can lengthen the ECG Q–T interval and increase the arrhythmic effects of epileptic seizures, and was present in chronic therapy in some series of epileptic patients presenting with sudden unexpected death (Timmings et al., 1998). Moreover, carbamazepine has been implicated in the development of asystole, sinoatrial, atrioventricular block and decreased Purkinje automaticity in elderly patients with trigeminal neuralgia (Hamilton, 1978). On the other hand, phenytoin, on the basis of experimental studies, acts by centrally depressing hyperactivity in cardiac sympathetic nerves and abolishing arrhythmias (Gillis et al., 1971; Evans and Gillis, 1974; Evans and Gillis, 1975). Therefore, this drug, already known to be effective in the treatment of tachyarrhythmias (Epstein et al., 1987; Rizzon et al., 1987; Callaham et al., 1988; Fogoros et al., 1988), could be particularly useful in cases of ictal tachycardia, but not in patients with ictal bradycardia. For these reasons, in Patient 1 we changed carbamazepine to lamotrigine, while in Patients 2 and 3 we did not change the phenytoin treatment as the seizures were completely controlled by this drug. The choice of a specific antiepileptic drug in patients with proven arrhythmogenic seizures should be tailored to the specific ictal pattern of the patient and the possible pre-existing heart disease. When antiepileptic drug treatment fails to control arrhythmogenic seizures, insertion of a cardiac pacemaker should be considered.
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Acknowledgements |
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We wish to thank Fabio Bisquoli and Giorgio Barletta for technical assistance in carrying out the polygraphic study and Elena Zoni for her help in editing the manuscript.
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References |
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Ahern GL, Soller JJ, Lane RD, Labiner DM, Herring AM, Weinard ME, et al. Heart rate and heart rate variability changes in the intracarotid sodium amoberbital test. Epilepsia 2001; 42: 912–21.[Web of Science][Medline]
Altenmüller DM, Schulze-Bonhage, Lücking CH, Zentner J. Second and third degree atrioventricular block during complex, partial seizures with left temporal origin [abstract]. Epilepsia 2000; 41 (Suppl Florence): 120.
Bailey P, Sweet WH. Effects on respiration, blood pressure and gastric motility of stimulation of orbital surface of frontal lobe. J Neurophysiol 1940; 3: 276–81.
Benarroch EE. Overview of the organization of the central autonomic network. In: Bennaroch EE. Central autonomic network. Armonk (NY): Futura Publishing; 1997. p. 3–28.
Bertholds E, Hedstrom A, Rydén L. Neurogen Kardiologi eller Kardiogen Neurologi? Lakartidningen 1988; 85: 24–6.
Blumhardt LD, Smith PE, Owen L. Electrocardiographic accompaniments of temporal lobe epileptic seizures. Lancet 1986; 1: 1051–6.[Web of Science][Medline]
Callaham M, Schumaker H, Pentel P. Phenytoin prophylaxis of cardiotoxicity in experimental amitriptyline poisoning. J Pharmacol Exp Ther 1988; 245: 216–20.
Constantin L, Martins JB, Fincham RW, Dagli RD. Bradycardia and syncope as manifestations of partal epilepsy. J Am Coll Cardiol 1990; 15: 900–5.[Abstract]
Coulter DL. Partial seizures with apnea and bradycardia. Arch Neurol 1984; 41: 173–4.
Critchley HD, Corfield DR, Chandler MP, Mathias CJ, Dolan RJ. Cerebral correlates of autonomic cardiovascular arousal: a functional neuroimaging investigation in humans. J Physiol (Lond) 2000; 523: 259–70.
Critchley HD, Mathias CJ, Dolan RJ. Neuroanatomical basis for first- and second-order representations of bodily states. Nat Neurosci 2001; 4: 207–12.[Web of Science][Medline]
Devinsky O, Price BH, Cohen SI. Cardiac manifestations of complex partial seizures. Am J Med 1986; 80: 195–202.[Web of Science][Medline]
Devinsky O, Pacia S, Tatambhotla G. Bradycardia and asystole induced by partial seizures: a case report and literature review. [Review]. Neurology 1997; 48: 1712–14.[Abstract]
DiLuzio TA, Rutecki PA. Complex partial seizures associated with asystole [abstract]. Epilepsia 1989; 30: 705.
Epstein AE, Plumb VJ, Henthorn RW, Waldo AL. Phenytoin in the treatment of inducible ventricular tachycardia: results of electrophysiologic testing and long-term follow-up. Pacing Clin Electrophysiol 1987; 10: 1049–57.[Medline]
Evans DE, Gillis RA. Effect of diphenylhydantoin and lidocaine on cardiac arrhythmias induced by hypothalamic stimulation. J Pharmacol Exp Ther 1974; 191: 506–17.
Evans DE, Gillis RA. Effect of ouabain and its interaction with diphenylhydantoin on cardiac arrhythmias induced by hypothalamic stimulation. J Pharmacol Exp Ther 1975; 195: 577–86.
Fincham RW, Shivapour ET, Leis AA, Martins JB. Ictal bradycardia with syncope: a case report. Neurology 1992; 42: 2222–3.
Fogoros RN, Fiedler SB, Elson JJ. Efficacy of phenytoin in suppressing inducible ventricular tachyarrhythmias. Cardiovasc Drugs Ther 1988; 2: 171–6.[Medline]
Gilchrist JM. Arrhythmogenic seizures: diagnosis by simultaneous EEG/ECG recording. Neurology 1985; 35: 1503–6.
Gillis RA, McClellan JR, Saueri TS, Standaert FG. Depression of cardiac sympathetic nerve activity by diphenylhydantoin. J Pharmacol Exp Ther 1971; 179: 599–610.
Gloor P. Physiology of the limbic system. In: Penry JK, Daly DD, editors. Complex partial seizures and their treatment. Adv Neurol, Vol. 11. New York: Raven Press; 1975. p. 27–55.
Hamilton DV. Carbamazepine and heart block [letter]. Lancet 1978; I: 1365.
Hewertson J, Boyd SG, Samuels MP, Neville BG, Southall DP. Hypoxaemia and cardiorespiratory changes during epileptic seizures in young children. Dev Med Child Neurol 1996; 38: 511–22.[Web of Science][Medline]
Howell SJ, Blumhardt LD. Cardiac asystole associated with epileptic seizures: a case report with simultaneous EEG and ECG. J Neurol Neurosurg Psychiatry 1989; 52: 795–8.
Iani C, Colicchio G, Attanasio A, Mattia D, Manfredi M. Cardiogenic syncope in temporal lobe epileptic seizures [letter]. J Neurol Neurosurg Psychiatry 1997; 63: 259–60.
Jacome D, Serropian E. Ictal bradycardia. Am J Med Sci 1988; 295: 469–71.[Web of Science][Medline]
Jallon P, Thomas P, Convert P. Life-threatening arrhythmogenic seizures [abstract]. Epilepsia 1997a; 38 Suppl 3: 154.[Web of Science][Medline]
Jallon P. Arrhythmogenic seizures. Epilepsia 1997b; 38 Suppl 11: S43–S47.[Web of Science]
Joske DJ, Davis MJ. Sino-atrial arrest due to temporal lobe epilepsy. Aust NZ J Med 1991; 21: 62–4.[Web of Science][Medline]
Kaada BR. Somato-motor autonomic and electrocorticographic responses to electrical stimulation of `rhinencephalic' and other structures in primates, cat and dogs. Acta Physiol Scand 1951; 24 Suppl 83.
Kahane P, Di Leo M, Hoffmann D, Munari C. Ictal bradycardia in a patient with a hypothalamic hamartoma: a stereo-EEG study. Epilepsia 1999; 40: 522–7.[Web of Science][Medline]
Katz RI, Tiger M, Harner RN. Epileptic cardiac arrhythmia: sinoatrial arrest in two patients: a potential cause of sudden death in epilepsy? [abstract]. Epilepsia 1983; 24: 248.
Kiok MC, Terrence CF, Fromm GH, Lavine S. Sinus arrest in epilepsy. Neurology 1986; 36: 115–16.
Kowalik A, Bauer J, Elger CE. Asystolic seizures. [German]. Nervenarzt 1998; 69: 151–7.[Web of Science][Medline]
Lathers CM, Schraeder PL. Autonomic dysfunction in epilepsy: characterization of autonomic cardiac neural discharge associated with pentylenetrazol-induced epileptogenic activity. Epilepsia 1982; 23: 633–47.[Web of Science][Medline]
Lathers CM, Schraeder PL, Weiner FL. Synchronization of cardiac autonomic neural discharge with epileptogenic activity: the lockstep phenomenon. Electroencephalogr Clin Neurophysiol 1987; 67: 247–59.[Web of Science][Medline]
Liedholm LJ, Gudjonsson O. Cardiac arrest due to partial epileptic seizures. Neurology 1992; 42: 824–9.
Lucas C, Lacroix D, Durieu I, Dagano J, Forunier Y, Leys D, et al. Bradycardie épileptique. Presse Med 1991; 20: 1685–6.
Mameli O, Melis F, Giraudi D, Cualbu M, Mameli S, De Riu PL, et al. The brainstem cardioarrhythmogenic triggers and their possible role in sudden epileptic death. Epilepsy Res 1993; 15: 171–8.[Web of Science][Medline]
Manitius-Robeck S, Schuler P, Feistel H, Platsch G, Stefan H. Ictal syncopes. Cardiac sympathetic innervation disorder as the etiology? [German]. Nervenarzt 1998; 69: 712–16.[Web of Science][Medline]
Marshall DW, Westmoreland BF, Sharbrough FW. Ictal tachycardia during temporal lobe seizures. Mayo Clin Proc 1983; 58: 443–6.[Web of Science][Medline]
Matthias JC, Bannister R. Investigation of autonomic disorders. In: Mathias CJ, Bannister R, editors. Autonomic failure. 4th ed. Oxford: Oxford University Press; 1999. p. 169–95.
Munari C, Tassi L, Di Leo M, Kahane P, Hoffman D, Francione S, et al. Video-stereo-electroencephalographic investigation of orbitofrontal cortex: ictal electroclinical patterns. In: Jasper HH, Riggio S, Goldman-Rakic PS, editors. Epilepsy and the functional anatomy of the frontal lobe. New York: Raven Press; 1995. p. 273–95.
Nashef L, Walker F, Allen P, Sander JW, Shorvon SD, Fish DR. Apnoea and bradycardia during epileptic seizures: relation to sudden death in epilepsy. J Neurol Neurosurg Psychiatry 1996; 60: 297–300.
Nei M, Ho RT, Sperling MR. EKG abnormalities during partial seizures in refractory epilepsy. Epilepsia 2000; 41: 542–8.[Web of Science][Medline]
Nousiainen U, Mervaala E, Uusitupa M, Ylinen A, Sivenius J. Cardiac arrhythmias in the differential diagnosis of epilepsy. J Neurol 1989; 236: 93–6.[Web of Science][Medline]
Oppenheimer SM, Cechetto DF, Hachinski VC. Cerebrogenic cardiac arrhythmias: cerebral electrocardiographic influences and their role in sudden death. [Review]. Arch Neurol 1990; 47: 513–19.
Oppenheimer SM, Gelb A, Girvin JP, Hachinski VC. Cardiovascular effects of human insular cortex stimulation. Neurology 1992; 42: 1727–32.
Ossentjuk E, Elink Sterk CJ, Storm van Leeuwen W. Flicker-induced cardiac arrest in a patient with epilepsy. Electroencephalogr Clin Neurophysiol 1966; 20: 257–9.[Web of Science][Medline]
Phizackerley PJR, Poole EW, Whitty CWM. Sino-auricular heart block as an epileptic manifestation. Epilepsia (3rd series) 1954; 3: 89–91.
Pool JL, Ransohoff J. Autonomic effects on stimulating rostral portion of cingulate gyri in man. J Neurophysiol 1949; 12: 385–92.
Pritchett EL, McNamara JO, Gallagher JJ. Arrhythmogenic epilepsy: an hypothesis. Am Heart J 1980; 100: 683–8.[Web of Science][Medline]
Rabending G, Fisher W. Epileptic psychosis and nonconvulsive status epilepticus with ictal bradycardia and asystole. Psychiatr Neurol Med Psychol (Leipzig) 1986; 38: 184–8.
Radtke RA. Cardiac asystole: an epileptic arrhythmia? [abstract]. Epilepsia 1989; 30: 705–6.
Reeves AL, Nollet KE, Klass DW, Sharbrough FW, So EL. The ictal bradycardia syndrome. Epilepsia 1996; 37: 983–7.[Web of Science][Medline]
Rizzon P, Di Biase M, Favale S, Visani L. Class 1B agents lidocaine, mexiletine, tocainide, phenytoin. Eur Heart J 1987; 8 Suppl A: 21–5.
Russell AE. Cessation of the pulse during the onset of epileptic fits. Lancet 1906; 2: 152–4.
Saussu F, van Rijckevorsel K, de Barsy T. Bradycardia: an unrecognized complication of some epileptic crises. [French]. Rev Neurol (Paris) 1998; 154: 250–2.[Medline]
Schernthaner C, Lindinger G, Potzelberger K, Zeiler K, Baumgartner C. Autonomic epilepsy. The influence of epileptic discharges on heart rate and rhythm. Wien Klin Wochenschr 1999; 111: 392–401.[Web of Science][Medline]
Schraeder PL, Lathers CM. Paroxysmal autonomic dysfunction, epileptogenic activity and sudden death. [Review]. Epilepsy Res 1989; 3: 55–62.[Web of Science][Medline]
Sindrup E, Thygesen N, Kristensen O, Aving J. Zygomatic electrodes: their use and value in complex partial epilepsy. In: Dam M, Gram L, Penry JK, editors. Advances in epileptology. The XIIth Epilepsy International Symposium. New York: Raven Press; 1981. p. 313–18.
Smaje JC, Davidson C, Teasdale GM. Sino-atrial arrest due to temporal lobe epilepsy. J Neurol Neurosurg Psychiatry 1987; 50: 112–3.
Smith PE, Howell SJ, Owen L, Blumhardt LD. Profiles of instant heart rate during partial seizures. Electroencephalogr Clin Neurophysiol 1989; 72: 207–17.[Web of Science][Medline]
Timmings PL. Sudden unexpected death in epilepsy: is carbamazepine implicated? Seizure 1998; 7: 289–91.[Web of Science][Medline]
Van Buren JM. Some autonomic concomitants of ictal automatism. A study of temporal lobe attacks. Brain 1958; 81: 505–28.
Van Buren JM, Ajmone-Marsan C. A correlation of autonomic and EEG components in temporal lobe epilepsy. Arch Neurol 1960; 3: 683–703.
Van Buren JM, Bucknam CA, Pritchard WL. Autonomic representation in the human orbitotemporal cortex. Neurology 1961; 11: 214–24.
van Rijckevorsel K, Saussu F, de Barsy T. Bradycardia, an epileptic ictal manifestation. Seizure 1995; 4: 237–9.[Web of Science][Medline]
Volpi L, Rubboli G, Parmeggiani L, Passerelli D, Rizzi R, Vigevano F, et al. Falling seizures with bradycardia in hypothalamic hamartoma [abstract]. Epilepsia 1995; 36 Suppl 3: S266.
Wall DP, Davis GD. Three cerebral cortical systems affecting autonomic function. J Neurophysiol 1951; 14: 507–17.
Wannamaker BB. Autonomic nervous system and epilepsy. [Review]. Epilepsia 1985; 26 Suppl 1: S31–9.
Wilder-Smith E. Complete atrio-ventricular conduction block during complex partial seizure. J Neurol Neurosurg Psychiatry 1992; 55: 734–6.
Zamrini EY, Meador KJ, Loring DW, Nichols FT, Lee GP, Figueroa RE, et al. Unilateral cerebral inactivation produces differential left/right heart rate responses. Neurology 1990; 40: 1408–11.
Received November 29, 2000. Revised May 1, 2001. Accepted July 26, 2001.
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