Scholarly article on topic 'Ictal bradyarrhythmias and asystole requiring pacemaker implantation: Combined EEG–ECG analysis of 5 cases'

Ictal bradyarrhythmias and asystole requiring pacemaker implantation: Combined EEG–ECG analysis of 5 cases Academic research paper on "Clinical medicine"

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Epilepsy & Behavior
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{"Ictal asystole" / "Ictal arrhythmia" / "Temporal lobe epilepsy" / SUDEP}

Abstract of research paper on Clinical medicine, author of scientific article — Roisin Bartlam, Rajiv Mohanraj

Abstract Background Seizures can lead to cardiac arrhythmias by a number of mechanisms including activation/inhibition of cortical autonomic centers, increase in vagal tone through activation of brainstem reflex centers, and respiratory failure. Ictal asystole (IA) is a potential mechanism underlying sudden unexpected death in epilepsy (SUDEP). We analyzed the clinical features of 5 patients who developed IA requiring pacemaker implantation. Methods Patients with ictal arrhythmias were identified from the video-telemetry and ambulatory EEG database at Greater Manchester Neurosciences Centre, as well as an independent epilepsy residential care facility. Only those who had IA requiring pacemaker implantation were included in the analysis. A total of 5 patients were identified. Results Of the 5 patients with IA, 4 were female. All 5 patients had focal epilepsy, and four had temporal lobe epilepsy. Ictal asystole occurred with focal seizures with impairment of awareness. Seizure onset was left-sided in 2 patients, right-sided in one, left-sided onset with switch of lateralization in one, and nonlateralized in one patient. Three patients had hippocampal sclerosis, one of whom had undergone epilepsy surgery, one had traumatic encephalomalacia of the temporal lobe, and one patient had no lesions detected on MRI. Interictal epileptiform activity was more pronounced during sleep in all patients. Asystole occurred in association with sleep-related seizures in 4 of 5 patients. Conclusions Ictal asystole (IA) occurred in association with sleep-related seizures in 4 out of 5 cases, predominantly in patients with temporal lobe epilepsy. These findings may be of relevance to SUDEP.

Academic research paper on topic "Ictal bradyarrhythmias and asystole requiring pacemaker implantation: Combined EEG–ECG analysis of 5 cases"

Ictal bradyarrhythmias and asystole requiring pacemaker implantation: Combined EEG-ECG analysis of 5 cases

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Roisin Bartlam3, Rajiv Mohanraj

a University of Manchester, Manchester, UK

b Department of Neurology, Salford Royal NHS Foundation Trust, Salford M6 8HD, UK

ARTICLE INFO

Article history: Received 13 February 2016 Revised 23 June 2016 Accepted 24 June 2016 Available online 14 October 2016

Keywords: Ictal asystole Ictal arrhythmia Temporal lobe epilepsy SUDEP

ABSTRACT

Background: Seizures can lead to cardiac arrhythmias by a number of mechanisms including activation/inhibition of cortical autonomic centers, increase in vagal tone through activation of brainstem reflex centers, and respiratory failure. Ictal asystole (IA) is a potential mechanism underlying sudden unexpected death in epilepsy (SUDEP). We analyzed the clinical features of 5 patients who developed IA requiring pacemaker implantation. Methods: Patients with ictal arrhythmias were identified from the video-telemetry and ambulatory EEG database at Greater Manchester Neurosciences Centre, as well as an independent epilepsy residential care facility. Only those who had IA requiring pacemaker implantation were included in the analysis. A total of 5 patients were identified.

Results: Of the 5 patients with IA, 4 were female. All 5 patients had focal epilepsy, and four had temporal lobe epilepsy. Ictal asystole occurred with focal seizures with impairment of awareness. Seizure onset was left-sided in 2 patients, right-sided in one, left-sided onset with switch of lateralization in one, and nonlateralized in one patient. Three patients had hippocampal sclerosis, one of whom had undergone epilepsy surgery, one had traumatic encephalomalacia of the temporal lobe, and one patient had no lesions detected on MRI. Interictal epileptiform activity was more pronounced during sleep in all patients. Asystole occurred in association with sleep-related seizures in 4 of 5 patients.

Conclusions: Ictal asystole (IA) occurred in association with sleep-related seizures in 4 out of 5 cases, predominantly in patients with temporal lobe epilepsy. These findings may be of relevance to SUDEP.

© 2016 Elsevier Inc. All rights reserved.

1. Background

Alterations in cardiac rhythm are common during seizures, and tachycardia is seen in up to 64% of temporal lobe seizures [1]. Ictal bradyarrhythmias (IB), including ictal asystole (IA), are rare but potentially serious occurrences. Ictal asystole has been proposed as a possible mechanism behind sudden unexplained death in epilepsy (SUDEP) [2]. The pathophysiology of IA/IB remains unconfirmed, and three possible mechanisms have been postulated: 1) activation or inhibition of cortical autonomic centers, including the insula [3-5]; 2) increase in vagal tone through activation of autonomic reflex centers located in the brainstem [6]; and 3) secondary to respiratory failure precipitated by the seizure [6,7]. Antiepileptic drugs (AEDs) have also been suggested as potentially contributing to seizure-related cardiac dysfunction; the introduction of carbamazepine has been shown to slow atrioventricular conduction, relatively increase sympathetic tone, and suppress autonomic function [8,9].

* Corresponding author at: Department of Neurology, Salford Royal NHS Foundation Trust, Stott Lane, Salford M6 8HD, UK. Tel.: +44161 206 4626; fax: +44 161 206 2993. E-mail address: Rajiv.Mohanraj@srft.nhs.uk (R. Mohanraj).

Temporal lobe epilepsy (TLE) has been shown to be a consistent risk factor for IA/IB [1,7,10]. Previous studies have suggested possible correlations between seizure lateralization and IA. It is thought that the left temporal lobe influences parasympathetic cardiac control, while the right affects the sympathetic [11,12]. Although one study suggested that left hemisphere seizures were a risk factor for IA [10], others have reported cases of IA associated with right-sided seizures [7]. It is likely that there is no consistent relationship between IA and seizure lateralization.

Ictal asystole/ictal bradyarrhythmias (IA/IB) should be considered in those who present with unexplained atonia and physical falls during focal seizures and those whose seizure activity is associated with marked pallor [7,13]. Definitive diagnosis relies upon capturing an episode of IA/IB, either through combined EEG/ECG recording or through the use of an implantable loop recorder [3]. While the implications of IA/IB are not fully understood, it is linked with an increased likelihood of traumatic falls. Additionally, IA could be a potential mechanism of sudden unexplained death in epilepsy (SUDEP) [2], although one recent study has suggested that postictal asystole has greater implications for SUDEP than asystole during a seizure [14]. While there is no confirmed link between seizure-related asystole and SUDEP, there is a need for

http ://dx.doi.org/10.1016/j.yebeh.2016.06.026 1525-5050/© 2016 Elsevier Inc. All rights reserved.

greater understanding of [A, including its risk factors and the potential implications. We report five cases of [A/[B treated with implantation of permanent pacemaker, to identify possible risk factors for the [A/[B.

2. Methods

All patients (n = 5) with [A/[B confirmed by ambulatory EEG and video-telemetry monitoring were identified from the epilepsy monitoring unit at Greater Manchester Neurosciences Centre (GMNC) as well as an independent residential assessment center. Cases were identified from urgent cardiology consults sent from the epilepsy monitoring units. Clinical and demographic data were collected by review of patient records.

The following variables were examined: age at epilepsy onset, type of epilepsy, seizure type, MR[ abnormalities, antiepileptic medication used, interictal EEG changes, ictal EEG and ECG changes, seizure lateralization, sleep-related epileptiform activity, and symptoms. The clinical features that should increase suspicion of [A were identified from the common features of the 5 cases. We did not seek ethics committee approval for this retrospective review, as all data were collected as part of routine clinical care. All patients had consented at the time of video-telemetry for the recordings to be used for teaching research and publication.

3. Results

3.1. Demographics

Of the five patients with EEG-ECG-recorded [B, four were female. The mean age was 42.6 years (range from 21 to 62 years; Table 1). None of the patients were known to have cardiac disease.

3.2. Epilepsy history

All 5 patients had refractory focal epilepsy. Duration of epilepsy ranged from 6 years to 57 years. Four of the patients had a diagnosis of temporal lobe epilepsy, while patient 3 was thought to have focal extratemporal epilepsy. For all five patients, the main seizure type was focal seizures with altered consciousness. Patient 1 had epilepsy caused by traumatic brain injury, with brain MR[ scan demonstrating encephalomalacia in the left medial subfrontal lobe and left inferior temporal gyrus of the midtemporal lobe. Patient 2 had evidence of right mesial temporal sclerosis (MTS), and patients 4 and 5 had left MTS. Patient 5 had previously undergone left anterior temporal lobectomy. Brian MR[ was normal in patient 3. Antiepileptic drugs (AEDs) taken by the patients are summarized in Table 1. All patients except patient 1 were taking carbamazepine as part of their AED regimen.

3.3. Interictal EEG

[nterictally, bilateral temporal epileptiform activity was seen in patients 1, 2, and 3. Patient 1 demonstrated spikes and sharp waves with phase reversal in the anterior temporal regions, more frequently on the left. Patient 2 displayed intermittent slow wave activity of 6-8 Hz with sharpened appearance in the right anterior temporal region. Patient 3 had right hemispheric spike and slow wave activity, associated with runs of raised amplitude slow waves. Patient 4 demonstrated occasional slow wave activity of 3-7 Hz over the left frontotemporal region. Patient 5 had bursts of raised amplitude sharp wave activity at 6-7 Hz lasting for approximately 1 -4 s in the left anterior temporal region. All patients exhibited an increase in interictal epileptiform discharges during sleep.

3.4. Ictal recordings

Patient 1 had bradyarrhythmia identified during a clinical seizure on cardiac monitoring using implantable loop recorder and had a permanent pacemaker inserted, prior to ictal recording using ambulatory EEG. The patient had experienced nocturnal episodes of becoming confused, as well as falls prior to implantation of pacemaker. During ambulatory EEG, he reported a 'spinning sensation' but no loss of awareness or recall. The EEG showed rhythmic theta/delta discharge in the right anterior temporal region. This was associated with fall of heart rate from 78 to 40 bpm for 35 s, but pacemaker was not activated on this occasion.

Patient 2 had seizures arising from sleep. She opened her eyes, sat up, picked up her glasses, and after 20 s, slumped back and was unresponsive. The fall occurred prior to [A. The EEG showed rhythmic theta activity in the right anterior temporal region, followed by rhythmic theta/delta discharge over the left hemisphere. [ctal asystole developed approximately 11 s after seizure activity started in the left hemisphere and lasted 42 s. The EEG was of low amplitude for 30 s (Fig. 1).

Patient 3 also had seizures during stage 2 sleep. She sat up and exhibited flapping movements of the right hand. Her head turned to the left, and she rubbed the right side of the face with the left hand. This was followed by large amplitude proximal movements of the limbs. The patient then fell backwards, which occurred around the time of [A onset but may have preceded it. The EEG was obscured by movement artifact, and seizure lateralization was not possible. Episodes of asystole occurred towards the end of all five recorded seizures; the length of which ranged from 14 to 42 s.

Patient 4 woke from sleep and demonstrated chewing and sucking movements of the mouth, distortion of face and automatisms of the right hand, and scissoring movements of the legs. The EEG showed sharp waves and irregular delta activity, evolving in frequency up to 5 Hz in the left midposterior temporal region (T3 and T5), followed by

Fig. 1. An EEG/ECG recording demonstrating temporal lobe seizure associated with ictal asystole. Ictal EEG onset was seen over right anterior midtemporal region, in the form of rhythmic theta-delta activity. After 45 s, ictal rhythm stops on the right and, 3 s later, reappears over the left midtemporal region. A few nonpropagated p waves appear at the onset ofleft-sided EEG activity, and complete asystole develops after a further 12 s. Asystole lasted for 42 s.

Clinical and epidemiological details of 5 patients with ictal bradyarrhythmias. Patient AgeM/F MRI brain AEDs at time ofIA/IB IA during sleep-related seizure History of atonia or unexpected fall

1 60 M Left temporal encephalomalacia Sodium valproate, lamotrigine No Atonia

2 62 F Right mesial temporal sclerosis Levetiracetam, carbamazepine Yes Atonia

3 51 F Normal Carbamazepine Yes Fall

4 38 F Left mesial temporal sclerosis Carbamazepine, lamotrigine, topiramate Yes No

5 21 F Left mesial temporal sclerosis Carbamazepine Yes Fall

flattening of EEG at the time of IA. Slow wave activity on EEG resumed as cardiac activity recovered. There was initial bradycardia for 8 s, followed by IA at the end of the seizure, which lasted 21 s.

Patient 5 also had seizures arising from sleep. She opened her eyes, sat up, and shouted. She then started walking out of the room when IA occurred. There was tachycardia at seizure onset, followed by bradycardia leading to 29 s of IA. After 10 s of IA, she became atonic and fell. The EEG showed sharp wave activity in the left anterior regions, followed by generalized delta activity.

All patients underwent permanent pacemaker implantation. No patients reported falls after implantation of pacemaker, although focal seizures with impairment of awareness and/or recall continued to occur in all 5 patients. It was not possible to ascertain whether IA/IB without falls continued to occur during seizures, as timing of seizures was not routinely recorded during pacemaker checks. Data regarding pacemaker activation were only available for patient 1, who continued to have IB with seizures, with pacemaker activation in a proportion of episodes (Table 2).

4. Discussion

Ictal asystole (IA) is a rare but potentially serious phenomenon that should be considered in patients with focal seizures, who present with the red flag symptoms of atonia, unexpected falls, and extreme pallor. However, all cases of IA recorded in our patients occurred during nocturnal seizures. Descriptions of typical red flag symptoms may not be forthcoming in patients who have predominantly nocturnal events, and concomitant EEG/ECG monitoring is required to identify IA/IB. Previous studies have identified temporal lobe epilepsy as a risk factor for IA. In our series of 5 patients, 4 had TLE, with one patient having undergone left temporal lobectomy. Although one patient was described as having extratemporal focal epilepsy, semiology and interictal EEG were suggestive of involvement of the temporal lobe in the seizures. Some previous studies have suggested a link between the lateralization of seizure onset and incidence of IB, although the relationship is not consistent [15,16]. Two of our patients had seizure onset in the right

hemisphere and two in the left hemisphere; seizure onset was unclear in the fifth patient. Therefore, there was no clear link in this group of patients between lateralization of seizure onset and IA/IB.

The most striking finding in our study is the association of IA/IB with nocturnal seizures, with 4 out of 5 patients experiencing IA in association with seizures arising from sleep. These patients also exhibited an increase in interictal activity during sleep. Our series suggests a potential link between nocturnal epileptiform activity and IA. One previous study has suggested a link between sleep and rates of ictal tachyarrhythmias but did not specify whether IA/IB occurred [16]. As nocturnal seizures are also a known risk factor for SUDEP [9,12], further research into the possible connection between nocturnal epileptiform activity and the risk of IA is required.

All five patients within the case study had a cardiac pacemaker inserted after the first episode of IB. However, the risk of reoccurrence of IB has not been fully ascertained, and it has been suggested that there is little to be gained from pacemaker insertion [17]. Strzelczyk et al. have suggested that a cardiac pacemaker should be inserted for ictal IA/IB, only in patients who continue to have seizures in spite of optimal treatment with AEDs, and after consideration of epilepsy surgery [18].

Gastaut in his sentinel paper on EEG findings during syncope described a sequence of EEG changes starting with hypersynchronous slowing followed by EEG attenuation [19]. However, as opposed to patients suffering from vasovagal syncope, patients with IA have impairment of consciousness because of seizure rather than cerebral anoxia, and hypersynchronous EEG activity seen during IA is more likely to be due to ictal activity rather than cerebral anoxia. The EEG characteristics of IA are likely to be different to that of syncope, because of the differences in pathophysiology.

Our series adds to the reported cases of IA/IB in the literature and highlights the need for further examination of both the predictive factors of IA and the short- and long-term risks of IA/IB. As a small retrospective study, data presented have limitations. Cases were drawn from 2 epilepsy monitoring units where patients were admitted for a variety of reasons including diagnosis of recurrent spells, presurgical

Table 2

Interictal and ictal EEG and ECG changes seen in 5 patients with ictal bradyarrhythmias.

Patient Interictal EEG Nocturnal Hemisphere Semiology Ictal EEG ECG changes seen

increase involved in IED

1 Bilateral temporal sharp waves, Yes more frequent on the left

2 Sharpened slow wave activity Yes right temporal regions

Spike and slow wave activity, Yes right hemispheric

Intermittent rhythmic theta-delta activity over left anterior temporal region

Left anterior temporal sharp Yes waves

Right Right-left

Unclear Left

Vertiginous aura

Arousal ^ manual automatism ^ fall

Arousal ^ right hand automatisms ^ hypermotor

Arousal ^ orofacial, right hand automatism ^ bipedal automatism ^ fall

Arousal ^ vocalization ^ leaving behavior ^ fall

Rhythmic theta-delta right anterior temporal region for 28 s.

Rhythmic 5- to 6-Hz discharge right anterior temporal region for 2 s, followed by rhythmic 5-to 6-Hz activity over left anterior temporal region for 25 s. Then of low amplitude for 30 s. Possible generalized attenuation, EEG then obscured by movement artifact.

40 bpm for 35 s (from 78) 42 s, asystole

Asystole, 14-43 s

Rhythmic delta evolving into theta discharge left frontotemporal region with spikes over the left midposterior temporal region. EEG attenuates during asystole, postictal left sided slow. Slow wave activity in the theta/delta range, then 29 s, asystole 5 Hz sharp waves left frontal followed by generalized delta. EEG isoelectric during asystole.

Bradycardic for 8 s, asystole for 21 s

assessment, and cognitive impairment. Therefore, a precise denominator is not available to calculate incidence figures. In addition, our observation of nocturnal seizures being associated with IA/IB has not been tested in comparison with a control group. To our knowledge, no other case series have noted association of IA/IB with nocturnal seizures. While the association seen in this uncontrolled study may be spurious, the possible link between nocturnal epileptiform activity and the risk of IA/IB should be explored further, particularly given potential links to SUDEP.

Conflict of interest

The authors have no conflict of interest to declare.

References

[1 ] Marshall DW, Westmoreland BF, Sharbrough FW. Ictal tachycardia during temporal

lobe seizures. Mayo Clin Proc 1983;58:443-6. [2] Hirsch LK, Haurser WA. Can sudden unexplained death in epilepsy be prevented?

Lancet 2004;364:2157-8. [3 ] Volkow ND, Wang GJ, Fowler JS, Logan J, Gatley JS, Pappas NR, et al. Increased activity of the temporal insula in subjects with bradycardia. Life Sci 2000;67:2213-20.

[4] Schuele SU, Bermeo AC, Locatelli E, Burgess RC, Luders HO. Ictal asystole: a benign condition? Epilepsia 2008;49:168-71.

[5] Sevcencu C, Struijk JJ. Autonomic alterations and cardiac changes in epilepsy. Epilepsia 2010;51:725-37.

[6] So EL, Sam MC, Lagerlund DL. Postictal central apnea as a cause of SUDEP: evidence from near-SUDEP incident. Epilepsia 2000;41:1494-7.

[7] Schuele SU, Bermeo AC, Alexopoulos AV, Locatelli ER, Burgess RC, Dinner DS, et al. Video-electrographic and clinical features in patients with asystole. Neurology 2007;69:434-41.

[8] Tomson T, Kenneback G. Arrhythmia, heart rate variability, and antiepileptic drugs. Epilepsia 1997;11(Suppl. 38):S48-51.

[9] Isojarvi JI, Ansakorpi H, Suominen K, Tolonen U, Repo M, Myllylä VV. Interictal cardiovascular autonomic responses in patients with epilepsy. Epilepsia 1998;39: 420-6.

[10] Rugg-Gunn FJ, Simister RJ, Squirrell M, Holdright DR Duncan JS. Cardiac arrhythmias in focal epilepsy: a prospective long-term study. Lancet 2004;364:2212-9.

[11] Oppenheimer SM, Gelb A, Girvin JP, Hachinski VC. Cardiovascular effects of human insular cortex stimulation. Neurology 1992;42:1727-32.

[12] Oppenheimer SM, Martin WM, Kedem G. Left insular cortex lesions perturb cardiac autonomic tone. Clin Auton Res 1996;6:131-40.

[13] Britton JW, Benarroch E. Seizures and syncope: anatomic basis and diagnostic considerations. Clin Auton Res 2006;16:18-28.

[14] van der Lende M, Surges R, Sander JW, Thijs RD. Cardiac arrhythmias during or after epileptic seizures. J Neurol Neurosurg Psychiatry 2015;0:1-6.

[15] Tinuper P, Bisulli F, Cerullo A, et al. Ictal bradycardia in partial epileptic seizures: autonomic investigation in three cases and literature review. Brain 2001;124:2361-71.

[16] Chen W, Guo C-L, Zhang P-S, Liu C, Qiao H, Zhang JG, etal. Heart rate changes in partial seizures: analysis of influencing factors among refractory patients. BMC Neurol 2014;14:135.

[17] Schuele SU. Effects of seizures on cardiac function. Clin Neurophysiol 2009;26: 302-8.

[18] StrzelczykA,Cenusa M, BauerS,HamerHM, Mothersill IW, GrunwaldT, etal. Management and long-term outcome in patients presenting with ictal asystole or brady-cardia. Epilepsia 2011;52:1160-7.

[19] Gastaut H, Fischer Williams M. Electroencephalographic study of syncope; its differentiation from epilepsy. Lancet 1957;273:1018-25.