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Semiologic, electroencephalographic and electrocardiographic correlates of seizure-like manifestations caused by cardiac asystole
Seizure 29 (2015) 15–19
Contents lists available at ScienceDirect
Seizure journal homepage: www.elsevier.com/locate/yseiz
Short communication
Semiologic, electroencephalographic and electrocardiographic correlates of seizure-like manifestations caused by cardiac asystole Anvesh Jackson a, Simon Bower a, Udaya Seneviratne a,b,* a b
Department of Neuroscience, Monash Medical Centre, Clayton, Victoria, Australia Department of Medicine, Monash University, Melbourne, Victoria, Australia
A R T I C L E I N F O
A B S T R A C T
Article history: Received 17 December 2014 Received in revised form 9 February 2015 Accepted 25 February 2015
Purpose: Cardiac asystole is known to cause clinical manifestations mimicking seizures. The recognition of this uncommon phenomenon is important to expedite appropriate clinical intervention and avoid unnecessary morbidity as well as potential mortality. Methods: We retrospectively reviewed video-electroencephalographic (EEG) records from January 2008 to December 2013 for relevant cases. Results: We identified four patients who experienced nine events of asystole accompanied by seizurelike activity captured on video-EEG. None had evidence of epilepsy on video-EEG. Semiological features of captured clinical events included aura, automatisms, generalized tonic activity and focal as well as generalized myoclonus. No patient had generalized tonic-clonic seizures. A peculiar rapid breathing pattern was seen preceding the onset of asystole. General pallor was observed during asystole, followed by flushing on recovery. Seizure-like semiology was observed in three stages; pre-asystole, during asystole and after resumption of cardiac rhythm. The EEG demonstrated generalized slowing followed by generalized suppression during asystole and generalized slowing again on resumption of sinus rhythm (‘‘slow-flat-slow’’ pattern). All patients had dual-chamber pacemakers implanted. On follow-up, they have remained symptom-free without antiepileptic medications. Conclusions: Cardiac asystole can be associated with features closely mimicking seizures. Recurrent episodes of cardiac asystole can be stereotypical in a given patient. There are some diagnostic clues in semiology. Crown Copyright ß 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Keywords: Anoxic seizures Convulsion Syncope EEG ECG
1. Introduction Determining the etiology of recurrent episodes of loss of consciousness (LOC) is a common clinical problem faced by neurologists. The differential diagnoses range from cardiac arrhythmias, syncope and psychogenic non-epileptic seizures to epileptic seizures; all of which require prompt and accurate diagnosis and treatment. This assessment becomes complicated as there is considerable semiological similarities and occasional interplay among these diagnoses. For instance, cardiac arrhythmias may be precipitated by seizures [1]. Furthermore, seizurelike activity may occur during syncope [2–10]. This case series
* Corresponding author at: Department of Neuroscience, Monash Medical Centre, 246 Clayton Rd, Clayton, Melbourne, Victoria 3168, Australia. Tel.: +61 03 9594 6666; fax: +61 03 9594 6241. E-mail addresses: [email protected] (A. Jackson), [email protected] (S. Bower), [email protected] (U. Seneviratne).
highlights the clinical importance of seizure-like activity related to cardiac asystole (SRCA). Additionally, we detail the timeline and interrelationship among electrocardiographic (ECG), EEG and clinical phenomena (Fig. 1, Supplementary Table 1, Video 1, Video 2).
2. Methods Medical records of all patients admitted for inpatient video-EEG monitoring at Monash Medical Center, Melbourne, Australia between January 2008 and December 2013 were reviewed retrospectively to identify those who had seizure-like events related to asystole. The demographic information, clinical details and investigations were collated from medical records. VideoEEGs were analyzed in detail by the same investigator (US) to ascertain the relationships among semiology, EEG and ECG. This study was approved by the Monash Health Human Research Ethics Committee.
http://dx.doi.org/10.1016/j.seizure.2015.02.029 1059-1311/Crown Copyright ß 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
16
A. Jackson et al. / Seizure 29 (2015) 15–19
Fig. 1. Interrelationship among ECG, EEG and semiology. (a) Electroencephalography and electrocardiography changes during asystole. This figure represents a single page of the video-electroencephalogram (EEG) recording of case 3, incorporating a single-channel electrocardiogram (ECG), corresponding to 120 s (time-base compressed to 120 s/ page). The EEG demonstrates ‘slow’ and ‘flat’ phases during cardiac asystole, followed by the second ‘slow’ phase after resumption of cardiac sinus rhythm. Myoclonic jerks (MJ) occur during asystole and after resumption of sinus rhythm. Tonic posturing (TONIC) occurs during asystole and note the tonic muscle artifact captured on the ECG channel. Reproduced with permission from the publisher (Xu et al. [8]). (b) Relationship among electrocardiogram, electroencephalogram and semiology of seizure-like activity related to cardiac asystole. This figure illustrates the evolution of semiology and EEG before, during and after asystole. Note the three phases of seizure-like activity (aura-myoclonus/tonic-myoclonus), EEG (slow-flat-slow) and ECG (pre-asystole, asystole, post-asystole).
3. Results From a total of 252 patients, four were identified who had nine typical clinical events captured on video-EEG. Two cases (cases 3 and 4) have been previously published [8]. 3.1. Case 1 A 69-year-old woman presented with four LOC episodes over 6 months. She described feeling light-headed before losing consciousness. During these episodes, she looked dazed and pale with her head slumped. She was unresponsive for a minute or two before complete recovery with no postictal symptoms. Whilst unconscious, though usually flaccid, she occasionally experienced right hand twitching. Her examination and cardiac investigations were normal (Table 1). The video-EEG captured facial grimacing, rapid breathing and pallor with generalized EEG slowing during the second half of the 29 second bradycardia phase. During asystole, the EEG illustrated generalized suppression accompanied by myoclonic activity of the right upper limb. With circulatory recovery, the EEG transitioned from a ‘flat’ waveform to generalized slowing and finally normal alpha rhythm (Table 1 and Supplementary Table 1). A dual-chamber permanent pacemaker (PPM) was implanted with no further events at 2-year follow-up. 3.2. Case 2 A 47-year-old man presented with LOC episodes since childhood. These episodes were preceded by light-headedness and lasted seconds before recovery with a mild headache. His wife
described him looking pale during unresponsive periods accompanied by jerky movements of his arms at the end. These episodes were diagnosed as epileptic seizures and treated with sodium valproate. His clinical examination and cardiac investigations were normal (Table 1). During video-EEG monitoring, he experienced an aura of light-headedness during sinus bradycardia. The transition to asystole coincided with generalized EEG slowing, followed by flattening. Semiologically, the asystole phase was characterized by rapid breathing and generalized tonic posturing. Upon sinus rhythm resumption, upper body myoclonus was observed. A dualchamber PPM was implanted and sodium valproate was ceased. He has not experienced any episodes of LOC for 2 years on follow-up. 3.3. Case 3 A 26-year-old female presented with eight LOC events over 7 years. She described a ‘butterfly sensation in her chest,’ heart ‘skipping a beat’ and occasional epigastric sensation (auras) that marked the onset of her LOC. This lasted a few seconds before transforming into generalized stiffening and some jerking of limbs associated with lateral tongue biting and urinary incontinence. These episodes were diagnosed as epileptic seizures and treated with lamotrigine. Her clinical examinations and cardiac investigations were normal (Table 1). During video-EEG, whilst her ECG and EEG were normal, the patient experienced an aura. The following bradycardia and asystole phases were associated with rapid breathing and eyes rolling back. Generalized EEG slowing occurred at the commencement of asystole. EEG flattening appeared at the conclusion of asystole and coincided with tonic posturing and myoclonic jerks. Myoclonic jerks were again witnessed with
A. Jackson et al. / Seizure 29 (2015) 15–19
17
Table 1 Comparison and summary of electroencephalography and semiology findings in patients with cardiac asystole reported in the literature. Case
Ref.
Sex
Age
Freq.
AL (s)
Aura
Semiology Sinus bradycardia
Asystole
Circulatory recovery
Video-EEG findings
Cause of asystole
Investigations performed
Irregular slow activity with increasing amplitude and decreasing frequency ‘‘Slow-flatslow’’ pattern
N/A
ECG; EEG
N/A
1
[2]
M
17
N/A
12–15
N/A
N/A
N/A
Tonic extension
2
[3]
M
46
9 over 2 months
28
Ticking sensation in chest
N/A
Tonic extension of arms, headslumping
N/A
3
[3]
F
29
1 every 1–3 years since adulthood
24
N/A
Restless, headslumping
Clonic jerks
‘‘Slow-flatslow’’ pattern
N/A
4
[3]
F
26
1 every 2–3 months since age 17
19
Epigastric sensation, burning electric wire smell Non-specified aura
N/A
Looked downwards, arms motionless
Clonic jerks
‘‘Slow-flatslow’’ pattern
N/A
5
[4]
F
9
10 over 6 years
N/A
N/A
N/A
N/A
N/A
Diffuse delta activity
6
[4]
F
17
9 over 5 years
N/A
N/A
N/A
N/A
N/A
7
[4]
M
13
10 over 12 years
N/A
N/A
N/A
N/A
N/A
Cardioinhibitory reflex syncope
Blood counts; ECG; awake, sleep and video EEG; tilttesting; MRIB
8
[4]
F
10
7 over 4 years
N/A
N/A
N/A
N/A
N/A
Diffuse delta activity followed by generalized suppression Diffuse delta activity followed by generalized suppression Diffuse delta activity
Cardioinhibitory reflex syncope Cardioinhibitory reflex syncope
Blood counts, ECG, routine and videoEEG, MRIB, carotid doppler, TTE, stress test, tilt-testing Blood counts, ECG, routine and videoEEG, MRIB, carotid doppler, TTE, tilttesting Blood counts, ECG, routine and videoEEG, MRIB, carotid doppler, TTE, stress test, tilt-testing Blood counts; ECG; awake, sleep and video EEG; tilttesting; MRIB Blood counts; ECG; awake, sleep and video EEG; tilttesting; MRIB
9
[5]
F
N/A
N/A
N/A
N/A
N/A
Tonic extension
Generalized suppression
Blood counts; ECG; awake, sleep and video EEG; tilttesting; MRIB N/A
10
[5]
F
N/A
N/A
N/A
N/A
N/A
Tonic extension
Generalized slowing
N/A
N/A
11 12
[5] [6]
M M
N/A 52
N/A 28
N/A Epigastric sensation
N/A N/A
N/A N/A
N/A Generalized slowing
N/A N/A
N/A ECG; awake, sleep and video-EEG; MRIB
13
[7]
F
22
N/A Multiple episodes over 1.5 years 4 over 3 years
Prolonged expiratory grunting Prolonged expiratory grunting N/A N/A
Cardioinhibitory reflex syncope N/A
2–7
Nausea, lightheadedness
N/A
N/A
N/A
N/A
ECG; video-EEG; tilt-testing; MRIB
14
[10]
a
a
a
a
N/A
Pallor, sweating
Pallor, head drops, fall, tonic spasm
Cyanosis, clonic jerk
‘‘Slow-flatslow’’ pattern
15
CP-1
F
69
4 over 6 months
15
Lightheadedness
Pallor, rapid breathing
Rapid breathing, myoclonus
No movements
‘‘Slow-flatslow’’ pattern
16
CP-2
M
47
Multiple episodes since childhood
12–16
Lightheadedness
Lightheadedness
Rapid breathing, tonic extension
Myoclonus
‘‘Slow-flatslow’’ pattern
Cardioinhibitory reflex syncope Cardioinhibitory reflex syncope Cardiac syncope (sinus node disease) Cardiac syncope (sinus node disease)
ECG; EEG; electrodermograms
Blood counts, 24 hECG, routine and video-EEG, TTE, MRIB, tilt-table test Blood counts, 24 hr-ECG, routine and video-EEG, TTE, tilt-table test, MRIB
A. Jackson et al. / Seizure 29 (2015) 15–19
18 Table 1 (Continued ) Case
Ref.
Sex
Age
Freq.
AL (s)
17
CP-3
F
26
8 over 7 years
45
18
CP-4
M
75
Multiple episodes over 5 years
27–31
Aura
Chest sensation, epigastric sensation, heart ‘ skipping a beat’ Nausea, head sensation
Semiology
Video-EEG findings
Cause of asystole
Investigations performed
Sinus bradycardia
Asystole
Circulatory recovery
Rapid breathing
Tachypnea, tonic extension, myoclonus
Flushing, myoclonus
‘‘Slow-flatslow’’ pattern
Cardioinhibitory reflex syncope
Blood counts, 24 hECG, routine and video-EEG, TTE, MRIB, tilt-table test
Pallor, rapid breathing, oral automatisms
Tonic extension, myoclonus
Flushing, tonic extension, myoclonus
‘‘Slow-flatslow’’ pattern
Cardioinhibitory reflex syncope or cardiac syncope
Blood counts, ECG, routine and videoEEG, TTE, tilt-table test, MRIB
Cardiologic investigations were within normal limits within the current paper’s cohort of patients (cases 15–18). Abbreviations: AL: asystole length measured in seconds; CP: current paper; ECG: electrocardiography; EEG: electroencephalography; F: female; Freq.: frequency of events; M: male; MRIB: magnetic resonance imaging of the brain; Ref., reference number; TTE: transthoracic echocardiogram; a: Gastaut [9] reported 71 cases of both sexes with cardiac asystole induced by ocular compression.
resumption of normal sinus rhythm and generalized slowing on EEG. A dual-chamber PPM was implanted and lamotrigine was ceased. On 3-year follow-up, she has remained asymptomatic. 3.4. Case 4 A 75-year-old man presented with a 5-year history of recurrent LOC and convulsions mostly in sleep and occasionally when awake. The events started with nausea and a strange sensation in his head followed by LOC and jerking of limbs. The events were diagnosed as epileptic seizures and several antiepileptic drugs were trialed. His clinical examination and cardiac investigations were normal (Table 1). The video-EEG captured five episodes of asystole – two whilst awake and three in light-sleep. He demonstrated oral automatisms (chewing) as cardiac rhythm transitioned from normal sinus rhythm to sinus bradycardia. The EEG was normal at this time. During asystole, the EEG transitioned from generalized slowing to generalized suppression. Early asystole coincided with pallor. Tonic posturing developed during asystole accompanied by EEG flattening. Flushing was seen with circulatory recovery. Furthermore, as the EEG transitioned back to slow waveforms, fast asymmetric myoclonic activity was noted. Recovery occurred with resumption of sinus rhythm on ECG and alpha rhythm on EEG (Videos 1 and 2). The patient underwent dual-chamber PPM insertion and has been symptom free for 6 years on follow-up.
4. Discussion We present four patients presenting with LOC and seizure-like semiology due to cardiac asystole. All episodes occurred in the supine position during video-EEG monitoring. Three patients had been treated with anti-epileptics prior to establishing the diagnosis of SRCA. No patient displayed signs of epilepsy during video-EEG monitoring. The semiology was characterized by an ‘aura’ (prior to asystole) followed by generalized tonic activity and myoclonus (during asystole) as well as a second phase of myoclonus (during cardiac rhythm resumption) (Fig. 1). Our study demonstrates that seizure-like semiology occurs in three phases; pre-asystole, during asystole (cerebral hypoperfusion), and immediately following cardiac rhythm resumption (cerebral reperfusion). A typical ‘‘slow-flat-slow’’ EEG pattern was observed, coinciding closely with the transitioning of ECG from sinus bradycardia, asystole and back to sinus bradycardia.
Table 1 summarizes cases of SRCA published to date. In our series of patients presenting with SRCA, typical signs and ‘auras’ preceding LOC included pallor, light-headedness and funny sensation in the chest. Often described as epileptic phenomena, auras are not uncommon in patients with SRCA [3,5–8]. Our observations are consistent with other reports suggesting that if present, auras occur prior to asystole [6–8]. An unidentified autonomic mechanism may be responsible for this phenomenon. During bradycardia and early asystole, three patients developed a peculiar rapid breathing pattern. A generalized pallor was also observed at the onset of sinus bradycardia, presumably related to hypoperfusion. This pallor extended through asystole until cardiac rhythm recommenced. The periods of asystole and EEG flattening coincided with tonic posturing and myoclonus. Flushing occurred with circulatory recovery. This period of cerebral reperfusion corresponded with repeated myoclonus concordant with previous reports [3,8]. One patient had five events of asystole displaying stereotypical semiology. Generalized EEG slowing was observed during sinus bradycardia and early asystole, a relatively consistent finding amongst other reports [3,4,6,8–10]. Subsequent EEG flattening was associated with generalized and sustained tonic activity. This seizurelike semiology was not associated with any epileptiform discharges. Furthermore, there was no rhythmic tonic-clonic phase as typically seen in true generalized tonic-clonic epileptic seizures. Following circulatory recovery, generalized EEG slowing was observed. During this second ‘‘slow’’ phase, myoclonic jerks were seen. Consistent with our observations, previous studies have reported minimal or absent post-ictal symptoms [2,3,8]. This ‘‘slow-flat-slow’’ EEG pattern was first described by Gastaut during asystole episodes lasting more than 13 s in a group of individuals with syncope induced by ocular compression [9,10]. In Gastaut’s observations, patients with asystole lasting less than 6 s had no clinical or EEG abnormalities, whereas cardiac arrest lasting between 7 and 13 s was accompanied by EEG slowwaves and variable disturbances of consciousness [9,10]. The underlying pathophysiology of seizure-like activity is thought to be related to the inhibitory actions of hypoxia in the telencephalon and other cortical structures [10]. This inhibition results in unopposed action of the subcortical structures, in particular the brainstem reticular formation, resulting in sustained tonic contractions [10]. The release of cortical inhibition coincides with spontaneous recovery of cardiac electrical activity and reemergence of theta and delta waves on EEG [10]. We postulate that
A. Jackson et al. / Seizure 29 (2015) 15–19
myoclonus during cerebral reperfusion may be related to impaired cerebral auto-regulation as described in cerebral hyperperfusion syndrome [11,12]. Syncope is classified into three major groups: reflex (neurally mediated), cardiac and due to orthostatic hypotension [13]. Based on pathophysiology, reflex syncope can be classified as ‘‘vasodepressive’’ characterized by blood pressure drop and ‘‘cardioinhibitory’’ characterized by bradycardia and asystole in severe cases [14]. Clinically, certain features may help determine the cause of syncope. Long history, presence of triggering factors, precipitation by prolonged standing and exertion usually points to neurally mediated syncope. Syncope due to orthostatic hypotension is usually posture-related. History of structural heart disease, family history of sudden death and occurrence during exertion or supine posture usually indicates cardiac syncope [13]. However, we have found in our series that regardless the etiology of asystole (cardio-inhibitory reflex syncope or cardiac syncope), the semiology of clinical events tends to be similar. We acknowledge some study limitations. This is a retrospective cohort and patients were not subjected to intra-cardiac electrophysiological studies. Some semiological features may not have been included due to small sample size. Loss of body tone was not commented upon as it was difficult to delineate by observing videos. Only nine events from four patients are described due to rarity of this phenomenon in the video-EEG setting. Nonetheless, this is the largest series of spontaneously occurring asystole with a detailed analysis of EEG, ECG and semiologic correlations highlighting clinical clues for early diagnosis. 5. Conclusion Our study demonstrates that cardiac asystole can be associated with clinical manifestations including aura, automatisms, tonic activity and myoclonus; semiology that may lead to misdiagnosis as epileptic seizures resulting in inappropriate antiepileptic therapy. Recurrent episodes of cardiac asystole can be stereotypical in a given patient, thereby further hampering the differential diagnosis between epileptic seizures and cardiac syncope. Clinically, early pallor and rapid breathing followed by flushing are useful in recognizing SRCA. Generalized tonic-clonic activity is conspicuous by its absence. The seizure-like semiology occurs in
19
three phases; pre-asystole, during asystole and post-asystole. The EEG demonstrates typical ‘‘slow-flat-slow’’ pattern with no epileptiform abnormalities. Pacemaker implantation resolves symptoms. Conflict of interest The authors have no conflicts of interest related to this paper. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.seizure.2015.02.029. References [1] Jallon P. Arrhythmogenic seizures. Epilepsia 1997;38(Suppl. 11):S43–7. [2] Andriola M. Pseudo-seizures secondary to cardiac asystole and apnea. Electroencephalogr Clin Neurophysiol 1983;56:7P. [3] Venkataraman V, Wheless JW, Willmore LJ, Motookal H. Idiopathic cardiac asystole presenting as an intractable adult onset partial seizure disorder. Seizure 2001;10:359–64. ¨ zyu¨rek R. Syncope or seizure? The [4] Yilmaz S, Go¨kben S, Levent E, Serdarog˘lu G, O diagnostic value of synchronous tilt testing and video-EEG monitoring in children with transient loss of consciousness. Epilepsy Behav 2012;24:93–6. [5] Stephenson JB. Anoxic seizures: self-terminating syncopes. Epileptic Disord 2001;3:3–6. [6] Ficker DM, Cascino GD, Clements IP. Cardiac asystole masquerading as temporal lobe epilepsy. Mayo Clin Proc 1998;73:784–6. [7] Loesch AM, Becker A, Noachtar S. Syncope: there is more than haemodynamic failure. BMJ Case Rep 2013. http://dx.doi.org/10.1136/bcr-2013-010347. pii:bcr2013010347. [8] Xu Z, Bower S, Seneviratne U. Severe cardioinhibitory vasovagal syncope in sleep and supine posture. Epileptic Disord 2014;16:101–6. [9] Gastaut H. Syncope and seizure. Electroencephalogr Clin Neurophysiol 1958;10:571–2. [10] Gastaut H, Fischer-Williams M. Electro-encephalographic study of syncope; its differentiation from epilepsy. Lancet 1957;273:1018–25. [11] van Mook WN, Rennenberg RJ, Schurink GW, van Oostenbrugge RJ, Mess WH, Hofman PA, et al. Cerebral hyperperfusion syndrome. Lancet Neurol 2005;4:877–88. [12] Adhiyaman Y, Alexander S. Cerebral hyperperfusion syndrome following carotid endarterectomy. QJM 2007;100:239–44. [13] Moya A, Sutton R, Ammirati F, Blanc JJ, Brignole M, Dahm JB. Guidelines for the diagnosis and management of syncope (version 2009). Eur Heart J 2009;30:2631–71. [14] van Dijk JG, Thijs RD, Benditt DG, Wieling W. A guide to disorders causing transient loss of consciousness: focus on syncope. Nat Rev Neurol 2009;5:438–48.
Contents lists available at ScienceDirect
Seizure journal homepage: www.elsevier.com/locate/yseiz
Short communication
Semiologic, electroencephalographic and electrocardiographic correlates of seizure-like manifestations caused by cardiac asystole Anvesh Jackson a, Simon Bower a, Udaya Seneviratne a,b,* a b
Department of Neuroscience, Monash Medical Centre, Clayton, Victoria, Australia Department of Medicine, Monash University, Melbourne, Victoria, Australia
A R T I C L E I N F O
A B S T R A C T
Article history: Received 17 December 2014 Received in revised form 9 February 2015 Accepted 25 February 2015
Purpose: Cardiac asystole is known to cause clinical manifestations mimicking seizures. The recognition of this uncommon phenomenon is important to expedite appropriate clinical intervention and avoid unnecessary morbidity as well as potential mortality. Methods: We retrospectively reviewed video-electroencephalographic (EEG) records from January 2008 to December 2013 for relevant cases. Results: We identified four patients who experienced nine events of asystole accompanied by seizurelike activity captured on video-EEG. None had evidence of epilepsy on video-EEG. Semiological features of captured clinical events included aura, automatisms, generalized tonic activity and focal as well as generalized myoclonus. No patient had generalized tonic-clonic seizures. A peculiar rapid breathing pattern was seen preceding the onset of asystole. General pallor was observed during asystole, followed by flushing on recovery. Seizure-like semiology was observed in three stages; pre-asystole, during asystole and after resumption of cardiac rhythm. The EEG demonstrated generalized slowing followed by generalized suppression during asystole and generalized slowing again on resumption of sinus rhythm (‘‘slow-flat-slow’’ pattern). All patients had dual-chamber pacemakers implanted. On follow-up, they have remained symptom-free without antiepileptic medications. Conclusions: Cardiac asystole can be associated with features closely mimicking seizures. Recurrent episodes of cardiac asystole can be stereotypical in a given patient. There are some diagnostic clues in semiology. Crown Copyright ß 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Keywords: Anoxic seizures Convulsion Syncope EEG ECG
1. Introduction Determining the etiology of recurrent episodes of loss of consciousness (LOC) is a common clinical problem faced by neurologists. The differential diagnoses range from cardiac arrhythmias, syncope and psychogenic non-epileptic seizures to epileptic seizures; all of which require prompt and accurate diagnosis and treatment. This assessment becomes complicated as there is considerable semiological similarities and occasional interplay among these diagnoses. For instance, cardiac arrhythmias may be precipitated by seizures [1]. Furthermore, seizurelike activity may occur during syncope [2–10]. This case series
* Corresponding author at: Department of Neuroscience, Monash Medical Centre, 246 Clayton Rd, Clayton, Melbourne, Victoria 3168, Australia. Tel.: +61 03 9594 6666; fax: +61 03 9594 6241. E-mail addresses: [email protected] (A. Jackson), [email protected] (S. Bower), [email protected] (U. Seneviratne).
highlights the clinical importance of seizure-like activity related to cardiac asystole (SRCA). Additionally, we detail the timeline and interrelationship among electrocardiographic (ECG), EEG and clinical phenomena (Fig. 1, Supplementary Table 1, Video 1, Video 2).
2. Methods Medical records of all patients admitted for inpatient video-EEG monitoring at Monash Medical Center, Melbourne, Australia between January 2008 and December 2013 were reviewed retrospectively to identify those who had seizure-like events related to asystole. The demographic information, clinical details and investigations were collated from medical records. VideoEEGs were analyzed in detail by the same investigator (US) to ascertain the relationships among semiology, EEG and ECG. This study was approved by the Monash Health Human Research Ethics Committee.
http://dx.doi.org/10.1016/j.seizure.2015.02.029 1059-1311/Crown Copyright ß 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
16
A. Jackson et al. / Seizure 29 (2015) 15–19
Fig. 1. Interrelationship among ECG, EEG and semiology. (a) Electroencephalography and electrocardiography changes during asystole. This figure represents a single page of the video-electroencephalogram (EEG) recording of case 3, incorporating a single-channel electrocardiogram (ECG), corresponding to 120 s (time-base compressed to 120 s/ page). The EEG demonstrates ‘slow’ and ‘flat’ phases during cardiac asystole, followed by the second ‘slow’ phase after resumption of cardiac sinus rhythm. Myoclonic jerks (MJ) occur during asystole and after resumption of sinus rhythm. Tonic posturing (TONIC) occurs during asystole and note the tonic muscle artifact captured on the ECG channel. Reproduced with permission from the publisher (Xu et al. [8]). (b) Relationship among electrocardiogram, electroencephalogram and semiology of seizure-like activity related to cardiac asystole. This figure illustrates the evolution of semiology and EEG before, during and after asystole. Note the three phases of seizure-like activity (aura-myoclonus/tonic-myoclonus), EEG (slow-flat-slow) and ECG (pre-asystole, asystole, post-asystole).
3. Results From a total of 252 patients, four were identified who had nine typical clinical events captured on video-EEG. Two cases (cases 3 and 4) have been previously published [8]. 3.1. Case 1 A 69-year-old woman presented with four LOC episodes over 6 months. She described feeling light-headed before losing consciousness. During these episodes, she looked dazed and pale with her head slumped. She was unresponsive for a minute or two before complete recovery with no postictal symptoms. Whilst unconscious, though usually flaccid, she occasionally experienced right hand twitching. Her examination and cardiac investigations were normal (Table 1). The video-EEG captured facial grimacing, rapid breathing and pallor with generalized EEG slowing during the second half of the 29 second bradycardia phase. During asystole, the EEG illustrated generalized suppression accompanied by myoclonic activity of the right upper limb. With circulatory recovery, the EEG transitioned from a ‘flat’ waveform to generalized slowing and finally normal alpha rhythm (Table 1 and Supplementary Table 1). A dual-chamber permanent pacemaker (PPM) was implanted with no further events at 2-year follow-up. 3.2. Case 2 A 47-year-old man presented with LOC episodes since childhood. These episodes were preceded by light-headedness and lasted seconds before recovery with a mild headache. His wife
described him looking pale during unresponsive periods accompanied by jerky movements of his arms at the end. These episodes were diagnosed as epileptic seizures and treated with sodium valproate. His clinical examination and cardiac investigations were normal (Table 1). During video-EEG monitoring, he experienced an aura of light-headedness during sinus bradycardia. The transition to asystole coincided with generalized EEG slowing, followed by flattening. Semiologically, the asystole phase was characterized by rapid breathing and generalized tonic posturing. Upon sinus rhythm resumption, upper body myoclonus was observed. A dualchamber PPM was implanted and sodium valproate was ceased. He has not experienced any episodes of LOC for 2 years on follow-up. 3.3. Case 3 A 26-year-old female presented with eight LOC events over 7 years. She described a ‘butterfly sensation in her chest,’ heart ‘skipping a beat’ and occasional epigastric sensation (auras) that marked the onset of her LOC. This lasted a few seconds before transforming into generalized stiffening and some jerking of limbs associated with lateral tongue biting and urinary incontinence. These episodes were diagnosed as epileptic seizures and treated with lamotrigine. Her clinical examinations and cardiac investigations were normal (Table 1). During video-EEG, whilst her ECG and EEG were normal, the patient experienced an aura. The following bradycardia and asystole phases were associated with rapid breathing and eyes rolling back. Generalized EEG slowing occurred at the commencement of asystole. EEG flattening appeared at the conclusion of asystole and coincided with tonic posturing and myoclonic jerks. Myoclonic jerks were again witnessed with
A. Jackson et al. / Seizure 29 (2015) 15–19
17
Table 1 Comparison and summary of electroencephalography and semiology findings in patients with cardiac asystole reported in the literature. Case
Ref.
Sex
Age
Freq.
AL (s)
Aura
Semiology Sinus bradycardia
Asystole
Circulatory recovery
Video-EEG findings
Cause of asystole
Investigations performed
Irregular slow activity with increasing amplitude and decreasing frequency ‘‘Slow-flatslow’’ pattern
N/A
ECG; EEG
N/A
1
[2]
M
17
N/A
12–15
N/A
N/A
N/A
Tonic extension
2
[3]
M
46
9 over 2 months
28
Ticking sensation in chest
N/A
Tonic extension of arms, headslumping
N/A
3
[3]
F
29
1 every 1–3 years since adulthood
24
N/A
Restless, headslumping
Clonic jerks
‘‘Slow-flatslow’’ pattern
N/A
4
[3]
F
26
1 every 2–3 months since age 17
19
Epigastric sensation, burning electric wire smell Non-specified aura
N/A
Looked downwards, arms motionless
Clonic jerks
‘‘Slow-flatslow’’ pattern
N/A
5
[4]
F
9
10 over 6 years
N/A
N/A
N/A
N/A
N/A
Diffuse delta activity
6
[4]
F
17
9 over 5 years
N/A
N/A
N/A
N/A
N/A
7
[4]
M
13
10 over 12 years
N/A
N/A
N/A
N/A
N/A
Cardioinhibitory reflex syncope
Blood counts; ECG; awake, sleep and video EEG; tilttesting; MRIB
8
[4]
F
10
7 over 4 years
N/A
N/A
N/A
N/A
N/A
Diffuse delta activity followed by generalized suppression Diffuse delta activity followed by generalized suppression Diffuse delta activity
Cardioinhibitory reflex syncope Cardioinhibitory reflex syncope
Blood counts, ECG, routine and videoEEG, MRIB, carotid doppler, TTE, stress test, tilt-testing Blood counts, ECG, routine and videoEEG, MRIB, carotid doppler, TTE, tilttesting Blood counts, ECG, routine and videoEEG, MRIB, carotid doppler, TTE, stress test, tilt-testing Blood counts; ECG; awake, sleep and video EEG; tilttesting; MRIB Blood counts; ECG; awake, sleep and video EEG; tilttesting; MRIB
9
[5]
F
N/A
N/A
N/A
N/A
N/A
Tonic extension
Generalized suppression
Blood counts; ECG; awake, sleep and video EEG; tilttesting; MRIB N/A
10
[5]
F
N/A
N/A
N/A
N/A
N/A
Tonic extension
Generalized slowing
N/A
N/A
11 12
[5] [6]
M M
N/A 52
N/A 28
N/A Epigastric sensation
N/A N/A
N/A N/A
N/A Generalized slowing
N/A N/A
N/A ECG; awake, sleep and video-EEG; MRIB
13
[7]
F
22
N/A Multiple episodes over 1.5 years 4 over 3 years
Prolonged expiratory grunting Prolonged expiratory grunting N/A N/A
Cardioinhibitory reflex syncope N/A
2–7
Nausea, lightheadedness
N/A
N/A
N/A
N/A
ECG; video-EEG; tilt-testing; MRIB
14
[10]
a
a
a
a
N/A
Pallor, sweating
Pallor, head drops, fall, tonic spasm
Cyanosis, clonic jerk
‘‘Slow-flatslow’’ pattern
15
CP-1
F
69
4 over 6 months
15
Lightheadedness
Pallor, rapid breathing
Rapid breathing, myoclonus
No movements
‘‘Slow-flatslow’’ pattern
16
CP-2
M
47
Multiple episodes since childhood
12–16
Lightheadedness
Lightheadedness
Rapid breathing, tonic extension
Myoclonus
‘‘Slow-flatslow’’ pattern
Cardioinhibitory reflex syncope Cardioinhibitory reflex syncope Cardiac syncope (sinus node disease) Cardiac syncope (sinus node disease)
ECG; EEG; electrodermograms
Blood counts, 24 hECG, routine and video-EEG, TTE, MRIB, tilt-table test Blood counts, 24 hr-ECG, routine and video-EEG, TTE, tilt-table test, MRIB
A. Jackson et al. / Seizure 29 (2015) 15–19
18 Table 1 (Continued ) Case
Ref.
Sex
Age
Freq.
AL (s)
17
CP-3
F
26
8 over 7 years
45
18
CP-4
M
75
Multiple episodes over 5 years
27–31
Aura
Chest sensation, epigastric sensation, heart ‘ skipping a beat’ Nausea, head sensation
Semiology
Video-EEG findings
Cause of asystole
Investigations performed
Sinus bradycardia
Asystole
Circulatory recovery
Rapid breathing
Tachypnea, tonic extension, myoclonus
Flushing, myoclonus
‘‘Slow-flatslow’’ pattern
Cardioinhibitory reflex syncope
Blood counts, 24 hECG, routine and video-EEG, TTE, MRIB, tilt-table test
Pallor, rapid breathing, oral automatisms
Tonic extension, myoclonus
Flushing, tonic extension, myoclonus
‘‘Slow-flatslow’’ pattern
Cardioinhibitory reflex syncope or cardiac syncope
Blood counts, ECG, routine and videoEEG, TTE, tilt-table test, MRIB
Cardiologic investigations were within normal limits within the current paper’s cohort of patients (cases 15–18). Abbreviations: AL: asystole length measured in seconds; CP: current paper; ECG: electrocardiography; EEG: electroencephalography; F: female; Freq.: frequency of events; M: male; MRIB: magnetic resonance imaging of the brain; Ref., reference number; TTE: transthoracic echocardiogram; a: Gastaut [9] reported 71 cases of both sexes with cardiac asystole induced by ocular compression.
resumption of normal sinus rhythm and generalized slowing on EEG. A dual-chamber PPM was implanted and lamotrigine was ceased. On 3-year follow-up, she has remained asymptomatic. 3.4. Case 4 A 75-year-old man presented with a 5-year history of recurrent LOC and convulsions mostly in sleep and occasionally when awake. The events started with nausea and a strange sensation in his head followed by LOC and jerking of limbs. The events were diagnosed as epileptic seizures and several antiepileptic drugs were trialed. His clinical examination and cardiac investigations were normal (Table 1). The video-EEG captured five episodes of asystole – two whilst awake and three in light-sleep. He demonstrated oral automatisms (chewing) as cardiac rhythm transitioned from normal sinus rhythm to sinus bradycardia. The EEG was normal at this time. During asystole, the EEG transitioned from generalized slowing to generalized suppression. Early asystole coincided with pallor. Tonic posturing developed during asystole accompanied by EEG flattening. Flushing was seen with circulatory recovery. Furthermore, as the EEG transitioned back to slow waveforms, fast asymmetric myoclonic activity was noted. Recovery occurred with resumption of sinus rhythm on ECG and alpha rhythm on EEG (Videos 1 and 2). The patient underwent dual-chamber PPM insertion and has been symptom free for 6 years on follow-up.
4. Discussion We present four patients presenting with LOC and seizure-like semiology due to cardiac asystole. All episodes occurred in the supine position during video-EEG monitoring. Three patients had been treated with anti-epileptics prior to establishing the diagnosis of SRCA. No patient displayed signs of epilepsy during video-EEG monitoring. The semiology was characterized by an ‘aura’ (prior to asystole) followed by generalized tonic activity and myoclonus (during asystole) as well as a second phase of myoclonus (during cardiac rhythm resumption) (Fig. 1). Our study demonstrates that seizure-like semiology occurs in three phases; pre-asystole, during asystole (cerebral hypoperfusion), and immediately following cardiac rhythm resumption (cerebral reperfusion). A typical ‘‘slow-flat-slow’’ EEG pattern was observed, coinciding closely with the transitioning of ECG from sinus bradycardia, asystole and back to sinus bradycardia.
Table 1 summarizes cases of SRCA published to date. In our series of patients presenting with SRCA, typical signs and ‘auras’ preceding LOC included pallor, light-headedness and funny sensation in the chest. Often described as epileptic phenomena, auras are not uncommon in patients with SRCA [3,5–8]. Our observations are consistent with other reports suggesting that if present, auras occur prior to asystole [6–8]. An unidentified autonomic mechanism may be responsible for this phenomenon. During bradycardia and early asystole, three patients developed a peculiar rapid breathing pattern. A generalized pallor was also observed at the onset of sinus bradycardia, presumably related to hypoperfusion. This pallor extended through asystole until cardiac rhythm recommenced. The periods of asystole and EEG flattening coincided with tonic posturing and myoclonus. Flushing occurred with circulatory recovery. This period of cerebral reperfusion corresponded with repeated myoclonus concordant with previous reports [3,8]. One patient had five events of asystole displaying stereotypical semiology. Generalized EEG slowing was observed during sinus bradycardia and early asystole, a relatively consistent finding amongst other reports [3,4,6,8–10]. Subsequent EEG flattening was associated with generalized and sustained tonic activity. This seizurelike semiology was not associated with any epileptiform discharges. Furthermore, there was no rhythmic tonic-clonic phase as typically seen in true generalized tonic-clonic epileptic seizures. Following circulatory recovery, generalized EEG slowing was observed. During this second ‘‘slow’’ phase, myoclonic jerks were seen. Consistent with our observations, previous studies have reported minimal or absent post-ictal symptoms [2,3,8]. This ‘‘slow-flat-slow’’ EEG pattern was first described by Gastaut during asystole episodes lasting more than 13 s in a group of individuals with syncope induced by ocular compression [9,10]. In Gastaut’s observations, patients with asystole lasting less than 6 s had no clinical or EEG abnormalities, whereas cardiac arrest lasting between 7 and 13 s was accompanied by EEG slowwaves and variable disturbances of consciousness [9,10]. The underlying pathophysiology of seizure-like activity is thought to be related to the inhibitory actions of hypoxia in the telencephalon and other cortical structures [10]. This inhibition results in unopposed action of the subcortical structures, in particular the brainstem reticular formation, resulting in sustained tonic contractions [10]. The release of cortical inhibition coincides with spontaneous recovery of cardiac electrical activity and reemergence of theta and delta waves on EEG [10]. We postulate that
A. Jackson et al. / Seizure 29 (2015) 15–19
myoclonus during cerebral reperfusion may be related to impaired cerebral auto-regulation as described in cerebral hyperperfusion syndrome [11,12]. Syncope is classified into three major groups: reflex (neurally mediated), cardiac and due to orthostatic hypotension [13]. Based on pathophysiology, reflex syncope can be classified as ‘‘vasodepressive’’ characterized by blood pressure drop and ‘‘cardioinhibitory’’ characterized by bradycardia and asystole in severe cases [14]. Clinically, certain features may help determine the cause of syncope. Long history, presence of triggering factors, precipitation by prolonged standing and exertion usually points to neurally mediated syncope. Syncope due to orthostatic hypotension is usually posture-related. History of structural heart disease, family history of sudden death and occurrence during exertion or supine posture usually indicates cardiac syncope [13]. However, we have found in our series that regardless the etiology of asystole (cardio-inhibitory reflex syncope or cardiac syncope), the semiology of clinical events tends to be similar. We acknowledge some study limitations. This is a retrospective cohort and patients were not subjected to intra-cardiac electrophysiological studies. Some semiological features may not have been included due to small sample size. Loss of body tone was not commented upon as it was difficult to delineate by observing videos. Only nine events from four patients are described due to rarity of this phenomenon in the video-EEG setting. Nonetheless, this is the largest series of spontaneously occurring asystole with a detailed analysis of EEG, ECG and semiologic correlations highlighting clinical clues for early diagnosis. 5. Conclusion Our study demonstrates that cardiac asystole can be associated with clinical manifestations including aura, automatisms, tonic activity and myoclonus; semiology that may lead to misdiagnosis as epileptic seizures resulting in inappropriate antiepileptic therapy. Recurrent episodes of cardiac asystole can be stereotypical in a given patient, thereby further hampering the differential diagnosis between epileptic seizures and cardiac syncope. Clinically, early pallor and rapid breathing followed by flushing are useful in recognizing SRCA. Generalized tonic-clonic activity is conspicuous by its absence. The seizure-like semiology occurs in
19
three phases; pre-asystole, during asystole and post-asystole. The EEG demonstrates typical ‘‘slow-flat-slow’’ pattern with no epileptiform abnormalities. Pacemaker implantation resolves symptoms. Conflict of interest The authors have no conflicts of interest related to this paper. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.seizure.2015.02.029. References [1] Jallon P. Arrhythmogenic seizures. Epilepsia 1997;38(Suppl. 11):S43–7. [2] Andriola M. Pseudo-seizures secondary to cardiac asystole and apnea. Electroencephalogr Clin Neurophysiol 1983;56:7P. [3] Venkataraman V, Wheless JW, Willmore LJ, Motookal H. Idiopathic cardiac asystole presenting as an intractable adult onset partial seizure disorder. Seizure 2001;10:359–64. ¨ zyu¨rek R. Syncope or seizure? The [4] Yilmaz S, Go¨kben S, Levent E, Serdarog˘lu G, O diagnostic value of synchronous tilt testing and video-EEG monitoring in children with transient loss of consciousness. Epilepsy Behav 2012;24:93–6. [5] Stephenson JB. Anoxic seizures: self-terminating syncopes. Epileptic Disord 2001;3:3–6. [6] Ficker DM, Cascino GD, Clements IP. Cardiac asystole masquerading as temporal lobe epilepsy. Mayo Clin Proc 1998;73:784–6. [7] Loesch AM, Becker A, Noachtar S. Syncope: there is more than haemodynamic failure. BMJ Case Rep 2013. http://dx.doi.org/10.1136/bcr-2013-010347. pii:bcr2013010347. [8] Xu Z, Bower S, Seneviratne U. Severe cardioinhibitory vasovagal syncope in sleep and supine posture. Epileptic Disord 2014;16:101–6. [9] Gastaut H. Syncope and seizure. Electroencephalogr Clin Neurophysiol 1958;10:571–2. [10] Gastaut H, Fischer-Williams M. Electro-encephalographic study of syncope; its differentiation from epilepsy. Lancet 1957;273:1018–25. [11] van Mook WN, Rennenberg RJ, Schurink GW, van Oostenbrugge RJ, Mess WH, Hofman PA, et al. Cerebral hyperperfusion syndrome. Lancet Neurol 2005;4:877–88. [12] Adhiyaman Y, Alexander S. Cerebral hyperperfusion syndrome following carotid endarterectomy. QJM 2007;100:239–44. [13] Moya A, Sutton R, Ammirati F, Blanc JJ, Brignole M, Dahm JB. Guidelines for the diagnosis and management of syncope (version 2009). Eur Heart J 2009;30:2631–71. [14] van Dijk JG, Thijs RD, Benditt DG, Wieling W. A guide to disorders causing transient loss of consciousness: focus on syncope. Nat Rev Neurol 2009;5:438–48.