TEST YOURSELF
Curious turns in the night-time Angharad Davis,1,2 Aidan Neligan,2,3 Nazia Raja,2 Andrew Kelso2 1
Department of Neurosciences, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University, London, UK 2 Department of Neurology, Barts Health NHS Trust, London, UK 3 Department of Neurosciences, Homerton University Hospital NHS Trust, London, UK Correspondence to Dr Angharad Grace Davis, Department of Neurosciences, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University, London, UK; [email protected] Accepted 4 May 2015 Published Online First 9 June 2015
A 63-year-old Caucasian man reported 1 year of sleep disturbance. He described waking repeatedly from sleep with feeling light-headed upon sitting up. He would then gasp for air, move his head from side to side, lose consciousness for a few seconds and recover immediately without confusion. He also had similar episodes during the daytime, although less frequently. He had frequently felt light-headed on standing for some time. He had been previously well apart from some situational vasovagal syncope as a teenager. He had a normal birth and early life, with normal developmental milestones. On examination, there was a postural drop in blood pressure from 120/90 mm Hg (lying) to 100/70 mm Hg (standing) after 3 min. Neurological and cardiology examinations were otherwise normal. Question 1 What are the unusual features, and what is your initial diagnosis? COMMENT The main differential diagnoses are syncope and epilepsy. While the episodes were stereotyped, suggesting epilepsy, other features—such as the consistent prodrome of preceding light-headedness and previous vasovagal episodes—might suggest autonomic dysregulation, possibly with sleep parasomnia or cardiac syncope. Misdiagnosing blackouts can increase mortality and morbidity: there are several well-recognised clinical markers that can help to differentiate seizures from syncope.
Question 2 What investigations would you perform, and how would you distinguish seizure from syncope? To cite: Davis A, Neligan A, Raja N, et al. Pract Neurol 2015;15:389–392.
COMMENT Cardiac investigations, including 24-h ECG monitoring and echocardiogram
were normal, as were an MR scan of brain and routine electroencephalogram (EEG). Subsequent video EEG telemetry recorded a total of 17 events during both sleep and wakefulness. At night, he would wake from sleep, panting uncontrollably with increasing agitation, occasionally sitting up followed suddenly by loss of consciousness. In some, he showed tonic stiffening of the upper body before abruptly regaining consciousness. The awake events occurred when sitting: he would raise his arms, reposition himself and turn his head from side to side and then slump to one side in the chair and hyperventilate. A typical event lasted about 1 min with immediate recovery of consciousness and full orientation. The EEG was abnormal during every event (figures 1–4). The start of an episode correlated with a right temporal ictal discharge, spreading bilaterally and then generalised high-amplitude polymorphic slowing. During this stage, he would lose consciousness, slump to one side, and then would regain consciousness as the EEG became normal. In all events, the ECG showed either bradycardia or asystole, which persisted for 21 s on one occasion. The ECG changes always occurred after the seizure had started. We diagnosed complex partial seizures with ictal asystole. Question 3 What clinical features suggest ictal asystole as well as epilepsy?
COMMENT Ictal asystole is a rare, but well-reported, complication of seizures.1 There may be scant clinical features to assist the diagnosis. In this patient, the pre-existing tendency to autonomic-mediated syncope was a further complication. Nevertheless, a small number of people have seizures complicated by syncope. In an observational study, the nine people
Davis A, et al. Pract Neurol 2015;15:389–392. doi:10.1136/practneurol-2014-001013
389
TEST YOURSELF
Figure 1
Seizure onset over right anterior temporal region (red box). The ECG shows normal sinus rhythm.
with ictal asystole more frequently showed pallor, atonia, early myoclonus, loss of consciousness, hypertonia and falls than people with epilepsy uncomplicated by ictal asystole. Other studies have made similar observations.2 Some studies suggest that people with temporal lobe epilepsy have the greatest risk of developing ictal
Figure 2
390
asystole. Given that the insular cortex forms part of the central autonomic network, it is not surprising that many researchers have attributed cardiac changes in temporal lobe epilepsy to the focal temporal epileptiform discharges. Others have found similar rates of ictal asystole in temporal and frontal lobe seizures with a lateralisation to the left cortex, although this is
Evolution of seizure with spread to left hemisphere. Onset of asystole (arrow). Davis A, et al. Pract Neurol 2015;15:389–392. doi:10.1136/practneurol-2014-001013
TEST YOURSELF
Figure 3
Generalised electrodecrement with return of bradycardia (arrow).
not consistent in the literature.1 Delayed loss of tone is uncommon in temporal lobe epilepsy, so if this accompanies the classic features of a temporal lobe seizure—with or without left hemisphere interictal epileptiform discharges—the physician should consider ictal asystole. Ictal arrhythmia is more common in people with lesional focal epilepsy. Video EEG–ECG
Figure 4
monitoring can distinguish syncope from ictal asystole. There are two distinct EEG patterns2: type 1 comprises persistent ictal discharges while type 2 comprises ictal discharges interrupted by EEG features of cerebral hypoperfusion (as in this case). Autonomic tests can identify patients with a propensity to ictal autonomic changes, for example,
Generalised polymorphic slowing with normal sinus rhythm.
Davis A, et al. Pract Neurol 2015;15:389–392. doi:10.1136/practneurol-2014-001013
391
TEST YOURSELF abnormal blood pressure and heart rate variability may indicate impaired baroreflex sensitivity. Changes in preictal vagal activity are already a recognised biomarker of seizures, and may in the future allow the prediction of ictal autonomic dysfunction in people with epilepsy fitted with vagus nerve stimulators.3 We suspect that this patient’s tendency to autonomic-mediated syncope gave him a higher risk of autonomic complications of seizures.3 Question 4 How would you manage him, and what is the evidence base for treatment?
COMMENT One small study of seven people with ictal asystole found that none required cardiac resuscitation despite ictal asystole episodes lasting up to 25 s; only one person opted to have a permanent pacemaker; all patients were alive after 4 years of follow-up.2 However, this small cohort study does not refute the need for pacemaker insertion. In another study, there were fewer seizure-related falls and episodes of loss of consciousness after pacemaker implantation in people with ictal asysole.5 The evidence for pacemaker insertion or the role of ictal arrhythmia as a risk factor for SUDEP is, therefore, inconclusive. Ultimately, the decision to implant a permanent pacemaker will be influenced by the duration of ictal asystole, the presence of collapse or atonia and individual patient factors and preferences.
Key points COMMENT Immediately following video telemetry, we started him on antiepileptic medication, inserted a permanent cardiac pacemaker and arranged further autonomic tests. Head-up tilt-table testing provoked a fall in blood pressure to 55/28 mm Hg with a ( paced) heart rate of 60/min. Ambulatory blood pressure monitoring showed normal nocturnal circadian fall in blood pressure with a low-normal blood pressure when sitting and at night with shortness of breath. He has remained seizure-free in the year following pacemaker insertion. The literature highlights conflicting opinions regarding the relative contributions of ictal arrhythmia and/ or autonomic dysfunction to sudden unexpected death in epilepsy (SUDEP). SUDEP probably has many causes, and although there could be an association with autonomic dysfunction, there is no definite evidence for this.4 The first-line treatment for ictal asystole is antiepileptic medication, although potential cardiac side effects might influence the choice of drug. Carbamazepine and other sodium channel antagonists might prolong the PR interval, and thus may provoke sinoatrial or atrioventricular block, and even asystole. Oxcarbazepine has been associated with sick sinus syndrome, which can mimic cardiac arrhythmia in coexisting epilepsy.
Question 5 Should such patients be considered for a permanent cardiac pacemaker?
392
▸ Patients whose seizures have additional symptoms that suggest autonomic-mediated syncope (eg, atonia) may have ictal asystole complicating their epilepsy. ▸ In these patients the asystole almost always follow the onset of epileptiform discharges. ▸ There is no established treatment protocol but clinicians should consider starting antiepileptic medication together with simultaneous permanent pacemaker insertion. Contributors All authors have contributed to the care of the patient described in the case report. The manuscript was prepared by AGD and subsequently edited by AN, NR and AK. There are no relevant funding sources. There are no competing interests with relation to this manuscript. Competing interests None declared. Patient consent Obtained. Provenance and peer review Not commissioned; externally peer reviewed. This paper was reviewed by Paul Cooper, Manchester, UK.
REFERENCES 1 Rugg-Gunn FJ, Simister RJ, Squirrell M, et al. Cardiac arrhythmias in focal epilepsy: a prospective long-term study. Lancet 2004;364:2212–19. 2 Nguyen-Michel VH, Adam C, Dinkelacker V, et al. Characterisation of seizure-indiced syncopes: EEG, ECG, and clinical features. Epilepsia 2014;55:146–55. 3 Sevcencu C, Struijk J. Autonomic alterations and cardiac changes in epilepsy. Epilepsia 2010;51:725–37. 4 Poh M, Loddenkemper T, Reinsbergere C, et al. Autonomic changes with seizures correlate with postictal EEG suppression. Neurology 2012;78:1868–76. 5 Moseley BD, Ghearing GR, Munger TM, et al. The treatment of ictal asystole with cardiac pacing. Epilepsia 2011;52:e16–19.
Davis A, et al. Pract Neurol 2015;15:389–392. doi:10.1136/practneurol-2014-001013
Curious turns in the night-time Angharad Davis,1,2 Aidan Neligan,2,3 Nazia Raja,2 Andrew Kelso2 1
Department of Neurosciences, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University, London, UK 2 Department of Neurology, Barts Health NHS Trust, London, UK 3 Department of Neurosciences, Homerton University Hospital NHS Trust, London, UK Correspondence to Dr Angharad Grace Davis, Department of Neurosciences, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University, London, UK; [email protected] Accepted 4 May 2015 Published Online First 9 June 2015
A 63-year-old Caucasian man reported 1 year of sleep disturbance. He described waking repeatedly from sleep with feeling light-headed upon sitting up. He would then gasp for air, move his head from side to side, lose consciousness for a few seconds and recover immediately without confusion. He also had similar episodes during the daytime, although less frequently. He had frequently felt light-headed on standing for some time. He had been previously well apart from some situational vasovagal syncope as a teenager. He had a normal birth and early life, with normal developmental milestones. On examination, there was a postural drop in blood pressure from 120/90 mm Hg (lying) to 100/70 mm Hg (standing) after 3 min. Neurological and cardiology examinations were otherwise normal. Question 1 What are the unusual features, and what is your initial diagnosis? COMMENT The main differential diagnoses are syncope and epilepsy. While the episodes were stereotyped, suggesting epilepsy, other features—such as the consistent prodrome of preceding light-headedness and previous vasovagal episodes—might suggest autonomic dysregulation, possibly with sleep parasomnia or cardiac syncope. Misdiagnosing blackouts can increase mortality and morbidity: there are several well-recognised clinical markers that can help to differentiate seizures from syncope.
Question 2 What investigations would you perform, and how would you distinguish seizure from syncope? To cite: Davis A, Neligan A, Raja N, et al. Pract Neurol 2015;15:389–392.
COMMENT Cardiac investigations, including 24-h ECG monitoring and echocardiogram
were normal, as were an MR scan of brain and routine electroencephalogram (EEG). Subsequent video EEG telemetry recorded a total of 17 events during both sleep and wakefulness. At night, he would wake from sleep, panting uncontrollably with increasing agitation, occasionally sitting up followed suddenly by loss of consciousness. In some, he showed tonic stiffening of the upper body before abruptly regaining consciousness. The awake events occurred when sitting: he would raise his arms, reposition himself and turn his head from side to side and then slump to one side in the chair and hyperventilate. A typical event lasted about 1 min with immediate recovery of consciousness and full orientation. The EEG was abnormal during every event (figures 1–4). The start of an episode correlated with a right temporal ictal discharge, spreading bilaterally and then generalised high-amplitude polymorphic slowing. During this stage, he would lose consciousness, slump to one side, and then would regain consciousness as the EEG became normal. In all events, the ECG showed either bradycardia or asystole, which persisted for 21 s on one occasion. The ECG changes always occurred after the seizure had started. We diagnosed complex partial seizures with ictal asystole. Question 3 What clinical features suggest ictal asystole as well as epilepsy?
COMMENT Ictal asystole is a rare, but well-reported, complication of seizures.1 There may be scant clinical features to assist the diagnosis. In this patient, the pre-existing tendency to autonomic-mediated syncope was a further complication. Nevertheless, a small number of people have seizures complicated by syncope. In an observational study, the nine people
Davis A, et al. Pract Neurol 2015;15:389–392. doi:10.1136/practneurol-2014-001013
389
TEST YOURSELF
Figure 1
Seizure onset over right anterior temporal region (red box). The ECG shows normal sinus rhythm.
with ictal asystole more frequently showed pallor, atonia, early myoclonus, loss of consciousness, hypertonia and falls than people with epilepsy uncomplicated by ictal asystole. Other studies have made similar observations.2 Some studies suggest that people with temporal lobe epilepsy have the greatest risk of developing ictal
Figure 2
390
asystole. Given that the insular cortex forms part of the central autonomic network, it is not surprising that many researchers have attributed cardiac changes in temporal lobe epilepsy to the focal temporal epileptiform discharges. Others have found similar rates of ictal asystole in temporal and frontal lobe seizures with a lateralisation to the left cortex, although this is
Evolution of seizure with spread to left hemisphere. Onset of asystole (arrow). Davis A, et al. Pract Neurol 2015;15:389–392. doi:10.1136/practneurol-2014-001013
TEST YOURSELF
Figure 3
Generalised electrodecrement with return of bradycardia (arrow).
not consistent in the literature.1 Delayed loss of tone is uncommon in temporal lobe epilepsy, so if this accompanies the classic features of a temporal lobe seizure—with or without left hemisphere interictal epileptiform discharges—the physician should consider ictal asystole. Ictal arrhythmia is more common in people with lesional focal epilepsy. Video EEG–ECG
Figure 4
monitoring can distinguish syncope from ictal asystole. There are two distinct EEG patterns2: type 1 comprises persistent ictal discharges while type 2 comprises ictal discharges interrupted by EEG features of cerebral hypoperfusion (as in this case). Autonomic tests can identify patients with a propensity to ictal autonomic changes, for example,
Generalised polymorphic slowing with normal sinus rhythm.
Davis A, et al. Pract Neurol 2015;15:389–392. doi:10.1136/practneurol-2014-001013
391
TEST YOURSELF abnormal blood pressure and heart rate variability may indicate impaired baroreflex sensitivity. Changes in preictal vagal activity are already a recognised biomarker of seizures, and may in the future allow the prediction of ictal autonomic dysfunction in people with epilepsy fitted with vagus nerve stimulators.3 We suspect that this patient’s tendency to autonomic-mediated syncope gave him a higher risk of autonomic complications of seizures.3 Question 4 How would you manage him, and what is the evidence base for treatment?
COMMENT One small study of seven people with ictal asystole found that none required cardiac resuscitation despite ictal asystole episodes lasting up to 25 s; only one person opted to have a permanent pacemaker; all patients were alive after 4 years of follow-up.2 However, this small cohort study does not refute the need for pacemaker insertion. In another study, there were fewer seizure-related falls and episodes of loss of consciousness after pacemaker implantation in people with ictal asysole.5 The evidence for pacemaker insertion or the role of ictal arrhythmia as a risk factor for SUDEP is, therefore, inconclusive. Ultimately, the decision to implant a permanent pacemaker will be influenced by the duration of ictal asystole, the presence of collapse or atonia and individual patient factors and preferences.
Key points COMMENT Immediately following video telemetry, we started him on antiepileptic medication, inserted a permanent cardiac pacemaker and arranged further autonomic tests. Head-up tilt-table testing provoked a fall in blood pressure to 55/28 mm Hg with a ( paced) heart rate of 60/min. Ambulatory blood pressure monitoring showed normal nocturnal circadian fall in blood pressure with a low-normal blood pressure when sitting and at night with shortness of breath. He has remained seizure-free in the year following pacemaker insertion. The literature highlights conflicting opinions regarding the relative contributions of ictal arrhythmia and/ or autonomic dysfunction to sudden unexpected death in epilepsy (SUDEP). SUDEP probably has many causes, and although there could be an association with autonomic dysfunction, there is no definite evidence for this.4 The first-line treatment for ictal asystole is antiepileptic medication, although potential cardiac side effects might influence the choice of drug. Carbamazepine and other sodium channel antagonists might prolong the PR interval, and thus may provoke sinoatrial or atrioventricular block, and even asystole. Oxcarbazepine has been associated with sick sinus syndrome, which can mimic cardiac arrhythmia in coexisting epilepsy.
Question 5 Should such patients be considered for a permanent cardiac pacemaker?
392
▸ Patients whose seizures have additional symptoms that suggest autonomic-mediated syncope (eg, atonia) may have ictal asystole complicating their epilepsy. ▸ In these patients the asystole almost always follow the onset of epileptiform discharges. ▸ There is no established treatment protocol but clinicians should consider starting antiepileptic medication together with simultaneous permanent pacemaker insertion. Contributors All authors have contributed to the care of the patient described in the case report. The manuscript was prepared by AGD and subsequently edited by AN, NR and AK. There are no relevant funding sources. There are no competing interests with relation to this manuscript. Competing interests None declared. Patient consent Obtained. Provenance and peer review Not commissioned; externally peer reviewed. This paper was reviewed by Paul Cooper, Manchester, UK.
REFERENCES 1 Rugg-Gunn FJ, Simister RJ, Squirrell M, et al. Cardiac arrhythmias in focal epilepsy: a prospective long-term study. Lancet 2004;364:2212–19. 2 Nguyen-Michel VH, Adam C, Dinkelacker V, et al. Characterisation of seizure-indiced syncopes: EEG, ECG, and clinical features. Epilepsia 2014;55:146–55. 3 Sevcencu C, Struijk J. Autonomic alterations and cardiac changes in epilepsy. Epilepsia 2010;51:725–37. 4 Poh M, Loddenkemper T, Reinsbergere C, et al. Autonomic changes with seizures correlate with postictal EEG suppression. Neurology 2012;78:1868–76. 5 Moseley BD, Ghearing GR, Munger TM, et al. The treatment of ictal asystole with cardiac pacing. Epilepsia 2011;52:e16–19.
Davis A, et al. Pract Neurol 2015;15:389–392. doi:10.1136/practneurol-2014-001013
