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Seizures on hearing the alarm clock
Case Report
Seizures on hearing the alarm clock Christian Vollmar*, Berend Feddersen*, Britt Maria Beckmann, Stefan Kääb, Soheyl Noachtar Lancet 2007; 370: 2172 *These authors contributed equally Department of Neurology (C Vollmar MD, B Feddersen MD, Prof S Noachtar MD) and Department of Internal Medicine (B M Beckmann MD, S Kääb PhD), Klinikum Grosshadern, University of Munich, Germany Correspondence to: Dr Berend Feddersen, Klinik für Neurologie, Klinikum Grosshadern, Universität München, Marchioninistraβe 15, D–81377 München, Germany [email protected]
See Online for webvideo
In October, 2006, a 25-year-old trainee graphic designer was referred to us to establish whether her seizures were epileptic or dissociative. For 8 years, she had had seizures triggered by unexpected auditory stimuli, such as the ringing of her telephone or alarm clock. She would become startled and have a “turning feeling in her head”, palpitations, and anxiety. She would then hyperventilate, lose consciousness, and collapse, often with urinary incontinence. These episodes had occurred less frequently when she had avoided stress, not even attending school. However, she was now having seizures, with loss of consciousness, every day. Her electroencephalogram (EEG) and MRI of her head had been normal, as had several electrocardiograms (ECGs). She had no risk factors for epilepsy; she had never received a psychiatric assessment. Nonetheless, she had been diagnosed with complex partial and generalised epilepsy. Trials of antiepileptic drugs (valproic acid, carbamazepine, oxcarbazepine, topiramate, clobazam, and levetiracetam) had been unsuccessful. During the patient’s first night at our EEG-video monitoring unit, she was startled while watching television, and her ECG showed a ventricular ectopic beat that rapidly evolved into torsade de pointes (figure, webvideo). The patient pushed the alarm button before losing consciousness. She started to hyperventilate, then gasp for air; her
A EEG
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2
3 1
ECG Breathing
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2
2 3
5 3
4
1
Consciousness
4 5
6
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0
50
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B
4
100
150 Time (seconds) 2
200
3
FP2-F8 F8-T8 T8-P8 P8-O2 FP1-F7 F7-T7 T7-P7 P7-O1 ECG
Figure: Hypoxia caused by LQTS (A) EEG trace showed: (1) α-rhythm, (2) generalised slowing, (3) burst suppression, (4) generalised suppression of brain activity, like that found in brain death, (5) generalised slowing. ECG showed (1) torsade de pointes, (2) ventricular flutter, (3) torsade de pointes, (4) sinus rhythm. Breathing: (1) normal, (2) hyperventilation, (3) gasping, (4) apnoea, (5) gasping, (6) hyperventilation. Consciousness: (1) awake, (2) unconscious. (B) Selections from the EEG and ECG, showing (1) onset of torsade de pointes, (2) ventricular flutter and generalised suppression of brain activity, (3) end of dysrhythmia. The surge in all leads after the end of dysrhythmia is an artifact.
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EEG showed generalised slowing, then burst suppression. For several seconds, she had a flat trace on the EEG—such as is found in brain death—and was apnoeic, in rapid polymorphic ventricular tachycardia. Her dysrhythmia resolved spontaneously after 165 s, and her breathing, EEG, and level of consciousness subsequently returned to normal. When the patient was at rest, the rate-corrected QT interval on her ECG was 430–480 ms (normal <460 ms). Genetic analysis revealed a hitherto undescribed heterozygous mutation of the KCNH2 gene (a deletion of two base pairs in exon 6, c.1275_1276delAC >p.Thr425fsX517) encoding the cardiac potassium channel IKr, a finding consistent with long-QT syndrome (LQTS). The patient’s sister, who had similar, less frequent episodes, and her asymptomatic father are carriers of the mutation. Since starting treatment with metoprolol, potassium, and magnesium, and changing her lifestyle to avoid unexpected noise and excessive stress, the patient has been asymptomatic. After informed discussion, she decided against having an implanted cardioverterdefibrillator, but may be given one in future. She works as a graphic designer, and sleeps early to avoid needing an alarm clock. We avoid contacting her by telephone. Features widely regarded as typical of epilepsy, like clonic movements, incontinence, and tongue biting, can occur during syncope1—which can be caused by LQTS. Causes of LQTS include antidysrhythmic, antibiotic, and antipsychotic drugs, electrolyte disturbances, cocaine use, and severe bradycardia.2 LQTS can also be congenital, when inheritance is usually autosomal dominant—so there may be a family history of “seizures”. Mutations in at least ten different genes can cause LQTS.3 Mutations either reduce the repolarising potassium current, or increase depolarising sodium or calcium currents. Triggers of dysrhythmia in patients with LQTS include physical exertion, swimming, emotion, auditory stimuli, rest, and sleep; to some extent, people with different mutations are susceptible to different triggers.4 We think our patient’s gasping for air was caused by adaptation of central oxygen-sensitive neurons to recurrent hypoxia; such an adaptation is found in people who are new to high altitude, or have chronic lung disease.5 We suspect this mechanism saved our patient from organ damage. References 1 Lempert T, Bauer M, Schmidt D. Syncope: a videometric analysis of 56 episodes of transient cerebral hypoxia. Ann Neurol 1994; 36: 233–37. 2 Khan IA. Clinical and therapeutic aspects of congenital and acquired long QT syndrome. Am J Med 2002; 112: 58–66. 3 Lehnart SE, Ackerman MJ, Benson DW, et al. Inherited arrhythmias. Circulation 2007; 116: 2325–45. 4 Schwartz PJ, Priori SG, Spazzolini C, et al. Genotype-phenotype correlation in the long-QT syndrome: gene-specific triggers for life-threatening arrhythmias. Circulation 2001; 103: 89–95. 5 Neubauer JA, Sunderram J. Oxygen-sensing neurons in the central nervous system. J Appl Physiol 2004; 96: 367–74.
www.thelancet.com Vol 370 December 22/29, 2007
Seizures on hearing the alarm clock Christian Vollmar*, Berend Feddersen*, Britt Maria Beckmann, Stefan Kääb, Soheyl Noachtar Lancet 2007; 370: 2172 *These authors contributed equally Department of Neurology (C Vollmar MD, B Feddersen MD, Prof S Noachtar MD) and Department of Internal Medicine (B M Beckmann MD, S Kääb PhD), Klinikum Grosshadern, University of Munich, Germany Correspondence to: Dr Berend Feddersen, Klinik für Neurologie, Klinikum Grosshadern, Universität München, Marchioninistraβe 15, D–81377 München, Germany [email protected]
See Online for webvideo
In October, 2006, a 25-year-old trainee graphic designer was referred to us to establish whether her seizures were epileptic or dissociative. For 8 years, she had had seizures triggered by unexpected auditory stimuli, such as the ringing of her telephone or alarm clock. She would become startled and have a “turning feeling in her head”, palpitations, and anxiety. She would then hyperventilate, lose consciousness, and collapse, often with urinary incontinence. These episodes had occurred less frequently when she had avoided stress, not even attending school. However, she was now having seizures, with loss of consciousness, every day. Her electroencephalogram (EEG) and MRI of her head had been normal, as had several electrocardiograms (ECGs). She had no risk factors for epilepsy; she had never received a psychiatric assessment. Nonetheless, she had been diagnosed with complex partial and generalised epilepsy. Trials of antiepileptic drugs (valproic acid, carbamazepine, oxcarbazepine, topiramate, clobazam, and levetiracetam) had been unsuccessful. During the patient’s first night at our EEG-video monitoring unit, she was startled while watching television, and her ECG showed a ventricular ectopic beat that rapidly evolved into torsade de pointes (figure, webvideo). The patient pushed the alarm button before losing consciousness. She started to hyperventilate, then gasp for air; her
A EEG
1
2
3 1
ECG Breathing
1
2
2 3
5 3
4
1
Consciousness
4 5
6
2
0
50
1
B
4
100
150 Time (seconds) 2
200
3
FP2-F8 F8-T8 T8-P8 P8-O2 FP1-F7 F7-T7 T7-P7 P7-O1 ECG
Figure: Hypoxia caused by LQTS (A) EEG trace showed: (1) α-rhythm, (2) generalised slowing, (3) burst suppression, (4) generalised suppression of brain activity, like that found in brain death, (5) generalised slowing. ECG showed (1) torsade de pointes, (2) ventricular flutter, (3) torsade de pointes, (4) sinus rhythm. Breathing: (1) normal, (2) hyperventilation, (3) gasping, (4) apnoea, (5) gasping, (6) hyperventilation. Consciousness: (1) awake, (2) unconscious. (B) Selections from the EEG and ECG, showing (1) onset of torsade de pointes, (2) ventricular flutter and generalised suppression of brain activity, (3) end of dysrhythmia. The surge in all leads after the end of dysrhythmia is an artifact.
2172
EEG showed generalised slowing, then burst suppression. For several seconds, she had a flat trace on the EEG—such as is found in brain death—and was apnoeic, in rapid polymorphic ventricular tachycardia. Her dysrhythmia resolved spontaneously after 165 s, and her breathing, EEG, and level of consciousness subsequently returned to normal. When the patient was at rest, the rate-corrected QT interval on her ECG was 430–480 ms (normal <460 ms). Genetic analysis revealed a hitherto undescribed heterozygous mutation of the KCNH2 gene (a deletion of two base pairs in exon 6, c.1275_1276delAC >p.Thr425fsX517) encoding the cardiac potassium channel IKr, a finding consistent with long-QT syndrome (LQTS). The patient’s sister, who had similar, less frequent episodes, and her asymptomatic father are carriers of the mutation. Since starting treatment with metoprolol, potassium, and magnesium, and changing her lifestyle to avoid unexpected noise and excessive stress, the patient has been asymptomatic. After informed discussion, she decided against having an implanted cardioverterdefibrillator, but may be given one in future. She works as a graphic designer, and sleeps early to avoid needing an alarm clock. We avoid contacting her by telephone. Features widely regarded as typical of epilepsy, like clonic movements, incontinence, and tongue biting, can occur during syncope1—which can be caused by LQTS. Causes of LQTS include antidysrhythmic, antibiotic, and antipsychotic drugs, electrolyte disturbances, cocaine use, and severe bradycardia.2 LQTS can also be congenital, when inheritance is usually autosomal dominant—so there may be a family history of “seizures”. Mutations in at least ten different genes can cause LQTS.3 Mutations either reduce the repolarising potassium current, or increase depolarising sodium or calcium currents. Triggers of dysrhythmia in patients with LQTS include physical exertion, swimming, emotion, auditory stimuli, rest, and sleep; to some extent, people with different mutations are susceptible to different triggers.4 We think our patient’s gasping for air was caused by adaptation of central oxygen-sensitive neurons to recurrent hypoxia; such an adaptation is found in people who are new to high altitude, or have chronic lung disease.5 We suspect this mechanism saved our patient from organ damage. References 1 Lempert T, Bauer M, Schmidt D. Syncope: a videometric analysis of 56 episodes of transient cerebral hypoxia. Ann Neurol 1994; 36: 233–37. 2 Khan IA. Clinical and therapeutic aspects of congenital and acquired long QT syndrome. Am J Med 2002; 112: 58–66. 3 Lehnart SE, Ackerman MJ, Benson DW, et al. Inherited arrhythmias. Circulation 2007; 116: 2325–45. 4 Schwartz PJ, Priori SG, Spazzolini C, et al. Genotype-phenotype correlation in the long-QT syndrome: gene-specific triggers for life-threatening arrhythmias. Circulation 2001; 103: 89–95. 5 Neubauer JA, Sunderram J. Oxygen-sensing neurons in the central nervous system. J Appl Physiol 2004; 96: 367–74.
www.thelancet.com Vol 370 December 22/29, 2007