GRAY M ATTERS LETTERS/COMMENTARY Commentary on ictal epileptic tachycardia and bradycardia To the Editors: Sevcencu and Struijk (2010) should be commended for their excellent review of ‘‘autonomic alterations and cardiac changes in epilepsy,’’ which also details ictal tachycardia, ictal bradycardia, and asystole. The autonomic system involvement, its interactions with various types of epilepsy, and underlying mechanisms are, as the authors conclude, complex and often with no definite answers. Conspicuously, relevant data of Panayiotopoulos syndrome (PS) are not considered in this review, although this syndrome is a primary autonomic epilepsy with welldocumented numerous ictal autonomic manifestations, including frequent tachycardia and more rarely bradycardia, asystole, and cardiorespiratory arrest (Parisi et al., 2005; Verrotti et al., 2005; Ferrie et al., 2006, 2007; Panayiotopoulos et al., 2008). PS is a common childhood-related epilepsy with lengthy and infrequent autonomic seizures and autonomic status epilepticus that may last for many hours. All functions of the central autonomic nervous system may be affected, although emesis is more prominent. Seizures may remain purely autonomic. Ictal tachycardia is a symptom in all electroencephalography/electrocardiography (EEG/ECG) recorded seizures, and may be the first detectable clinical manifestation (Parisi et al., 2005), or occur later in the course of the seizure with heart rates as high as 240 bpm (Specchio et al., 2010). This has occurred in right- or left-sided seizures with posterior or anterior ictal onsets. Bradycardia and asystole are probably very rare. There are four reported cases with documented cardiorespiratory arrest of approximately 1,000 cases with PS; all of them had an uneventful recovery (Ferrie et al., 2006). Syncopal-like attacks (or ictal syncope) are another intriguing and common ictal manifestation of PS. In these attacks the child becomes totally unresponsive and flaccid ‘‘like a rag doll’’ prior to or without convulsions. Syncopal-like attacks may be a distinct seizure-type symptom similar to atonic seizures, but on some occasions they may be due to transient cerebral ischemia (owing to, for example, apnea or bradycardia/asystole) as in true syncope. The EEG during one such episode showed ictal epileptiform activity, rather than diffuse slowing. As regards to the ‘‘autonomic neurobiological structure’’ and the lack of the clinical–anatomic–EEG correla-
tions in epileptic patients, this is even more complex in PS, where ictal epileptic autonomic symptomatology appears to pertain to any epileptogenic cortical onset zone, be that occipital, frontotemporal, or frontal (Panayiotopoulos et al., 2008). The autonomic clinical manifestations of PS are likely to be generated by variable and widely spread epileptogenic foci acting upon a temporarily hyperexcitable central autonomic network. It is hypothesized that central autonomic networks have a lower threshold to epileptogenic activation than those producing focal cortical semiology. Therefore, seizures might remain purely autonomic if ictal neuronal activation of nonautonomic cortical areas fails to reach the symptomatogenic threshold. In conclusion, I believe that expert reviews on this important topic should consider PS as a common and important model of autonomic epilepsy to study. DISCLOSURE I confirm that I have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. I have no conflict of interest in publishing this letter.
Pasquale Parisi
[email protected],
[email protected] Child Neurology, Chair of Paediatrics, Second Faculty of Medicine, Sapienza University, Rome, Italy REFERENCES Ferrie C, Caraballo R, Covanis A, Demirbilek V, Dervent A, Kivity S, Koutroumanidis M, Martinovic Z, Oguni H, Verrotti A, Vigevano F, Watanabe K, Yalcin D, Yoshinaga H. (2006) Panayiotopoulos syndrome: a consensus view. Dev Med Child Neurol 48:236–240. Ferrie CD, Caraballo R, Covanis A, Demirbilek V, Dervent A, Fejerman N, Fusco L, Grunewald RA, Kanazawa O, Koutroumanidis M, Lada C, Livingston JH, Nicotra A, Oguni H, Martinovic Z, Nordli DR Jr, Parisi P, Scott RC, Specchio N, Verrotti A, Vigevano F, Walker MC, Watanabe K, Yoshinaga H, Panayiotopoulos CP. (2007) Autonomic status epilepticus in Panayiotopoulos syndrome and other childhood and adult epilepsies: a consensus view. Epilepsia 48:1165–1172. Panayiotopoulos CP, Michael M, Sanders S, Valeta T, Koutroumanidis M. (2008) Benign childhood focal epilepsies: assessment of established and newly recognized syndromes. Brain 131:2264– 2286. Parisi P, Ferri R, Pagani J, Cecili M, Montemitro E, Villa MP. (2005) Ictal video-polysomnography and EEG spectral analysis in a child with severe Panayiotopoulos syndrome. Epileptic Disord 7:333– 339. Sevcencu C, Struijk JJ. (2010) Autonomic alterations and cardiac changes in epilepsy. Epilepsia 51:725–737. Specchio N, Trivisano M, Balestri M, Cappelletti S, Di Ciommo V, Gentile S, Masciarelli G, Silvestri D, Volkov J, Fusco L, Vigevano F.
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GRAY MATTERS (2010) Panayiotopoulos syndrome: a clinical, EEG and neuropsychological study of 93 consecutive patients. Epilepsia 28 May [Epub ahead of print]. Verrotti A, Salladini C, Trotta D, di Corcia G, Chiarelli F. (2005) Ictal cardiorespiratory arrest in Panayiotopoulos syndrome. Neurology 64:1816–1817.
Response to commentary by Dr. Parisi To the Editors: We thank Dr. Parisi for his kind remarks on our work and for his interesting and useful comments on the Panayiotopoulos syndrome (PS) and the associated autonomic effects (Parisi, 2010). Undoubtedly, PS is a type of epilepsy in which the ictal autonomic manifestations are prominent and sometimes intriguing (Ferrie et al., 2006, 2007). However, our review is not focused on the autonomic manifestations of seizures in general, but on central autonomic alterations that may support the observed interictal and ictal cardiac changes, and which were the only manifestations of seizures that we have analyzed. From this perspective of brain–heart interaction during and between seizures, PS seems rather similar to all other types of epilepsy where such changes occur. On the other hand, all data regarding the interictal autonomic alterations discussed in our review refer to changes in the sympatho-parasympathetic balance as revealed by heart rate variability studies and autonomic tests in epilepsy patients. Apparently, no such studies have been performed in patients with PS, at least not until our documentation for the review was completed. In the phenomenologic analysis of the ictal cardiac effects we primarily used data from clinical studies and review articles especially designed to investigate ictal tachycardia and bradycardia patterns, and/or electrocardiography changes associated with seizures, or case reports focused on such changes. Although several case reports (Parisi et al., 2005; Verrotti et al., 2005) and review articles (Ferrie et al., 2006, 2007) mention that some of those effects may also occur in patients with PS, we could not find any systematic study on heart rate characteristics or electrocardiographic changes associated with this syndrome in the literature searched as described in the methodologic section of our review. On the other hand, the phenomenologic characteristics mentioned by Dr Parisi (e.g., the onset, prevalence, and magnitude of ictal tachycardia and bradycardia), of which some are apparently reported in a yet unpublished study (Specchio et al., 2010), indicate again that the cardiac effects in PS are essentially similar to those described in our paper. As we have emphasized in the Discussion and Conclusions sections, ‘‘no clear correlation could be established Epilepsia, 51(8):1643–1646, 2010
between the origin or patterns of seizures, and the type, magnitude, or complexity of the ictal cardiac effects,’’ and the comments of Dr Parisi seem consistent with this observation. With respect to the mechanistic support of the analyzed effects, we exclusively cited experimental evidence on sympathetic and/or parasympathetic activation prior to, during, and after seizures, and experimental work with cardiac effects induced by chemical or electrical stimulation of various cortical and subcortical structures. However, we consider that the hypothesis of ‘‘central autonomic networks with lower threshold to epileptogenic activation’’ (Parisi, the ‘‘Commentary on ictal epileptic tachycardia and bradycardia’’), although not sufficient to explain the dichotomy ictal tachycardia versus bradycardia, the combined tachycardia/bradycardia patterns, or the oscillatory ictal heart rate associated with seizures, is very interesting and deserves further investigation, as do the cardiac manifestations in PS. DISCLOSURE Neither of the authors has any conflict of interest to disclose. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.
Cristian Sevcencu
[email protected] Johannes J. Struijk Center for Sensory-Motor Interaction (SMI) and Medical Informatics Group, Department of Health Science and Technology, Aalborg University, Denmark REFERENCES Ferrie C, Caraballo R, Covanis A, Demirbilek V, Dervent A, Kivity S, Koutroumanidis M, Martinovic Z, Oguni H, Verrotti A, Vigevano F, Watanabe K, Yalcin D, Yoshinaga H. (2006) Panayiotopoulos syndrome: a consensus view. Dev Med Child Neurol 48:236–240. Ferrie CD, Caraballo R, Covanis A, Demirbilek V, Dervent A, Fejerman N, Fusco L, Grunewald RA, Kanazawa O, Koutroumanidis M, Lada C, Livingston JH, Nicotra A, Oguni H, Martinovic Z, Nordli DR Jr, Parisi P, Scott RC, Specchio N, Verrotti A, Vigevano F, Walker MC, Watanabe K, Yoshinaga H, Panayiotopoulos CP. (2007) Autonomic status epilepticus in Panayiotopoulos syndrome and other childhood and adult epilepsies: a consensus view. Epilepsia 48:1165–1172. Parisi P, Ferri R, Pagani J, Cecili M, Montemitro E, Villa MP. (2005) Ictal video-polysomnography and EEG spectral analysis in a child with severe Panayiotopoulos syndrome. Epileptic Disord 7:333– 339. Parisi P. (2010) Commentary on ictal epileptic tachycardia and bradycardia. Epilepsia 51:1643–1644. Specchio N, Trivisano M, Balestri M, Cappelletti S, Di Ciommo V, Gentile S, Masciarelli G, Silvestri D, Volkov J, Fusco L, Vigevano F. (2010). Panayiotopoulos syndrome: a clinical, EEG and Neuropsychological study of 93 consecutive patients. Epilepsia May 28 [Epub ahead of print]. Verrotti A, Salladini C, Trotta D, di Corcia G, Chiarelli F. (2005) Ictal cardiorespiratory arrest in Panayiotopoulos syndrome. Neurology 64: 1816–1817.
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