CONTROVERSY IN EPILEPSY

Consciousness as a useful concept in epilepsy classification *†‡Hal Blumenfeld, and §Kimford J. Meador Epilepsia, 55(8):1145–1150, 2014 doi: 10.1111/epi.12588

Dr. Hal Blumenfeld is Professor of Neurology, Neurobiology and Neurosurgery and Director of the Clinical Neuroscience Imaging Center (CNIC) at Yale School of Medicine.

Summary: Impaired consciousness has important practical consequences for people living with epilepsy. Recent pathophysiologic studies show that seizures with impaired level of consciousness always affect widespread cortical networks and subcortical arousal systems. In light of these findings and their clinical significance, efforts are underway to revise the International League Against Epilepsy (ILAE) 2010 report to include impaired consciousness in the classification of seizures. Lüders and colleagues have presented one such effort, which we discuss here. We then propose an alternative classification of impaired consciousness in epilepsy based on functional neuroanatomy. Some seizures involve focal cortical regions and cause selective deficits in the content of consciousness but without impaired overall level of consciousness or awareness. These include focal aware conscious seizures (FACS) with lower order cortical deficits such as somatosensory or visual impairment as well as FACS with higher cognitive deficits including ictal aphasia or isolated epileptic amnesia. Another category applies to seizures with impaired level of consciousness leading to deficits in multiple cognitive domains. For this category, we believe the terms “dyscognitive” or “dialeptic” should be avoided because they may create confusion. Instead we propose that seizures with impaired level of consciousness be described based on underlying pathophysiology. Widespread moderately severe deficits in corticothalamic function are seen in absence seizures and in focal impaired consciousness seizures (FICS), including many temporal lobe seizures and other focal seizures with impaired consciousness. Some simple responses or automatisms may be preserved in these seizures. In contrast, generalized tonic–clonic seizures usually produce widespread severe deficits in corticothalamic function causing loss of all meaningful responses. Further work is needed to understand and prevent impaired consciousness in epilepsy, but the first step is to keep this crucial practical and physiologic aspect of seizures front-and-center in our discussions. KEY WORDS: Epilepsy, Consciousness, Complex partial seizures, Simple partial seizures, Absence seizures, Generalized tonic–clonic seizures, Classification.

Dr. Kimford J. Meador is Professor of Neurology & Neurological Sciences and Director of the Epilepsy Monitoring Unit at Stanford School of Medicine.

Accepted February 1, 2014; Early View publication June 30, 2014. Departments of * Neurology, † Neurobiology, and ‡ Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, U.S.A.; and §Department of Neurology and Neurological Sciences, Stanford School of Medicine, Stanford, California,U.S.A. Address correspondence to Hal Blumenfeld, Departments of Neurology, Neurobiology, Neurosurgery, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520-8018, U.S.A. E-mail: [email protected] Wiley Periodicals, Inc. © 2014 International League Against Epilepsy

1145

1146 H. Blumenfeld and K. J. Meador Consciousness is a challenging concept. Many people have strong opinions about what consciousness is or is not, perhaps because ultimately consciousness is what determines our personal individual experience throughout life. Consciousness also has tremendous clinical importance, particularly in epilepsy. Because of the great challenges in defining and understanding consciousness, some have advocated avoiding the term altogether when engaging in serious clinical or scientific discussion of epilepsy. However, loss of consciousness is a critical disability imposed by epilepsy, and one that clinicians must address in relation to safety and legal issues. Furthermore, the scientific investigation of the mechanisms of consciousness has become a legitimate and important endeavor for modern neuroscience. Fortunately, individuals such as Lüders and colleagues seek to confront the challenge.1 Only by having the temerity to investigate and discuss consciousness can we ensure continued progress and improved understanding of this important topic. The classification presented by Lüders and colleagues1 has several merits but also has weaknesses. On the positive side, they have emphasized the central importance of consciousness in the description and classification of epileptic seizures. In contrast, the Blume et al.2 “Glossary of Descriptive Terminology for Ictal Semiology” provides >80 descriptors of seizures, but the word “consciousness” appears not once. The 2010 International League Against Epilepsy (ILAE) report concludes that “the distinction based on impairment of consciousness or awareness, although of great pragmatic social importance (e.g., for driving), was impossible to define precisely,” and therefore the ILAE committee chose to lump all focal seizures into one undifferentiated category.3 As support for this approach, they cited Gloore’s 1986 opinion piece based on his anecdotal observations of individual patients during seizures.4 Although Piere Gloore was certainly a respected figure in epilepsy, other well-respected clinician-scientists in epilepsy have viewed consciousness as an important area for research (e.g., Penfield and Jasper). Furthermore, there has been much scientific progress on the fundamental pathophysiology and behavioral characterization of impaired consciousness in epilepsy in recent years.5–9 The ILAE

report succeeds in finding sufficient scientific and clinical evidence to distinguish 12 types of generalized seizures, including five types of absence and three types of myoclonic seizures, yet it does not distinguish even one subtype of focal seizures and instead combines them all under one heading.3 The ILAE report does allow the use of descriptive terms to replace the traditional categories of simple partial and complex partial seizures (Table 1). A recent commentary provides more concise terms compatible with the ILAE report, namely focal impaired consciousness seizures (FICS) and focal aware conscious seizures (FACS).10 Lüders and colleagues go further than prior classifications by introducing descriptive categories of impaired consciousness, not just in focal seizures but also in generalized seizures and in epileptic delirium.1 Another strength of their work is that it represents the consensus opinion of a large number of distinguished clinical epileptologists. Dr. Lüders deserves credit for promoting, discussing, and sharing his views on epilepsy classification with colleagues and collaborators over the years, and for keeping consciousness at the forefront of this discussion. However, their proposal has two main weaknesses. The first is that insufficient data are presented to justify their proposed five types of alterations of consciousness. The second is that the proposal introduces terms that may be confusing. We will discuss each of these concerns in turn.

The Need for More Data The proposed five types of alterations of consciousness in seizures are “auras with illusions or hallucinations, dyscognitive seizures, epileptic delirium, dialeptic seizures, and epileptic coma.”1 Additional discussion is needed of the altered physiology and behavior in these conditions and how they relate to other disorders of consciousness. In an effort to provide this information, we will now discuss the types of impaired consciousness in epilepsy using functional neuroanatomy as a framework (Table 2). Plum and Posner distinguished systems contributing to the content of consciousness (including specific sensory, motor, memory, and emotional systems) from systems

Table 1. Accepted terminology for impaired consciousness in focal or partial seizures ILAE 1981 Classification46

ILAE 2010 Commission Report3

Simple partial seizure

Focal seizure without impairment of consciousness or awareness. Subtypes include: (1) With observable motor or autonomic components; (2) Involving subjective sensory or psychic phenomenon only Focal seizure with impairment of consciousness or awareness. “Dyscognitive” a is a term that has been proposed for this concept Evolving to a bilateral, convulsive seizure (involving tonic, clonic, or tonic and clonic components)b

Complex partial seizure Partial seizure evolving to secondary generalized seizure a b

The term “dyscognitive” is confusing, as discussed in the text. Note that focal seizures that evolve to bilateral atonic seizures are not included.

Epilepsia, 55(8):1145–1150, 2014 doi: 10.1111/epi.12588

1147 Consciousness in Epilepsy Classification Table 2. Proposed anatomically based classification for impaired consciousness in epilepsy Type of deficits Impaired content of consciousness Selective lower-order cortical deficits Selective higher-order cortical deficits Impaired level of consciousness Widespread cortical deficits, moderate Widespread cortical deficits, severe Impaired content and level of consciousness Combined selective and widespread deficits

Seizure examplesa

Mechanisms

FACSb without cognitive dysfunction FACS with selective cognitive dysfunctionc

Focal seizure discharge Focal seizure discharge

Absence seizures and FICSd Generalized tonic–clonic seizurese

Widespread spike-wave, or slow waves Widespread polyspike discharge

Postictal period following focal motor seizure with secondary generalization

Focal and widespread abnormal activity

a

The list of seizure examples provided here is not intended to be exhaustive; there are several other possible examples for each category. Focal aware conscious seizures (FACS). This includes both motor and purely sensory seizures (i.e., auditory, olfactory, somatosensory, visual). Focal aware conscious seizures (FACS) with focal cognitive dysfunction such as ictal aphasia, ictal neglect, ictal visual agnosia, or epileptic amnesia. d Focal impaired consciousness seizures (FICS). Temporal lobe seizures with impaired consciousness show widespread depressed cerebral blood flow and cortical slow waves unlike temporal lobe seizures without impaired level of consciousness.8,32,33 Parietal lobe seizures with impaired consciousness show similar abnormal thalamocortical rhythms.47 Other FICS (i.e., frontal and occipital) may have similar mechanisms but have not yet been thoroughly investigated. e May also include secondary generalized seizures. b c

controlling the level of consciousness.11 Lesions or dysfunction affecting widespread bilateral regions of the cerebral hemispheres, the diencephalon, or the upper brainstem arousal systems can result in impaired level of consciousness. Typically disorders such as stroke—which cause focal deficits such as somatosensory loss, motor loss, aphasia, visual changes, or memory impairment—are not considered disorders of consciousness. Although a deficit in the content of consciousness is present, these patients are considered conscious because they are aware and can respond in a voluntary (not just reflexive) manner; overall function is relatively preserved. By analogy, patients who have seizures in focal regions causing a somatosensory aura, focal motor seizure, ictal aphasia, visual distortions, or epileptic amnesia without full loss of awareness and responsiveness are considered conscious despite having selective deficits in the content of consciousness (Table 2). The mechanism for impairment in these patients is focal seizure discharge confined to a limited region of the brain.12 This gives rise to focal deficits without impairment in the overall level of consciousness. These categories of FACS with “impaired content of consciousness” (Table 2) are roughly analogous to the Lüders et al.1 proposed categories of auras and dyscognitive seizures. Lüders et al. also point out that in these two categories focal deficits do not interfere with the overall level of consciousness. The only real distinction (aside from the terminology, discussed later) is that we include not just auras, which have no overt behavioral manifestations, but any focal seizures (including motor seizures) that interfere with selective aspects of sensory, motor, mnemonic, or emotional experience without disrupting the level of consciousness. In addition, because the scheme that we present is tied directly to anatomy (Table 2), some “auras” in the Lüders et al. terminology (e.g. simple visual hallucinations) fall into the category of selective lower-order cortical deficits,

whereas others (e.g. formed visual hallucinations) lie in the category of higher-order cortical deficits. Disorders of consciousness are usually considered to be conditions that affect the level of consciousness. These include coma, vegetative state, minimally conscious state, delirium, and certain types of epileptic seizures13 (Table 2). Again, according to classical principles of neurology described by Plum and Posner,11 impaired level of consciousness occurs in disorders that interfere with subcortical arousal systems, or with widespread bilateral corticothalamic networks, or with both. The same holds true for seizures that impair overall responsiveness (Table 2). In absence seizures, spike-wave discharges invade widespread cortical and subcortical networks,14–16 usually causing loss of responsiveness to higher-order tasks including choice reaction time, memory encoding, and verbal or motor responses to commands,; but sometimes sparing simpler more automatic behaviors such as finger tapping.17–20 The widespread moderately severe deficits of cortical function seen in absence seizures where some responsiveness may be preserved have been compared to the minimally conscious state.21–23 In focal seizures with impaired level of consciousness, there are also moderately severe deficits in widespread cortical function interfering with responses to verbal and nonverbal questions and commands24–28; but they may spare simpler responses such as reactive automatisms, visual tracking, ball grasp, or blink to visual threat.29,30 The physiology is best understood in temporal lobe seizures where impaired consciousness is associated with widespread depressed cerebral blood flow and cortical slow waves resembling deep sleep, coma, or encephalopathy.8,31–33 In such temporal lobe seizures, the widespread corticothalamic dysfunction is postulated to result from the spread of the focal temporal lobe seizure to subcortical structures (e.g., lateral septum, anterior hypothalamus, thalamus), which in turn depress the subcortical arousal systems Epilepsia, 55(8):1145–1150, 2014 doi: 10.1111/epi.12588

1148 H. Blumenfeld and K. J. Meador (e.g., cholinergic and serotonergic).6,34–36 In contrast, these widespread cortical-subcortical network changes are not seen in temporal lobe seizures in which consciousness is spared.7,8,32,33 Generalized tonic–clonic seizures usually cause widespread severe cortical deficits (Table 2), leading to lack of even simple responses such as visual tracking, ball grasp, or blink to visual threat.30 As noted by Lüders et al., 1 these behavioral deficits resemble the profound unresponsiveness seen in coma except that the eyes are usually open during seizures. In terms of pathophysiology, in the ictal phase there are widespread polyspike discharges associated with abnormally increased cortical and subcortical cerebral blood flow, which evolves to polyspike-and-wave in the clonic phase.37–40 Postictally behavioral responses remain depressed along with decreased cortical activity and widespread reduced cerebral blood flow, which, of interest, is correlated with increased cerebellar activity, suggesting a possible inhibitory role for the cerebellum in postictal depression.38 Finally, in many seizures there is a combination of intense focal discharges along with more widespread abnormalities, leading to impairment in both the content and level of consciousness (Table 2). This can occur in the postictal phase of focal seizures with secondary generalization, where localized postictal deficits often occur in the region of onset (e.g., postictal hemiparesis or aphasia), together with more global impaired responsiveness.41,42 These categories of “impaired level of consciousness” in seizures (Table 2) correspond roughly to the Lüders et al.1 proposed categories of dialeptic seizures, epileptic delirium, and epileptic coma. The main difference is that unlike the Lüders et al. proposal, we consider these to all affect the level of consciousness to a varying degree. As we have already discussed, in focal limbic (temporal lobe) seizures with impaired consciousness, there is direct evidence of sleep-like cortical slow wave activity, depressed cerebral blood flow, and reduced subcortical cholinergic arousalproducing behavior resembling the minimally conscious state or deep sleep parasomnias such as somnambulism.8,21,32–34 Therefore, although the eyes are usually open and some simple responses remain, we feel it is incorrect to state that these seizures do not affect arousal. In addition, since abnormal level of consciousness can occur with either impaired subcortical arousal or with widespread bilateral cortical network dysfunction, we would also consider the level of consciousness to be abnormal in absence seizures and in generalized tonic–clonic seizures, where widespread cortical dysfunction is associated with globally decreased responsiveness. The delirium-like state that exists in nonconvulsive status epilepticus again involves widespread, moderately severe cortical dysfunction and in that sense does not differ fundamentally from other epileptic seizures that cause impaired level of consciousness (Table 2). We agree that pathophysiEpilepsia, 55(8):1145–1150, 2014 doi: 10.1111/epi.12588

ology of increased behavioral arousal that occurs in some cases of epileptic and nonepileptic delirium requires further investigation.

The Need for Clear Terms There are some additional concerns with the Lüders et al.1 proposal that relate to the specific terms used. We should note that unlike the preceding discussion these concerns are not based on data but rather on opinion, and ultimately the choice of terminology is a matter of subjective preference. Our first concern is not with the accuracy of a term but with the confusion its use may create. We fully agree with Lüders et al. that the term “dyscognitive” offered by the ILAE2,3 is not an appropriate substitute for complex partial seizures or for “focal seizures with impaired consciousness” (FICS). As emphasized by Lüders et al. and as we have argued previously,10 selective cognitive deficits are not the same thing as impaired level of consciousness. For example, patients with ictal aphasia, memory loss, or other specific sensory, motor or cognitive dysfunction may remain fully alert and responsive, exhibiting selective deficits in content rather than overall level of consciousness (Table 2). In contrast, when focal seizures impair the level of consciousness there are widespread deficits across virtually all cognitive tasks.28 “Dyscognitive” is in fact very correctly used in the proposal by Lüders et al. to mean seizures with focal cognitive deficits, but without impaired overall level of consciousness. The only problem is that this term has already been widely (and incorrectly, in our opinion) promoted by the ILAE to mean focal seizures with impaired level of consciousness. Therefore, coopting the same term to mean something else has the potential to create much confusion and we therefore advocate avoiding the term “dyscognitive” altogether. Another potential concern is the term “dialepsis.”1,43 Although there are similarities in the behavioral state of staring unresponsiveness seen in absence seizures and in focal seizures with impaired consciousness, there are also many important differences in pathophysiology, behavior, treatment, outcome, and patient populations. It therefore seems inadvisable to unify these seizure types under a single term, particularly one that has the potential to sound arcane to the nonspecialist (this is a matter of personal opinion). Finally, the term “epileptic coma” for the postictal state following generalized tonic–clonic seizures may also create confusion. The term “epileptic coma” might suggest a prolonged state of coma-like unresponsiveness such as that seen in some patients in the intensive care unit with unexplained coma who turn out to be in status epilepticus.44,45 However, Lüders et al. intended this term to refer to the relatively brief state following generalized tonic–clonic seizures that commonly lasts less than an hour. Use of the term “epileptic coma” for this transient postictal impairment

1149 Consciousness in Epilepsy Classification seems confusing. Postictal impairment of content and/or level of consciousness would seem more appropriate terms.

Summary and Conclusions Lüders and colleagues have made a valuable contribution by raising the general interest in altered consciousness as an important concept in epilepsy description and classification. They proposed several categories of seizures in which altered consciousness may play a role. We have endeavored to bolster this effort by proposing alternate categories of seizures based on established anatomy and physiology (Table 2) and to discuss some of the existing data to support these categories. With this approach, seizures can be classified as disrupting the content of consciousness through effects on localized cortical circuits; or the level of consciousness through effects on subcortical arousal systems and/or widespread bilateral regions of cortex. Some of our categories roughly correspond to those of Lüders and colleagues, but we did not use their proposed terms because we felt some of them may add confusion rather than clarity. Further investigation of the pathophysiology and treatment of impaired consciousness is essential for the field. Ongoing discussions of terminology and classification are also important, and fortunately are continuing through several groups including the ILAE.

Acknowledgments HB was supported by NIH R01NS055829, R01NS066974, U01NS04 5911, and the Betsy and Jonathan Blattmachr Family.

Disclosure None 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.

References 1. Lüders H, et al. Proposal: different types of alteration and loss of consciousness in epilepsy. Epilepsia 2014;55:1140–1144. 2. Blume WT, Lüders HO, Mizrahi E, et al. Glossary of descriptive terminology for ictal semiology: report of the ILAE task force on classification and terminology. Epilepsia 2001;42:1212–1218. 3. Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005–2009. Epilepsia 2010;51:676–685. 4. Gloor P. Consciousness as a neurological concept in epileptology: a critical review. Epilepsia 1986;27(Suppl. 2):S14–S26. 5. Cavanna AE, Monaco F. Brain mechanisms of altered conscious states during epileptic seizures. Nat Rev Neurosci 2009;5:267–276. 6. Blumenfeld H. Impaired consciousness in epilepsy. Lancet Neurol 2012;11:814–826. 7. Lee KH, Meador KJ, Park YD, et al. Pathophysiology of altered consciousness during seizures: subtraction SPECT study. Neurology 2002;59:841–846. 8. Englot DJ, Yang L, Hamid H, et al. Impaired consciousness in temporal lobe seizures: role of cortical slow activity. Brain 2010;133:3764–3777.

9. Bartolomei F. Coherent neural activity and brain synchronization during seizure-induced loss of consciousness. Arch Ital Biol 2012;150:164–171. 10. Blumenfeld H, Jackson GD. Should consciousness be considered in the classification of focal (partial) seizures? Epilepsia 2013;54:1125– 1130. 11. Plum F, Posner JB. The diagnosis of stupor and coma. Philadelphia: Davis; 1982. 12. Ebersole JS, Pedley TA. Current practice of clinical electroencephalography, 3rd edn. Philadelphia, PA: Lippincott Williams & Wilkins; 2003. 13. Laureys S, Tononi G. The neurology of consciousness: cognitive neuroscience and neuropathology. Waltham, MA: Academic Press; 2008. 14. Avoli M, Gloor P, Kostopoulos G, Naquet T (Eds) Generalized epilepsy, Boston: Birkhauser; 1990. 15. Blumenfeld H. Cellular and network mechanisms of spike-wave seizures. Epilepsia 2005;46(Suppl. 9):21–33. 16. McCormick DA, Contreras D. On the cellular and network bases of epileptic seizures. Annu Rev Physiol 2001;63:815–846. 17. Blumenfeld H. Consciousness and epilepsy: why are patients with absence seizures absent? Prog Brain Res 2005;150:271–286. 18. Mirsky AF, Van Buren JM. On the nature of the “absence” in centrencephalic epilepsy: a study of some behavioral, electroencephalographic, and autonomic factors. Electroencephalogr Clin Neurophysiol 1965;18:334–348. 19. Berman R, Negishi M, Vestal M, et al. Simultaneous EEG, fMRI, and behavioral testing in typical childhood absence seizures. Epilepsia 2010;51:2011–2022. 20. Bai X, Vestal M, Berman R, et al. Dynamic time course of typical childhood absence seizures: EEG, behavior, and functional magnetic resonance imaging. J Neurosci 2010;30:5884–5893. 21. Blumenfeld H. Epilepsy and the consciousness system: transient vegetative state? Neurol Clin 2011;29:801–823. 22. Giacino J, Whyte J. The vegetative and minimally conscious states: current knowledge and remaining questions. J Head Trauma Rehabil 2005;20:30–50. 23. Giacino JT, Ashwal S, Childs N, et al. The minimally conscious state: definition and diagnostic criteria. Neurology 2002;58:349–353. 24. Escueta AV, Bacsal FE, Treiman DM. Complex partial seizures on closed-circuit television and EEG: a study of 691 attacks in 79 patients. Ann Neurol 1982;11:292–300. 25. Escueta AV, Kunze U, Waddell G, et al. Lapse of consciousness and automatisms in temporal lobe epilepsy: a videotape analysis. Neurology 1977;27:144–155. 26. Yang L, Shklyar I, Lee HW, et al. Impaired consciousness in epilepsy investigated by a prospective responsiveness in epilepsy scale (RES). Epilepsia 2012;53:437–447. 27. Bauerschmidt A, Koshkelashvili N, Ezeani CC, et al. Prospective assessment of ictal behavior using the revised Responsiveness in Epilepsy Scale (RES-II). Epilepsy Behav 2013;26:25–28. 28. Cunningham C, Chen WC, Shorten A, et al. Impaired consciousness in partial seizures is bimodally distributed. Neurology 2014;82:1736– 1744. 29. Jasper HH. Some physiological mechanisms involved in epileptic automatisms. Epilepsia 1964;5:1–20. 30. McPherson A, Rojas L, Bauerschmidt A, et al. Testing for minimal consciousness in complex partial and generalized tonic-clonic seizures. Epilepsia 2012;53:e180–e183. 31. Englot DJ, Mishra AM, Mansuripur PK, et al. Remote effects of focal hippocampal seizures on the rat neocortex. J Neurosci 2008;28:9066– 9081. 32. Blumenfeld H, McNally KA, Vanderhill SD, et al. Positive and negative network correlations in temporal lobe epilepsy. Cereb Cortex 2004;14:892–902. 33. Arthuis M, Valton L, Regis J, et al. Impaired consciousness during temporal lobe seizures is related to increased long-distance corticalsubcortical synchronization. Brain 2009;132:2091–2101. 34. Motelow JE, Gummadavelli A, Zayyad Z, et al. Brainstem cholinergic and thalamic dysfunction during limbic seizures: possible mechanism for cortical slow oscillations and impaired consciousness. Soc Neurosci Abstr 2012; Abstract number 487.25 Online at http://www. sfn.org/ Epilepsia, 55(8):1145–1150, 2014 doi: 10.1111/epi.12588

1150 H. Blumenfeld and K. J. Meador 35. Englot DJ, Blumenfeld H. Consciousness and epilepsy: why are complex-partial seizures complex? Prog Brain Res 2009;177:147– 170. 36. Englot DJ, Modi B, Mishra AM, et al. Cortical deactivation induced by subcortical network dysfunction in limbic seizures. J Neurosci 2009;29:13006–13018. 37. Varghese G, Purcaro MJ, Motelow JE, et al. Clinical use of ictal SPECT in secondarily generalized tonic-clonic seizures. Brain 2009;132:2102–2113. 38. Blumenfeld H, Varghese G, Purcaro MJ, et al. Cortical and subcortical networks in human secondarily generalized tonic-clonic seizures. Brain 2009;132:999–1012. 39. Jobst BC, Williamson PD, Neuschwander TB, et al. Secondarily generalized seizures in mesial temporal epilepsy: clinical characteristics, lateralizing signs, and association with sleep-wake cycle. Epilepsia 2001;42:1279–1287. 40. Theodore WH, Porter RJ, Albert P, et al. The secondarily generalized tonic-clonic seizure: a videotape analysis. Neurology 1994;44:1403– 1407.

Epilepsia, 55(8):1145–1150, 2014 doi: 10.1111/epi.12588

41. Blumenfeld H, Westerveld M, Ostroff RB, et al. Selective frontal, parietal and temporal networks in generalized seizures. Neuroimage 2003;19:1556–1566. 42. Rolak LA, Rutecki P, Ashizawa T, et al. Clinical features of Todd’s post-epileptic paralysis. J Neurol Neurosurg Psychiatry 1992;55:63–64. 43. Lüders H, Acharya J, Baumgartner C, et al. Semiological seizure classification. Epilepsia 1998;39:1006–1013. 44. Hirsch LJ. Classification of EEG patterns in patients with impaired consciousness. Epilepsia 2011;52(Suppl. 8):21–24. 45. Claassen J, Mayer SA, Kowalski RG, et al. Detection of electrographic seizures with continuous EEG monitoring in critically ill patients. Neurology 2004;62:1743–1748. 46. ILAE. Proposal for revised clinical and electroencephalographic classification of epileptic seizures. From the commission on classification and terminology of the international league against epilepsy. Epilepsia 1981;22:489–501. 47. Lambert I, Arthuis M, McGonigal A, et al. Alteration of global workspace during loss of consciousness: a study of parietal seizures. Epilepsia 2012;53:2104–2110.