The quantitative measurement of consciousness during epileptic seizures

The quantitative measurement of consciousness during epileptic seizures

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Epilepsy & Behavior 30 (2014) 2–5

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The quantitative measurement of consciousness during epileptic seizures Andrea Nani a,b, Andrea E. Cavanna a,b,c,d,⁎ a

Michael Trimble Neuropsychiatry Research Group, BSMHFT, UK Section of Neuropharmacology and Neurobiology, School of Clinical and Experimental Medicine, University of Birmingham, UK c School of Life and Health Sciences, Aston University, Birmingham, UK d Sobell Department of Motor Neuroscience and Movement Disorders, UCL, Institute of Neurology, London, UK b

a r t i c l e

i n f o

Article history: Accepted 4 September 2013 Available online 7 October 2013 Keywords: Epilepsy Seizure Consciousness Scales Level Contents

a b s t r a c t The assessment of consciousness is a fundamental element in the classification of epileptic seizures. It is, therefore, of great importance for clinical practice to develop instruments that enable an accurate and reliable measurement of the alteration of consciousness during seizures. Over the last few years, three psychometric scales have been specifically proposed to measure ictal consciousness: the Ictal Consciousness Inventory (ICI), the Consciousness Seizure Scale (CSS), and the Responsiveness in Epilepsy Scale—versions I and II (RES-I and RES-II). The ICI is a self-report psychometric instrument which retrospectively assesses ictal consciousness along the dimensions of the level/arousal and contents/awareness. The CSS has been used by clinicians to quantify the impairment of consciousness in order to establish correlations with the brain mechanisms underlying alterations of consciousness during temporal lobe seizures. The most recently developed observer-rated instrument is the RES-I, which has been used to assess responsiveness during epileptic seizures in patients undergoing video-EEG. The implementation of standardized psychometric tools for the assessment of ictal consciousness can complement clinical observations and contribute to improve accuracy in seizure classification. This article is part of a Special Issue entitled Epilepsy and Consciousness. © 2013 Elsevier Inc. All rights reserved.

1. Introduction. Assessment of ictal consciousness and calssification of epileptic seizures. The classification of seizures has the twofold function of assisting the clinical assessment of patients with epilepsy and facilitating communication between health professionals. The history of seizure classification systems has largely relied upon accurate clinical observations and expert opinions, which converged in the dichotomy between generalized seizures (characterized by loss of consciousness and other clinical correlates of synchronous spike–wave discharges occurring in both hemispheres) and partial seizures (occasionally associated with complex alterations of consciousness and other clinical correlates of focal cortical disturbances) [1]. This was already formally established in the first classification of epileptic seizures proposed by Gastaut in 1970, which based the assessment of ictal consciousness on the clinical evaluation of ‘loss of contact’ with the external environment, in line with the approach of the French epileptology school [2]. When the International League Against Epilepsy (ILAE) formalized the first classification system [3,4], partial seizures were further divided into simple partial seizures (in which conscious awareness is

⁎ Corresponding author at: Department of Neuropsychiatry, The Barberry National Centre for Mental Health, 25 Vincent Drive, Birmingham B152FG, UK. E-mail address: [email protected] (A.E. Cavanna). 1525-5050/$ – see front matter © 2013 Elsevier Inc. All rights reserved.

preserved) and complex partial seizures (in which conscious awareness is disrupted) [5]. As new scientific information was acquired through the refinement of neurophysiology research and the development of neuroimaging and genetic and molecular biology, the ILAE put forward proposals to revise the classification system [6–8]. Within this new conceptual framework, partial seizures were termed focal and are still categorized into seizures ‘without impairment of consciousness or awareness’ (corresponding to the classical category of simple partial seizures) and seizures ‘with impairment of consciousness or awareness’ (corresponding to the classical category of complex partial seizures). Recently, this approach was further developed by Blumenfeld and Jackson [9], who proposed two categories of focal seizures which build on both the old and new classification systems: ‘focal aware consciousness seizures’ (FACS) and ‘focal impaired consciousness seizures’ (FICS). Thus, alterations of consciousness continue to be a widely accepted distinguishing feature of focal seizures. Over the last few years, a few psychometric instruments have been developed to measure alterations of consciousness which are specific to epileptic seizures. In this article, we review the first three scales proposed for the measurement of consciousness in epilepsy, focusing on their development and validation process, clinimetric characteristics, and practical use (Table 1): the Ictal Consciousness Inventory (ICI), the Consciousness Seizure Scale (CSS), and the Responsiveness in Epilepsy Scale—versions I and II (RES-I and RES-II).

A. Nani, A.E. Cavanna / Epilepsy & Behavior 30 (2014) 2–5 Table 1 Summary of the clinimetric characteristics of the scales specifically developed to assess consciousness in epilepsy. Scale





Cavanna et al. 2008 Italy Patient 20 No + Yes Yes

Arthuis et al. 2009 France Assessor 8 Yes + No No

Yang et al./Bauerschmidt et al.

Year Country Rater Items Direct observation of seizure Administration/scoring burdena Psychometric testing Used in nonepileptic attacks

2012/2013 USA Assessor 12/10 + 1 Yes ± Yes No

Abbreviations: ICI, Ictal Consciousness Inventory; CSS, Consciousness Seizure Scale; RES, Responsiveness in Epilepsy Scale. a Administration burden was rated as follows: “+” (easy) and “±” (moderate).

2. Ictal Consciousness Inventory (ICI) The ICI is a self-report psychometric instrument specifically developed in 2008 to measure ictal consciousness as reported by patients with epilepsy [10]. This scale consists of 20 items which evaluate both the level of general awareness/responsiveness (items 1–10) and the “vividness” of ictal subjective experiences (items 11–20) during epileptic seizures. The scale was originally proposed by its authors as a guide within the bidimensional model for the evaluation of ictal consciousness. The model addresses both the level of awareness and the subjective content of conscious experience [11]. Within this theoretical framework, patients with generalized seizures present with complete unresponsiveness and the absence of any ictal subjective conscious experience (i.e., cluster around the 0 level and 0 contents point). By contrast, during complex partial seizures, both the level and content of consciousness can be reported with different degrees of intensity. In particular, complex partial seizures originating in the temporal lobe are often associated with specific subjective feelings (so-called experiential phenomena). The ICI has specifically been developed and validated to quantify the vividness of these experiential phenomena during ictal consciousness. The ICI was developed in three stages. In the first stage, 20 items measuring alterations of ictal consciousness were derived from patient interviews, expert opinion, and literature review [12]. The first 10 items refer to the level of consciousness and evaluate self-consciousness; general awareness of time, place, and other people's presence; comprehension of other people's words; verbal and nonverbal responsiveness; gaze control; forced attention; and voluntary initiative. Items 11 to 20 concern the contents of consciousness and evaluate the following subjective experiences: dreamy states, symptoms of derealization (with both temporal and spatial features), feeling of the presence of an absent person, illusions, hallucinations, déjà vu/vécu, and unpleasant and pleasant ictal emotions. Overall, each item can be rated by the patient on a 0–2 Likert-type scale. Therefore, the ICI yields two subscores ranging from 0 to 20: the first one for the level and the second one for the contents of ictal consciousness. Higher scores indicate increased alertness and more vivid experiential symptoms, respectively. In the second stage, 110 outpatients, recruited in three secondary referral centers for the diagnosis and management of epilepsy, completed the two ICI subscales along with a battery of standardized psychometric instruments. The diagnosis of epilepsy was made according to the ILAE criteria [4] by at least two different neurologists who were not involved in the development of the scale. All patients younger than 18 years old, with an uncertain diagnosis of epilepsy, a reading level less than sixth grade, a diagnosis of learning disability, or a Mini Mental State Examination score inferior to 24, were excluded from the validation study. As part of the second stage, all the patients were assessed by a


neurologist/neuropsychiatrist with experience in epilepsy. Following a thorough clinical interview, each participant was administered standardized psychometric rating scales to evaluate common psychiatric comorbidities, including depression, anxiety, and dissociative disorders. After this evaluation, the patients were asked to think about their witnessed seizures and complete an ICI form for every seizure they could remember. In the third stage, the psychometric properties of the ICI were tested via standard statistical methods, including principal component factor analysis. The ICI performed well in terms of acceptability, validity, and reliability. Ictal Consciousness Inventory scores were in the expected directions: patients diagnosed with generalized epilepsy (n = 32) reported low scores on both level and content subscales, whereas patients with partial epilepsy (n = 78) reported higher scores, and patients with temporal lobe epilepsy (n = 67) scored higher than patients with frontal lobe epilepsy (n = 11), especially with regard to the contents subscale. The results of the development and validation process led the authors to conclude that the ICI is an accurate clinical instrument for collecting retrospective accounts of the complex phenomenology of seizures along the dimensions of the level and contents of consciousness, with focus on the ictal experiential phenomena. The relatively small sample size (especially with regard to the group with frontal lobe epilepsy) and the recruitment from specialist settings (introducing possible referral bias) were the main limitations of the ICI validation study. Finally, both ictal and postictal amnesia could affect the accuracy of retrospective self-report ICI scores [13]. A study by Ali et al. [14] employed the ICI to quantitatively evaluate ictal alterations of consciousness in 95 adult outpatients attending general neuropsychiatry and epilepsy clinics with established diagnoses of either epilepsy (n = 66) or nonepileptic attack disorder (n = 29), excluding patients with uncertain or dual diagnoses. The scores for ICI-level and ICI-contents were calculated for the 167 questionnaires answered by patients with epilepsy (n = 119, of which 58 were patients with temporal lobe epilepsy, 14 with frontal lobe epilepsy, and 47 with idiopathic generalized epilepsy) and patients with NEAD (n = 48). The authors found significantly higher scores in both the level and content domains for patients with nonepileptic attack disorder, who reported significantly greater levels of general awareness/responsiveness and more vivid subjective experiences during attacks. The ICI was therefore proposed as a potentially useful self-report instrument to supplement clinical and instrumental tests for the differential diagnosis of epilepsy and nonepileptic attack disorder.

3. Consciousness Seizure Scale (CSS) The CSS was developed in a study from 2009 originally aimed at analyzing the mechanisms underlying loss of consciousness during temporal lobe seizures [15]. This scale takes into consideration different features of conscious experience, delineating 8 criteria: unresponsiveness (criteria 1 and 2); visual attention (criterion 3); consciousness of the seizure (criterion 4); adapted behavior (criterion 5); amnesia (criteria 6 and 7); and global appreciation of consciousness by an experienced physician (criterion 8). All items are rated by the epileptologist: items 1 to 7 can be scored 0 or 1, while the eighth item from 0 to 2, thus yielding a possible total score of 0 to 9. Higher scores indicate more severe loss of consciousness. Temporal seizures are characterized by neuronal discharges that originate in the temporal lobe and propagate along networks interconnecting both cortical and subcortical regions [16]. The CSS has been proposed to quantitatively assess loss of consciousness within the theoretical framework of the ‘global workspace’ theory of consciousness [17,18]. According to this model, conscious information becomes available through the synchronized activity of neuronal modules linked to widespread networks within different brain regions. Thalamocortical communication plays a crucial role in this dynamic system [19,20], as the deactivation of thalamic structures, along with


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parietal and frontal cortices, can impair the conscious processing of information by preventing it from entering the global workspace [21–25]. In the original study by Arthuis et al. [15], 12 patients with intractable temporal lobe epilepsy were selected among 125 patients who underwent presurgical assessment between 2000 and 2006. All patients were investigated with the use of intracerebral electrodes and comprehensively assessed through neurological examination, neuropsychological testing, routine magnetic resonance imaging (MRI), surface electroencephalography (EEG), and stereo-EEG (depth electrodes). Selection criteria included seizure focus in the temporal lobe, with at least one intracerebral electrode reaching the thalamus, or the lateral parietal lobe and the posterior cingulate gyrus. After removing the electrodes, a brain MRI scan was performed so that the trajectory of every electrode could be visualized. All seizures captured in the study were either spontaneous or induced by electrical stimulation. In total, 99 videos of seizures were recorded from the 12 participants. The CSS was then used to evaluate the degree of loss of consciousness. In this study, each seizure was independently scored by two clinicians, and the mean of the two scores was retained for the analysis. Both intrarater and interrater interclass correlation coefficients were computed for the CSS quotations in order to test the validity of the scale. Seizures were excluded if their video recording was of poor quality, the patient was not tested or tested too late or developed a secondarily generalized seizure, or more than two CSS items were not scored. Thirty-five seizures were scored using the CSS, which allowed the authors to divide them into three groups: Group A without loss of consciousness (score ≤1); Group B with an intermediate or partial loss of consciousness (score ranging from 2 to 5); and Group C with profound loss of consciousness (score ≥6). Comparison of electrophysiological signals between Groups A and C revealed significant differences in the synchronization of neural networks, which was found to be more widespread in Group C. The most indicative feature in seizures characterized by loss of consciousness was a higher synchronization within ‘extratemporal’ structures, including precuneus/posterior cingulate cortex [26–28]. These findings are consistent with neuroscientific studies suggesting that the deactivation or dysfunction of these regions might play a pivotal role in determining loss of consciousness during epileptic seizures [29]. Based on these findings, the authors proposed the CSS as a valid tool for the assessment of the degree of consciousness impairment in temporal lobe seizures, suggesting a reliable correlation between this index and the objective measures of neural signal synchronization. The main limitation of the CSS scale is that the development of this instrument was not based on standardized prospective testing, suggesting that more research is needed to evaluate its psychometric properties.

Both adult and pediatric patients referred to video-EEG for the investigation of epilepsy (n = 52; minimum age: 7 years) took part in the original development and validation study of the RES-I. Patients with cognitive or motor impairment that could prevent task performance, as well as patients with previously documented nonepileptic attacks, were excluded from the study [14,33,34]. A total of 59 seizures from 18 patients were captured and tested with the RES-I. Neurologists who specialized in epilepsy reviewed the video-EEG recordings and classified the captured episodes as subclinical seizures, auras, partial seizures, or generalized tonic–clonic seizures. Scoring for the RES-I began immediately after seizure onset and was repeated through the ictal and postictal periods until the patients returned to their baseline performance level. Interictal memory was tested at least 6 h after real-time RES-I assessments. Ten healthy controls without a history of neurologic conditions were also enrolled in the study to measure how different examiners and raters can influence the results of the scale. Control subjects were asked to simulate two types of seizures for about 1 min: a simple partial seizure (without impairment of consciousness) and a complex partial seizure (with impairment of consciousness). All simulated seizures were recorded and independently scored on the RES-I items by two trained examiners, who also scored the items of Levels 1 and 2 on a total of 20 video recordings of real seizures from 10 different patients. Both intra- and interrater reliability were found to be high. The authors found that the measurement of consciousness impairment on the RES-I was related to the seizure type: consciousness scores were lowest in generalized tonic–clonic seizures, intermediate in partial seizures, and highest in auras and subclinical seizures. Of note, impairment of consciousness was rated as higher in partial seizures with EEG changes than those with no EEG changes. The delay of postictal recovery and memory deficits also correlated with lower RES-I scores during seizures. These results were in line with the clinical distinction between simple partial seizures (higher RES-I scores) and complex partial seizures (lower RES-I scores). Limitations of this study included the variability in seizure phenomenology within participants and the relatively small sample size. Furthermore, it was acknowledged that the RES-I requires personnel training and skills. The RES-II scale is a more recent refinement of the RES-I [35]. The new version has the same structure as the RES-I, with a reduction of the number of items to 10. It is possible to score an additional item assessing responsiveness to a painful stimulus, which is tested only in case the patient has failed to respond to any of the 10 items. Therefore, the RES-II appears to be more user-friendly and less time-consuming than the RES-I, thereby increasing efficiency and preserving the reliability of its predecessor.

4. Responsiveness in Epilepsy Scale (RES-I and RES-II)

5. Measurement of ictal consciousness in clinical practice and research

The RES was recently developed in two versions to assess ictal responsiveness in patients with epilepsy during video-EEG [30]. This scale was modified from the JFK Coma Recovery Scale—Revised [31] to enable testing within the typical short (1–2 min) time frame of seizures [32]. The RES-I consists of 12 items across three levels: 8 items in Level 1, 2 items in Level 2, and 2 items in Level 3. Items in Level 1 include orientation questions and other verbal questions and commands to test receptive and expressive language, visual processing, and motor praxis. Items in Level 2 involve sensorimotor responses and visual tracking. Items in Level 3 assess responses to visual threats and noxious tactile stimulation. In addition to these 3 levels, the RES-I includes tests for memory recall at seizure onset and postictal motor performance. Item scores range from 0 to 5. Level 2 is scored only if the patient's score is less than 3 on any two consecutive items on Level 1. In turn, Level 3 is scored only if the patient's score is 0–1 on all the items in Level 2. Item scores are subsequently normalized on a scale from 0 to 1; finally, normalized scores concur to yield a composite 0–1 consciousness score.

The assessment of consciousness during epileptic seizures is often challenging, especially because in the scientific literature, there is no comprehensive and widely accepted definition of consciousness [36]. This term is linked to a plethora of other concepts which are sometimes erroneously used as synonyms, such as ‘awareness’, ‘responsiveness’, ‘subjective experience’, and ‘wakefulness’ [37]. In clinical practice, however, the need for conceptual clarity and standardization of assessment tools is of the greatest importance. This is reflected by the pivotal role that the assessment of consciousness has traditionally played in the classification and evaluation of both focal and generalized seizures [9,38,39]. Over the last few years, three scales have been specifically developed for the measurement of consciousness during epileptic seizures. These psychometric instruments have been shown to have different characteristics and advantages for the quantitative assessment of alterations of consciousness as part of the ictal phenomenology. Initial results obtained from the administration of these instruments are promising

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in terms of better characterization of seizure semiology. Moreover, some of the findings are in line with neurophysiological and neuroimaging data suggesting that seizure-induced alterations of the level of consciousness (arousal) and alterations of the subjective contents of consciousness (awareness) represent separate dimensions and have different brain correlates. Specifically, impairment of the overall level of consciousness which characterizes both primarily and secondarily generalized seizures seems to be associated with transient dysfunction of the default mode network [40–47]. By contrast, alterations in the qualitative features of subjective contents of consciousness (e.g., experiential phenomena reported in the context of focal seizures) have long been known to be associated with temporal lobe epilepsy [48–50]. Based on these initial results, future research should focus on further testing of these instruments and their application to clinical practice, in order to improve the diagnostic accuracy of epileptic seizures [51] and clinicopathological correlations [52]. References [1] Cavanna AE, Ali F. Epilepsy: the quintessential pathology of consciousness. Behav Neurol 2011;24:3–10. [2] Gastaut H. Clinical and electroencephalographic classification of epileptic seizures. Epilepsia 1970;11:102–13. [3] Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised clinical and electroencephalographic classification of epileptic seizures. Epilepsia 1981;22:489–501. [4] Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for a revised classification of epilepsies and epileptic syndromes. Epilepsia 1989;30:389–99. [5] Cavanna AE, Rickards H, Ali F. What makes a simple partial seizure complex? Epilepsy Behav 2011;22:651–8. [6] Engel J. A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: report of the ILAE Task Force on Classification and Terminology. Epilepsia 2001;42:796–803. [7] Engel J. Report of the ILAE Classification Core Group. Epilepsia 2006;47:1558–68. [8] Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde Boas W, 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;51:676–85. [9] Blumenfeld H, Jackson GD. Should consciousness be included in the classification of focal (partial) seizures? Epilepsia 2013;54(6):1125–30. [10] Cavanna AE, Mula M, Servo S, Strigaro G, Tota G, Barbagli D, et al. Measuring the level and contents of consciousness during epileptic seizures: the Ictal Consciousness Inventory. Epilepsy Behav 2008;13:184–8. [11] Monaco F, Mula M, Cavanna AE. Consciousness, epilepsy and emotional qualia. Epilepsy Behav 2005;7:150–60. [12] Cavanna AE. Seizures and consciousness. In: Schachter SC, Holmes G, KasteleijnNolst Trenite D, editors. Behavioral aspects of epilepsy: principles and practice. New York: Demos; 2008. p. 99–104. [13] Heo K, Han S, Lim SR, Kim MA, Lee BI. Patient awareness of complex partial seizures. Epilepsia 2006;47:1931–5. [14] Ali F, Rickards H, Bagary M, Greenhill L, McCorry D, Cavanna AE. Ictal consciousness in epilepsy and nonepileptic attack disorder. Epilepsy Behav 2010;19:522–5. [15] Arthuis M, Valton L, Régis J, Chauvel P, Wendling F, Naccache L, et al. Impaired consciousness during temporal lobe seizures is related to increased long-distance cortical–subcortical synchronization. Brain 2009;132:2091–101. [16] Guye M, Regis J, Tamura M, Wendling F, McGonigal A, Chauvel P, et al. The role of corticothalamic coupling in human temporal lobe epilepsy. Brain 2006;129:1917–28. [17] Dehaene S, Naccache L. Towards a cognitive neuroscience of consciousness: basic evidence and a workspace framework. Cognition 2001;79:1–37. [18] Baars BJ. Global workspace theory of consciousness: toward a cognitive neuroscience of human experience. Prog Brain Res 2005;150:45–53. [19] Tononi G, Edelman GM. Consciousness and complexity. Science 1998;282:1846–51. [20] Llinas R, Ribary U. Consciousness and the brain. The thalamocortical dialogue in health and disease. Ann N Y Acad Sci 2001;929:166–75.


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