CRITICAL REVIEW AND INVITED COMMENTARY
The new ILAE report on terminology and concepts for organization of epileptic seizures: A clinician’s critical view and contribution
Address correspondence to Chrysostomos P. Panayiotopoulos, Neurosciences Offices, West Wing -Third Floor, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, U.K. E-mail: CPanayiotopoulos@aol.com
The International League Against Epilepsy (ILAE) standardized classification and terminology for “epileptic seizures” of 1981 and “epilepsies and epileptic syndromes” of 1989 provide a fundamental framework for organizing and differentiating the epilepsies. However, a revision of these classifications is mandated by recent major technologic and scientific advances. Since 1997, the relevant ILAE Commissions have made significant efforts to achieve better and internationally uniform classifications as reflected in their reports of 2001, 2006, and 2010. Their initial aim to construct a “new scientific classification from application of methods used in biology that determines separate species and natural classes” proved elusive and, therefore, the last Commission in their report of 2010 confined their revisions to “new terminology and concepts” instead of “proposing a new classification (in the sense of organization) of epilepsies.” It is unfortunate that most of the proposals in this report are modified interpretations and nomenclature of previous ILAE classifications; new terms are not better than the old ones, and recent advances have not been incorporated. Hence, the new ILAE report met with considerable protest from several expert epileptologists. This critical review refers mainly to the epileptic seizures, the classification of which may be an easier and less controversial task in the ILAE revisions. A revised classification should incorporate advanced knowledge of seizure pathophysiology, and clinical, interictal, and ictal manifestations. Such an attempt was made and detailed in the 2006 report of the ILAE Classification Core Group. However, these changes were largely discarded in the new ILAE report of 2010, without justification. This is inexplicable considering that the scientific advances that were available to the two Commissions were the same or had improved between 2006 and 2010. Of major concern is that “No specific classification is recommended for focal seizures which should be described according to their manifestations.” Such a proposition defies the essence and the principle of any classification that requires an organization and a common language for communication. Free text descriptions are fine in a manual of differential diagnosis but not as a classification system. Another striking weakness is that even the accepted types of epileptic seizure are listed by name only, without defining them. The result is avoidable confusion. Furthermore, the report fails to consider reflex epileptic seizures. Status epilepticus is the most conspicuous omission despite immense advances of our understanding of it and its relevance on the classification. It appears that the new ILAE report does not fulfill its intent to improve the previous classifications and it may be premature to submit anything similar to this for approval by the ILAE General Assembly. The ILAE Commission could benefit by asking experts in basic and clinical science to provide a concise statement in their field of expertise as, for example, what are focal, myoclonic, or absence seizures, and their subtypes, their manifestations, and their possible pathophysiology. Areas of certainties and uncertainties, agreements and disagreements should be identified and stated clearly, with documentation of the reasons for it. Probably this is the only way forward for a truly scientific, sound, and clinically meaningful organizational system for the epileptic seizures and the epilepsies.
Outstanding achievements in the scientific and social aspects of epilepsies in the past 100 years can be largely attributed to the leaders of the International League Against Epilepsy (ILAE). The ILAE standardized classification and terminology for epileptic seizures (Commission, 1981) and syndromes (Commission, 1989) provides a fundamental framework for organizing and differentiating the epilepsies. These classifications were made through lengthy and thorough assessments of the clinical, electroencephalography (EEG), neurosurgical, neuropathologic, and other data that were then available. The Commissions explained their procedures and reasoning behind their decisions at length. Furthermore, they provided a brief definition of each epileptic seizure and epileptic syndrome. “This (classification) provided a universal vocabulary that not only facilitated communication among clinicians, but also established a taxonomic foundation for performing quantitative clinical and basic research on epilepsy” (Engel, 2001). However, others have been “viewing the old system as both antiquated and arbitrary” (Berg & Scheffer, 2011a).
There is general agreement that a thorough revision of these classifications is overdue because of advances and insights at all levels of epileptogenesis, from elementary structures and functions of brain cells, networks and oscillations, genes and their interactions, clinical-EEG manifestations of epileptic seizures and syndromes, video-EEG information, functional and structural imaging, investigative procedures and neurosurgery, molecular genetics, neuropharmacology, psychosocial science, and neuropsychology.
Since 1997, members of the ILAE Commissions on Classification and Terminology chaired by Pete Engel (1997–2005) and Anne Berg (2005–2009) have invested a lot of time and energy to incorporate these advances in order to achieve better and internationally uniform classifications (Engel, 2001, 2006; Berg et al., 2010). Their initial aim was to construct a “new scientific classification from application of methods used in biology that determines separate species and natural classes for the organization of seizures and epilepsies: As the tree of life (for living organisms) or the periodic table of the elements is our vision” (Berg & Scheffer, 2011a). However, such a scientific classification proved elusive and, therefore, the last Commission confined their revisions to “new terminology and concepts” instead of “proposing a new classification (in the sense of organization) of epilepsies” (Berg et al., 2010). It is unfortunate that most of the proposals in the new ILAE report (Berg et al., 2010) are modified interpretations and nomenclature of the previous ILAE classifications; new terms are not better than the old ones, and there are no definitions for each of the accepted epileptic seizure, syndrome, or disease, despite the significant advance made in their recognition from then (1981 and 1989) to now (2010). Hence, the new ILAE report met with considerable protest from several expert epileptologists, including two previous ILAE presidents (Avanzini, 2010; Wolf, 2010, 2011) and two editors of Epilepsia (Fisher, 2010; Shorvon, 2011a,b,c).
This critical review aims to assist the Commissions in their noble task of creating a modern organization of epileptic seizures and epilepsies that would be universally accepted, also considering that “The current Commission on Classification (2009–2013; Chair: Ingrid Scheffer) is preparing a final draft, to be submitted for approval by the ILAE General Assembly at the 2013 International Epilepsy Congress as the official ILAE position on classification” (Moshe, 2011). I purposely refer mainly to epileptic seizures because updating the classification and definitions for these should take priority and represents an easier and less controversial task in the ILAE revisions. The classification and terminology of epilepsies as proposed in the ILAE report (Berg et al., 2010) are much more problematic and contentious (Avanzini, 2010; Ferrie, 2010; Guerrini, 2010; Panayiotopoulos, 2010; Shinnar, 2010; Wolf, 2010; Beghi, 2011; Duncan, 2011; Shorvon, 2011a,b,c; Wolf, 2011; Wong, 2011).
In preparing this commentary, I have followed the advice of the Chairpersons on Classification to “carefully read the original report (Berg et al., 2010) and contribute to future discussions” (Berg & Scheffer, 2011b). I have also carefully studied previous original reports of the ILAE classifications and the relevant debates as stated in the new edition of my book A Clinical Guide of Epileptic Syndromes and Their Treatment; Based on the ILAE Classifications (Panayiotopoulos, 2010).
Definitions and Terminology of Epileptic Seizures and Epilepsies
These have been the subject of a continuing process of discussion and debate; they have been evolved, been clarified, or have been replaced through the various ILAE proposals. There is concern that certain terminology is “imprecise, misused or misunderstood” (Berg et al., 2010). Terms need to be clarified and redefined when new information arrives, rather than abandoned or replaced every time that something new comes to light. New terms may not be better understood or apply and may be as easily misconstrued and misused as the established ones (Ferrie, 2010). An extreme example of inappropriate terminological interventions in the new ILAE report (Berg et al., 2010) refers to “Disease versus syndrome: Although there is reason to distinguish the concepts of disease and syndrome, these terms are not consistently used in medicine. Ultimately, it was decided not to insist on the disease-syndrome distinction in referring to the epilepsies at this time, although either or both terms may be used depending on the context and custom” (Berg et al., 2010). However, “disease” is clearly differentiated from “syndrome” in any medical book and the ILAE classifications; it is the core term in “the International Classification of Diseases (ICD),” which is the international standard diagnostic classification for all general epidemiologic, many health management purposes, and clinical use.
We must recognize that even the definition of epilepsies is elusive, with at least four different ILAE proposals that are all referring to “epilepsy” (as if this were a single disease) (Berg, 2010; Panayiotopoulos, 2010). The definition of what epilepsies are may be a good example of an item to prioritize for an ILAE consensus. The most recent ILAE definition is that “Epilepsy is a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures and by the neurobiologic, cognitive, psychological, and social consequences of this condition. The definition of epilepsy requires the occurrence of at least one epileptic seizure” (Fisher et al., 2005). This met with significant protest by leading epileptologists (Beghi et al., 2005); epilepsy is not “a (single) disorder” and many patients with one or a few seizures may never manifest with psychological and social consequences, which are often the result of stigmatization. We should also be alerted to the notion that some terminologies and statements may promote re-stigmatization, as for example “The term benign is not recommended because it belies the growing understanding of the relationship between the epilepsies and a wide variety of brain disorders including cognitive, behavioral, and psychiatric illnesses as well as sudden death and suicide” (Berg et al., 2010). Such a decision contrasts the multiexpert recommendation of maintaining the term “benign” in the Monreale workshop (Vigevano et al., 2009) that “aided the Commission’s work” (Berg et al., 2010) and devalues the statement in the official ILAE report that “this remains an area where long-held beliefs and ignorance often clash with reason and evidence” (Berg et al., 2010).
Classification and Terminology as it Relates to Epileptic Seizures
Epileptic seizures are the essential components of epileptology that would need precise definition and understanding prior to attempting any further classification of the epilepsies. The currently valid 1981 “clinical and electroencephalographic classification of epileptic seizures” (Commission, 1981) is 30 years old, and its original authors emphasized the need for updating: “It must be stressed that the present classification is weighted clinically and should not be construed as representing the last word in identification of the origin of the epileptic seizure, ….Nor is the classification sacrosanct….With increasing knowledge, the categories may change, the skeleton will be “fleshed out” and the nuances elaborated. It is hoped that the classification in itself will aid in mobilizing those concepts which will lead to its modification in time…. This compilation of knowledge has been brought in line with the state-of-the-art technology without extrapolating to what cannot be observed, but cognizant of the evanescence of any living semantic endeavor which must remain subject to continual revision” (Commission, 1981). Contrary to this statement, Berg et al. (2010) assert that the previous classifications of seizures and epilepsies were “autocratic,”“not flexible,”“dominated by expert opinion and assertion,” and “often treated as rigid doctrine.”
The 1981 seizure classification (Commission, 1981) was the result of numerous workshops and lengthy discussions on various types of epileptic seizures utilizing the foremost epileptologists at the time, and the proposal was published after feedback and revisions made from the ILAE Chapters, the International Federation of Societies of Electroencephalography and Clinical Neurophysiology, and the World Federation of Neurosurgical Societies (Commission, 1981). The epileptic seizures were tabulated according to their (a) clinical, (b) ictal EEG, and (c) interictal EEG manifestations. They were broadly classified as (1) Generalized (convulsive and non-convulsive), (2) Partial (Focal, Local), and (3) Unclassified. Terms used and each type of seizure were precisely defined and fully described. [Correction added after online publication 17-Oct-2011: Wording of previous sentence has been updated.]
It should be expected that a revised classification would incorporate advanced current knowledge of pathophysiologic, clinical, interictal, and ictal manifestations derived from EEG and other modes of modern investigative procedures. Such an attempt was made and detailed in the 2006 report of the ILAE Classification Core Group (Engel, 2006). However, this revision is largely discarded in the new ILAE report (Berg et al., 2010), and without justification. This change of direction is inexplicable given that the scientific advances that were available to the two Commissions were the same or had improved between 2006 (Engel, 2006) and 2010 (Berg et al., 2010). According to Wolf, in the new ILAE report (Berg et al., 2010) ‘‘a classification of seizures is presented that is unrelated to the new concepts and is even more primitive than what was proposed in 1964. This is of no use” (Wolf, 2011).
The proposals certainly contain a better but all-inclusive definition/concept for focal and generalized seizures (Avanzini, 2010; Berg et al., 2010), but otherwise most of the report focuses on:
The distinction between focal and generalized seizures, terms that are rightly maintained in the classification with the clarification that they may not represent a clear dichotomy. That the differences between “generalized and focal seizures” are not as sharp as initially thought is not new and was certainly known by our mentors of the 1981 and 1989 classifications.
Discarding the term complex focal seizures because of “misuse or misunderstanding” of its meaning rather than new evidence. The original report (Commission, 1981) did not allow such a misuse and “complex partial seizures” were not used as synonymous to “temporal lobe seizures.” Furthermore, its authors had thoroughly considered that “a more persuasive argument existed for abolishing the words “simple” and “complex” in favor of “partial seizures with retention of consciousness” and “partial seizures with disturbance of consciousness” (Commission, 1981). Therefore, there is nothing novel in the new ILAE report that proposes that these seizures are described as “With impairment of consciousness or awareness which roughly corresponds to the concept of complex partial seizure. Dyscognitive is a term that has been proposed for this concept (Blume et al., 2001)” (Berg et al., 2010). Moreover, dyscognitive is a poor and confusing term that is not synonymous with impairment of consciousness (Blume et al., 2001; Fisher et al., 2005). This is particularly important to note for the 2010 report “that a guiding principle has been to strive for clarity and simplicity so that terms refer to single qualities and are not a mixture of different concepts and dimensions.” Similarly it is difficult to understand why “aura” is considered as a concept.
No Specific Classification Is Recommended in the New ILAE Report for Focal Seizures
Of major concern and in a marked departure from the 1981 classification (Commission, 1981) and the previous ILAE proposals of 2001 and 2006, is that “No specific classification is recommended for focal seizures which should be described according to their manifestations (e.g., dyscognitive, focal motor) or terms to describe degree of disability caused by the seizures” and we are encouraged to “consult the Glossary of Ictal Semiology (Blume et al., 2001) for well-defined descriptive terms” (Berg et al., 2010; Berg & Scheffer, 2011a).
Such a proposition of the ILAE report not to recommend a classification for the various types of focal epileptic seizures, defies the essence and the principle of any classification that requires an organization and a common language for communication. As Fisher emphasizes: “Free text descriptions of the numerous types of focal epileptic seizure are fine in a manual of differential diagnosis but should not be used as a classification system and makes future research, epidemiology and comparisons difficult” (Fisher, 2010). Furthermore, The Glossary of Ictal Semiology (Blume et al., 2001) recommended for consultation is already 10 years old, and many of its terms and descriptions need revision and clarity.
Accepted Types of Epileptic Seizures in the New ILAE Report Are Listed by Name Only
Another striking weakness of the new ILAE report is that even the accepted types of epileptic seizures are listed by name only in Table 2 (Berg et al., 2010); they are not defined. The result is again avoidable confusion. Let us consider two examples:
Absence seizures, which the Commission proposes to “simplify” into typical, atypical, and absence with special features (myoclonic absence and eyelid myoclonia). This oversimplification neglects rather than promotes the recent advances made in all aspects of absence seizures (Crunelli & Leresche, 2002; Hirsch & Valenti, 2006; Helbig et al., 2008; van Luijtelaar & Coenen, 2009; Berman et al., 2010; Mullen et al., 2010; Vestal & Blumenfeld, 2010). In addition, there is no direction or clarification on what the current defining criteria are, even for typical absence seizures, a matter recently debated in Epilepsia (Panayiotopoulos, 2008; Scheffer & Berg, 2008). Shall we accept that “An absence seizure is defined as a clinical change associated with generalized spike-and-slow-wave or multiple spike-and-slow-wave with a frequency of >2.5 Hz at the onset” as the Chairpersons of the ILAE Commission appear to support? (Scheffer & Berg, 2008). Even if this were so, a minimal requirement would be to specify the type of “clinical change” and whether impairment of cognition is a mandatory symptom in absence seizures.
Myoclonic seizures are listed in Table 2 (Berg et al., 2010) under “Generalized seizures.” Focal myoclonic seizures are not even mentioned, and certainly describing them by their clinical manifestations is not contributing to classification. No effort is made to incorporate our advanced knowledge on epileptic myoclonic seizures (Caviness & Brown, 2004; Genton et al., 2005; Guerrini et al., 2005; Caviness, 2009; Caviness & Truong, 2011). The report does not even clarify what epileptic myoclonic seizures are; the glossary is not informative, and we still depend on the 1997 Commission Report “on myoclonus and epilepsy in childhood” (Commission, 1997). Without defining the type of epileptic myoclonic seizures, it would be impossible to “organize specific forms of epilepsy (electroclinical syndromes)” as in the illustrated example by Berg and Scheffer on the basis of myoclonic seizures (Berg & Scheffer, 2011a). Myoclonic seizures are different in most syndromes and diseases, even if these are their defining epileptic manifestations (myoclonic epilepsy in infancy, juvenile myoclonic epilepsy, progressive myoclonus epilepsy, early myoclonic encephalopathy).
Other Specific Changes of the New Report Made to the 1981 Classification Include
“Neonatal seizures are no longer regarded as a separate entity. Seizures in neonates can be classified within the proposed scheme” (Berg et al., 2010). This oversimplification may be valid, but on what evidence? The immediately preceding ILAE report of 2006 stated “Although the components of neonatal seizures can be described in terms of the seizure types itemized above, they often display unique organizational features. Therefore, a study group will be created to more completely define and characterize the various types of neonatal seizures” (Engel, 2006). Has this advice been taken into account?
“Spasms are now included. The more general term epileptic spasms is used, which includes infantile spasms. There was inadequate knowledge to make a firm decision regarding whether spasms should be classified as focal, generalized, or both; consequently, they have been placed in their own group as unknown” (Berg et al., 2010). This may be an example of how the 1981 classification (Commission, 1981) could be improved by correcting the omissions. However, the meaning of the term “spasms” and what it includes should be clarified as suggested in the ILAE 2006 report: “The semiology and pathophysiology of epileptic spasms in the more mature brain need to be better defined” (Engel, 2006).
The report fails to consider reflex epileptic seizures, which are not cited even by name, although they should be classified and precisely defined.
Classification and Terminology as Related to Status Epilepticus
Status epilepticus is the most conspicuous omission in this new ILAE report (Berg et al., 2010), despite immense advances of our understanding of it, its various types, and their impact and relevance on the classification, pathophysiology, and management of epilepsies. There is much updated information as, for example, found in the proceedings of the three Colloquia on Status Epilepticus in London, Innsbruck, and Oxford (Colloqium on Status epilepticus, 2007, 2009).
A Proposal to Achieve a Truly Modernized Classification
It appears that the new ILAE report (Berg et al., 2010) does not fulfill its intent to “incorporate the tremendous advances in the neurosciences that have taken place in the last decade and that continue to occur” (Berg & Scheffer, 2011b). It is, therefore, premature to submit anything similar to this for approval by the ILAE General Assembly at the 2013 International Epilepsy Congress as the official ILAE position on classification.
In my view, it is preferable to continue using the previous ILAE classifications with certain modifications until we achieve our set targets. In our modern era of harmonization, it is surprising how much disarmonization would be caused by this proposed classification system. [Correction added after online publication 17-Oct-2011: Wording of previous sentence has been updated.] The advantages of a uniform nomenclature, however imperfect, are obvious to everyone.
There is today a wealth of experts in basic and clinical science to provide a consensus of opinion in their field of expertise as, for example, what are focal, myoclonic, or absence seizures, and their subtypes, their manifestations, investigative procedures, and their possible pathophysiology. It is up to the ILAE Commission to take advantage of the knowledge of these experts. In addition, Epilepsia could commission such consensus reports. Areas of certainties and uncertainties, agreements and disagreements, and the reasons for these should be identified, stated clearly, and documented. This will take no longer than 8–12 months to complete. These reports can generate at least a brief and clear (500–800 words) statement of consensus that everyone understands. Probably this is the only way out of this complex and unsatisfactory situation and toward a truly scientific, sound, and clinically meaningful organizational system for the epileptic seizures and the epilepsies that incorporates the tremendous advances in our field and is accepted by the wider community of clinicians and scientists.
I have no conflicts of interest to disclose. 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.