Epilepsia, 53(3):405–411, 2012 doi: 10.1111/j.1528-1167.2011.03376.x
CRITICAL REVIEW AND INVITED COMMENTARY
Modern technology calls for a modern approach to classification of epileptic seizures and the epilepsies *Hans O. Lu¨ders, *Shahram Amina, yChristopher Baumgartner, zSelim Benbadis, xAdriana Bermeo-Ovalle, *Michael Devereaux, {Beate Diehl, **Jonathan Edwards, *Guadalupe Fernandez Baca-Vaca, yyHajo Hamer, zzAkio Ikeda, *Kitti Kaiboriboon, xxChristoph Kellinghaus, *Mohamad Koubeissi, {{David Lardizabal, *Samden Lhatoo, ***Ju¨rgen Lu¨ders, yyyJayanti Mani, zzzLuis Carlos Mayor, *Jonathan Miller, xxxSoheyl Noachtar, *Elia Pestana, {{{Felix Rosenow, ****Americo Sakamoto, *Asim Shahid, yyyyBernhard J. Steinhoff, *Tanvir Syed, ***Adriana Tanner, and zzzzSadatoshi Tsuji *Epilepsy Center, Case Medical Center, University Hospitals, Cleveland, Ohio, U.S.A.; yKarl Landsteiner Institute for Clinical Epilepsy Research and Cognitive Neurology, General Hospital Hietzing with Neurological Center Rosenhugel, Vienna, Austria; zTampa General Hospital, University of South Florida, Tampa, Florida, U.S.A.; xRush University Medical Center, Department of Neurological Sciences, Section of Epilepsy, Chicago, Illinois, U.S.A.; {Institute of Neurology, University College London, London, United Kingdom; **Comprehensive Epilepsy Center, The Medical University of South Carolina, Charleston, South Carolina, U.S.A.; yyEpilepsy Center, Department of Neurology, University of Erlangen, Erlangen, Germany; zzDepartment of Neurology, Kyoto University School of Medicine, Kyoto, Japan; xxDepartment of Neurology, Klinikum Osnabru¨ck, Osnabru¨ck, Germany; {{Epilepsy Center, University of Missouri, Columbia, Missouri, U.S.A.; ***Epilepsy Program, Saint Mary’s Neuroscience Program, Grand Rapids, Michigan, U.S.A.; yyyEpilepsy, Kokilaben Dhirubhai Ambani Hospital, Mumbai, India; zzzColombia University Hospital, Santa Fe of Bogota Foundation, Bogota, Colombia; xxxEpilepsy Center and Neurological Sleep Center, Department of Neurology, University of Munich, Munich, Germany; {{{Epilepsy Center Hessen (EZH), Philipps-University and University Hospitals Marburg, Marburg, Germany; ****Ribeirao Preto Clinic, Ribeirao Preto, Sa˜o Paulo, Brazil; yyyyKork Epilepsy Center, Landstrasse, Kehl-Kork, Germany; and zzzzDepartment of Neurology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Fukuoka, Japan
SUMMARY In the last 10–15 years the ILAE Commission on Classification and Terminology has been presenting proposals to modernize the current ILAE Classification of Epileptic Seizures and Epilepsies. These proposals were discussed extensively in a series of articles published recently in Epilepsia and Epilepsy Currents. There is almost universal consensus that the availability of new diagnostic techniques as also of a modern understanding of epilepsy calls for a complete revision of the Classification of Epileptic Seizures
In recent debates about the classification of epileptic seizures and epilepsies (Beghi, 2011; Berg & Scheffer, 2011a,b; Duncan, 2011; Engel, 2011; Jackson, 2011; Moshe, 2011; Shorvon, 2011a; Wolf, 2011; Wong, 2011) Accepted November 17, 2011; Early View publication February 14, 2012. Address correspondence to Hans Lders, Epilepsy Center, Case Medical Center, University Hospitals, 6 Whisperwood Lane, Chagrin Falls, OH 44022, U.S.A. E-mail:
[email protected] Wiley Periodicals, Inc. ª 2012 International League Against Epilepsy
and Epilepsies. Unfortunately, however, the Commission is still not prepared to take a bold step ahead and completely revisit our approach to classification of epileptic seizures and epilepsies. In this manuscript we critically analyze the current proposals of the Commission and make suggestions for a classification system that reflects modern diagnostic techniques and our current understanding of epilepsy. KEY WORDS: Critical review, Classification proposal, Four-dimensional classification.
there seems to be a consensus that the availability of modern diagnostic technologies now calls for a complete revision of the approach we use to classify epilepsies, and to a lesser degree epileptic seizures. Traditionally epileptic seizures have been primarily classified as ‘‘electroclinical entities’’ taking into account mainly the symptomatologic characteristics of the epileptic seizures and the interictal and ictal EEG. So far the epilepsies too have been classified mainly by the electroclinical characteristics of the seizures (a patient with a given epilepsy could have one or more types of epileptic seizures). However, such other
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406 H. O. Lu¨ders et al. features as the age of onset of the seizures, seizure frequency, and associated brain lesions, also have contributed to the definition of ‘‘epileptic syndromes.’’ It is important to realize that this ‘‘electroclinical’’ approach (in which the dominant feature of the classification of epileptic seizures and epilepsies are the ‘‘electroclinical entities’’ and ‘‘epileptic syndromes’’) leads (1) to confusion between epileptic seizures and epilepsies and (2) in many instances also too rigidly defines the relationship between epileptic syndromes (epilepsies) and epileptic seizures. For example, when classifying a seizure as a complex partial seizure we are already specifying that the patient has focal epilepsy and when classifying a patient as having absence seizures we imply that the patient has generalized epilepsy. From the ongoing debates on classification mentioned above (Beghi, 2011; Berg & Scheffer, 2011a,b; Duncan, 2011; Engel, 2011; Jackson, 2011; Moshe, 2011; Shorvon, 2011a; Wolf, 2011; Wong, 2011) it is clear that, with few exceptions, everybody agrees that it is time to find a new approach to classify the epilepsies and epileptic seizures. At the same time, it seems that some authors are not ready to take a bold step ahead and break out of the old classification system. Others suggest some radical changes, but then advocate preservation of the old and in our view obsolete terminology. We certainly agree that replacing the terms idiopathic, symptomatic, and cryptogenic respectively by genetic, structural-metabolic, and unknown has advantages but we feel that it would be even more important to develop new concepts of how to classify epileptic seizures and the epilepsies. We certainly agree with Prof. Shorvon (Shorvon, 2011a) that etiology is one of the fundamental aspects of a classification of the epilepsies. However, etiology is only one of the dimensions that define a given epilepsy. As we mention below, we feel that the primary objective of an etiological classification (or database) should be the precise definition of the etiology of the epilepsy in an individual patient. In other words, it is not enough to define in an individual patient whether he/she has epilepsy due to one of the broad categories of genetic, metabolic or structural causes. What we need to know is the exact cause of the epilepsy (for example not only that there is a brain tumor, but the precise type and location of the tumor is also important). We certainly agree with Dr. Berg that we should list etiology as unknown if we do not know the cause of the epilepsy. We also support Dr Wong’s position (Wong, 2011) that a multidimensional classification of the epilepsies is necessary and such a multidimensional system should include among others, the etiology and the characteristics of the epileptic seizures. However, as outlined below we strongly feel that the dimensions we create should be independent and it is time to abandon the concept of ‘‘electroclinical syndromes.’’ Epilepsia, 53(3):405–411, 2012 doi: 10.1111/j.1528-1167.2011.03376.x
A Critique and Recommendations on the ILAE Commission on Classification and Terminology While it is easy to criticize a classification system, we feel that criticism should always be closely linked to an alternative that the authors feel addresses the criticism and has advantages over the criticized system. Therefore, we would like to make the following suggestions to the ILAE Commission on Classification and Terminology: Break tradition We would like to encourage the Commission on Classification and Terminology to develop a new classification system that takes advantages of all the modern diagnostic technologies even if it completely breaks with the currently accepted ILAE classification systems that were developed at an era in which diagnostic tools were limited to clinical observations and electroencephalography, in the absence of access to modern diagnostic techniques. In the design of such a new classification system the Commission should not be concerned that ‘‘traditionalists’’ will have to learn to approach classification of epilepsies and epileptic seizures from a completely new point of view. It is clear that the current Commission on Classification and Terminology is trying to find a smooth transition between the old system and a still poorly defined new system. Such a tentative approach, however, will greatly limit the ability of the Commission to develop a really new classification that takes advantage of all modern diagnostic tools and corrects all the limitations of the old classification systems. Besides, extensive experience in our Institutions, in which for many years we have been using and teaching the Four-dimensional Classification of Epilepsies and Epileptic Seizures, has shown that such a modern classification can be easily taught to a new generation of epileptologists. Define and specify purpose The Commission should clearly specify the purpose of the classification system it is developing. The Commission should then explain how the proposed Classification best satisfies the purpose it has agreed on. For example, is a classification of epileptic syndromes really necessary if the purpose of the classification system is to guide therapeutic options and prognosis, while the proposed new classification already calls for specification of the etiology and symptomatologic seizure type? It is clear that for different purposes different classification systems can be employed. For example, geneticists may be interested in studying patients with a given ‘‘epileptic syndrome’’ to investigate if the epileptic syndrome is due to a defect in a specific gene. Certainly researchers must use whatever classification system they find most useful for their research objectives. However, we feel that the mission of the Commission is to define the purpose of a classification system and then to
407 Classification of Epilepsies develop a classification system that best accomplishes that purpose and then can be used universally when classifying the epilepsy of individuals. To advocate for open-mindedness and flexibility and to merely state that epilepsies can be classified by many parameters (seizure type, EEG patterns, gene associations, etc.) is of little help. Simple and nonredundant The new classification system developed by the Commission should be simple with as little redundancy as possible. Moreover, assuming that the new classification system calls for a multidimensional approach (very likely), it will be essential that the parameters in one dimension are independent or at least as independent as possible from the parameters in the other dimensions. This requires that every dimension is necessary and substantially contributes to the synthesis of all dimensions. As was mentioned above, disregard for this principle determines that classifying an epileptic seizure or epilepsy in one dimension already defines the category to which it has to be classified in another dimension. For example, if in the ‘‘seizure dimension’’ we specify that a patient has a simple partial seizure we already specify that in the ‘‘epileptogenic zone dimension’’ the patient will have focal epilepsy. Classify the individual The Commission should also decide, as Drs. Berg and Scheffer mentioned, wheather it is trying to ‘‘organize knowledge’’ or is it trying to classify individual cases ‘‘within an organizational framework.’’ The two concepts are closely related, but we would assume that the focus of a practical classification for a clinician is to classify any given case within the organizational framework. In other words, the categories within the organizational framework must be relevant when we classify a case within such a system. For example, for research purposes, it may make sense to divide etiologies into only genetic and nongenetic causes. Such an organizational framework has, however, very limited applications when we try to classify individual cases (assuming that the purpose of the classification is to guide therapeutic choices and define prognosis). In an individual a precise etiological classification is essential. In this context, we would urge the Commission to consider the following points: 1 Is it really worthwhile to spend so much time subdividing etiologies into 3 or 4 major abstract subcategories that will have very limited value when classifying an individual case? When classifying an individual case we have to define the etiology of the epilepsy as precisely as possible. Example: If we have a case with Down syndrome or with West syndrome it would be of limited value to classify the case as being of ‘‘predominantly genetic or developmental causation.’’ Indeed, even in the case of West syndrome, we would like to specify with more precision the condition that is ‘‘causing the West syndrome.’’ Is the etiology unknown? Does the patient have
tuberous sclerosis? Has the patient suffered a severe anoxic episode? 2 Most of the discussion in the debate on classification was spent in trying to establish major subcategories of etiologies (genetic, structural-metabolic, provoked) and then defining the different terms. However, as already mentioned above, such a classification may be useful for selected research purposes, but is often of limited or no value in the classification of individual cases. 3 As discussed in many of the commentaries in the debate (Beghi, 2011; Berg & Scheffer, 2011a; Duncan, 2011; Engel, 2011; Jackson, 2011; Moshe, 2011; Shorvon, 2011a; Wolf, 2011; Wong, 2011), modern concepts about the etiology of the epilepsies clearly shows that epilepsy is determined by many ‘‘etiologies’’ which complement each other to different degrees (the extremes are infrequent, but even in those cases, as for example ‘‘monogenetic epilepsies,’’ the phenotype is influenced by susceptibility genes and provoking ambient factors). Four-dimensional classification It seems that the Commission agrees that the main purpose of the classification system it is developing is to classify individual cases to help in the selection of therapeutic approaches and to define prognosis. The Commission also appears to agree that this objective will be best accomplished by using a multidimensional system. We strongly support both points which in our view are the most important cornerstones of the Commission’s mission. If these assumptions are correct, we would urge the Commission to first take a critical look at the dimensions such a classification would require to accomplish the stated objectives. As previously described (Loddenkemper et al., 2005; Kellinghaus et al., 2006) we believe that such a system should include the following dimensions: Seizures. The seizure symptomatology is essential because (1) it defines the ‘‘essential’’ symptom of the epilepsies, namely the epileptic seizure in pure symptomatologic terms. (Example: generalized myoclonic seizures, vs. left hand clonic seizures vs. right hemifield visual auras); (2) detailed symptomatologic description of the seizure not infrequently is the only evidence we have to support the diagnosis of epilepsy; (3) seizure symptomatology together with the classification of the epileptogenic zone are the most important factors in defining the type of antiepileptic medication to use (for example, patients with generalized myoclonic seizures vs. generalized tonic– clonic seizures or left hand clonic seizures); (4) The seizure classification should also specify the frequency of the seizures and the presence or absence of epileptic seizure triggering (provoking) factors. Location. We know that the concept of an epileptogenic zone (defined as the minimum brain tissue that must be removed to produce seizure freedom) is controversial. However, all classification systems need to make Epilepsia, 53(3):405–411, 2012 doi: 10.1111/j.1528-1167.2011.03376.x
408 H. O. Lu¨ders et al. simplifying assumptions to have value. For example, antiepileptic drugs have been tested by subdividing epileptic patients in two broad categories, namely generalized and focal epilepsies. From these studies we have learned that all focal epilepsies independent of the symptomatology of the focal seizures respond to the same antiepileptic drugs, whereas generalized epilepsies respond to different antiepileptic drugs depending on the symptomatologic type of the epileptic seizures and to a lesser degree the etiology of the epilepsy. In the debate, considerable time was spent in trying to define focal and generalized epilepsy. We sympathize and agree that the theoretical differentiation between focal and generalized epilepsies is difficult, but when classifying individual cases this is seldom a problem. Besides, when considering epilepsy surgery a clear and as precise as possible, definition of the epileptogenic zone and its extent is essential. Etiology. Prof. Shorvon and most authors agree that etiology should be one of the essential dimensions when classifying the epilepsies (Menzler et al., 2011; Shorvon, 2011a,b). Often prognosis is primarily an expression of etiology. Moreover, etiology frequently decides some essential therapeutic strategies (progressive tumor vs. a remote cerebrovascular accident) and in many cases guides our approach to epilepsy surgery (cortical dysplasia vs. cavernous angioma). Related medical conditions. Specifying the main related medical conditions is essential to get a clear and comprehensive picture of the clinical condition from which a patient is suffering. The underlying medical condition also contributes frequently to therapeutic decisions and the well-being and quality of life of an epileptic patient. For example, in a patient with right face clonic seizures due to a left inferior frontal glioma it is also important to specify that he has a severe right hemiparesis, depression and a marked expressive aphasia. Examples. Below find examples of two patiens classified using the Four Dimensional Classification System Example One. Location: Left frontal lobe Seizures: Right hand clonic seizure fi Generalized tonic–clonic seizure Frequency: 1–2 seizures/day Etiology: Left frontal cortical dysplasia Related Medical Condition: Mild left hand paresis Example Two Location: Right mesial frontal Seizures: Bilateral asymmetric tonic seizures Frequency: 2–3 seizures/day Etiology: Tuberous sclerosis Related Medical Conditions: Moderate mental retardation At this point we should ask ourselves if the ‘‘database approach’’ specified above (the Four-Dimensional Classification System) really satisfies our main objectives of guiding our therapeutic options and assisting in prognosis. As Epilepsia, 53(3):405–411, 2012 doi: 10.1111/j.1528-1167.2011.03376.x
already mentioned above, therapeutic measures have only been assessed objectively in patients with a defined epileptogenic zone (generalized vs. focal) and a specific symptomatologic seizure type. Prognosis is usually defined by the etiology (for example, neoplasm, cortical dysplasia, mesial temporal sclerosis, tuberous sclerosis, etc.). It is true, however, that identification of the ‘‘benign focal epilepsies of childhood’’ provides us with prognostic information that is difficult to extract if we merely specify the above mentioned four dimensions. We can expect, however, that in the near future epilepsy geneticists will identify the genes responsible for this condition explaining its favorable evolution with maturation. Is epilepsy a disease or a symptom? The debate also spends time in discussing if epilepsy is a disease or a symptom. Dr. Wong avoids defining ‘‘disease,’’ but then concludes that the identification of ‘‘etiologies of many epilepsies redefines them as specific pathophysiological entities or diseases.’’ We had difficulty understanding why the identification of an etiology of a condition which includes epileptic seizures necessarily establishes that the condition is an epileptic disease? The observations below compare spastic paresis, usually considered a symptom of other diseases with epileptic seizures. We conclude from this comparison that the differentiation between symptoms of a disease or the disease itself is arbitrary and depends on the definition of ‘‘disease.’’ We see no practical value in such a differentiation. 1 Almost any structural, metabolic or genetic etiology that affects the cerebral cortex can produce epileptic seizures frequently in addition to other neurological symptoms or signs. That is not much different from the observation that lesions to the pyramidal tract will produce a spastic paresis. 2 Some investigators have argued that we are dealing with an ‘‘epileptic disease’’ when the main or only symptoms are epileptic seizures and the etiology is genetic, unique and clearly defined (example: juvenile absence epilepsy). The same is also true for spastic paresis (Example: hereditary spastic paraplegia). 3 In the other extreme, in situations in which there is a clear etiology that produces a variety of symptoms and signs including among many other epileptic seizures, we usually consider the epileptic seizures just as another symptom or sign. For example, a patient with a glioma that affects eloquent cortex with a variety of neurological symptoms and signs in addition to epileptic seizures. The same is also true for spastic paresis (also take, as an example, a glioma in an eloquent cortex with a variety of symptoms and signs including spastic paresis). The points outlined here and in paragraph b suggest that epileptic seizures and spastic paresis are similar and in the majority of cases just represent symptoms or signs of a variety of diseases. However, in special situations they
409 Classification of Epilepsies could probably also be defined as ‘‘epileptic diseases’’ or ‘‘spastic paresis diseases.’’ Besides, both are devastating symptoms or ‘‘diseases.’’ Given this striking similarity, why do we have on one hand ‘‘epileptologists’’; innumerable ‘‘epilepsy associations’’ worldwide; and extensive discussions in an attempt to find ‘‘biologically meaningful’’ classifications of ‘‘epilepsies and epileptic seizures’’ while at the same time there are no ‘‘spastic paresisologists,’’ no ‘‘spastic paresis associations’’ and no great interest in finding ‘‘biological meaningful’’ classifications of spastic paresis? The difference is most probably related to the (1) high prevalence rate; (2) the great variability of clinical manifestations; and (3) the extensive therapeutic armamentarium available for epilepsy in contrast to spastic paresis. A situation very similar to epilepsy is also encountered for headaches. Headaches, in many cases are considered ‘‘just’’ a symptom of an underlying disease. There are ‘‘headache’’ specialists. There are many classifications of headaches. There are ‘‘headache associations’’ worldwide and innumerable therapies, and extensive experience is required to use the appropriate therapy for different types of headaches. 4 These examples help us understand that epileptic seizures as is the case for spastic paresis and headaches, are primarily a symptom or sign of a disease which, at least in the case of epilepsy and spastic paresis, are usually or at least very frequently the expression of an underlying structural, genetic or metabolic ‘‘disease’’ (cortical dysplasia, tuberous sclerosis, hemimegalencephaly, hypothalamic hamartoma, etc). 5 In all these cases in which epileptic seizures are primarily a symptom of an ‘‘underlying disease,’’ a logical approach is a ‘‘database’’ specifying in each case, with as much precision as possible, the etiology of the condition that produced the epilepsy; the symptomatologic type of the epileptic seizures; the location of the insult to the brain (location and extent of the epileptogenic zone); and other underlying major related medical conditions. As explained below, any search for a ‘‘biologically meaningful’’ classification of the epilepsies or epileptic seizures observed in these patients will most probably be futile.
table for inanimate objects there should also be a ‘‘scientific, biologically meaningful’’ way to classify epileptic seizures and epilepsies. The problem, however, is that ‘‘scientific, biologically meaningful’’ classifications do not exist for many targets we would like to classify. It is very likely that no such ‘‘scientific, biologically meaningful’’ classification for epileptic seizures and epilepsiescan ever exist. Epileptic seizures are ‘‘events’’ that have certain characteristics (‘‘symptomatologic seizure classification’’); have certain causative agents (‘‘etiology’’) that trigger the event; have an epileptic discharge; and frequently are associated with other symptoms or signs (‘‘related medical conditions’’). This is not so different from a headache which also has clinical characteristics, an etiology and frequently is associated with other symptoms or signs. The same is also true for other ‘‘events’’ like for example, a car crash which will have specific characteristics (for example a specific injury to the driver); will have a cause (driver falling asleep, drunken driving, etc); and may have related signs (injury to accompanying passengers, etc). None of these events can be classified ‘‘scientifically or biologically.’’ We can only try to define as precisely as possible the ‘‘phenotype’’ of the events (symptomatologic seizure characteristics, headache characteristics, injury to the driver); the cause of the events (etiology of the seizures or headaches or the cause of the car accident); its related signs; and then try to uncover mutual correlations between these different variables. These studies may help us to identify, measure and thereby prevent future ‘‘events.’’ For example, we may discover that a certain gene abnormality frequently produces a certain type of symptomatologic seizures, or that a space occupying tumor produces a relatively typical headache or that a car crush at high velocity frequently results in death to the driver. All these correlation, if established following the scientific method, are certainly scientific, but do not necessarily lead to a ‘‘biological ordering’’ of the events we are studying because the material we are trying to classify (‘‘events’’) are very different from material that has been classified ‘‘biologically’’ (animated and unanimated naturally occurring ‘‘objects’’).
The search for a ‘‘biological classification of the epilepsies’’ In the nineteenth century John Hughlings Jackson subdivided classification systems into ‘‘scientific’’ and ‘‘practical’ giving as an example the scientist botanist who classified plants according to the ‘‘live tree’’ (evolution) and gardeners who grouped plants according to the color of their flowers or shape of their leaves. Wolf and others used these observations to stress the advantages of trying to define a ‘‘scientific, biologically meaningful’’ classification of epileptic seizures and epilepsies. The implication was that if there was a ‘‘live tree’’ for living organisms and a periodic
All these considerations outlined above, if accepted, could lead to a significant change in attitude in our approach to patients with epilepsy: 1 As has been stressed by Dr. Benbadis (Benbadis & Luders, 1996; Benbadis, 2001) in the past, the nonspecific, unacceptable vague expressions such as ‘‘patient with seizures’’ or ‘‘patient with seizure disorder’’ should be abandoned. 2 In all patients with epileptic seizures the four dimensions mentioned above, namely seizure symptomatology, location of the epileptogenic zone, etiology and related medical conditions should be defined in as much detail
Conclusions
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410 H. O. Lu¨ders et al.
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as possible. The precision with which we can specify the therapeutic approach and also prognosis will depend on the exact definition of these dimensions. The ILAE Commission on Classification and Terminology should abandon the current approach of defining hundreds of epileptic syndromes that are difficult to memorize, with few exceptions are rare, and add little or nothing to our therapeutic approach or prediction of prognosis if the above mentioned four dimensions are defined in detail. Adoption of such a four-dimensional classification system would establish a classification of the epilepsies that is similar to the classification approach used in general neurology. This would be of great help and hopefully would encourage our general neurology colleagues to also adopt this epilepsy classification system. This should greatly improve the acceptance and the role of the epilepsy classification within the field of general neurology. It would be very helpful if the ILAE Commission on Classification and Terminology would define each of the dimensions mentioned above establishing clear categories for each dimension to make sure that epileptic patients are ‘‘classified’’ uniformly worldwide (or entered into a uniform ‘‘database’’ worldwide). Previous ILAE Commissions on Classifications and Terminology have gathered expert epileptologists to discuss classifications of epilepsies and epileptic seizures. Many of those Commissions (Engel, 2001) have used consensus to decide on a classification scheme which in reality was never tested on individual patients. That would be similar to a software development company releasing a new operating system in the market without first testing it extensively in the field and then correcting exposed ‘‘bugs.’’ At our Institutions, we have been using a Fourdimension classification system for years to classify all our epileptic patients and have been continuously correcting it as we identified deficiencies. We have found that such a Four-Dimensional Classification System is easy to understand, teach and use in clinical practice, allowing us to concisely confer all relevant data regarding the epilepsy of individual patients. We urge the Commission to similarly develop an epilepsy classification that is primarily designed to be applied to individual patients and to release it as the official ILAE Classification System only after it has been tested extensively in the clinical epilepsy arena. Classification systems have a major impact on research related to a disease and, therefore, also on the advances we make in the understanding of a disease. For example, with the current emphasis on syndromes pharmaceutical companies frequently look for drugs effective for patients with a specific epileptic syndrome (West syndrome, Lennox–Gastaut syndrome, Juvenile Absence Epilepsy, etc). However, classifying epilepsies
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in the four independent dimensions outlined above not only will specify better the characteristics of the epilepsy in a given individual case, but also will orient pharmaceutical research to comparing the effectiveness of an antiepileptic drug in different subgroups of patients within any given dimension (different seizures, etiologies, localizations, etc.) or combination of groups between two or more dimensions (for example, patients with focal epilepsy and focal clonic seizures or patients with generalized epilepsy and generalized myoclonic seizures). 8 It is important to stress here again that it is crucial that the different dimensions of such a database should be as independent from each other, as possible to allow meaningful cross-correlation studies. For example: a. Cross-correlation between seizure symptomatology and localization of the epileptogenic zone. Example: prevalence of different symptomatologic seizure types in patients with left frontal lobe epilepsy. b. Cross-correlation between the localization of the epileptogenic zone and etiology. Example: distribution of epileptogenic zones in patients with tuberous sclerosis. c. Cross-correlation between seizure symptomatology and etiology. Example: symptomatologic seizure types observed in patients with SLC2A1 mutations. We certainly are encouraged seeing that the Commission is starting to look at epilepsy from a new perspective. We hope also that this article will be accepted as a positive contribution encouraging the Commission to take a decisive step to break out of the current classification system and propose a new classification which will incorporate all the recent diagnostic advances and thus opening a new era in epileptology.
Disclosures 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.
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