|Year : 2017 | Volume
| Issue : 2 | Page : 83-87
Classifications of the generalized epilepsies: Rationale, strengths, and weaknesses
Aminu T Abdullahi1, Lukman F Owolabi2
1 Department of Psychiatry, Bayero University, Kano, Nigeria
2 Department of Medicine, Bayero University, Kano, Nigeria
|Date of Web Publication||5-Oct-2017|
Aminu T Abdullahi
Department of Psychiatry, Bayero University, Kano
Source of Support: None, Conflict of Interest: None
Background: The classification of generalized epilepsy is characterized by conflicting tendencies on what purpose a classification should serve. It has evolved over the years to reflect these conflicting needs. Objective: We aim to review the various classifications of generalized epilepsy to evaluate their respective rationale, strengths, and weaknesses. Materials and Methods: A literature search of electronic databases supplemented by a search of cross-references was conducted. The search results were subjected to a narrative review. Results: Epilepsy classification is based primarily on the type of seizure, as well as evidence from clinical, neurological, electrophysiological, and neuroimaging evaluations. The main challenge of epilepsy classification is to balance the pragmatic needs of the clinician with the varied needs of the researcher. Various classifications of generalized epilepsy have been proposed but the most important are those proposed by the International League Against Epilepsy. Conclusions: We are a long way from an ideal classification that is grounded in evidence, flexible enough to accommodate new findings, and versatile enough to classify individual patients.
Keywords: Classification, generalized epilepsies, strengths, weaknesses
|How to cite this article:|
Abdullahi AT, Owolabi LF. Classifications of the generalized epilepsies: Rationale, strengths, and weaknesses. Niger J Basic Clin Sci 2017;14:83-7
|How to cite this URL:|
Abdullahi AT, Owolabi LF. Classifications of the generalized epilepsies: Rationale, strengths, and weaknesses. Niger J Basic Clin Sci [serial online] 2017 [cited 2018 Sep 22];14:83-7. Available from: http://www.njbcs.net/text.asp?2017/14/2/83/216054
| Introduction|| |
Epilepsy is a group of neurological disorders characterized by recurrent unprovoked or reflex seizures caused by abnormal discharges of brain neurones. Although seizures are the hallmark of the condition, they are usually conceptualized as syndromes. An epileptic syndrome is “an epileptic disorder characterized by a cluster of signs and symptoms customarily occurring together.” These signs and symptoms may be clinical, such as seizure type, age of onset, neurological findings, or findings from investigations, such as electroencephalograph (EEG), or neuroimaging such as magnetic resonance imaging (MRI) and computerized tomography (CT).
This review aims to critically appraise all previous classifications of generalized epilepsy, with an emphasis on their respective rationale, strengths, and weaknesses.
| Materials and Methods|| |
A literature search using PubMed, HINARI, and Google Scholar was performed for articles written in English without any date limit. Search terms used were “generalised seizures,” “generalised epilepsy,” and “classification.” A cross-reference search was used to suppliment the electronic search and articles not found in the database searches were added to the data. A critical review of all releavnt articles was then carried out.
| Results|| |
Although the classification system originating from the World Health Organisation (WHO) has been adopted by all member nations, the classfication system developed by the Intenational League Aganist Epilepsy (ILAE) is widely preferred by epileptologists worldwide. The ILAE sysytem has even found acceptance with the American National Institute of Neurological Disorders and Stroke (NINDS). However, the level of dissatisfaction with the current classifications remains high.
| Discussion|| |
Generalized epilepsy syndrome is defined by the occurrence of recurrent seizures which are “seizures in which the first clinical changes indicate initial involvement of both hemispheres.” It is further charaterized by bilateral motor manifestations and ictal EEG patterns that are initially bilateral. These seizures may be tonic–clonic, clonic, tonic, myoclonic, atonic, or absence. Spasms, which occur in West's syndrome, have recently been designated as neither focal nor generalized seizures but as “unknown.”
Disease classification or nosology is important from many perspectives. A nosological system by summarizing knowledge and information enhances communication between professionals and provides a teaching tool regarding the subject. It provides guidance regarding treatment and prognostication and can facilitate research into disease mechanisms and the search for therapy.
Classification with regards to epilepsy may be conceptualized on numerous dimensions, including the list of entities or classes recognized as forms of epilepsy, the process of assigning a patient to a class, the structural relationship between entities in a system, and the processes that determine how entities are recognized and organized.,
The importance of classification in epilepsy is aptly illustrated by the fact that the earliest recorded description of epilepsy dating back to about 700 BC was also a classification with symptomatic, etiological, and prognostic dimensions. Epilepsy classification has been a subject of debate since the nineteenth century, ranging from the question of how entities are identified to that of how they are organized into coherent groups. At the heart of the debate is an issue over which Hughlings Jackson has been extensively quoted, namely, the purpose of classifications. What constitutes a good classification? The one that mirrors the botanist's taxonomy or the pragmatic “arrangement” of the gardener? Various classifications of generalized epilepsy have been proposed, but the most important are those proposed by the ILAE.
Another important classification is the International Classification of Diseases (ICD) developed by the WHO. It is without doubt valuable as a tool for defining disease burden, mortality, cost, and cause and effect relationships. However, though the ICD has been accepted by 194 member states, it has often been subjected to modifications intended to address national clinical needs. This has tended to make it difficult to use for communication among international researchers. The system has also been described as incongruous because of its grouping of disparate conditions as epilepsy, headaches, sleep disorders, and transient ischaemic attacks into a single group. The concept of “seizures” and “epilepsy” are also not clearly distinguished from one another. The system has, therefore, not been favored by practicing epileptologists. Even the Common Data Elements (CDE), the National Institute of Neurological Disorders and Stroke of the United States has adopted the ILAE classification in the section on “seizures and syndromes.” Finally, the ICD-11, the latest version of the ICD has been organized to be in line with the ILAE classification.
The ILAE, established in 1909 as a professional association of epileptologists, initiated and has been updating the classification of epilepsy through its Commission on Classification and Terminology. This review will, therefore, focus on the ILAE classifications of 1970, 1985, 1989, 2001, 2006, and 2010 to asses their respective rationale, strengths, and weaknesses.
The 1970 classification
This was the first ILAE classification which was explicitly operational and electroclinical. It is operational in the sense that it spells out objective criteria that must be satisfied before a patient could be given a diagnosis. It classified generalized epilepsy on the basis of clinical criteria of seizure types, neurological findings, age of onset, and etiology. The “electrical” component was the interictal and ictal EEG. Generalized epilepsies were divided into three broad categories on the basis of this twin criteria, namely, “electrical” and “clinical.” The “primary generalized epilepsies” were characterized by the occurrence in singles or in combinations of absences, bilateral myoclonus, and tonic–clonic seizures. They begin in childhood or adolescence, have normal neurological and psychological assesments, lack clear etiology, and show an interictal EEG of spikes, polyspikes, spike-and-wave, or polyspike-wave of approximately 3 per se cond. The ictal EEG shows synchronous and symmetrical discharges that depend on the seizure type. The “secondary generalized epilepsies” manifest tonic and atonic seizures in addition to seizures that occur in primary generalized epilepsies. They mostly begin in childhood although they can occur at any age and are associated with neurological or psychological evidence of diffuse cerebral pathology. The interictal EEG has a slow background and slow sharp and slow wave complexes as well as variable ictal EEG that may be electrodecrement, slow wave, spike-and wave polysike-wave at approximately 2 per se cond or a low voltage fast rythm. In contrast to the primary generalized epilepsy, both the ictal and interictal EEG may be asymmetrical or asynchronous. The category “undetermined generalized epilepsies” is used when there is inadequate information to fit a patient into either of the two above categories.
The major strengths of the classification was its acceptability as it was a product of concensus. It was easy to use, allowing most patients to be classified. Its structure was a summary of the extant understanding of generalized epilepsies such that it was a good clinical guide and teaching tool for its time. Its main weaknesses were lack of elaboration and the confusion it generated regarding the term “secondary” in secondary generalized epilepsy as some understood it to mean secondary generalized seizures.
The 1985/1989 classification
These two classifications are being considered together because the 1989 classification was simply a refinement of the 1985 one. Like the 1970 classification, the classification of 1985 was a product of consensus. Although it listed EEG along side X-ray, “CT” and “MRI” as “ancillary studies,” it was also electroclinical as virtually every syndrome was described together with its EEG features. It broadly divided generalized epilepsies on the etiological dimension into the categories of “idiopathic generalized epilepsies” (IGEs) such as childhood absence epilepsy, “idiopathic and/or symptomatic” such as Lennox-Gastaut syndrome, and “symptomatic” such as early infantile epileptic encephalopathy. Similar to the 1970 scheme, it classified syndromes in chronological order for the first two categories. It also subdivided the symptomatic into “nonspecific aetiology” and “specific syndromes,” the latter referring to conditions such as Lafora's disease.
Revision of the 1985 classification that produced the 1989 one involved inclusion of reflex generalized epilepsies in the idiopathic category, the redesignation of the category “idiopathic and/or symptomatic” to “cryptogenic or symptomatic” and the addition of the class “other idiopathic GEs” under the IGEs category. This resolved some of the weaknesses of the 1985 scheme regarding terminology and the problem of the reflex generalized epilepsies which hitherto could be classified as IGE and a “special syndrome” at the same time. The scheme was made more comprehensive by adding the class “other symptomatic GEs” and of the specific syndrome of early infantile epileptic encephalopathy to the symptomatic generalized epilepsy group.
The 1989 classification had wide acceptabilty and has been found to be workable across a range of clinical and research situations.,,, Its coherence and ease of use makes it a good teaching and communication tool. Its syndromal emphasis helps clinicians to develop treatment strategies that capture the natural history and treatment responses of syndromes.
A weakness of the 1989 classification is its plethora of rigid syndromes that often overlapped., It also seemed to grant the same status to clearly defined syndromes such as childhood absence epilepsy and less clearly defined ones such as myoclonic-astatic epilepsy. The scheme has not been effective at the primary care and population levels, leaving many cases unclassified.,,, It classified neonatal seizures as IGEs with neither clinical nor electrical basis. The term “cryptogeneic” has been a source of confusion particularly for epidemiologists who interprete it to mean “cause unknown” as opposed to its intended meaning of “presumed symptomatic.” Further, the term “idiopathic,” an etiologic dimension, has taken on therapeutic and prognostic connotations to mean pharmacoresponsive and benign. Finally, the scheme has been overtaken by neuroscience and neuroimaging research that require classification to go beyond only the clinical and electrical.
The 2001 classification
The themes of the 2001 proposal were achievement of diagnostic coherence through use of a diagnostic scheme, clarification of confusing terms in the 1989 scheme, elevation of seizure types to diagnostic entities, incorporation of genetic findings into the classification system, and flexible grouping of syndromes. “Cryptogenic,” the confusing term in the 1989 classification, was replaced with “probably symptomatic” and new terms such as “epileptic disease” were introduced to qualify conditions with specific etiology such as Lafora's disease. Seizure types could be diagnostic entities in patients who could not be given a syndromal diagnosis. A five-axis diagnostic scheme that included ictal phenomenology, seizure type, syndrome, etiology, and impairment was proposed. The scheme discarded the “focal” and “generalised” distinctions and grouped the 1989 syndromes of generalized epilepsies into four groups – IGEs, reflex epilepsies, epileptic encephalopathies, and progressive myoclonus epilepsies. Neonatal seizures were classified as either focal epilepsies or “seizures not requiring a diagnosis of epilepsy.” Taking evidence from genetics on board, it proposed “syndromes of families” such as “GE with febrile seizures plus” and “IGEs with variable phenotypes.”
Marrying a diagnostic manual with a classification scheme is a strength of the 2001 proposal, as is the removal of neonatal seizures from the GEs category. Elevation of seizure types to diagnostic status may be useful to clinicians who generally use seizure types as the basis for medical treatment. The flexibilty of the scheme and its linkage to a multiaxial diagnostic scheme could help practitioners in low income countries where investigative facilities are minimal.
The flexibilty of the scheme is also its weakness as this introduces uncertainty into the clinical realm. As it was basically a diagnostic manual, the scheme failed to answer the taxonomic question.
The 2006 classfication
A continuation of the 2001 proposal, the 2006 scheme sees classification as a working hypothesis to be falsified, supported, or revised by scientific evidence. It maintained the move away from electroclinical classification to one based on pathophysiology with the aim of identifying natural classes of seizures or syndromes that could be objectively identified. Syndromes of the 2001 scheme were, therefore, assesed based on their respetive distinctiveness from the viewpoints of the traditional “electroclinical” dimensions of age of onset, interictal EEG, etc., as well as additional criteria of pathophysiologic mechanisms, anatomical substrates, etiological categories, and specific genetic mechanisms. It produced a syndrome listing by age and jettisoned the category of generalized epilepsies.
The strength of the 2006 classification is that it was evidence based. Its main weakness was its failure to organize syndromes into a specific format, leading to loss of some expected teaching value of a classification.
The 2010 classification
The 2010 classification is the culmination of the “revolution” that started with the 2001/2006 classifications. It sought to “bring epilepsy out of the shadows of expert opinion” to a system that utilizes advances in basic and clinical neuroscience. The focus of the scheme was etiological, and therefore, eliminated the traditional categories of idiopathic and symptomatic and replaced them with “genetic,” “structural/metabolic,” and “unknown.” The network concept was incorporated to define seizures and the position of the two preceding classifications of not using the term “generalised” to describe any epilepsy syndrome was maintained. It also proposed a flexible scheme for organizing syndromes. Although it is not electroclinical, it recognized established syndromes and organized them in descending levels of specificity into “electroclinical syndromes,” “constellations,” “structural/metabolic epilepsies,” and “epilepsies of unknown cause.”
Departure from the electroclinical emphasis is a strength of the 2010 classification as this is congruent with advances in neuroscience. Its emphasis on etiology is its main strength as this ought to be the basis of any nosology. Paradoxically, this is also its weakness as cause is dependent on the degree of investigation. Further, genetic generalized epilepsies may manifest the same phenotypes from different genetic abnormalities just as different genetic defects may produce similar phentypes.
| Conclusions|| |
Epilepsy classification is based on the seizure, a basic response of the brain to different insults. An epilepsy classification should balance the pragmatic needs of the clinician with the rather different needs of the researcher. These appear to be the two main challenges for epilepsy classifications, and their relative strengths and weaknesses depend on how they meet them. Hughlings Jackson had been extensively quoted in the classification debate on how pragmatic or scientific a classification should be. As quoted by Loiseau et al., Jackson also cautioned against “arbitrary divisions where there are no divisions in nature” and suggested that “we require two classifications, or rather a classification and an arrangement.” The challenge for the future, therefore, is a classification that is grounded in evidence, flexible enough to accomodate new findings and functioning as a tool for classifying individual patients.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Fisher RS, Boas WVE, Blume W, Elger C, Genton P, Lee P, et al
. Epileptic Seizures and Epilepsy: Definitions Proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia 2005;46:470-2.
ILAE Commission on Classification and Terminology. Proposal for Classification of Epilepsies and Epileptic Syndromes. Epilepsia 1985;26:268-78.
ILAE Commission on Classification and Terminology. Proposal for Revised Clinical and Electroencephalographic Classification of Epileptic Seizures. Epilepsia 1981;22:489-501.
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.
Berg AT, Blackstone NW. Concepts in classification and their relevance to epilepsy. Epilepsy Res 2006;70:11-9.
Fisher RS. What is a classification essay? Epilepsia 2010;51:714-5.
Berg AT, Scheffer IE. What is at stake in a classification? Epilepsia 2011;52:1205-8.
Wilson JVK, Reynolds EH. Texts and documents: Translation and analysis of a cuneiform text forming part of a Babylonian treatise on epilepsy. Med History 1990;34:185.
Reynolds EH, Rodin E. The clinical concept of epilepsy. Epilepsia 2009;50:2-7.
Jette N, Beghi E, Hesdorffer D, Moshe SL, Zuberi SM, Medina MT, et al
. ICD coding for epilepsy: Past, present, and future--a report by the International League Against Epilepsy Task Force on ICD codes in epilepsy. Epilepsia 2015;56:348-55.
Loring DW, Lowenstein DH, Barbaro NM, Fureman BE, Odenkirchen J, Jacobs MP, et al
. Common Data Elements in Epilepsy Research: Development and Implementation of the NINDS Epilepsy CDE Project. Epilepsia 2011;52:1186-91.
Bergen DC, Beghi E, Medina MT. Revising the Icd-10 Codes For Epilepsy and Seizures. Epilepsia 2012;53(Suppl 2):3-5.
Merlis JK. Proposal for an International Classification of the Epilepsies. Epilepsia 1970;11:114-9.
Viani F, Beghi E, Atza MG, Gulotta MP. Classifications of Epileptic Syndromes: Advantages and Limitations for Evaluation of Childhood Epileptic Syndromes in Clinical Practice. Epilepsia 1988;29:440-5.
ILAE Commission on Classification and Terminology. Proposal for Revised Classification of Epilepsies and Epileptic Syndromes. Epilepsia 1989;3:389-99.
Eslava-Cobos J, Naririo D. Experience with the International League Against Epilepsy Proposals for Classification of Epileptic Seizures and the Epilepsies and Epileptic Syndromes in a Pediatric Outpatient Epilepsy Clinic. Epilepsia 1989;30:112-5.
Loiseau P, Duché B, Loiseau J. Classification of Epilepsies and Epileptic Syndromes in Two Different Samples of Patients. Epilepsia 1991;32:303-9.
Shah KN, Rajadhyaksha SB, Shah VS, Shah NS, Desai VG. Experience with the International League Against Epilepsy Classifications of Epileptic Seizures (1981) and Epilepsies and Epileptic Syndrome (1989) in Epileptic Children in a Developing Country. Epilepsia 1992;33:1072-7.
Berg AT, Shinnar S, Levy SR, Testa FM, Smith-Rapaport S, Beckerman B. How Well Can Epilepsy Syndromes Be Identified at Diagnosis? A Reassessment 2 Years After Initial Diagnosis. Epilepsia 2000;41:1269-75.
Berkovic SF, Andermann F, Andermann E, Gloor P. Concepts of absence epilepsies: Discrete syndromes or biological continuum? Neurology 1987;37:993-1000.
Reutens DC, Berkovic SF. Idiopathic generalized epilepsy of adolescence: Are the syndromes clinically distinct? Neurology 1995;45:1469-76.
Avoli M, Rogawski MA, Avanzini G. Generalized Epileptic Disorders: An Update. Epilepsia 2001;42:445-57.
Olafsson E, Ludvigsson P, Hesdorffer D, Kjartansson O, Hauser WA, Gudmundsson G. Incidence of unprovoked seizures and epilepsy in Iceland and assessment of the epilepsy syndrome classification: A prospective study. Lancet Neurol 2005;4:627-34.
Jallon P, Loiseau P, Loiseau J. Newly Diagnosed Unprovoked Epileptic Seizures: Presentation at Diagnosis in CAROLE Study. Epilepsia 2001;42:464-75.
Manford M, Hart YM, Sander JS, Shorvon SD. The national general practice study of epilepsy: The syndromic classification of the international league against epilepsy applied to epilepsy in a general population. Arch Neurol 1992;49:801-8.
Oka E, Ishida S, Ohtsuka Y, Ohtahara S. Neuroepidemiological Study of Childhood Epilepsy by Application of International Classification of Epilepsies and Epileptic Syndromes (ILAE, 1989). Epilepsia 1995;36:658-61.
Wolf P. Basic principles of the ILAE syndrome classification. Epilepsy Res 2006;70:20-6.
ILAE Commission on Epidemiology and Prognosis. Guidelines for Epidemiologic Studies on Epilepsy. Epilepsia 1993;34:592-6.
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.
Glauser T, Ben-Menachem E, Bourgeois B, Cnaan A, Chadwick D, Guerreiro C, et al
. ILAE Treatment Guidelines: Evidence-based Analysis of Antiepileptic Drug Efficacy and Effectiveness as Initial Monotherapy for Epileptic Seizures and Syndromes. Epilepsia 2006;47:1094-120.
Wolf P. Of Cabbages and Kings: Some Considerations on Classifications, Diagnostic Schemes, Semiology, and Concepts. Epilepsia 2003;44:1-3.
Engel JR. ILAE classification of epilepsy syndromes. Epilepsy Res 2006;70:5-10.
Shorvon SD. The etiologic classification of epilepsy. Epilepsia 2011;52:1052-7.
Berg AT, Scheffer IE. New concepts in classification of the epilepsies: Entering the 21st
century. Epilepsia 2011;52:1058-62.
Zuberi SM, Brunklaus A, Birch R, Reavey E, Duncan J, Forbes GH. Genotype–phenotype associations in SCN1A-related epilepsies. Neurology 2011;76: 594-600.