Indian J Pediatr (September 2014) 81(9):883–887 DOI 10.1007/s12098-014-1547-8
REVIEW ARTICLE
Proposed International League Against Epilepsy Classification 2010: New Insights Vrajesh Udani & Neelu Desai
Received: 1 May 2014 / Accepted: 17 July 2014 / Published online: 15 August 2014 # Dr. K C Chaudhuri Foundation 2014
Abstract The International League Against Epilepsy (ILAE) Classification of Seizures in 1981 and the Classification of the Epilepsies, in 1989 have been widely accepted the world over for the last 3 decades. Since then, there has been an explosive growth in imaging, genetics and other fields in the epilepsies which have changed many of our concepts. It was felt that a revision was in order and hence the ILAE commissioned a group of experts who submitted the initial draft of this revised classification in 2010. This review focuses on what are the strengths and weaknesses of this new proposed classification, especially in the context of a developing country. Keywords Epilepsy . Classification
imaging. Specialists in the field were finding the old classification outdated and arbitrary [1]. In 2009, The Commission on Classification and Terminology of International League against Epilepsy came forth with a flexible and multidimensional revision of the previous classification to incorporate the advances in genetics, neuroimaging and neurophysiology made over the last couple of decades. The proceedings of the Monreale workshop were instrumental in bringing these modifications [2]. Although these recommendations have been appreciated by some, many epileptologists are in disagreement and have made alternate suggestions. In this review the authors have briefly discussed the need of a classification, history of past epilepsy classifications, salient changes in the proposed revision with pros and cons of the same.
Introduction Classification of seizures and epilepsy is one of the first steps when approaching a case of epilepsy. Not only does it help in establishing a diagnosis, ascertaining treatment options or defining prognosis in an individual patient but on a wider perspective serves as a foundation stone for international research with a uniform terminology. Classifying epilepsy is a tough task and full of controversies. Experts in epileptology with a lifetime experience in the field come together to formulate the classification. Since the last recommendations of the commission in 2001, there were no further revisions for a long time despite the vast knowledge accumulated in genetics, neurophysiology and V. Udani (*) : N. Desai Section of Child Neurology, Hinduja National Hospital & Medical Research Centre, Veer Savarkar Marg, Mahim, Mumbai 400 016, India e-mail: [email protected]
Why do we need a Classification? Classifying epilepsy helps in ascertaining a diagnosis, offering therapeutic options and deciding long term prognosis to an individual patient. It also provides a uniform vocabulary among clinicians across the world and serves as a cornerstone for international research. Upgrading the classification periodically helps to adapt to the evolving understanding of epilepsy with advances in epidemiology, electrophysiology, neuroimaging and molecular genetics. An ideal classification should be flexible, multidimensional and dynamic in keeping with the scientific breakthroughs in epilepsy including drug discovery, molecular genetics and all areas of investigations [3]. At the same time it should be practical, easy to apply and locally relevant. It should also be useful and applicable to the vast developing world in a resource-limited setting [4].
884
History The earliest attempts to classify seizures and epilepsy were made in the late 1960s by the International League Against Epilepsy (ILAE). The first formal epilepsy classification system was proposed by Henri Gastaut in 1969, which was further updated in 1981 for seizures and in 1989 for the epilepsies by the Classification and Terminology Commission of the ILAE [5–7]. These stood as the most workable classifications of seizures and epilepsies till date. The 1969 ILAE seizure classification was based on 6 criteria: clinical seizure type, electroencephalographic (EEG) abnormality, EEG interictal changes, anatomic abnormality, etiology, and age [5]. It distinguished between seizures that were generalized at onset from those that were partial or focal at start and had become secondarily generalized. The 1981 ILAE system classified seizures on the basis of only 2 criteria: their clinical features and their EEG features [6]. It separated partial seizures into simple and complex, depending on impairment of consciousness. Dichotomies of symptomatic, cryptogenic, and idiopathic were used in the 2001 and 2006 proposals [8, 9]. Since then there has been a limited change in underlying concepts until 2010 where the concepts have been reshaped into new dimensions [3] Classifications will evolve and new changes will take time to be accepted and implemented.
Indian J Pediatr (September 2014) 81(9):883–887
For seizures, based on current electroclinical evidence, a dichotomy of focal and generalized seizures remains useful. Though majority of seizures can be classified as generalized and focal, overlap is present and some cannot be classified. The terms simple and complex partial seizures have been abandoned for several reasons. Consciousness is often difficult to determine especially in the young and in the disabled. Also auras are often not reported in the same groups. However the classification allows details as add-on e.g., focal seizures with retained awareness and hence can be used when semiology is critical to making for example, surgical decisions. Also if a focal seizure is described by its ictal semiology e.g., hemiconvulsion, versive, retained responsiveness then it would convey a lot more meaningful information than just the use of terms such as simple and complex partial. The previous sub-classification of absence seizures has been simplified and myoclonic absence seizures and eyelid myoclonia are now recognized. Myoclonic atonic (also referred to as myoclonic astatic) seizures are now included. Epileptic spasms have now been recognized as a separate category and include infantile spasms. This makes ample sense as spasms are different both in semiology and have a different prognosis for both outcome and treatment. Neonatal seizures are now classified in the same scheme and not as a separate category. It is assumed that these could be classified in the new system and do not need a separate category. The category of unclassified epileptic seizures has been eliminated. Epilepsies and Syndromes
Key Differences Between the Proposed and Old Classification Classification of Seizures The terms ‘focal’ and ‘generalized’ were used in the past classifications to express a dichotomy for both seizures and the epilepsies. Generalised seizures were assumed to originate in the entire cortex while focal seizures in focal areas of cortex. Concepts have changed in the current recommendations where focal seizures are assumed to originate in networks limited to one cerebral hemisphere which may be discretely localized or maybe more widely distributed. They may spread to the other hemisphere and evolve to a bilateral convulsive seizure. On the other hand, generalised seizures are conceptualized to originate at some point within, and rapidly engaging, bilaterally distributed networks, may involve cortical and subcortical structures, but not necessarily involve the entire cortex. The network construct is now used in all branches of neurosciences and can be even imaged using functional MRI [1].
The dichotomy of generalized and focal epilepsies has been abandoned. This probably makes sense as some epilepsies may have focal lesions causing generalized seizures (e.g., West syndrome) or some generalised epilepsies may have focal seizures (e.g., Dravet syndrome). Unlike the 1989 report where syndrome and epilepsy were used interchangeably, the current recommendations restrict the use of term ‘electro-clinical syndrome’ to a group of clinical entities which are identified by a cluster of electroclinical characteristics and which are well accepted in the literature as specific conditions with a generally uniform clinical/EEG signature. Patients who do not satisfy these specifics are not lumped into non-specific categories like “cryptogenic focal epilepsies” or “symptomatic generalized epilepsies” but are rather described by their seizure type, etiology etc. which could give more specific information. The disease-syndrome distinction has been abandoned. This has drawn criticisms from many as in most medical literatures the term “disease” is still in common usage and denotes more specificity than the term “syndrome”.
Indian J Pediatr (September 2014) 81(9):883–887
Etiological Categories As a major change to past classifications, the previous terms of idiopathic, cryptogenic and symptomatic have been abandoned. Focus on mechanisms and causal factors plays a major role in epilepsy [10]. Epilepsies are now classified according to etiology as. Genetic This group consists of presumed hereditary causes based on family and molecular studies where epilepsy is the direct effect of a known genetic defect e.g., SCN1a related epilepsies. Structural/Metabolic Most of these would fall into the old symptomatic category though specificity would be better e.g., epilepsy with focal seizures due to focal cortical dysplasia in the left frontal lobe rather than symptomatic focal epilepsy.
885
a “structural” change i.e., lissencephaly causing confusion as to which category to classify it. Natural Evolution The “benign” terminology has now been substituted with ‘self limited’ (epilepsy resolves with time) and ‘pharmacoresponsive’ (epilepsy responds well to medications). This has advantages as some benign syndromes like benign focal epilepsies of childhood are not always “benign” and may evolve into a more catastrophic epileptic encephalopathy like electrical status in slow wave sleep (ESES) causing significant morbidity. The new proposed terms hence could be more appropriate in individual children. The term “catastrophic” has been removed and the concept of epileptic encephalopathy (EE) has been reinstated where cognitive and behavior worsening is a direct result of the epileptic activity. This has therapeutic implications as early effective intervention may reduce the irrevocable damage of epilepsy on the developing brain. The concept EE now accepts that the deterioration may be also partially be due to the cause.
Unknown Organization of Epilepsy This term simply denotes ignorance and that further investigations are required to ascertain the etiology. This subgroup accounts for the most poorly understood group and perhaps the most useful area for future research. This is more honest than the term “cryptogenic” as the latter often was thought to be “presumed symptomatic” which may not be true always e.g., Autosomal Dominant Nocturnal Frontal Lobe Epilepsy (ADNFLE) was thought to be a cryptogenic focal epilepsy and therefore, conceptualized as “presumed symptomatic” till it was found to be a monogenic syndrome. In the new classification it would have been in the unknown category initially and then moved to the genetic category later. There have been some criticisms about the genetic vs. structural-metabolic categories as well. Genetic etiology is often presumed rather than confirmed in actual practice, especially in resource-poor countries. Also, genetic variations often are not found in all patients of that epilepsy e.g., SCN1A is seen in ~70 % of Dravet syndrome patients. Also the same genetic mutation may be responsible for completely different epilepsies with different outcomes e.g., SCN1A is seen in ~10 % of genetic epilepsies febrile seizures plus (GEFS+) where the outcome is much more benign compared to Dravet syndrome. Hence, the connotation of the old “idiopathic” category with easily treatable epilepsy and a benign outcome in normal children no longer holds. The other criticism is that epilepsy may fit into two categories at the same time e.g., mutations in the ARX homeobox gene, which underlie some infantile epilepsies may also cause
In the 1989 classification, syndromes were sub-classified according to the mode of presentation (generalised or focal) or cause (idiopathic, cryptogenic or symptomatic). This organization structure has been abandoned and a multidimensional approach emphasizing on age of onset or cause or type of seizure etc. have been suggested. Age at onset categories are defined as per standard use: neonate (
REVIEW ARTICLE
Proposed International League Against Epilepsy Classification 2010: New Insights Vrajesh Udani & Neelu Desai
Received: 1 May 2014 / Accepted: 17 July 2014 / Published online: 15 August 2014 # Dr. K C Chaudhuri Foundation 2014
Abstract The International League Against Epilepsy (ILAE) Classification of Seizures in 1981 and the Classification of the Epilepsies, in 1989 have been widely accepted the world over for the last 3 decades. Since then, there has been an explosive growth in imaging, genetics and other fields in the epilepsies which have changed many of our concepts. It was felt that a revision was in order and hence the ILAE commissioned a group of experts who submitted the initial draft of this revised classification in 2010. This review focuses on what are the strengths and weaknesses of this new proposed classification, especially in the context of a developing country. Keywords Epilepsy . Classification
imaging. Specialists in the field were finding the old classification outdated and arbitrary [1]. In 2009, The Commission on Classification and Terminology of International League against Epilepsy came forth with a flexible and multidimensional revision of the previous classification to incorporate the advances in genetics, neuroimaging and neurophysiology made over the last couple of decades. The proceedings of the Monreale workshop were instrumental in bringing these modifications [2]. Although these recommendations have been appreciated by some, many epileptologists are in disagreement and have made alternate suggestions. In this review the authors have briefly discussed the need of a classification, history of past epilepsy classifications, salient changes in the proposed revision with pros and cons of the same.
Introduction Classification of seizures and epilepsy is one of the first steps when approaching a case of epilepsy. Not only does it help in establishing a diagnosis, ascertaining treatment options or defining prognosis in an individual patient but on a wider perspective serves as a foundation stone for international research with a uniform terminology. Classifying epilepsy is a tough task and full of controversies. Experts in epileptology with a lifetime experience in the field come together to formulate the classification. Since the last recommendations of the commission in 2001, there were no further revisions for a long time despite the vast knowledge accumulated in genetics, neurophysiology and V. Udani (*) : N. Desai Section of Child Neurology, Hinduja National Hospital & Medical Research Centre, Veer Savarkar Marg, Mahim, Mumbai 400 016, India e-mail: [email protected]
Why do we need a Classification? Classifying epilepsy helps in ascertaining a diagnosis, offering therapeutic options and deciding long term prognosis to an individual patient. It also provides a uniform vocabulary among clinicians across the world and serves as a cornerstone for international research. Upgrading the classification periodically helps to adapt to the evolving understanding of epilepsy with advances in epidemiology, electrophysiology, neuroimaging and molecular genetics. An ideal classification should be flexible, multidimensional and dynamic in keeping with the scientific breakthroughs in epilepsy including drug discovery, molecular genetics and all areas of investigations [3]. At the same time it should be practical, easy to apply and locally relevant. It should also be useful and applicable to the vast developing world in a resource-limited setting [4].
884
History The earliest attempts to classify seizures and epilepsy were made in the late 1960s by the International League Against Epilepsy (ILAE). The first formal epilepsy classification system was proposed by Henri Gastaut in 1969, which was further updated in 1981 for seizures and in 1989 for the epilepsies by the Classification and Terminology Commission of the ILAE [5–7]. These stood as the most workable classifications of seizures and epilepsies till date. The 1969 ILAE seizure classification was based on 6 criteria: clinical seizure type, electroencephalographic (EEG) abnormality, EEG interictal changes, anatomic abnormality, etiology, and age [5]. It distinguished between seizures that were generalized at onset from those that were partial or focal at start and had become secondarily generalized. The 1981 ILAE system classified seizures on the basis of only 2 criteria: their clinical features and their EEG features [6]. It separated partial seizures into simple and complex, depending on impairment of consciousness. Dichotomies of symptomatic, cryptogenic, and idiopathic were used in the 2001 and 2006 proposals [8, 9]. Since then there has been a limited change in underlying concepts until 2010 where the concepts have been reshaped into new dimensions [3] Classifications will evolve and new changes will take time to be accepted and implemented.
Indian J Pediatr (September 2014) 81(9):883–887
For seizures, based on current electroclinical evidence, a dichotomy of focal and generalized seizures remains useful. Though majority of seizures can be classified as generalized and focal, overlap is present and some cannot be classified. The terms simple and complex partial seizures have been abandoned for several reasons. Consciousness is often difficult to determine especially in the young and in the disabled. Also auras are often not reported in the same groups. However the classification allows details as add-on e.g., focal seizures with retained awareness and hence can be used when semiology is critical to making for example, surgical decisions. Also if a focal seizure is described by its ictal semiology e.g., hemiconvulsion, versive, retained responsiveness then it would convey a lot more meaningful information than just the use of terms such as simple and complex partial. The previous sub-classification of absence seizures has been simplified and myoclonic absence seizures and eyelid myoclonia are now recognized. Myoclonic atonic (also referred to as myoclonic astatic) seizures are now included. Epileptic spasms have now been recognized as a separate category and include infantile spasms. This makes ample sense as spasms are different both in semiology and have a different prognosis for both outcome and treatment. Neonatal seizures are now classified in the same scheme and not as a separate category. It is assumed that these could be classified in the new system and do not need a separate category. The category of unclassified epileptic seizures has been eliminated. Epilepsies and Syndromes
Key Differences Between the Proposed and Old Classification Classification of Seizures The terms ‘focal’ and ‘generalized’ were used in the past classifications to express a dichotomy for both seizures and the epilepsies. Generalised seizures were assumed to originate in the entire cortex while focal seizures in focal areas of cortex. Concepts have changed in the current recommendations where focal seizures are assumed to originate in networks limited to one cerebral hemisphere which may be discretely localized or maybe more widely distributed. They may spread to the other hemisphere and evolve to a bilateral convulsive seizure. On the other hand, generalised seizures are conceptualized to originate at some point within, and rapidly engaging, bilaterally distributed networks, may involve cortical and subcortical structures, but not necessarily involve the entire cortex. The network construct is now used in all branches of neurosciences and can be even imaged using functional MRI [1].
The dichotomy of generalized and focal epilepsies has been abandoned. This probably makes sense as some epilepsies may have focal lesions causing generalized seizures (e.g., West syndrome) or some generalised epilepsies may have focal seizures (e.g., Dravet syndrome). Unlike the 1989 report where syndrome and epilepsy were used interchangeably, the current recommendations restrict the use of term ‘electro-clinical syndrome’ to a group of clinical entities which are identified by a cluster of electroclinical characteristics and which are well accepted in the literature as specific conditions with a generally uniform clinical/EEG signature. Patients who do not satisfy these specifics are not lumped into non-specific categories like “cryptogenic focal epilepsies” or “symptomatic generalized epilepsies” but are rather described by their seizure type, etiology etc. which could give more specific information. The disease-syndrome distinction has been abandoned. This has drawn criticisms from many as in most medical literatures the term “disease” is still in common usage and denotes more specificity than the term “syndrome”.
Indian J Pediatr (September 2014) 81(9):883–887
Etiological Categories As a major change to past classifications, the previous terms of idiopathic, cryptogenic and symptomatic have been abandoned. Focus on mechanisms and causal factors plays a major role in epilepsy [10]. Epilepsies are now classified according to etiology as. Genetic This group consists of presumed hereditary causes based on family and molecular studies where epilepsy is the direct effect of a known genetic defect e.g., SCN1a related epilepsies. Structural/Metabolic Most of these would fall into the old symptomatic category though specificity would be better e.g., epilepsy with focal seizures due to focal cortical dysplasia in the left frontal lobe rather than symptomatic focal epilepsy.
885
a “structural” change i.e., lissencephaly causing confusion as to which category to classify it. Natural Evolution The “benign” terminology has now been substituted with ‘self limited’ (epilepsy resolves with time) and ‘pharmacoresponsive’ (epilepsy responds well to medications). This has advantages as some benign syndromes like benign focal epilepsies of childhood are not always “benign” and may evolve into a more catastrophic epileptic encephalopathy like electrical status in slow wave sleep (ESES) causing significant morbidity. The new proposed terms hence could be more appropriate in individual children. The term “catastrophic” has been removed and the concept of epileptic encephalopathy (EE) has been reinstated where cognitive and behavior worsening is a direct result of the epileptic activity. This has therapeutic implications as early effective intervention may reduce the irrevocable damage of epilepsy on the developing brain. The concept EE now accepts that the deterioration may be also partially be due to the cause.
Unknown Organization of Epilepsy This term simply denotes ignorance and that further investigations are required to ascertain the etiology. This subgroup accounts for the most poorly understood group and perhaps the most useful area for future research. This is more honest than the term “cryptogenic” as the latter often was thought to be “presumed symptomatic” which may not be true always e.g., Autosomal Dominant Nocturnal Frontal Lobe Epilepsy (ADNFLE) was thought to be a cryptogenic focal epilepsy and therefore, conceptualized as “presumed symptomatic” till it was found to be a monogenic syndrome. In the new classification it would have been in the unknown category initially and then moved to the genetic category later. There have been some criticisms about the genetic vs. structural-metabolic categories as well. Genetic etiology is often presumed rather than confirmed in actual practice, especially in resource-poor countries. Also, genetic variations often are not found in all patients of that epilepsy e.g., SCN1A is seen in ~70 % of Dravet syndrome patients. Also the same genetic mutation may be responsible for completely different epilepsies with different outcomes e.g., SCN1A is seen in ~10 % of genetic epilepsies febrile seizures plus (GEFS+) where the outcome is much more benign compared to Dravet syndrome. Hence, the connotation of the old “idiopathic” category with easily treatable epilepsy and a benign outcome in normal children no longer holds. The other criticism is that epilepsy may fit into two categories at the same time e.g., mutations in the ARX homeobox gene, which underlie some infantile epilepsies may also cause
In the 1989 classification, syndromes were sub-classified according to the mode of presentation (generalised or focal) or cause (idiopathic, cryptogenic or symptomatic). This organization structure has been abandoned and a multidimensional approach emphasizing on age of onset or cause or type of seizure etc. have been suggested. Age at onset categories are defined as per standard use: neonate (
