Abstract
The Turkish Epilepsy Society, the International League Against Epilepsy (ILAE), our close ally, completed the preliminary evaluation of the study range on August 12, 2024. This evaluation included recommendations for updating the role of the “2017 Seizure Classification” (2017 SC) in clinical practice worldwide. Following this study, an update document was presented to us, and we were invited to provide individual opinions by October 16, 2024. In this article, we summarize the pre-2017 stages, the 2017 classification, the findings of the Turkish Epilepsy Society, and the results of an e-mail survey conducted in 2018. This summary aims to enhance the understanding of the subject and revisit the process. Furthermore, we incorporate the forward-looking scientific basis and explanations of the changes made by the ILAE task force, presented in the working group’s own words. The final version of the classification, along with the classifier and descriptor tables, has been included in Turkey directly from the original article without altering the terminology used in the 2017 SC. We must consider what new options we propose and whether they will address the shortcomings of the 2017 SC. Together with colleagues from around the globe, we are committed to determining the future direction of this classification.
MAIN POINTS
• The International League Against Epilepsy announced on August 12, 2024 that the update work for the “2017 Seizure Classification” (2017 SC) has been completed.
• As in the 2017 SC, the main purpose is to create a common language and framework, to provide flexibility, and to prepare a well-defined classification that can be used at every stage, is suitable for research.
• As a result of this work, the update document has been presented to us, and our individual opinions have been requested until October 16, 2024.
• You can access the online form where you can enter your opinions and contributions on the proposed classification at the link https://www.surveymonkey.com/r/FY657FN
INTRODUCTION
The International League Against Epilepsy (ILAE), with which we are in close contact as the Turkish Epilepsy Society maintains close contact, published a preliminary report from the Executive Committee’s working group in its electronic newsletter on August 12, 2024. This group was formed to evaluate the role of the “2017 Seizure Classification” (2017 SC) in clinical practice worldwide and to make updated recommendations. They announced the completion of their studies and presented an updated document to us, requesting our individual opinions by October 16, 2024. What new proposals will be introduced and will they address the shortcomings of the 2017 SC?
Historical Process During the 2017 Seizure Classification
First, we explore the historical journey of the seizure classifications up to the 2017 classification system. Prior to 1964, clinics that pioneered the study of epilepsy worldwide utilized their own classification systems for diagnosis, follow-up, and prognosis determination. In April 1964, the first formal joint classification study was initiated in Marseille, involving 120 participants from the ILAE European group chaired by Gastaut. Representatives from six countries - France, Germany, Sweden, Britain, Spain, and Italy - developed a preliminary classification. This study was subsequently discussed at the Dutch “Meer en Bosch” meeting in May 1964, which included participation from the ILAE Terminology Commission, comprising both American and European representatives, as well as members from the World Federation of Neurology, the International Federation of Societies for Electroencephalography (EEG), and the Clinical Neurophysiology Societies. A classification was established that avoided the introduction of new terminology.1 According to the clinical type of seizures, they were categorized into five main categories: partial seizures, generalized seizures, unilateral seizures (in children), variable seizures in neonates, and unclassifiable seizures. This classification was presented in this format at the 8th International Neurology Congress in Vienna in 1965.
After the 1965 congress presentation, the classification was developed based on the recommendations of 170 neurologists who were in direct contact with Gastaut, ultimately taking its final form in New York in 1967. It was presented at the 1969 ILAE Congress with minor terminological changes.2
After the acceptance of the 1969 classification, the use of objective methods - now referred to as video EEG monitoring - has increased. This technique involves the simultaneous recording of seizures on videotape and EEG data on a split screen for examination. Following a workshop on complex partial seizures in 1975 and a subsequent workshop on generalized epilepsy held in Berlin in 1977, a primary framework for this classification was proposed. A commission established in Florence in 1979 was charged with planning the new classification. The commission’s objectives included revising the classification by analyzing video footage, coordinating the classification with other international bodies, promoting its use, and developing standardized terminology. This process continued in Copenhagen in 1980.
In 1981, anatomical relationships, etiology, and age - previously considered to be based on speculative information rather than objective findings - were removed. The second significant change was the distinction between simple and complex partial seizures, determined by whether consciousness is impaired. Although many epileptologist have argued that the definition of “complex” is confusing and suggests “higher cortical integrated dysfunction” rather than simply indicating whether consciousness is preserved, these concerns were not addressed until 2017, nearly half a century later. An attempt was made to clarify these issues in the dictionary published alongside the classification.3 In the final paragraph of the 1981 revision statement, where this classification was first introduced, it is noted that the “epileptic syndrome classification” will be the next topic the commission will tackle.
Despite its widespread use, the 1989 classification has faced criticism for being trapped in a partial and generalized dichotomy, for the incorrect application of idiopathic, symptomatic, and cryptogenic definitions, and for being perceived as a grouping method rather than a true classification system.
After a considerable period, in 1998, Engel4 proposed the necessity for a renewal that would be more clinically user-friendly and emphasize clinical features. In 2001, efforts were initiated to standardize ictal semiology. A list was presented under the title of epilepsy syndromes to distinguish these syndromes from epileptic seizure conditions that do not require a diagnosis of epilepsy. Additionally, syndromes that are still evolving were also noted. However, the criteria that the accepted syndromes must meet to be included in this list remain unclear. An exemplary classification was introduced, but the omission of age at onset classification became one of the most significant criticisms.5 Subsequently, disagreements arose. While Wolf6 stated, “this is not a classification but a diagnostic regulation,” Engel7 mitigated the criticism by asserting, “the studies will continue with your contributions”. Luders et al.8 remarked, “it has many steps; it is not useful for the center at all levels (semiological classification is easier). Do not confuse dictionary and classification studies. Try it first and then publish it.” Berg and Blackstone9 criticized this approach, stating, “There is no systematic approach; even though the definition of the syndrome is known, it is unclear what criteria are used to classify or categorize it.” The scientific purpose of the classification is to be easy to use.”
These dissident writers also joined the group, and a core group study was conducted in August 2003, December 2003, and May 2005. Although there has been no change in the definition of the syndrome, a decision was made regarding which features should be evaluated. Although Luders stated that he will continue to work with the group, he has expressed that he does not wish to be listed as an author in the final article.10 The classification of epileptic syndromes was based on various criteria, including the type of epileptic seizure, age at onset, progressive course, interictal EEG findings, associated interictal signs and symptoms, pathophysiological mechanisms, anatomical relationships, etiological categories, and genetics. Epileptic syndromes were classified using background criteria.11
In 2010, the waters appeared to have partially calmed, and although there was no retreat on either side, it seemed that everyone was continuing on their own path. In addition to significant changes in terminology for epilepsy classification (e.g., instead of in the syndromic approach. The report stated that “in forward-looking comments, it is believed that classification studies will evolve into a comprehensive database over time, and as general scientific progress advances (including epidemiology, electrophysiology, imaging, developmental neurobiology, genomics, computational neuroscience, and neurochemistry), the autocratic approach characterized by simple and rigid rules will diminish. In the 2010 report, the ILAE did not introduce a new classification but rather provided an update that could serve as a foundation for the existing classification system.12
Berg13stated, “There is still much to be done.” The team, which was formed in 2013, developed the new classification in 2017.14-17 2017 SC is presented as both a simplified version and an extended version, tailored to different levels of expertise.18
2017 Seizure Classification
The first step in classifying seizures is based on their onset. Seizures with an untraceable, unrecorded, or unknown onset are categorized under the subheading “unknown onset. Seizures with monitored and/or recorded onset are further divided into focal onset and generalized onset. Focal-onset seizures refer to those that originate from networks confined to one hemisphere, are clearly defined or have a widespread distribution, and may also arise from subcortical structures. Generalized-onset seizures are characterized by their origin from a single focus that rapidly spreads to bilateral networks.
The next stage in the evaluation of focal-onset seizures is awareness assessment. In practice, if the patient reports being aware of the seizure after the conclusion has been reached, then awareness is considered preserved. The patient’s inability to answer questions or follow commands during an examination while the seizure is occurring does not necessarily indicate a lack of awareness. The primary criterion for assessing awareness was the patient’s recollection of their experiences during the seizure. Additionally, it is important to determine whether the patient loses awareness at any point during the seizure and, if so, for how long. If awareness is lost, the seizure must be classified as impaired awareness. If a definitive conclusion regarding awareness cannot be reached, this step is bypassed, and the classification process continues.
In focal-onset seizures, it is sufficient to specify whether the seizures have motor or non-motor onset. An explanation of motor and non-motor findings, along with additional information, is provided in the expanded version of the seizure classification. Although it is not classified as a separate seizure type, the term “focal to bilateral tonic-clonic” is used to describe the pattern of seizure activity spread, given its frequent occurrence and significance.
Generalized-onset seizures are categorized into two types: motor and non-motor (absence) seizures. The level of awareness is not a criterion for the classification of generalized-onset seizures. In the most straightforward classification of generalized motor seizures, they can be divided into tonic-clonic seizures and other types of motor seizures. EEG data may be necessary to differentiate absence from focal seizures, particularly when awareness is compromised.
Although terms such as simple partial seizure, complex partial seizure, and secondary generalized tonic-clonic seizure in the 1981 classification have been used for many years, they have been supplanted by more comprehensible and widely accepted terminology in the new classification due to their inherent limitations. This is particularly evident in the case of partial seizures, where the level of awareness is uncertain and a clear distinction cannot be made between simple and complex seizures. Consequently, these seizures were categorized as which has been a significant motivating factor for the development of the new classification. Additionally, tonic, atonic, myoclonic, and epileptic spasms, previously classified solely under generalized seizures in the original classification, can also manifest in focal seizures. As a result, they are now included under focal and generalized-onset seizures in the new classification. Furthermore, seizures that are prevalent but were not addressed in the old classification, such as myoclonic-tonic-clonic seizures, have been incorporated into the new framework.
Widespread adoption of this classification was encouraged, with the expectation that it would become more effective as both positive and negative feedback increased during its use. This continued until an electronic newspaper was published by the ILAE on August 12, 2024.
We examined the historical development of classification studies, the conflicts between various groups, and the significance of the 2017 SC. However, exploring why the 2017 SC was necessary and how it was established is essential. Providing a brief answer to these questions is crucial for gaining a comprehensive understanding of classification studies.
Some seizure types could not be classified, they did not fit into the classification of seizures with no apparent onset, and the definition of consciousness or consciousness did not meet the situation that occurs in seizures other than its classical place in neurological examination. The patient does not lose consciousness during the seizure and does not become a coma as we know it classically; therefore, this situation had to be defined differently. Some confusing terminological terms were used in old classifications; such as psychic, simple partial (completely different from the simple complex distinction in febrile seizures), complex partial (complex is a word that describes confusion as a term, but this is confusing in the definition of seizure), or dyscognitive.
As a result, the 2017 SC was not a completely new classification; rather, it was a restructuring of the 1981 classification, organized in accordance with the International Classification of Diseases.
2024 Proposal
A working group established in 2023 conducted the evaluation in three phases: identifying strengths and weaknesses in the 2017 NS, identifying proposals and updates, and building consensus through an iterative Delphi process to reach a comprehensive conclusion.
A working group consisting of 37 experts was established at the beginning of 2023. Care was taken to ensure that the members were specialists in both adult and pediatric epileptology and represented diverse regions of the world: 7 members from North America, 5 from Latin America, 11 were from Europe, 2 from the Eastern Mediterranean, 9 from Asia and Oceania, and 9 from Africa. Additionally, 4 members of the team that developed the 2017 SC. Meetings were held in April, May, and September 2023.
They conducted a systematic evaluation to identify the strengths and weaknesses of the 2017 SC.18 They searched the PubMed and Embase databases for research articles, reviews, and commentaries that assessed the applicability of the 2017 SC. Conference papers were also included in the screening if they provided sufficient information. In total, 41 articles were evaluated.
The 2017 SC examined seizures in 4 main categories and included seizures of unknown onset in its classification, which were considered significant strengths. Although there were varying opinions regarding the “focus to bilateral tonic-clonic seizure,” it was still deemed useful. The additional strengths of the present study included the extensive range of common descriptors and the differentiation of focal epileptic spasms.
A vigorous debate has emerged regarding the appropriateness of the term “awareness” to describe seizure semiology.19-22 For general neurologists, epileptic seizures are included in the differential diagnosis of temporary loss or impairment of consciousness. In contrast, others define consciousness simply as the ability to react and remember. It is frequently reported that patient responsiveness is impaired during history-taking. The ability to respond is often assessed through awareness in epilepsy centers. However, it is not possible to evaluate awareness among children aged four and under.23 One of the main challenges is that the meanings of awareness and consciousness may be similar or differ across various languages. It is widely accepted that the term is more familiar in the field of neurology.
It was determined that the dichotomous classification of “with or without observable manifestations” was more practical than the definitions of “motor and non-motor”.24 The precise meaning cannot be established. For example, findings are observable in non-motor aphasic seizures.
Classifying absence seizures as non-motor seizures in the 2017 SC is misleading. Marked automatism, head tremors, blinking, which can be clearly observed in typical absence seizures, and atonia in atypical absence seizures. Additionally, eyelid myoclonia or myoclonus that can occur in the absence of seizures are also included in this category.
Negative myoclonus, which is distinctly different from asterixis observed in metabolic encephalopathies, was not included in the 2017 SC, although it has been well defined over the years.25
Focal onset has been observed in generalized seizures in both human studies and animal models.26, 27 2017 “generalized onset” in 2017 SC is inaccurate when assessed from this perspective.
As a result, the four primary categories were adhered to. Simple and extended classifications are presented in Figures 1 and 2. Table 1 illustrates the hierarchy of seizure classification taxonomy. “Classifiers” determine the type of seizure and are directly related to diagnosis, treatment decisions, and prognosis. “Descriptors”, along with other clinical information, play a crucial role in the overall patient management. Focal seizures originate from networks confined to one hemisphere. These seizures may be distinctly localized or more diffuse and can arise from either cortical or subcortical origins. Each seizure type may have an evident ictal onset and preferred propagation pattern to the opposite hemisphere. Occasionally, more than one network may be responsible for multiple seizure types; however, there is a specific starting point for each type of seizure.
The focal to bilateral tonic seizures are focal seizures that spread to both hemispheres. Along with this, semiological consciousness is impaired, and bilateral tonic-clonic muscle activity occurs. During the clonic phase, there is a notable decrease in the frequency of muscle contractions, and the silent periods between contractions gradually lengthen. In contrast, generalized seizures originate from a specific point and involve cortical or subcortical structures that rapidly integrate into bilaterally spreading networks, although they do not engage the entire cortex. The onset of these seizures may be localized, and they can also present asymmetrically. When insufficient information is available to classify a seizure as either focal or generalized, it can be categorized as “unknown if it started focal or generalized”. However, if the clinician is confident that seizures are occurring but lacks adequate information for classification, they should be documented under the “unclassifiable”.
“Consciousness” is primarily defined by an assessment of awareness and responsiveness based on data obtained from the patient’s medical history or an examination by healthcare professionals during a seizure. Essentially, it is characterized by the ability to recall the seizure in a manner that the patient and his/her relatives can comprehend, or by the capacity to respond appropriately during the seizure. It is more accurate to evaluate the patient’s recollection of the seizure or question their responsiveness during the event than to rely solely on the accounts of the patient and their relatives regarding their consciousness. An inappropriate response, or a response that is ineffective or significantly delayed compared to the interictal period, should also be considered indicative of impaired responsiveness. Patients and their relatives should be informed that the patient’s consciousness may be compromised even if the patient’s eyes are open and they attempt to engage with their surroundings. The narrative may only encompass information about awareness or responsiveness. Any impairment should be classified as a “seizure with impaired consciousness.” It should also be kept in mind that epileptic amnesia, ictal paresis, or ictal sensory aphasia may be the main cause of unresponsiveness.
Descriptors encompass additional characteristics that describe seizures. In the simplified version, the dichotomy is quite clear: with and without observable manifestations. Observable findings refer to signs, apart from voluntary movements, that can be perceived by individuals monitoring the seizure (Table 2). Impairment of consciousness is one such observable finding. In the expanded version, seizures are elaborated on, and chronological semiological features are organized using arrows. For instance, the sequence may be represented as follows: epigastric aura → automatism in the right hand → impairment of responsiveness + impairment of awareness. The features outlined in Table 2 were organized according to the ILAE dictionary.
Generalized seizures in simple classification; they are divided into two main categories: absence seizures and generalized motor seizures. The latter category is further subdivided into tonic-clonic seizures and other types based on distinct motor signs. In the expanded version, all generalized seizures are listed, and “generalized negative myoclonus” has been included in addition to the updates from the 2017 SC.
Epileptic spasms can be classified as generalized, focal, or generalized/focal spasms with an unknown distinction. Although they are presented as separate categories among generalized seizures, the other types are considered semiological features.
Epileptic seizures are categorized under four main headings and subheadings according to the taxonomic hierarchy. While the 2017 SC lists 63 seizure types, the new approach consolidates these into 20 types, allowing for the flexibility to specify additional seizures using descriptors (Table 2). Until the characteristics of a seizure are fully understood, it should be classified as unknown or unclassifiable. This aspect aligns with the 2017 SC.
DISCUSSION
The new classification is, of course, based on the 2017 SC. The necessary changes were implemented based on the clinical experience gained since 2017. In fact, approximately 1 year after the introduction of the new classification, we obtained similar results from a survey conducted via email with members of the Turkish Epilepsy Society prior to the May 2018 National Epilepsy Congress, of which 92% were adult neurologists. Among this group, 16% were specialists and 84% were academicians. Notably, 97% were familiar with the classification, and 73% had used it in their clinical practice. However, only 35% of respondents believed that the 2017 NS could replace the 1981 classification. In contrast, 56% of respondents expressed the opinion that certain modifications should be made before the classification can be deemed sufficient for use. Additionally, 9% of the group felt that the 2017 SC could not replace the old classification, regardless of any changes.
When we asked participants for their contributions and suggestions for changes based on the survey results;
1. The definition of “awareness” may be confusing, while the definition of “consciousness” may be more accurate,
2. Simple, easy, and understandable stories or video recordings are required,
3. It is preferred to use the term complex partial seizure,
4. Typical absence seizures can be divided into simple and complex,
5. The new classification is still unclear and non-didactic and does not address clinical and research problems,
6. It is incorrect to call bilateral generalized tonic-clonic instead of secondary generalization does not fully correspond to each other,
7. This classification drowns in the semiological details of seizures rather than using practical and easy-to-say definitions,
8. It is not easy or usable,
9. Epileptic seizures that start focal and become generalized cannot be well categorized,
10. It was answered that it was incomplete to define epileptic syndromes.
The responses received largely aligned with the findings obtained from the ILAE core group through database analysis. They also indicated that both existing and new changes were implemented based on the results obtained from the database.
As outlined in the 2017 SC, the primary objective is to establish a common language and framework that offers flexibility and provides a well-defined basis applicable at all levels of care, from primary to tertiary, while also being suitable for research purposes. Within this framework of taxonomic rules, four main categories, two subclasses (specifically for generalized seizures), and a total of 20 seizure types were defined. To simplify the classification process, the aim was to avoid the introduction of new terminology and to utilize a common language that was accessible to patients and their families.
Changes made;
1. Removed “onset” from the main 4 groups (based specifically on evidence of focal onset generalized seizures).
2. Classifiers and descriptors were distinguished from each other within the framework of taxonomic rules.
3. The term “awareness” was removed, and the term “consciousness” was employed as a classifier (based on evidence that consciousness functionally defines both awareness and responsiveness).
4. Instead of motor and non-motor dichotomy, “with or without observable findings” was used (it was evaluated that it would be more useful for clinical studies).
5. Seizure semiology was arranged chronologically rather than relying on the first finding to explain the seizure (based on the evidence that it is more accurate to evaluate not only the seizure as the first symptom but also all the findings sequentially, especially during video EEG monitoring follow-ups and surgery preparation).
6. The term non-motor was removed for absence seizures (based on evidence that myoclonic absence and eyelid myoclonus may occur in absence).
7. Negative myoclonus was classified as seizure (it was not in the 2017 SC).
8. In generalized seizures, epileptic spasm was considered a seizure type, whereas focal seizures or seizures of unknown onset were considered part of the seizure semiology.
CONCLUSION
As a result, ILAE proposes the changes outlined in the 2017 SC in its electronic newsletter, which was published on August 12, 2024. This article summarizes the pre-2017 stages of seizure classification studies, the 2017 classification, and the e-mail survey evaluations conducted among members of the Turkish Epilepsy Society in 2018. The aim is to provide a comprehensive understanding of the subject and to remind readers of the process. Subsequently, the academic foundation for the changes proposed by the ILAE working group, based on a review of the database and the justifications for these changes, is presented in the words of the working group. The final version of the classification, along with the classifier and descriptor tables, was extracted from the original article and translated into Turkish without altering the terminology used in the 2017 SC.
As a result of this study, an updated document has been presented to us, and we are requested to submit our individual opinions by October 16, 2024. You can access the online form at the following link: https://www.surveymonkey.com/r/FY657FN. In this form, you can enter your name, e-mail address, title, or competency level, and, in the final box, share your opinions and contributions regarding the proposed classification. Together, we will explore the potential impact of the new proposals and assess whether they can address the shortcomings of the 2017 SC and what form they will take with the contributions from us and our colleagues worldwide.