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Keywords:

  • Classification;
  • Terminology;
  • Reflex epilepsy;
  • Seizure precipitants;
  • Content analysis

Summary

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. Disclosure
  8. References
  9. Supporting Information

Seizure precipitation is a defining characteristic of reflex seizures and epilepsies, but seizure precipitants are also commonly reported for patients with epilepsies not considered to be reflex in nature. This raises the questions of exactly how reflex and nonreflex epilepsies with seizure precipitants are defined, and how these concepts are differentiated from one another in current practice. In this systematic literature review, definitions of reflex seizures, reflex epilepsies, and precipitation in a nonreflex context were extracted from published primary research papers. Content analysis was applied to these definitions to identify their main features, allowing comparisons to be made between definitions of the different concepts. Results indicated that there was little consistency within definitions of a given term, and that although some differences in definition content were found between terms, it was evident that clear defining characteristics to differentiate them from one another were lacking. These findings are discussed in the context of current debates regarding classification of the reflex epilepsies and the extent to which the distinction between reflex and nonreflex epilepsies is a meaningful one. Suggestions are made for how clarity might be increased in ongoing research in this area.

Reflex seizures are defined by the International League Against Epilepsy (ILAE) as those that are “objectively and consistently demonstrated to be evoked by a specific afferent stimulus or by activity of the patient” (Blume et al., 2001) and reflex epilepsy syndromes as syndromes “in which all epileptic seizures are precipitated by sensory stimuli” (Engel, 2001). The presence of some degree or form of seizure precipitation is a necessary, defining feature of both concepts. However, seizure precipitants for epileptic seizures not classed as reflex seizures are also commonly referred to in the epilepsy literature. Indeed, surveys of individuals with epilepsy (Verduyn et al., 1988; Antebi & Bird, 1993; Spatt et al., 1998; Frucht et al., 2000; Spector et al., 2000; Nakken et al., 2005; Pinikahana & Dono, 2009; Lunardi et al., 2011) as well as prospective studies of seizure precipitation (Temkin & Davis, 1984; Neugebauer et al., 1994; Haut et al., 2007) indicate that the likelihood of occurrence of seizures not classed as reflex seizures may also be raised in association with a range of emotional, physical, or environmental factors. This suggests that seizure precipitation may be necessary but not sufficient for a reflex classification, or that it is sufficient only if it takes a certain form. This observation raises the questions of how, in current practice, reflex seizures are distinguished from other seizures whose likelihood of occurrence is thought to be increased by emotional, physical, or environmental factors, and further, the extent to which this distinction is justified.

A number of authors have raised the question of how meaningful is the distinction between reflex seizures and nonreflex seizures thought to have precipitants. Kasteleijn-Nolst Trenité (2012) associates reflex seizures with specific as opposed to more general provoking stimuli, although argues that the distinction between reflex and nonreflex appears to be an artificial one, and instead advocates for the wider concept of “provoked seizures” proposed by Shorvon (2011b).

It has been proposed that theoretically there is no clear distinction even between those seizures deemed spontaneous and those deemed to be reflex seizures. Various authors have suggested that there is a conceptual continuum between reflex and spontaneous seizures, rather than there being a dichotomy as suggested by current terminology, or argue that to some extent all or most seizures may be precipitated (Antebi & Bird, 1992; Dreifuss, 1998; Eggers, 2007). Historically it has been argued by many epileptologists that seizures result from an interaction between an underlying predisposition and a precipitating event (see review by Shorvon, 2011a), suggesting that the role of the latter is not limited to reflex seizures and epilepsies.

The classification of reflex seizures and reflex epilepsies remains a point of discussion and debate. It was identified by the ILAE task force on classification and terminology (Engel, 2001) as an unresolved issue regarding which comments would be particularly welcomed from those working in the field. Since then, the more recent ILAE report on classification and terminology (Berg et al., 2010) has been criticized by Panayiotopoulos (2011) for failing to address reflex seizures, which, he states, must be “classified and precisely defined.” Similarly, in a review of the field presented at the ILAE European Congress on Epileptology, Kasteleijn-Nolst Trenité (2012) argues that although the term “reflex” should not be replaced, it needs to be much more clearly defined.

In the context of current debates regarding classification and terminology in this area, an investigation into how reflex seizures, reflex epilepsies, and seizure precipitation in a nonreflex context are currently defined and distinguished from one another is warranted. The aims of the current review were as follows:

  1. To determine how these concepts (reflex seizures, reflex epilepsies, and seizure precipitation in a nonreflex context) are currently defined in the research literature by those working in the field
  2. To ascertain, using content analysis, the key features of these definitions that distinguish these concepts from one another in research publications
  3. To appraise on the basis of these findings the extent to which these concepts, and the distinctions between them, are meaningful in current practice

We do not intend to be prescriptive regarding future use of these terms and concepts; rather, we hope to contribute to the debate regarding classification and terminology by illustrating and critically appraising current practice, as reflected by recent usage of these terms in published primary research papers.

Methods

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. Disclosure
  8. References
  9. Supporting Information

Identification of relevant literature

ProQuest MEDLINE and EMBASE databases were searched to identify research articles published over a 10-year period between 2002 and 2012. The searches sought journal articles in which the title, abstract, or Medical Subject Headings referred to reflex epilepsies, reflex seizures, or seizure precipitants in epilepsy, but which did not concern animal models (see Data S1: Search Strategy). A wide range of terms are used to describe seizure precipitants (e.g., triggers, evoking factors, facilitators), and the search terms used were informed by extensive prior reading of literature on this topic.

Following removal of duplicates, identified articles were screened according to inclusion and exclusion criteria. To be eligible for inclusion, journal articles had to have been published in English between January 2002 and May 2012, and to report original research (including case reports), where a primary objective of the research concerned reflex seizures, reflex epilepsy, or seizure precipitation in an individual or group with epilepsy. Articles were excluded if the “precipitant” in question was an iatrogenic event, external stimulation of the brain (e.g., transcranial magnetic stimulation), or a change in antiepileptic drug (AED) levels or treatment. Articles were also excluded if they investigated precipitants in patients with new-onset seizures, acute symptomatic seizures, or diagnostic uncertainty, or if they concerned animal models only. The aim of screening was to remove articles that were not relevant to reflex seizures or seizure precipitation, with the intention that the definitions extracted represent those employed by the research community working in this area.

Conference abstracts were excluded, but additional searches were conducted to identify any articles published by the authors on the topic of the conference presentation. Articles that investigated electroencephalography (EEG) sensitivity to stimuli in people with epilepsy (but not seizure precipitation directly) were included, as the association between these topics suggested some relevant definitions might be contained within these articles.

The first stage of screening was on the basis of titles and abstracts only; in the second stage the remaining articles were subject to full text review. Where it was unclear whether an article should be considered eligible or not, the article was retained to minimize the risk of missing any relevant definitions. Finally, reference lists of all included articles were checked for additional relevant publications.

Extraction of definitions from included articles

Definitions of (1) seizure precipitation in a nonreflex context, (2) seizure precipitants in a nonreflex context, (3) seizure precipitants in a reflex context, (4) specific reflex epilepsies (e.g., photosensitive epilepsy), (5) reflex epilepsies (in general), (6) specific reflex seizures (e.g., musicogenic seizures), and (7) reflex seizures (in general) were extracted. There was only a single definition of (3) precipitants in a reflex context, so although the components of this definition were initially identified using content analysis as for definitions of the other terms (see 'Data analysis methodology'), this category of definition was excluded from subsequent comparisons between definition types. The remaining definitions were grouped together for analysis into three “clinical domains,” in accordance with the aims of the review set out earlier. The three clinical domains comprised (1) definitions in a nonreflex context (including definitions of precipitants and precipitation), (2) definitions of reflex seizures (including both general and specific definitions), and (3) definitions of reflex epilepsies (including both general and specific definitions).

Definitions were included only if they appeared to be explicitly intended as such, and statements that appeared to include only an implicit definition were not included. If definitions were quoted but not clearly endorsed by the authors of the article (e.g., they were quoted but debated or criticised) these were not extracted as they would not have represented the definition actually employed in the article. Statements or partial definitions referring to common but not defining characteristics (e.g., “usually occurring in patients with structural brain damage” or “the most common seizure type is…”) were not included. Definitions were extracted by JI; in cases where it was unclear whether a statement was intended as a definition, this was resolved in discussion with the second author, HR.

Some articles gave two very similar definitions for the same term. In these cases the most complete definition was included. In addition, certain definitions were cited by a number of different articles. In such cases, every time the definition was presented in a different article, this was counted as a separate entry into the dataset, allowing the analysis to reflect the prevalence of the various definitions and their associated key components in the published literature.

Data analysis methodology

Content analysis has been defined classically as “a research technique for the objective, systematic and quantitative description of the manifest content of communication” (Berelson, 1952). A number of quantitative and qualitative approaches have since been covered by this term. In this study, a quantitative approach was taken that involved counting the frequency of key components (words or very short phrases) contained in the definitions and then categorizing these components. This reflects the method of no-theory manifest content analysis as described by Potter and Levine-Donnerstein (1999) in which only directly observable components are counted, and the data are approached without any predetermined components or categories of interest. Similar approaches have proved useful in the study of definitions used in other fields (Fennell, 2001; Dahlsrud, 2008; Baregheh et al., 2009; Levasseur et al., 2010).

Each definition was initially studied to identify all words or phrases that constituted individual components of the definition, and these were added to a cumulative emergent list of components. For example, the components of a definition of reflex seizures as “seizures reliably provoked by an external stimulus” would be “reliably,” “provoked,” “external,” and “stimulus.” Components were arranged in categories according to the context in which they occurred in the definition. For example, in the definition above, the words “reliably” and “provoked” refer to the relationship between precipitant and seizure, and “external” and “stimulus” are referring to precipitant characteristics. Categories emerged from the data and were based on sentence structure alone with the intention of maintaining objectivity. Three overarching categories emerged comprising terms describing the following: the nature or properties of the precipitating factor, the outcome event (i.e., the resulting seizures or epilepsies), and the relationship between the precipitant and outcome event. The resulting list of components within these categories formed a coding scheme that was then used in the second stage of the analysis to code each definition with regard to which of the listed components it contained.

Therefore, definitions were examined along three dimensions: the clinical domain to which each definition referred (nonreflex precipitation, reflex seizures, and reflex epilepsies), the individual components that comprised the definition, and the three overarching categories into which each of these individual components fell (the nature or properties of the precipitating factor, the outcome event, and the relationship between the precipitant and outcome event).

Comparison of definitions between clinical domains

The results of the content analysis were summarized for each clinical domain, allowing comparison between the three domains. First, components encountered in each of the three domains were identified in order to ascertain which components were common to definitions across domains and which were unique to a certain domain. Second, the frequency of occurrence within each domain of particular components and the frequency of the overarching categories into which they fell were identified, highlighting which components or categories were more consistently considered important within the different domains. Together these results allowed consideration of how the definitions in the literature differed between the three clinical domains.

Interrater agreement

A sample of definitions of each of the seven types of term sought from included articles (listed above) was randomly selected to assess interrater agreement in the use of the final coding scheme. Twenty percent of definitions of each type were selected (where 20% was a noninteger quantity, this was rounded up), resulting in a sample of 33 definitions stratified across the seven types. An independent rater who was blind to the initial analysis (HR) coded this sample of definitions using the established coding scheme. Across this sample of definitions, the components identified by the two raters were then compared and the percentage of components that were similarly identified by both raters (percentage agreement) was calculated.

Results

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. Disclosure
  8. References
  9. Supporting Information

Quantities of definitions extracted

Numbers of articles considered in different stages of the review process are reported in Figure 1. The literature search and screening process resulted in a final dataset of 288 articles meeting the eligibility criteria. Of these articles, 122 contained at least one relevant definition (see Fig. 1). There were a total of 161 definitions extracted from these articles. The number of definitions of each type of term can be found in Figure 2. The number of definitions concerning precipitants or precipitation not in a reflex context was small, reflecting the small number of research articles in this area. The actual terms defined, and the definitions themselves, may be found in Data S2: Extracted Definitions.

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Figure 1. Results of literature search and screening process.

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Figure 2. Graph showing number of definitions extracted of each type.

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Interrater agreement of coding scheme

From the stratified sample of 20% of definitions randomly selected for assessment of interrater agreement, a total of 155 components were identified by one or both raters. Of these, percentage agreement between the two independent raters was 88%.

Nature of components identified in content analysis

To ascertain which components were shared between domains and which were unique to a particular domain, all components encountered at least once within each of the three domains were identified. Figure 3 shows all definition components that were present in each of the three clinical domains under investigation (nonreflex precipitation, reflex seizures, and reflex epilepsies). Components identified in the content analysis belonged to one of three broad categories: those describing features of the precipitating factor (e.g., “sensory”) in Figure 3A, those describing the resulting seizures or epilepsies (e.g., “partial”) in Figure 3B, and those describing the relationship between the two (e.g., “consistent”) in Figure 3C.

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Figure 3. Components identified in the content analysis of definitions. In each figure, each of the three circles contains components identified in a particular definition type (“clinical domain”). “Non-reflex precipitation” refers to definitions of precipitation or precipitants not in a reflex context. “Reflex seizures” and “reflex epilepsies” refer to definitions of these concepts in general or in the context of a specific precipitant (e.g., musicogenic seizures, photosensitive epilepsy). Components in overlapping sections were identified in more than one clinical domain. Components are presented in separate figures according to broader categories as follows. (A) Components referring to the nature or properties of the factor thought to be associated with seizure occurrence. (B) Components referring to the outcome event that is thought to be associated with the precipitant. (C) Components referring to the nature or properties of the relationship between the precipitant and outcome event. Sz, seizure; Ep, epilepsy; Rel, relationship between precipitant and outcome; EEG, electroencephalography; GTCS, generalized tonic–clonic seizure; PPR, photoparoxysmal response.

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Common to all clinical domains were references to characteristics of the precipitant as being a stimulus and being specific (Fig. 3A), and references to seizures being “induced” or “triggered,” and occurring during the precipitating event (Fig. 3C). Although many components were present in definitions in at least two of the three clinical domains, a number were unique to a particular domain. For example, many components concerning the nature of the outcome (seizures or epilepsies) were unique to definitions of reflex epilepsies (Fig. 3B). Many of these were components describing seizure types and semiology associated with the specific reflex epilepsies, such as references to orofacial myoclonus and alexia in definitions of reading epilepsy. It is noteworthy that no definitions of the general terms “reflex epilepsy” or “reflex seizures” referred to specific seizure types. This suggests that although specific reflex epilepsies such as reading epilepsy may have characteristic seizure types, reflex epilepsy in general is not considered to be associated with any particular seizure types and no seizure type is excluded from this concept. Other components unique to this domain referred to the epilepsy itself, such as describing reflex epilepsy as a “syndrome,” “condition” or “disease.”

Regarding precipitant characteristics, the types of characteristics mentioned in definitions in the different clinical domains do not appear widely dissimilar. Perhaps noteworthy, however, is the use of the term “sensory” exclusively in definitions of reflex seizures and reflex epilepsies. However, reflex definitions also referred to other characteristics including “extrasensory,” “activity,” and “internal,” which are inconsistent with “sensory” as being a necessary defining characteristic (Fig. 3A).

Regarding components describing the relationship between precipitant and outcome event (Fig. 3C), many were unique to nonreflex definitions, in particular several regarding timing of the relationship. Other components were unique to definitions of reflex epilepsies or shared with definitions of reflex seizures, in particular, a number of components referring to the certainty or consistency of the relationship. In relation to these components, those unique to a reflex context refer to a higher degree of certainty, for example, referring to the relationship being clear, reliable, and consistent as opposed to there just being a “belief” that there is a relationship. Components referring to the effect of the precipitant on the outcome tended to be relatively simple (e.g., “seizures are triggered”) in definitions of reflex seizures and epilepsies, whereas in a nonreflex context, more elaborate components, defining what this might actually mean, were presented.

Frequency of occurrence of components identified

In addition to comparing domains with respect to nature of components encountered, the frequencies with which the various components (and the categories within which they fell) were encountered within each domain were considered. The full list of component frequencies, which shows how many definitions of each type mentioned each component, may be found in Data S3: Component frequencies. Table 1 shows the five most common components occurring in definitions in each of the three clinical domains. Those of reflex seizures and epilepsies are broadly similar, differing from definitions in a nonreflex context.

Table 1. Most common definition components
Clinical domain (no. of definitions)Five most commonly encountered componentsNo. (%)of definitions in clinical domain including the component
Nonreflex context (n = 19)Seizure occurs during precipitant 7 (36.8)
Precipitant is physiologic 5 (26.3)
Precipitant is endogenous 5 (26.3)
It's believed/considered there's a relationship 5 (26.3)
Seizures are induced 5 (26.3)
Reflex seizures (n = 33)Precipitant is stimulus20 (60.6)
Precipitant is specific12 (36.4)
Seizures are triggered11 (33.3)
Reflex seizures are rare 6 (18.2)
Precipitant is sensory 5 (15.2)
Reflex epilepsies (n = 108)Precipitant is stimulus52 (48.1)
Reflex epilepsies are rare32 (30.0)
Seizures are precipitated29 (26.9)
Precipitant is specific20 (18.5)
Precipitant is external16 (14.8)

Regarding the overarching categories of definition components, Figure 4 summarizes the percentage of definitions that included a component in each of the three categories (characteristics of the precipitant, characteristics of the outcome event, characteristics of the relationship between the precipitant and the outcome), for each clinical domain (nonreflex precipitation, reflex epilepsies, and reflex seizures). In all three clinical domains, features of the relationship between the precipitant and the outcome were almost always mentioned, and around half of the definitions referred to characteristics of the precipitant itself. Characteristics of the outcome event were commonly referred to in definitions of reflex epilepsies, less commonly in definitions of reflex seizures, and rarely in nonreflex definitions. This is consistent with the previously noted finding that many components in this category were unique to the reflex epilepsy domain.

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Figure 4. Graph showing percentage of definitions containing components in each of the three categories (nature or properties of the precipitating factor; the outcome event; the relationship between the precipitant and outcome event). Results are organized by clinical domain. “Nonreflex precipitation” refers to definitions of precipitation or precipitants not in a reflex context. “Reflex epilepsies” and “reflex seizures” refer to definitions of these concepts in general or in the context of a specific precipitant (e.g., musicogenic seizures, photosensitive epilepsy).

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Because almost all definitions, across all types, referred to features of the relationship between the precipitant and outcome, these frequencies were considered in further detail. Components in this broad category can be divided, as in Figure 3C, into those concerning timing, those concerning the nature of the effect of the precipitant on the outcome event, those concerning the consistency or certainty of the relationship, and any others. These subcategories emerged from the data during analysis. Figure 5 illustrates the frequency with which components in these subcategories are mentioned for definitions in the different clinical domains. Definitions in the three domains were similar with regard to frequency of references to the consistency or certainty of the relationship, and all commonly mentioned the effect of the precipitant on the outcome event, although the nature of these components differed between clinical domains, as discussed earlier. However, it is noteworthy that an account of the timing of the outcome event relative to the precipitant was rare in articles considering reflex seizures and reflex epilepsies but common in those describing events that were not by definition “reflex.” This is in line with the finding noted earlier that many of these components were unique to nonreflex contexts.

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Figure 5. Graph showing percentage of definitions containing a component in each of the subcategories concerning the relationship between the precipitant and outcome event. Results are organized by clinical domain.

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Discussion

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. Disclosure
  8. References
  9. Supporting Information

In this systematic review, we have identified definitions referring to seizure precipitation in articles concerning nonreflex contexts, reflex seizures, and reflex epilepsies. These definitions were analyzed in order to identify their key components, with the ultimate purpose of assessing how meaningful are the distinctions between these concepts as they are currently defined and understood. This is in the context of the ongoing debate concerning classification and terminology in this area and arguments surrounding whether there is a real dichotomy between reflex and other precipitated seizures.

Consistency within definitions of a particular type

The list of extracted definitions demonstrated that few definitions were identical, and definitions of a particular type (i.e., definitions of the same or similar terms) varied considerably with a wide range of components being referred to. Many definitions were not cited from other sources, but rather were formulated by the authors of the article in question, particularly regarding reflex seizures and epilepsies. This is surprising in cases where International League Against Epilepsy (ILAE) definitions are available (e.g., definitions of reflex and reactive seizures provided by Blume et al., 2001), and raises the question of why these definitions are not more frequently cited. This might be explained by a lack of awareness of these definitions. Alternatively, it may be that they are known but not accepted by all authors. Recent books on the topic of reflex seizures and epilepsies reflect the finding that the ILAE definitions are not always used. In his introduction to a book dedicated to reflex epilepsies, Wolf (2004) introduces the reflex epilepsies in his own words, and references to ILAE terminology are rare throughout subsequent chapters. Panayiotopoulos (2012) quotes the ILAE definition of a reflex epilepsy syndrome in his book on the subject, but he suggests it is possibly too restrictive.

Many of the terms do not have specific ILAE definitions (for example, definitions of the specific reflex epilepsies). Indeed, some of these concepts do not appear in current classification (e.g., Mah-jong epilepsy) and perhaps have no formal definition as they are not in fact recognized beyond the article in which they are described. Although such concepts may be seen as erroneous by some, they may also be understood as attempts by authors to best describe the clinical phenomena they observe in the context of a lack of specific guidance regarding broader definitions of reflex seizures and reflex epilepsies. In any case, the wide range of definitions identified by this review indicates that, if there is to be the degree of consistency between authors that would support the meaningful pooling of results concerning specific phenomena, then specific definitions, agreed upon by the epilepsy community and published by the ILAE, may be helpful. Therefore, in this way our results support the recent calls from Panayiotopoulos (2011) and Kasteleijn-Nolst Trenité (2012) to clarify classification and terminology in this area. Carefully considered ILAE definitions of these terms would be highly valued, and might be more frequently cited if they could be shown to be based on a firm consensus within the epilepsy community.

Features distinguishing the different terms from one another

In addition to consistency within definition types, it is important to consider the extent to which definitions in the different clinical domains (nonreflex precipitation, reflex seizures, and reflex epilepsies) actually overlap and whether, in current practice, there are clear features differentiating these concepts.

Features of the precipitant were mentioned fairly frequently in all clinical domains; however, they were least often referred to in nonreflex definitions. The notion of “sensory” precipitants as being an important defining characteristic in reflex seizures and epilepsies (Engel, 2001; Shorvon, 2011a) and the historical equivalence between “sensory-provoked” and reflex seizures was supported to some extent by the data in that this term was used only in definitions of reflex seizures and epilepsies. However, a relatively small percentage of reflex definitions included this component so it is not considered by all authors to be a necessary defining feature. Furthermore, a range of often somewhat contradictory other terms referring to precipitant characteristics were also used in definitions in a reflex context, suggesting that precipitants need not be limited to sensory ones. This extension beyond sensory precipitants is reflected in recent books on the topic, with Wolf (2004) stating that the stimulus is “sensory or cognitive,” and Panayiotopoulos (2012) suggesting it can be “extrinsic, intrinsic or both.” The question of whether it is appropriate to take the nature of the precipitant into account when defining reflex epilepsies (and if so, what the exact nature of the precipitant must be) currently remains unresolved.

In terms of features of the outcome event, there was a clear difference between the definitions of the different clinical domains. Most of the references to the outcome event encountered in the analysis were limited to definitions in a reflex context (mainly reflex epilepsies), and definitions in a reflex context were considerably more likely to mention outcome events. The relatively greater frequency of features of the outcome event in definitions of reflex epilepsies is largely the result of descriptions within definitions of specific seizure types associated with specific types of reflex epilepsy. Although frequently included in reflex definitions and rarely mentioned in a nonreflex context, references to the outcome event are however far from universal in a reflex context. Whether stereotyped outcome events are necessary for a diagnosis of reflex seizures or reflex epilepsies, but not for precipitated seizures occurring in a nonreflex context, is an interesting question and perhaps should be explicitly considered when defining the meaning of the terms “reflex seizures” and “reflex epilepsies.”

Not surprisingly, all or almost all definitions in each clinical domain referred to some feature of the relationship between the precipitant and outcome event. However, there were some important differences between clinical domains with regard to the features specified. References to the timing of the seizure relative to the precipitating event were found mainly in definitions in a nonreflex context. This is interesting given that a short latency from precipitant to outcome is often considered characteristic of reflex seizures. For example, in a discussion of the classification of musicogenic epilepsy, Pittau et al. (2008) point out that some authors do not consider it a reflex epilepsy due to the latency to the response, and Wolf (2004) asserts that in reflex epilepsies the seizures are precipitated “immediately or with short delays.” It may indeed be that in the literature the term “reflex” is used to imply that the outcome is either concurrent with or follows immediately after precipitation, but without description of the specific temporal relationship between precipitant and outcome event, this remains unclear. We suggest that it would be helpful, with respect to understanding more about relationships between precipitants and seizures, if in future articles that describe reflex epilepsies and seizures authors were more explicit in their account of the actual temporal relationships observed. Such data would also help to clarify whether there are meaningful differences between those events described as being reflex epilepsies or seizures and those described in the context of being precipitated but not reflex.

References to the certainty and consistency of the relationship were found in all three clinical domains, but the components differed, with definitions in a reflex context tending to refer to relationships being clear and consistent, as opposed to just being considered or believed to exist as in a nonreflex context. This may be considered consistent with the ILAE definition of reflex seizures, requiring that the relationship is “objectively and consistently demonstrated” (Blume et al., 2001). However, there may be various difficulties in identifying relationships between the events (Kasteleijn-Nolst Trenité, 2012), and judgements can be influenced by a number of factors (Spatt et al., 1998; Sperling et al., 2008). Therefore, confidence in the existence of a relationship may be an important element of defining reflex events. Sensory precipitants are likely to be easier to identify compared with cognitive and emotional ones—which is interesting given that definitions of reflex seizures and epilepsies are sometimes restricted to sensory precipitants. The following question arises: is it the features of the relationship, or the level of confidence in the relationship that these features arouse in the observer, that are distinguishing these concepts? If confidence in the relationship per se is a defining characteristic of reflex seizures and epilepsies, then the distinction between reflex and nonreflex may relate more to observational ability than to objective fundamental differences in seizure phenomena.

Components that refer to the nature of the effect of the precipitant on the outcome event, while commonly mentioned in definitions across the three clinical domains, also differed considerably between domains. Of interest, relatively nonspecific words and phrases were used in reflex contexts, whereas in nonreflex contexts more detail was given about the nature of the relationship. Indeed, the finding discussed earlier that timing is rarely referred to in a reflex context is consistent with this, again representing a failure to specify exactly the details of the relationship. It could be argued that the difference in the degree to which the relationship is specified occurred because in a nonreflex context the definitions were of precipitants and precipitation (thus, defining a “precipitated seizure” as “a seizure that is precipitated” would be tautologic and more detail is therefore required), whereas in a reflex context the definitions referred to the broader concepts of reflex seizures and epilepsies within which precipitation occurs. It is important to note, however, this is not a consequence of the design of the review; definitions of precipitants in a reflex context were sought but only one definition was identified, further emphasizing the neglect of defining the meaning of precipitation in reflex contexts. In addition, the fact that a broader concept is being defined does not preclude clarifying or further specifying narrower concepts (i.e., precipitation) referred to within the definition. The finding that the meaning of precipitation in reflex contexts is rarely defined is an important one because, with some form of relationship between precipitant and seizure being common to all the concepts investigated here, the nature of this relationship may be crucial in differentiating between reflex and nonreflex precipitation. It is possible that authors use the term “reflex” to imply a variety of assumptions about the relationship between precipitant and seizure. However, in these definitions the lack of sufficient detail means that the nature of these assumptions is not made explicit, thereby limiting the extent to which they can be tested.

Dichotomy or continuum?

Some interesting differences were found concerning defining features of seizure precipitation in reflex compared with nonreflex contexts, suggesting that reflex and nonreflex epilepsies as currently defined might be distinguished from one another to some extent. However, confusion remains regarding how reflex events are distinguished from nonreflex events, largely because consistency across definitions of a given concept is considerably lacking. Although this might cast some doubt on how meaningful these terms are in current practice, we suggest that our observations should not be seen to constitute evidence either for or against a continuum between “reflex” and nonreflex events or that the term reflex should be abandoned, but rather that further work in choosing the most appropriate terms to use, and defining them, is needed.

Some authors have suggested that reflex epilepsies, and precipitation, may be subcategorized, suggesting a number of categories rather than a simple dichotomy between reflex and nonreflex events. The 1985 classification of epilepsies (ILAE, 1985) divides reflex epilepsies (those “characterized by specific modes of seizure precipitation”) into simple and complex forms. They are differentiated in terms of how elaborate the stimulus is, whether intensity or pattern of the stimulus is important, latency of seizure, and whether “mental anticipation” of the stimulus is an effective precipitant. Therefore, these classes of reflex epilepsy are differentiated on a number of dimensions including some identified in this review.

With respect to seizure precipitation, several authors have differentiated between types. Antebi and Bird (1992) make a distinction between seizure facilitators (which indirectly increase seizure likelihood, “sensitizing the CNS [central nervous system] to some other stimulus” that may result in seizure) and seizure evokers (a seizure is evoked directly, and exposure to such stimuli is highly likely to result in a seizure “within a matter of seconds”), while acknowledging that the distinction between facilitators and evokers is arbitrary to some extent. Aird (1983) refers to inducing factors and precipitating or triggering factors, which appear to correspond approximately with Antebi and Bird's (1992) facilitators and evokers, respectively. Panayiotopoulos (2012) distinguishes between facilitating and precipitating stimuli, with the former increasing the frequency of seizures or electroencephalography (EEG) discharges but only the latter consistently provoking them.

We argue that whether a dichotomy, a greater number of categories, or a continuum does indeed best reflect the relationship between “reflex” and “nonreflex” events, clearer definition is required. Even with a continuum approach, the variables defining the continuum are currently not well specified. The observability of the stimulus or identifiability of the relationship (Antebi & Bird, 1992), and the percentage increase in seizures or discharges that follows the precipitant (Kasteleijn-Nolst Trenité, 2012) have both been suggested as important variables. Although these have been identified as occasional components of definitions in this review, neither these nor any other variables are consistently used in current practice.

Suggestions for ongoing work in this area

According to Zhang et al. (2012), classification attempts “all have the common goal of providing usable, reliable, reproducible, and standardized epilepsy diagnoses and terminologies. This is done, however, in the near absence of agreed-upon, standardized terminology and concepts.” There is clearly much to be done in clarifying terminology and classification and as demonstrated by this review, the reflex seizures and epilepsies are no exception.

The work to be done goes beyond increasing consistency of these terms in current practice; it requires consensus in how to conceptualize seizures and epilepsies in relation to the physical, sensory, and emotional environments in which they occur. If the terms in use are thought to represent different phenomena in reality, the difference should be better reflected in the definitions; if the terms are not thought to represent different phenomena in reality, they should arguably be abandoned altogether.

This represents a significant challenge, and one for which even the approach to resolving it is not clear. However, perhaps while this debate continues, the best authors can do is specify with as much detail as possible the phenomena they are discussing. The analysis in this review identifies the following as potentially important features to be specified: precipitant characteristics, seizure (outcome event) characteristics, timing of precipitant relative to precipitant, and the effect of the precipitant on seizure likelihood. The latter might include observations concerning the proportion of seizures that follow a precipitating event and the proportion of precipitant occurrences that result in seizure. Specifying these objective characteristics of the relationship would, we argue, be of great value and considerably more informative than references to judgments by observers as to how certain they are in their beliefs in the association between precipitant and outcome.

Although the questions addressed in this review were conceptual ones, we argue that they are potentially of considerable relevance to epilepsy treatment in practice. In particular, the extent to which nonpharmacologic treatment approaches (Fenwick, 1990; Dahl, 1992; Goldstein, 1997; Wolf, 2002) should be attempted for individual patients will depend very much on how their epilepsies are classified and conceptualized. This may be of particular importance for those whose epilepsies are difficult to treat using currently available antiepileptic drugs. Given the high proportion of patients who believe that their seizures are precipitated by something (Antebi & Bird, 1993; Spatt et al., 1998; Frucht et al., 2000; Spector et al., 2000; Nakken et al., 2005; Pinikahana & Dono, 2009) and the importance of these beliefs in their coping with epilepsy (Velissaris et al., 2007; Kilinc & Campbell, 2009) this will remain an important field of study.

Strengths and limitations

It is important to make clear that this study of clinical definitions does not address actual biologic processes that may or may not underlie the clinical phenomena, and in that sense does not test the biologic validity of concepts of reflex seizures and reflex epilepsies. However, analyzing definitions should illuminate current understanding and use of these concepts. Consideration of the consistency with which terms are defined and the features distinguishing one concept from another allowed fulfilment of the purpose of the review; that is, to appraise how meaningful these terms are in current practice.

However, several limitations require acknowledgment. Only English language research articles were included owing to resources available and the potential difficulty of combining findings across several languages when the structure of the analysis was focused on the terminology and vocabulary used. In addition, articles older than 10 years, and text books, were not included because of limited time and resources available. This precludes consideration of how these concepts have changed over time and how they are defined in educational contexts.

High interrater agreement of the coding scheme, and the use of an analytic approach in which themes emerged directly from the data rather than being predetermined by the researchers, are strengths of this work and suggest that the results accurately reflect current usage of these terms. Therefore, despite the limitations listed earlier, this work will have considerable value in illuminating current practice, making suggestions for a way forward and, hopefully, encouraging future work in clarifying this important area.

Acknowledgments

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. Disclosure
  8. References
  9. Supporting Information

JI was funded by a grant from Epilepsy Action (www.epilepsy.org.uk). During the preparation of this work, HR received financial support from the NIHR (UK) CLAHRC for Cambridgeshire and Peterborough.

Disclosure

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. Disclosure
  8. References
  9. Supporting Information

Neither author 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.

References

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. Disclosure
  8. References
  9. Supporting Information

Supporting Information

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. Disclosure
  8. References
  9. Supporting Information
FilenameFormatSizeDescription
epi12340-sup-0001-DataS1.docWord document25KData S1. Search strategy used in systematic literature search.
epi12340-sup-0002-DataS2.docWord document1029KData S2. Definitions extracted from articles.
epi12340-sup-0003-DataS3.docWord document66KData S3. Component frequencies from content analysis.

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