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.