The following commentaries were invited by the Editors-in-Chief
Acute symptomatic seizures—Should we retain the term?
Article first published online: 1 APR 2010
© 2010 International League Against Epilepsy
Volume 51, Issue 4, pages 722–723, April 2010
How to Cite
Shorvon, S. and Guerrini, R. (2010), Acute symptomatic seizures—Should we retain the term?. Epilepsia, 51: 722–723. doi: 10.1111/j.1528-1167.2010.02501.x
- Issue published online: 1 APR 2010
- Article first published online: 1 APR 2010
The concept of acute symptomatic seizures is a troubled one. It was first widely applied in the 1980s at a time before there was modern neuroimaging, when the term was devised to differentiate these seizures from those in the “remote symptomatic” and “idiopathic” epilepsies (the latter term in its previous usage as meaning “no cause found,” and not in its current usage as indicating a genetic cause). It then fell largely from fashion for obvious reasons, but recently the Epidemiology Commission of the International League Against Epilepsy (ILAE) convened a subgroup to reconsider the definition of acute symptomatic seizures for epidemiologic studies. This group has slightly modified the meaning of the original term and defined an acute symptomatic seizure as “a clinical seizure occurring at the time of a systemic insult or in close temporal association with a documented brain insult” (Hauser et al., 2010).
In our view, the concept of acute symptomatic remains problematic for three major reasons. The first is the problem of heterogeneity. The term, as recommended, includes two distinct types of seizure: (1) the “early seizures” in acute brain insults and (2) the seizures provoked by reversible environmental, metabolic, and toxic factors. The premise inherent in the term is that there is something fundamentally different about acute symptomatic seizures that differentiates them from other types of symptomatic epilepsy. In the early seizures after acute brain insult this is clearly the case. For instance, the early seizures after head injury have a physiology that is different from that in chronic posttraumatic epilepsy. The early seizures are caused by contusions, hemorrhage, metabolic change, endocrine change, hypotension, and so on—all mechanisms that have nothing in common with the late seizures of posttraumatic epilepsy. Similar considerations apply to the early seizures in stroke and infection, for instance.
However, the seizures provoked by metabolic disturbance, fever, or toxic exposure, for instance, have no underlying brain pathology and there are no known physiologic differences in these seizures from seizures in patients with epilepsy (idiopathic or symptomatic), which are provoked by the same cause, or indeed from individuals who do not have seizures when exposed to the same precipitant. These seizures are surely simply “provoked” or “precipitated” seizures, and reflect the interplay of the provoking factor and the individual “seizure threshold.”
In addition, the term is too simplistic when referring to such conditions as febrile seizures in which the causal influences are complex. Some cases of febrile seizures have genetic causes (SCN1A or PCDH 19 gene mutations, for example). Body temperature elevation alone (whether produced by fever or heating) is sufficient to induce seizures when an SCN1A mutation is present (Oakley et al., 2009), but the underlying mode of epileptogenesis is the same as that producing spontaneous seizures. Because the definition of “simple” or “complex” febrile seizures is based purely on clinical history and semiology, but underlying causes are variable, to consider them as simply “acute symptomatic” risks mixing different conditions with different physiology and clinical features, which carry significantly different risk rates of subsequent epilepsy. Epidemiologic studies on febrile seizures will require definitions and information that are not easily incorporated within the proposed “acute symptomatic” denotation.
The second problem with the current usage is the arbitrary nature of the criteria for inclusion, and indeed of the list of included conditions. Why, for instance, in the ILAE scheme is the period for categorizing a seizure as “acute symptomatic” within 1 week of trauma and stroke, but longer (not specified) for a subdural hematoma or infections? Why are parasitic infections included but congenital toxoplasmosis excluded? Alcohol withdrawal seizures are included but not alcohol-induced seizures? Why are “reflex seizures” due to environmental triggers such as visual stimulation not included, although seizures induced by hypoglycemia are included? Why are age-related influences not considered?
Third is the issue of age. The pathophysiologic dynamics leading from acute to postacute and stable brain damage and related epileptogenesis differ in the young compared to the adult brain. For example, the 1-week limit set to define acute symptomatic seizures occurring after stroke or ischemic encephalopathy might not apply to hypoxic–ischemic brain injury of newborns, in which it is often impossible to know the precise duration of the causative factors and timing of damage. Likewise, various metabolic derangements in the very young child may remain undetected for a long time until seizures develop, as is often the case, for example, with neonatal hypoglycemia (Volpe, 2000). There are further issues also. The timing of the causal insult is important. For instance, the duration of hypoglycemia is a major determinant of whether seizures will occur. The suggestion that metabolic derangements should be documented within 24 h (from seizure occurrence?) in order to satisfy the requirements for acute symptomatic seizures might not apply to a number of other metabolic conditions exhibiting a similar insidious course in their early stages. In the metabolic conditions, arbitrary cutoff levels are cited for inclusion as “acute symptomatic epilepsy” despite the fact that there is individual variation in susceptibility (“seizure threshold”) that much depends on the homeostatic mechanisms. Also, the rate of change of metabolic factors is probably as important as the extent of change.
Furthermore, the term was originally extended to include initial seizures that led to the diagnosis of progressive conditions such as tumors (primary and secondary) (Hauser et al., 1991; Annegers et al., 1995), which obviously makes no sense, and there is no mention of how these conditions would be classified in the current recommendations. A statement that such conditions would not be now included (as they had been previously) would be welcome.
A classification in our view must have a physiologic underpinning and must apply definitions in a systematic and nonarbitrary way. It is for these reasons that the classification of epilepsy into acute symptomatic (and remote symptomatic and idiopathic seizures) had been previously largely abandoned. In our view, if the term acute symptomatic seizure is to be reintroduced, it should be restricted to the physiologically distinct “early seizures” after acute brain injury and other acute destructive brain insults, which mechanistically are clearly completely different from any subsequent consequential chronic epilepsy.
Neither of the authors has any conflicts 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.
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