Syndromes and Epilepsies:

The term, “syndrome,” has been used in various and at times imprecise ways.  A previous Task Force report defined a syndrome as “a complex of signs and symptoms that define a unique epileptic condition.”  In more operational terms, a syndrome is a condition that is a clinically recognizable pattern; the clustering of signs and symptoms that form this pattern suggests shared mechanisms.  Those who have a particular syndrome differ in some fundamental way(s) from those who have other forms of epilepsy.  The vast majority of the syndromes recognized in epilepsy are genetic and developmental disorders with onset predominantly in infancy, childhood and adolescence.  The 1989 classification of the epilepsies attempted to fit all seizure disorders into a unified system of classification.  That does not mean, however, that everything listed in the 1989 scheme is a “syndrome” in the sense just defined.  Future efforts for classifying and organizing our information about the epilepsies will explicitly acknowledge this and will treat syndromes in a system separate from other forms of epilepsies which do not (yet) belong to recognized syndromes.

Epilepsy “Syndromes:”
The Genetic and Developmental Epilepsy syndromes that are recognized based on expert opinion and varying degrees of evidence concerning the potential for shared underlying mechanisms, are listed in table 1.  Rather than organize them according to the previous categories from 1989, they are simply listed by age at onset.

Previous groupings or families of these syndromes may still be convenient to acknowledge and use, particularly the cluster called “Idiopathic Generalized Epilepsies” (IGE) and the “Idiopathic Localization-Related Epilepsies” (ILRE).  Whether and how to incorporate recently recognized syndromes such as autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) or autosomal dominant partial epilepsy with auditory features (ADPEAF) or any of the other familial focal epilepsies is not clear at the present time.  The Genetic (formerly Generalized) Epilepsy with Febrile Seizure-Plus (GEFS+) cluster, does not fit our current understanding of a syndrome as disorder with relative phenotypic homogeneity that can recognized on an individual level.  In addition, because it is familial-genetic and with predominantly generalized features, it would probably best be described as an idiopathic generalized form of epilepsy under the 1989 system;  however, evidence indicates that the GEFS+ phenomenon is distinct from the entities traditionally grouped under the IGE cluster.  Consequently, for now, it will be recognized as its own cluster or phenomenon.

The concept of “Epileptic encephalopathy” has been in use for several years and embodies the notion that certain forms of epileptic activity, particularly in the developing brain, alter brain development and function and lead to severe cognitive and behavioral impairment.  Inherent in this concept is the idea that by suppressing or preventing the epileptic activity, one may improve the cognitive and behavioral outlook of the disorder.  This is premised on rapid effective intervention before the abnormal epileptic activity interferes irrevocably with normal processes of brain development.  At the present time, we are largely unable to distinguish effects of the epileptic activity itself from the underlying cause of the disorder and the drugs used to treat the disorder.  For this reason, “epileptic encephalopathy” should be viewed as a concept and a description of what is observed clinically with the recognition that a better understanding of mechanisms is needed for accurate attribution of cause and effect.

The term catastrophic epilepsy is generally discouraged largely for valid emotional reasons in that it is a terrible type of diagnosis to present to a family.

The terms “secondary” and “secondarily” have been the source of considerable confusion in epilepsy. The first (secondary) has been used in reference to epilepsies that occur as a consequence of (secondary to) a distinct other disorder or condition (e.g. secondary to stroke or a brain malformation). Secondary generalized epilepsies is an expression sometimes used and includes syndromes and disorders that are not necessarily part of the epileptic encephalopathy concept and epileptic encephalopathy includes syndromes that were not previously considered secondary generalized (e.g. Dravet, Landau-Kleffner). The syndromes that are currently recognized as epileptic encephalopathies and other conditions that might be described as secondary generalized epilepsies are listed in table 2.

By contrast, “secondarily” generalized is used to refer to seizure that begin focally and then later go on to generalize generalize (i.e. secondarily).

Organization of  Genetic and Developmental Epilepsies:
In the future, syndromes, as defined above, will be classified and organized in a system of their own.  They will not be uniquely assigned to a given category or class, but may be associated with multiple clusters of syndromes or arranged accordingly to a set of dimensions reflecting the features that are used to recognize syndromes in the first place (e.g. age at onset, seizure types, EEG signatures, specific causes, etc).  Syndromes could then be arranged according to one or more of these dimensions depending on the specific purposes.  For example, in the 1989 classification, Dravet syndrome was listed as a cryptogenic disorder with both focal and generalized features.  At the present time, we would consider it as an epileptic encephalopathy with onset during the first year of life and of a fundamental genetic basis, most frequently a sodium channelopathy (what might have been called “idiopathic” in 1989).  It is perhaps also part of the GEFS+ spectrum.

Diseases versus syndromes:
Although some forms of epilepsy are perhaps best considered as specific diseases, the disease-syndrome distinction has not been consistently recognized throughout medicine.  It does not seem that the field of epilepsy has a specific mandate to enforce such a distinction.  Consequently, at the present time, we are not separating specific disease-like entities from syndromes per se.

Other epilepsies not yet recognized as belonging to specific syndromes:
Other Focal epilepsies (and other epilepsies) that are not as yet part of genetic and developmental syndromes compromise the majority of epilepsies in the population.  Within these epilepsies, there are some well-recognized entities that have very specific implications for surgery.  These entities may fit our concept of a syndrome although not always in the same was as do the genetic and developmental epilepsies. Some of the better known in this category are mesial temporal lobe epilepsy with hippocampal sclerosis, gelastic seizures with hypothalamic hamartoma, and Rasmussen’s syndrome.

The remaining focal epilepsies are typically characterized by presence or absence of an identifiable lesion or other form of insult and by localization.  Although well delineated genetic syndromes have been found from among the other focal epilepsies, (e.g. ADNFLE, ADPEAF, etc), the “classification” of these epilepsies by presence of a recognized insult and lobe does not identify specific syndromes but merely describes broad groups of epilepsies which do not, by virtue of having been grouped by description, represent coherent entities and should not be taken as such.

For the present, use of these descriptive categories is inevitable.  Future directions, however, will encourage much more precise characterization of individual patients. Patients can be grouped according to one or more characteristics.  These groups do not themselves represent syndromes, however.  Further research to identify biologically coherent and clinically relevant entities whether or not they ultimately are considered as genetic-developmental epilepsy syndromes is encouraged.  The Commission will be making recommendations in the future regarding methods and evidence needed to accomplish this goal.