Thursday, September 10, 2015

Epilepsy with encephalopathy rather than epileptic encephalopathy

Korff CM, Brunklaus A, Zuberi SM. Epileptic activity is a surrogate for an
underlying etiology and stopping the activity has a limited impact on
developmental outcome. Epilepsia. 2015 Aug 21. doi: 10.1111/epi.13105. [Epub
ahead of print]


The concept of epileptic encephalopathy is important in clinical practice, but its relevance to an individual must be assessed in the appropriate context. Except in rare situations, epileptic activity is a surrogate for an underlying etiology, and stopping the activity has a limited impact on developmental outcome. Labeling a group of epilepsies as "the epileptic encephalopathies," risks minimizing the impact of epileptic activity on cognition and behavior more widely in epilepsy. Similarly, describing the encephalopathy associated with many infantile onset epilepsies as "epileptic" may be misleading. Finally, concentrating on the epileptic activity alone and not considering the wider consequences of the underlying etiology on cognitive and behavioral development, may focus research efforts and the search for improved therapies on too narrow a target. Therefore, epileptic encephalopathies should not be considered as a specific group of epilepsies but, rather, the concept of epileptic encephalopathy should be applicable to all types of epilepsies and epilepsy syndromes, whenever it is relevant in the clinical course of a particular individual, at any age.

From the article:

 Early control of spasms and the epileptic component of the encephalopathy may improve developmental outcomes in certain groups, but the evidence is much less certain in those with a known etiology. However, broad distinctions such as etiology defined or undefined are only helpful to a limited degree in predicting outcome. More detailed stratification of etiology is necessary; for example, an infant with spasms and lissencephaly associated with a Lis-1 gene mutation may have a better developmental outcome than an infant with no structural lesion who has a CDKL5 mutation. Why and how the etiology causes the spasms in an individual child is typically not known. For example why does one infant with an antenatal stroke develop spasms and another not? The terms cryptogenic, symptomatic, and idiopathic as previously used to classify infantile spasms are imprecise and poorly understood and should be discarded in favor of a more specific etiologic classification...

The shared genetic underpinnings of epilepsy and other neurodevelopmental disorders has led to the call for a reappraisal of the 19th century concepts of the broader genetic neurologic trait and its applicability in modern epilepsy genetics. The neuropsychiatric comorbidities have often been regarded as consequences of the epilepsy, the stigma related to the epilepsy or medications used to treat the epilepsy; however, there is evidence that cognitive and behavioral problems predate the epilepsy even in the more common epilepsies with presumed complex inheritance.

We Need to Assess Comorbidities in All Epilepsies, Not Just those Labeled Epileptic Encephalopathies

The term benign when used in lay parlance means something that is mild, gentle, or harmless and does not threaten life or health. It is widely applied to epilepsies when they are not thought to be associated with significant comorbidities, are pharmacoresponsive, or are self-limited in their duration. The benign epilepsies of childhood are not truly benign. They are often age-limited but they are not always pharmacoresponsive, and they are often associated with specific and more general cognitive impairments. Benign myoclonic epilepsy in infancy was listed as an epilepsy syndrome in the ILAE Diagnostic Scheme of 2001; however, by the 2010 Proposal for an Organization of the Epilepsies, it was termed myoclonic epilepsy in infancy. Observational studies had demonstrated that up to one third of individuals with this condition will go on to have specific or more general cognitive impairment. Benign familial neonatal seizures associated with mutations in the KCNQ2 gene may recur in later life in up to one third of cases. In some familial cases and more commonly in de novo cases with KCNQ2 mutations, there may be a severe neonatal onset KCNQ2 encephalopathy with some intermediate forms between the “benign” familial and de novo encephalopathic forms...


There is insufficient evidence in most cases of epilepsy to determine the relative importance of the epileptic activity on the cognitive, neuropsychiatric, and behavioral problems compared to other consequences of the underlying etiology. Where evidence exists, it points to etiology being the major determinant of developmental outcome. We suggest that in many circumstances the term epilepsy with encephalopathy rather than epileptic encephalopathy may be more appropriate. This would encourage clinicians to consider and evaluate, when appropriate, cognitive and behavioral problems in all people with epilepsy, as well as to search for other potential sources of intellectual dysfunction, such as treatment side effects. Etiology should be defined in as much detail as possible within the constraints of the local health care system.

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