Assessing the behavioral and cognitive effects of seizures on the developing brain

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The degree to which seizures lead to 'brain damage' is not fully known, but this question has important clinical implications. Seizure-induced brain damage can be defined in several ways: structural, physiological, and behavioral. The behavioral and cognitive effects of seizures are difficult to ascertain in patients, because it is hard to differentiate the effects of the seizures from the underlying brain pathology, anticonvulsant treatment, and developmental variables. In animal models, the ability to control seizure variables allows detailed investigation of factors that cannot be easily distinguished in clinical studies. In models of experimental epilepsy, both brief and prolonged seizures lead to brain damage. While the consequences of seizures are much more extensive in the adult brain, long-term alterations are also seen in the developing brain. This chapter focuses on the effects of seizures during development on subsequent behavior and cognition in experimental epilepsy models. The investigator must choose carefully among the various tests of behavior, learning, memory, and cognition, since the existence or extent of deficits may depend upon which test is selected and how the data are analyzed. The experimental evidence suggests that seizures early in life are associated with subtle deficits in behavior and cognition, even in the absence of overt structural neuronal damage. These deficits are dependent upon the age at which seizures occur (less severe deficits at younger ages), seizure frequency and seizure severity, but are largely independent of seizure etiology, occurring after several types of chemoconvulsants and electrical stimulation. Seizure-induced behavioral and cognitive deficits, which may not become obvious until long after the onset of the epilepsy, might be equally or more detrimental to a child's overall function than the seizures themselves.