A rich literature dating back to the early twentieth century has characterized the cognitive morbidity associated with the epilepsies and the association of this morbidity with the cause, course, and treatment of the disorder. Critical reviews over the decades have cataloged the links between cognitive disorders and specific clinical features of the epilepsies including their etiology; seizure frequency and severity; complications of the disorder (e.g. status epilepticus); antiseizure medications; and electroencephalographic abnormalities, such as the type, frequency, and distribution of interictal epileptiform and slow wave activity.1–6
The understanding of the neuropsychological consequences of the epilepsies evolved in concert with advancements in the wider worlds of cognitive psychology and epilepsy. First, early studies were typically but not exclusively limited to the evaluation of intelligence. Assessment of higher cognitive functions was in its formative years7 and with the introduction of the Binet-Simon scales, and especially their adaption for use in the United States (eg, the early Vineland translation and the later Stanford-Binet revision), characterization of intellectual status in epilepsy followed quickly.8 As a deeper understanding of human cognition developed, and newer tests and measures became available to assess those concepts, appreciation of the cognitive correlates of epilepsy expanded apace. Second, much of the early literature came from very limited segments of the population of people with epilepsy, typically from specialized institutions (or colonies) serving the more complicated and severely affected individuals.3 Over time more representative portions of the population were sought out and investigated, which yielded a less biased but still imperfect characterization of the relationship between epilepsy and intelligence and broader cognitive status.2,9,10 The focus of research has continued to be on persons with epilepsy presenting to specialized tertiary care medical centers, although more representative population-based studies of cognition are available, particularly among children with epilepsy.11–14 Third, classification and taxonomy of the epilepsies developed from early rudimentary systems to the evolving and increasingly sophisticated international classification of epileptic seizures and syndromes.15,16 The neuropsychological features of these syndromes and their primary cognitive signatures have developed accordingly.6,11,17–20 Finally, as medical technology evolved patients with epilepsy have been studied with increasing sophistication to understand the underlying neurobiology of cognitive impairment in epilepsy, a primary focus of this article.
A critical and fundamental feature of the neuropsychology of epilepsy literature is that throughout its history a primary focus has been the relationship of cognition and cognitive disorders to core clinical features of the epilepsies including but not limited to the age of onset of epilepsy, etiology, seizure type and syndrome, medications, duration of epilepsy, and electroencephalographic features.21–26 Unequivocal associations between these clinical characteristics and neuropsychological impairments have been reported and repeatedly replicated through the decades, but the neurobiologic mechanisms through which they exert their effects have been investigated less intensively. A new literature is now under way, one linking cognitive abnormalities directly to indices of structural, functional, metabolic, and other neurobiological markers of cerebral integrity, independent of their association with clinical epilepsy characteristics. These trends are reviewed in the material to follow. The initial focus is on temporal lobe epilepsy (TLE) as a model with which to address the core points, because this form of localization-related epilepsy has been very carefully studied from both a cognitive and imaging standpoint. Some pertinent historical issues are touched on first, followed by more detailed reviews of the cognitive and neuroimaging abnormalities that have been found in TLE, followed by an overview of studies examining direct structure-function relationships in TLE and other epilepsies.