Abstracts

Experimental studies in chronic rodent models of epilepsy have shown that kindled seizures induce progressive cellular alterations, neuronal loss, increasing susceptibility to evoked and spontaneous seizures, and behavioral and cognitive deficits that worsen as a function of the cumulative number of seizures. Whether chronic temporal lobe epilepsy (TLE) in humans is associated with progressive adverse cognitive change remains controversial. The purpose of this investigation was to characterize the nature and extent of cognitive change among patients with temporal lobe epilepsy versus healthy controls over a prospective 4-year test-retest interval.
A cohort of 80 patients with early onset temporal lobe epilepsy and 80 healthy controls (friends and family of patients), ranging in age from 14 to 60 years of age, underwent baseline neuropsychological evaluation four years ago. These patients are now returning for prospective neuropsychological re-examination. Cognitive testing is comprehensive and includes assessment of intelligence, language, perception, verbal and nonverbal memory, psychomotor processing, executive function, and speeded fine motor dexterity. At this writing, a consecutive series of 31 subjects (17 TLE, 14 controls) have completed the neuropsychological re-assessment.
Examination of test-retest performance reveals two core findings: 1) TLE patients exhibit significant (p [lt] 0.01) decline in Performance IQ over the four year test-retest interval compared to controls, 2) healthy controls exhibit significant (p [lt] 0.05) practice effects (i.e., performance improvements from baseline to follow-up) across a wide variety of test measures including intelligence (Full Scale IQ), language (naming), and memory (immediate and delayed), with a trend (p = 0.10) for executive function (response inhibition). No such effects were found for TLE patients.
Prospective (4-year) neuropsychological reassessment reveals divergent patterns of cognitive performance among patients with TLE versus healthy controls. Patients with TLE exhibit significant decline in aspects of mentation (Performance IQ) in the context of a broader pattern of a lack of normal practice effects across multiple cognitive domains that are evident in healthy controls. These findings are consistent with the hypothesis that chronic epilepsy may have cumulative adverse effects on higher cognitive abilities.
[Supported by: NIH NS 2RO1-37738 and MO1 RR03186]