Abstracts

Research examining the predictors of cognitive impairment in epilepsy has traditionally focused on clinical variables associated with the cause (e.g., etiology), course (e.g., seizure frequency), or treatment (e.g., medications) of the disorder. Structural brain changes associated with chronic epilepsy, particularly temporal lobe epilepsy (TLE), have been characterized in regions both related to and distant from the primary areas of epileptogenesis, but their associations with cognitive morbidity have been examined infrequently. The purpose of this study was to determine the association between cognitve morbidity and reductions in total gray and white matter and increased CSF volumes. Healthy controls (n = 67) and patients with TLE (n = 77), ranging in age from 14 to 60 years, underwent comprehensive neuropsychological assessment of intelligence, language, perception, verbal and nonverbal memory, psychomotor processing, and speeded fine motor dexterity. Twenty cognitive indices were derived for each subject from this test battery. Test scores were converted to adjusted (age, gender, education) z-scores and an impairment index computed for each subject, defined as the proportion of test scores exceeding z = -1.5. Test score performance was related to adjusted (ICV) quantitative volumetric measures of total cerebral gray and white matter and total CSF. Poorer cognitive function was especially associated with increased CSF volume. Specifically, increased total CSF was associated with poorer Full Scale and Performance IQ (WAIS-III), immediate and delayed visual and auditory memory (WMS-III), simple and complex psychomotor processing (Trails A and B), speeded fine motor dexterity (Grooved Pegs), and response inhibition (Stroop Test). Reductions in total cerebral white and gray matter were also significantly associated with poorer cognitive performance, but to a lesser extent. Examining the degree of cognitive morbidity exhibited by individual TLE patients (i.e., impairment index), increasing cognitive morbidity was significantly associated with increased CSF (r = .36, p [lt] 0.001) and decreased cerebral white matter (r = .28, p [lt] 0.01). Quantitative MRI volumetric abnormalities in chronic TLE are associated with significantly increased cognitive morbidity. Increased total CSF was an especially strong correlate of neuropsychological dysfunction, with significant but somewhat weaker effects for reductions in cerebral gray and white matter. The pathways through which clinical seizure features (e.g., etiology, seizure frequency, duration, medications) result in abnormalities in brain structure remain to be clarified, but these structural changes, especially markers of atrophy such as total CSF, appear to be of clinical consequence. (Supported by NIH NS 2RO1-37738 and M01 RR03186)