Abstracts

RATIONALE: Higher cognitive functioning relies on the coordinated activity of distributed neuronal networks linked by projection, association and commissural white matter fiber tracks. We previously reported that childhood onset temporal lobe epilepsy was associated with reduction in the total volume of normal appearing cerebral white matter suggesting an adverse neurodevelopmental impact of early epilepsy onset. This study investigated: 1) the volume of the corpus callosum as a function of the age of onset of recurrent temporal lobe seizures controlling for duration of epilepsy, and 2) the clinical neuropsychological significance of identified anomalies in brain connectivity.
METHODS: Subjects were 32 patients with TLE (16 with childhood onset and 16 with adult onset, matched for duration of epilepsy) and 15 healthy controls. Patients were 14 to 60 years of age with no MRI evidence of neocortical lesions or other developmental or neurological disorders. Controls were healthy friends or family members of the patients. Using 3 co-registered image sets, manual trace of the corpus callosum was performed in the midsagittal and parasagittal planes. Total volume measures were based on traces spanning 5 sagittal slices (midsagittal plus the 2 adjacent bilateral slices). In addition, each trace was divided into the 7 subregions by applying a BRAINS2 software utility modeled according to the Witelson partitioning method. Patients and controls were administered a battery of cognitive tests including measures of intelligence (WAIS-3), memory (WMS-3), speeded psychomotor processing (Trails A and B), and speeded fine motor dexterity (Grooved Pegboard).
RESULTS: Total corpus callosum volume (ANCOVA with age, gender and height as covariates) differed among groups (p = 0.004) and post-hoc comparisons showed childhood onset patients to have significantly smaller corpus callosum volume compared to healthy controls (p = 0.003) and late onset patients (p = 0.006), with no difference between the late onset patients and controls (p=0.994). Volume for the childhood onset patients was reduced 15% compared to both healthy controls and late onset patients. Examination of Witelson regions showed significant (p [lt] 0.05) reductions in childhood compared to late onset patients in the posterior half of the corpus callosum (areas 5, 6 and 7) and area 2. Partial correlations between total corpus callosum volume and neuropsychological measures (total ICV as covariate) showed reduced corpus callosum volume to be associated with significantly lower Performance IQ, immediate but not delayed memory, complex psychomotor processing and speeded fine motor dexterity with both hands.
CONCLUSIONS: Childhood onset temporal lobe epilepsy is associated with a significant reduction in corpus callosum volume (-15%) compared to healthy controls and late onset patients matched for duration of epilepsy. Volumetric reductions in childhood onset patients are most prominent in posterior corpus callosum. This reduction in brain connectivity appears to be of clinical consequence in that volumetric reductions were associated with poorer performance on measures of nonverbal intelligence, immediate memory, and speeded motor and psychomotor processing.
[Supported by: NIH NS RO1 37738.]