Abstracts

RATIONALE: Neuropsychological studies have demonstrated that an earlier age of onset of recurrent seizures is associated with poorer cognitive functioning. This relationship has been noted in studies of adult patients with diverse seizure types including temporal lobe epilepsy. The cognitive impairment associated with early onset partial seizures appears more generalized than would be expected from a focal epileptogenic process. Generalized cognitive impairment in association with early onset localization-related syndromes of epilepsy, such as temporal lobe epilepsy, raises the question of whether focal seizures in childhood may be associated with a more widespread influence on brain development and structure.
METHODS: Healthy controls (n = 62) and patients with early (n = 37) and late (n = 16) age of onset of temporal lobe epilepsy were compared with high-resolution quantitative MRI volumetrics of segmented whole brain and lobar volumes of gray and white matter and CSF. Patients also underwent comprehensive neuropsychological assessment.
RESULTS: Patients with childhood onset temporal lobe epilepsy (mean onset age= 7.8 yrs) exhibited significant widespread compromise in neuropsychological performance and substantial reduction in brain tissue volumes extending to extratemporal regions compared to healthy controls and late onset temporal lobe epilepsy patients (mean onset age = 23.3 yrs). Most significant was reduced total white matter volume among the childhood onset patients. Reduction in brain tissue volume, especially total white matter volume, was associated with significantly poorer cognitive status, attesting to the clinical significance of the volumetric abnormalities.
CONCLUSIONS: Early onset temporal lobe epilepsy is associated with significant volumetric abnormalities in both temporal and extratemporal regions, especially affecting white matter. Widespread abnormalities in neuropsychological function are also evident in early onset patients compared to controls and late onset patients, consistent with the generalized pattern of volumetric abnormalities. Late onset patients exhibit considerably fewer volumetric and cognitive abnormalities compared to healthy controls despite a long duration of chronic seizures (16.2 yrs). The greater volumetric and neuropsychological abnormalities in early onset temporal lobe epilepsy remained unchanged even after controlling for duration of epilepsy and other factors in supplementary analyses. The overall pattern of findings therefore raises the hypothesis that childhood onset temporal lobe epilepsy is associated with a generalized adverse neurodevelopmental impact on brain structure and function.
Support: NIH RO1 37738