Abstracts

Rationale: Children with epilepsy are at increased risk of cognitive impairment (CI) which has a significant impact on their quality of life. Age of onset appears to be important, with children with early onset epilepsy (CWE) particularly at risk. The underlying pathophysiology of this is not well understood and overall risk of CI does not correlate well to clinical factors such as seizure frequency or semiology. Decreased white matter (WM) integrity has been associated with reduced cognitive ability in a number of epilepsy syndromes, including childhood frontal lobe epilepsy, temporal lobe epilepsy and benign epilepsy with centro-temporal spikes. To date no studies have been performed in CWE; we hypothesise that pre-existing WM abnormalities form part of the neural substrate underlying CI in CWE and that CWE and CI will have decreased WM integrity compared to those without CI.Methods: As part of an ongoing prospective study of newly diagnosed CWE (NEUROPROFILES, < 5 years age), children underwent MRI including diffusion tensor imaging (DTI; isotropic 2.5mm3 voxel size, 64 diffusion directions with 7 b0 images, b=1000s/mm2) and age-appropriate neurocognitive assessment using Bayley Scales of Infant and Toddler Development (BSID-III) or Wechsler Pre-School and Primary Scales of Intelligence (WPPSI-III). Children with cognitive scores <1.5 standard deviations below population means were considered to have cognitive impairment. Probabilistic neighbourhood tractography was used to identify 16 major WM tracts and tract-averaged fractional anisotropy (FA), mean diffusivity (MD), axial and radial diffusivity calculated for each pathway. Comparison was made between CWE with/without CI using univariate ANOVA co-varying for age.Results: 17 children (11 male:6 female), mean age 32(±19) months (s.d.) successfully underwent DTI and cognitive testing. Mean age at first seizure was 25(±20) months (s.d.), 7/17 had focal seizures, 5/17 had macroscopic abnormalities on MRI. Mean DQ/IQ was 87(±19) and 6/17 had scores < 1.5sd below population means. After correcting for age, FA in the right inferior longitudinal fasiculus(ILF) was significantly reduced in children with CI (0.323 vs 0.405, p=0.009). This was primarily due to increased radial diffusivity, with axial diffusivity similar between groups. No significant differences were found in other WM tracts.Conclusions: To our knowledge this study provides the first evidence that reduced cognitive ability in CWE < 5 years age may be associated with specific WM abnormalities. The ILF is thought to play an important role in object/face recognition and has also been associated with general cognitive ability and processing speed. Visual processing difficulties have also been associated with poor cognitive outcomes in forms of EOE such as West syndrome. Due to the modest numbers involved, further investigation is needed to determine if decreased FA is specific to the ILF as well as recruitment of an age-matched control group to determine the normal age related maturation of WM along these tracts and its utility as a biomarker of CI; this work is ongoing.