Abstracts

Rationale: Prolonged febrile seizures (PFS) are the most common type of status epilepticus in childhood. Although changes in hippocampus and associated structures have been found in the acute period following PFS, the long term evolution of these changes is not known. A childhood history of PFS has been strongly associated with temporal lobe epilepsy with mesial temporal sclerosis (TLE:MTS) but prospective evidence to support a causal link remains weak. This longitudinal study was undertaken to investigate the pattern and longevity of white matter abnormalities following PFS and any progressive changes that may lead to TLE:MTS. Methods: 29 children were recruited following PFS and underwent serial magnetic resonance imaging (MRI) including diffusion tensor imaging (DTI) 1 month (n=29, mean age: 2.06yr), 6 months (n = 17, mean age: 2.40yr) and 12 months (n = 19, mean age: 2.95yr), after PFS. A control group of 18 children with no seizures and normal neurodevelopment (mean age: 2.76yr) had similar investigations at one time point. Tract-based spatial statistics (TBSS) was used to align all subjects fractional anisotropy (FA) maps and project them onto a common white matter skeleton. A voxelwise statistical analysis of all subjects was performed between PFS and control groups at each time point using a nonparametric permutation test with a cluster size threshold of >3 and a p value of <0.05 for significance, after correcting for multiple comparisons. Manual masks were drawn over the anterior corpus callosum (aCC) and the mean FA measured in each subject over these masks as well as over the entire FA skeleton. Univariate ANOVA with age adjustment was used to compare FA between subjects and controls and between timepoints.Results: Widespread reductions in FA were found in the PFS group at 1 month post-PFS involving multiple white matter tracts such as corpus callosum, anterior corona radiata, external capsule and sagittal stratum. Similar changes were present at 6 months but had resolved by 1 year post-PFS (Figure 1). FA over the entire white matter skeleton was reduced by an average of 0.023 (p = 0.004) at 1 month in the PFS group after adjusting for age, but no significant differences were found at either 6 months or 1 year. Looking specifically within the anterior corpus callosum, there were significant differences in aCC FA (p=0.009) at 1 month after adjusting for age, with an average 0.057 reduction in FA. This was still present at 6 months (0.069, p = 0.004) however at 1 year there were no significant differences in aCC FA between controls and PFS groups. Conclusions: There is widespread and long lasting disruption of white matter tract structure following PFS. However over time this resolves and no progressive changes are seen. This is suggestive of a self-limiting seizure-related insult or a resolving developmental abnormality, with no evidence of long-term progression to TLE:MTS.