Abstracts

Rationale: While emerging evidence indicates that there is frontal-subcortical network dysfunction in Juvenile Myoclonic Epilepsy (JME)1, the relationship between white matter (WM) abnormalities, seizures, and neuropsychologic deficits is uncertain. Diffusion Kurtosis Imaging (DKI) is a novel MRI method that uses high diffusion sensitivity (b values ≥2000 s/mm2) to yield parameters proposed to be more tightly linked to tissue micro-structure than conventional diffusion tensor imaging (DTI)2. DKI may be more sensitive than DTI to reveal WM abnormalities in idiopathic generalized epilepsy (IGE)3. This study aims to use DTI and DKI to assess WM in JME, and to determine whether WM abnormalities correlate with neuropsychologic deficits.Methods: Fifteen JME patients (mean 24.3 yrs, range 18-32 yrs, 4 males) and fifteen age and sex-matched controls (mean 24.5 yrs, range 17-34 yrs, 4 males) were scanned on a Varian Inova 4.7T MRI. DKI was acquired in 11.5 min with b=0, 1000, 3000 s/mm2 and 60 slices with 2x2x2 mm3 resolution. Tensor/kurtosis calculation and tractography was performed using ExploreDTI v. 4.8.4 to identify: fornix (Fx), dorsal cingulum (dCg), genu/body/splenium of corpus callosum (gCC/bCC/sCC), inferior fronto-occipital fasciculi (IFO), and corticospinal tracts (CST). Diffusion parameters extracted were fractional anisotropy (FA), mean (MD), axial (D||), and radial (D┴) diffusivities; kurtosis anisotropy (KA), and mean (MK), axial (K||), and radial (K┴) kurtosis values per tract, combining left and right tracts. Neuropsychological testing included verbal (Rey Auditory Verbal Learning Test, RAVLT) and non-verbal memory (Aggie Figural Learning Test, AFLT), verbal fluency (Controlled Oral Word Association Test, COWAT), processing speed (Weschler Adult Intelligence Scale Processing Speed Index, WAIS-PSI), and a mood survey (Beck Depression Inventory, BDI). Results were assessed using Student's unpaired t-test (α = 0.05),with correction for multiple comparisons using the Holm-Sidak method, with linear correlation calculated by Pearson's correlation coefficient.Results: DTI showed lower FA of bCC in JME vs controls (mean ± SD: 0.58 ± 0.02 vs 0.55 ± 0.02, p<0.001). KA was lower in gCC in JME vs controls (mean ± SD: 0.40 ± 0.03 vs 0.37 ± 0.03, p<0.005). There were no significant differences among other tracts for other metrics (MD, D┴, D||, MK, K┴, K||). JME subjects had lower T-scores on the COWAT and WAIS-PSI scales vs controls (mean ± SD: 37.7 ± 7.9 vs 54.4 ± 10.0, p<0.0001; 45.0 ± 8.5 vs. 61.3 ± 8.5, p<0.0001), but not on the RAVLT, AFLT, or BDI. There were no significant correlations between cognitive scores and tractography metrics.Conclusions: DTI showed decreases in FA of the bCC in JME, as previously reported4. DKI of JME subjects showed decreased KA only in the gCC, unlike a recent report of extensive kurtosis abnormalities using whole brain voxel wise analysis, although the subjects were a mixture of IGE and JME3. The impairments in verbal fluency and processing speed are consistent with diffuse frontal lobe dysfunction, but did not correlate with DKI or DTI metrics.