Abstracts

Rationale: Sodium valproate is one of the most widely used antiepileptic medications. Mental deterioration with reversible brain pseudoatrophy has been reported as a rare adverse effect associated with valproate [1]. The aim of this study was to determine if there are group-level structural brain changes associated with valproate use for seizure control in epilepsy. We used quantitative analysis of structural MRI to investigate cortical thickness and brain volume differences in epilepsy patients currently taking valproate, compared with epilepsy patients not currently taking valproate and controls. Methods: Cohort A: Intractable epilepsy subjects referred for 3T imaging as part of the Comprehensive Epilepsy Program, Austin Hospital, Melbourne. Cohort B: Community-based childhood-onset epilepsy subjects recruited as part of the Connecticut Study of Epilepsy in Children. Age-matched controls were included for each cohort. Whole brain T1-weighted MRI was acquired. MRI scans were processed using Freesurfer 5.1. Cortical thickness values were averaged over each major brain lobe (frontal, parietal, occipital and temporal). Total brain (TBV) and white matter volume (WMV) was measured. Thickness and volume differences were investigated in epilepsy subjects currently taking valproate relative to epilepsy subjects not currently taking valproate and controls. Age was included as a covariate in all analyses. Cohort A was the primary cohort; Cohort B was used to confirm findings from Cohort A. Results: Cohort A: Nine epilepsy subjects currently taking valproate (age 33 ± 8.1 years), 27 epilepsy subjects not taking valproate (34.7 ± 10.3 years), 45 controls (age 29.5 ± 10.2 years) were included. All subjects were male. Parietal lobe thickness was reduced in the valproate group relative to controls (0.1 mm, p < 0.01). No thickness differences were observed in other lobes. White matter and whole brain volumes were reduced in the valproate group relative to controls (WMV & TBV: p < 0.05). No changes were observed in the non-valproate epilepsy group. Cohort B: Eleven epilepsy subjects taking valproate (age 24.6 ± 3.7 years, 4 female), 122 epilepsy subjects not taking valproate (23 ± 3.1 years, 63 female) and 38 controls (age 23.3 ± 3.3 years, 19 female) were included. The finding of reduced parietal thickness in the valproate group was replicated in Cohort B (0.07 mm, p < 0.05). White matter and brain volumes were reduced in the valproate group (WMV: p < 0.05, TBV: p < 0.1). No thickness or volume reductions were observed in the non-valproate epilepsy group or other cortical lobes. Conclusions: Valproate treatment for seizure control in epilepsy is associated with subtle cortical thinning in the parietal lobes, and white matter and whole brain volume reductions. Because a significant proportion of the non-valproate groups would have taken valproate in the past, the observed effect is likely transient. Funding: NHMRC program grant 628952 (Australia), NIH-NINDS R37-NS31146 References:[1] Guerrini, R. et al (1998).Epilepsia 39(1):27-32.