Pharmacological Effects on Brain Morphology and Cognitive Functions in Idiopathic Generalized Epilepsy

Sodium Valproate (VPA) is one of the first-generation Antiepileptic Drugs (AEDs) which mediates epileptic activities by releasing stimulators of Gamma-Aminobutyric Acid (GABA) and is greatly used to treat partial and generalized seizures. Lamotrigine )LTG( is commonly used as AEDs that are widely utilized in first-line monotherapy or in combination with other AEDs. Our specific goal was to compare these two AEDs with different molecular mechanisms on both cortical and subcortical brain structures, along with cognitive performance and dysfunctions.

We conducted a retrospective study comparing LTG with sodium VPA, both administrated as monotherapy. Twenty patients with a confirmed generalized-epilepsy tonic-clonic seizure who had been treated at least 6 months with LTG (n=8) and Sodium VPA (n=12) were retrospectively recruited. We also included 12 age, gender, and education-matched Healthy Controls (HC). We evaluated cognitive performances. All participants underwent a Magnetic Resonance Imaging (MRI) scanner and T1-weighted MR images were acquired. Voxel-based morphometric alterations in the brain cortex, as well as subcortical structures, were inspected using Statistical Parametric Mapping (SPM) software.

The cognitive performance was revealed inferior in patients on Sodium VPA. Poor performance was associated with significant volume reduction in insula bilaterally, and subcortical structures of thalamus, cerebellum, and hippocampus compared to the HC. Comparing patients on LTG to HC revealed significant volume reduction in the anterior cingulate cortex in concordance with slight cognitive dysfunctions.

These findings suggested that different molecular mechanisms of Antiepileptic Drugs (AEDs) may affect brain structures and cognition with different severity levels, presumably with more adverse effects induced by GABA mediations from sodium VPA.