The GABAergic Inhibitory System in Drug Resistant Epilepsy

This study investigates the potential therapeutic effects of lovastatin, a drug known for its anti-inflammatory and neuroprotective properties, in patients with temporal lobe drug-resistant epilepsy (DRE). Emerging evidence suggests that inflammation plays a significant role in epileptogenesis, and preclinical models of epilepsy have demonstrated the efficacy of statins in reducing seizure susceptibility.

This pilot, double-blinded, placebo-controlled crossover study included five participants with focal-onset DRE. The primary objectives were to evaluate the impact of lovastatin on cortical inhibition, oxidative stress, and seizure activity. Participants received 60 mg/day of lovastatin or placebo for a specified period, with treatment phases separated by a washout period.

Key assessments included magnetic resonance spectroscopy (MRS) to measure brain metabolites such as GABA, glutamate, and glutathione in the occipital cortex. Event-related potentials (ERP) were recorded during a facial recognition task to examine visual evoked potentials, while resting EEG was used to analyze interictal epileptiform discharges (IEDs).

Inclusion criteria

• diagnosis of pharmacoresistant epilepsy as defined by the International League Against Epilepsy,
• focal temporal lobe onset
• nonpregnant and nonlactating in women

Exclusion criteria

• history of cardiovascular or cerebrovascular disease,
• history of dyslipidemia, previous use of statins or a previously documented adverse reaction to statins,
• having any metal inside the head but outside the mouth,
• implanted devices such as cardiac pacemakers or cochlear implants,
• having a vagal nerve stimulation device and the presence of other comorbid neurologic conditions