The GABAergic Inhibitory System in Drug Resistant Epilepsy

Lovastatin Modulation of the Inhibition-excitation Balance in Temporal Lobe Onset Drug Resistant Epilepsy

This study aims to investigate the effect of lovastatin on neurotransmission and neuroinflammation in patients with temporal lobe onset drug resistant epilepsy.

Structure: (1) Visit 1: 3 consecutive days of physiologically probing drug/placebo intake, (2) Visit 2: Outcome measures and additional evaluations in the day after the last drug/placebo intake, (3) Washout period of 4 weeks, (4) 3 consecutive days of drug/placebo intake, (5) Visit 3: Outcome measures and additional evaluations in the day after the last placebo/drug intake.

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