Alterations of intracerebral γ-aminobutyric acid (GABA) levels by titration with levetiracetam in patients with focal epilepsies

P>Purpose: The objective of this study was to determine if levetiracetam (LEV) modulates brain gamma-aminobutyric acid (GABA) in patients with epilepsy. Methods: Occipital GABA was assessed by protein magnetic resonance spectroscopy (1H-MRS) in 16 patients with focal epilepsy at baseline and following the initiation of oral administration of LEV as monotherapy. Responder profiles were calculated as percentage of baseline seizure frequency. Alterations of GABA/Cr (creatine) of baseline measurements compared to GABA/Cr under LEV therapy were analyzed by Student's t-test for paired samples. Results: After administration of LEV, partial seizure reduction (> 50%) was noticed in 5 of 16 patients (31%; 7 of 16 (44%) patients turned out to be free of seizures. Patients with 50-100% seizure reduction under LEV titration were referred to as LEV responders. Of the 32 GABA spectra, only 22 (approximately 70%) yielded a result that met the criteria for spectral quality; therefore, GABA/Cr data from only seven patients were paired. A significant increase of GABA/Cr during titration with LEV was noted in patients responding to LEV (n = 5; p = 0.007). No differences in baseline GABA/Cr levels were detected between patients with and without previous antiepileptic treatment (p = 0.74). Discussion: The increasing GABA/Cr levels under drug titration only in LEV-responding epilepsy patients suggest a more complex and indirect influence of LEV on the GABAergic system.