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

Abstract

SUMMARYPurpose: The objective of this study was to determine if levetiracetam (LEV) modulates brain c-aminobutyric acid (GABA) in patients with epilepsy. Methods: Occipital GABA was assessed by protein magnetic resonance spectroscopy ( 1 H-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.

Frontal and thalamic changes of GABA concentration indicate dysfunction of thalamofrontal networks in juvenile myoclonic epilepsy

“…Previous data revealed that antiepileptic drugs (AED) have an effect on brain metabolites in 1 H MRS. It has been shown that valproate induces changes in cerebral myoinositol and glutamine concentrations, whereas new AEDs may increase GABA levels in patients with epilepsy . Therefore, we divided the patients into two groups: one group included patients with valproate treatment, whereas the other group covered all patients who received any medication but no valproate.…”

The neurochemical profile quantified by in vivo 1H NMR spectroscopy

“…Higher magnetic fields, on the other hand, provide increased spectral resolution making GABA quantifiable (Deelchand et al, 2010;Gambarota et al, 2009;Mekle et al, 2009;Oz et al, 2006). GABA concentrations were found to be affected by neurological disorders like epilepsy (Doelken et al, 2010;Goddard et al, 2001;Simister et al, 2003), schizophrenia (Yoon et al, 2010), depression (Sanacora et al, 2004) or substance abuse (Behar et al, 1999;Ke et al, 2004).…”

GABAergic contributions to alcohol responsivity during adolescence: Insights from preclinical and clinical studies

“…There is a compelling literature implicating low GABA in epilepsy and documenting successful pharmacological interventions for seizure disorders that are effective via the modulation of GABA (Doelken, et al, 2010; Mueller, et al, 2001; Petroff, Behar, Mattson, & Rothman, 1996a; Petroff, Rothman, Behar, Hyder, & Mattson, 1999; Petroff, Rothman, Behar, & Mattson, 1996b)except (Simister, McLean, Barker, & Duncan, 2003, 2009). Low brain GABA levels were associated with poor seizure control in patients with complex partial seizures (Petroff, et al, 1996b).…”