Effects of vigabatrin intake on brain GABA activity as monitored by spectrally edited magnetic resonance spectroscopy and positron emission tomography

• Published in: Magnetic resonance imaging Vol. 17; no. 3; pp. 417 - 425
• Main Authors: Weber, Oliver M, Verhagen, Aalt, Duc, Corinne O, Meier, Dieter, Leenders, Klaus L, Boesiger, Peter
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.04.1999; Elsevier Science
• Subjects: Adult; Anticonvulsants - pharmacology; Biological and medical sciences; Brain - drug effects; Brain - pathology; Brain Mapping - instrumentation; Brain MRS; Dose-Response Relationship, Drug; Epilepsy; Female; gamma-Aminobutyric Acid - analogs & derivatives; gamma-Aminobutyric Acid - pharmacology; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Humans; Image Processing, Computer-Assisted - instrumentation; Magnetic resonance spectroscopy (MRS); Magnetic Resonance Spectroscopy - instrumentation; Male; Medical sciences; Nervous system (semeiology, syndromes); Neurology; Phantoms, Imaging; Positron emission tomography (PET); Receptors, GABA-A - drug effects; Receptors, GABA-A - metabolism; Reference Values; Tomography, Emission-Computed - instrumentation; Vigabatrin; γ-Aminobutyric acid (GABA); Positron emission tomography (PET); γ-Aminobutyric acid (GABA); Vigabatrin; Brain MRS; Epilepsy; Magnetic resonance spectroscopy (MRS); Radionuclide study; Human; Nervous system diseases; 4-Aminobutyrate transaminase; Enzyme; Transferases; Enzyme inhibitor; Anticonvulsant; Binding site; NMR spectrometry; Cerebrospinal fluid; Carbon; Cerebral disorder; Transaminases; Central nervous system disease; GABA; Biological effect; Monitoring; Brain (vertebrata); Positron; Emission tomography
• ISSN: 0730-725X; 1873-5894
• DOI: 10.1016/S0730-725X(98)00184-2

A deficit in gamma-aminobutyric acid (GABA) levels in the brain or the cerebrospinal fluid (CSF) is found in many epilepsy patients. Frequency and severity of seizures may be reduced by treatment with GABA increasing medicaments as e.g. vigabatrin, an irreversible inhibitor of GABA-transaminase. For a better understanding of the associated effects, healthy volunteers were examined with magnetic resonance spectroscopy (MRS) and positron emission tomography (PET) before and after intake of different doses of vigabatrin. For the MRS examinations, a dedicated localized spectral editing method was developed to determine GABA levels. The 11C-flumazenil (FMZ)-PET protocol allowed determination of GABA-A receptor binding. The results show a clear and dose-dependent increase in the brain GABA levels after the medication period as compared to the baseline values. The GABA-A receptor binding, on the other hand, did not change significantly.