Effects of vigabatrin on the GABAergic system as determined by [123I]iomazenil SPECT and GABA MRS

Nicolaas Paul L.G. Verhoeff, Ognen A.C. Petroff, Fahmeed Hyder, Sami S. Zoghbi, Masahiro Fujita, Nallakkandi Rajeevan, Douglas L. Rothman, John P. Seibyl, Richard H. Mattson, Robert B. Innis

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Purpose: To evaluate effects of vigabatrin (VGB) by using [123I]iomazenil single-photon emission computed tomography (SPECT) to estimate central γ-aminobutyric acid (GABA(A))/benzodiazepine receptors (BZRs), and magnetic resonance spectroscopy (MRS) to assess tissue GABA levels. Methods: Six patients with partial seizures had both SPECT and MRS before and 25-84 days after starting VGB (3 g p.o., q.d.). SPECT was acquired by using the constant-infusion method and, after nonuniform attenuation correction, coregistered with T1-weighted MR Imaging (MRI) A volume of interest (VOI) of 3 x 2 x 2 cc over the occipital cortex, used for MRS acquisition, was positioned on both MRI and coregistered SPECT. Occipital activity was divided by either total plasma activity or plasma [123I]iomazenil concentration to estimate BZR distribution volume (V(T)-p and V(T)/', respectively). Wilcoxon's test was used for VOI differences in GABA levels, BZR V(T)-p or V(T)/'. SPM96 (either no global normalization or proportional scaling) was used to compare BZR V(T)-p changes in the patients with and without VGB with test-retest data in eight healthy age-matched controls. Results: Occipital GABA levels were increased threefold (without VGB, 1.1 ± 0.1 μmol/g; with VGB, 2.9 ± 0.5 μmol/g; p = 0.027). BZR distribution volumes showed no change, when estimated by either V(T)-p (without VGB, 6.00 ± 0.91 ml/g; with VGB, 5.86 ± 0.44 ml/g; p = 0.92) or V(T)/' (without VGB, 41.1 ± 11.2 ml/g; with VGB, 41.2 ± 9.9 ml/g; p = 0.75). No significant changes were detected by SPM96. Conclusions: A clinically effective dose of VGB caused a threefold increase in tissue GABA levels but was not associated with a substantial BZR downregulation.

Original languageEnglish (US)
Pages (from-to)1433-1438
Number of pages6
JournalEpilepsia
Volume40
Issue number10
DOIs
StatePublished - 1999

Keywords

  • Benzodiazepine receptor
  • GABA
  • MRS
  • SPECT
  • Vigabatrin

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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