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

Abstract:

PURPOSE:To evaluate effects of vigabatrin (VGB) by using [123I]iomazenil single-photon emission computed tomography (SPECT) to estimate central gamma-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 micromol/g; with VGB, 2.9+/-0.5 micromol/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.

journal_name

Epilepsia

journal_title

Epilepsia

authors

Verhoeff NP,Petroff OA,Hyder F,Zoghbi SS,Fujita M,Rajeevan N,Rothman DL,Seibyl JP,Mattson RH,Innis RB

doi

10.1111/j.1528-1157.1999.tb02016.x

subject

Has Abstract

pub_date

1999-10-01 00:00:00

pages

1433-8

issue

10

eissn

0013-9580

issn

1528-1167

journal_volume

40

pub_type

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