TY - JOUR
T1 - Effects of vigabatrin on the GABAergic system as determined by [123I]iomazenil SPECT and GABA MRS
AU - Verhoeff, Nicolaas Paul L.G.
AU - Petroff, Ognen A.C.
AU - Hyder, Fahmeed
AU - Zoghbi, Sami S.
AU - Fujita, Masahiro
AU - Rajeevan, Nallakkandi
AU - Rothman, Douglas L.
AU - Seibyl, John P.
AU - Mattson, Richard H.
AU - Innis, Robert B.
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
KW - Benzodiazepine receptor
KW - GABA
KW - MRS
KW - SPECT
KW - Vigabatrin
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U2 - 10.1111/j.1528-1157.1999.tb02016.x
DO - 10.1111/j.1528-1157.1999.tb02016.x
M3 - Article
C2 - 10528940
AN - SCOPUS:0032879876
VL - 40
SP - 1433
EP - 1438
JO - Epilepsia
JF - Epilepsia
SN - 0013-9580
IS - 10
ER -