MRI monitoring of vigabatrin–induced intramyelinic edema in dogs

K. L. Weiss, Charles E. Schroeder, S. J. Kastin, J. P. Gibson, J. T. Yarrington, W. E. Heydorn, R. G. McBride, N. M. Sussman, Joseph C. Arezzo

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Chronic administration of vigabatrin (gamma-vinyl GABA) in dogs produces reversible microvacuolation (intramyelinic edema) in discrete brain regions. Histologic changes are most notable in the columns of the fornix and regions of the hypothalamus, thalamus, optic tract, and hippocampus. In an attempt to image these changes in vivo, we performed high-field MRI on seven treated and four control dogs at baseline and after 15 weeks of dosing with vigabatrin (300 mg/kg/d). All dogs underwent parallel electrophysiologic assessment to determine the effects of vigabatrin on afferent conduction. At 15 weeks, all treated dogs showed increased T<inf>2</inf>- and decreased T<inf>1</inf>-weighted signals, with changes from baseline most prominent in the columns of the fornix and to a lesser degree in the surrounding hypothalamus and thalamus. MRIs performed on control dogs were unremarkable. We then perfused a random selection of four treated and two control dogs and imaged their brains ex vivo prior to sectioning. Ex vivo imaging confirmed the in vivo findings and strongly correlated with both electrophysiologic and subsequent histopathologic findings. Imaging was repeated in the surviving dogs 5 and 12 weeks after discontinuation of dosing. Signal abnormalities in the treated dogs progressively diminished during recovery, paralleling the electrophysiologic and histopathologic results. These findings demonstrate that MRI can detect signal changes anatomically congruent with vigabatrin-induced intramyelinic edema and suggest that MRI may provide a useful noninvasive tool for monitoring patients during clinical trials.

Original languageEnglish (US)
Pages (from-to)1944-1949
Number of pages6
JournalNeurology
Volume44
Issue number10
StatePublished - 1994

Fingerprint

Vigabatrin
Edema
Dogs
Thalamus
Hypothalamus
Monitoring
Dog
Brain
Physiologic Monitoring
Hippocampus
Clinical Trials

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Clinical Neurology
  • Neuroscience(all)

Cite this

Weiss, K. L., Schroeder, C. E., Kastin, S. J., Gibson, J. P., Yarrington, J. T., Heydorn, W. E., ... Arezzo, J. C. (1994). MRI monitoring of vigabatrin–induced intramyelinic edema in dogs. Neurology, 44(10), 1944-1949.

MRI monitoring of vigabatrin–induced intramyelinic edema in dogs. / Weiss, K. L.; Schroeder, Charles E.; Kastin, S. J.; Gibson, J. P.; Yarrington, J. T.; Heydorn, W. E.; McBride, R. G.; Sussman, N. M.; Arezzo, Joseph C.

In: Neurology, Vol. 44, No. 10, 1994, p. 1944-1949.

Research output: Contribution to journalArticle

Weiss, KL, Schroeder, CE, Kastin, SJ, Gibson, JP, Yarrington, JT, Heydorn, WE, McBride, RG, Sussman, NM & Arezzo, JC 1994, 'MRI monitoring of vigabatrin–induced intramyelinic edema in dogs', Neurology, vol. 44, no. 10, pp. 1944-1949.
Weiss KL, Schroeder CE, Kastin SJ, Gibson JP, Yarrington JT, Heydorn WE et al. MRI monitoring of vigabatrin–induced intramyelinic edema in dogs. Neurology. 1994;44(10):1944-1949.
Weiss, K. L. ; Schroeder, Charles E. ; Kastin, S. J. ; Gibson, J. P. ; Yarrington, J. T. ; Heydorn, W. E. ; McBride, R. G. ; Sussman, N. M. ; Arezzo, Joseph C. / MRI monitoring of vigabatrin–induced intramyelinic edema in dogs. In: Neurology. 1994 ; Vol. 44, No. 10. pp. 1944-1949.
@article{efd98f0e3959464d849fc8b3dacc2086,
title = "MRI monitoring of vigabatrin–induced intramyelinic edema in dogs",
abstract = "Chronic administration of vigabatrin (gamma-vinyl GABA) in dogs produces reversible microvacuolation (intramyelinic edema) in discrete brain regions. Histologic changes are most notable in the columns of the fornix and regions of the hypothalamus, thalamus, optic tract, and hippocampus. In an attempt to image these changes in vivo, we performed high-field MRI on seven treated and four control dogs at baseline and after 15 weeks of dosing with vigabatrin (300 mg/kg/d). All dogs underwent parallel electrophysiologic assessment to determine the effects of vigabatrin on afferent conduction. At 15 weeks, all treated dogs showed increased T2- and decreased T1-weighted signals, with changes from baseline most prominent in the columns of the fornix and to a lesser degree in the surrounding hypothalamus and thalamus. MRIs performed on control dogs were unremarkable. We then perfused a random selection of four treated and two control dogs and imaged their brains ex vivo prior to sectioning. Ex vivo imaging confirmed the in vivo findings and strongly correlated with both electrophysiologic and subsequent histopathologic findings. Imaging was repeated in the surviving dogs 5 and 12 weeks after discontinuation of dosing. Signal abnormalities in the treated dogs progressively diminished during recovery, paralleling the electrophysiologic and histopathologic results. These findings demonstrate that MRI can detect signal changes anatomically congruent with vigabatrin-induced intramyelinic edema and suggest that MRI may provide a useful noninvasive tool for monitoring patients during clinical trials.",
author = "Weiss, {K. L.} and Schroeder, {Charles E.} and Kastin, {S. J.} and Gibson, {J. P.} and Yarrington, {J. T.} and Heydorn, {W. E.} and McBride, {R. G.} and Sussman, {N. M.} and Arezzo, {Joseph C.}",
year = "1994",
language = "English (US)",
volume = "44",
pages = "1944--1949",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "10",

}

TY - JOUR

T1 - MRI monitoring of vigabatrin–induced intramyelinic edema in dogs

AU - Weiss, K. L.

AU - Schroeder, Charles E.

AU - Kastin, S. J.

AU - Gibson, J. P.

AU - Yarrington, J. T.

AU - Heydorn, W. E.

AU - McBride, R. G.

AU - Sussman, N. M.

AU - Arezzo, Joseph C.

PY - 1994

Y1 - 1994

N2 - Chronic administration of vigabatrin (gamma-vinyl GABA) in dogs produces reversible microvacuolation (intramyelinic edema) in discrete brain regions. Histologic changes are most notable in the columns of the fornix and regions of the hypothalamus, thalamus, optic tract, and hippocampus. In an attempt to image these changes in vivo, we performed high-field MRI on seven treated and four control dogs at baseline and after 15 weeks of dosing with vigabatrin (300 mg/kg/d). All dogs underwent parallel electrophysiologic assessment to determine the effects of vigabatrin on afferent conduction. At 15 weeks, all treated dogs showed increased T2- and decreased T1-weighted signals, with changes from baseline most prominent in the columns of the fornix and to a lesser degree in the surrounding hypothalamus and thalamus. MRIs performed on control dogs were unremarkable. We then perfused a random selection of four treated and two control dogs and imaged their brains ex vivo prior to sectioning. Ex vivo imaging confirmed the in vivo findings and strongly correlated with both electrophysiologic and subsequent histopathologic findings. Imaging was repeated in the surviving dogs 5 and 12 weeks after discontinuation of dosing. Signal abnormalities in the treated dogs progressively diminished during recovery, paralleling the electrophysiologic and histopathologic results. These findings demonstrate that MRI can detect signal changes anatomically congruent with vigabatrin-induced intramyelinic edema and suggest that MRI may provide a useful noninvasive tool for monitoring patients during clinical trials.

AB - Chronic administration of vigabatrin (gamma-vinyl GABA) in dogs produces reversible microvacuolation (intramyelinic edema) in discrete brain regions. Histologic changes are most notable in the columns of the fornix and regions of the hypothalamus, thalamus, optic tract, and hippocampus. In an attempt to image these changes in vivo, we performed high-field MRI on seven treated and four control dogs at baseline and after 15 weeks of dosing with vigabatrin (300 mg/kg/d). All dogs underwent parallel electrophysiologic assessment to determine the effects of vigabatrin on afferent conduction. At 15 weeks, all treated dogs showed increased T2- and decreased T1-weighted signals, with changes from baseline most prominent in the columns of the fornix and to a lesser degree in the surrounding hypothalamus and thalamus. MRIs performed on control dogs were unremarkable. We then perfused a random selection of four treated and two control dogs and imaged their brains ex vivo prior to sectioning. Ex vivo imaging confirmed the in vivo findings and strongly correlated with both electrophysiologic and subsequent histopathologic findings. Imaging was repeated in the surviving dogs 5 and 12 weeks after discontinuation of dosing. Signal abnormalities in the treated dogs progressively diminished during recovery, paralleling the electrophysiologic and histopathologic results. These findings demonstrate that MRI can detect signal changes anatomically congruent with vigabatrin-induced intramyelinic edema and suggest that MRI may provide a useful noninvasive tool for monitoring patients during clinical trials.

UR - http://www.scopus.com/inward/record.url?scp=0028007217&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028007217&partnerID=8YFLogxK

M3 - Article

C2 - 7936252

AN - SCOPUS:0028007217

VL - 44

SP - 1944

EP - 1949

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 10

ER -