De. Ray et al., NEUROTOXIC EFFECTS OF GADOPENTETATE DIMEGLUMINE - BEHAVIORAL DISTURBANCE AND MORPHOLOGY AFTER INTRACEREBROVENTRICULAR INJECTION IN RATS, American journal of neuroradiology, 17(2), 1996, pp. 365-373
Citations number
35
Categorie Soggetti
Clinical Neurology","Radiology,Nuclear Medicine & Medical Imaging
PURPOSE: To determine the neurotoxic potential of gadopentetate dimegl
umine in an animal model that allowed the agent to avoid the blood-bra
in barrier. Gadopentetate dimeglumine is known to produce functional c
hanges when injected into the cerebrospinal fluid, and we hypothesized
that such changes might. be associated with morphologic damage. METHO
DS: Conscious rats, surgically prepared with a lateral ventricular can
nula, were given a slow injection of gadopentetate dimeglumine into th
e lateral ventricle, and behavioral and neuropathologic changes were n
oted. RESULTS: Gadopentetate dimeglumine produced signs of acute neuro
toxicity over several hours (stereotyped movements and myoclonus), med
ium-term signs over several days (ataxia and tremor), and neuropatholo
gic changes over 24 hours, with reactive changes persisting for 42 day
s. All of the above were dose-dependent over the range of 2.5 to 15 mu
mol/g brain. The lowest dose producing morphologic or behavioral chan
ges was 5 mu mol/g brain. Iso-osmotic, isovolumetric injections of suc
rose produced no such effects. Focal lesions occurred within the thala
mus, brain stem, and spinal cord, with necrosis of glia, loss of myeli
n, and, usually, sparing of neurons and nerve fibers. Persisting ataxi
a was always associated with brain stem or spinal cord lesions. CONCLU
SION: Intraventricular administration of contrast medium allows toxici
ty to be evaluated in areas such as the spinal cord that are not acces
sible by osmotic opening. While it is unlikely that these toxic effect
s would be seen at the doses used for clinical imaging by the intraven
ous route, gadopentetate dimeglumine clearly has some neurotoxic and n
europathologic potential. Although the acute excitation could be attri
buted to a transiently high local concentration of the agent at the in
jection site, the lesions were widely distributed through the brain an
d spinal cord and may reflect a region-specific neurotoxic action, pos
sibly related to central pontine myelinolysis.