NEUROTOXIC EFFECTS OF GADOPENTETATE DIMEGLUMINE - BEHAVIORAL DISTURBANCE AND MORPHOLOGY AFTER INTRACEREBROVENTRICULAR INJECTION IN RATS

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.