VIGABATRIN-INDUCED LESIONS IN THE RAT-BRAIN DEMONSTRATED BY QUANTITATIVE MAGNETIC-RESONANCE-IMAGING

Rats treated with 250 mg/kg/day vigabatrin showed lesions detected by magnetic resonance imaging (MRI) in the cerebellar white matter in viv o. No lesions were seen in any control animal. As well as these visual ly apparent lesions, quantitative T2 relaxation time measurements show ed a 12 ms increase in cerebellar white matter from 66 +/- 4 ms (SD, n = 5) to 78 +/- 2 ms (SD, n = 7). This region, as expected from previo us studies, showed microvacuolation on post-mortem pathology. Addition ally, significant increases in T2 relaxation times of 4-9 ms were foun d in the cerebral cortex, thalamus and hippocampus. Microvacuolation w as not detected by post-mortem histopathology in the cerebral cortex o r hippocampus, however, immunohistochemical staining for glial fibrill ary acidic protein and for macrophages (ED1) showed reactive astrocyte s (gliosis) and in more severe cases, microglial proliferation in thes e regions; such changes were also seen in association with the microva cuoles. No T2 increase was found in the cerebellar grey matter or olfa ctory bulbs. MRI techniques, including T2 relaxometry, are therefore s ensitive for detecting vigabatrin-induced changes, including reactive astrocytosis, microglial proliferation and vacuolation in the rat brai n. These results suggest that quantitative MRI should be a useful meth od for evaluating whether vigabatrin has neuropathological effects whe n given to patients.