MRI DETECTS ACUTE DEGENERATION OF THE NIGROSTRIATAL DOPAMINE SYSTEM AFTER MPTP EXPOSURE IN HEMIPARKINSONIAN MONKEYS

Exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can ca use an acute chemical toxicity resulting in a parkinsonian state in hu mans and nonhuman primates. We wished to assess whether the toxicity f rom MPTP is associated with changes on magnetic resonance images of br ain structures containing dopamine neuronal processes or with disruptu re of the blood-brain barrier. Normal rhesus monkeys and monkeys at va rious times after being subjected to unilateral intracarotid injection of MPTP (0.4 mg/kg) were studied with magnetic resonance imaging usin g T1- and T2-weighted spin-echo and gradient-echo sequences. Disruptur e of the blood-brain barrier was assessed also with magnetic resonance imaging after administration of gadolinium-diethylenetriamine pentaac etic acid. Parkinsonian symptoms contralateral to the infused carotid usually appeared within 1 day after MPTP exposure, reaching their peak severity by 7 days, when all monkeys showed clear clinical abnormalit ies. Magnetic resonance imaging changes developed in concomitance with the clinical signs and were characterized by increased signal intensi ty on T2-weighted images as well as decreased intensity on T1-weighted images of the ipsilateral caudate and putamen. T2 hyperintensity was also present just dorsal to the pars compacta of the substantia nigra, in the region of the proximal nigrostriatal tract. All magnetic reson ance imaging changes dissipated in the next 2 weeks. There were no abn ormalities at any time in the globus pallidus, nucleus actumbens, and other structures innervated by the mesocorticolimbic dopamine system. After MPTP exposure, there was no evidence of blood-brain barrier disr upture, suggesting that vasogenic edema was an unlikely factor in the production of the observed abnormalities. The signal intensity changes on magnetic resonance images are most probably asociated with cytotox ic edema caused by the acute MPTP-induced degeneration of nigrostriata l dopamine nerve terminals and axons. Follow-up by magnetic resonance imaging, to 3 years after MPTP infusion, failed to reveal any residual abnormalities.