RSA 2007 Abstracts

SRI

SELECTIVE DISTRIBUTION OF THIAMINE-DEFICIENCY INDUCED NEURAL DAMAGE AND EVIDENCE FOR RECOVERY IN A RAT MODEL OF WERNICKE’S ENCEPHALOPATHY: AN MR IMAGING AND SPECTROSCOPY STUDY: A. Pfefferbaum; E. Adalsteinsson; R. L. Bell; E. V. Sullivan. Neuroscience Program, SRI International, Department of Psychiatry & Behavioral Sciences, Stanford University Department of Electrical Engineering and Computer Science and Harvard-MIT Division of Health, Sciences and Technology, MIT Department of Psychiatry, Indiana University School of Medicine

Wernicke's Encephalopathy (WE) occurs most frequently with chronic alcoholism, although its etiology is thiamine deficiency. WE presents with lesions in thalamus, mammillary nuclei, and inferior colliculi, and improvement ensues with thiamine repletion. Whether alcoholism exacerbates the neuropathology or retards its resolution remains controversial, and little is known about the status of the recovering neural tissue. To examine the pattern of brain damage and recovery resulting from thiamine deprivation with and without alcohol-exposure, we used in vivo imaging (MRI) and spectroscopy (MRS) in alcohol-preferring P rats, which had voluntarily consumed large amounts of alcohol prior to thiamine manipulation. 18 adult male P rats (9 pre-exposed to alcohol) received a thiamine deficient diet for 2 weeks; 10 (5 alcohol-exposed) rats received intraperitoneal (IP) pyrithiamine and 8 (4 alcohol-exposed) received IP thiamine supplementation. Neurological signs developed by day 14. Rats were scanned before thiamine depletion and 18 and 35 days after thiamine repletion. MRI with full-brain coverage was acquired at 3T. 2D J-resolved proton MRS spectra and water reference were collected in a voxel subtending the thalamus; metabolites were corrected for tissue content. Prior alcohol exposure was not related to any radiological finding, but 2 of 5 alcohol-exposed and pyrithiamine-treated (PT) rats died prior to the third scanning session. Regardless of alcohol history, MRI revealed significant enlargement of dorsal ventricles and increase in signal intensities in the thalamus, inferior colliculus, and mammillary nuclei of PT compared with thiamine-treated (TT) groups from MRI to 2, followed by significant normalization from MRI 2 to 3 in all regions but mammillary nuclei. MRS revealed a significant decline and then partial rise in N-acetylaspartate (NAA) in PT but not TT; no change occurred in creatine, choline, or glutamate. Parenchymal and ventricular changes with thiamine manipulation concur with human radiological signs of WE. The enduring limbic abnormality may carry liability for development of amnesia. Thalamic NAA reduction followed by partial restoration indicated impaired neuronal integrity and recovery. (Support: AA13521 (INIA), AA13522 (INIA), AA05965)