NEURONAL CELL-DEATH IN WERNICKES ENCEPHALOPATHY - PATHOPHYSIOLOGIC MECHANISMS AND IMPLICATIONS FOR PET IMAGING

Thiamine deficiency in humans is associated with Wernicke's encephalop athy (WE) which is characterized neuropathologically by neuronal loss in selective brain regions, Pyrithiamine-induced thiamine-deficiency i n the rat results in lesions which are similar in nature and distribut ion to those seen in human WE. Several mechanisms have been implicated in the pathogenesis of neuronal loss in thiamine deficiency including , (i) impaired cerebral energy metabolism, (ii) focal lactic acidosis, (iii) NMDA-receptor mediated excitotoxicity and (iv) blood-brain barr ier breakdown. WE is difficult to diagnose during life and a large num ber of cases are missed by routine clinical neurological evaluation. R ecently, non-invasive diagnostic procedures such as CT and MRI have be en used for the evaluation of acute and chronic WE. Autoradiographic s tudies reveal that increased densities of binding sites for the astroc ytic ligand H-3-PK11195 closely parallel the topographic distribution of reactive gliosis and neuronal loss in selective brain regions of py rithiamine-induced thiamine-deficient rats. In contrast, binding sites for the neuronal ligand H-3-Ro15-1788 show poor regional correlation with neuronal loss in thiamine deficiency. Both of these ligands are a vailable, and have been used in PET assessment of various disorders in humans. The results of autoradiographic studies suggest that C-11-PK1 1195 may offer a useful PET ligand for the assessment of brain damage in WE in humans.