Thiamine deficiency in humans is associated with
Wernicke's encephalopathy (WE) which is characterized neuropathologically by neuronal loss in selective brain regions.
Pyrithiamine-induced
thiamine-deficiency in the rat results in lesions which are similar in nature and distribution 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 barrier breakdown. WE is difficult to diagnose during life and a large number of cases are missed by routine clinical neurological evaluation. Recently, non-invasive diagnostic procedures such as CT and MRI have been used for the evaluation of acute and chronic WE. Autoradiographic studies reveal that increased densities of binding sites for the astrocytic
ligand 3H-PK11195 closely parallel the topographic distribution of reactive
gliosis and neuronal loss in selective brain regions of
pyrithiamine-induced
thiamine-deficient rats. In contrast, binding sites for the neuronal
ligand 3H-Ro15-1788 show poor regional correlation with neuronal loss in
thiamine deficiency. Both of these
ligands are available, and have been used in PET assessment of various disorders in humans. The results of autoradiographic studies suggest that 11C-PK11195 may offer a useful PET
ligand for the assessment of brain damage in WE in humans.