title: Neuronal cell death in Wernicke's encephalopathy: pathophysiologic mechanisms and implications for PET imaging.
abstract: 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.
authors.affiliation: Neuroscience Research Unit, Hôpital Saint-Luc, Montréal, Quebéc, Canada.
authors.forename: D K
authors.initials: DK
authors.lastname: Leong
authors.forename: R F
authors.initials: RF
authors.lastname: Butterworth
mesh_terms: D000818:Animals; D016923:Cell Death / Q000502:physiology; D006801:Humans; D009410:Nerve Degeneration / Q000502:physiology; D051381:Rats; D014055:Tomography, Emission-Computed; D014899:Wernicke Encephalopathy / Q000175:diagnosis / Q000473:pathology* / Q000503:physiopathology