Biomarkers of delirium as a clue to diagnosis and pathogenesis of Wernicke−Korsakoff syndrome

Authors:
Publisher website
Google Scholar
Abstract
Background and purpose: Wernicke's encephalopathy (WE) and Korsakoff's syndrome are considered to be different stages of the same disorder due to thiamine deficiency, which is called Wernicke−Korsakoff syndrome (WKS). The earliest biochemical change is the decrease of α‐ketoglutarate‐dehydrogenase activity in astrocytes. According to autopsy‐based series, mental status changes are present in 82% of WE cases. The objective of the present review is to identify possible underlying mechanisms relating the occurrence of delirium to WKS.Methods: Studies involving delirium in WKS, however, are rare. Therefore, first, a search was done for candidate biomarkers of delirium irrespective of the clinical setting. Secondly, the results were focused on identification of these biomarkers in reports on WKS.Results: In various settings, 10 biochemical and/or genetic biomarkers showed strong associations with the occurrence of delirium. For WKS three of these candidate biomarkers were identified, namely brain tissue cell counts of CD68 positive cells as a marker of microglial activation, high cerebrospinal fluid lactate levels, and MHPG, a metabolite of norepinephrine. Based on current literature, markers of microglial activation may present an interesting patho‐etiological relationship between thiamine deficiency and delirium in WKS.Conclusions: In WKS cases, changes in astroglia and microglial proliferation were reported. The possible loss‐of‐function mechanisms following thiamine deficiency in WKS are proposed to come from microglial activation, resulting in a delirium in the initial phase of WKS.

This publication has 44 references indexed in Scilit: