Biomarkers of delirium as a clue to diagnosis and pathogenesis of Wernicke−Korsakoff syndrome
Article first published online: 21 JUN 2013
© 2013 The Author(s) European Journal of Neurology © 2013 EFNS
European Journal of Neurology
Volume 20, Issue 12, pages 1531–1538, December 2013
How to Cite
Wijnia, J. W. and Oudman, E. (2013), Biomarkers of delirium as a clue to diagnosis and pathogenesis of Wernicke−Korsakoff syndrome. European Journal of Neurology, 20: 1531–1538. doi: 10.1111/ene.12217
- Issue published online: 8 NOV 2013
- Article first published online: 21 JUN 2013
- Manuscript Accepted: 16 MAY 2013
- Manuscript Received: 26 JAN 2013
- thiamine deficiency;
- Wernicke encephalopathy;
- Wernicke−Korsakoff syndrome
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.
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.
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.
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.