What is the pathophysiology of Wernicke encephalopathy (WE)?

Updated: Nov 20, 2018
  • Author: Philip N Salen, MD; Chief Editor: Andrew K Chang, MD, MS  more...
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Answer

Thiamine is an essential vitamin critical to glucose metabolism. Without thiamine, glucose is metabolized through less efficient anaerobic pathways that produce lactic acid. Acidosis affecting periventricular structures (i.e., thalami, mammillary bodies, oculomotor nuclei, cerebellar vermis) accounts for the clinical presentation. Because thiamine crosses the blood–brain barrier via passive and active transport, correction of brain thiamine deficiency is promoted by maximizing serum thiamine concentrations. [4]

Thiamine plays a vital role in the metabolism of carbohydrates. Thiamine is a cofactor for several essential enzymes in the Krebs cycle and the pentose phosphate pathway, including alpha-ketoglutarate dehydrogenase, pyruvate dehydrogenase, and transketolase. [5]  In the setting of thiamine deficiency, thiamine-dependent cellular systems begin to fail, resulting eventually in cell death. Because thiamine-dependent enzymes play an essential role in cerebral energy utilization, thiamine deficiency may propagate brain tissue injury by inhibiting metabolism in brain regions with higher metabolic demands and high thiamine turnover. [5]

Pyruvate dehydrogenase and alpha-ketoglutarate are essential enzymes in the Krebs cycle, and the lack of these enzymes alters cerebral energy utilization. If cells with high metabolic requirements have inadequate stores of thiamine to draw from, energy production drops, and neuronal damage ensues. Increased cell death then feeds the localized vasogenic response. [11]  Additionally, the reduced production of succinate, which plays a role in gamma-aminobutyric acid (GABA) metabolism and the electrical stimulation of neurons, leads to further central nervous system injury.

Increased lactic acid production ensues in the absence of pyruvate dehydrogenase function, as the reduced conversion of pyruvate to acetyl coenzyme A results in less efficient oxidative phosphorylation. [12]

Thiamine pyrophosphate is also essential for nucleotide synthesis, production of nicotinamide adenine dinucleotide phosphate (NADPH), and maintenance of reduced glutathione within erythrocytes. [12]


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