Wernicke-Korsakoff syndrome

Wernicke Korsakoff syndrome is named after Carl Wernicke and Sergei Korsakoff, the physicians who discovered the condition in the late 1800s. Wernicke Korsakoff syndrome is caused by Vitamin B1 or thiamine deficiency and it refers to a spectrum of disease. Wernicke's encephalopathy is the acute, reversible stage of the syndrome, and if left untreated it can later lead to Korsakoff syndrome, which is chronic and irreversible.

Thiamine is typically stored in the liver and absorbed in the jejunum and ileum, and then moves throughout the body, where it’s involved in numerous cellular processes that require thiamine. The enzyme thiamine pyrophosphate synthetase transfers a pyrophosphate group from ATP to thiamine, turning it into the coenzyme thiamine pyrophosphate - which is the metabolically active form of thiamine. Now, as a coenzyme, thiamine pyrophosphate functions to assist other enzymes such as pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and transketolase carry out reactions, particularly regarding glucose metabolism. Furthermore, within the brain, thiamine pyrophosphate helps metabolize lipids and carbohydrates as well as maintain normal amino acid and neurotransmitter levels. In some neurons, thiamine even helps with propagation of a neural impulses down the axon.

Given it’s multifaceted role, a deficiency of thiamine can have serious consequences. Specifically, thiamine deficiency impairs glucose metabolism and this leads to a decrease in cellular energy. One of the major causes of thiamine deficiency, and therefore Wernicke Korsakoff syndrome, is alcohol abuse. Alcohol leads to decreased thiamine levels in various ways. First, alcohol interferes with the conversion of thiamine to its active form, thiamine pyrophosphate by blocking the phosphorylation of thiamine. Second, thiamine is normally absorbed through the first portion of the small intestine called the duodenum. However, ethanol prevents this absorption process, and it is believed that alcohol does this by reducing the gene expression for thiamine transporter-1 within the intestinal brush border. Third, chronic alcohol abuse can lead to fatty liver or cirrhosis which interferes with the storage of thiamine within the liver. Other causes of thiamine deficiency are inadequate intake like in malnutrition and anorexia or due to malabsorption like in stomach cancer and inflammatory bowel disease.

The brain is particularly vulnerable to impaired glucose metabolism since it utilizes so much energy. Early on in thiamine deficiency, the cerebellum gets affected and that can affect movement and balance. In addition, the brainstem can be affected, and that’s the region that gives rise to the cranial nerves that provide motor and sensory innervation to the face and eyes. If the medulla region of the brainstem is affected, it can impair the heart rate and breathing. Later findings in thiamine deficiency are hemorrhage and necrosis of the mammillary bodies. The mammillary bodies are two small round structures located under the brain and are part of the limbic system which is responsible for memory, emotion, and behavior.

Now Wernicke Korsakoff syndrome can be thought of as a spectrum of disorders: Wernicke's encephalopathy symptoms occur first, and can eventually develop into the more severe symptoms found in Korsakoff syndrome. Wernicke's encephalopathy is characterized by ophthalmoplegia, meaning weakness or paralysis of the eye muscles, ataxia or unsteady gait, and changes in mental state like confusion, apathy, and difficulty concentrating. And untreated Wernicke's encephalopathy can lead to coma and death if not treated quickly.