Wernicke-Korsakoff syndrome

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Wernicke-Korsakoff syndrome

Nervous system

Autonomic nervous system disorders

Horner syndrome

Orthostatic hypotension


Wernicke-Korsakoff syndrome


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USMLE® Step 1 questions

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Wernicke-Korsakoff syndrome

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USMLE® Step 1 style questions USMLE

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An 85-year-old man is brought in by his niece to the clinic after finding him confused outside his house. He denies the incident and says that he was “just walking his dog around the neighborhood” after having a meal with his friends. After the consultation, his niece states that “He doesn't own a dog, he lives alone, and most of his meals consist of reheating canned foods.” Past medical history includes hypertension, hypercholesterolemia and type 2 diabetes. Medications include hydrochlorothiazide, atorvastatin and metformin.  Family history is noncontributory. He has been drinking 5-6 beers daily for the past 30 years. Temperature is 37.0°C (98.6°F), pulse is 92/min, respirations are 17/min, and blood pressure is 135/85 mmHg. He is oriented to place and person but not time. Immediate and delayed memory recall is poor. Pupils are equal and reactive, and horizontal nystagmus is elicited on lateral gaze. Fundoscopy is normal. There is no nuchal rigidity on examination. Motor strength is 5/5 in the upper extremities and 2/4 in bilateral lower extremities. Deep tendon reflexes of the knee and ankle are 1+ bilaterally. MRI reveals necrosis in the mamillary bodies and medial thalamus. Which of the following is the most likely diagnosis?

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Wernicke-Korsakoff syndrome p. 64, 528, 595

Mammillary bodies p. 521, 528

Wernicke-Korsakoff syndrome p. 595

Memory loss

Wernicke-Korsakoff syndrome p. 64, 528, 595

Ophthalmoplegia p. 64

Wernicke-Korsakoff syndrome p. 64, 595

Vitamin B1 deficiency

Wernicke-Korsakoff syndrome p. 595

Wernicke-Korsakoff syndrome p. 528, 595

vitamin B1 deficiency p. 64


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.


Wernicke-Korsakoff syndrome (WKS) is a neurological disorder caused by a deficiency of thiamine (vitamin B1), often due to chronic alcohol abuse. It is a combination of Wernicke encephalopathy and Korsakoff syndrome, presenting with confusion, ophthalmoplegia, and ataxia. Wernicke encephalopathy can progress to Korsakoff syndrome, which causes severe memory loss, disorientation, and confabulation. Treatment includes thiamine supplements, rehabilitation, and cognitive therapy to manage symptoms.


  1. "Robbins Basic Pathology" Elsevier (2017)
  2. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  3. "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
  5. "Health problems and care needs in patients with Korsakoff’s syndrome: A systematic review" Journal of Psychiatric and Mental Health Nursing (2020)

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