What is Wernicke-Korsakoff syndrome?

What is Wernicke-Korsakoff Syndrome?

Wernicke-Korsakoff syndrome (WKS) is a severe neurological disorder caused by thiamine (vitamin B1) deficiency that consists of two phases: an acute, potentially reversible phase called Wernicke encephalopathy (WE), and a chronic, often irreversible phase called Korsakoff syndrome (KS) characterized by profound memory impairment. 1, 2

Pathophysiology

• Thiamine deficiency leads to neurological damage manifesting as mental status changes, ocular dysfunction, and gait ataxia 1
• When Wernicke encephalopathy goes unrecognized or undertreated, it progresses to Korsakoff syndrome, which presents with chronic amnesia, particularly anterograde amnesia and impaired word memory 1, 3
• The two conditions share a common etiology and represent acute versus chronic stages of the same disease process 3

Clinical Presentation

Wernicke Encephalopathy (Acute Phase)

The classic triad includes 1, 4:

• Mental status changes: confusion, disorientation, altered consciousness ranging from mild cognitive impairment to coma 1
• Ocular abnormalities: nystagmus, ophthalmoplegia, conjugate gaze palsy 1
• Ataxia: cerebellar dysfunction with gait incoordination 1

Critical caveat: Most cases do NOT present with the complete classic triad, leading to missed diagnoses 5. Additional presenting features include 2, 4:

• Blurred vision or optic neuropathy (present in approximately one-fourth of patients) 2
• Loss of appetite, dizziness, tachycardia 4
• Urinary bladder retention 4
• Severe concomitant infections including sepsis of unknown origin 4
• Unexplained metabolic lactic acidosis 1

Korsakoff Syndrome (Chronic Phase)

• Profound anterograde amnesia (inability to form new memories) 1
• Decreased word memory 1
• Often irreversible despite treatment 3

Risk Factors

Alcoholic Patients

• Chronic alcohol consumption is the most well-known risk factor 6, 7
• Alcohol-related WKS may present as delirium in malnourished alcoholic patients with difficulty walking 4

Non-Alcoholic Patients (Often Missed)

Physicians frequently underestimate or are unaware of non-alcoholic WKS risk 2. Key risk factors include 6, 1, 2:

• Post-bariatric surgery (118 cases in systematic review) 2
• Hyperemesis gravidarum (177 cases in systematic review) 2
• Malignancy/cancer (129 cases in systematic review) 2
• Prolonged vomiting or dysphagia 6, 1
• Malnutrition and poor oral intake 1
• Prolonged intravenous feeding without thiamine supplementation 1
• Anorexia nervosa (12 cases) 2
• Inflammatory bowel disease (Crohn's disease: 21 cases; ulcerative colitis: 10 cases) 2
• Chronic diuretic therapy and continuous renal replacement therapy 1
• Pregnancy (increased metabolic requirements) 1

Strong predictors in adults: Vomiting and extreme weight loss 2

Diagnostic Considerations

• Do not wait for laboratory confirmation before initiating treatment - this is a critical pitfall 1
• Thiamine diphosphate (ThDP) in whole blood or red blood cells can be measured, along with lactate, pyruvate, alpha-ketoglutarate, and glyoxylate concentrations 1
• Hepatic encephalopathy may coexist with WKS and complicate diagnosis, particularly in patients with cirrhosis 6, 1
• The cerebral symptoms of thiamine deficiency (disorientation, altered consciousness, ataxia, dysarthria) cannot be differentiated from hyperammonemia by clinical examination alone 6

Treatment

Acute Management

Thiamine must ALWAYS be administered before any glucose-containing solutions - giving glucose first can precipitate or worsen Wernicke-Korsakoff syndrome 6, 1, 7. This is the most critical treatment principle.

Recommended dosing 1, 7, 2:

• Initial treatment: 500 mg thiamine IV three times daily for 3-5 days 1, 7
• Continuation: 250 mg IV daily for a minimum of 3-5 additional days 1, 7
• Maintenance: Transition to oral thiamine 50-100 mg daily after parenteral treatment 1, 7

Special Considerations

• Hypomagnesemia: Patients may fail to respond to thiamine if magnesium deficient, especially in alcohol withdrawal or with proton pump inhibitor/diuretic use 4. Correct magnesium deficiency concurrently 4
• At-risk patients: Give oral thiamine 200-300 mg daily and vitamin B compound strong (1-2 tablets three times daily) immediately if clinical suspicion exists 6
• Unable to tolerate oral: Use full-dose daily intravenous vitamin B preparation 6

Common Treatment Pitfalls

• Inadequate dosing: Lower doses of thiamine frequently lead to chronic Korsakoff syndrome 2. Many cases receive insufficient treatment 2
• Relying on oral thiamine in acute cases: Oral absorption is limited, especially in alcoholic patients 7
• Delaying treatment for test results: Treatment should begin immediately based on clinical suspicion 1

Monitoring and Follow-up

• Monitor for improvement in neurological symptoms and cognitive function 1
• Assess for resolution of ocular abnormalities, mental status changes, and ataxia 1
• Neurological consultation is recommended for patients with persistent neurological symptoms 7
• For alcohol use disorders, consider psychiatric consultation for long-term alcohol abstinence planning 7

Prognosis

• Early diagnosed cases are relatively easy to cure 3
• Unrecognized and untreated WE poses serious threats to health and life, worsens brain aging, and increases Alzheimer's disease risk 3
• The dramatic paradox: WE is difficult to detect but easy to treat when recognized early 3