1. Wernicke-Korsakoff Syndrome [WKS]
PHM142 Presentation
Instructor: Dr. J. Henderson
Wernicke-Korsakoff Syndrome
[WKS]
Andrew Trickey, Ahmed Karaki, Jeffrey Ta, Zhi Lun Zhang

2. Table of Contents Overview Causes Symptoms Pathophysiology Diagnosis
Treatment
Summary
References

3. Overview Discovered by Carl Wernicke and Sergei Korsakoff
Combination of two seperate disorders
Wernicke’s Encephalopathy/Disease (WE/WD)
Characterized by lesions in the CNS caused by thiamine deficiency
Korsakoff Syndrome (KS)
Characterized by amnesia caused by thiamine deficiency and alcohol abuse
WE occurs first, if left untreated, KS will develop and you will have two separate diseases occuring at the same time
WKS associated with thiamine deficiency affects essential cellular processes in the brain impairing memory, coordination, vision and mental state

4. Causes of Wernicke-Korsakoff Syndrome
Deficiency in thiamine (vitamin B1) causes lesions on the brain which results in Wernicke’s Encephalopathy
Reversible acute phase if immediately treated
If left untreated, Korsakoff Syndrome will develop
Irreversible chronic phase with permanent brain damage
Chronic alcoholism
Alcohol interferes with conversion of thiamine to thiamine pyrophosphate (active form of thiamine)
Prevents absorption of thiamine in the small intestines
Alcohol abuse can cause cirrhosis interfering with storage of thiamine
Malabsorption from stomach cancer or inflammatory bowel disease which impairs thiamine absorption (Chandrakumar et al. 2018)

5. Symptoms of Wernicke-Korsakoff Syndrome
Wernicke Encephalopathy
Confusion and loss mental activity (may lead to violent behaviour)
Loss of muscle coordination (ataxia)
Affected vision such as abnormal eye movements, double vision and upper eyelid drooping
Korsakoff Syndrome
Inability to learn new information
Anterograde amnesia (inability to create new memories) & retrograde amnesia (inability to recall previous memories)
Confabulation (exaggerated storytelling to fill gaps in memory)
House Scene diagnosing WKS patient:
(Chandrakumar et al. 2018)

6. Pathophysiology: Deficiency with Alcohol Consumption
Alcohol affects thiamine uptake at the cellular level in two ways:
Reduces absorption from the gastrointestinal tract into cells
Thiamine is transported via active transport and is associated with phosphorylation by thiamine diphosphokinase (TPK) which has decreased activity with alcohol exposure
Utilization
Phosphorylated thiamine (ThDP) enzyme binding requires magnesium which is usually deficient in alcoholics as well
(Martin et al., 2003)

7. Pathophysiology: The Molecular Level (Brain)
Thiamine is a cofactor for the enzyme transketolase
This is essential for the pentose phosphate pathway
The pathway creates ribose-5-phosphate and NADPH
Ribose-5-phosphate is needed for nucleic acid and complex sugar molecule synthesis
NADPH provides hydrogen for the synthesis of many other essential cellular elements as well as neurotransmitters
NADPH is also involved the synthesis of glutathione, an antioxidant
(Martin et al., 2003)

8. Thiamine is also a cofactor for pyruvate dehydrogenase (PDH) of glycolysis and alpha-ketoglutarate dehydrogenase (α-KGDH) of the citric acid cycle
(Martin et al., 2003)

9. Pathophysiology: Result
Transketolase can be up to 90% inhibited in some areas of the brain with thiamine deficiency
Glutathione cannot combat oxidative stress in the cell
Decreased efficiency of glycolysis and ATP production can lead to cell apoptosis
Cell necrosis leads to lesions on the brain
PDH is needed for myelin and acetylcholine synthesis
α-KGDH helps maintain GABA levels and protein synthesis
Cell death and hindered neuron function leads to the disease
(Martin et al., 2003)

10. Diagnosis: physical examinations
Liver function test
Look for signs of alcoholism
Kidney function test
Eye exam
Checking freedom of eye movement
Reflex and gait
Blood test
Serum albumin test.
Serum vitamin B1 test
RBC enzyme activity test
Low levels of albumin may signal nutritional deficiencies as well as kidney or liver problems.
Low enzyme activity in the RBCs signals a vitamin B-1 deficiency.

11. Diagnosis: imaging tests
CT scan to look for brain lesions related to Wernicke-Korsakoff
MRI scan to look for changes in brain metabolism
An electrocardiogram before and after taking vitamin B1

12. Treatments: Thiamine Vitamin B1 (thiamine hydrochloride)
Intravenous (IV)
Intramuscular (IM)
Oral supplements
Diet
Foods naturally high in B1 (meats, vegetables, nuts, etc.)
Foods fortified with B1 (grain products)
Acute treatment:
500 mg in normal saline IV, tid for at least 3 days
250 mg in normal saline IV, qd for 3 days
100 mg PO tid for the rest of the hospitalization
100 mg PO daily after discharge

13. Treatments: Others Magnesium (magnesium sulfate)
Phosphorylated B1 binding and uptake requires magnesium
Cofactor for carbohydrate metabolism through B1-dependent pathways
Potassium (potassium acid phosphate)
Alcoholics tend to have low potassium levels
Reduce Alcoholism (long-term solution)
Stop inhibition of thiamine diphosphokinase
Reduced renal excretion of magnesium (and other electrolytes)
Long-term care
Permanent cognitive disabilities (cognitive and memory, confabulation)
Permanent physical disabilities

14. Summary
WKS is combination of Wernicke Encephalopathy and Korsakoff’s Syndrome caused by deficiency of thiamine (Vit. B1)
Alcoholism decreases thiamine uptake and utilization
Permanent cognitive/physical damage
Thiamine deficiency hinders biochemical pathways:
Pentose phosphate pathway decreasing glutathione synthesis and increasing oxidative stress
Glycolysis leading to apoptosis and the citric acid cycle impairing acetylcholine and GABA synthesis
WKS is diagnosed with a series of physical examination and brain imaging tests
Liver/kidney function tests (alcoholic damage), eye exam, reflex and gait, blood test (B1, albumin, RBC enzyme)
CT scan (brain lesions), MRI (metabolic changes), ECG (see changes before/after treatment with thiamine)
Acute treatment with IV thiamine to restore hindered pathways and further supplementation of thiamine afterwards
IV to bypass impaired thiamine B1 absorption
Reduce alcohol consumption and give magnesium sulfate to restore phosphorylated-thiamine binding and uptake by active transporters

15. References
Martin, P.R., Singleton, C.K., & Hiller-Sturmhofel, S. (2003). The role of thiamine deficiency in alcoholic brain disease. Alcohol Research & Health, 27(2); Retrieved November, 2018, from
Mccormick LM, Buchanan JR, Onwuameze OE, Pierson RK, Paradiso S. Beyond Alcoholism. Cognitive And Behavioral Neurology. 2011;24(4): 209–16. (Accessed on November 2018)
Rivlin RS. Magnesium deficiency and alcohol intake: mechanisms, clinical significance and possible relation to cancer development (a review). Journal of the American College of Nutrition. 1994;13(5): 416–23. (Accessed on November 2018)
Chandrakumar A, Bhardwaj A, Jong GW. Review of thiamine deficiency disorders: Wernicke encephalopathy and Korsakoff psychosis. Journal of Basic Clinical Physiology and Pharmacology. 2018;1-10. Doi: