1. Wernicke-Korsakoff Syndrome
Krishan Kanesalingam, Halina Lam, Tony Liu, Puja Modi
PHM Fall 2014
Instructor: Dr. Jeffrey Henderson

2. In this Presentation... Background information Causes Symptoms
Biological significance of thiamine
Relevant pathways
Diagnosis
Treatment
Testing

3. Background Also known as “wet brain”
Combination of two diseases: Wernicke’s encephalopathy and Korsakoff’s syndrome
Very close relationship
Begins with Wernicke’s encephalopathy, if not properly treated quickly, lead to Korsakoff’s syndrome
N- CEF-LO-PATHY

4. Causes Alcohol abuse/chronic alcoholism (Main cause)
Thiamine (Vitamin B1) deficiency (Secondary cause to alcoholism)
Malnutrition caused by dietary restriction or eating disorder
Surgeries related to obesity including bariatric surgery and gastric bypass surgery

5. Symptoms Anterograde amnesia (inability to form new memories)
Memory loss
Loss of muscle coordination
Vision changes such as eyelid drooping, abnormal eye movements, double vision
Hallucinations/confusion

6. Wernicke’s Encephalopathy
Damage to central nervous system tissue
Characterized by paralysis of the eye muscles, lack of muscle coordination, and confusion
Various other effects occur depending on the area of the lesion (hypothalamus - temperature regulation, medulla - ataxia)

7. Korsakoff’s Syndrome
Characterized by amnesia, creation of new memories, apathy
Both of these diseases are caused by vitamin B1 (thiamine) deficiencies, simultaneous occurrence makes wernicke-korsakoff disorder

8. Biological Significance of Thiamine
Convert carbohydrates into glucose (sugar) for energy; important for intense physical activity
Breakdown of fats and proteins
AKA vitamin B1, B complex vitamins maintain muscle tone along the walls of digestive tract
Promotes the health of the nervous system, skin, hair, eyes, mouth and liver
“anti-stress”

9. Relevant Pathways
Transketolase requires thiamine as a cofactor → Defense against oxidative stress
NADPH is crucial in the elimination of H2O2
NADPH plays an important role in the synthesis of glutathione, a compound that is essential in the body’s defense against oxidative stress. To function properly, all cells require certain levels of NADPH and ribose–5–phosphate, and the biochemical reaction mediated by transketolase is crucial for maintaining the appropriate levels of both molecules. With lowered levels of thiamine, the body cannot get rid of hydrogen peroxide properly, leading to cell damage or death from oxidative stress.

10. Relevant Pathways Pyruvate dehydrogenase uses thiamine as a cofactor
Pyruvate → Acetyl CoA after glycolysis
Also necessary for the citric acid cycle; alpha ketoglutarate dehydrogenase needs thiamine as a cofactor to catalyze alpha-ketoglutarate → succinyl CoA
Important for myelin synthesis and neurotransmitter regulation
In general, thiamine is extremely important for energy production in the body
Acetyl-CoA plays a role in myelin formations, so proper functioning of PDH is essential for the synthesis of myelin, which forms an integral part of the neuron sheath, thereby supporting the conduction of action potentials along the axon and synaptic transmission. So in this disorder, we have a buildup of pyruvate and not enough acetyl CoA, leading to myeline damage and central nervous system damage symptoms. The citric acid cycle and α–KGDH also play a role in maintaining the levels of the neurotransmitters glutamate, gamma–aminobutyric acid (GABA), and aspartate, as well as in protein synthesis.
Mechanisms of thiamine deficiency induce cell damage in the central nervous system. The changes in carbohydrate metabolism, i.e. reduction in α–KGDH (Alpha-ketoglutarate dehydrogenase) activity, can lead to damage to the mitochondria. Because the mitochondria make most of the energy required for cellular function the damage can result in cell death.

11. Relevant Pathways

12. Diagnosis WKS is often missed as a diagnosis
Acute phase physical examination
Nutritional testing should be done
Full medical history necessary
Diagnostic imaging may help
WKS is often missed as a diagnosis. In the acute phase, a physical examination may reveal skin changes and a red “beefy” tongue. In addition, blood count, electrolytes and liver function tests should be conducted. Even in the chronic phase, an MRI may show shrunken mammillary bodies and other changes in the brain. CT scans have showed enlarged ventricles and diencephalic lesions.
In cases of suspected non-alcohol related WKS, the physician may investigate anorexia nervosa, hypermesis gravidarum, severe malnutrition and other disorders or surgical procedures which impair intestinal absorption of thiamine.

13. Testing for the Syndrome
Several simple examinations can be performed, most of which are of the nervous/muscular systems and are used to check the damage done to the nerve system.
abnormal eye movement
decreased or abnormal reflexes
fast pulse
low blood pressure
low body temperature
muscle weakness and atrophy
problems with walking (gait), coordination and balance ( ataxia)
skin changes
red “beefy” tongue
poor eating habits or eating disorders
drowsiness or confusion
skin changes-- reddening or jaundice
eating disordes--anorexia

14. Testing for the Syndrome
There are multiple nutritional tests that may be done. A few of them are:
Serum albumin = LOW
LFTs
Serum Vitamin B1 Tests = LOW
Transketolase (enzyme) activity in the RBCs = LOW
Pyruvate Levels testing = HIGH
Serum of urine alcohol level testing
Diagnostic imaging tests for WKS include:
Electrocardiograph (ECG)
Computed Tomography (CT)
Magnetic Resonance Imaging (MRI)
Recently there has been a testing discovery of genetic marker APOE4 which is being used for WKS.
serum albumin test-Low levels may signal nutritional deficiencies as well as kidney or liver problems.
Transketolase (enzyme) activity in the red blood cells: Low enzyme activity signals a vitamin B1 deficiency.
pyruvate= high
If the history is significant for chronic (long-term) alcohol abuse, serum or urine alcohol levels may be elevated.
electrocardiograph (ECG), which looks for abnormalities before and after giving vitamin B1
computed tomography (CT) scan to check for brain lesions related to WD
magnetic resonance imaging (MRI) scan to look for brain changes related to WD
Physicians may also use neuropsychological tests to judge the severity of mental deficiencies.
It is a significant predictor of global intellectual deficits in people with WKS. Individuals with the ApoE genotype may experience a certain interaction with heavy alcohol use which could predispose them to WKS. Concerns about an inherited susceptibility to WKS should be discussed with a genetic counselor.

15. Treatment
WKS treatment should begin immediately and initially treatment may involve hospitalization.
There are 3 types:
Nutritional
balanced diet with vitamin B1
Medicational
intravenous vitamin B1
oral vitamin B1
In some cases treatment of vitamin B1 deficiency an adverse reaction may occur.
Psychological/Social
alcoholism (withdrawal sympotms , quitting)
brain damage
WKS treatment should begin immediately. Prompt treatment may delay or stop disease progression. Treatments are also able to reverse non-permanent brain abnormalities.
Treatment may first involve hospitalization. At the hospital, the patient will be monitored to ensure that his or her digestive system is absorbing food properly. The doctor may also administer vitamin B1 to the patient through an IV.
Treatment for WKS may include:
intravenous vitamin B1 (vitamin B1 given through an IV in the arm or hand)
oral vitamin B1 (for continued maintenance after initial treatment)
balanced diet (to keep vitamin B1 levels up)
treatment for alcoholism (help with withdrawal, support in quitting, etc.)
In a small number of cases, treatment of vitamin B1 deficiency produces a negative reaction. This is more common in alcoholics.
Negative reactions to receiving vitamin B1 may vary. Reactions may include alcohol withdrawal symptoms like insomnia, sweating, or mood swings. The patient may also experience hallucinations, confusion, and/or agitation.

16. Summary Slide
This illness is a combination of Wernicke’s encephalopathy and Korsakoff syndrome.
Number one cause: alcohol abuse/chronic alcoholism, thiamine deficiency is also a major cause
Common symptoms: Confusion, loss of memories, loss of muscle coordination, hallucinations and vision problems.
A diagnosis involves physical examinations and nutritional testing. Medical history and diagnostic imaging may be used additionally.
Treatment involves having a balanced diet, taking vitamin B1 supplements and receiving psychological aid where necessary.
Thiamine is important for converting carbohydrates into glucose (sugar) for energy, breakdown of fats and proteins, maintaining muscle tone along the walls of digestive tract, promoting the health of the nervous system, skin, hair, eyes, mouth and liver
Thiamine is needed as a cofactor of transketolase to make NADPH for maintenance of oxidative stress
Pyruvate dehydrogenase uses thiamine as a cofactor to make acetyl CoA after glycolysis
Alpha ketoglutarate dehydrogenase needs thiamine as a cofactor to creat succinyl CoA from alpha-ketoglutarate in the citric acid cycle

17. Works Cited
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“Korsakoff's Syndrome” Korsakoff's Syndrome - Neurobiology Of Disease 07. Web. 25 Nov
Nunes, G.D.F., Y. Poitelon, E. Hurley, M. Patel, K.A. Nave, L. Wrabetz, and M.L. Feltri. "Metabolic Crosstalk between Neurons and Myelinating Cells: A Means to Keep Axons Functional at Distance from the Neuronal Cell Body?" CURCA: Center for Undergraduate Research and Creative Activities. University of Buffalo, The State University of New York. Web. 25 Nov
"Wernicke-Korsakoff Syndrome | Doctor | Patient.co.uk." Patient.co.uk. Web. 25 Nov
"Wernicke-Korsakoff Syndrome." Family Caregiver Alliance. Web. 25 Nov
“Wernicke-Korsakoff Syndrome”. Judith Brown CPD. Web. 25 Nov
"Wernicke-Korsakoff Syndrome: MedlinePlus Medical Encyclopedia." U.S National Library of Medicine. U.S. National Library of Medicine. Web. 25 Nov
"Wernicke-Korsakoff Syndrome." : Risk Factors, Causes & Symptoms. Web. 25 Nov
"Wernicke-Korsakoff Syndrome ."Wernicke-Korsakoff Syndrome. Web. 25 Nov