Presentation on theme: "Wernicke-Korsakoff Syndrome"— Presentation transcript:
1Wernicke-Korsakoff Syndrome Krishan Kanesalingam, Halina Lam, Tony Liu, Puja ModiPHM Fall 2014Instructor: Dr. Jeffrey Henderson
2In this Presentation... Background information Causes Symptoms Biological significance of thiamineRelevant pathwaysDiagnosisTreatmentTesting
3Background Also known as “wet brain” Combination of two diseases: Wernicke’s encephalopathy and Korsakoff’s syndromeVery close relationshipBegins with Wernicke’s encephalopathy, if not properly treated quickly, lead to Korsakoff’s syndromeN- CEF-LO-PATHY
4Causes Alcohol abuse/chronic alcoholism (Main cause) Thiamine (Vitamin B1) deficiency (Secondary cause to alcoholism)Malnutrition caused by dietary restriction or eating disorderSurgeries related to obesity including bariatric surgery and gastric bypass surgery
5Symptoms Anterograde amnesia (inability to form new memories) Memory lossLoss of muscle coordinationVision changes such as eyelid drooping, abnormal eye movements, double visionHallucinations/confusion
6Wernicke’s Encephalopathy Damage to central nervous system tissueCharacterized by paralysis of the eye muscles, lack of muscle coordination, and confusionVarious other effects occur depending on the area of the lesion (hypothalamus - temperature regulation, medulla - ataxia)
7Korsakoff’s SyndromeCharacterized by amnesia, creation of new memories, apathyBoth of these diseases are caused by vitamin B1 (thiamine) deficiencies, simultaneous occurrence makes wernicke-korsakoff disorder
8Biological Significance of Thiamine Convert carbohydrates into glucose (sugar) for energy; important for intense physical activityBreakdown of fats and proteinsAKA vitamin B1, B complex vitamins maintain muscle tone along the walls of digestive tractPromotes the health of the nervous system, skin, hair, eyes, mouth and liver“anti-stress”
9Relevant PathwaysTransketolase requires thiamine as a cofactor → Defense against oxidative stressNADPH is crucial in the elimination of H2O2NADPH 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.
10Relevant Pathways Pyruvate dehydrogenase uses thiamine as a cofactor Pyruvate → Acetyl CoA after glycolysisAlso necessary for the citric acid cycle; alpha ketoglutarate dehydrogenase needs thiamine as a cofactor to catalyze alpha-ketoglutarate → succinyl CoAImportant for myelin synthesis and neurotransmitter regulationIn general, thiamine is extremely important for energy production in the bodyAcetyl-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.
12Diagnosis WKS is often missed as a diagnosis Acute phase physical examinationNutritional testing should be doneFull medical history necessaryDiagnostic imaging may helpWKS 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.
13Testing 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 movementdecreased or abnormal reflexesfast pulselow blood pressurelow body temperaturemuscle weakness and atrophyproblems with walking (gait), coordination and balance ( ataxia)skin changesred “beefy” tonguepoor eating habits or eating disordersdrowsiness or confusionskin changes-- reddening or jaundiceeating disordes--anorexia
14Testing for the Syndrome There are multiple nutritional tests that may be done. A few of them are:Serum albumin = LOWLFTsSerum Vitamin B1 Tests = LOWTransketolase (enzyme) activity in the RBCs = LOWPyruvate Levels testing = HIGHSerum of urine alcohol level testingDiagnostic 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= highIf 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 B1computed tomography (CT) scan to check for brain lesions related to WDmagnetic resonance imaging (MRI) scan to look for brain changes related to WDPhysicians 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.
15TreatmentWKS treatment should begin immediately and initially treatment may involve hospitalization.There are 3 types:Nutritionalbalanced diet with vitamin B1Medicationalintravenous vitamin B1oral vitamin B1In some cases treatment of vitamin B1 deficiency an adverse reaction may occur.Psychological/Socialalcoholism (withdrawal sympotms , quitting)brain damageWKS 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.
16Summary SlideThis illness is a combination of Wernicke’s encephalopathy and Korsakoff syndrome.Number one cause: alcohol abuse/chronic alcoholism, thiamine deficiency is also a major causeCommon 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 liverThiamine is needed as a cofactor of transketolase to make NADPH for maintenance of oxidative stressPyruvate dehydrogenase uses thiamine as a cofactor to make acetyl CoA after glycolysisAlpha ketoglutarate dehydrogenase needs thiamine as a cofactor to creat succinyl CoA from alpha-ketoglutarate in the citric acid cycle
17Works Cited"Korsakoff Syndrome." Alzheimer's Disease and Dementia. Web. 25 Nov“Korsakoff's Syndrome” Korsakoff's Syndrome - Neurobiology Of Disease 07. Web. 25 Nov https://sites.google.com/a/conncoll.edu/neurobiology-of-disease-07/home/korsakoffs-syndrome#TOC-CausesNunes, 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 https://www.caregiver.org/wernicke-korsakoff-syndrome“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