Wernicke Encephalopathy


Article Author:
Sarayu Vasan


Article Editor:
Anil Kumar


Editors In Chief:
Susan Johnson
Alexandra Caley


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
Benjamin Eovaldi
Radia Jamil
Sobhan Daneshfar
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes


Updated:
11/14/2018 2:58:52 PM

Introduction

Wernicke encephalopathy (WE) is an acute neurological condition characterized by a clinical triad of ophthalmoparesis with nystagmus, ataxia, and confusion. This is a life-threatening illness caused by thiamine deficiency, which primarily affects the peripheral and central nervous systems. This should be differentiated from Korsakoff syndrome which is preventable and is usually suspected as a consequence of at least one episode of Wernicke’s encephalopathy. Korsakoff syndrome is a neuropsychiatric disorder associated with memory disturbances in which there are significant deficits in anterograde and retrograde memory. Immediate memory is maintained, but short-term memory is diminished with intact sensorium. The disorder is associated with patients fabricating stories in the setting of clear consciousness. Confabulations can be spontaneous or provoked with provoked confabulation commonly seen in chronic Korsakoff syndrome and spontaneous confabulation usually noted in the acute Wernicke state.[1][2]

Etiology

Thiamine deficiency is characteristically associated with severe alcohol use disorder. Although Wernicke encephalopathy mostly affects people who have a thiamine deficiency due to chronic alcoholism, various other causes include severe malnutrition, hyperemesis gravidarum, prolonged parenteral nutrition, malignancies, immunodeficiency syndromes, liver disease, hyperthyroidism, and severe anorexia nervosa. Chronic alcohol consumption may cause thiamine deficiency due to impaired absorption of thiamine from the intestine, a possible genetic predisposition, inadequate diet, reduced storage of thiamine in the liver, and other nutritional deficiencies.[3][2][4]

Epidemiology

Prevalence data on Wernicke encephalopathy comes mainly from autopsy studies with rates ranging between 1% and 3%. Several studies indicate that prevalence rates via analysis of clinical records are lower in comparison to necropsy studies as the diagnosis is easily overlooked or missed. The incidence of Wernicke encephalopathy is believed to be higher in developing countries due to vitamin deficiencies and malnutrition. The female to male ratio for Wernicke encephalopathy is 1:1.7, and there are no studies that show a particular race predisposed to Wernicke encephalopathy.[5]

Pathophysiology

Thiamine, one of the first B vitamins to be discovered also known as Vitamin B1, is a coenzyme that is essential for intricate organic pathways and plays a central role in cerebral metabolism. This vitamin acts as a cofactor for several enzymes in the Krebs cycle and the pentose phosphate pathway, including alpha-keto-glutamic acid oxidation and pyruvate decarboxylation. Thiamine-dependent enzymes function as a connection between glycolytic and citric acid cycles. Therefore, deficiency of thiamine will lead to decreased levels of alpha-keto-glutarate, acetate, citrate, acetylcholine and accumulation of lactate and pyruvate. This deficiency can cause metabolic imbalances leading to neurologic complications including neuronal cell death. Neuronal death in the mammillary bodies and thalamus were implicated in multiple cases of Wernicke encephalopathy studied. Studies involving computed tomography (CT) and magnetic resonance imaging (MRI) of patients with Wernicke encephalopathy revealed lesions in the thalamus with dilated ventricles and volume loss in the mammillary bodies. The lesions are usually symmetrical in the midbrain, hypothalamus, and cerebellum.[6][7]

History and Physical

Wernicke encephalopathy should be suspected in any patient with chronic alcohol abuse or any form of malnutrition and any of the following: acute altered mental status, ophthalmoplegia, ataxic gait, delirium, and hypotension. The classic triad of Wernicke encephalopathy is altered mental status, ataxic gait, and ophthalmoplegia. The diagnosis is made based on clinical presentation, and a definitive diagnosis is complicated as the clinical triad may not be present in up to 90% of patients. 

The hallmark sign of Wernicke encephalopathy is ocular abnormalities especially nystagmus. Other oculomotor symptoms include cranial nerve involvement of oculomotor, abducens, and vestibular nuclei causing conjugate gaze palsies. Gait ataxia is also a significant finding in Wernicke encephalopathy where patients will present with a broad-based gait. Also, gait can worsen, and in many cases, patients are unable to walk. Physical examination may include a complete neurological exam with cerebellar testing. Disorientation and altered sensorium characterize encephalopathy. Some patient can present with hyperactive delirium secondary to possible alcohol withdrawal symptoms alongside Wernicke encephalopathy. Less than 5% of patients with Wernicke encephalopathy can present with the severely depressed level of consciousness that will eventually lead to coma and death. Some other warning signs could include hyperthermia and hypotension. The patient could also present with peripheral neuropathy and commonly includes the lower extremity, and an examination would reveal distal sensory loss.

Evaluation

Evaluation should include a thorough patient history with a focused physical exam and laboratory workup with appropriate imaging. There are no specific laboratory tests for diagnosing Wernicke encephalopathy as it is a clinical diagnosis with the above mentioned classic signs and symptoms. However, a complete blood count and the comprehensive metabolic panel can be completed to exclude other causes of central nervous system abnormalities. Moreover, normal brain imaging cannot rule out Wernicke encephalopathy and therefore not very beneficial either. Caine et al. criteria were established in 1997 which is now 85% sensitive if patients have two or more of the classic features that include: ataxia, confusion, and ophthalmoplegia. Also, looking for risk factors helps in evaluating the patient as Wernicke encephalopathy were classically thought of as a disease exclusively due to alcoholism. However, in recent years Wernicke encephalopathy is also seen in patients that are chronically malnourished, post-bariatric surgery, hyperemesis gravidarum, liver disease, hyperthyroidism, and severe anorexia nervosa.[1][8][9]

Treatment / Management

The aim of treatment is prompt and quick correction of the thiamine deficiency in the brain. Wernicke encephalopathy is a medical emergency and considered a reversible condition, therefore, requiring immediate emergent attention although the onset of the disease may be acute or chronic. Parenteral administration of thiamine is most effective and provides for rapid administration, however, in some cases, there are persistent neurological deficits, and the acute condition can progress to chronic Korsakoff syndrome. The preferred dose of thiamine treatment for Wernicke encephalopathy may be as high as 500 mg given one to three times daily parenterally. All malnourished patient may need higher doses of thiamine. There is some evidence that thiamine treatment can improve the confusional state, quick resolution of ataxia, ophthalmoplegia, and nystagmus. Thiamine is generally administered before or together with glucose solutions because the glucose oxidation can decrease thiamine levels thereby exacerbating the neurological symptoms of Wernicke encephalopathy. Patient with magnesium deficiency should also be treated as this can result in reduced recovery from Wernicke encephalopathy especially in patients with alcoholism.[10][11][12]

Differential Diagnosis

Differential diagnoses include:

  • Hepatic encephalopathy
  • Stroke
  • Alcohol withdrawal syndrome
  • Delirium tremens
  • Chronic hypoxia
  • Normal pressure hydrocephalus 

Complications

  • Neurological injury
  • Ataxia
  • Korsakoff syndrome
  • Ophthalmoplegia

Consultations

  • Internist
  • Endocrinologist
  • Psychiatrist
  • Neurologist
  • Intensivist

Enhancing Healthcare Team Outcomes

The management of WE is complex and usually requires a team approach. Because the disorder can present with various manifestations, the patient is best managed by a neurologist and an intensivist. Other specialists may be required according to organ involvement. The role of the nurse, dietitian, social worker, and pharmacist cannot be overemphasized. These patients are sick, frail and malnourished. A dietary consult should be done to assess the calorie needs and determine how to provide the food as well as thiamine. Since many WE patients are managed as outpatients, the pharmacist should encourage abstinence from alcohol. Since the cornerstone of therapy is thiamine, the importance of compliance is vital. At the same time, the electrolyte deficiencies should be corrected. Finally, the family should be educated about the prognosis of these individuals and make preparations for long-term care, in case the patient develops korsakoff syndrome. The ultimate goal is to improve the quality of life and lessen the burden on the family.[13][14] (Level V)

Outcomes

WE is a serious medical disorder which carries an enormous morbidity and mortality. Even when the condition is managed with thiamine, the global confusion usually improves rapidly, but the ataxia and ophthalmoplegia may persist for some time. Patients who minimal or neurological signs have the best outcomes with thiamine supplement. However, survivors of WE may develop korsakoff psychosis and require long-term institutionalization. Of these, less than 10% will recover to be discharged from long-term care. A significant number of patients will have long-term neurological deficits like ataxia, nystagmus and korsakoff syndrome, which seriously diminishes the quality of life. Unfortunately, there are no long-term follow-up studies and anecdotal reports indicate that many of these patients do die prematurely. [15][16][17](Level V)


Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Wernicke Encephalopathy - Questions

Take a quiz of the questions on this article.

Take Quiz
Which of the following is a hallmark presentation of Wernicke encephalopathy?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 60-year-old chronic alcoholic with Wernicke encephalopathy presents with cardiac dilation, sight loss, peripheral neuropathy, muscle wasting, and generalized edema. The most likely cause is a deficiency in which of the following?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A patient with a long history of severe alcohol use disorder presents with paralysis of lateral gaze, difficulty walking, and dementia. The patient is deficient in a vitamin required as a cofactor for which of the following?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following is true about Wernicke encephalopathy?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 54-year-old with severe chronic alcohol use disorder presents with paralysis of lateral gaze, gait problems, and memory loss. The patient is found to be deficient in a vitamin required as a cofactor for which of the following?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 72-year-old formerly obese female patient presents with mental confusion, gait problems, psychosis, ophthalmoplegia, and polyneuropathy. She has lost 150 pounds after a gastric bypass 9 months ago. What vitamin should be administered?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following is least likely to be present in Wernicke encephalopathy?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following statements about Wernicke encephalopathy is incorrect?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 70 year old chronic alcoholic presents with malnutrition and Wernicke encephalopathy. He is given intravenous thiamine. What is the next necessary medication to give before starting intravenous dextrose?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following findings strongly suggests alcoholic encephalopathy?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 65-year-old female develops ovarian cancer and requires an abdominal hysterectomy. She has a history of benzodiazepine and alcohol use disorder. Five days postoperatively she becomes delusional, agitated, and suspicious. There is no evidence of infection. There is no evidence of renal or hepatic abnormalities and electrolytes are normal. MRI of the brain is normal. The patient develops a generalized tonic-clonic seizure. Lumbar puncture shows normal cerebrospinal fluid. What should have been given preoperatively to prevent this complication?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 62-year-old male is brought to the emergency department by his family. He is confused and disoriented to person, place, and time. The family states that he is an alcoholic but they have convinced him to quit but he has been taking lorazepam. The patient is unsteady on his feet, has horizontal nystagmus, and paresis of conjugate gaze. What is the most likely nutritional deficiency?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following is a complication of chronic alcoholism?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Wernicke syndrome, often seen in chronic alcoholics typically presents with which of the following symptoms:



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following is not true of Wernicke encephalopathy?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Wernicke Encephalopathy - References

References

Karakonstantis S,Galani D,Korela D,Maragou S,Arna D,Basta M, Missing the early signs of thiamine deficiency. A case associated with a liquid-only diet. Nutritional neuroscience. 2018 Aug 9     [PubMed]
Oudman E,Wijnia JW,Oey MJ,van Dam MJ,Postma A, Preventing Wernicke's encephalopathy in anorexia nervosa: A systematic review. Psychiatry and clinical neurosciences. 2018 Jul 8     [PubMed]
Shabbir S,Tong O,Gluck L,Robbins M, Convergence Spasm in Wernicke Encephalopathy. The Neurohospitalist. 2018 Jan     [PubMed]
Tang L,Alsulaim HA,Canner JK,Prokopowicz GP,Steele KE, Prevalence and predictors of postoperative thiamine deficiency after vertical sleeve gastrectomy. Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery. 2018 Jul     [PubMed]
Arts NJ,Walvoort SJ,Kessels RP, Korsakoff's syndrome: a critical review. Neuropsychiatric disease and treatment. 2017     [PubMed]
Kim WJ,Kim MM, Wernicke's Encephalopathy Presenting with Bilateral Complete Horizontal and Downward Gaze Palsy in a Malnourished Patient. Korean journal of ophthalmology : KJO. 2017 Aug     [PubMed]
Sukop PH,Kessler FH,Valerio AG,Escobar M,Castro M,Diemen LV, Wernicke's encephalopathy in crack-cocaine addiction. Medical hypotheses. 2016 Apr     [PubMed]
Jan K, Wernicke encephalopathy: (MRI) picture worth a thousand words. Oxford medical case reports. 2018 May     [PubMed]
Diekfuss JA,De Larwelle J,McFadden SH, Diagnosis makes a difference: Perceptions of older persons with dementia symptoms. Experimental aging research. 2018 Mar-Apr     [PubMed]
Onishi H,Ishida M,Uchida N,Shintani D,Nishikawa T,Hasegawa K,Fujiwara K,Akechi T, Subclinical thiamine deficiency identified by preoperative evaluation in an ovarian cancer patient: Diagnosis and the need for preoperative thiamine measurement. Palliative     [PubMed]
Johnson JM,Fox V, Beyond Thiamine: Treatment for Cognitive Impairment in Korsakoff's Syndrome. Psychosomatics. 2018 Jul - Aug     [PubMed]
Oudman E,Wijnia JW,van Dam M,Biter LU,Postma A, Preventing Wernicke Encephalopathy After Bariatric Surgery. Obesity surgery. 2018 Jul     [PubMed]
McKeon A,Frye MA,Delanty N, The alcohol withdrawal syndrome. Journal of neurology, neurosurgery, and psychiatry. 2008 Aug     [PubMed]
Donnelly A, Wernicke-Korsakoff syndrome: recognition and treatment. Nursing standard (Royal College of Nursing (Great Britain) : 1987). 2017 Mar 29     [PubMed]
Nakamura ZM,Tatreau JR,Rosenstein DL,Park EM, Clinical Characteristics and Outcomes Associated With High-Dose Intravenous Thiamine Administration in Patients With Encephalopathy. Psychosomatics. 2018 Jul - Aug     [PubMed]
Sanvisens A,Zuluaga P,Fuster D,Rivas I,Tor J,Marcos M,Chamorro AJ,Muga R, Long-Term Mortality of Patients with an Alcohol-Related Wernicke-Korsakoff Syndrome. Alcohol and alcoholism (Oxford, Oxfordshire). 2017 Jul 1     [PubMed]
Zahr NM,Kaufman KL,Harper CG, Clinical and pathological features of alcohol-related brain damage. Nature reviews. Neurology. 2011 May     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of CNS-Adult-Gerontology. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for CNS-Adult-Gerontology, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in CNS-Adult-Gerontology, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of CNS-Adult-Gerontology. When it is time for the CNS-Adult-Gerontology board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study CNS-Adult-Gerontology.