Signs and symptoms of Wernicke encephalopathy (WE) stem from alterations of carbohydrate metabolism (inadequate absorption, accelerated metabolism or increased intake) together with the deficiency of thiamine (vitamin B1), as thiamine is a vital coenzyme of the Krebs cycle, the key step in metabolism of carbohydrates and energy production [1] [2] [3] [4]. Conditions that disrupt this process include hyperemesis (especially in pregnancy, known as hyperemesis gravidarum), acquired immunodeficiency syndrome (AIDS), administration of intravenous dextrose and other forms of parenteral nutrition, gastrointestinal tract (GI) surgery, but also malignancy and severe infections, all reducing the thiamine levels in the central nervous system (CNS) [1] [3] [5]. Chronic alcoholism, however, is by far the most widely recognized caused of WE, as a combination of poor diet, reduced storage of thiamine and long-term impairment of thiamine absorption from the GI tract [6]. Regardless of the cause, accumulation of toxic metabolites from impaired carbohydrate formation and degradation occurs, leading to a typical clinical presentation comprised of an altered mental state, ataxia, and ophthalmoplegia [4] [7]. Many reports have confirmed, however, that not all signs of WE may be present and that the diagnosis is often not recognized [1] [3] [4] [5] [7]. In fact, up to 68% of alcohol abusers and 94% of patients in whom alcoholism is not the cause of WE remain undiagnosed [1] [2]. WE can be life-threatening, as ischemia of the CNS can lead to irreversible neuronal damage or even death in the absence of an early diagnosis, which is why it is considered to be a medical emergency [1] [7].

• Malnutrition

  Wernicke encephalopathy secondary to thiamine deficiency should be considered as a possible cause of acute mental status changes in patients with acute pancreatitis and malnutrition. [ncbi.nlm.nih.gov]

  Etiology Thiamine deficiency results from malnutrition or malabsorption, which can occur for a number of reasons 6,7 : alcohol abuse (up to 90% in industrialised countries 5 ) starvation/fasting prolonged total parenteral nutrition without supplementation [radiopaedia.org]

  Causes  Chronic alcoholism – Malnutrition – reduced thiamine uptake and utilization  Prolonged starvation  Hyperemesis Gravidarum  Bariatric Surgery (Bariatric BeriBeri)  Malabsorption Syndromes  Infants on formula diet deficient in thiamine 5 6 [slideshare.net]

  Wernicke’s encephalopathy due to thiamine (vitamin B 1 ) deficiency can be a complication of hyperemesis gravidarum; it can also occur in the context of alcohol use, bariatric surgery, or malnutrition. [nejm.org]

• Prisoner of War

  Cerebral beriberi (Wernicke's encephalopathy); review of 52 cases in a Singapore prisoner-of-war hospital. Lancet. 1947 Jan 4. 1(6436):11-7. [Medline]. Smithline HA, Donnino M, Greenblatt DJ. [emedicine.medscape.com]

  Cerebral beriberi (Wernicke's Encephalopathy): review of 52 cases in a Singapore prisoner-of-war hospital. Lancet, 1, 11–17. CrossRef Google Scholar Diaz, G. A., Banikazemi, M., Oishi, K., Desnick, R. J., & Gelb, B. D. (1999). [doi.org]

  Cerebral beriberi (Wernicke's encephalopathy); review of 52 cases in a Singapore prisoner-of-war hospital. Lancet 1947;1:11-7. 22. Donnino M. Gastrointestinal beriberi: A previously unrecognized syndrome. Ann Intern Med 2004;141:898-9. 23. [ruralneuropractice.com]

• Diplopia

  We present a developmentally appropriate adolescent boy who presented with upper and lower extremity glove-and-stocking paresthesias, distal weakness, vertigo, high-pitched voice, inattention, ataxia, and binocular diplopia after a voluntary 59-kg weight [ncbi.nlm.nih.gov]

  Thereafter, her blood pressure stabilized, the acidosis improved, and her deafness, diplopia, and confusion were resolved. [doi.org]

  History may reveal difficulties with walking and diplopia that precedes cognitive changes by a few days or weeks. [clinicaladvisor.com]

• Strabismus

  We recommend inquiring about any obesity surgery in one's history and including Wernicke encephalopathy in possible differential diagnoses in those patients who have a recent onset of strabismus or nystagmus, altered mental status, and/or gait ataxia. [ncbi.nlm.nih.gov]

  Common signs are confusion, apathy, diplopia, strabismus, nystagmus, weakness or paralysis of eye abduction, ptosis, vestibular dysfunction without hearing loss, and ataxia. [clinicaladvisor.com]

• Pupillary Abnormality

  Less frequently noted manifestations are: pupillary abnormalities such as sluggishly reactive pupils, ptosis, scotomata, and anisocoria. [emedicine.medscape.com]

  and vestibular nuclei pupillary abnormalities such as sluggishly reactive pupils, ptosis, scotomata, and anisocoria OTHER SYMPTOMS Vestibular dysfunction Hypotension. [rnpedia.com]

• Hyperhidrosis

  At age 53 began an acute condition with intense hypothermia, hyperhidrosis and lethargy, without fever. Was initially mistaken with a respiratory infection. [enfermedad-de-wernicke.weebly.com]

  […] drowsiness, psycho and/or motor slowing [8] dysphagia, [14] blush, sleep apnea, epilepsy [15] and stupor lactic acidosis [16] memory impairment, [7] amnesia, [17] depression, [18] psychosis [19] [20] hypothermia, [11] [21] [22] polyneuropathy, [23] hyperhidrosis [en.wikipedia.org]

• Ataxia

  WE should be considered in any patient who presents with acute delirium or ataxia. [clinicaladvisor.com]

  A few days later, her consciousness and limb ataxia began to improve. However, truncal ataxia and polyneuropathy became evident. [hyperemesis.org]

  Here we describe a teenage girl who develops vomiting after Roux-en-Y gastric bypass and presented with nystagmus, irritability, and ataxia. [ncbi.nlm.nih.gov]

• Confusion

  Confusion is the most common presenting symptom, followed by ataxia and visual problems. Some patients show a disproportionate disorder of retentive memory. [clinicaladvisor.com]

  Snapshot A 44-year-old male presents with confusion and gait instability. Medical history is significant for alcohol use disorder, requiring multiple hospitalizations for alcohol intoxication. He drinks one to two pints of vodka daily. [medbullets.com]

  Two patients had confusion, ataxia, or ocular changes and low serum thiamine levels, which resolved with parenteral thiamine. [ncbi.nlm.nih.gov]

  Persistent or prolonged vomiting, confusion, and unintentional weight loss are red flags indicating a high risk of WE. [hyperemesis.org]

• Nystagmus

  Nystagmus (usually horizontal) is the most common ocular finding. Prominent nystagmus in the abducting eye is characteristic of internuclear ophthalmoplegia. [clinicaladvisor.com]

  An examination revealed spontaneous upbeat nystagmus ( Video 1 ), gaze-evoked nystagmus ( Video 2 ), and gait ataxia. She had no ophthalmoplegia. [nejm.org]

  The oculomotor manifestations are: nystagmus, bilateral lateral rectus palsies, and conjugate gaze palsies reflecting cranial nerve involvement of the oculomotor, abducens, and vestibular nuclei. [emedicine.medscape.com]

  The classic triad of confusion, ophthalmoplegia (or nystagmus) and ataxia may be absent, and the history of alcohol abuse or other causes of thiamine deficiency may be unknown. [ncbi.nlm.nih.gov]

• Confabulation

  […] originally described as characterized by the triad of: acute confusion ataxia ophthalmoplegia Wernicke encephalopathy can evolve into the chronic form of thiamine deficiency known as Korsakoff psychosis, characterized by: memory loss (global amnesia) confabulation [radiopaedia.org]

  Confabulation - Patient fills in gaps of memory with data that can be recalled at that moment 1. 1 Wernicke’s Encephalopathy AMITESHWAR SINGH INTERN, KMC MANIPAL. 2. 2 Dr Carl Wernicke A Polish neurologist, who described this neuropsychiatric syndrome [slideshare.net]

  Confabulation can be associated with both phases of WKS. The implication that confabulation is a deliberate attempt to hide the memory defect is probably incorrect since, as the patient improves, the tendency to confabulate diminishes. E. [clinicaladvisor.com]

  […] seen in chronic alcoholism, and other conditions of poor nutritions ( e.g., malabsorption) Epidemiology alcoholics are mostly affected Presentation Symptoms Wernicke's encephalopathy confusion opthalmoplegia ataxia Korsakoff's psychosis memory loss confabulation [medbullets.com]

  Eight weeks after onset, she developed Korsakoff's psychosis such as anterograde and retrograde amnesia, disorientation and confabulation. [ncbi.nlm.nih.gov]

• Amnesia

  The second patient was a man who lost 10 kg after surgical gastrectomy; he developed diplopia, ophthalmoplegia, cerebellar ataxia, lower limb paresthesias, and amnesia. [ncbi.nlm.nih.gov]

  It was originally described as characterized by the triad of: acute confusion ataxia ophthalmoplegia Wernicke encephalopathy can evolve into the chronic form of thiamine deficiency known as Korsakoff psychosis, characterized by: memory loss (global amnesia [radiopaedia.org]

  Of patients surviving WE, an important percentage will manifest WKS, characterized by the following: retrograde amnesia (inability to recall information), anterograde amnesia (inability to assimilate new information), decreased spontaneity and initiative [emedicine.medscape.com]

  Korsakoff’s syndrome Characterised by: Anterograde amnesia (inability to form new memories) Retrograde amnesia (inability to remember old memories) Confabulation (fabricating/false perceptions of memories) Hallucinations The damage to the memory is mostly [dundeemedstudentnotes.wordpress.com]

The diagnosis of WE can be made only if clinical suspicion exists for this condition, which is based on findings obtained during history taking and a physical examination, the two most important parts of the workup. Information about preexisting conditions that could've caused WE may be provided either by the patient him/herself or from family members/friends if the patient presents with confusion and is unable to provide adequate answers, whereas the progression of symptoms is also of great importance. Moreover, gait disturbances, ophthalmoplegia or nystagmus, and an altered mental state are all confirmed during the physical examination, and the diagnosis should be suspected in all patients who present with two of the three mentioned symptoms accompanied by dietary insufficiency (known as the Caine criteria) [1] [2] [3] [4]. If clinical criteria are fulfilled, laboratory and imaging studies must be promptly employed to confirm WE. Although no specific markers in blood suggest WE, a thorough biochemical workup comprised of a complete blood count (CBC), liver and kidney function tests, serum electrolytes, arterial blood gas (ABG) analyses and evaluation of inflammatory parameters is vital. On the other hand, alterations in the T2 signal intensity in the mammillary bodies, periaqueductal areas, and the medial thalami are characteristic features of WE on magnetic resonance imaging (MRI), the recommended imaging study in this group of patients [1] [5] [7]. Signal intensities of the cerebellum, cerebral cortex, as well as cranial nerve, dentate, caudate and red nuclei are less common but reported signs of WE on MRI [5]. Thiamine levels are not routinely measured, as its exact concentration in the CNS cannot be determined based on serum values, indicating that the diagnosis rests on clinical and MRI findings.

• Thiamine Decreased

  Alcoholics with a history of nutritional deficiency, who present with slightly lower TDP levels than those without such history may be more susceptible to the combined effects of alcohol and thiamine decreases, or lower TDP levels may be an enduring marker [nature.com]

• Glucose Increased

  Because glucose increases thiamine demand and will worsen encephalopathy, IV glucose infusions must be administered AFTER thiamine ! [amboss.com]

[…] and prognosis Treatment of acute Wernicke-Korsakoff syndrome is with intravenous thiamine hydrochloride, along with other vitamins/minerals. [radiopaedia.org]

Here we review representative cases of both conditions to highlight specific and relevant neurologic features that prompted effective diagnosis and treatment. [ncbi.nlm.nih.gov]

Where there is no response, treatment may be discontinued after two or three days. [clinicaladvisor.com]

The disorder may remit with treatment, persist, or degenerate into Korsakoff psychosis. Treatment consists of thiamin and supportive measures. [merckmanuals.com]

[…] can also be seen in the same regions, most commonly of the mamillary bodies 4 DWI/ADC: restricted diffusion can also be seen in the same regions 4 MR spectroscopy: may show decreased or normal NAA with the notable presence of lactate 4 Treatment and prognosis [radiopaedia.org]

Delay in diagnosis, particularly in obese individuals due to lack of suspicion, can lead to grim prognosis. [ncbi.nlm.nih.gov]

[…] level low non-specific Erythrocyte thiamine transketolase can establish thiamine deficiency Differential Alcohol intoxication Early Alzheimer's disease Treatment Intravenous thiamine administer immediately leads to improvement of reversible symptoms Prognosis [medbullets.com]

Etiology Thiamine deficiency results from malnutrition or malabsorption, which can occur for a number of reasons 6,7 : alcohol abuse (up to 90% in industrialised countries 5 ) starvation/fasting prolonged total parenteral nutrition without supplementation [radiopaedia.org]

Any patient with coma of unknown etiology should be given parenteral thiamine. [ncbi.nlm.nih.gov]

More than half a century lapsed before the common etiology of thiamine deficiency was discovered as the cause of the signs, symptoms, and link between these conditions (for historical reviews, see Charness, et al. 1989 ; Victor, et al. 1989 ). [doi.org]

However, these tests, as well as laboratory tests (eg, blood tests, glucose, CBC, liver function tests, ABG measurements, toxicology screening), should typically be done to rule out other etiologies. [merckmanuals.com]

[…] alpha-ketoglutarate dehydrogenase increased thiamine demand when metabolic demand is increased or increased glucose intake must give thiamine before glucose administration seen in chronic alcoholism, and other conditions of poor nutritions ( e.g., malabsorption) Epidemiology [medbullets.com]

In this review, we provide an update on the factors and clinical settings that predispose to Wernicke's encephalopathy, and discuss the most recent insights into epidemiology, pathophysiology, genetics, diagnosis, and treatment. [ncbi.nlm.nih.gov]

Epidemiology  The 6 incidence can be as high as 12.5% in a population of alcoholics.  The prevalence approximately 2%.  The male-to-female ratio is 1.7 : 1  Average age at onset is 50 years. 7. [slideshare.net]

[…] syndrome resulting from thiamine (vitamin B1) deficiency Korsakoff syndrome: a disproportionate impairment in memory relative to other features of cognition secondary to thiamine deficiency that usually follows or accompanies Wernicke encephalopathy Epidemiology [pathologyoutlines.com]

However, epidemiological data on TD and depression are scarce. [doi.org]

Increased lactate and typical MR imaging findings are discussed in the context of the known pathophysiology of Wernicke encephalopathy. [ncbi.nlm.nih.gov]

and Complications Prevention adeqaute thiamine intake Complications lead to Korsakoff syndrome if Wernicke's encephalopathy is not treated Please rate topic. [medbullets.com]

Abstract Background: Although Wernicke encephalopathy (WE) is a preventable and treatable disease it still often remains undiagnosed during life. Objectives: To create practical guidelines for diagnosis, management and prevention of the disease. [doi.org]

Although Wernicke encephalopathy (WE) is a preventable and treatable disease it still often remains undiagnosed during life. To create practical guidelines for diagnosis, management and prevention of the disease. [ncbi.nlm.nih.gov]

Prevention and treatment of Wernicke’s encephalopathy (WE) in the Accident & Emergency (A&E) department 1. [alcalc.oxfordjournals.org]

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3. Chamorro AJ, Marcos-Martin M, Martin-Polo J, Garcia-Diez LC, Luna G. Wernicke encephalopathy in alcoholics with diabetic ketoacidosis. Intern Med. 2009;48(13):1187-1189.
4. Udyavara Kudru C, Kaniyoor Nagiri S, Rao S. Wernicke’s encephalopathy in a patient with gastric carcinoma: a diagnosis not to miss. BMJ Case Rep. 2014;2014:bcr2013203511.
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6. Delavar Kasmaei H, Baratloo A, Soleymani M, Nasiri Z. Imaging-Based Diagnosis of Wernicke Encephalopathy: A Case Report. Trauma Mon. 2014;19(4):e17403.
7. Zuccoli G, Gallucci M, Capellades J, et al. Wernicke encephalopathy: MR findings at clinical presentation in twenty-six alcoholic and nonalcoholic patients. AJNR Am J Neuroradiol. 2007;28(7):1328-1331.