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]

  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]

  Etiology Causes Thiamine deficiency is characteristically associated with chronic alcoholism, because it affects thiamine uptake and utilization. [2] In long-term alcoholics, malnutrition can reduce intestinal thiamine absorption by 70%, decreasing serum [emedicine.com]

• 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 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]

• Strabismus

  Simultaneously, unsteady gait and strabismus occurred. [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

  […] 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

  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]

  Gait ataxia is often a presenting physical examination manifestation. [12] Ataxia is likely to be a combination of polyneuropathy, cerebellar damage, and vestibular paresis. [emedicine.medscape.com]

• Confusion

  Wernicke's classic triad (confusion, ocular abnormalities, and ataxia) manifested in only 46.9% (23 of 49) of the patients. [ncbi.nlm.nih.gov]

  However, loss of balance and confusion may persist days to months, and memory loss may not completely resolve. [msdmanuals.com]

  […] thiamine, Show Information [Source] Wernicke encephalopathy is a syndrome characterised by ataxia, ophthalmoplegia, nystagmus, confusion, and impairment of short-term memory. [house.wikia.com]

• Nystagmus

  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]

  […] thiamine, Show Information [Source] Wernicke encephalopathy is a syndrome characterised by ataxia, ophthalmoplegia, nystagmus, confusion, and impairment of short-term memory. [house.wikia.com]

  Here we describe a teenage girl who develops vomiting after Roux-en-Y gastric bypass and presented with nystagmus, irritability, and ataxia. [pediatrics.aappublications.org]

  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

  […] confusion ataxia ophthalmoplegia (most commonly horizontal nystagmus and conjugate gaze palsies) Wernicke encephalopathy can evolve into the chronic form of thiamine deficiency known as Korsakoff psychosis, characterized by: memory loss (global amnesia) confabulation [radiopaedia.org]

  Chronic thiamine deficiency, especially in patients with alcohol use disorder, frequently evolves into Korsakoff syndrome, which is characterized by irreversible personality changes, anterograde and retrograde amnesia, and confabulation. [amboss.com]

  Wernicke's encephalopathy Pathology Symptoms nystagmus, gaze palsies, and ophthalmoplegia, especially of the lateral rectus muscles), gait ataxia, confusion, confabulation, and short-term memory los Treatments intravenous or intramuscular injection of [house.wikia.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]

  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]

• 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]

  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]

  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]

  […] acute confusion ataxia ophthalmoplegia (most commonly horizontal nystagmus and conjugate gaze palsies) Wernicke encephalopathy can evolve into the chronic form of thiamine deficiency known as Korsakoff psychosis, characterized by: memory loss (global amnesia [radiopaedia.org]

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, and treatment of the underlying cause (e.g. alcohol cessation). [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]

[…] can also be seen in the same regions, most commonly of the mammillary 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]

Even with psychiatric and psychological interventions, the prognosis for patients with Korsakoff syndrome remains poor. Etiology Wernicke encephalopathy and Korsakoff syndrome are caused by a severe deficiency of thiamine ( vitamin B1 ). [amboss.com]

Any patient with coma of unknown etiology should be given parenteral thiamine. [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]

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]

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]

[…] 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]

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]

Method The authors review the literature on the pathophysiology, presentation, and treatment of WKS, focusing on the acute identification and treatment of WE. [psychosomaticsjournal.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]

This is a more common disease than is generally recognised, one which can be readily treated and, more importantly, prevented by adequate nutrition. [ncbi.nlm.nih.gov]

This emphasizes the importance of awareness of this clinical entity and the need for early detection and prevention. [omicsonline.org]

This type of neglect is preventable and Powers Taylor LLP is committed to fighting for victims of Wernicke’s Encephalopathy or Wernicke-Korsakoff Syndrome due to delayed diagnosis. [powerstaylor.com]

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2. Day GS, del Campo CM. Wernicke encephalopathy: a medical emergency. CMAJ. 2014;186(8):E295.
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.