Wernicke encephalopathy

The classic triad of symptoms found in Wernicke encephalopathy is:{{cite journal | vauthors = Lough ME | title = Wernicke's encephalopathy: expanding the diagnostic toolbox | journal = Neuropsychology Review | volume = 22 | issue = 2 | pages = 181–194 | date = June 2012 | pmid = 22577001 | doi = 10.1007/s11065-012-9200-7 | s2cid = 18884274 }}

• Ophthalmoplegia: later expanded to include other eye movement disorders; typically affecting the lateral rectus muscle. Lateral nystagmus is the most commonly seen disorder, but lateral rectus palsy—usually bilateral—is common, as well.
• Ataxia: later expanded to include imbalance or any cerebellar dysfunction.
• Confusion: later expanded to include any neuropsychological disturbances. Prevalent in roughly eight in 10 diagnosed cases.{{medical citation needed|date=February 2025}}

Other possible symptoms include:

• Pupillary changes, Retinal haemorrhage, papilledema,{{cite journal | vauthors = Mumford CJ | title = Papilloedema delaying diagnosis of Wernicke's encephalopathy in a comatose patient | journal = Postgraduate Medical Journal | volume = 65 | issue = 764 | pages = 371–373 | date = June 1989 | pmid = 2608577 | pmc = 2429353 | doi = 10.1136/pgmj.65.764.371 }} and impaired vision and hearing.{{cite journal | vauthors = Chitra S, Lath KV | title = Wernicke's encephalopathy with visual loss in a patient with hyperemesis gravidarum | journal = The Journal of the Association of Physicians of India | volume = 60 | pages = 53–56 | date = May 2012 | pmid = 23029727 }}{{cite journal | vauthors = Flabeau O, Foubert-Samier A, Meissner W, Tison F | title = Hearing and seeing: Unusual early signs of Wernicke encephalopathy | journal = Neurology | volume = 71 | issue = 9 | pages = 694 | date = August 2008 | pmid = 18725598 | doi = 10.1212/01.wnl.0000324599.66359.b1 | doi-access = free }}{{cite journal | vauthors = Jethava A, Dasanu CA | title = Acute Wernicke encephalopathy and sensorineural hearing loss complicating bariatric surgery | journal = Connecticut Medicine | volume = 76 | issue = 10 | pages = 603–605 | year = 2012 | pmid = 23243762 }}
• Fatiguability, apathy, irritability, drowsiness, psychological slowing and/or motor slowing.
• Dysphagia,{{cite book | vauthors = Puiggros C |title=Tratado de Neurología |date=1994 |publisher=Editorial Libro del Año |location=Madrid |isbn=9788487748547 | pages = 823–824 }} blushing, sleep apnea, epilepsy{{cite journal | vauthors = Meierkord H, Boon P, Engelsen B, Göcke K, Shorvon S, Tinuper P, Holtkamp M | title = EFNS guideline on the management of status epilepticus in adults | journal = European Journal of Neurology | volume = 17 | issue = 3 | pages = 348–355 | date = March 2010 | pmid = 20050893 | doi = 10.1111/j.1468-1331.2009.02917.x | s2cid = 1032139 | doi-access = | url = https://biblio.ugent.be/publication/936808/file/936994 | url-access = subscription }} and stupor.
• Lactic acidosis.{{cite journal | vauthors = Kondo K, Fujiwara M, Murase M, Kodera Y, Akiyama S, Ito K, Takagi H | title = Severe acute metabolic acidosis and Wernicke's encephalopathy following chemotherapy with 5-fluorouracil and cisplatin: case report and review of the literature | journal = Japanese Journal of Clinical Oncology | volume = 26 | issue = 4 | pages = 234–236 | date = August 1996 | pmid = 8765181 | doi = 10.1093/oxfordjournals.jjco.a023220 | doi-access = free }}
• Memory impairment, amnesia,{{cite journal | vauthors = Becker JT, Furman JM, Panisset M, Smith C | title = Characteristics of the memory loss of a patient with Wernicke-Korsakoff's syndrome without alcoholism | journal = Neuropsychologia | volume = 28 | issue = 2 | pages = 171–179 | year = 1990 | pmid = 2314572 | doi = 10.1016/0028-3932(90)90099-A | s2cid = 41693535 }} depression,{{cite journal | vauthors = Zhang G, Ding H, Chen H, Ye X, Li H, Lin X, Ke Z | title = Thiamine nutritional status and depressive symptoms are inversely associated among older Chinese adults | journal = The Journal of Nutrition | volume = 143 | issue = 1 | pages = 53–58 | date = January 2013 | pmid = 23173173 | pmc = 3521461 | doi = 10.3945/jn.112.167007 }} and psychosis.{{cite journal | vauthors = Worden RW, Allen HM | title = Wernicke's encephalopathy after gastric bypass that masqueraded as acute psychosis: a case report | journal = Current Surgery | volume = 63 | issue = 2 | pages = 114–116 | year = 2006 | pmid = 16520112 | doi = 10.1016/j.cursur.2005.06.004 }}{{cite journal | vauthors = Jiang W, Gagliardi JP, Raj YP, Silvertooth EJ, Christopher EJ, Krishnan KR | title = Acute psychotic disorder after gastric bypass surgery: differential diagnosis and treatment | journal = The American Journal of Psychiatry | volume = 163 | issue = 1 | pages = 15–19 | date = January 2006 | pmid = 16390883 | doi = 10.1176/appi.ajp.163.1.15 }}
• Hypothermia,{{cite journal | vauthors = Truswell AS | title = Australian experience with the Wernicke-Korsakoff syndrome | journal = Addiction | volume = 95 | issue = 6 | pages = 829–832 | date = June 2000 | pmid = 10946433 | doi = 10.1046/j.1360-0443.2000.9568291.x }}{{cite journal | vauthors = Lindberg MC, Oyler RA | title = Wernicke's encephalopathy | journal = American Family Physician | volume = 41 | issue = 4 | pages = 1205–1209 | date = April 1990 | pmid = 2181837 }}{{cite journal | vauthors = Mann MW, Degos JD | title = [Hypothermia in Wernicke's encephalopathy] | language = fr | journal = Revue Neurologique | volume = 143 | issue = 10 | pages = 684–686 | year = 1987 | pmid = 3423584 | trans-title = Hypothermia in Wernicke's encephalopathy | id = {{INIST|7514445}} }} polyneuropathy,{{cite book | vauthors = Reinhard R |title=Color Atlas of Neurology |isbn=978-1-58890-191-0|year=2004 |publisher=Thieme }}{{page needed|date=June 2014}}{{failed verification|was p.148, but I can't find it there|date=June 2014}} and hyperhidrosis.{{cite book |last1=Biller J |title=The Interface of Neurology & Internal Medicine |date=2008 |publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins |location=Philadelphia |isbn=978-0-7817-7906-7|page=444}}

Although hypothermia is usually diagnosed with a body temperature of 35 °C (95 °F) or less, incipient cooling caused by deregulation in the central nervous system (CNS) needs to be monitored because it can promote the development of an infection. The patient may report feeling cold, followed by mild chills, cold skin, moderate pallor, tachycardia, hypertension, tremor, or piloerection. External warming techniques are advised to prevent hypothermia.{{citation needed|date=December 2020}}

Among the frequently altered functions is the cardio-circulatory. There may be tachycardia, dyspnea, chest pain, orthostatic hypotension, changes in heart rate and blood pressure.{{cite book | vauthors = Rohkamm R |title=Color Atlas of Neurology |page=148 |isbn=978-1-58890-191-0 |chapter=Hemodynamic abnormalities |chapter-url=https://books.google.com/books?id=EK08J953yzgC&pg=PA148|year=2004 |publisher=Thieme }} The lack of thiamine sometimes affects other major energy consumers, the myocardium, and also patients may have developed cardiomegaly.{{cite journal | vauthors = Ishiko T, Taguchi T, Takeguchi M, Saito H, Nanri K | title = [Case of Wernicke's encephalopathy and subacute combined degeneration of the spinal cord due to vitamin deficiency showing changes in the bilateral corpus striatum and cardiac arrest due to beriberi heart disease] | language = ja | journal = Brain and Nerve = Shinkei Kenkyu No Shinpo | volume = 61 | issue = 9 | pages = 1069–1073 | date = September 2009 | pmid = 19803406 | url = http://medicalfinder.jp/ejournal/openUrl.do?issn=18816096&genre=article&volume=61&issue=9&spage=1069 | trans-title = Case of Wernicke's encephalopathy and subacute combined degeneration of the spinal cord due to vitamin deficiency showing changes in the bilateral corpus striatum and cardiac arrest due to beriberi heart disease }} Heart failure with lactic acidosis syndrome has been observed.{{cite journal | vauthors = Harper C, Fornes P, Duyckaerts C, Lecomte D, Hauw JJ | title = An international perspective on the prevalence of the Wernicke-Korsakoff syndrome | journal = Metabolic Brain Disease | volume = 10 | issue = 1 | pages = 17–24 | date = March 1995 | pmid = 7596325 | doi = 10.1007/BF01991779 | s2cid = 9751459 }} Cardiac abnormalities are an aspect of the WE, which was not included in the traditional approach, and are not classified as a separate disease.

Infections have been pointed out as one of the most frequent triggers of death in WE. Furthermore, infections are usually present in pediatric cases.{{cite journal | vauthors = Vasconcelos MM, Silva KP, Vidal G, Silva AF, Domingues RC, Berditchevsky CR | title = Early diagnosis of pediatric Wernicke's encephalopathy | journal = Pediatric Neurology | volume = 20 | issue = 4 | pages = 289–294 | date = April 1999 | pmid = 10328278 | doi = 10.1016/s0887-8994(98)00153-2 }}{{cite journal | vauthors = Fattal-Valevski A, Kesler A, Sela BA, Nitzan-Kaluski D, Rotstein M, Mesterman R, Toledano-Alhadef H, Stolovitch C, Hoffmann C, Globus O, Eshel G | display-authors = 6 | title = Outbreak of life-threatening thiamine deficiency in infants in Israel caused by a defective soy-based formula | journal = Pediatrics | volume = 115 | issue = 2 | pages = e233–e238 | date = February 2005 | pmid = 15687431 | doi = 10.1542/peds.2004-1255 | s2cid = 2230681 | doi-access = }}

In the last stage, other symptoms may occur: hyperthermia, increased muscle tone, spastic paralysis, choreic dyskinesias, and coma.{{citation needed|date=December 2020}}

Because of the frequent involvement of the heart, eyes, and peripheral nervous system, several authors prefer to call it Wernicke disease rather than simply encephalopathy.

Early symptoms are nonspecific,{{cite web | vauthors = Johnson LE | date = November 2022 | title = Thiamin Deficiency | work = Merk Manuals | url = http://www.merckmanuals.com/professional/nutritional_disorders/vitamin_deficiency_dependency_and_toxicity/thiamin.html?qt=wernicke%20encephalopathy&alt=sh }} and it has been stated that WE may present nonspecific findings.{{cite journal | vauthors = Sechi G, Serra A | title = Wernicke's encephalopathy: new clinical settings and recent advances in diagnosis and management | journal = The Lancet. Neurology | volume = 6 | issue = 5 | pages = 442–455 | date = May 2007 | pmid = 17434099 | doi = 10.1016/S1474-4422(07)70104-7 | s2cid = 15523083 }} In Wernicke Korsakoff's syndrome some single symptoms are present in about one-third.{{cite book | vauthors = Shand F, Gates J, Fawcett J, Mattick R | date = October 2003 | title = Guidelines for the Treatment of Alcohol Problems | chapter = Wernicke Korsakoff's syndrome | publisher = National Drug and Alcohol Research Centre, Commonwealth of Australia | isbn = 978-0-642-82383-0 | page = 48 | url = http://www.alcohol.gov.au/internet/alcohol/publishing.nsf/Content/2C3FC9166082567DCA257260007F81F8/$File/alcprobguide.pdf | archive-url = https://web.archive.org/web/20140214092650/http://www.alcohol.gov.au/internet/alcohol/publishing.nsf/Content/2C3FC9166082567DCA257260007F81F8/$File/alcprobguide.pdf | archive-date = 14 February 2014 }}

Depending on the location of the brain lesion, different symptoms are more frequent:{{citation needed|date=December 2020}}

• Brainstem tegmentum. – Ocular: pupillary changes. Extraocular muscle palsy; gaze palsy: nystagmus.
• Hypothalamus. Medulla: dorsal nuc. of vagus. – Autonomic dysfunction: temperature, cardiocirculatory, respiratory.
• Medulla: vestibular region. Cerebellum. – Ataxia.
• Dorsomedial nuc. of the thalamus. Mammillary bodies. – Amnestic syndrome for recent memory.

Mamillary lesions are characteristic-small petechial hemorrhages.

• Diffuse cerebral dysfunction.- Altered cognition: global confusional state.
• Brainstem: periaqueductal gray.- Reduction of consciousness{{cite book | vauthors = Haberland C | title = Clinical neuropathology: text and color atlas | date = 2007 | publisher = Demos Medical Publishing | page = 200 | isbn = 978-1-888799-97-2}}
• Hypothalamic lesions may also affect the immune system, which is known in people who consume excessive amounts of alcohol, causing dysplasias and infections.

Korsakoff syndrome, characterised by memory impairment, confabulation, confusion, and personality changes, has a strong and recognised link with WE.{{cite journal | vauthors = Thomson AD, Guerrini I, Marshall EJ | title = The evolution and treatment of Korsakoff's syndrome: out of sight, out of mind? | journal = Neuropsychology Review | volume = 22 | issue = 2 | pages = 81–92 | date = June 2012 | pmid = 22569770 | pmc = 3545191 | doi = 10.1007/s11065-012-9196-z }} A very high percentage of patients with Wernicke–Korsakoff syndrome also have peripheral neuropathy, and many people who consume excess alcohol have this neuropathy without other neurologic signs or symptoms.{{cite book | chapter = Chapter 443 | veditors = Goldman L, Ausiello DA, Arend W, Armitage JO, Clemmons D, Drazen J, Griggs R, LaRusso N, Newman J, Foster E | display-editors = 6 | title = Cecil Medicine | edition = 23rd | date = 2007| publisher = Saunders, Elsevier | isbn = 978-1-4160-4478-9 }} Korsakoff's occurs much more frequently in WE due to chronic alcoholism. It is uncommon among those who do not consume excessive amounts of alcohol. Up to 80% of WE patients who misuse alcohol develop Korsakoff's syndrome. In Korsakoff's, atrophy of the thalamus and the mammillary bodies and frontal lobe involvement is usually observed. In a study, half of Wernicke–Korsakoff cases had good recovery from the amnesic state, which may take from 2 months to 10 years.

Wernicke encephalopathy has classically been thought of as a disease solely of people who drink excessive amounts of alcohol, but it is also found in the chronically undernourished, and in recent years has been discovered post bariatric surgery. Without being exhaustive, the documented causes of Wernicke encephalopathy have included:

• pancreatitis, liver dysfunction, chronic diarrhea, celiac disease, Crohn's disease, uremia, thyrotoxicosis{{MedlinePlusEncyclopedia|000771|Wernicke-Korsakoff syndrome}}
• vomiting, hyperemesis gravidarum, malabsorption, gastrointestinal surgery or diseases
• incomplete parenteral nutrition, starvation/fasting
• chemotherapy, renal dialysis, diuretic therapy, stem cell/marrow transplantation
• cancer, AIDS,{{cite journal | vauthors = Ng KL, ((Nguyễn LT)) | title = The role of thiamine in HIV infection | journal = International Journal of Infectious Diseases | volume = 17 | issue = 4 | pages = e221–e227 | date = April 2013 | pmid = 23274124 | doi = 10.1016/j.ijid.2012.11.019 | doi-access = free }} Creutzfeldt–Jakob disease,{{cite journal | vauthors = Rosen A, van Kuilenburg A, Assmann B, Kuhlen M, Borkhardt A | title = Severe encephalopathy, lactic acidosis, vegetative instability and neuropathy with 5-Fluorouracil treatment – pyrimidine degradation defect or beriberi? | journal = Case Reports in Oncology | volume = 4 | issue = 2 | pages = 371–376 | date = May 2011 | pmid = 21941485 | pmc = 3177792 | doi = 10.1159/000328803 }} febrile infections
• this disease may even occur in some people with normal, or even high blood thiamine levels, or people with deficiencies in intracellular transport of this vitamin. Selected genetic mutations, including presence of the X-linked transketolase-like 1 gene, SLC19A2 thiamine transporter protein mutations, and the aldehyde dehydrogenase-2 gene, which may predispose to alcohol use disorder. The APOE epsilon-4 allele, involved in Alzheimer's disease, may increase the chance of developing neurological symptoms.

Thiamine deficiency and errors of thiamine metabolism are believed to be the primary cause of Wernicke encephalopathy. Thiamine, also called B₁, helps to break down glucose. Specifically, it acts as an essential coenzyme to the TCA cycle and the pentose phosphate shunt. Thiamine is first metabolised to its more active form, thiamine diphosphate (TDP), before it is used. The body only has 2–3 weeks of thiamine reserves, which are readily exhausted without intake, or if depletion occurs rapidly, such as in chronic inflammatory states or in diabetes. Thiamine is involved in:{{cite journal | vauthors = Martin PR, Singleton CK, Hiller-Sturmhöfel S | title = The role of thiamine deficiency in alcoholic brain disease | journal = Alcohol Research & Health | volume = 27 | issue = 2 | pages = 134–142 | year = 2003 | pmid = 15303623 | pmc = 6668887 }}

1. Metabolism of carbohydrates, releasing energy.
2. Production of neurotransmitters including glutamic acid and GABA.
3. Lipid metabolism, necessary for myelin production.
4. Amino acid modification. Probably linked to the production of taurine, of great cardiac importance.{{cite journal | vauthors = Soukoulis V, Dihu JB, Sole M, Anker SD, Cleland J, Fonarow GC, Metra M, Pasini E, Strzelczyk T, Taegtmeyer H, Gheorghiade M | display-authors = 6 | title = Micronutrient deficiencies an unmet need in heart failure | journal = Journal of the American College of Cardiology | volume = 54 | issue = 18 | pages = 1660–1673 | date = October 2009 | pmid = 19850206 | doi = 10.1016/j.jacc.2009.08.012 | doi-access = free }}{{cite journal | vauthors = Lee JH, Jarreau T, Prasad A, Lavie C, O'Keefe J, Ventura H | title = Nutritional assessment in heart failure patients | journal = Congestive Heart Failure | volume = 17 | issue = 4 | pages = 199–203 | year = 2011 | pmid = 21790970 | doi = 10.1111/j.1751-7133.2011.00239.x | doi-access = }}

The primary neurological-related injury caused by thiamine deficiency in WE is three-fold: oxidative damage, mitochondrial injury leading to apoptosis, and directly stimulating a pro-apoptotic pathway.{{cite journal | vauthors = Hirsch JA, Parrott J | title = New considerations on the neuromodulatory role of thiamine | journal = Pharmacology | volume = 89 | issue = 1–2 | pages = 111–116 | year = 2012 | pmid = 22398704 | doi = 10.1159/000336339 | s2cid = 22555167 }} Thiamine deficiency affects both neurons and astrocytes, glial cells of the brain. Thiamine deficiency alters the glutamate uptake of astrocytes, through changes in the expression of astrocytic glutamate transporters EAAT1 and EAAT2, leading to excitotoxicity. Other changes include those to the GABA transporter subtype GAT-3, GFAP, glutamine synthetase, and the Aquaporin 4 channel.{{cite journal | vauthors = Hazell AS | title = Astrocytes are a major target in thiamine deficiency and Wernicke's encephalopathy | journal = Neurochemistry International | volume = 55 | issue = 1–3 | pages = 129–135 | year = 2009 | pmid = 19428817 | doi = 10.1016/j.neuint.2009.02.020 | s2cid = 12615886 }} Focal lactic acidosis also causes secondary oedema, oxidative stress, inflammation and white matter damage.{{cite journal | vauthors = Hazell AS, Todd KG, Butterworth RF | title = Mechanisms of neuronal cell death in Wernicke's encephalopathy | journal = Metabolic Brain Disease | volume = 13 | issue = 2 | pages = 97–122 | date = June 1998 | pmid = 9699919 | doi = 10.1023/A:1020657129593 | s2cid = 25130884 }}

File:Cerebellum small.gif

Despite its name, WE is not related to Wernicke's area, a region of the brain associated with speech and language interpretation.

Brain lesions in WE are usually credited to focal lactic acidosis. An absence of thiamine can lead to too much pyruvate within the cells since it is not available to help convert pyruvate through the TCA cycle. An increase in pyruvate causes an increase in lactate concentration leading to focal lactic acidosis.{{Cite journal |last1=Kohnke |first1=Sara |last2=Meek |first2=Claire L |date=January 2021 |title=Don't seek, don't find: The diagnostic challenge of Wernicke's encephalopathy |journal=Annals of Clinical Biochemistry: International Journal of Laboratory Medicine |language=en |volume=58 |issue=1 |pages=38–46 |doi=10.1177/0004563220939604 |issn=0004-5632 |pmc=7791272 |pmid=32551830}}

Lesions can be reversed in most cases with immediate supplementation of thiamine.{{citation needed|date=May 2024}}

Lesions are usually symmetrical in the periventricular region, diencephalon, the midbrain, hypothalamus, and cerebellar vermis. Brainstem lesions may include cranial nerve III, IV, VI and VIII nuclei, the medial thalamic nuclei, and the dorsal nucleus of the vagus nerve. Oedema may be found in the regions surrounding the third ventricle, and fourth ventricle, also appearing petechiae and small hemorrhages. Chronic cases can present the atrophy of the mammillary bodies.{{cite journal | vauthors = Zuccoli G, Pipitone N | title = Neuroimaging findings in acute Wernicke's encephalopathy: review of the literature | journal = AJR. American Journal of Roentgenology | volume = 192 | issue = 2 | pages = 501–508 | date = February 2009 | pmid = 19155417 | doi = 10.2214/AJR.07.3959 | s2cid = 32749934 }}

In 1949, the idea that WE lesions are a result of a disruption to the blood-brain barrier was introduced. Large proteins passing into the brain can put neurological tissue at risk of toxic effects. The blood-brain barrier junctions are typically found to have WE lesions located at that region of the brain.

An altered blood–brain barrier may cause a perturbed response to certain drugs and foods.{{cite web | vauthors = Cernicchiaro L | date = September 2017 | title = Wernicke's Disease (or Wernicke's Encephalopathy). Symptoms and new treatments. Clinical and practical approach. Daily monitoring for twelve years of a reversed severe case. | url = http://enfermedad-de-wernicke.weebly.com/}} {{self-published inline|date=August 2015}}{{MEDRS|date=August 2015}}

Diagnosis of Wernicke encephalopathy or disease is made clinically.{{cite book | veditors = McPhee SJ, Papadakis MA, Rabow MW |title=Current medical diagnosis & treatment 2012|publisher=McGraw-Hill Medical|location=New York|isbn=978-0-07-176372-1|edition=51st|date=2011-09-12|url-access=registration |url= https://archive.org/details/currentmedicaldi00step|page=986}} Caine et al. in 1997 established criteria that Wernicke encephalopathy can be diagnosed in any patient with just two or more of the main symptoms noted above.{{cite journal | vauthors = Caine D, Halliday GM, Kril JJ, Harper CG | title = Operational criteria for the classification of chronic alcoholics: identification of Wernicke's encephalopathy | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 62 | issue = 1 | pages = 51–60 | date = January 1997 | pmid = 9010400 | pmc = 486695 | doi = 10.1136/jnnp.62.1.51 }} The sensitivity of the diagnosis by the classic triad was 23% but increased to 85% taking two or more of the four classic features. These criteria are challenged because all the cases he studied were people who drank excessive amounts of alcohol. Some consider it sufficient to suspect the presence of the disease with only one of the principal symptoms. Some British hospital protocols suspect WE with any one of these symptoms: confusion, decreased consciousness level (or unconsciousness, stupor or coma), memory loss, ataxia or unsteadiness, ophthalmoplegia or nystagmus, and unexplained hypotension with hypothermia. The presence of only one sign should be sufficient for treatment.{{cite report | publisher = East Kent Hospitals NHS Trust | title = Protocol for: The management of the alcohol withdrawal syndrome and Wernicke encephalopathy }}

The sensitivity of magnetic resonance imaging (MR) was 53% and the specificity was 93%. The reversible cytotoxic edema was considered the most characteristic lesion of WE. The location of the lesions were more frequently atypical among people who drank appropriate amounts of alcohol, while typical contrast enhancement in the thalamus and the mammillary bodies was observed frequently associated with alcohol misuse. These abnormalities may include:

• Dorsomedial thalami, periaqueductal gray matter, mamillary bodies, tectal plate and brainstem nuclei are commonly affected.{{cite journal | vauthors = Hegde AN, Mohan S, Lath N, Lim CC | title = Differential diagnosis for bilateral abnormalities of the basal ganglia and thalamus | journal = Radiographics | volume = 31 | issue = 1 | pages = 5–30 | date = 2011 | pmid = 21257930 | doi = 10.1148/rg.311105041 | s2cid = 207707771 }} Involvement is always bilateral and symmetric. Value of DWI in the diagnosis of WE is minimal. Axial FLAIR MRI images represent the best diagnostic MRI sequence. Contrast material may highlight involvement of the mamillary bodies.

There appears to be very little value for CT scans.

Thiamine can be measured using an erythrocyte transketolase activity assay, or by activation by measurement of in vitro thiamine diphosphate levels. Normal thiamine levels do not necessarily rule out the presence of WE, as this may be a patient with difficulties in intracellular transport.

There are hospital protocols for prevention, supplementing with thiamine in the presence of: history of alcohol misuse or related seizures, requirement for IV glucose, signs of malnutrition, poor diet, recent diarrhea or vomiting, peripheral neuropathy, intercurrent illness, delirium tremens or treatment for DTs, and others.{{cite web | vauthors = Attard A, Torrens N, Holvey C | title = Clinical Guideline: The Management of Wernicke's Encephalopathy (WE) | date = June 2012 | work = Guy's and St. Thomas Hospitals | url = http://www.guysandstthomas.nhs.uk/resources/our-services/acute-medicine-gi-surgery/elderly-care/alcohol-withdrawal-syndrome.pdf | archive-url= https://web.archive.org/web/20150709175514/http://www.guysandstthomas.nhs.uk/resources/our-services/acute-medicine-gi-surgery/elderly-care/alcohol-withdrawal-syndrome.pdf | archive-date=9 July 2015 }}{{cite web | vauthors = Wood VM | date = June 2006 | title = Guidelines for the Management of Alcohol Issues in the Acute Hospital Setting | work = Doncaster and Bassetlaw Hospitals | url = http://www.alcohollearningcentre.org.uk/_library/17__Doncaster_Guidelines_For_The_Management_Of_Patients_with_Alcohol_Misuse_In_The_Acute_General_Hospital_Setting.pdf | archive-url = https://web.archive.org/web/20130921054552/http://www.alcohollearningcentre.org.uk/_library/17__Doncaster_Guidelines_For_The_Management_Of_Patients_with_Alcohol_Misuse_In_The_Acute_General_Hospital_Setting.pdf |archive-date=21 September 2013 }}

Some experts advise parenteral thiamine should be given to all at-risk patients in the emergency department.

In the clinical diagnosis should be remembered that early symptoms are nonspecific, and it has been stated that WE may present nonspecific findings. There is consensus to provide water-soluble vitamins and minerals after gastric operations.{{Cite journal |last1=Habas |first1=Elmukhtar |last2=Farfar |first2=Kalifa |last3=Errayes |first3=Nada |last4=Rayani |first4=Amnna |last5=Elzouki |first5=Abdel-Naser |date=2023 |title=Wernicke Encephalopathy: An Updated Narrative Review |journal=Saudi Journal of Medicine & Medical Sciences |volume=11 |issue=3 |pages=193–200 |doi=10.4103/sjmms.sjmms_416_22 |doi-access=free |issn=1658-631X |pmid=37533659|pmc=10393093 }}

In some countries certain foods have been supplemented with thiamine, and have reduced WE cases. Improvement is difficult to quantify because they applied several different actions. Avoiding or moderating alcohol consumption and having adequate nutrition reduces one of the main risk factors in developing Wernicke–Korsakoff syndrome.{{citation needed|date=December 2020}}.

Most symptoms will improve quickly if deficiencies are treated early. Memory disorder may be permanent.

In patients suspected of WE, thiamine treatment should be started immediately. Blood should be immediately taken to test for thiamine, other vitamins and minerals levels. Following this an immediate intravenous or intramuscular dose of thiamine should be administered{{cite book | vauthors = Hauser S |title=Harrison's Neurology in Clinical Medicine. |date=2010 |publisher=McGraw-Hill Publishing |location=New York |isbn=978-0-07-174123-1 |edition=2nd}} two or three times daily. Thiamine administration is usually continued until clinical improvement ceases.

Considering the diversity of possible causes and several surprising symptomatologic presentations, and because there is low assumed risk of toxicity of thiamine, because the therapeutic response is often dramatic from the first day, some qualified authors indicate parenteral thiamine if WE is suspected, both as a resource for diagnosis and treatment. The diagnosis is highly supported by the response to parenteral thiamine, but is not sufficient to be excluded by the lack of it.{{cite journal | vauthors = Thomson AD, Cook CC, Guerrini I, Sheedy D, Harper C, Marshall EJ | title = Wernicke's encephalopathy revisited. Translation of the case history section of the original manuscript by Carl Wernicke 'Lehrbuch der Gehirnkrankheiten fur Aerzte and Studirende' (1881) with a commentary | journal = Alcohol and Alcoholism | location = Oxford, Oxfordshire | volume = 43 | issue = 2 | pages = 174–9 | date = 2008 | pmid = 18056751 | doi = 10.1093/alcalc/agm144 | doi-access = free }} Parenteral thiamine administration is associated with a very small risk of anaphylaxis.Thomson A, Guerrini I, Marshall EJ. "Incidence of Adverse Reactions to Parenteral Thiamine in the Treatment of Wernicke's Encephalopathy, and Recommendations." Alcohol and Alcoholism. 2019 Nov;54(6):609-614. doi:https://doi.org/10.1093/alcalc/agy091

People who consume excessive amounts of alcohol may have poor dietary intakes of several vitamins, and impaired thiamine absorption, metabolism, and storage; they may thus require higher doses.{{cite book |title=Current Medical Diagnosis & Treatment 2012 |date=2009 |publisher=McGraw-Hill Medical |location=New York |isbn=978-0-07-176372-1 |edition=48th}}

If glucose is given, such as in people with an alcohol use disorder who are also hypoglycaemic, thiamine must be given concurrently. If this is not done, the glucose will rapidly consume the remaining thiamine reserves, exacerbating this condition.

The observation of edema in MR, and also the finding of inflation and macrophages in necropsied tissues,{{cite book | vauthors = Powell SZ, Schochet Jr SS | chapter = Intoxications and Metabolic Diseases of the Central Nervous System | veditors = Nelson JS, Mena H, Parisi JE, Schochet SS | title = Principles and Practice of Neuropathology | publisher = Oxford University Press | date = March 2003 | page = 193 | isbn = 978-0-19-802907-6 }} has led to successful administration of antiinflammatories.{{cite journal | vauthors = Iwamoto Y, Okuda B, Miyata Y, Tachibana H, Sugita M | title = [Beneficial effect of steroid pulse therapy on Wernicke-Korsakoff syndrome due to hyperemesis gravidarum] | journal = Rinsho Shinkeigaku = Clinical Neurology | volume = 34 | issue = 6 | pages = 599–601 | date = June 1994 | pmid = 7955722 }}{{cite journal | vauthors = Warot P, Lesage R, Dupuys P | title = [Corticotherapy of the severe forms of the Gayet-Wernicke encephalopathy] | journal = Lille Medical | volume = 7 | pages = 123–124 | date = February 1962 | pmid = 14005025 }} (article in French)

Other nutritional abnormalities should also be looked for, as they may be exacerbating the disease.{{cite book| vauthors = Brown AH, Ropper RH |title=Principios de neurología de Adams y Victor |year=2007 |publisher=McGraw-Hill |location=México |isbn=978-9701057070 |pages=1132 | language = Spanish |edition=8th}}{{cite book| vauthors = Zarranz JJ |title=Neurologia.|year=2007|publisher=Harcourt Brace De Espana SA |location= Madrid, España|isbn=978-8480862288|pages=821 | language = Spanish |edition=4th}} In particular, magnesium, a cofactor of transketolase which may induce or aggravate the disease.

Other supplements may also be needed, including: cobalamin, ascorbic acid, folic acid, nicotinamide, zinc,{{cite book | vauthors = Harrison TR, Braunwald E, Agud Aparicio JL | title = Medicina Interna | page = 2462 | date = 2002 }}{{cite book | vauthors = Kelley WN, DeVita VT, DuPont HL, Harris ED, Hazzard WR |title=Medicina Interna |date=1990 |publisher=Médica Panamericana |location=Buenos Aires |isbn=9789500612401 |edition=1st | pages = 621, 974 }} phosphorus (dicalcium phosphate){{cite journal | vauthors = Thomson AD, Cook CC, Touquet R, Henry JA | title = The Royal College of Physicians report on alcohol: guidelines for managing Wernicke's encephalopathy in the accident and Emergency Department | journal = Alcohol and Alcoholism | volume = 37 | issue = 6 | pages = 513–521 | year = 2002 | pmid = 12414541 | doi = 10.1093/alcalc/37.6.513 | doi-access = }} and in some cases taurine, especially suitable when there cardiocirculatory impairment.{{cite journal | vauthors = Lourenço R, Camilo ME | title = Taurine: a conditionally essential amino acid in humans? An overview in health and disease | journal = Nutricion Hospitalaria | volume = 17 | issue = 6 | pages = 262–270 | year = 2002 | pmid = 12514918 | url = http://www.nutricionhospitalaria.com/pdf/3337.pdf }}{{cite journal | vauthors = Iwamoto Y, Okuda B, Miyata Y, Tachibana H, Sugita M | title = [Beneficial effect of steroid pulse therapy on Wernicke-Korsakoff syndrome due to hyperemesis gravidarum] | language = ja | journal = Rinsho Shinkeigaku = Clinical Neurology | volume = 34 | issue = 6 | pages = 599–601 | date = June 1994 | pmid = 7955722 }}

Patient-guided nutrition is suggested. In patients with Wernicke–Korsakoff syndrome, even higher doses of parenteral thiamine are recommended. Concurrent toxic effects of alcohol should also be considered.

There are no conclusive statistical studies, all figures are based on partial studies.

Wernicke's lesions were observed in 0.8 to 2.8% of the general population autopsies, and 12.5% of people with an alcohol use disorder. This figure increases to 35% of such individuals if including cerebellar damage due to lack of thiamine.{{cite journal | vauthors = Torvik A, Lindboe CF, Rogde S | title = Brain lesions in alcoholics. A neuropathological study with clinical correlations | journal = Journal of the Neurological Sciences | volume = 56 | issue = 2–3 | pages = 233–48 | date = November 1982 | pmid = 7175549 | doi = 10.1016/0022-510x(82)90145-9 | s2cid = 26100578 }}

Most autopsy cases were from people with an alcohol use disorder. Autopsy series were performed in hospitals on the material available which is unlikely to be representative of the entire population. Considering the slight affectations, previous to the generation of observable lesions at necropsy, the percentage should be higher. There is evidence to indicate that Wernicke encephalopathy is underdiagnosed.{{cite journal | vauthors = Harper CG, Giles M, Finlay-Jones R | title = Clinical signs in the Wernicke-Korsakoff complex: a retrospective analysis of 131 cases diagnosed at necropsy | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 49 | issue = 4 | pages = 341–345 | date = April 1986 | pmid = 3701343 | pmc = 1028756 | doi = 10.1136/jnnp.49.4.341 }}{{cite journal | vauthors = Harper C | title = Wernicke's encephalopathy: a more common disease than realised. A neuropathological study of 51 cases | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 42 | issue = 3 | pages = 226–231 | date = March 1979 | pmid = 438830 | pmc = 490724 | doi = 10.1136/jnnp.42.3.226 }} For example, in one 1986 study, 80% of cases were diagnosed postmortem. Is estimated that only 5–14% of patients with WE are diagnosed in life.{{cite journal | vauthors = Blansjaar BA, Van Dijk JG | title = Korsakoff minus Wernicke syndrome | journal = Alcohol and Alcoholism (Oxford, Oxfordshire) | volume = 27 | issue = 4 | pages = 435–7 | date = July 1992 | pmid = 1418116 | doi = 10.1093/oxfordjournals.alcalc.a045269 }}

In a series of autopsy studies held in Recife, Brazil, it was found that only 7 out of 36 had consumed excessive amounts of alcohol, and only a small minority had malnutrition.{{cite journal | vauthors = Lana-Peixoto MA, Dos Santos EC, Pittella JE | title = Coma and death in unrecognized Wernicke's encephalopathy. An autopsy study | journal = Arquivos de Neuro-Psiquiatria | volume = 50 | issue = 3 | pages = 329–333 | date = September 1992 | pmid = 1308411 | doi = 10.1590/S0004-282X1992000300012 | doi-access = free }} In a reviewed of 53 published case reports from 2001 to 2011, the relationship with alcohol was also about 20% (10 out of 53 cases).

WE related to alcohol misuse is more common in males and is more common in females when not related to alcohol misuse. In alcohol-related cases, WE patients average the age of 40, and non-alcohol-related cases typically occur in younger people.

WE was first identified in 1881 by the German neurologist Carl Wernicke, although the link with thiamine was not identified until the 1930s.{{citation needed|date=May 2024}}

Carl Wernicke discovered the sensory center of speech. Wernicke figured out that Broca's area was not the only center of speech, it was also able to distinguish motor aphasia from sensory aphasia.{{Cite journal |last1=Bem Junior |first1=Luiz Severo |last2=Lemos |first2=Nilson Batista |last3=de Lima |first3=Luís Felipe Gonçalves |last4=Dias |first4=Artêmio José Araruna |last5=Neto |first5=Otávio da Cunha Ferreira |last6=de Lira |first6=Carlos Cezar Sousa |last7=Diniz |first7=Andrey Maia Silva |last8=Rabelo |first8=Nicollas Nunes |last9=Barroso |first9=Luciana Karla Viana |last10=Valença |first10=Marcelo Moraes |last11=de Azevedo Filho |first11=Hildo Rocha Cirne |date=2021-06-28 |title=The anatomy of the brain – learned over the centuries |url=http://surgicalneurologyint.com/surgicalint-articles/the-anatomy-of-the-brain-learned-over-the-centuries/ |journal=Surgical Neurology International |language=en |volume=12 |pages=319 |doi=10.25259/SNI_200_2021 |issn=2152-7806 |pmc=8326080 |pmid=34345460}} He also pointed to the possibility of conduction aphasia since he came to understand the arrangement of the brain's extrinsic and intrinsic connections. He demonstrated that the sensory information reached its corresponding area in the cerebral cortex through projection fibers. From there, this information, following the association system, would be distributed to different regions of the cortex, integrating sensory processing.

He reported three patients with WE, including two men (aged 33 and 36) who were alcoholics and one woman (aged 20) who ingested sulfuric acid, leading to pyloric stenosis. All three had ocular motor abnormalities and he performed an autopsy on each, providing a clinical-pathological correlation.{{Cite journal |last1=Isen |first1=Danielle R. |last2=Kline |first2=Lanning B. |date=2020-06-30 |title=Neuro-ophthalmic Manifestations of Wernicke Encephalopathy |journal=Eye and Brain |language=English |volume=12 |pages=49–60 |doi=10.2147/EB.S234078 |pmc=7335288 |pmid=32636690 |doi-access=free }}

A similar presentation of this disease was described by the Russian psychiatrist Sergei Korsakoff in a series of articles published 1887–1891; where the chronic version of WE was described as Korsakoff's Syndrome, involving symptoms of amnesia.{{cite journal | vauthors = Isenberg-Grzeda E, Kutner HE, Nicolson SE | title = Wernicke-Korsakoff-syndrome: under-recognized and under-treated | journal = Psychosomatics | volume = 53 | issue = 6 | pages = 507–516 | date = 2012-11-01 | pmid = 23157990 | doi = 10.1016/j.psym.2012.04.008 | doi-access = }}{{cite journal | vauthors = Sechi G, Serra A | title = Wernicke's encephalopathy: new clinical settings and recent advances in diagnosis and management | language = English | journal = The Lancet. Neurology | volume = 6 | issue = 5 | pages = 442–455 | date = May 2007 | pmid = 17434099 | doi = 10.1016/S1474-4422(07)70104-7 | s2cid = 15523083 }}

{{reflist}}

{{Medical resources

| ICD10 = {{ICD10|E|51|2||}} + {{ICD10|G32.8}}

| ICD9 = {{ICD9|291.1}}

| DiseasesDB =14107

| MedlinePlus =

| eMedicineSubj =

| eMedicineTopic =

| MeSH=D014899

}}

{{Nutritional pathology}}

{{Psychoactive substance use}}

Category:Alcohol and health

Category:Malnutrition

Category:Central nervous system disorders

Category:Vitamin deficiencies

Category:Thiamine

Category:Medical triads