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Wernicke encephalopathy

Yuen T So, MD, PhD
Section Editor
Michael J Aminoff, MD, DSc
Deputy Editor
Janet L Wilterdink, MD


Wernicke-Korsakoff syndrome is the best known neurologic complication of thiamine (vitamin B1) deficiency [1]. The term refers to two different syndromes, each representing a different stage of the disease. Wernicke encephalopathy (WE) is an acute syndrome requiring emergent treatment to prevent death and neurologic morbidity. Korsakoff syndrome (KS) refers to a chronic neurologic condition that usually occurs as a consequence of WE.

In 1881, Carl Wernicke described an acute encephalopathy characterized by mental confusion, ophthalmoplegia, and gait ataxia and associated it with autopsy findings of punctate hemorrhages around the third and fourth ventricles and the aqueduct. A few years later, Russian psychiatrist Sergei Korsakoff described a chronic amnestic syndrome in which memory was impaired far out of proportion to other cognitive domains. While both observations were described in the context of chronic alcoholism, neither Wernicke nor Korsakoff initially recognized the relationship between the disorders, which was not appreciated until later by other investigators.

This topic will review Wernicke encephalopathy. Korsakoff syndrome and other chronic neurologic complications of alcohol abuse, including alcohol withdrawal are discussed separately. (See "Overview of the chronic neurologic complications of alcohol" and "Management of moderate and severe alcohol withdrawal syndromes".)


Prevalence — Typical brain lesions of Wernicke encephalopathy (WE) are observed at autopsy in 0.4 to 2.8 percent of the general population in the Western world, and the majority of affected patients are alcoholic [2,3]. The prevalence of WE lesions seen on autopsy was 12.5 percent of alcohol abusers in one report [4]. Among those with alcohol-related deaths, it has been reported to be even higher, 29 to 59 percent [5,6]. Autopsy studies have consistently revealed a higher incidence of Wernicke lesions in the general population than is predicted by clinical studies, suggesting that it is under-recognized clinically [1,7].

While cases of WE in men outnumber those in women, women appear to be more susceptible to developing WE than men. In several series, the female to male ratio for WE was higher than the ratio for alcohol dependence [1,7].

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Literature review current through: Nov 2017. | This topic last updated: Aug 30, 2016.
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  1. Victor, M, Adams, RA, Collins, GH. The Wernicke-Korsakoff syndrome and related disorders due to alcoholism and malnutrition. FA Davis, Philadelphia 1989.
  2. Harper C, Fornes P, Duyckaerts C, et al. An international perspective on the prevalence of the Wernicke-Korsakoff syndrome. Metab Brain Dis 1995; 10:17.
  3. Galvin R, Bråthen G, Ivashynka A, et al. EFNS guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy. Eur J Neurol 2010; 17:1408.
  4. Torvik A, Lindboe CF, Rogde S. Brain lesions in alcoholics. A neuropathological study with clinical correlations. J Neurol Sci 1982; 56:233.
  5. Naidoo DP, Bramdev A, Cooper K. Autopsy prevalence of Wernicke's encephalopathy in alcohol-related disease. S Afr Med J 1996; 86:1110.
  6. Skullerud K, Andersen SN, Lundevall J. Cerebral lesions and causes of death in male alcoholics. A forensic autopsy study. Int J Legal Med 1991; 104:209.
  7. Harper C. The incidence of Wernicke's encephalopathy in Australia--a neuropathological study of 131 cases. J Neurol Neurosurg Psychiatry 1983; 46:593.
  8. Lindboe CF, Løberg EM. Wernicke's encephalopathy in non-alcoholics. An autopsy study. J Neurol Sci 1989; 90:125.
  9. Sharma S, Sumich PM, Francis IC, et al. Wernicke's encephalopathy presenting with upbeating nystagmus. J Clin Neurosci 2002; 9:476.
  10. Gárdián G, Vörös E, Járdánházy T, et al. Wernicke's encephalopathy induced by hyperemesis gravidarum. Acta Neurol Scand 1999; 99:196.
  11. Spruill SC, Kuller JA. Hyperemesis gravidarum complicated by Wernicke's encephalopathy. Obstet Gynecol 2002; 99:875.
  12. Parkin AJ, Blunden J, Rees JE, Hunkin NM. Wernicke-Korsakoff syndrome of nonalcoholic origin. Brain Cogn 1991; 15:69.
  13. Vortmeyer AO, Hagel C, Laas R. Haemorrhagic thiamine deficient encephalopathy following prolonged parenteral nutrition. J Neurol Neurosurg Psychiatry 1992; 55:826.
  14. Suzuki Y, Matsuda T, Washio N, Ohtsuka K. Transition from upbeat to downbeat nystagmus observed in a patient with Wernicke's encephalopathy. Jpn J Ophthalmol 2005; 49:220.
  15. Chaves LC, Faintuch J, Kahwage S, Alencar Fde A. A cluster of polyneuropathy and Wernicke-Korsakoff syndrome in a bariatric unit. Obes Surg 2002; 12:328.
  16. Peltier G, Hermreck AS, Moffat RE, et al. Complications following gastric bypass procedures for morbid obesity. Surgery 1979; 86:648.
  17. Paulson GW, Martin EW, Mojzisik C, Carey LC. Neurologic complications of gastric partitioning. Arch Neurol 1985; 42:675.
  18. Foster D, Falah M, Kadom N, Mandler R. Wernicke encephalopathy after bariatric surgery: losing more than just weight. Neurology 2005; 65:1987; discussion 1847.
  19. Singh S, Kumar A. Wernicke encephalopathy after obesity surgery: a systematic review. Neurology 2007; 68:807.
  20. Aasheim ET. Wernicke encephalopathy after bariatric surgery: a systematic review. Ann Surg 2008; 248:714.
  21. Pittella JE, de Castro LP. Wernicke's encephalopathy manifested as Korsakoff's syndrome in a patient with promyelocytic leukemia. South Med J 1990; 83:570.
  22. Engel PA, Grunnet M, Jacobs B. Wernicke-Korsakoff syndrome complicating T-cell lymphoma: unusual or unrecognized? South Med J 1991; 84:253.
  23. Macleod AD. Wernicke's encephalopathy and terminal cancer: case report. Palliat Med 2000; 14:217.
  24. Bleggi-Torres LF, de Medeiros BC, Werner B, et al. Neuropathological findings after bone marrow transplantation: an autopsy study of 180 cases. Bone Marrow Transplant 2000; 25:301.
  25. Hung SC, Hung SH, Tarng DC, et al. Thiamine deficiency and unexplained encephalopathy in hemodialysis and peritoneal dialysis patients. Am J Kidney Dis 2001; 38:941.
  26. Jagadha V, Deck JH, Halliday WC, Smyth HS. Wernicke's encephalopathy in patients on peritoneal dialysis or hemodialysis. Ann Neurol 1987; 21:78.
  27. Descombes E, Dessibourg CA, Fellay G. Acute encephalopathy due to thiamine deficiency (Wernicke's encephalopathy) in a chronic hemodialyzed patient: a case report. Clin Nephrol 1991; 35:171.
  28. Davtyan DG, Vinters HV. Wernicke's encephalopathy in AIDS patient treated with zidovudine. Lancet 1987; 1:919.
  29. Schwenk J, Gosztonyi G, Thierauf P, et al. Wernicke's encephalopathy in two patients with acquired immunodeficiency syndrome. J Neurol 1990; 237:445.
  30. Soffer D, Zirkin H, Alkan M, Berginer VM. Wernicke's encephalopathy in acquired immune deficiency syndrome (AIDS): a case report. Clin Neuropathol 1989; 8:192.
  31. Kono S, Miyajima H, Yoshida K, et al. Mutations in a thiamine-transporter gene and Wernicke's-like encephalopathy. N Engl J Med 2009; 360:1792.
  32. Koguchi K, Nakatsuji Y, Abe K, Sakoda S. Wernicke's encephalopathy after glucose infusion. Neurology 2004; 62:512.
  33. Todd KG, Butterworth RF. Evaluation of the role of NMDA-mediated excitotoxicity in the selective neuronal loss in experimental Wernicke encephalopathy. Exp Neurol 1998; 149:130.
  34. Langlais PJ, Mair RG. Protective effects of the glutamate antagonist MK-801 on pyrithiamine-induced lesions and amino acid changes in rat brain. J Neurosci 1990; 10:1664.
  35. McLean J, Manchip S. Wernicke's encephalopathy induced by magnesium depletion. Lancet 1999; 353:1768.
  36. Martin PR, Singleton CK, Hiller-Sturmhöfel S. The role of thiamine deficiency in alcoholic brain disease. Alcohol Res Health 2003; 27:134.
  37. Thomson AD, Ryle PR, Shaw GK. Ethanol, thiamine and brain damage. Alcohol Alcohol 1983; 18:27.
  38. Blass JP, Gibson GE. Abnormality of a thiamine-requiring enzyme in patients with Wernicke-Korsakoff syndrome. N Engl J Med 1977; 297:1367.
  39. Mukherjee AB, Svoronos S, Ghazanfari A, et al. Transketolase abnormality in cultured fibroblasts from familial chronic alcoholic men and their male offspring. J Clin Invest 1987; 79:1039.
  40. Jeyasingham MD, Pratt OE, Burns A, et al. The activation of red blood cell transketolase in groups of patients especially at risk from thiamin deficiency. Psychol Med 1987; 17:311.
  41. Greenwood J, Jeyasingham M, Pratt OE, et al. Heterogeneity of human erythrocyte transketolase: a preliminary report. Alcohol Alcohol 1984; 19:123.
  42. McCool BA, Plonk SG, Martin PR, Singleton CK. Cloning of human transketolase cDNAs and comparison of the nucleotide sequence of the coding region in Wernicke-Korsakoff and non-Wernicke-Korsakoff individuals. J Biol Chem 1993; 268:1397.
  43. Heap LC, Pratt OE, Ward RJ, et al. Individual susceptibility to Wernicke-Korsakoff syndrome and alcoholism-induced cognitive deficit: impaired thiamine utilization found in alcoholics and alcohol abusers. Psychiatr Genet 2002; 12:217.
  44. Martin PR, McCool BA, Singleton CK. Molecular genetics of transketolase in the pathogenesis of the Wernicke-Korsakoff syndrome. Metab Brain Dis 1995; 10:45.
  45. Nixon PF. Is there a genetic component to the pathogenesis of the Wernicke-Korsakoff syndrome? Alcohol Alcohol 1984; 19:219.
  46. Wang JJ, Martin PR, Singleton CK. A transketolase assembly defect in a Wernicke-Korsakoff syndrome patient. Alcohol Clin Exp Res 1997; 21:576.
  47. Guerrini I, Thomson AD, Cook CC, et al. Direct genomic PCR sequencing of the high affinity thiamine transporter (SLC19A2) gene identifies three genetic variants in Wernicke Korsakoff syndrome (WKS). Am J Med Genet B Neuropsychiatr Genet 2005; 137B:17.
  48. Todd K, Butterworth RF. Mechanisms of selective neuronal cell death due to thiamine deficiency. Ann N Y Acad Sci 1999; 893:404.
  49. Torvik A. Two types of brain lesions in Wernicke's encephalopathy. Neuropathol Appl Neurobiol 1985; 11:179.
  50. Malamud, N, Skillicorn, SA. Relationship between the Wernicke and the Korsakoff syndrome: a clinicopathologic study of seventy cases. Arch Neurol Psychiat 1956; 76:586.
  51. Antunez E, Estruch R, Cardenal C, et al. Usefulness of CT and MR imaging in the diagnosis of acute Wernicke's encephalopathy. AJR Am J Roentgenol 1998; 171:1131.
  52. Harper CG, Giles M, Finlay-Jones R. Clinical signs in the Wernicke-Korsakoff complex: a retrospective analysis of 131 cases diagnosed at necropsy. J Neurol Neurosurg Psychiatry 1986; 49:341.
  53. Wallis WE, Willoughby E, Baker P. Coma in the Wernicke-Korsakoff syndrome. Lancet 1978; 2:400.
  54. Ghez C. Vestibular paresis: a clinical feature of Wernicke's disease. J Neurol Neurosurg Psychiatry 1969; 32:134.
  55. Goor C, Endtz LJ, Muller Kobold MJ. Electro-nystagmography for the diagnosis of vestibular dysfunction in the Wernicke-Korsakow syndrome. Clin Neurol Neurosurg 1975; 78:112.
  56. Victor M, Adams RD, Mancall EL. A restricted form of cerebellar cortical degeneration occurring in alcoholic patients. Arch Neurol 1959; 1:579.
  57. Wood B, Currie J, Breen K. Wernicke's encephalopathy in a metropolitan hospital. A prospective study of incidence, characteristics and outcome. Med J Aust 1986; 144:12.
  58. Choi KD, Oh SY, Kim HJ, Kim JS. The vestibulo-ocular reflexes during head impulse in Wernicke's encephalopathy. J Neurol Neurosurg Psychiatry 2007; 78:1161.
  59. Harper C. Wernicke's encephalopathy: a more common disease than realised. A neuropathological study of 51 cases. J Neurol Neurosurg Psychiatry 1979; 42:226.
  60. Fischbeck KH, Simon RP. Neurological manifestations of accidental hypothermia. Ann Neurol 1981; 10:384.
  61. Philip G, Smith JF. Hypothermia and Wernicke's encephalopathy. Lancet 1973; 2:122.
  62. O'Keeffe ST, Tormey WP, Glasgow R, Lavan JN. Thiamine deficiency in hospitalized elderly patients. Gerontology 1994; 40:18.
  63. Older MW, Dickerson JW. Thiamine and the elderly orthopaedic patient. Age Ageing 1982; 11:101.
  64. Pepersack T, Garbusinski J, Robberecht J, et al. Clinical relevance of thiamine status amongst hospitalized elderly patients. Gerontology 1999; 45:96.
  65. Yoneoka Y, Takeda N, Inoue A, et al. Acute Korsakoff syndrome following mammillothalamic tract infarction. AJNR Am J Neuroradiol 2004; 25:964.
  66. Renou P, Ducreux D, Batouche F, Denier C. Pure and acute Korsakoff syndrome due to a bilateral anterior fornix infarction: a diffusion tensor tractography study. Arch Neurol 2008; 65:1252.
  67. Caine D, Halliday GM, Kril JJ, Harper CG. Operational criteria for the classification of chronic alcoholics: identification of Wernicke's encephalopathy. J Neurol Neurosurg Psychiatry 1997; 62:51.
  68. Leigh, D. Erythrocyte transketolase activity in the Wernicke-Korsakoff syndrome. Br J Psychol 1981; 138:153.
  69. O'Keeffe ST. Thiamine deficiency in elderly people. Age Ageing 2000; 29:99.
  70. Lu J, Frank EL. Rapid HPLC measurement of thiamine and its phosphate esters in whole blood. Clin Chem 2008; 54:901.
  71. Davies SB, Joshua FF, Zagami AS. Wernicke's encephalopathy in a non-alcoholic patient with a normal blood thiamine level. Med J Aust 2011; 194:483.
  72. Warach, SJ, Charness, ME. Imaging the brain lesions of alcoholics. In: Neuroimaging: A Companion to Adams and Victor's Principles of Neurology, Greenberg, JO (Ed), McGraw-Hill, New York 1994. p.503.
  73. McDowell JR, LeBlanc HJ. Computed tomographic findings in Wernicke-Korsakoff syndrome. Arch Neurol 1984; 41:453.
  74. Mensing JW, Hoogland PH, Slooff JL. Computed tomography in the diagnosis of Wernicke's encephalopathy: a radiological-neuropathological correlation. Ann Neurol 1984; 16:363.
  75. Hofmann E, Friedburg H, Rasenack J, et al. [Wernicke's encephalopathy on CT and MR]. Rofo 1988; 148:97.
  76. Kitaguchi T, Kobayashi T, Tobimatsu S, et al. Computed tomography and magnetic resonance imaging in a young patient with Wernicke's encephalopathy. J Neurol 1987; 234:449.
  77. Roche SW, Lane RJ, Wade JP. Thalamic hemorrhages in Wernicke-Korsakoff syndrome demonstrated by computed tomography. Ann Neurol 1988; 23:312.
  78. Ostertun B, Dewes W, Hanisch E, Harder T. [MR tomography and computer tomography of alcohol-induced brain tissue changes]. Rofo 1990; 152:87.
  79. Gallucci M, Bozzao A, Splendiani A, et al. Wernicke encephalopathy: MR findings in five patients. AJNR Am J Neuroradiol 1990; 11:887.
  80. Yokote K, Miyagi K, Kuzuhara S, et al. Wernicke encephalopathy: follow-up study by CT and MR. J Comput Assist Tomogr 1991; 15:835.
  81. Yamashita M, Yamamoto T. Wernicke encephalopathy with symmetric pericentral involvement: MR findings. J Comput Assist Tomogr 1995; 19:306.
  82. Zuccoli G, Pipitone N. Neuroimaging findings in acute Wernicke's encephalopathy: review of the literature. AJR Am J Roentgenol 2009; 192:501.
  83. Doherty MJ, Watson NF, Uchino K, et al. Diffusion abnormalities in patients with Wernicke encephalopathy. Neurology 2002; 58:655.
  84. Elefante A, Puoti G, Senese R, et al. Non-alcoholic acute Wernicke's encephalopathy: role of MRI in non typical cases. Eur J Radiol 2012; 81:4099.
  85. Ha ND, Weon YC, Jang JC, et al. Spectrum of MR imaging findings in Wernicke encephalopathy: are atypical areas of involvement only present in nonalcoholic patients? AJNR Am J Neuroradiol 2012; 33:1398.
  86. Watson WD, Swallow CE, Landau ME. MR imaging and post LP headache. Neurology 2003; 61:1450.
  87. Liou KC, Kuo SF, Chen LA. Wernicke encephalopathy with atypical magnetic resonance imaging. Am J Emerg Med 2012; 30:2086.e1.
  88. Park SH, Kim M, Na DL, Jeon BS. Magnetic resonance reflects the pathological evolution of Wernicke encephalopathy. J Neuroimaging 2001; 11:406.
  89. Beh SC, Frohman TC, Frohman EM. Isolated mammillary body involvement on MRI in Wernicke's encephalopathy. J Neurol Sci 2013; 334:172.
  90. Charness ME. Intracranial voyeurism: revealing the mammillary bodies in alcoholism. Alcohol Clin Exp Res 1999; 23:1941.
  91. Charness, ME, DeLaPaz, RL. Periodic alternating nystagmus in an alcoholic with small mamillary bodies. Neurology 1988; 38 (Suppl):421.
  92. Charness ME, DeLaPaz RL. Mamillary body atrophy in Wernicke's encephalopathy: antemortem identification using magnetic resonance imaging. Ann Neurol 1987; 22:595.
  93. Wrenn KD, Murphy F, Slovis CM. A toxicity study of parenteral thiamine hydrochloride. Ann Emerg Med 1989; 18:867.
  94. Agabio R. Thiamine administration in alcohol-dependent patients. Alcohol Alcohol 2005; 40:155.
  95. Cook CC, Hallwood PM, Thomson AD. B Vitamin deficiency and neuropsychiatric syndromes in alcohol misuse. Alcohol Alcohol 1998; 33:317.
  96. McIntosh C, Chick J. Alcohol and the nervous system. J Neurol Neurosurg Psychiatry 2004; 75 Suppl 3:iii16.
  97. Thomson AD, Cook CC, Touquet R, et al. The Royal College of Physicians report on alcohol: guidelines for managing Wernicke's encephalopathy in the accident and Emergency Department. Alcohol Alcohol 2002; 37:513.
  98. Day E, Bentham P, Callaghan R, et al. Thiamine for Wernicke-Korsakoff Syndrome in people at risk from alcohol abuse. Cochrane Database Syst Rev 2004; :CD004033.
  99. Ambrose ML, Bowden SC, Whelan G. Thiamin treatment and working memory function of alcohol-dependent people: preliminary findings. Alcohol Clin Exp Res 2001; 25:112.
  100. Hoyumpa AM Jr. Alcohol and thiamine metabolism. Alcohol Clin Exp Res 1983; 7:11.
  101. Chu K, Kang DW, Kim HJ, et al. Diffusion-weighted imaging abnormalities in wernicke encephalopathy: reversible cytotoxic edema? Arch Neurol 2002; 59:123.
  102. Zhong C, Jin L, Fei G. MR Imaging of nonalcoholic Wernicke encephalopathy: a follow-up study. AJNR Am J Neuroradiol 2005; 26:2301.
  103. Carota A, Schnider A. Dramatic recovery from prolonged Wernicke-Korsakoff disease. Eur Neurol 2005; 53:45.
  104. Schabelman E, Kuo D. Glucose before thiamine for Wernicke encephalopathy: a literature review. J Emerg Med 2012; 42:488.
  105. Harper CG, Sheedy DL, Lara AI, et al. Prevalence of Wernicke-Korsakoff syndrome in Australia: has thiamine fortification made a difference? Med J Aust 1998; 168:542.
  106. Martin PR, Adinoff B, Weingartner H, et al. Alcoholic organic brain disease: nosology and pathophysiologic mechanisms. Prog Neuropsychopharmacol Biol Psychiatry 1986; 10:147.