Neuropsychology Review

, Volume 22, Issue 2, pp 170–180 | Cite as

Neuroimaging of Wernicke’s Encephalopathy and Korsakoff’s Syndrome

  • Young-Chul Jung
  • Sandra Chanraud
  • Edith V. Sullivan


There is considerable evidence that neuroimaging findings can improve the early diagnosis of Wernicke’s encephalopathy (WE) in clinical settings. The most distinctive neuroimaging finding of acute WE are cytotoxic edema and vasogenic edema, which are represented by bilateral symmetric hyperintensity alterations on T2-weighted MR images in the periphery of the third ventricle, periaqueductal area, mammillary bodies and midbrain tectal plate. An initial bout of WE can result in Korsakoff’s syndrome (KS), but repeated bouts in conjunction with its typical comorbidity, chronic alcoholism, can result in signs of tissue degeneration in vulnerable brain regions. Chronic abnormalities identified with neuroimaging enable examination of brain damage in living patients with KS and have expanded the understanding of the neuropsychological deficits resulting from thiamine deficiency, alcohol neurotoxicity, and their comorbidity. Brain structure and functional studies indicate that the interactions involving the thalamus, mammillary bodies, hippocampus, frontal lobes, and cerebellum are crucial for memory formation and executive functions, and the interruption of these circuits by WE and chronic alcoholism can contribute substantially to the neuropsychological deficits in KS.


Wernicke’s encephalopathy Korsakoff’s syndrome MRI Thalamus Mammillary body Hippocampus 


  1. Aggleton, J. P., O’Mara, S. M., et al. (2010). Hippocampal-anterior thalamic pathways for memory: uncovering a network of direct and indirect actions. The European Journal of Neuroscience, 31(12), 2292–2307.PubMedCrossRefGoogle Scholar
  2. Antunez, E., Estruch, R., et al. (1998). Usefulness of CT and MR imaging in the diagnosis of acute Wernicke’s encephalopathy. AJR. American Journal of Roentgenology, 171(4), 1131–1137.PubMedGoogle Scholar
  3. Ashikaga, R., Araki, Y., et al. (1997). FLAIR appearance of Wernicke encephalopathy. Radiation Medicine, 15(4), 251–253.PubMedGoogle Scholar
  4. Aupee, A. M., Desgranges, B., et al. (2001). Voxel-based mapping of brain hypometabolism in permanent amnesia with PET. NeuroImage, 13(6 Pt 1), 1164–1173.PubMedCrossRefGoogle Scholar
  5. Biswal, B., Yetkin, F. Z., et al. (1995). Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magnetic Resonance in Medicine, 34(4), 537–541.PubMedCrossRefGoogle Scholar
  6. Brokate, B., Hildebrandt, H., et al. (2003). Frontal lobe dysfunctions in Korsakoff’s syndrome and chronic alcoholism: continuity or discontinuity? Neuropsychology, 17(3), 420–428.PubMedCrossRefGoogle Scholar
  7. Butters, N., & Brandt, J. (1985). The continuity hypothesis: the relationship of long-term alcoholism to the Wernicke-Korsakoff syndrome. Recent Developments in Alcoholism, 3, 207–226.PubMedCrossRefGoogle Scholar
  8. Butterworth, R. F., Kril, J. J., et al. (1993). Thiamine-dependent enzyme changes in the brains of alcoholics: relationship to the Wernicke-Korsakoff syndrome. Alcoholism, Clinical and Experimental Research, 17(5), 1084–1088.PubMedCrossRefGoogle Scholar
  9. Cardenas, V. A., Studholme, C., et al. (2007). Deformation-based morphometry of brain changes in alcohol dependence and abstinence. NeuroImage, 34(3), 879–887.PubMedCrossRefGoogle Scholar
  10. Caulo, M., Van Hecke, J., et al. (2005). Functional MRI study of diencephalic amnesia in Wernicke-Korsakoff syndrome. Brain, 128(Pt 7), 1584–1594.PubMedCrossRefGoogle Scholar
  11. Chanraud, S., Pitel, A. L., et al. (2011). Disruption of functional connectivity of the default-mode network in alcoholism. Cerebral Cortex, 21(10), 2272–2281.PubMedCrossRefGoogle Scholar
  12. Charness, M. E., & DeLaPaz, R. L. (1987). Mamillary body atrophy in Wernicke’s encephalopathy: antemortem identification using magnetic resonance imaging. Annals of Neurology, 22(5), 595–600.PubMedCrossRefGoogle Scholar
  13. Chung, T. I., Kim, J. S., et al. (2003). Diffusion weighted MR imaging of acute Wernicke’s encephalopathy. European Journal of Radiology, 45(3), 256–258.PubMedCrossRefGoogle Scholar
  14. Ciccia, R. M., & Langlais, P. J. (2000). An examination of the synergistic interaction of ethanol and thiamine deficiency in the development of neurological signs and long-term cognitive and memory impairments. Alcoholism, Clinical and Experimental Research, 24(5), 622–634.PubMedCrossRefGoogle Scholar
  15. Crowe, S. F., & El-Hadj, D. (2002). Phenytoin ameliorates the memory deficit induced in the young chick by ethanol toxicity in association with thiamine deficiency. Pharmacology Biochemistry and Behavior, 71(1–2), 215–221.CrossRefGoogle Scholar
  16. d’Ydewalle, G., & Van Damme, I. (2007). Memory and the Korsakoff syndrome: not remembering what is remembered. Neuropsychologia, 45(5), 905–920.PubMedCrossRefGoogle Scholar
  17. Fama, R., Marsh, L., et al. (2004). Dissociation of remote and anterograde memory impairment and neural correlates in alcoholic Korsakoff syndrome. Journal of International Neuropsychological Society, 10(3), 427–441.CrossRefGoogle Scholar
  18. Fama, R., Pfefferbaum, A., et al. (2006). Visuoperceptual learning in alcoholic Korsakoff syndrome. Alcoholism, Clinical and Experimental Research, 30(4), 680–687.PubMedCrossRefGoogle Scholar
  19. Fama, R., & Pitel, A. L. (2012). Anterograde episodic memory in Korsakoff syndrome. Neuropsychology Review, 22(2).Google Scholar
  20. Fei, G. Q., Zhong, C., et al. (2008). Clinical characteristics and MR imaging features of nonalcoholic Wernicke encephalopathy. AJNR. American Journal of Neuroradiology, 29(1), 164–169.PubMedCrossRefGoogle Scholar
  21. Friston, K. J., Frith, C. D., et al. (1993). Functional connectivity: the principal-component analysis of large (PET) data sets. Journal of Cerebral Blood Flow and Metabolism, 13(1), 5–14.PubMedCrossRefGoogle Scholar
  22. Gallucci, M., Bozzao, A., et al. (1990). Wernicke encephalopathy: MR findings in five patients. AJR. American Journal of Roentgenology, 155(6), 1309–1314.PubMedGoogle Scholar
  23. Gangolf, M., Czerniecki, J., et al. (2010). Thiamine status in humans and content of phosphorylated thiamine derivatives in biopsies and cultured cells. PLoS One, 5(10), e13616.PubMedCrossRefGoogle Scholar
  24. Halavaara, J., Brander, A., et al. (2003). Wernicke’s encephalopathy: is diffusion-weighted MRI useful? Neuroradiology, 45(8), 519–523.PubMedCrossRefGoogle Scholar
  25. Harding, A., Halliday, G., et al. (2000). Degeneration of anterior thalamic nuclei differentiates alcoholics with amnesia. Brain, 123(Pt 1), 141–154.PubMedCrossRefGoogle Scholar
  26. Harper, C. (1983). The incidence of Wernicke’s encephalopathy in Australia–a neuropathological study of 131 cases. Journal of Neurology, Neurosurgery, and Psychiatry, 46(7), 593–598.PubMedCrossRefGoogle Scholar
  27. Harper, C. (2009). The neuropathology of alcohol-related brain damage. Alcohol and Alcoholism, 44(2), 136–140.PubMedCrossRefGoogle Scholar
  28. Harper, C., Gold, J., et al. (1989). The prevalence of the Wernicke-Korsakoff syndrome in Sydney, Australia: a prospective necropsy study. Journal of Neurology, Neurosurgery, and Psychiatry, 52(2), 282–285.PubMedCrossRefGoogle Scholar
  29. Harper, C. G., Giles, M., et al. (1986). Clinical signs in the Wernicke-Korsakoff complex: a retrospective analysis of 131 cases diagnosed at necropsy. Journal of Neurology, Neurosurgery, and Psychiatry, 49(4), 341–345.PubMedCrossRefGoogle Scholar
  30. Hayes, S. M., Fortier, C. B., et al. (2012). Implicite memroy in Korsakoff’s syndrome: a review of procedural learning and priming studies. Neuropsychology Review, 22(2).Google Scholar
  31. Hazell, A. S., Todd, K. G., et al. (1998). Mechanisms of neuronal cell death in Wernicke’s encephalopathy. Metabolic Brain Disease, 13(2), 97–122.PubMedCrossRefGoogle Scholar
  32. He, X., Sullivan, E. V., et al. (2007). Interaction of thiamine deficiency and voluntary alcohol consumption disrupts rat corpus callosum ultrastructure. Neuropsychopharmacology, 32(10), 2207–2216.PubMedCrossRefGoogle Scholar
  33. Hunter, R., McLuskie, R., et al. (1989). The pattern of function-related regional cerebral blood flow investigated by single photon emission tomography with 99mTc-HMPAO in patients with presenile Alzheimer’s disease and Korsakoff’s psychosis. Psychological Medicine, 19(4), 847–855.PubMedCrossRefGoogle Scholar
  34. Janowsky, J. S., Shimamura, A. P., et al. (1989). Cognitive impairment following frontal lobe damage and its relevance to human amnesia. Behavioral Neuroscience, 103(3), 548–560.PubMedCrossRefGoogle Scholar
  35. Jiang, W., Gagliardi, J. P., et al. (2006). Acute psychotic disorder after gastric bypass surgery: differential diagnosis and treatment. The American Journal of Psychiatry, 163(1), 15–19.PubMedCrossRefGoogle Scholar
  36. Josseaume, T., Auffray Calvier, E., et al. (2007). Acute anterograde amnesia by infarction of the mamillothalamic tracts. Journal of Neuroradiology, 34(1), 59–62.CrossRefGoogle Scholar
  37. Kawamata, T., Mori, T., et al. (2007). Tissue hyperosmolality and brain edema in cerebral contusion. Neurosurgical Focus, 22(5), E5.PubMedCrossRefGoogle Scholar
  38. Kim, E., Ku, J., et al. (2010). Restoration of mammillothalamic functional connectivity through thiamine replacement therapy in Wernicke’s encephalopathy. Neuroscience Letters, 479(3), 257–261.PubMedCrossRefGoogle Scholar
  39. Kim, E., Ku, J., et al. (2009). Mammillothalamic functional connectivity and memory function in Wernicke’s encephalopathy. Brain, 132(Pt 2), 369–376.PubMedGoogle Scholar
  40. Kopelman, M., & Kessels, R. (2012). Context memory in Korsakoff’s syndrome. Neuropsychology Review, 22(2).Google Scholar
  41. Kopelman, M. D. (1991). Frontal dysfunction and memory deficits in the alcoholic Korsakoff syndrome and Alzheimer-type dementia. Brain, 114(Pt 1A), 117–137.PubMedGoogle Scholar
  42. Kopelman, M. D. (1995). The Korsakoff syndrome. The British Journal of Psychiatry, 166(2), 154–173.PubMedCrossRefGoogle Scholar
  43. Kopelman, M. D. (2002). Disorders of memory. Brain, 125(Pt 10), 2152–2190.PubMedCrossRefGoogle Scholar
  44. Krabbendam, L., Visser, P. J., et al. (2000). Normal cognitive performance in patients with chronic alcoholism in contrast to patients with Korsakoff’s syndrome. The Journal of Neuropsychiatry and Clinical Neurosciences, 12(1), 44–50.PubMedGoogle Scholar
  45. Kril, J. J., & Harper, C. G. (2012). Neuroanatomy and neuropathology associated with Korsakoff’s syndrome. Neuropsychology Review, 22(2).Google Scholar
  46. Kwong, K. K., Belliveau, J. W., et al. (1992). Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation. Proceedings of the National Academy of Sciences of the United States of America, 89(12), 5675–5679.PubMedCrossRefGoogle Scholar
  47. Langlais, P. J., & Savage, L. M. (1995). Thiamine deficiency in rats produces cognitive and memory deficits on spatial tasks that correlate with tissue loss in diencephalon, cortex and white matter. Behavioural Brain Research, 68(1), 75–89.PubMedCrossRefGoogle Scholar
  48. Lapergue, B., Klein, I., et al. (2006). Diffusion weighted imaging of cerebellar lesions in Wernicke’s encephalopathy. Journal of Neuroradiology, 33(2), 126–128.CrossRefGoogle Scholar
  49. Mair, W. G., Warrington, E. K., et al. (1979). Memory disorder in Korsakoff’s psychosis: a neuropathological and neuropsychological investigation of two cases. Brain, 102(4), 749–783.PubMedCrossRefGoogle Scholar
  50. Mascalchi, M., Belli, G., et al. (2002). Proton MR spectroscopy of Wernicke encephalopathy. AJNR. American Journal of Neuroradiology, 23(10), 1803–1806.PubMedGoogle Scholar
  51. Mascalchi, M., Simonelli, P., et al. (1999). Do acute lesions of Wernicke’s encephalopathy show contrast enhancement? Report of three cases and review of the literature. Neuroradiology, 41(4), 249–254.PubMedCrossRefGoogle Scholar
  52. Mayes, A. R., Meudell, P. R., et al. (1988). Location of lesions in Korsakoff’s syndrome: neuropsychological and neuropathological data on two patients. Cortex, 24(3), 367–388.PubMedGoogle Scholar
  53. Mulholland, P. J. (2006). Susceptibility of the cerebellum to thiamine deficiency. Cerebellum, 5(1), 55–63.PubMedCrossRefGoogle Scholar
  54. Murata, T., Fujito, T., et al. (2001). Serial MRI and (1)H-MRS of Wernicke’s encephalopathy: report of a case with remarkable cerebellar lesions on MRI. Psychiatry Research, 108(1), 49–55.PubMedCrossRefGoogle Scholar
  55. Ogawa, S., Lee, T. M., et al. (1990). Oxygenation-sensitive contrast in magnetic resonance image of rodent brain at high magnetic fields. Magnetic Resonance in Medicine, 14(1), 68–78.PubMedCrossRefGoogle Scholar
  56. Oscar-Berman, M. (2012). Function and dysfunction of prefrontal brain circuit in alcoholic Korsakoff’s syndrome. Neuropsychol Review, 22(2).Google Scholar
  57. Oscar-Berman, M., Kirkley, S. M., et al. (2004). Comparisons of Korsakoff and non-Korsakoff alcoholics on neuropsychological tests of prefrontal brain functioning. Alcoholism, Clinical and Experimental Research, 28(4), 667–675.PubMedCrossRefGoogle Scholar
  58. Pfefferbaum, A., Adalsteinsson, E., et al. (2007). Development and resolution of brain lesions caused by pyrithiamine- and dietary-induced thiamine deficiency and alcohol exposure in the alcohol-preferring rat: a longitudinal magnetic resonance imaging and spectroscopy study. Neuropsychopharmacology, 32(5), 1159–1177.PubMedCrossRefGoogle Scholar
  59. Pfefferbaum, A., Sullivan, E. V., et al. (1997). Frontal lobe volume loss observed with magnetic resonance imaging in older chronic alcoholics. Alcoholism, Clinical and Experimental Research, 21(3), 521–529.PubMedCrossRefGoogle Scholar
  60. Pitel, A. L., Beaunieux, H., et al. (2008). Episodic and working memory deficits in alcoholic Korsakoff patients: the continuity theory revisited. Alcoholism, Clinical and Experimental Research, 32(7), 1229–1241.PubMedCrossRefGoogle Scholar
  61. Pitel, A. L., Chetelat, G., et al. (2012). Macrostructural abnormalities in Korsakoff syndrome compared with uncomplicated alcoholism. Neurology, 78(17), 1330–1333.Google Scholar
  62. Pitel, A. L., Zahr, N. M., et al. (2010). Signs of preclinical Wernicke’s encephalopathy and thiamine levels as predictors of neuropsychological deficits in alcoholism without Korsakoff’s syndrome. Neuropsychopharmacology, 36(3), 580–588.PubMedCrossRefGoogle Scholar
  63. Race, E., & Verfaellie, M. (2012). Remote memory function and dysfunction in Korsakoff’s syndrome. Neuropsychology Review, 22(2).Google Scholar
  64. Reed, L. J., Lasserson, D., et al. (2003). FDG-PET findings in the Wernicke-Korsakoff syndrome. Cortex, 39(4–5), 1027–1045.PubMedCrossRefGoogle Scholar
  65. Rugilo, C. A., Uribe Roca, M. C., et al. (2003). Proton MR spectroscopy in Wernicke encephalopathy. AJNR. American Journal of Neuroradiology, 24(5), 952–955.PubMedGoogle Scholar
  66. Sechi, G., & Serra, A. (2007). Wernicke’s encephalopathy: new clinical settings and recent advances in diagnosis and management. Lancet Neurology, 6(5), 442–455.PubMedCrossRefGoogle Scholar
  67. Shear, P. K., Sullivan, E. V., et al. (1996). Mammillary body and cerebellar shrinkage in chronic alcoholics with and without amnesia. Alcoholism, Clinical and Experimental Research, 20(8), 1489–1495.PubMedCrossRefGoogle Scholar
  68. Sheedy, D., Lara, A., et al. (1999). Size of mamillary bodies in health and disease: useful measurements in neuroradiological diagnosis of Wernicke’s encephalopathy. Alcoholism, Clinical and Experimental Research, 23(10), 1624–1628.PubMedGoogle Scholar
  69. Shogry, M. E., & Curnes, J. T. (1994). Mamillary body enhancement on MR as the only sign of acute Wernicke encephalopathy. AJNR. American Journal of Neuroradiology, 15(1), 172–174.PubMedGoogle Scholar
  70. Sullivan, E. V., Deshmukh, A., et al. (2000). Cerebellar volume decline in normal aging, alcoholism, and Korsakoff’s syndrome: relation to ataxia. Neuropsychology, 14(3), 341–352.PubMedCrossRefGoogle Scholar
  71. Sullivan, E. V., Harding, A. J., et al. (2003). Disruption of frontocerebellar circuitry and function in alcoholism. Alcoholism, Clinical and Experimental Research, 27(2), 301–309.PubMedCrossRefGoogle Scholar
  72. Sullivan, E. V., Lane, B., et al. (1999). In vivo mammillary body volume deficits in amnesic and nonamnesic alcoholics. Alcoholism, Clinical and Experimental Research, 23(10), 1629–1636.PubMedCrossRefGoogle Scholar
  73. Sullivan, E. V., & Marsh, L. (2003). Hippocampal volume deficits in alcoholic Korsakoff’s syndrome. Neurology, 61(12), 1716–1719.PubMedCrossRefGoogle Scholar
  74. Sullivan, E. V., & Pfefferbaum, A. (2009). Neuroimaging of the Wernicke-Korsakoff syndrome. Alcohol and Alcoholism, 44(2), 155–165.PubMedCrossRefGoogle Scholar
  75. Thomson, A. D. (2000). Mechanisms of vitamin deficiency in chronic alcohol misusers and the development of the Wernicke-Korsakoff syndrome. Alcohol and Alcoholism. Supplement, 35(1), 2–7.PubMedGoogle Scholar
  76. Thomson, A. D., Cook, C. C., et al. (2008). Wernicke’s encephalopathy: ‘plus ca change, plus c’est la meme chose’. Alcohol and Alcoholism, 43(2), 180–186.PubMedCrossRefGoogle Scholar
  77. Thomson, A. D., & Marshall, E. J. (2006). The natural history and pathophysiology of Wernicke’s Encephalopathy and Korsakoff’s Psychosis. Alcohol and Alcoholism, 41(2), 151–158.PubMedCrossRefGoogle Scholar
  78. Torvik, A. (1987). Brain lesions in alcoholics: neuropathological observations. Acta Medica Scandinavica. Supplementum, 717, 47–54.PubMedGoogle Scholar
  79. Torvik, A., Lindboe, C. F., et al. (1982). Brain lesions in alcoholics. A neuropathological study with clinical correlations. Journal of Neurological Sciences, 56(2–3), 233–248.CrossRefGoogle Scholar
  80. Unlu, E., Cakir, B., et al. (2006). MRI findings of Wernicke encephalopathy revisited due to hunger strike. European Journal of Radiology, 57(1), 43–53.PubMedCrossRefGoogle Scholar
  81. Verfaellie, M., Cermak, L. S., et al. (1990). Strategic and automatic priming of semantic memory in alcoholic Korsakoff patients. Brain and Cognition, 13(2), 178–192.PubMedCrossRefGoogle Scholar
  82. Vetreno, R. P., Ramos, R. L., et al. (2012). Brain and behavioral pathology in an animal model of Wernicke’s encephalopathy and Wernicke-Korsakoff Syndrome. Brain Research, 1436, 178–192.PubMedCrossRefGoogle Scholar
  83. Victor, M., Adams, R. D., et al. (1971). The Wernicke-Korsakoff syndrome; a clinical and pathological study of 245 patients, 82 with post-mortem examinations. Philadelphia: F. A. Davis.Google Scholar
  84. Victor, M., Adams, R. D., et al. (1989). The Wernicke-Korsakoff syndrome and related neurologic disorders due to alcoholism and malnutrition. Philadelphia: F.A. Davis Co.Google Scholar
  85. Visser, P. J., Krabbendam, L., et al. (1999). Brain correlates of memory dysfunction in alcoholic Korsakoff’s syndrome. Journal of Neurology, Neurosurgery, and Psychiatry, 67(6), 774–778.PubMedCrossRefGoogle Scholar
  86. Worden, R. W., & Allen, H. M. (2006). Wernicke’s encephalopathy after gastric bypass that masqueraded as acute psychosis: a case report. Current Surgery, 63(2), 114–116.PubMedCrossRefGoogle Scholar
  87. Yoneoka, Y., Takeda, N., et al. (2004). Acute Korsakoff syndrome following mammillothalamic tract infarction. AJNR. American Journal of Neuroradiology, 25(6), 964–968.PubMedGoogle Scholar
  88. Zahr, N. M., Kaufman, K. L., et al. (2011). Clinical and pathological features of alcohol-related brain damage. Nature Reviews. Neurology, 7(5), 284–294.PubMedCrossRefGoogle Scholar
  89. Zhong, C., Jin, L., et al. (2005). MR Imaging of nonalcoholic Wernicke encephalopathy: a follow-up study. AJNR. American Journal of Neuroradiology, 26(9), 2301–2305.PubMedGoogle Scholar
  90. Zuccoli, G., Gallucci, M., et al. (2007). Wernicke encephalopathy: MR findings at clinical presentation in twenty-six alcoholic and nonalcoholic patients. AJNR. American Journal of Neuroradiology, 28(7), 1328–1331.PubMedCrossRefGoogle Scholar
  91. Zuccoli, G., & Pipitone, N. (2009). Neuroimaging findings in acute Wernicke’s encephalopathy: review of the literature. AJR. American Journal of Roentgenology, 192(2), 501–508.PubMedCrossRefGoogle Scholar
  92. Zuccoli, G., Santa Cruz, D., et al. (2009). MR imaging findings in 56 patients with Wernicke encephalopathy: nonalcoholics may differ from alcoholics. AJNR. American Journal of Neuroradiology, 30(1), 171–176.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Young-Chul Jung
    • 1
    • 2
  • Sandra Chanraud
    • 3
    • 4
  • Edith V. Sullivan
    • 2
  1. 1.Department of PsychiatryYonsei University College of MedicineSeoulSouth Korea
  2. 2.Department of Psychiatry and Behavioral SciencesStanford University School of MedicineStanfordUSA
  3. 3.IMF, UMR-CNRS 5231BordeauxFrance
  4. 4.EPHEBordeauxFrance

Personalised recommendations