Hektoen International

A Journal of Medical Humanities

Wernicke-Korsakoff encephalopathy: A historical note

JMS Pearce
Hull, England

Fig 1. Wernicke’s Lehrbuch der Gehirnkrankheiten. Internet Archive. Public domain.

Before Sergei Sergeivich Korsakoff described the psychosis that bears his name, Carl Wernicke reported a closely related and often coexistent syndrome. It is variously named Wernicke-Korsakoff encephalopathy, syndrome, or psychosis. Two more different personalities would be hard to imagine.

Wernicke’s encephalopathy

The crucial clinical account of Wernicke’s encephalopathy is found in the second of his three-volume Lehrbuch der Gehirnkrankheiten (1881–1883) (Fig 1).

He described three patients, two men with alcoholism and a woman with persistent vomiting two months after drinking sulphuric acid.1,2 They all exhibited an illness marked by a triad of acute mental confusion, ataxia, and ophthalmoplegia.3 The patients died and autopsies showed punctate hemorrhages of the grey matter around the third and fourth ventricles and aqueduct, which he called “polioencephalitis haemorrhagica superioris.”

In up to 80% of patients, the diagnosis of Wernicke’s encephalopathy is not recognized in life. Recent criteria require two of four signs: dietary deficiencies, oculomotor abnormalities, cerebellar dysfunction, and either an altered mental state or mild memory impairment.4 Their application has improved antemortem diagnosis.

Carl Wernicke* (1848–1905)

Fig 2. Carl Wernicke. US National Library of Medicine. Via Wikimedia. Public domain.

Wernicke (Fig 2) graduated MD from Breslau in 1876. He studied psychiatry and nervous diseases with Ostrid Foerster and Theodor Meynert. He was an early advocate of cerebral localization of brain functions. Aged twenty-six, in 1874 he described Der aphasische Symptomenkompleks—the receptive aphasia that carries his name, located in the auditory association area in the superior temporal gyrus. He was also the first to identify a “center” adjacent to the sixth nerve nucleus in the pons for conjugate gaze. He jointly founded the journal Monatsschrift für Psychiatrie und Neurologie.

Wernicke was appointed head of the Breslau University and later Halle University Departments of Neurology and Psychiatry. Reputedly a shy, taciturn, and inflexible man, his demonstrations to students were lucid and inspiring. He died young, from injuries sustained in a bicycle accident.

Korsakoff’s psychosis

Korsakoff described thirty or more alcoholic cases and fourteen non-alcoholic cases of a mental disorder associated with alcoholic polyneuropathy:

Only after prolonged conversation does it become noticeable that the patient occasionally confuses issues and does not recall anything which he has had in mind. He does not recall whether or not he has eaten, or risen from his bed. The patient often promptly forgets what has transpired; someone has approached him and addressed him, has left him alone for a few moments and when they return he has no idea that anyone has been with him. It is notable that, while the patient has forgotten everything which has just occurred, he remembers earlier incidents, which transpired, prior to his illness. Usually that which has occurred during the illness or immediately– preceding it disappears from memory. – This is typical of most cases. In other cases, the memory of earlier events is also lost. Besides these mental symptoms, other symptoms appear, as previously mentioned, which correspond with multiple degenerative neuritis expressed as paralysis of the lower extremities, but also of the upper extremities. However, the fact must be emphasised that the symptoms are not always clearly manifest…A thorough examination will almost always reveal signs of neuritis which thus facilitate diagnosis of a mental aberration.5’6

In his 1887 article, Korsakoff mentioned ophthalmoplegia, nystagmus, and speech disturbances observed in some of his patients, but he failed to stress their importance. Friedrich Jolly (1844–1904) introduced the eponym Korsakoff’s psychosis, but the self-effacing Korsakoff gave priority to the Swedish physician Magnus Huss in 1849–51.

Sixty-five years before Korsakoff’s account, James Jackson at Massachusetts General Hospital had reported a similar syndrome in a review of the peripheral neuritis of alcoholism.7 And in 1868, the prolific Sir Samuel Wilks of Guy’s Hospital in an article on alcoholic paraplegia8 also reported the characteristic mental symptoms. The French ophthalmologist Charles Gayet in 1875 gave a commonly cited description of a twenty-eight-year-old man with agitation, weakness, drowsiness, and third nerve palsy sparing the pupils, with prolonged drowsiness and later left hemiplegia. Gayet ascribed it to diffuse encephalitis. However, the case was unlike Wernicke’s encephalopathy: there was no recorded amnesia or ataxia and the “capillary apoplexies” in the thalamus, third and fourth ventricles crucially spared the mammillary bodies.9

Sergei Sergeivich Korsakoff (1854–1900)

Fig 3. Sergei Sergeivich Korsakoff. Via Wikimedia. Public domain.

Sergei Korsakoff (Fig 3) graduated from Moscow State University in 1875. The association of Wernicke’s syndrome with amnesia and confabulation relates to Korsakoff’s doctoral thesis: Cerebropathia Psychica Toxaemica. He was a pupil of the eminent Theodor Meynert in Vienna, and became Professor Extraordinarius at the Moscow Preobrazhenskii mental hospital. Noted for his scholarship, he was a dedicated, intensely humane physician, always at the service of his students and patients. He opposed strait-jackets, isolation cells, and forced sterilization of the mentally ill. He published acclaimed texts on paranoia, general psychiatry and neuropathology, and founded the Russian Association of Psychiatrists and Neurologists. He died of heart disease, aged forty-six.

Subsequently in Wernicke-Korsakoff’s encephalopathy, the punctate hemorrhages were confirmed (pathologically, and by fluid-attenuated inversion recovery [FLAIR] MRI) in the mammillary bodies, cranial nerve nuclei III, IV, VI and VIII, and in the thalamus, hypothalamus, periaqueductal grey, cerebellar vermis, with variable cortical lesions.10

The syndrome is caused by thiamine deficiency. Alcoholism is the most frequent precipitant, though not primarily responsible for its neuropathology. Its characteristics are impairment of memory and learning disproportionate to other cognitive functions in an otherwise alert and responsive patient.10,11 A reasonable perspective is that Korsakoff’s syndrome is a residue of Wernicke encephalopathy:12 two facets of the same disease. It is distinct from, but may coincide with so-called alcoholic dementia and hepatic encephalopathy. More than 80% of patients show signs of polyneuropathy, and associated liver disease is found in two-thirds of the patients.10

Suzuki and Shimamura first isolated thiamine in 1911. Deficiency of thiamine (a coenzyme of three critical enzymes in the Krebs cycle: transketolase, ketoglutarate dehydrogenase, and pyruvate dehydrogenase complex) leads to glutamate enhanced excitatory neurotoxicity. This culminates in oxidative damage and mitochondrial injury causing nerve cell death. The critical area for amnesia lies in the connections between anterior thalamic nuclei and the hippocampus.

Common causes are alcoholism, dietary deficiencies, protracted vomiting, carbohydrate loading, hyperalimentation, and renal dialysis. A genetic abnormality of transketolase increases the risk of thiamine deficiency.

In Wernicke’s encephalopathy, when 500–1000 mg intravenous thiamine is given urgently for three to seven days, about 10% recover. Despite this, approximately 20% die and 70% develop Korsakoff’s psychosis, of whom 50% need long-term care for memory and other cognitive defects.10

Prophylactic intravenous thiamine should be considered in patients with repeated vomiting of any cause, especially in alcoholics.


* Often spelled Karl Wernicke


  1. Wernicke C. Die acute, hämorrhagische Polioencephalitis superior. Lehrbuch der Gehirnkrankheiten fur Aerzte und Studirende; Kassel, Fischer. 1881; 22: 229-242.
  2. Thomson AD, Cook CCH, Guerrini I, Sheedy D, Harper C, Marshall EJ. Wernicke’s Encephalopathy Revisited. Alcohol & Alcoholism 2008;43(2): 174–179. [Translation of the case history of the original manuscripts]
  3. Pearce JMS. Wernicke-Korsakoff encephalopathy. European Neurol 2008;59(1-2):101-4.
  4. 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(1):51-60.
  5. Korsakoff SS. Psychic Disorder in Conjunction with Multiple Neuritis (Psychosis Polyneuritica s. Cerebropathia Psychica Toxaemica). Medizinskioje Obozrenije 1889, No. 13. Translation by Victor M., Yakovlev P. Neurology Jun 1955, 5 (6) 394.
  6. Blansjaar B. Korsakoff’s syndrome. In: Neurological Eponyms. Ed. Koehler PJ, Bruyn GW, Pearce JMS. Oxford, New York. OUP 2000. pp. 234-8.
  7. Jackson J. On a peculiar disease resulting from the use of ardent spirits. New Engl J Medicine 1822; 2: 351-3. Cited in http://www.whonamedit.com/synd.cfm/930.html.
  8. Wilks S. Alcoholic paraplegia. Medical Times and Gazette, London 1868; 2: 467-72.
  9. Walusinski O, Wijdicks EFM. Gayet-Wernicke Syndrome: The eye surgeon in a French neurologic eponym. Rev Neurol (Paris). 2022;178(8):766-770.
  10. Victor M, Adams R, Collins G H. The Wernicke– Korsakoff Syndrome and Related Neurologic Disorders Due to Alcoholism and Malnutrition. Philadelphia, F. A. Davis, 1989.
  11. Lishman WA. Cerebral disorder in alcoholism: Syndromes of impairment. Brain 1981;104 (Pt 1):1–20.
  12. Arts NJ, Walvoort SJ, Kessels RP. Korsakoff’s syndrome: a critical review. Neuropsychiatr Dis Treat. 2017;13:2875-2890.

JMS PEARCE is a retired neurologist and author with a particular interest in the history of medicine and science.

Highlighted in Frontispiece Volume 15, Issue 1 – Winter 2023

Fall 2022




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