Wernicke encephalopathy

However, clinical diagnosis is often elusive as the full triad is present in fewer than 20% of cases. The condition most commonly arises in the context of chronic alcohol use but may also follow protracted vomiting, malnutrition, bariatric surgery, and parenteral nutrition without supplementation.

First described in the late 19th century by Carl Wernicke, a German neuropsychiatrist who described the syndrome in 1881 . The syndrome has become closely associated with chronic alcohol misuse and is a medical emergency due to its potential reversibility with early thiamine replacement. Left untreated, WE often progresses to Korsakoff syndrome—a chronic memory disorder marked by profound anterograde amnesia and confabulation.

The condition stems from impaired oxidative metabolism, leading to cytotoxic and vasogenic edema primarily affecting the periventricular grey matter—particularly the mammillary bodies, thalami, and periaqueductal region. MRI remains the most sensitive imaging modality but is neither definitive nor universally diagnostic, requiring clinical vigilance for early treatment with parenteral thiamine.

Although the condition now bears Wernicke’s name, earlier clinicians had described partial syndromes. Advances in imaging and neuropathology have confirmed the predilection of lesions in the mammillary bodies, thalamus, periaqueductal grey matter, and cerebellum. Recognition and prompt treatment remain essential. The entity is now commonly paired with Korsakoff syndrome, reflecting its chronic amnestic sequel.

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History of Wernicke encephalopathy

1822 – James Jackson (1777–1867) Physician at Massachusetts General Hospital in a review of the peripheral neuritis of alcoholism described an illness resembling WE in alcoholics.

1849 – Magnus Huss (1807–1890), a Swedish physician, publishes Alcoholismus chronicus, coining the term “alcoholism” and linking chronic alcohol use to neurologic, psychiatric, and systemic manifestations.

1868 – Sir Samuel Wilks (1824–1911), Guy’s Hospital, described the features of alcoholic polyneuritis (then called alcoholic paraplegia). In these cases he describes characteristic mental changes such as clouding of consciousness, confusion and memory impairment. Later recognised as early observations of WE and Korsakoff psychosis

1875 – Charles Gayet (1833–1904), French ophthalmologist, publishes a vivid case of strabismus, somnolence, and midbrain inflammation, consistent with Wernicke’s later findings. He described a patient with ophthalmoplegia, drowsiness, right-sided weakness and post-mortem findings consistent with midbrain inflammation.

1881 – Carl Wernicke (1848–1905) in Lehrbuch der Gehirnkrankheiten, vol. 2, described three patients (two with alcoholism, one with vomiting from acid ingestion) who developed confusion, ataxia, and ophthalmoplegia. Autopsies revealed haemorrhagic lesions near the third and fourth ventricles

They exhibited an illness marked by a triad of acute mental confusion, ataxia and ophthalmoplegia…

He named the autopsy findings hämorrhagische Polioencephalitis superior, identifying hemorrhagic lesions in the periaqueductal and periventricular grey matter.

1887 – Sergei Sergeivich Korsakoff (1854–1900) publishes on chronic amnestic syndrome (later called Korsakoff psychosis) associated with alcoholic neuropathy, expanding the spectrum of Wernicke’s pathology into a chronic phase.

1897 – Friedrich Jolly (1844–1904) proposes the term “Morbus Korsakov” for the chronic amnestic phase; later both acute and chronic phases are jointly known as Wernicke-Korsakoff syndrome.

1930s – Thiamine (vitamin B1) deficiency is experimentally shown to induce Wernicke-like pathology, confirming the metabolic basis of the syndrome.

1997 – Caine Criteria introduced offering a more sensitive diagnostic standard requiring 2 of 4 signs: (1) dietary deficiency, (2) oculomotor abnormality, (3) cerebellar dysfunction, and (4) altered mental status or memory impairment. This shifted diagnosis from reliance on the classical triad to a broader and clinically more useful approach.

2000s onward – MRI confirmed as the most sensitive imaging modality, with T2/FLAIR hyperintensities in the mammillary bodies, medial thalami, periaqueductal grey, and tectal plate. MRI shows abnormalities in up to 53% of cases, supporting clinical suspicion where the classical triad is incomplete.

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Associated Persons

• James Jackson (1777–1867) – Provided an early account of alcohol-related amnestic illness
• Magnus Huss (1807–1890) – Early descriptions of alcohol-related neurologic disease
• Sir Samuel Wilks (1824–1911) – Linked mental changes with alcoholic paraplegia
• Charles Gayet (1833–1904) – Described clinical-pathological features suggestive of WE.
• Carl Wernicke (1848–1905) – Described the acute encephalopathy, eponymous triad and pathology.
• Sergei Sergeivich Korsakoff (1854–1900) – Defined the chronic amnestic phase now known as Korsakoff syndrome

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Alternative names

• Polioencephalitis haemorrhagica superioris
• Gayet-Wernicke syndrome

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Is it a bird? Is it a plane?

Which terms should we use?

Modern clinicians prefer the term Korsakoff syndrome or Wernicke–Korsakoff syndrome. “Korsakoff’s psychosis” is retained mostly in historical literature and Wernicke encephalopathy is reserved for the acute reversible phase.

Modern usage recognises Wernicke–Korsakoff syndrome as a dual-phase disorder—early diagnosis and thiamine repletion may prevent the chronic stage.

Wernicke–Korsakoff Syndrome (WKS)

An umbrella term combining Wernicke encephalopathy (acute) and Korsakoff syndrome (chronic). Reflects the continuum of thiamine-deficiency-related brain damage. While Wernicke encephalopathy is potentially reversible, progression to Korsakoff syndrome implies chronic impairment.

Korsakoff syndrome (KS)

An amnestic disorder marked by severe anterograde and retrograde amnesia, confabulation, and apathy, typically secondary to thiamine deficiency from chronic alcoholism. Some authors emphasise non-alcoholic causes of KS (e.g. hyperemesis gravidarum, cancer cachexia), in line with Korsakoff’s original broader view.

Term	Phase	Symptoms	Relation to Alcohol	Pathophysiology
Wernicke encephalopathy (WE)	Acute	Confusion, ataxia, ophthalmoplegia	Strongly associated	Mammillary body, thalamic and periaqueductal damage
Korsakoff syndrome (KS)	Chronic	Anterograde amnesia, confabulation	Often follows WE	Thalamic & mammillary degeneration
Wernicke–Korsakoff syndrome (WKS)	Both	Combined spectrum	Alcoholism, vomiting, starvation, etc.	Thiamine deficiency neuropathology
Korsakoff’s psychosis	Chronic	Historical term for KS	Alcohol + systemic illness	Same as KS

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References

Historical articles

• Jackson J. On a peculiar disease resulting from the use of ardent spirits. N Engl J Med Surg 1822; 11: 351-353
• Huss M. Alcoholismus chronicus eller kronisk alkoholsjukdom. 2 parts; Stockholm. 1849 and 1851. German translation [van dem Busch G. Chronische Alkoholskrankheit, oder, Alcoholismus chronicus. 1952]
• Wilks S. ‘Drunkard’s or Alcoholic Paraplegia‘. In: Paraplegia. Lectures on diseases in the nervous system. Medical Times and Gazette 1868; 37(2): 467–472
• Wilks S. Alcoholic paraplegia. Lancet. 1872; 99(2532): 320–321
• Gayet CJA. Affection encéphalique (encéphalite diffuse probable). Localisée aux étages superieurs des pédoncles cérébraux et aux couches optiques, ainsi qu’ou plancher due quatrième ventricule et aux parois laterales du troisième. Observation recueillie. Archives de physiologie normale et pathologique. 1875; 2(2): 341-351.
• Wernicke C. Die acute, hämorrhagische Polioencephalitis superior. In: Lehrbuch der Gehirnkrankheiten. 1881; II(47): 229-242
• Korsakoff SS. Об алкогольном параличе [On alcoholic paralysis]. Doctoral dissertation, Moscow. 1877
• Korsakoff SS. Disturbance of psychic function in alcoholic paralysis and its relation to the disturbance of the psychic sphere in multiple neuritis of nonalcoholic origin. Vestnik klinicheskoi i sudebnoi psikhiatrii i nevropatologii. 1887; 4(2): 1-102. [Victor M, Yakovlev PI. Korsakoff’s Psychic Disorder in Conjunction with Peripheral Neuritis (English translation). Neurology. 1955; 5(6): 394-406]
• Korsakoff SS. Eine psychische Störung combinirt mit multipler Neuritis (Psychosis polyneuritica seu Cerebropathia psychica toxaemica) [Psychic disorder in conjunction with multiple neuritis]. Allgemeine Zeitschrift für Psychiatrie 1890; 46: 475–485 [also Medizinskoje Obozrenije 1889; 31(13)]
• 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 Jan;62(1):51-60.

Review articles

• Pearce JM. Wernicke-Korsakoff encephalopathy. Eur Neurol. 2008;59(1-2):101-4.
• Sullivan EV, Fama R. Wernicke’s encephalopathy and Korsakoff’s syndrome revisited. Neuropsychol Rev. 2012 Jun;22(2):69-71.
• Sullivan EV, Fama R. Wernicke’s encephalopathy and Korsakoff’s syndrome revisited. Neuropsychol Rev. 2012 Jun;22(2):69-71.
• Eling P, Vein A. Valentin Magnan and Sergey Korsakov: French and Russian pioneers in the study of alcohol abuse, Journal of the History of the Neurosciences. 2018; 27(2): 190-197
• Ota Y, Capizzano AA, Moritani T, Naganawa S, Kurokawa R, Srinivasan A. Comprehensive review of Wernicke encephalopathy: pathophysiology, clinical symptoms and imaging findings. Jpn J Radiol. 2020 Sep;38(9):809-820.