Wernicke-Korsakoff syndrome not related to alcohol use: a systematic review

J Neurol Neurosurg Psychiatry. 2015 Dec;86(12):1362-8. doi: 10.1136/jnnp-2014-309598. Epub 2015 Jan 14.


Objective: Although Wernicke-Korsakoff syndrome (WKS) is a common condition, diagnosis remains difficult. WKS not associated with alcohol is rare and thought to present differently to alcohol-related WKS. We conducted a systematic review of WKS not related to alcohol to enhance understanding of WKS not related to alcohol and WKS in general.

Methods: A systematic review was conducted of case reports, published in English, of Wernicke's encephalopathy and WKS in patients without a history of alcohol-use disorder. Main data sources: MEDLINE, Index Medicus. Eligible cases totaled 623. Publication dates ranged from 1867 to 2014. Comparisons of clinical presentation were made with published data on samples comprising, almost exclusively, alcohol-related WKS.

Results: A wide array of illnesses precipitated WKS. When diagnosis of WKS was performed postmortem, non-alcohol-related cases presented a similar number of signs of the classic triad as alcohol-related cases (p=0.662, Cohen's w=0.12) but more signs when diagnosed antemortem (p<0.001, Cohen's w=0.46). The most common sign was altered mental state. Korsakoff syndrome or ongoing memory impairment was reported in 25% of non-alcohol-related WKS, although cognitive status was not explicitly reported in many cases. When duration of memory impairment was reported, 56% had clinically obvious memory impairment lasting beyond the period of acute presentation. Non-alcohol-related WKS was more often associated with female gender, younger age, shorter duration of precipitating illness and better survival rate compared to alcohol-related WKS.

Conclusions: Thiamine deficiency in the absence of an alcohol-use disorder can cause the full clinical spectrum of WKS, including chronic cognitive impairment and Korsakoff syndrome.


Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Alcohol Drinking / adverse effects*
  • Alcoholism / complications*
  • Female
  • Humans
  • Korsakoff Syndrome / epidemiology
  • Korsakoff Syndrome / etiology*
  • Korsakoff Syndrome / psychology
  • Male
  • Middle Aged
  • Risk Factors
  • Sex Factors