Clinical and pathological features of alcohol-related brain damage

Abstract

One of the sequelae of chronic alcohol abuse is malnutrition. Importantly, a deficiency in thiamine (vitamin B1) can result in the acute, potentially reversible neurological disorder Wernicke encephalopathy (WE). When WE is recognized, thiamine treatment can elicit a rapid clinical recovery. If WE is left untreated, however, patients can develop Korsakoff syndrome (KS), a severe neurological disorder characterized by anterograde amnesia. Alcohol-related brain damage (ARBD) describes the effects of chronic alcohol consumption on human brain structure and function in the absence of more discrete and well-characterized neurological concomitants of alcoholism such as WE and KS. Through knowledge of both the well-described changes in brain structure and function that are evident in alcohol-related disorders such as WE and KS and the clinical outcomes associated with these changes, researchers have begun to gain a better understanding of ARBD. This Review examines ARBD from the perspective of WE and KS, exploring the clinical presentations, postmortem brain pathology, in vivo MRI findings and potential molecular mechanisms associated with these conditions. An awareness of the consequences of chronic alcohol consumption on human behavior and brain structure can enable clinicians to improve detection and treatment of ARBD.

Key Points

  • Alcohol can cause a spectrum of untoward structural and functional changes in the brain

  • The spectrum of disruption includes alcohol-related brain damage at one end and complications such as hepatic encephalopathy, Wernicke encephalopathy, Korsakoff syndrome, Marchiafava–Bignami disease and central pontine myelinolysis at the other

  • The clinical diagnoses of alcohol-related brain damage and even Wernicke encephalopathy can be difficult to make, and many cases of these conditions are missed

  • Changes to the brain associated with alcohol intake are regionally specific and can affect both gray and white matter; some of these changes are reversible with abstinence

  • Pathogenic mechanisms associated with alcoholism are under investigation, with neuroinflammation currently receiving particular attention

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Figure 1: Brain regions targeted by alcohol-related disease.
Figure 2: Interactions between alcohol consumption and thiamine deficiency.
Figure 3: Functions and associated brain regions targeted by alcohol abuse and alcoholism.
Figure 4: Graded brain-volume deficits in alcoholism and its sequelae.

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Acknowledgements

The authors would like to thank E. V. Sullivan for her invaluable support and advice in preparing this Review. The authors would also like to thank A. Pfefferbaum for contributing the illustrations.

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The authors all contributed to researching data for the article, discussion of content and writing. N. M. Zahr reviewed the manuscript before submission.

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Correspondence to Clive G. Harper.

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Zahr, N., Kaufman, K. & Harper, C. Clinical and pathological features of alcohol-related brain damage. Nat Rev Neurol 7, 284–294 (2011). https://doi.org/10.1038/nrneurol.2011.42

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