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, 13, 2875-2890

Korsakoff's Syndrome: A Critical Review


Korsakoff's Syndrome: A Critical Review

Nicolaas Jm Arts et al. Neuropsychiatr Dis Treat.


In this review, we present a survey on Korsakoff's syndrome (KS), a residual syndrome in patients who suffered from a Wernicke encephalopathy (WE) that is predominantly characterized by global amnesia, and in more severe cases also by cognitive and behavioral dysfunction. We describe the history of KS and its definition, its epidemiology, and the lack of consensus criteria for its diagnosis. The cognitive and behavioral symptoms of KS, which include anterograde and retrograde amnesia, executive dysfunction, confabulation, apathy, as well as affective and social-cognitive impairments, are discussed. Moreover, recent insights into the underlying neurocognitive mechanisms of these symptoms are presented. In addition, the evidence so far on the etiology of KS is examined, highlighting the role of thiamine and alcohol and discussing the continuity hypothesis. Furthermore, the neuropathology of KS is reviewed, focusing on abnormalities in the diencephalon, including the mammillary bodies and thalamic nuclei. Pharmacological treatment options and nonpharmacological interventions, such as those based on cognitive rehabilitation, are discussed. Our review shows that thiamine deficiency (TD) is a crucial factor in the etiology of KS. Although alcohol abuse is by far the most important context in which TD occurs, there is no convincing evidence for an essential contribution of ethanol neurotoxicity (EN) to the development of WE or to the progression of WE to KS. Future research on the postmortem histopathological analysis of brain tissues of KS patients is crucial for the advancement of our knowledge of KS, especially for associating its symptoms with lesions in various thalamic nuclei. A necessary requirement for the advancement of studies on KS is the broad acceptance of a comprehensive definition and definite diagnostic criteria. Therefore, in this review, we propose such a definition of KS and draft outlines for prospective diagnostic criteria.

Keywords: Korsakoff’s syndrome; Wernicke encephalopathy; alcohol amnestic disorder; ethanol neurotoxicity; executive function; history; memory; thalamus; thiamine deficiency.

Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.


Figure 1
Figure 1
Memory systems in the brain. Structures that are important for procedural memory are depicted in red; structures that are important for emotional memory are depicted in yellow. The hippocampal-diencephalic memory circuit is depicted in green: hippocampus (1) > fornix (2; loop around the thalamus), with one branch (3) to the anterior thalamic nuclei (7), another (4) to the mammillary bodies > mammillary bodies (5) > mammillothalamic tract (6) > anterior thalamic nuclei (7); projections to the cingulate cortex (8) > cingulate cortex (9) > retrosplenial cortex (10) > parahippocampal gyrus (11). Courtesy of Peter van Domburg, © 2017. Department of Neurology, Zuyderland Medical Center, Sittard, The Netherlands.
Figure 2
Figure 2
Histopathological damage due to ethanol neurotoxicity (EN) and thiamine deficiency (TD). The yellow areas (1) indicate superior frontal cortical damage due to EN; red and orange areas indicate damage due to TD. The red area indicates the damage to the anterior thalamic nuclei (3) that is probably the critical lesion for the memory disorder in KS. Highlighted in orange are: dorsomedial thalamic nuclei (2), mammillary bodies (4), basal forebrain (5), dorsal and median raphe nuclei with floor and walls of the 3rd and 4th ventricles (6), and the cerebellar vermis (7). This figure is based on Table 2, which is a summary of the findings of the NSWTRC. In addition, color is added to structures not investigated explicitly by the New South Wales Tissue Resource Centre, based on histopathological findings reported by other authors., Courtesy of Peter van Domburg, © 2017. Department of Neurology, Zuyderland Medical Center, Sittard, The Netherlands.
Figure 3
Figure 3
Three fluid-attenuated inversion recovery (FLAIR) images (5 mm thick with a 2.5 mm skip) of a 35-year-old man with schizophrenia and acute nutritional deficiency-induced Wernicke encephalopathy (WE). Note the hyperintense signal in the characteristic loci for WE pathology. Reproduced with permission from Sullivan & Pfefferbaum, © 2008 Sullivan & Pfefferbaum, Department of Psychiatry & Behavioral Sciences, Stanford University, Stanford, CA, USA.

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