Korsakoff’s syndrome: a critical review

Abstract

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.

Thiamine Substitution in Alcohol Use Disorder: A Narrative Review of Medical Guidelines

“…WE and WKS are unifactorial disorders caused by thiamine deficiency [9,18], potentially mediated by alcohol use and dependence. The prevalence of WE has been shown to be substantially higher in patients with chronic alcohol abuse (12.5%), but diagnosis is missed in up to 80% of cases.…”

“…Since individuals with AUD may not always appear clinically malnourished and alteration of mental state, which is the most common symptom of WE, might be confused for drunkenness, withdrawal delirium or hepatic encephalopathy, people at risk for WE might be missed. Also, Arts et al [9] hypothesized that alleged "uncomplicated alcoholics" may not actually always be "unproblematic" since reports of irreversible cognitive deficits after alcohol cessation might be a direct cause of undiagnosed and untreated thiamine deficiency. Considering safety of treatment, incidence of anaphylaxis during parenteral substitution is considerably low (1 in 4 mio.…”

“…Different pathophysiological mechanisms of neurotoxicity of alcohol have been proposed such as glutamate excitotoxicity, oxidative stress, and disruption of neurogenesis [1,2,5]. Yet, one of the most clearly established reasons for alcohol-related brain damage is thiamine deficiency [2,6], which can lead to the development of Wernicke encephalopathy (WE) and Wernicke-Korsakoff syndrome (WKS) [7][8][9].…”

“…Especially in early stages, these symptoms are often accompanied by confabulation. Behavioral abnormalities and cognitive dysfunction can be seen in more severe cases [9]. WKS is a chronic state of disease usually not responding to thiamine substitution [9,12].…”

“…Behavioral abnormalities and cognitive dysfunction can be seen in more severe cases [9]. WKS is a chronic state of disease usually not responding to thiamine substitution [9,12]. Due to severe deficits, about 20% of these patients require full-time institutional care [18].…”