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      Neuropsychiatric Disease and Treatment (submit here)

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      A patient with Korsakoff syndrome of psychiatric and alcoholic etiology presenting as DSM-5 mild neurocognitive disorder

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          Abstract

          Background: Wernicke’s encephalopathy (WE) and Korsakoff syndrome (KS) are underdiagnosed. The DSM-5 has raised the diagnostic threshold by including KS in the major neurocognitive disorders, which requires that the patient needs help in everyday activities.

          Methods: We report clinical, neuropsychological, and radiological findings from a patient who developed Wernicke-Korsakoff syndrome as a result of alcohol use and weight loss due to major depression. We assess the diagnosis in the context of the scientific literature on KS and according to the DSM-IV and the DSM-5.

          Results: The patient developed ataxia during a period of weight loss, thus fulfilling current diagnostic criteria of WE. WE was not diagnosed, but the patient partially improved after parenteral thiamine treatment. However, memory problems became evident, and KS was considered. In neuropsychological examination, the Logical Memory test and the Word List test were abnormal, but the Verbal Pair Associates test was normal (Wechsler Memory Scale-III). There were intrusions in the memory testing. The Wisconsin Card Sorting Test was broadly impaired, but the other test of executive functions (difference between Trail Making B and Trail Making A tests) was normal. There was atrophy of the mammillary bodies, the thalamus, the cerebellum, and in the basal ganglia but not in the frontal lobes. Diffusion tensor imaging showed damage in several tracts, including the uncinate fasciculi, the cinguli, the fornix, and the corona radiata. The patient remained independent in everyday activities. The patient can be diagnosed with KS according to the DSM-IV. According to the DSM-5, the patient has major neurocognitive disorders.

          Conclusions: Extensive memory testing is essential in the assessment of KS. Patients with a history of WE and typical clinical, neuropsychological, and radiological KS findings may be independent in everyday activities. Strict use of the DSM-5 may worsen the problem of Wernicke-Korsakoff syndrome underdiagnosis by excluding clear KS cases that do not have very severe functional impairment.

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          Most cited references68

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          The Wisconsin Card Sorting Test and the cognitive assessment of prefrontal executive functions: a critical update.

          For over four decades the Wisconsin Card Sorting Test (WCST) has been one of the most distinctive tests of prefrontal function. Clinical research and recent brain imaging have brought into question the validity and specificity of this test as a marker of frontal dysfunction. Clinical studies with neurological patients have confirmed that, in its traditional form, the WCST fails to discriminate between frontal and non-frontal lesions. In addition, functional brain imaging studies show rapid and widespread activation across frontal and non-frontal brain regions during WCST performance. These studies suggest that the concept of an anatomically pure test of prefrontal function is not only empirically unattainable, but also theoretically inaccurate. The aim of the present review is to examine the causes of these criticisms and to resolve them by incorporating new methodological and conceptual advances in order to improve the construct validity of WCST scores and their relationship to prefrontal executive functions. We conclude that these objectives can be achieved by drawing on theory-guided experimental design, and on precise spatial and temporal sampling of brain activity, and then exemplify this using an integrative model of prefrontal function [i.e., Miller, E. K. (2000). The prefrontal cortex and cognitive control. Nature Reviews Neuroscience, 1, 59-65.] combined with the formal information theoretical approach to cognitive control [Koechlin, E., & Summerfield, C. (2007). An information theoretical approach to prefrontal executive function. Trends in Cognitive Sciences, 11, 229-235.].
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            Korsakoff’s syndrome: a critical review

            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.
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              Alcohol’s Effects on the Brain: Neuroimaging Results in Humans and Animal Models

              Brain imaging technology has allowed researchers to conduct rigorous studies of the dynamic course of alcoholism through periods of drinking, sobriety, and relapse and to gain insights into the effects of chronic alcoholism on the human brain. Magnetic resonance imaging (MRI) studies have distinguished alcohol-related brain effects that are permanent from those that are reversible with abstinence. In support of postmortem neuropathological studies showing degeneration of white matter, MRI studies have shown a specific vulnerability of white matter to chronic alcohol exposure. Such studies have demonstrated white-matter volume deficits as well as damage to selective gray-matter structures. Diffusion tensor imaging (DTI), by permitting microstructural characterization of white matter, has extended MRI findings in alcoholics. MR spectroscopy (MRS) allows quantification of several metabolites that shed light on brain biochemical alterations caused by alcoholism. This article focuses on MRI, DTI, and MRS findings in neurological disorders that commonly co-occur with alcoholism, including Wernicke’s encephalopathy, Korsakoff’s syndrome, and hepatic encephalopathy. Also reviewed are neuroimaging findings in animal models of alcoholism and related neurological disorders. This report also suggests that the dynamic course of alcoholism presents a unique opportunity to examine brain structural and functional repair and recovery.
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                Author and article information

                Journal
                Neuropsychiatr Dis Treat
                Neuropsychiatr Dis Treat
                NDT
                neurodist
                Neuropsychiatric Disease and Treatment
                Dove
                1176-6328
                1178-2021
                22 May 2019
                2019
                : 15
                : 1311-1320
                Affiliations
                [1 ]Satakunta Hospital District, Psychiatric Care Division, General Psychiatry Outpatient Clinic , Pori, Finland
                [2 ]HUS Medical Imaging Center, Department of Clinical Neurophysiology, Helsinki University Hospital , Helsinki, Finland
                [3 ]Terveystalo Pulssi Medical Center , Turku, Finland
                [4 ]Department of Radiology, University of Turku , Turku, Finland
                [5 ]Department of Psychiatry, University of Turku , Turku, Finland
                Author notes
                Correspondence: Georgios NikolakarosDepartment of Clinical Neurophysiology, HUS Medical Imaging Center, Helsinki University Central Hospital , Stenbäckinkatu 9, PL 100, HUS00029, FinlandPhone +35 894 718 2010Fax +35 894 717 5500Email georgios.nikolakaros@ 123456utu.fi
                Author information
                http://orcid.org/0000-0003-0398-5231
                http://orcid.org/0000-0001-5532-3534
                Article
                203513
                10.2147/NDT.S203513
                6535456
                31190835
                47aa20d0-7b12-47ca-af7e-20500c6c832c
                © 2019 Nikolakaros et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 31 January 2019
                : 04 April 2019
                Page count
                Figures: 2, Tables: 4, References: 82, Pages: 10
                Categories
                Original Research

                Neurology
                alcoholism,depressive disorder,diffusion tensor imaging,korsakoff syndrome,neurocognitive disorders,wernicke encephalopathy

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