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Vol 22, No 3
Table of Contents

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<p class="frontmatter-fieldnotes disclaimernew" style="margin-bottom:15px;">This work may not be copied, distributed, displayed, published, reproduced, transmitted, modified, posted, sold, licensed, or used for commercial purposes. By downloading this file, you are agreeing to the publisher’s <a href="/pages/termsofuse.aspx" target="_blank">Terms & Conditions</a>.</p> <div>
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  <div id="_idContainer000"> <img src="/publishingimages/2011_brief_report.gif" >
    <p class="title-left"><span class="bold">Wernicke-Korsakoff Syndrome:</span></p>
    <p class="subtitle">A Case Series in Liaison Psychiatry</p>
    <p class="byline-regular">Pedro C. Barata, MD<span class="superscript">a,</span><span class="asterisk">*</span>; Raquel Serrano, MD<span class="superscript">a</span>; Hugo Afonso, MD<span class="superscript">a,b</span>; Alice Luís, MD<span class="superscript">a</span>; and Teresa Maia, MD, PhD<span class="superscript">a</span></p>
    <div id="abstract"> <img src="/publishingimages/new_articles/grey_side_rule.jpg" alt="Vertical divider">
      <p class="subheads-abstract-head"><span class="semibold">ABSTRACT</span></p>
      <p class="abstract-text">Wernicke-Korsakoff syndrome (WKS) is a life-threatening and underdiagnosed neuropsychiatric condition caused by thiamine deficiency that comprises Wernicke encephalopathy and Korsakoff syndrome. Although mainly associated with chronic alcoholism, WKS can arise from other circumstances. This report describes a series of cases of WKS that were clinically evaluated by liaison psychiatrists on a nonpsychiatric inpatient unit. The cases illustrate a deficit in the recognition and adequate treatment of WKS, demonstrating its clinical complexity and the need to improve physicians’ knowledge.</p>
      <p class="abstract-citation"><span class="italic">Prim Care Companion CNS Disord 2020;22(3):19br02538</span></p>
      <p class="to-cite first"><span class="bold-italic">To cite:</span> Barata PC, Serrano R, Afonso H, et al. Wernicke-Korsakoff syndrome: a case series in liaison psychiatry. <span class="italic">Prim Care Companion CNS Disord</span>. 2020;22(3):19br02538.</p>
      <p class="doi-line"><span class="bold-italic">To share:</span> https://doi.org/<span class="doi">10.4088/PCC.19br02538</span></p>
      <p class="abstract-copyright"><span class="italic">© Copyright 2020 Physicians Postgraduate Press, Inc.</span></p>
      <p class="front-matter first"><span class="superscript">a</span>Department of Psychiatry, Prof. Dr. Fernando da Fonseca Hospital, Amadora, Portugal</p>
      <p class="front-matter"><span class="superscript">b</span>Department of Psychiatry, Centro Hospitalar Barreiro-Montijo, Barreiro, Portugal</p>
      <p class="front-matter"><span class="asterisk">*</span><span class="italic">Corresponding author:</span> Pedro C. Barata, MD, Department of Psychiatry, Prof. Dr. Fernando da Fonseca Hospital, IC19, 2720-276 Amadora, Portugal <span class="hyperlink">(<a href="mailto:p.barata9@gmail.com">p.barata9@gmail.com</a>)</span>.</p>
    </div>
    <p class="drop-cap-with-body-text"><span class="bold-14pt-for-cap"><span class="bold">W</span></span>ernicke-Korsakoff syndrome (WKS) is a potentially lethal neuropsychiatric condition caused by thiamine deficiency.<span class="htm-cite"><a href="#ref1">1–5</a></span> This syndrome includes Wernicke encephalopathy and Korsakoff syndrome and frequently occurs in patients with chronic alcoholism.<span class="htm-cite"><a href="#ref1">1–4</a>,<a href="#ref6">6</a></span> Nevertheless, WKS may also be precipitated by several illnesses unrelated to alcohol, such as malnutritional and hypermetabolic states,<span class="htm-cite"><a href="#ref1">1–3</a></span> several gastrointestinal tract diseases (eg, pancreatitis, obstruction, Crohn’s disease), hyperemesis gravidarum, human immunodeficiency virus infection,<span class="htm-cite"><a href="#ref1">1</a></span> or psychiatric disorders (eg, schizophrenia spectrum, anorexia nervosa).<span class="htm-cite"><a href="#ref1">1</a>,<a href="#ref5">5</a></span> WKS can be iatrogenic, occurring for instance in hemodialyzed patients<span class="htm-cite"><a href="#ref1">1</a>,<a href="#ref2">2</a></span> or in intravenous feeding<span class="htm-cite"><a href="#ref1">1</a></span> (providing glucose before thiamine is known to precipitate this syndrome<span class="htm-cite"><a href="#ref5">5</a></span>). WKS is underdiagnosed in most patients.<span class="htm-cite"><a href="#ref4">4–8</a></span></p>
    <p class="body-text">Classically, Wernicke encephalopathy is associated with a triad of symptoms: mental status changes, ophthalmoplegia, and ataxia. However, these symptoms occur in only 20%–30% of cases.<span class="htm-cite"><a href="#ref4">4</a>,<a href="#ref5">5</a></span> Caine criteria<span class="htm-cite"><a href="#ref9">9</a></span> allow the diagnosis of Wernicke encephalopathy in the presence of at least 2 of 4 signals: (1) dietetic deficiencies, (2) oculomotor abnormalities, (3) cerebellar dysfunction, or (4) mental state changes or mild memory deficits.<span class="htm-cite"><a href="#ref2">2</a>,<a href="#ref3">3</a></span> Wernicke encephalopathy is a potentially reversible medical emergency,<span class="htm-cite"><a href="#ref2">2</a>,<a href="#ref3">3</a>,<a href="#ref5">5</a>,<a href="#ref6">6</a></span> leading to death in 20% of cases.<span class="htm-cite"><a href="#ref6">6</a></span> Residual symptoms are common,<span class="htm-cite"><a href="#ref5">5</a></span> as is the progression to Korsakoff syndrome.<span class="htm-cite"><a href="#ref3">3</a>,<a href="#ref5">5</a>,<a href="#ref6">6</a></span> In Wernicke encephalopathy, early treatment with high doses of parenteral thiamine can reduce the probability of progression to Korsakoff syndrome<span class="htm-cite"><a href="#ref3">3</a></span> and improve prognosis.<span class="htm-cite"><a href="#ref6">6</a></span></p>
    <p class="body-text">Korsakoff syndrome can be defined as a probably permanent neuropsychiatric condition that usually follows an episode of Wernicke encephalopathy,<span class="htm-cite"><a href="#ref3">3</a>,<a href="#ref5">5</a></span> mainly characterized by a retrograde and anterograde amnesia<span class="htm-cite"><a href="#ref3">3</a>,<a href="#ref5">5</a>,<a href="#ref6">6</a></span> in a patient with apparent clear consciousness.<span class="htm-cite"><a href="#ref3">3</a></span> Provoked confabulations are common.<span class="htm-cite"><a href="#ref6">6</a></span></p>
    
        <div class="clinical-article">
      <div class="heading"><img src="/publishingimages/new_tocs/clinical_points.gif" alt="clinical points"></div>
      <ul>
        <li class="clinical-points">Wernicke-Korsakoff syndrome is not rare nor is it exclusive to alcoholics. </li>
        <li class="clinical-points">Wernicke-Korsakoff syndrome can occur in malnutritional and hypermetabolic states, gastrointestinal tract diseases, hyperemesis gravidarum, human immunodeficiency virus infection, and psychiatric disorders and can be iatrogenic.</li>
        <li class="clinical-points">A shift from the classical Wernicke-Korsakoff syndrome clinical triad to a greater use and awareness of Caine criteria would most certainly increase detection rates.</li>
      </ul>
    </div>
    
    <p class="body-text">Deaths associated with WKS are often caused by comorbid diseases, namely cirrhosis or infections—unspecified infections are commonly reported.<span class="htm-cite"><a href="#ref4">4</a></span> Bronchopneumonia has been reported to be a common specific related infection.<span class="htm-cite"><a href="#ref4">4</a></span></p>
    <p class="body-text">This report describes a series of cases of WKS that were clinically evaluated by the liaison psychiatrists of the Prof. Dr. Fernando da Fonseca Hospital, Amadora, Portugal, in the nonpsychiatric inpatient units between October 2017 and March 2018.</p>
    <p class="subheads_subhead-1-left"><span class="bold">CASE DESCRIPTIONS</span></p>

    <p class="body-text">We identified 4 cases of patients with WKS through medical record review. Their sociodemographic and clinical features are presented in <span class="callout"><a href="#" onclick="createFigure('T1'); return false;" title="">Table 1</a></span>. All patients had symptomatic WKS diagnosed in medical units on the basis of a detailed anamnesis, complementary diagnostic examination, and a clinical presentation consistent with this diagnosis. Three of four patients had the classic Wernicke encephalopathy triad—1 patient had no ophthalmoplegia. All patients met more than 2 Caine criteria.</p>
    <p class="body-text">Patient 2 had dementia prior to WKS onset (see <span class="callout"><a href="#" onclick="createFigure('T1'); return false;" title="">Table 1</a></span>). However, we are not in a position to state categorically the degree of severity or how or if the dementia contributed to the behaviors leading to WKS.</p>
    <p class="body-text">All patients received psychotropic drugs: antipsychotics to control confusional states and psychomotor agitation (patients 1, 2, and 4), benzodiazepines for the prevention of alcohol withdrawal syndrome (patient 1), and antidepressants for the treatment of a major depressive episode with suicidal ideation (patient 3). All 4 patients were given thiamine to treat WKS (see <span class="callout"><a href="#" onclick="createFigure('T1'); return false;" title="">Table 1</a></span> for dosage details). WKS improvement was partial in all cases. Two patients progressed to a significant dependence on others and required future institutionalization.</p>
    <div id="figure-2"> <a href="#" onclick="createFigure('T1'); return false;"><img src="19br02538T1.gif" alt="Table 1" id="T1" border="0" /></a>
      <p class="click-to-enlarge">Click figure to enlarge</p>
    </div>
    <p class="subheads_subhead-1-left"><span class="bold">DISCUSSION</span></p>
    <p class="body-text">Half of the WKS cases occurred in the sequence of hunger or malnutrition and not in an alcoholic context. Patient 4’s presentation seemed to correspond to an iatrogenic Wernicke encephalopathy diagnosis.</p>
    <p class="body-text">Notwithstanding the sample size, it is important to highlight that WKS manifested the complete classic triad in 75% of the cases—a significant difference from the 15%–30% mentioned in the scientific literature.<span class="htm-cite"><a href="#ref5">5</a></span> In contrast, all patients fulfilled Caine criteria.</p>
    <p class="body-text">Diagnosis was delayed in the patients with more clinical comorbidities, which may be due to the attribution of WKS symptoms to already existing pathologies. As clinical examination remains the standard in diagnosing WKS, and the classic signs of such a syndrome have low sensitivity, a shift to greater use and awareness of the Caine criteria would most certainly increase WKS detection rates. Other factors that could improve WKS diagnosis include clarifying misconceptions about WKS, as it is not rare or exclusive to alcoholics, and being aware of the associated nonalcoholic medical conditions.<span class="htm-cite"><a href="#ref4">4</a></span></p>
    <p class="body-text">There are clinical guidelines to support the clinical management of Wernicke encehalopathy.<span class="htm-cite"><a href="#ref2">2</a>,<a href="#ref4">4</a>,<a href="#ref7">7</a>,<a href="#ref10">10–12</a></span> The Royal College of Physicians guidelines<span class="htm-cite"><a href="#ref13">13</a></span> recommend that thiamine 500 mg be given parenterally 3 times per day for at least 3 days. If there is any improvement, it is advised to continue thiamine at 250 mg/d parenterally for 5 days. The guidelines<span class="htm-cite"><a href="#ref13">13</a></span> also recommend that all hypoglycemic patients (who are treated intravenously [IV] with glucose) with evidence of chronic alcohol ingestion be given IV thiamine immediately because IV glucose without thiamine may acutely precipitate Wernicke encephalopathy.<span class="htm-cite"><a href="#ref2">2</a>,<a href="#ref4">4</a></span> For the treatment of suspected or manifest Wernicke encephalopathy, the European Federation of Neurologic Societies<span class="htm-cite"><a href="#ref10">10</a></span>recommends that thiamine 200 mg be given before any carbohydrate 3 times per day, preferably IV diluted with 100 mL of normal saline and given over 30 minutes. Treatment should be continued until there is no further improvement in signs and symptoms.<span class="htm-cite"><a href="#ref2">2</a>,<a href="#ref4">4</a>,<a href="#ref10">10</a></span> There is insufficient evidence of the efficacy of thiamine for the treatment of Wernicke-Korsakoff syndrome, and recommendations about the dosage and duration of treatment are acknowledged to be arbitrary.<span class="htm-cite"><a href="#ref9">9</a>,<a href="#ref11">11</a></span> In half of the cases identified here, the administered doses were lower than those of the recommendations, therefore limiting the treatment’s therapeutic potential.</p>
    <p class="body-text">The partial recovery verified in all cases aligns with data from the literature. The residual symptomatology identified in patient 2 (one of the cases concerning subtherapeutic thiamine administration) included confabulations, a possible progression from Wernicke encephalopathy to Korsakoff syndrome.</p>
    <p class="body-text">It is important to highlight that this report does not specify the medical investigations that indicated that WKS was the most probable etiology (which were elaborated by the medical doctors from the hospital units were the patients were admitted). We consider this a limitation because 3 of 4 patients had several comorbidities that could constitute confusional state causes (eg, hypertension, cardiac insufficiency, dementia, ischemic heart disease, chronic renal disease), and the reader might find that the published data are insufficient to be conclusive of WKS only.</p>
    <p class="body-text">Our study shows the diagnostic complexity of WKS and illustrates that it is imperative to be aware of diagnostic and treatment approaches. The deficit in this syndrome’s recognition (particularly when several medical comorbidities are present or in nonalcoholic WKS) and the unfamiliarity with thiamine’s therapeutic dosage identified in this study reinforce the importance of being acquainted with this medical entity, paving the way for an early diagnosis, a suitable treatment, and a better prognosis.</p>
    <p class="end-matter"><span class="bold-italic">Submitted:</span> September 2, 2019; accepted December 9, 2019.</p>
    <p class="end-matter"><span class="bold-italic">Published online:</span> May 7, 2020.</p>
    <p class="end-matter"><span class="bold-italic">Potential conflicts of interest:</span> None. </p>
    <p class="end-matter"><span class="bold-italic">Funding/support:</span> None.</p>
    <p class="end-matter"><span class="bold-italic">Additional information:</span> The ethical committee of Prof. Dr. Fernando da Fonseca Hospital approved a waiver of consent to conduct this study. All information has been de-identified to protect anonymity.</p>
    <p class="references_references-heading"><span class="bold">REFERENCES</span></p>
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  </div>
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Edit in Report Builder
/PCC/article/_layouts/ReportServer/RSAction.aspx?RSAction=ReportBuilderDatasetContext&list={ListId}&ID={ItemId}
0x0
0x4
FileType
rsd
250
Manage Caching Options
/PCC/article/_layouts/ReportServer/DatasetCachingOptions.aspx?list={ListId}&ID={ItemId}
0x0
0x4
FileType
rsd
350
Manage Cache Refresh Plans
/PCC/article/_layouts/ReportServer/CacheRefreshPlanList.aspx?list={ListId}&ID={ItemId}&IsDataset=true
0x0
0x4
FileType
rsd
351
Manage Data Sources
/PCC/article/_layouts/ReportServer/DataSourceList.aspx?list={ListId}&ID={ItemId}
0x0
0x20
FileType
rsd
352
View Dependent Items
/PCC/article/_layouts/ReportServer/DependentItems.aspx?list={ListId}&ID={ItemId}
0x0
0x4
FileType
rsd
353
Compliance Details
javascript:commonShowModalDialog('{SiteUrl}/_layouts/itemexpiration.aspx?ID={ItemId}&List={ListId}', 'center:1;dialogHeight:500px;dialogWidth:500px;resizable:yes;status:no;location:no;menubar:no;help:no', function GotoPageAfterClose(pageid){if(pageid == 'hold') {STSNavigate(unescape(decodeURI('{SiteUrl}'))+'/_layouts/hold.aspx?ID={ItemId}&List={ListId}'); return false;} if(pageid == 'audit') {STSNavigate(unescape(decodeURI('{SiteUrl}'))+'/_layouts/Reporting.aspx?Category=Auditing&backtype=item&ID={ItemId}&List={ListId}'); return false;} if(pageid == 'config') {STSNavigate(unescape(decodeURI('{SiteUrl}'))+'/_layouts/expirationconfig.aspx?ID={ItemId}&List={ListId}'); return false;}}, null); return false;
0x0
0x1
ContentType
0x01
898
Document Set Version History
javascript:SP.UI.ModalDialog.ShowPopupDialog('{SiteUrl}/_layouts/DocSetVersions.aspx?List={ListId}&ID={ItemId}')
0x0
0x0
ContentType
0x0120D520
330
Send To other location
javascript:GoToPage('{SiteUrl}/_layouts/docsetsend.aspx?List={ListId}&ID={ItemId}')
0x0
0x0
ContentType
0x0120D520
350

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