When a patient presents with confusion, persistent memory, and learning deficits, one should suspect the presence of Wernicke-Korsakoff syndrome. This syndrome usually presents with a clinical triad consisting of altered mental status (i.e., confusion or dementia), nystagmus (or ophthalmoplegia), and ataxia. Unfortunately, less than a third of patients present with this clinical triad.
To better understand this disorder, practitioners should think of Wernicke encephalopathy and Wernicke-Korsakoff syndrome as two separate syndromes: (1) Wernicke encephalopathy is characterized by an acute confusional state and often reversible clinical features, and (2) Wernicke-Korsakoff syndrome with persistent but often irreversible clinical features including dementia and gait abnormalities.
The cause of Wernicke-Korsakoff syndrome is a deficiency of thiamine or vitamin B1. Individuals with poor nutrition for any reason are at risk for this disorder. The most common social factor associated with Wernicke-Korsakoff syndrome is chronic alcohol abuse which leads to decreased absorption and utilization of thiamine. However, it is important to note that there are nonalcoholic causes of thiamine deficiency which can also produce Wernicke-Korsakoff syndrome. These include individuals with malnutrition, starvation, schizophrenia, anorexia nervosa, prisoners of war, and terminal malignancies. In the past, baby formula which was deficient in thiamine also led to Wernicke-Korsakoff syndrome. Wernicke-Korsakoff syndrome also can develop during the first trimester of pregnancy in women who develop hyperemesis gravidarum. Another common cause is bariatric surgery and malignancies of the gastrointestinal (GI) tract.
The prevalence is between 0% and 2% worldwide. Specific subpopulations have higher prevalence rates including people who are homeless, older individuals living alone or in isolation, and psychiatric inpatients. Prevalence is not connected to alcohol consumption per capita. For example, in France, a country that is well known for its consumption of wine, the prevalence is approximately 0.4%, while Australia has a prevalence of approximately 3%.
Brain atrophy associated with Wernicke-Korsakoff Syndrome occurs in the mammillary bodies, the cerebellum, the thalamus, the frontal lobe, the periaqueductal grey, the walls of the third ventricle, and the floor of the fourth ventricle. In addition to the damage seen in these areas, there may be damage to the cortex, although this may be due to the direct toxic effects of alcohol as opposed to thiamine deficiency.
The amnesia associated with Wernicke-Korsakoff Syndrome is a result of atrophy of the structures of the diencephalon (thalamus, hypothalamus, and mammillary bodies) and is similar to amnesia that is present as a result of damage to the medial temporal lobe. It has been argued that the memory impairment can occur as a result of damage along any part of the mammillothalamic tract, which may explain how Wernicke-Korsakoff Syndrome can develop in patients with damage exclusively to either the thalamus or the mammillary bodies.
An individual with Wernicke-Korsakoff syndrome will usually present with (1) ocular disturbances which may include diplopia, painless vision loss, or strabismus, (2) gait abnormalities that include a wide-based, short-stepped gait and an inability to stand or ambulate without assistance, and (3) mental status changes that include apathy, paucity of speech, and indifference to the environment. As the disorder progresses, other symptoms that may develop include agitation, anger, hallucinations, and confabulations.
The diagnosis of Wernicke-Korsakoff syndrome is made by the history and clinical findings supplemented with lab studies showing thiamine deficiency. Treatment aims to prevent the disorder from getting worse. One should maintain a high level of suspicion for thiamine deficiency to avoid precipitation of severe symptoms of Wernicke-Korsakoff syndrome. Prophylactic thiamine administration is relatively safe and should be started even if the diagnosis has not been confirmed.
Unfortunately, unlike Wernicke encephalopathy, Wernicke-Korsakoff syndrome is a long-term disorder which is often progressive. It is very rare for the individual with Wernicke-Korsakoff syndrome to recover fully even with aggressive treatment. After thiamine treatment, the symptoms of encephalopathy will improve in 5 to 12 days. The patient should be offered oral thiamine and consulted for rehabilitation and treatment of other comorbid conditions. Most patients with Wernicke-Korsakoff syndrome need long-term care in a chronic care facility. Their prognosis is guarded.
The differential diagnosis includes the following:
Approximately 25% of patients with Wernicke-Korsakoff syndrome require long-term institutionalization. Patients depending on long-term care often have one or more comorbidity (somatic and psychiatric).
Mental Status Complications
Global confusional often resolves gradually after treatment.
If an amnestic deficit is present, it may manifest as the signs of apathy and global confusion resolve.
One in five patients who demonstrate signs of the amnestic state after treatment has been initiated will have a complete with most patients having varying degrees of persistent learning and memory impairment.
Maximum recovery may take years and depends on abstinence from alcohol.
Once patients with Korsakoff psychosis have recovered, they do not demand alcohol, but they will accept it if offered.
Approximately half of the patients recover completely from ataxic symptoms, and the other half have incomplete recovery, with a residual slow, shuffling, wide-based gait and the inability to tandem walk.
Vestibular dysfunction also improves about half the time.
Patients who recover do so in a particular sequence.
Improvement of ocular abnormalities is the most dramatic, usually occurring within hours of thiamine administration.
Failure of ocular abnormalities to respond to thiamine should raise doubt as to the diagnosis.
Vertical nystagmus may persist for months.
Fine horizontal nystagmus can persist indefinitely, but patients completely recover from sixth nerve palsies, ptosis, and vertical-gaze palsies.
Mortality may occur secondary to infections and hepatic failure, but some deaths are attributable to defects of prolonged thiamine deficiency.
The mortality rate is 10-15% in severe cases.
Prognosis depends on the stage of disease at presentation and time of treatment.
Korsakoff syndrome often follows or accompanies Wernicke encephalopathy.
To reduce the risk of Wernicke-Korsakoff syndrome, limit the intake of alcohol and ensure that proper nutrition needs are met.
Wernicke Korsakoff syndrome is often encountered by the primary care physician, nurse practitioner or internist. While the diagnosis is relatively simple, the management is unsatisfactory. The disorder is progressive and carries very high morbidity and mortality. The condition is best managed by a multidisciplinary team that includes a neurologist, mental health nurse, psychiatrist, gastroenterologist, ophthalmologist, and an intensivist. Despite optimal treatment, full recovery does not occur. the majority of patients end up in a long term care facility and have a guarded prognosis.
|||Gerridzen IJ,Joling KJ,Depla MF,Veenhuizen RB,Verschuur EML,Twisk JWR,Hertogh CMPM, Awareness and its relationships with neuropsychiatric symptoms in people with Korsakoff syndrome or other alcohol-related cognitive disorders living in specialized nursing homes. International journal of geriatric psychiatry. 2019 Mar 10; [PubMed PMID: 30854733]|
|||Yoon C,Gedzior J,DePry D, Wernicke-Korsakoff syndrome: Focus on low-threshold diagnosis and prompt treatment in the primary care setting. International journal of psychiatry in medicine. 2019 Mar 1; [PubMed PMID: 30823858]|
|||van Dongen LCM,Wingbermühle E,van der Veld WM,Vermeulen K,Bos-Roubos AG,Ockeloen CW,Kleefstra T,Egger JIM, Exploring the behavioral and cognitive phenotype of KBG syndrome. Genes, brain, and behavior. 2019 Feb 21; [PubMed PMID: 30786142]|
|||Polegato BF,Pereira AG,Azevedo PS,Costa NA,Zornoff LAM,Paiva SAR,Minicucci MF, Role of Thiamin in Health and Disease. Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition. 2019 Jan 15; [PubMed PMID: 30644592]|
|||Doğan İG,Altiokka GU,Türker F,Saka B,Bilgiç B,Orhan EK, Wernicke's Encephalopathy due to Non-Alcoholic Gastrointestinal Tract Disease. Noro psikiyatri arsivi. 2018 Dec; [PubMed PMID: 30622385]|
|||Heirene R,John B,Roderique-Davies G, Identification and Evaluation of Neuropsychological Tools Used in the Assessment of Alcohol-Related Cognitive Impairment: A Systematic Review. Frontiers in psychology. 2018; [PubMed PMID: 30619013]|
|||McGlacken-Byrne D,Wallace E, Vitamin Deficiency and Systemic Failure: The Case For Greater Focus On Wernicke-Korsakoff Syndrome Irish medical journal. 2018 Dec 6; [PubMed PMID: 30560643]|
|||Arts NJ,Walvoort SJ,Kessels RP, Korsakoff's syndrome: a critical review. Neuropsychiatric disease and treatment. 2017; [PubMed PMID: 29225466]|
|||Nakamura ZM,Tatreau JR,Rosenstein DL,Park EM, Clinical Characteristics and Outcomes Associated With High-Dose Intravenous Thiamine Administration in Patients With Encephalopathy. Psychosomatics. 2018 Jul - Aug; [PubMed PMID: 29482863]|
|||Junghanns K,Wetterling T, [Alcohol withdrawal and its major complications]. Fortschritte der Neurologie-Psychiatrie. 2017 Mar; [PubMed PMID: 28320026]|
|||Latt N,Dore G, Thiamine in the treatment of Wernicke encephalopathy in patients with alcohol use disorders. Internal medicine journal. 2014 Sep; [PubMed PMID: 25201422]|
|||Isenberg-Grzeda E,Chabon B,Nicolson SE, Prescribing thiamine to inpatients with alcohol use disorders: how well are we doing? Journal of addiction medicine. 2014 Jan-Feb; [PubMed PMID: 24343128]|
|||Feeney GF,Connor JP, Wernicke-Korsakoff syndrome (WKS) in Australia: no room for complacency. Drug and alcohol review. 2008 Jul; [PubMed PMID: 18584388]|
|||Harper C, The neurotoxicity of alcohol. Human [PubMed PMID: 17439928]|
|||Day E,Bentham P,Callaghan R,Kuruvilla T,George S, Thiamine for Wernicke-Korsakoff Syndrome in people at risk from alcohol abuse. The Cochrane database of systematic reviews. 2004; [PubMed PMID: 14974055]|
|||Sanvisens A,Zuluaga P,Fuster D,Rivas I,Tor J,Marcos M,Chamorro AJ,Muga R, Long-Term Mortality of Patients with an Alcohol-Related Wernicke-Korsakoff Syndrome. Alcohol and alcoholism (Oxford, Oxfordshire). 2017 Jul 1; [PubMed PMID: 28340112]|