EXPERIMENTAL AND THERAPEUTIC MEDICINE 22: 1132, 2021 Korsakoff syndrome: An overlook (Review) IONUŢ POPA1*, IOANA RĂDULESCU1*, ANA MIRUNA DRĂGOI1*, SIMONA TRIFU2 and MIHAI BOGDAN CRISTEA3 1Department of Psychiatry, ‘Prof. Dr. Alex. Obregia’ Clinical Hospital of Psychiatry, 041914 Bucharest; Departments of 2Clinical Neurosciences, 3Morphological Sciences, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania Received June 18, 2021; Accepted July 20, 2021 DOI: 10.3892/etm.2021.10566 Abstract. This review aimed to analyze the latest neurobiolog‑ 3. Clinical features ical findings regarding Korsakoff syndrome, since alcoholism 4. Neurobiology is the most prevalent addiction worldwide. In addition, we 5. Treatment strategies analyzed the optimal treatment that can be administered in 6. Conclusions order to minimize the symptoms and improve the outcome of these patients. The disruption of memory circuits within the brain of alcoholic patients results in the amnestic syndrome 1. Research methods known as Korsakoff syndrome. It is generally characterized by a chronic neuropsychiatric syndrome caused by vitamin B1 The review started from an extensive search of Korsakoff (thiamine) deficiency. Other categories of patients can develop syndrome for the last 10 years over the database Korsakoff syndrome without consuming alcohol such as AIDS PubMed®/MEDLINE (http://www.ncbi.nlm.nih.gov/pubmed). patients, terminally ill cancer patients, or patients with chronic Even if the trigger for this disease can be found in more than infections and malnutrition. Vitamin B1 is required in the 2,700 scientific articles and 9 clinical trials, the Korsakoff Krebs cycle for production of adenosine triphosphate (ATP). keyword returned only 160 published scientific papers, 91 It is also a cofactor in the production of acetylcholine and in the last 5 years and only one clinical trial. As research certain neurotransmitters. Alcohol consumption can decrease keywords we used ‘Korsakoff’ OR ‘Korsakoff syndrome’ OR the intake, gastrointestinal absorption and cellular utilization ‘Wernicke’ AND ‘Wernicke encephalopathy’ AND ‘alcohol’ of vitamin B1. Treatment of alcohol withdrawal along with AND ‘Thiamine’ AND ‘brain structures’ AND ‘treatment’. high doses of vitamin B1 can improve the general outcome In the same time ‘Korsakoff’ search over Web of Knowledge of patients. A small percentage of patients can recover from returned 342 scientific articles but only one published in Wernicke's encephalopathy with no permanent brain damage. Romania. We constructed an Excel table highlighting these The onset of Korsakoff syndrome darkens the prognosis. findings, we eliminated the duplicates, we kept the review Alcohol abstinence is an absolute recommendation and articles because some of them bring upfront old results or prevents the extension of neural damage. ideas that are still valid and useful. 2. Introduction Contents Korsakoff syndrome is a chronic memory disorder that is gener‑ 1. Research methods ally preceded by an acute manifestation and illness named 2. Introduction Wernicke's encephalopathy. The symptoms of Wernicke's encephalopathy include confusion, oculomotor disturbances and incoordination of movement especially ataxia. After an acute episode, approximately 80% of unmedicated patients develop behavioral abnormalities and memory impairments Correspondence to: Dr Simona Trifu, Department of Clinical that are later diagnosed as Korsakoff syndrome. Neurosciences, ‘Carol Davila’ University of Medicine and Pharmacy, Neuroimaging techniques performed on patients with 37 Dionie Lupu Street, 020021 Bucharest, Romania Korsakoff syndrome demonstrate that there are specific abnor‑ E‑mail: [email protected] malities in the grey and white matter of alcoholic patients. *Contributed equally Alcohol damages the structure and decreases the volume of the white matter. In alcoholic patients, there have been studies Key words: Korsakoff syndome, Wernicke's encephalopathy, suggesting atrophy and metabolic abnormalities in the frontal addiction, alcohol, GABA receptors, neurobiology, neurogenesis lobe, amygdala, thalamus, hippocampus and cerebellum. The lesions within these brain regions involve the neurological circuits of both anterograde and retrograde memory. In severe 2 POPA et al: KORSAKOFF SYNDROME OVERVIEW cases, procedural memory and emotional processing can be Caine criteria have been developed to diagnose Wernicke's affected (1). encephalopathy, but due to the frequent overlap with Korsakoff Over time, autopsies have shown that Korsakoff syndrome is syndrome, they can also be used to diagnose Korsakoff not a rare condition, especially in alcohol‑abusing patients (2). syndrome (11). In order to diagnose Wernicke's encepha‑ Although no clear definition of Korsakoff syndrome has lopathy at least two of the following signs must be present: been established, it is generally characterized by a chronic Oculomotor disorders, cerebellar dysfunction, nutritional neuropsychiatric syndrome caused by vitamin B1 (thiamine) deficiency, altered mental status or mild memory disorder (8). deficiency (3). Korsakoff syndrome occurs in those who Although Korsakoff syndrome is defined as a memory have suffered from Wernicke encephalopathy and have not disorder, it is obvious that it contains multiple behavioral and received adequate and rapid treatment with thiamine (4). cognitive symptoms. As reported in review articles, in addition This syndrome is most often associated with chronic alcohol to amnesia, Bonhoeffer and Gudden also specified blunt affect, consumption, but it can also be caused by other processes that confabulations and apathy as characteristic symptoms (4,12). lead to thiamine deficiency, such as malnutrition, metabolic Memory disorder is the most studied symptom of pathologies, gastrointestinal diseases (e.g. Crohn's disease or Korsakoff syndrome. Patients have trouble with episodic pancreatitis), hyperemesis gravidarum, HIV, infections, and memory (13), but also with spatial, contextual and other types anorexia nervosa (5). Its effects can be observed after bariatric of memory (14,15). surgery; thus, supplementation of the diet with vitamin B1 is The diagnosis of Korsakoff syndrome is made based on required in order to achieve adequate prevention (3). mainly clinical symptoms, in addition to laboratory and Patients who develop Korsakoff syndrome for reasons imaging tests. Doctors often have to deliberate about the other than alcohol use are mostly women and young patients. possibility of this diagnosis because it is easy to be missed Unlike alcoholic patients who develop Korsakoff syndrome, and because delaying treatment greatly increases mortality. non‑alcoholic patients exhibit better survival and higher Even if the diagnosis has not been confirmed, it is relatively cure rates (6). Korsakoff syndrome is in the same family as safe to administer thiamine prophylactically. Thiamine Wernicke's encephalopathy, but a major difference is that should be administered before glucose to avoid the onset of Wernicke's encephalopathy is acute and often reversible, and Wernicke‑Korsakoff syndrome (16,17). Korsakoff syndrome is chronic and often irreversible (7). When the two pathological entities (Wernicke's encepha‑ 4. Neurobiology lopathy and Korsakoff syndrome) present together, it is stated that the patient suffers from Wernicke‑Korsakoff syndrome. The neurobiology of Korsakoff syndrome is closely linked Wernicke's encephalopathy is characterized by acute confu‑ to the direct neurotoxic effects of alcohol. The neuropatho‑ sion, while Korsakoff syndrome is characterized by confusion, logical findings regarding Korsakoff syndrome conclude memory disorders and gait abnormalities (4,7). that chronic alcoholism can disrupt neural pathways at both Research concerning Korsakoff syndrome have made a macroscopically and microscopical level. Postmortem studies great contribution and a better definition of the concepts of have confirmed that the brain of alcoholic patients consists of memory; and moreover, have indicated that the structures of multiple site atrophy, especially in the frontal lobes, limbic the diencephalon play a crucial role in memory (4). system, the hypothalamus and cerebellum (18). These regions Thiamine has been the first‑line treatment for more than are the most vulnerable of being damaged by alcohol. 50 years, but there are still some uncertainties about the dose The frontal lobe, especially the prefrontal cortex, is the and duration of treatment (2). center of our personality and executive abilities. In addition, this region of the brain connects to multiple association 3. Clinical features areas, thus being at the root of our logical thinking and understanding of the world. Disruption of this circuitry due to It is often difficult to differentiate Wernicke's encephalopathy atrophy and direct neurotoxicity causes episodic and executive from Korsakoff syndrome because both belong to the same memory loss, along with personality and emotional processing spectrum of disease, with their etiology consisting of thiamine changes (19,20). deficiency. Doctors must screen for both pathologies when Patients with impaired frontal lobe activity due to alco‑ certain clinical features are present (8). holism or Korsakoff syndrome tend to be more impulsive and Normally, Wernicke's encephalopathy is unraveled by the aggressive. There are multiple explanations for their inability triad ataxia, ophthalmoplegia and altered mental status. Few to control their