9 Wernicke’s Encephalopathy and Korsakoff’s Syndrome

Korsakoff’s syndrome and Wernicke’s encephalopathy are disorders which result in impairment of short-term memory. Wernicke’s encephalopathy is the acute phase, which can then lead to Korsakoff’s syndrome if left untreated (Latt & Dore, 2014). Korsakoff’s syndrome is the chronic phase of the disorder. During the median stages between the two, often times they are named together. The memory deficits of Korsakoff’s syndrome become more obvious as the confusional stage of Wernicke’s encephalopathy improve (Jung et al., 2012). Therefore, these two conditions are often coupled as the Wernicke-Korsakoff syndrome.

Korsakoff’s syndrome is a disorder resulting from a severe deficiency of thiamine, which is an essential vitamin that functions in metabolic processes. Thiamine is also known as vitamin B1 and it is involved in essential brain metabolic and cellular functions, such as carbohydrate metabolism and neurotransmitter production. (Mulholland, 2006). Dietary thiamine is found in whole grains, legumes such as beans and peas, as well as some meats and fishes. People with a well-balanced diet consume sufficient thiamine, however gastrointestinal illnesses can cause an inability to adequately absorb thiamine properly. In addition to gastrointestinal illness, chronic alcohol misuse also impairs the body’s ability to take up thiamine and is often a leading cause of Korsakoff’s syndrome.

People with Korsakoff’s syndrome experience both retrograde and anterograde amnesia, as well as severely impaired short-term memory. Anterograde amnesia refers to an impaired capacity for new learning and retrograde amnesia refers to the loss of information that was acquired before the onset of amnesia (Smith et al., 2013). The patients may experience a very strange behavior called confabulation, which is the fabrication of false memories ranging from subtle to wildly fantastical. People who confabulate do not consciously recognize that their statements are untrue, and are not intentionally trying to deceive others, which is why it is sometimes called “honest lying”. Generally, confabulation only happens as a person is trying to recall recent autobiographical memories which are discrete moments of your life such as what you had for dinner last night The patient’s semantic and procedural memories are less susceptible to confabulation. Furthermore, scientists suggest that people confabulate as a compensatory mechanism to make up for their retrograde amnesia.

Destruction of both neurons and glia cells are seen in the brains of people with Korsakoff’s syndrome. Often, the loss of these cells results in the shrinking of the cortex, thalamus, the hippocampus, cerebellum, and the mammillary bodies. Mammillary bodies are paired structures located at the ventral surface of the brain close to the brain stem and they are part of the limbic system. Findings indicate that mammillary body degeneration might be involved in the memory impairment of Korsakoff’s syndrome but is not sufficient to account for it entirely (Jung et al., 2012). The primary role of the anterior thalamus in Korsakoff’s syndrome is supported by neuroimaging studies. It is shown that Korsakoff’s syndrome results from structural lesion in the mammillo-thalamic tract—white matter projections from the mammillary body to the anterior thalamus (Yoneoka et al. 2004; Josseaume et al. 2007; Jung et al., 2012). Furthermore, hippocampal volume deficits in patients with Korsakoff’s syndrome and alcohol dependency were of a similar extent to what has been observed in patients with Alzheimer’ disease (Sullivan & Marsh 2003; Jung et al., 2012). Therefore, the loss of cells due to thiamine deficiency also impacts the volume of the hippocampus. Lastly, the cerebellum is also at risk of damage due to thiamine deficiency (Mulholland, 2006). It makes sense that damage to these structures results in memory impairment as the hippocampus, cerebellum, anterior thalamus and mammillary bodies are all structures associated with memory.

Neuroimaging studies of Wernicke’s encephalopathy have also found cytotoxic edema and vasogenic edema in the brain. Edema refers to brain swelling and is caused by accumulation of fluid. Cytotoxic edema refers to intracellular accumulation of fluid, and vasogenic edema refers to extracellular accumulation of fluid (Michinaga & Koyama, 2015).  At the acute symptomatic stage of Wernicke’s encephalopathy, thiamine-related glucose and oxidative cellular energy metabolism are disturbed , resulting in imbalance of ionic gradients across the cell membrane, thus leading to vasogenic edema (Hazell et al. 1998; Sechi & Serra 2007; Jung et al., 2012). Inadequate functioning of the ionic pump results in imbalance of ionic gradients across the cell membrane and intracellular water-shift leads to cytotoxic edema  (Jung et al., 2012).   Computerized tomography (CT) scans can detect edematous lesions as low-density abnormalities . Magnetic resonance imaging (MRI) is also useful for visualizing and quantifying these lesions due to their high water content, which appear as signal hyperintensities on T2-weighted images (Jung et al., 2012).

Wernicke’s encephalopathy can be treated by giving thiamine supplements and eliminating alcohol consumption.  Current recommendations for thiamine deficiency are outlined by Praharaj and colleagues (2021), and states that patients at risk for thiamine deficiency should receive 250 mg of thiamine daily intramuscularly for 3–5 days, followed by oral thiamine 100 mg daily. Thiamine deficient individuals with features of Wernicke encephalopathy should receive thiamine orally three times a day (Praharaj et al., 2021).   Furthermore, if treated within days after the onset of symptoms, patients are expected to make a complete recovery. However, since the symptoms of Wernicke’s encephalopathy and Korsakoff’s syndrome present similarly to other disorders, diagnosing these patients properly is often a major challenge. Wernicke’s encephalopathy is not only difficult to differentiate from drunkenness and other causes of confusion, but it also often coexists with other disorders that cause confusion, such as alcohol withdrawal, head injury, and hepatic encephalopathy (Latt & Dore, 2014). If Wernicke’s encephalopathy is not diagnosed early however, it will most likely develop into Korsakoff’s syndrome. Korsakoff’s syndrome is much more complex to treat and 20% of patients require long-term institutionalised care (Latt & Dore, 2014).