Korsakoff Syndrome

Background

• Korsakoff syndrome is characterized by irreversible short-term episodic memory impairments, while other cognitive functions are relatively preserved or much less impaired. Korsakoff syndrome almost always occurs following thiamine deficiency and Wernicke encephalopathy, which may have been subclinical or undiagnosed.
• Korsakoff syndrome has been reported in about half of patients with Wernicke encephalopathy who survive.
• The most common cause of underlying Wernicke encephalopathy is alcohol-related thiamine deficiency, although thiamine deficiency may be due to other causes, including prolonged vomiting (such as due to hyperemesis gravidarum), cancer and chemotherapy, starvation, gastrointestinal disease, and bariatric or other gastrointestinal surgery.

Evaluation

• Suspect Korsakoff syndrome in patients with severe, irreversible amnesia and a history of Wernicke encephalopathy or risk factors for thiamine deficiency.
• Diagnosis of Korsakoff syndrome is made clinically based on thorough history-taking of knowledgeable informant and mental status exam assessing several areas of cognitive functioning.
  • Episodic memory (related to personal events) is affected more than other types of memory. Semantic (factual) and procedural (verbal, motor, and cognitive skills) are less affected.
  • Short-term memory deficits (minutes-to-days) are most severe. Recall of immediate memories (within past few minutes) and long-term memories (from prior to onset of Wernicke encephalopathy) are relatively intact.
  • Patient may confabulate (involuntarily form false memories) as an adaptive response to explain memory impairments, especially early in disease course.
  • Other behavioral and neuropsychiatric symptoms are often present, including executive dysfunction, apathy, emotional blunting, and/or emotional instability.
• Evidence of prior Wernicke encephalopathy supports the diagnosis of Korsakoff syndrome, including clinical diagnosis of Wernicke encephalopathy, magnetic resonance imaging (MRI), and/or blood testing showing low serum thiamine.
• MRI findings associated with Korsakoff syndrome include atrophy of medial thalami, mammillary bodies, anterior corpus callosum, areas around third and fourth ventricles (especially in diencephalon), and/or frontal lobes.

Management

• Abstinence from alcohol is strongly advised.
  • Patients with Korsakoff syndrome are reported to have a reduced alcohol tolerance and higher risk for subsequent episodes of Wernicke encephalopathy and further cognitive decline.
  • Refer patient to treatment for alcohol use disorder if appropriate.
• Consider occupational therapy evaluation to determine a patient's ability to complete the activities of daily living and determine appropriate level of care.
• Consider cognitive and behavioral strategies tailored to patient's memory deficits to support new learning, such as providing a calm and well-structured environment, memory aids, and errorless learning techniques.
• Consider day programming or long-term residential care as needed to alleviate caregiver burden.
• No effective medications are currently available for the management of chronic cognitive deficits in Korsakoff syndrome.
  • Memantine or donepezil may be considered on a trial basis for Korsakoff syndrome, but evidence is extremely limited.
  • For the management of behavioral symptoms, consider medications to manage concurrent depression, anxiety, insomnia, or psychosis.