Korsakoff Syndrome: A Review of Neuropsychiatric Manifestations and Management Strategies for the Consultation-Liaison Psychiatrist

Abstract: Background/Significance:
Korsakoff syndrome (KS) is a neuropsychiatric disorder caused by thiamine deficiency characterized by severe anterograde amnesia. CL Psychiatrists are often consulted in the management of complex neuropsychiatric sequelae, including aggression and disinhibition; however, the evidence base for diagnostication and management is sparse and fragmented. This narrative review aims to address this gap by centralizing data to provide CL psychiatrists with uptodate clinical considerations and management strategies.

Methods:
We conducted a PubMed database search through March of 2024 using search terms (Korsakoff OR Wernicke-Korsakoff) AND (neuropsychiatric OR psychiatric OR management). Sources describing Korsakoff Syndrome etiology, diagnostics, symptomatology, pathophysiology, and management were included. Data were synthesized to develop a narrative review intended for CL Psychiatrists.

Results:
Of the 530 publications, 14 met criteria of methodological rigor, presentation of novel findings, or focus on KS neuropsychiatric sequelae and management.

Discussion:
The evolving nosology of Korsakoff syndrome contributes to its complexity and complicates diagnosis. CL Psychiatrists should be aware of ongoing debate and that recent definitions acknowledge a spectrum of presentation with abnormal mental state and amnesia as defining features. They should also identify additional symptoms that include executive dysfunction and behavioral disorders, with severe forms including anterograde amnesia, retrograde amnesia, confabulation, apathy, anxiety, depression, psychosis, irritability, aggression, disinhibition and emotional lability.

Regarding pathophysiology, while alcohol misuse is the most common risk factor for KS, CL psychiatrists should be aware of various non-alcoholic causes of thiamine deficiency that can result in KS. These include nutritional deficiencies (malnutrition or inadequate intake seen in poverty, homelessness, restrictive diets), gastrointestinal disorders (chronic inflammatory bowel diseases such as Crohn’s and ulcerative colitis, bariatric surgery), varied medical conditions (hyperemesis gravidarum, end-stage cancer, and severe prolonged infections), and genetic predispositions for those with thiamine transporter gene polymorphisms.

There are no FDA approved medications for the neuropsychiatric sequelae of KS, with early prevention via high dose IV-thiamine remaining essential. But, CL Psychiatrists are often called upon to manage the sequelae spectrum with fragmented literature due to, in part, fragmented nosology. A full review of neuropsychiatric symptom management will be discussed at the annual meeting. In short, certain pharmacologic agents show promise at targeting cognitive symptoms, including noradrenergic agents (clonidine), dopaminergic agents (modafinil, methylphenidate), NMDA antagonists (memantine) and SSRIs (fluvoxamine). Antipsychotics may be used acutely for aggression, with limited evidence suggesting a possible mortality benefit.

Non-pharmacologic interventions include procedural learning and memory rehabilitation. Memory compensation techniques such as diaries, calendars, and smartphone apps, can assist with memory and improve independence. In addition, structured and predictable environments with clear communication can be beneficial.

Conclusion/Implications:
This narrative review provides a centralized resource for KS that clarifies the evolving nosology, acknowledges the spectrum of presentations, and explores management approaches. It is designed to equip CL Psychiatrists with the knowledge necessary to promote early diagnosis, implement evidence-based interventions, and ultimately contribute to improved patient outcomes.