Jan W. Wijnia

Biomarkers of delirium as a clue to diagnosis and pathogenesis of Wernicke-Korsakoff syndrome.

Wernickes encephalopathy (WE) and Korsakoffs syndrome are considered to be different stages of the same disorder due to thiamine deficiency, which is called Wernicke−Korsakoff syndrome (WKS). The earliest biochemical change is the decrease of α‐ketoglutarate‐dehydrogenase activity in astrocytes. According to autopsy‐based series, mental status changes are present in 82% of WE cases. The objective of the present review is to identify possible underlying mechanisms relating the occurrence of delirium to WKS.

The Montreal Cognitive Assessment (MoCA) is Superior to the Mini Mental State Examination (MMSE) in Detection of Korsakoff’s Syndrome

The Montreal Cognitive Assessment (MoCA) and Mini Mental State Examination (MMSE) are brief screening instruments for cognitive disorders. Although these instruments have frequently been used in the detection of dementia, there is currently little knowledge on the validity to detect Korsakoff’s syndrome (KS) with both screening instruments. KS is a chronic neuropsychiatric disorder associated with profound declarative amnesia after thiamine deficiency. A representative sample of 30 patients with KS and 30 age-, education-, gender- and premorbid-IQ-matched controls was administered the MoCA and MMSE. The area under the receiver operating characteristic curve (AUC) was calculated in addition to the sensitivity, specificity, positive predictive value, and negative predictive value for various cut-off points on the MoCA and MMSE. Compared with the MMSE, the MoCA demonstrated consistently superior psychometric properties and discriminant validity—AUC: MoCA (1.00 SE .003) and MMSE (0.92 SE .033). When applying a cut-off value as suggested in the manuals of both instruments, the MMSE (< 24) misdiagnosed 46.7% of the patients, while the MoCA (< 26) diagnosed all patients correctly. As a screening instrument with the most optimal cut-offs, the MoCA (optimal cutoff point 22/23, 98.3% correctly diagnosed) was superior to the MMSE (optimal cutoff point 26/27, 83.3% correctly diagnosed). We conclude that both tests have adequate psychometric properties as a screening instrument for the detection of KS, but the MoCA is superior to the MMSE for this specific patient population.

Procedural Learning and Memory Rehabilitation in Korsakoff's Syndrome - a Review of the Literature

Korsakoff’s syndrome (KS) is a chronic neuropsychiatric disorder caused by alcohol abuse and thiamine deficiency. Patients with KS show restricted autonomy due to their severe declarative amnesia and executive disorders. Recently, it has been suggested that procedural learning and memory are relatively preserved in KS and can effectively support autonomy in KS. In the present review we describe the available evidence on procedural learning and memory in KS and highlight advances in memory rehabilitation that have been demonstrated to support procedural memory. The specific purpose of this review was to increase insights in the available tools for successful memory rehabilitation and give suggestions how to apply these tools in clinical practice to increase procedural learning in KS. Current evidence suggests that when memory rehabilitation is adjusted to the specific needs of KS patients, this will increase their ability to learn procedures and their typically compromised autonomy gets enhanced.

Acquisition of an instrumental activity of daily living in patients with Korsakoff's syndrome: A comparison of trial and error and errorless learning

Patients with Korsakoffs syndrome show devastating amnesia and executive deficits. Consequently, the ability to perform instrumental activities such as making coffee is frequently diminished. It is currently unknown whether patients with Korsakoffs syndrome are able to (re)learn instrumental activities. A good candidate for an effective teaching technique in Korsakoffs syndrome is errorless learning as it is based on intact implicit memory functioning. Therefore, the aim of the current study was two-fold: to investigate whether patients with Korsakoffs syndrome are able to (re)learn instrumental activities, and to compare the effectiveness of errorless learning with trial and error learning in the acquisition and maintenance of an instrumental activity, namely using a washing machine to do the laundry. Whereas initial learning performance in the errorless learning condition was superior, both intervention techniques resulted in similar improvement over eight learning sessions. Moreover, performance in a different spatial layout showed a comparable improvement. Notably, in follow-up sessions starting after four weeks without practice, performance was still elevated in the errorless learning condition, but not in the trial and error condition. The current study demonstrates that (re)learning and maintenance of an instrumental activity is possible in patients with Korsakoffs syndrome.

Route learning in Korsakoff's syndrome: Residual acquisition of spatial memory despite profound amnesia.

Korsakoffs syndrome (KS) is characterized by explicit amnesia, but relatively spared implicit memory. The aim of this study was to assess to what extent KS patients can acquire spatial information while performing a spatial navigation task. Furthermore, we examined whether residual spatial acquisition in KS was based on automatic or effortful coding processes. Therefore, 20 KS patients and 20 matched healthy controls performed six tasks on spatial navigation after they navigated through a residential area. Ten participants per group were instructed to pay close attention (intentional condition), while 10 received mock instructions (incidental condition). KS patients showed hampered performance on a majority of tasks, yet their performance was superior to chance level on a route time and distance estimation tasks, a map drawing task and a route walking task. Performance was relatively spared on the route distance estimation task, but there were large variations between participants. Acquisition in KS was automatic rather than effortful, since no significant differences were obtained between the intentional and incidental condition on any task, whereas for the healthy controls, the intention to learn was beneficial for the map drawing task and the route walking task. The results of this study suggest that KS patients are still able to acquire spatial information during navigation on multiple domains despite the presence of the explicit amnesia. Residual acquisition is most likely based on automatic coding processes.

A case of chronic Wernicke's encephalopathy: A neuropsychological study

A 54-year-old woman was referred to our Korsakoff Center because of extensive cognitive problems following acute Wernicke’s encephalopathy (WE). She had a relatively short history of alcohol abuse and was found lying on the floor in her home by her son. After 5 days without treatment, she was diagnosed with WE in a general hospital. During the course of the disease, minimal change to the acute situation occurred, with chronic confusion, attention deficits, and incoherent behavior symptoms most notable unlike classical Korsakoff’s syndrome. Neuropsychological assessment after 4 and 16 months after admission to the hospital revealed global cognitive decline, with striking impairments in attentional, executive, and memory functions. The present case study suggests that the state of confusion and the neuropsychological symptoms in WE can become chronic in case of very late treatment. We therefore recommend that confused alcoholics should receive appropriate parenteral thiamine according to the current clinical standards.

Visuospatial declarative learning despite profound verbal declarative amnesia in Korsakoff’s syndrome

ABSTRACT Korsakoffs syndrome (KS) is a neuropsychiatric disorder characterised by severe amnesia. Although the presence of impairments in memory has long been acknowledged, there is a lack of knowledge about the precise characteristics of declarative memory capacities in order to implement memory rehabilitation. In this study, we investigated the extent to which patients diagnosed with KS have preserved declarative memory capacities in working memory, long-term memory encoding or long-term memory recall operations, and whether these capacities are most preserved for verbal or visuospatial content. The results of this study demonstrate that patients with KS have compromised declarative memory functioning on all memory indices. Performance was lowest for the encoding operation compared to the working memory and delayed recall operation. With respect to the content, visuospatial memory was relatively better preserved than verbal memory. All memory operations functioned suboptimally, although the most pronounced disturbance was found in verbal memory encoding. Based on the preserved declarative memory capacities in patients, visuospatial memory can form a more promising target for compensatory memory rehabilitation than verbal memory. It is therefore relevant to increase the number of spatial cues in memory rehabilitation for KS patients.

Korsakoff's syndrome is preventable.

Wernicke-Korsakoff syndrome (WKS) is a life-threatening neuropsychiatric disorder caused by thiamine (vitamin B1) deficiency. Wernicke-Korsakoff syndrome is associated with mammillary body edema and small vessel ischemia. Many patients who develop WKS have a history of serious alcoholism and self-neglect. It is a common condition as around 15% of the alcoholics show specific WKS neuropathology. Originally, the syndrome was described as a triad of ataxia, eye movement disorders, and mental status change, but recent studies have suggested that patients frequently only show the mental status change [1]. Although it has been known for over 60 years that treatment with high doses of parenteral (intravenous or intramuscular) thiamine replacement therapy has the potency to improve the neuropsychiatric syndrome in the early stage of WKS [2], this is still uncommon medical practice. Recently published studies on treatment perspectives of WKS in general and psychiatric hospitals are alarming: European as well as American studies demonstrated that most patients did not receive thiamine at all or only received it orally in low doses [3] and [4]. Both types of treatment lead to unnecessary cases of chronic WKS (also Korsakoffs syndrome) characterized by severe amnesia and lifelong impaired autonomy [4]. Based on the currently available literature, we suggest that any sign of mental confusion, cognitive defect, or change in mobility in an admitted alcoholic should alarm a clinician for treatable WKS. Parenteral thiamine replacement therapy is well tolerated and regularly ameliorates neuropathology in WKS. According to the European Federation of Neurological Societies and the Royal College of Physicians, parenteral thiamine should be given 200 mg up to 500 mg 3 times daily until symptoms of acute WKS resolute [5]. Importantly, in many cases, the benefit of treating WKS outweighs the risks of treating unnecessarily. The treatment is lifesaving and has the potential to reverse this acute neuropsychiatric syndrome. It is recommended to have a high suspicion of WKS in alcoholic patients and preventively treat them as such.

BNF Recommendations for the Treatment of Wernicke's Encephalopathy: Lost in Translation?

We agree with Thomson and Marshall (2013) that the current prescribing of thiamine replacement therapy for Wernickes Encephalopathy (WE) is ambiguous. In response to their article, we also advocate that any consensus on accurate thiamine treatment for WE should receive sufficient international attention, since too many patients with WE are currently inaccurately treated leading to unnecessary cases of Korsakoffs syndrome. WE is a neurologic disease caused by thiamine …

Preventing Wernicke's encephalopathy in anorexia nervosa: A systematic review: Wernicke's and anorexia nervosa

Anorexia nervosa (AN) is a common eating disorder that affects 2.9 million people worldwide. Not eating a balanced diet or fasting can cause neurological complications after severe vitamin B1 malnourishment, although the precise signs and symptoms of Wernickes encephalopathy (WE) are not clear. Our aim was to review the signs and symptoms of WE in patients with AN. We searched MEDLINE, EMBASE, Scopus, and PiCarta on all case descriptions of WE following AN. All case descriptions of WE in AN, irrespective of language, were included. Twelve WE cases were reviewed, suggesting that WE following AN is still a relatively rare neuropsychiatric disorder. WE is characterized by a triad of: mental status change, ocular signs, and ataxia. In alcoholism, this triad is present in 16% of cases, but eight out of 12 AN cases presented themselves with a full triad of symptomatology. Importantly, patients often had a more complex triad than has been previously described, involving vertigo, diplopia, and the consequences of refeeding syndrome. The development of a full triad and additional symptomatology suggests a late recognition of signs and symptoms of WE in AN. A complicating factor is the overlap between symptoms of thiamine deficiency and the symptoms of WE. Specifically, patients who show rapid weight loss are vulnerable for the development of WE. Eating disorders, such as AN, can lead to WE. Prophylactic thiamine checks and treatment in patients with AN are relevant, and in case of suspicion of WE, adequate parenteral thiamine supplementation is necessary.