What is the Korsakoff syndrome? - a paper in tribute to Prof Alwyn Lishman.

INTRODUCTION: Alwyn Lishman was interested in how memory research could be applied to clinical psychiatry. After a brief review of his major contributions, this paper will focus on his research on the alcoholic Korsakoff syndrome. It will consider how his findings relate to contemporary debates, particularly on how the syndrome should be defined, and its relationship to broader alcohol-induced cognitive impairments. METHODS: A review of the contribution of Alwyn Lishman, Robin Jacobson and colleagues to our knowledge of Korsakoff's syndrome, together with a review of the pertinent recent literature. RESULTS: Lishman and colleagues followed earlier authors in defining the Korsakoff syndrome in terms of disproportionate memory impairment, but they also noted a variable degree of IQ, frontal-executive, and timed visuo-spatial impairment in their cases. More recent authors have included such features in their definitions of the syndrome. Lishman also argued for a specific "alcoholic dementia". The present paper argues that recent definitions of the Korsakoff syndrome confound its core and associated features, and also fail to recognise the multifactorial basis of alcohol-related brain damage. CONCLUSIONS: Korsakoff's syndrome is best defined in terms of disproportionate memory impairment, and more widespread cognitive impairment is best encompassed within "alcohol-related brain damage".

The specificity of thalamic alterations in Korsakoff's syndrome: Implications for the study of amnesia.

The pathophysiological mechanisms behind amnesia are still unknown. Recent literature, through the study of patients with Alcohol Use Disorder with and without Korsakoff's syndrome, increasingly shows that physiological alterations to the thalamus have an important role in the development of amnesia. This review gives an overview of neuropsychological, neuropathological and neuroimaging contributions to the understanding of Korsakoff's syndrome, highlighting the central role of the thalamus in this amnesia. The thalamus being a multi-nucleus structure, the limitations regarding the loci, nature and alterations to specific nuclei are discussed, along with potential solutions. Finally, future directions for clinical research are laid out to unravel the intricacies inherent to amnesia. They consider the need to evaluate the physiological role of the thalamus, not only as an entity but also as part of a brain circuit through a more integrative approach.

Participation of cAMP/PKA-Mediated Signaling Pathways in Functional Activity of Regeneration-Competent Cells in the Nervous Tissue under Conditions of Ethanol-Induced Neurodegeneration.

We studied the involvement of cAMP/PKA signaling in the realization of the growth potential of neural progenitors and secretion of neurotrophic growth factors by glial elements under conditions of ethanol-induced neurodegeneration in vitro and in vivo. The stimulating role of cAMP and PKA in cell cycle progression of the neural progenitor cells and in production of neurotrophins by the cells in nervous tissue under the optimal conditions to vital activity was demonstrated. Ethanol inverted the role of cAMP/PKA signaling pathways in determination of the proliferation-differentiation status of neural stem cells. Selective blockade of adenylate cyclase or PKA in neural stem cells increased the rate of their division against the background of relative decrease in differentiation rate. In addition, cAMP/PKA signaling does not longer participate in neurotrophin production by glial cells in neurodegeneration. These findings suggest that inhibitors of activity/expression of adenylate cyclase and PKA can be considered as possible drugs with regenerative activity for the treatment of nervous system pathologies provoked by alcohol.

Forgetting the new locations of one's keys: spatial-memory interference in Korsakoff's amnesia.

The present study focused on interference in a group of patients with amnesia due to Korsakoff's syndrome (KS) within the domain of spatial memory. An object-location memory task was used in which participants first learned an array of objects on a computer screen, followed by a reconstruction of the object positions. Next a trial was given in which the same objects were presented only now in different locations. Participants had to place the objects a second time but at the new locations. This was repeated for seven pairs of baseline/interference trials. Both Korsakoff patients and matched controls did worse on the interference trials than on the baseline trials, indicating that it is difficult to relearn new spatial locations for objects that previously were remembered in other locations. When computing relative interference effects (that is the percentage change from baseline in the interference trials), Korsakoff patients were less affected than controls. It is discussed in how far interference depends on the strength of the original memories, which are markedly lower in KS patients.

[The possibilities of neurostimulation (sympathetic correction) in the treatment of amnestic (Korsakoff's) psychosis]. / Vozmozhnosti neirostimuliatsii (simpatokorrektsii) v terapii amnesticheskogo (korsakovskogo) psikhoza.

AIM: To evaluate the efficacy of non-invasive multichannel electrical stimulation (sympathetic correction) in patients with alcohol amnesic (Korsakoff's) psychosis. MATERIAL AND METHODS: Thirty-seven men, aged 33-48 years, with Korsakoff's (amnestic) psychosis were studied. The duration of disease varied from 12 to 24 month. The device of electrical stimulation of neck nerve structures was used for neuroelectrostimulation. Treatment included 15 sessions within 3 weeks. During this period, patients did not receive pharmacological therapy. The Frontal Assessment Battery (FAB), the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE) were used to determine changes in cognitive state of patients. Electroencephalography with qEEG analysis and spectral analysis of heart rate variability (HRV) were carried out as well. RESULTS AND CONCLUSION: Positive effects of treatment were observed in all patients that suggested the high therapeutic potential of the neuroelectrostimulation method.

Blackouts among male and female youth seeking emergency department care.

BACKGROUND: Alcohol-related blackouts are a common consequence of heavy drinking, and these blackouts pose risk for injury and other adverse health outcomes. OBJECTIVE: To examine the prevalence and correlates of blackouts among underage drinkers. METHODS: Youth (ages 14-20) presenting to a suburban Emergency Department (ED) completed screening surveys. Among those reporting past-year alcohol consumption, we examined past 3-month blackouts in relation to: background characteristics (e.g., demographics, fraternity/sorority involvement), substance use, sexual risk behaviors and incapacitated sexual assault (unaware/unable to consent due to alcohol/drugs), forced sexual assault, positive depression screening, and reason for ED visit (injury vs. medical). RESULTS: In total, 2,300 past-year drinkers participated: 58% female, 75% Caucasian, and mean age = 18.4. Regarding past 3-month blackouts, 72.7% reported none, 19.3% reported monthly or less, and 8% reported monthly or more. Multivariate cumulative logit regression indicated that blackout frequency was positively associated with: college involvement in Greek life, alcohol use severity, prescription drug misuse, marijuana, screening positive for depression, incapacitated sexual assault, and a gender by alcohol use severity interaction. CONCLUSION: With one-quarter of this clinical sample reporting recent blackouts, as well as the association between blackout frequency and health risk behaviors and other outcomes, findings underscore the need for programs focusing on substance use, depression, and preventing sexual assault. Interventions should also address poly-substance use and drinking motives. Although findings highlight how college students in Greek life may be at high risk for blackouts, many participants not in college also reported blackouts, suggesting that interventions in other settings are also needed.

Preventing and diagnosing dementia.

While dementia is an umbrella term for a range of degenerative brain disorders, many share similar presentations. Nurses are ideally placed to identify those at risk and empower them to access treatment and plan and prepare for their future needs--as such, they need up-to-date knowledge of the signs and symptoms of the different types of dementia to identify risk factors and make an informed diagnosis. This article, the third in a four-part series on dementia, examines the risk factors, signs, symptoms and diagnosis of dementia, as well as outlining lifestyle factors such as diet and exercise that may help to prevent the development of the condition.

Into the future with little past: exploring mental time travel in a patient with damage to the mammillary bodies/fornix.

OBJECTIVE: Remembering the past and imaging the future are both manifestations of 'mental time travel'. These processes have been found to be impaired in patients with bilateral hippocampal lesions. Here, we examined the question of whether future thinking is affected by other Papez circuit lesions, namely: damage to the mammillary bodies/fornix. METHOD: Case (SL) was a 43-year-old woman who developed dense anterograde and retrograde amnesia suddenly, as a result of Wernicke-Korsakoff's syndrome. A region of interest volumetric Magnetic resonance imaging (MRI) analysis was performed. We assessed past and future thinking in SL and 11 control subjects of similar age and education with the adapted Autobiographical Interview (AI). Participants also completed a battery of neuropsychological tests. RESULTS: Volumetric MRI analyses revealed severely reduced fornix and mammillary body volumes, but intact hippocampi. SL showed substantial, albeit temporally graded retrograde memory deficits on the adapted AI. Strikingly, whilst SL could not provide any specific details of events from the past two weeks or past two years and had impaired recall of events from her late 30s, her descriptions of potential future events were normal in number of event details and plausibility. CONCLUSIONS: This dissociation of past and future events' performance after mammillary body and fornix damage is at odds with the findings of the majority of patients with adult onset hippocampal amnesia. It suggests that these non-hippocampal regions of the Papez circuit are only critical for past event retrieval and not for the generation of possible future events.

Rewriting the valuation and salience of alcohol-related stimuli via memory reconsolidation.

The transient period of memory instability that can be triggered when memories are retrieved under certain conditions offers an opportunity to modify the maladaptive memories at the heart of substance use disorders (SUDs). However, very well-learned memories (such as those in excessive drinking and alcohol use disorders) are resistant to destabilisation when retrieved or may not destabilise at all. Memory retrieval and intervention procedures that reliably destabilise and update maladaptive motivational memories may help to improve the long-term treatment of SUDs. In 59 hazardous drinkers, we tested a novel retrieval procedure for destabilising well-learned cue-drinking memory networks that maximises prediction error (PE) via guided expectancy violation during retrieval of these memories. This was compared with a retrieval procedure without PE and no-retrieval controls. We subsequently counterconditioned alcohol cues with disgusting tastes and images in all groups and assessed responding to alcohol stimuli 1 week later. Counterconditioning following PE retrieval produced generalised reductions in oculomotor attentional bias, explicit valuation and outcome expectancies in response to alcohol cues 1 week after intervention, evidence of updating of distributed motivational drinking memory networks. These findings demonstrate that well-learned cue-drinking memories can be destabilised and that learning history need not constrain memory destabilisation if PE is maximised at retrieval. Broad rewriting of diverse aspects of maladaptive memory by counterconditioning is achievable following this procedure. The procedure described may provide a platform for the development of novel memory-modifying interventions for SUDs.

Thalamic abnormalities are a cardinal feature of alcohol-related brain dysfunction.

Two brain networks are particularly affected by the harmful effect of chronic and excessive alcohol consumption: the circuit of Papez and the frontocerebellar circuit, in both of which the thalamus plays a key role. Shrinkage of the thalamus is more severe in alcoholics with Korsakoff's syndrome (KS) than in those without neurological complication (AL). In accordance with the gradient effect of thalamic abnormalities between AL and KS, the pattern of brain dysfunction in the Papez's circuit results in anterograde amnesia in KS and only mild-to-moderate episodic memory disorders in AL. On the opposite, dysfunction of the frontocerebellar circuit results in a similar pattern of working memory and executive deficits in the AL and KS. Several hypotheses, mutually compatible, can be drawn to explain that the severe thalamic shrinkage observed in KS has different consequences in the neuropsychological profile associated with the two brain networks.

What does a comparison of the alcoholic Korsakoff syndrome and thalamic infarction tell us about thalamic amnesia?

In this review, the clinical, neuropsychological, and neuroimaging findings in the alcoholic Korsakoff syndrome and in thalamic amnesia, resulting from focal infarction, are compared. In both disorders, there is controversy over what is the critical site for anterograde amnesia to occur-damage to the anterior thalamus/mammillo-thalamic tract has most commonly been cited, but damage to the medio-dorsal nuclei has also been advocated. Both syndromes show 'core' features of an anterograde amnesic syndrome; but retrograde amnesia is generally much more extensive (going back many years or decades) in the Korsakoff syndrome. Likewise, spontaneous confabulation occurs more commonly in the Korsakoff syndrome, although seen in only a minority of chronic cases. These differences are attributed to the greater prevalence of frontal atrophy and frontal damage in Korsakoff cases.

Component processes of memory in alcoholism: pattern of compromise and neural substrates.

Initially, alcohol-related memory deficits were considered only through the prism of Korsakoff's syndrome (KS). It is now clear, however, that chronic alcohol consumption results in memory disorders in alcoholics without ostensible neurologic complications, such as Wernicke's encephalopathy and KS. Most of the principal memory components are affected, including working memory, episodic memory, semantic memory, perceptual memory, and procedural memory. The extent of those cognitive impairments depends on several factors, such as age, gender, nutritional status, and psychiatric comorbidity. While memory disorders, especially episodic memory deficits, are largely definitive in patients with KS, recovery of memory abilities has been described with abstinence in uncomplicated alcoholics. Neuropsychologic impairments, and especially memory disorders, must be evaluated at alcohol treatment entry because they could impede patients from benefiting fully from cognitive and behavioral treatment approaches for alcohol dependence. Screening of memory deficits could also enable clinicians to detect, among alcoholics without ostensible neurologic complications, those at risk of developing permanent and debilitating amnesia that features KS.

Alcoholic metabolic emergencies.

Ethanol intoxication and ethanol use are associated with a variety of metabolic derangements encountered in the Emergency Department. In this article, the authors discuss alcohol intoxication and its treatment, dispel the myth that alcohol intoxication is associated with hypoglycemia, comment on electrolyte derangements and their management, review alcoholic ketoacidosis, and end with a section on alcoholic encephalopathy.

Pellagra and alcoholism: a biochemical perspective.

Historical and clinical aspects of pellagra and its relationship to alcoholism are reviewed from a biochemical perspective. Pellagra is caused by deficiency of niacin (nicotinic acid) and/or its tryptophan (Trp) precursor and is compounded by B vitamin deficiencies. Existence on maize or sorghum diets and loss of or failure to isolate niacin from them led to pellagra incidence in India, South Africa, Southern Europe in the 18th century and the USA following the civil war. Pellagra is also induced by drugs inhibiting the conversion of Trp to niacin and by conditions of gastrointestinal dysfunction. Skin photosensitivity in pellagra may be due to decreased synthesis of the Trp metabolite picolinic acid → zinc deficiency → decreased skin levels of the histidine metabolite urocanic acid and possibly also increased levels of the haem precursor 5-aminolaevulinic acid (5-ALA) and photo-reactive porphyrins. Depression in pellagra may be due to a serotonin deficiency caused by decreased Trp availability to the brain. Anxiety and other neurological disturbances may be caused by 5-ALA and the Trp metabolite kynurenic acid. Pellagra symptoms are resolved by niacin, but aggravated mainly by vitamin B6. Alcohol dependence can induce or aggravate pellagra by inducing malnutrition, gastrointestinal disturbances and B vitamin deficiencies, inhibiting the conversion of Trp to niacin and promoting the accumulation of 5-ALA and porphyrins. Alcoholic pellagra encephalopathy should be managed with niacin, other B vitamins and adequate protein nutrition. Future studies should explore the potential role of 5-ALA and also KA in the skin and neurological disturbances in pellagra.

Chronic alcohol consumption and its effect on nodes of frontocerebellar and limbic circuitry: comparison of effects in France and the United States.

Alcohol use disorders present a significant public health problem in France and the United States (U.S.), but whether the untoward effect of alcohol on the brain results in similar damage in both countries remains unknown. Accordingly, we conducted a retrospective collaborative investigation between two French sites (Caen and Orsay) and a U.S. laboratory (SRI/Stanford University) with T1-weighted, structural MRI data collected on a common imaging platform (1.5T, General Electric) on 288 normal controls (NC), 165 uncomplicated alcoholics (ALC), and 26 patients with alcoholic Korsakoff's syndrome (KS) diagnosed at all sites with a common interview instrument. Data from the two countries were pooled, then preprocessed and analyzed together at the U.S. site using atlas-based parcellation. National differences indicated that thalamic volumes were smaller in ALC in France than the U.S. despite similar alcohol consumption levels in both countries. By contrast, volumes of the hippocampus, amygdala, and cerebellar vermis were smaller in KS in the U.S. than France. Estimated amount of alcohol consumed over a lifetime, duration of alcoholism, and length of sobriety were significant predictors of selective regional brain volumes in France and in the U.S. The common analysis of MRI data enabled identification of discrepancies in brain volume deficits in France and the U.S. that may reflect fundamental differences in the consequences of alcoholism on brain structure between the two countries, possibly related to genetic or environmental differences.

[Anti-NMDA encephalitis in psychiatry; malignant catatonia, atypical psychosis and ECT].

The symptoms of malignant (lethal) catatonia has been reported similar to initial symptoms of anti-NMDAR encephalitis. Subsequently, this autoimmune limbic encephalitis has been noticed in many psychiatrists. We have experienced several cases with malignant catatonia having anti-NMDAR antibody without clinical signs of encephalitis. Thereafter, we have also found anti-NMDAR antibody positive patients of young females with acute florid psychiatric symptoms without clinical signs of encephalitis. The features of these patients mirror-those of "Atypical psychosis" proposed by Mitsuda in Japan, a notion derived from "Cycloid psychosis" conceptualized by German psychiatrist, Leonhard. Both cycloid and atypical psychosis have coinciding features of acute onset, emotional disturbances, psychomotor disturbances, alternations of consciousness, high prevalence in women and oriented premorbid personality. Both malignant catatonia and atypical psychosis have been known to be effectively treated with modified electro convulsion therapy (m-ECT). Our 5 cases with anti-NMDAR antibody, m-ECT treatments were effective. Infectious encephalitis is contra indication of m-ECT, but this autoimmune encephalitis would be careful indication. Schizophrenia is a common, heterogeneous, and complex disorder with unknown etiology. There is established evidence of NMDAR hypofunction as a central component of the functional disconnectivity; this is one of the most accepted models for schizophrenia. Moreover, autoimmune mechanisms have been proposed to be involved, at least in subgroups of schizophrenia patients. Further research of anti-NMDAR antibody and encephalitis would be important clues for the investigation of schizophrenia, catatonia and atypical psychosis.

[Alcohol induced cognitive deficits]. / Alkohol induzierte kognitive Dysfunktion.

Previous studies could show a complex relationship between alcohol consumption and cognition but also with processes of ageing both social and biological. Acute effects of alcohol during intoxication include clinical signs such as excitation and reduced inhibition, slurred speech, and increased reaction time but also cognitive dysfunction, especially deficits in memory functions. However, these cognitive deficits during alcohol intoxication are reversible while patients with alcohol addiction and chronic alcohol intake show severe impairments of cognitive functions especially deficits in executive functions. Frontal executive impairments in these patients include deficits in problem solving, abstraction, planning, organizing, and working memory.Additionally, gender specific deficits are relevant for the course of the disease and its concomitant health problems with female alcoholics showing a higher vulnerability for cognitive dysfunction and brain atrophy at earlier stages of alcoholism history.

Pellagra encephalopathy in the context of alcoholism: review and case report.

AIMS: The aim of the study was to review and describe the Alcoholic Pellagra Encephalopathy, a severe neuropsychiatric condition caused by a combination of niacin (vitamin B3) deficiency and alcohol abuse. METHODS: PsychInfo, Medline and Embase databases were searched for peer-reviewed studies addressing this illness. RESULTS: A historical and conceptual review of the psychopathological aspects of this condition is offered, followed by the report of a patient with a history of chronic alcohol consumption showing signs of pellagra, delusions and visual hallucinations, which was treated successfully with niacin. CONCLUSION: Pellagra encephalopathy should still be considered in the differential diagnosis of acute psychotic disorders seen in the context of chronic alcoholism.