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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".

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., (Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.)

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.

The purpose of this study was to determine whether meeting historical criteria for unsuspected Wernicke's encephalopathy (WE), largely under-diagnosed in vivo, explains why some alcoholics have severe neuropsychological deficits, whereas others, with a similar drinking history, exhibit preserved performance. Demographic, clinical, alcohol related, and neuropsychological measures were collected in 56 abstinent alcoholics and 38 non-alcohol-dependent volunteers. Alcoholics were classified using the clinical criteria established by Caine et al (1997) and validated in their neuropathological study of alcoholic cases. Our alcoholics who met a single criterion were considered 'at risk for WE' and those with two or more criteria with 'signs of WE'. Whole blood thiamine was also measured in 22 of the comparison group and 28 alcoholics. Of the alcoholics examined, 27% met no criteria, 57% were at risk for WE, and 16% had signs of WE. Neuropsychological performance of the alcoholic subgroups was graded, with those meeting zero criteria not differing from controls, those meeting one criterion presenting mild-to-moderate deficits on some of the functional domains, and those meeting two or more criteria having the most severe deficits on each of the domains examined. Thiamine levels were selectively related to memory performance in the alcoholics. Preclinical signs of WE can be diagnosed in vivo, enabling the identification of ostensibly 'uncomplicated' alcoholics who are at risk for neuropsychological complications. The graded effects in neuropsychological performance suggest that the presence of signs of WE explains, at least partially, the heterogeneity of alcoholism-related cognitive and motor deficits.

We investigated the role of feedback processing in decision making under risk conditions in 50 patients with amnesia in the course of alcoholic Korsakoff's syndrome (KS). Half of the patients were administered the Game of Dice Task (GDT) and the remaining 25 patients were examined with a modified version of the GDT in which no feedback was provided. Patients' results in the GDT and in the modified version were compared with that of 50 healthy subjects of whom 25 subjects performed the original GDT and 25 performed the modified version. While performance on the original GDT was superior to performance on the modified GDT in healthy subjects, KS patients performed similarly on both the GDT with and GDT without feedback. Performance on both task versions was correlated with categorization and set-shifting. The findings indicate that amnesic patients do not profit from receiving feedback for their decisions in explicit risk conditions.

Besides forgetting, memory is also prone to distortions, errors and illusions. Confabulation is one type of memory distortion that may occur in cases of brain damage. Although confabulations are described anecdotally in patients with alcoholic Korsakoff syndrome (KS), there are few systematic investigations of the presence and nature of these types of false memories in KS. Moreover, it is unclear whether KS patients' confabulations evenly affect all types of memories, or whether certain memory domains are more susceptible. Our study attempted to clarify two questions: first, whether confabulations are a critical feature of the cognitive impairment associated with long-term KS in a large sample of patients (N=42). Second, we investigated which memory domain is most likely affected by confabulations in KS. To elicit confabulations, we used a Confabulation Interview containing questions from different memory domains. We found that KS patients overall confabulated more compared to a group of healthy subjects. Furthermore, we found that patients confabulated most within the episodic/autobiographical memory domain. Our results imply that besides pronounced memory deficits typically associated with KS, confabulation can also be regarded as a clinical feature of the disease. The preponderance of episodic confabulation obtained here by using a standardized test, confirms anecdotic reports that KS patients confabulate in everyday life mainly with respect to their personal past and present. Thus, for a detailed description of the memory profile of KS patients, the screening of confabulation tendencies may be a useful supplementary clinical tool.

This article compared alcoholics and healthy controls on the Buschke Selective Reminding Task. Alcoholics demonstrated deficits in memory and learning when compared to healthy controls, even when controlling for age. Examination of the alcoholic sample initially showed that age predicted memory deficits; however, age was no longer a significant predictor once the number of years of heavy drinking was entered into the regression equation. Findings suggest a direct link or mechanism of action between alcohol use and memory impairments, above and beyond effects of age or education.

Alcoholic Korsakoff's syndrome (KS) is marked by remote memory impairment together with characteristic profound anterograde memory deficits. Despite previous studies of memory processes in KS, questions remain regarding the nature and severity of these impairments and identification of brain systems that underlie these different memory impairments. This study examined remote and anterograde memory function in 5 KS patients in comparison with 8 patients with Alzheimer's disease (AD) and 24 normal control subjects (NC). In addition, relationships between memory performance and regional brain volumes were examined in the KS group. Overall, the KS group showed severe impairment on both remote and anterograde memory measures, performing at the level of the AD group on most measures. Differences were observed on the pattern of temporal gradient for verbal recognition, with KS exhibiting a more steeply graded rate of decline over the most recent period examined. Severity of the remote memory deficit in KS was not associated with severity of anterograde memory deficit. Examination of brain structure-function relationships in the KS subjects revealed that photo naming of remote historical information was related to posterior cortical white matter volumes but not hippocampal volumes; sequencing was related to prefrontal but not hippocampal volumes. By contrast, a measure of anterograde memory for nonverbal visual material showed a relationship to hippocampal but not regional cortical white matter volumes. This set of dissociations, which parallels that observed in our earlier study of AD, is now documented in KS and provides further evidence that these separate cortical and limbic brain systems are principal neural substrates of the remote and anterograde memory and sequencing deficits in KS.

Conventional wisdom, and even well-reasoned theoretical mechanisms, suggests that the chronic use of psychoactive substances would impair cognitive functioning of individuals. This article summarizes the research literature with regard to specific drugs of abuse. Undoubtedly, acute intoxication and immediate and protracted withdrawal produce transient alterations of cognitions that can persist for weeks to months. Some subtle residual effects remain for up to 1 year for certain drugs. Evidence of irreversible effects is less clear. Even subtle lingering effects can impact treatment efforts, yet they often go undetected or unaddressed.

Objective: To examine whether the amnesic syndrome of alcoholic Korsakoff's syndrome (KS) originates from pathology of the hippocampus and not solely the diencephalon., Methods: The authors studied 5 patients with KS and two comparison groups: 20 patients with Alzheimer's disease (AD) with known bilateral hippocampal volume loss and 36 healthy control subjects. The authors used quantitative MRI to characterize the hippocampus and comparison brain structures (temporal cortex, lateral ventricles, temporal horns, and third ventricle)., Results: Relative to healthy control subjects, the KS and AD groups had comparable, significant bilateral hippocampal volume deficits. Although both patient groups also had extensive volume abnormalities in temporal lobe cortical gray matter, temporal horns, and lateral and third ventricles, declarative memory test performance was selectively related to hippocampal volumes in KS and not to any of the comparison volumes., Conclusions: The characteristic memory deficit of Korsakoff's syndrome involves hippocampal and diencephalic pathology.

The effect of familiarity to word-stem completion priming in amnesic patients was studied. A smaller priming effect of low familiarity of words in amnesic patients indicated that the process of lexical access may be involved in word-stem completion in amnesic patients.

The Tower of Hanoi has been widely accepted as an evaluation of cognitive procedural learning in amnesia but inconsistent findings have raised questions about the nature of the learning process involved in this task. This article presents the performance of a hippocampal amnesic, MS, who, showing poor learning across daily sessions of a formal evaluation, subsequently solved the puzzle through spontaneous use of a declarative-level strategy (the odd-even rule), suggesting that his primary approach to the task was the deployment of declarative solution-searching strategies. The presented data suggest normal learning within daily sessions, but subnormal learning across daily sessions due to the forgetting of acquired declarative information. It is suggested that tasks that are potentially solvable by an algorithm or rule, as is the Tower of Hanoi, be regarded as inappropriate for use in cognitive procedural assessments., (Copyright 2001 Academic Press.)

False recognition occurs when people mistakenly claim that a novel item is familiar. After studying lists of semantically related words, healthy controls show extraordinarily high levels of false recognition to nonstudied lures that are semantic associates of study list words. In previous experiments, we found that both Korsakoff and non-Korsakoff amnesic patients show reduced levels of false recognition to semantic associates, implying that the medial temporal/diencephalic structures that are damaged in amnesic patients are involved in the encoding and/or retrieval of information that underlies false recognition. These data contrast with earlier results indicating greater false recognition in Korsakoff amnesics than in control subjects. The present experiment tests the hypothesis that greater or lesser false recognition of semantic associates in amnesic patients, relative to normal controls, can be demonstrated by creating conditions that are more or less conducive to allowing true recognition to suppress false recognition. With repeated presentation and testing of lists of semantic associates, control subjects and both Korsakoff and non-Korsakoff amnesics showed increasing levels of true recognition across trials. However, control subjects exhibited decreasing levels of false recognition across trials, whereas Korsakoff amnesic patients showed increases across trials and non-Korsakoff amnesics showed a fluctuating pattern. Consideration of signal detection analyses and differences between the two types of amnesic patients provides insight into how mechanisms of veridical episodic memory can be used to suppress false recognition.

Background: The cholinergic nucleus basalis (Ch4) is an exclusive site of neurofibrillary degeneration in alcoholic patients with Wernicke's encephalopathy., Aim: To test the hypothesis that the loss of Ch4 neurons contributes to the memory disorder, Korsakoff's psychosis, commonly seen in Wernicke's encephalopathy., Methods: Magnocellular basal forebrain neurons were quantified in alcoholic patients with Wernicke's encephalopathy, both with and without Korsakoff's psychosis, and neurologically asymptomatic alcoholic and non-alcoholic controls. Because amnesic and non-amnesic patients with Wernicke's encephalopathy share common periventricular lesions, both thiamine deficient groups as well as alcoholic patients with no neurological complications were included to determine the lesion specific to memory impairment., Results: Ch4 cell number did not differ significantly between alcoholic and non-alcoholic controls and there was no correlation between cell number and lifetime alcohol intake. However, Ch4 cell number in all groups was significantly correlated with the volume of its major projection target, the cerebral cortex. Ch4 cell number in the non-amnesic Wernicke's encephalopathy group was significantly below controls (24%), with cell number in patients with Korsakoff's psychosis 21% below controls. There was considerable overlap in cell number between groups. On discriminant analysis, there was significantly greater cell loss in three non-amnesic patients with Wernicke's encephalopathy than in some patients with Korsakoff's psychosis. The nonamnesic patient with the greatest cell loss was impaired on attentional tasks., Conclusion: Whereas neurons in the nucleus basalis are at risk in thiamine deficient alcoholic patients, cell loss is minor and does not account for the profound memory disorder.

The Wernicke-Korsakoff syndrome (WKS) is a picture of oculomotor alterations, ataxia and confusion presented in chronic alcoholics. It has more rarely been described in non alcoholic patients with malnutrition. The case of a patient with ulcerous peptic disease of long evolution who consulted for a picture compatible with WKS following clinical manifestations of repeated vomiting secondary to complete pyloric stenosis is presented. The peculiarity of the picture and the convenience of prevention in malnourished patients receiving intravenous glucose sera is discussed.

Recent genetic studies show that the apolipoprotein E (ApoE) epsilon 4 allele is a risk factor for Alzheimer's disease (AD). Whether this allele is associated with other dementing diseases is the next important question. The information could provide a clue to the pathogenetic role of ApoE. In the present study, patients with Wernicke-Korsakoff syndrome (WKS) of alcoholic etiology were divided into two groups according to the severity of intellectual deficits, i.e., those of "classical" Korsakoff patients with preserved intellectual function other than amnesia and those with global intellectual deficits. Genotyping showed that the frequency of ApoE epsilon 4 allele was significantly higher in the patients with global deficits, suggesting the involvement of this allele in the intellectual decline of WKS. In contrast, distributions of other two markers, alpha 1-antichymotrypsin and presenilin-1, did not differ between the two groups. These results added further support to the notion that the consequence of acute insult to the brain is influenced by the ApoE genotype, and suggested ApoE's role in the development of a certain group of "alcoholic dementia."

Alcohol abuse is one of most serious problems in public health and the Wernicke-Korsakoff syndrome one of the gravest consequences of alcoholism. The pathology is often undiagnosed in its less evident presentations, therefore an accurate diagnostic approach is a critical step in planning treatment. Besides new pharmacological proposals, treatment is based on the restoration of thiamine, although this is insufficient to prevent the psychological decline of a great number of patients. The cognitive impact of the pathology is derived from the interaction of alcoholic neurotoxicity, thiamine deficiency and personal susceptibility. In this article the history, epidemiology, clinical and neuropathological features of the Wernicke-Korsakoff syndrome, as well as some aspects of its treatment and prognosis, are described.

Objective: To estimate the incidence of Wernicke-Korsakoff syndrome (WKS) before and after the introduction of thiamine enrichment of bread flour in 1991., Design: Retrospective survey of hospital records. Patient records with the diagnostic codes for Wernicke's encephalopathy (WE) or Korsakoff's psychosis (KP) were reviewed and details of acceptable cases were entered onto a data form., Setting: All 17 major public general hospitals in the Sydney area (New South Wales), between 1978 and 1993., Outcome Measures: Numbers of confirmed or probable diagnoses of WE, KP or WKS and associated deaths, patient demographic and social characteristics and alcohol intake., Results: 1,267 patients with WKS were found, with 1,012 acute cases. Although numbers of acute cases may have started to fall before 1991, numbers for the last two years were the lowest of all the 16 years (P = 0.004). Cases of KP outnumbered those of WE by about 3:1 and men outnumbered women 4:1. The peak age was 60-64 years (17%) and beer was the most commonly cited alcoholic drink (71%). The red-cell transketolase test was seldom used for diagnosis (3% of acute cases)., Conclusions: The lower number of "acute" cases in 1992 and 1993 is consistent with a preventive effect of mandatory enrichment of bread with thiamine, but is not conclusive evidence. Longer follow-up of Sydney hospitals, results of postmortem examinations and follow-up in other areas of Australia are required.

The Cognitive Estimation Test (CET) was devised by Shallice & Evans (1978) in an attempt to quantify the tendency observed in some patients with frontal lobe lesions to produce bizarre estimates in response to questions to which people do not usually know exact answers (e.g. 'what is the height of a double-decker bus?'), despite performing normally on standard intelligence tests. In the present study, the CET performance of a large number of patients suffering from head injury, brain tumour, ruptured aneurysm (anterior communicating artery and other), multiple sclerosis, dementia, encephalitis, Korsakoff's syndrome and anxiety/depression were compared with CET scores from 150 healthy controls. Patients with Korsakoff syndrome demonstrated significantly impaired CET performance. A subgroup of patients with discrete frontal lesions was compared with a group with localized non-frontal lesions. No significant difference in CET performance was observed between anterior and posterior lesioned patients. The sensitivity of the CET to anterior brain dysfunction is called into question by the present findings.

Background: Investigations of the Korsakoff syndrome by researchers from different disciplines have proliferated in recent years, making it apposite to review the various findings., Method: This review is based on the author's knowledge of reports in the major clinical and neuropsychological journals, supplemented by Medline searches to update particular subtopics., Results: The Korsakoff syndrome is defined as a disproportionate impairment in memory, relative to other aspects of cognitive function, resulting from a nutritional (thiamine) depletion. The initial manifestations of the disorder are variable, and a persistent memory impairment can result from a non-alcoholic aetiology, although this seems to happen much less commonly than in the past - presumably because of generally higher standards of nutrition. Although there is agreement on the underlying neuropathology, the critical lesion sites for memory disorder have been debated. Recent evidence suggests that the circuit involving the mammillary bodies, the mammillo-thalamic tract and the anterior thalamus, rather than the medial dorsal nucleus of the thalamus, is particularly critical in the formation of new memories. The relationship of these deficits to thiamine depletion remains a topic of current investigation, as does the purported role of neurotransmitter depletions in the cholinergic, glutamate/GABA and catecholamine and serotonergic systems. Neuro-imaging studies have confirmed autopsy findings of more widespread structural and metabolic abnormalities, particularly involving the frontal lobes., Conclusions: The relationship of these neuropathological, neurochemical, and metabolic abnormalities to cognitive functioning, with particular reference to specific aspects of memory processing, has been considered in some detail. Whereas structural and/or neurochemical abnormalities within the limbic/diencephalic circuits account for anterograde amnesia, some other factor, such as frontal lobe dysfunction, must underlie the severe retrograde memory loss which is characteristically found in this syndrome.

The effects upon regional brain function of infusing either saline or clonidine (1.5 microgram/kg) has been examined in 18 patients with alcoholic Korsakoff's psychosis using 99mTc-hexamethylpropyleneamineoxime (99mTc-HMPAO or 99mTc-Exametazime) and Single Photon Emission Tomography (SPET or SPECT). The hypothesis tested was that frontal lobe function would be increased by adrenoceptor stimulation. This was confirmed by an increase in the uptake of 99mTc-Exametazime into anterior cingulate regions of the frontal lobes. Patients were scanned before and after saline or clonidine infusion during performance of a verbal fluency task. There was a significantly increased performance of verbal fluency in patients given clonidine. This effect was variable and could not be unequivocably distinguished from increases in performance in the saline treated group. Nevertheless, the increase in neuropsychological performance was also correlated with increased function in left dorsolateral frontal cortex within the clonidine treated group. An exploratory examination of other brain areas suggested that relative increases in posterior cingulate cortex and changes in the symmetry of function within the thalamus may also be produced by acute infusion of clonidine in Korsakoff patients. The findings support the idea that adrenergic mechanisms may modulate cognitive performance by actions on attentional systems within the brain. These appear to be located primarily within limbic cortex. It is, of course, notable that this can occur in patients with profound and disabling amnesia.

Until very recently, memory impairment was not considered to be a central feature of schizophrenia, except in chronic, deteriorated patients. In this study of a heterogeneous sample of 40 patients with DSM-III-R schizophrenia, episodic memory impairment was found to be prevalent, and in some cases, severe. The degree of memory impairment was not attributable to neuroleptic or anticholinergic medication, or to poor motivation or cooperation. These results, therefore, replicate those reported by McKenna et al. (1990) and Tamlyn et al. (1992), who suggested that the pattern of memory impairment in schizophrenia may conform in important respects to that of the classic amnesic syndrome. However, in a direct comparison of the schizophrenic sample with 18 patients suffering from the Alcoholic Korsakoff Syndrome (AKS), both quantitative and qualitative differences were found to exist between the two groups of patients. In particular, the level of long-term episodic memory impairment was found in the AKS sample to be far greater than that in the schizophrenic group. An interesting possible double-dissociation emerged between the two groups; although demonstrating superior episodic memory functioning, the schizophrenic sample were found to perform significantly more poorly than the AKS sample on a test of semantic memory.

The Wernicke-Korsakoff syndrome is a neuropathological term which encompasses two clinical syndromes in thiamine-deficient alcoholics, Wernicke's encephalopathy and Korsakoff's psychosis. Wernicke's encephalopathy is characterised by eye and gait disorders and mental confusion, and can lead to the profound and permanent amnesia known as Korsakoff's psychosis. Despite this specific difference, both conditions appear to have identical neuropathology with haemorrhages and other lesions around the ventricular system. The memory deficit has been attributed to a number of brain lesions, including a recent suggestion that brain pathways utilising particular neurotransmitters are specifically damaged. To examine this, the number of chemically identified neurons in particular brain regions was quantified in patients with Wernicke's encephalopathy alone or in combination with Korsakoff's psychosis and compared with age- and sex-matched controls. Noradrenaline, a neurotransmitter thought to be involved in the process of selective attention, is localised in pathways projecting to the cortex. Our patients with either Wernicke's encephalopathy or additional Korsakoff's psychosis do not differ from controls in the distribution and number of these cells. Serotonin is another neurotransmitter that has been linked with alcohol dependency. Both patient groups have a profound loss of serotonin-containing neurons compared with controls. The loss of forebrain neurons containing acetylcholine in patients with Alzheimer's disease has implicated this neurotransmitter in the maintenance of memory functions. There was a large variation in the number of these forebrain neurons in thiamine-deficient alcoholics compared with controls. Cholinergic cell loss reflected the severity of cognitive dysfunction, but was not exclusive to patients with amnesia. Two thalamic nuclei are involved in relaying memories for storage and retrieval, the anterior and mediodorsal thalamic nuclei. While patients with Wernicke's encephalopathy often had neuronal loss in the mediodorsal nucleus, only patients with Korsakoff's psychosis had cell loss in both medial thalamic nuclei. The results suggest that cumulative lesions contribute to the amnesia seen in thiamine-deficient alcoholics, including deficits in serotonergic, cholinergic and medial thalamic pathways.

Patients with amnesia resulting from alcoholic Korsakoff syndrome and elderly control patients studied a list of words in two typographies (typed and handwritten) and then received a word-fragment completion test (e.g., -ys-e-y for mystery) in which the test cues also varied in typography. Unlike the elderly control patients, the amnesic patients did not show greater priming effect when the typography at test matched that at study. The amount of typography-dependent priming was positively correlated with the score on the Wechsler Memory Scale. These results suggest that the effects of typography change on repetition priming in word-fragment completion reflect explicit recollection, and that the representation that supports repetition priming effects observed with amnesic subjects in the word-fragment completion task does not code typography information.

In order to support the concept that a lesion of the thalamus is sufficient to cause a Korsakoff syndrome, we are presenting 5 patients, all of whom developed the syndrome after sustaining a left (dominant) thalamic infarction. Two patients had pure thalamic strokes followed by a permanent Korsakoff syndrome. One of these patients was studied with neuropsychometric testing, as well as with a modern MRI scan. In 2 other patients, clinical and imaging data indicate that infarction was not limited to the thalamus. Another patient had bilateral thalamic infarcts but only a temporary Korsakoff syndrome. Neuropathological data are needed to elucidate the exact anatomical substrate of dominant thalamic Korsakoff syndrome.

Background: Wernicke encephalopathy (WE), acute (microhaemorrhages) and chronic (proliferation of capillaries) is actually considered as a not uncommon, and curable, condition in several diseases, and not only in alcoholic patients. Why serotoninergic nuclei, and whether blood brain barrier (BB) are involved were our questions., Methods: In a dramatic series of AIDS cases we selected 380 brains, all belonging to drug addicted subjects. In all Thiamine administration had been under 20 mg pro die and by oral way. In the cases considered, opportunistic infections were present in the 40%, and/or HIV specificity in the 35%., Results: "Acute" WE was found in nearly the 10%. All patients presented with CNS lesions, other than those of WE, but HIV specificity was found only in 5. They all showed changes in Choroid Plexus, namely alterations of various type of the cuboid epithelium, such as swelling, disruption, hyperplasia., Discussion: WE is set in connection with pyruvate accumulation at capillary level, likely bound to the Thiamine deficiency and to the lack of energy thus induced. Apart from obvious haemorrhagic aspects, CFS studies in WE are lacking. Choroid structure is not merely a permeable membrane (CSF is not a filtrate). Our findings would suggest that Thiamine plays a role in the energy supply to BB. Moreover, the existence of free nerve endings through the ependyma for the release and uptake of monoamines, allows to consider the elective involvement of serotoninergic neurons as somehow connected to the choroid plexus changes described.

Malnutrition rather than alcohol abuse is the common element in most cases of WKS. Our report may be the first to identify both the clinical and neuropathologic features of the syndrome in a patient with T-cell lymphoma. The coincidence of these two illnesses underscores a need to consider Wernicke's encephalopathy in debilitated individuals with malignancy or other chronic illnesses, highlights an atypical presentation of acute Wernicke's encephalopathy, and demonstrats the precipitation of that syndrome by glucose feeding. Attention to a patient's nutritional status and the liberal use of thiamine may prompt early recognition of the syndrome or prevent it entirely.

Two patients with chronic alcohol abuse and central pontine myelinolysis are described. One developed a Korsakoff syndrome 2 days before admission to our hospital and the other showed signs of a incipient delirium without Korsakoff syndrome. Diagnosis of incipient central pontine myelinolysis was based on acute brain-stem dysfunction, serum electrolyte disturbances, malnutrition with vitamin B1 (thiamine), B6 (pyridoxine) and B12 (cyanocobalamin) deficiency in combination with typical neuroradiological findings. Hypokalaemia but no disturbance in serum sodium levels was found in both patients. After correction of hypokalaemia and vitamin deficiency the patients showed complete recovery of neurological and neuropsychological function. The findings are interpreted as suggesting that disturbances in serum potassium levels as well as rapid correction of hyponatraemia may be associated with pontine swelling and dysfunction which, if undetected, leads to central pontine myelinolysis.

Memory may fail in a variety of ways. Patients with Korsakoff's syndrome demonstrate global memory deficits similar to those seen in patients with early progressive dementia. Korsakoff's patients, however, may recall rules and principles for organizing information and can gain access to their previously acquired knowledge (semantic memory), whereas recent memory may be grossly impaired. In contrast, dementia patients may have little access to previously acquired knowledge and therefore have great difficulty in organizing and encoding ongoing events. These contrasting forms of memory failure have implications for understanding the structure and mechanisms of memory and learning, particularly the relationship between episodic and semantic memory, as well as the development of therapeutic strategies for cognitive impairments.

Olfactory dysfunction, a finding prevalent among alcoholic Korsakoff patients, was investigated in long-term alcoholics with Korsakoff's Syndrome. The results demonstrate that alcoholics are impaired on odor quality discrimination but performed normally on complex hue discriminations. These findings support the hypothesis that chronic alcoholics and alcoholic Korsakoff patients represent two points on a single continuum of cognitive deterioration associated with alcohol abuse.

Delirium tremens in a common feature in the alcoholic population. The Fat Embolism Syndrome (FES) is characterized by fever, encephalopathy, respiratory failure and skin petechiae. Fat embolism has been associated with alcoholics but the diagnosis was apparent only at autopsy. We present an alcoholic male who developed delirium tremens unresponsive to therapy, followed by features of the FES. Asterixis and Korsakoff's psychosis are newly described features of this syndrome. Corticosteroids were a definitive therapy in this case.

The authors report a clinico-pathological study dealing with the limbic nuclei of the thalamus in 11 cases of Korsakoff syndrome of alcoholic aetiology. There is no parallelism between the involvement of the latero-dorsal nucleus (L.D.), the medio-dorsal nucleus, the pulvinar and the importance of the retrograde amnesia. The mamillary bodies are always affected. The latero-dorsal nucleus was modified in 9 cases out of 11, the medio-dorsal in 7 cases and the pulvinar in 6 cases. In contrast, the anterior nucleus is normal. The frequency of the involvement of the L.D. is an argument to relate this nucleus with the limbic system. But the lesion of this nucleus is inconstant whereas that of the mamillary bodies is always observed.

The development of hypothermia and coma are rare complications of the Wernicke-Korsakoff syndrome. This report describes three patients with Wernicke's encephalopathy in whom hypothermia was a presenting feature. The second patient described was also comatose. The frequency of occurrence and the significance of these signs are reviewed in detail, as is their potential reversibility with adequate doses of parenteral thiamine. More careful attention to the rectal temperature in patients with Wernicke's encephalopathy may reveal a higher frequency of hypothermia than has been previously suspected.

A group of amnesic patients with Korsakoff's disease were treated with a single 1 g dose of DL-threo-3,4-dihydroxyphenylserine (DOPS) and placebo (lactose) in a double-blind crossover study. Three hours following administration, patients were given a battery of psychometric tests to determine the effects of the treatment on memory functions. Administration of DOPS had a significant effect on performance on the Memory Passages test but not on any of the other measures of memory. The effect of DOPS on Memory Passages is similar to the response observed following administration of clonidine in Korsakoff patients. Blood pressure and pulse, measured before and every 2 h after treatment, were unaffected by DOPS.

Performance of 10 alcoholic Korsakoff patients was compared to that of 10 normal and 10 alcoholic control subjects on each of three different schedules of spatial probability learning (50:50, 70:30, and 30:70) using monetary reinforcement and a correction procedure. There was some evidence that the Korsakoff patients were less sensitive than normals to the effects of reward: Although on all three schedules, choice ratios by normal subjects approximated the reinforcement ratios, the choice ratios of Korsakoffs on the second and third schedules remained close to the reinforcement ratio acquired with the first schedule. In addition, the Korsakoffs made an abnormal number of perseverative errors early in training. On most measures, performance by alcoholic controls fell between that of the other two groups.

A 35-year-old woman developed upbeating nystagmus while recovering from presumed Wernicke-Korsakoff syndrome. The upbeating nystagmus changed to downbeating nystagmus with convergence. The slow-phase velocity of the downbeating nystagmus varied with the convergence effort. We believe that this unusual nystagmus pattern implies convergence input to the supranuclear centers for vertical gaze.

Eleven alcoholic patients with Korsakoff's disease and 15 control subjects were given three tests of retrograde amnesia. The first consisted of photographs of famous faces from the past, the second was a recall test of famous people and events, and the third was a multiple-choice questionnaire. To determine whether previously reported temporal gradients (ie, preservation of remote events) were related to item difficulty, half of the questions dealt with events of transient fame while half concerned subjects that continued to receive public attention for many years. The findings indicate that alcoholic patients with Korsakoff's disease have a marked retrograde amnesia that is characterized by a steep temporal gradient, and that this gradient is not an artifact due to the difficulty of the questions or the method of testing.