Structural brain substrates of the deficits observed on the BEARNI test in alcohol use disorder and Korsakoff's syndrome.

Chronic and excessive alcohol consumption can result in alcohol use disorder (AUD) without neurological complications and in Korsakoff's syndrome (KS) when combined with thiamine deficiency. These two clinical forms are accompanied by widespread structural brain damage in both the fronto-cerebellar (FCC) and Papez circuits (PC) as well as in the parietal cortex, resulting in cognitive and motor deficits. BEARNI is a screening tool especially designed to detect neuropsychological impairments in AUD. However, the sensitivity of this tool to the structural brain damage of AUD and KS patients remains unknown. Eighteen KS patients, 47 AUD patients and 27 healthy controls (HC) underwent the BEARNI test and a 3 T-MRI examination. Multiple regression analyses conducted between GM density and performance on each BEARNI subtest revealed correlations with regions included in the FCC, PC, thalamus and posterior cortex (precuneus and calcarine regions). All these brain regions were altered in KS compared to HC, in agreement with the cognitive deficits observed in the corresponding BEARNI subtests. The comparison between KS and AUD regarding the GM density in the several nodes of the FCC and calcarine regions revealed that they were atrophied to the same extent, suggesting that BEARNI is sensitive to the severity of alcohol-related GM abnormalities. Within the PC, the density of the cingulate cortex and thalamus, which correlated with the memory and fluency subscores, was smaller in KS than in AUD, suggesting that BEARNI is sensitive to specific brain abnormalities occurring in KS.

Intentional and unintentional mind-wandering in Korsakoff syndrome.

Mind-wandering refers to the intentional and unintentional tendency to withdraw from the external environment and engage in internally generated thoughts. We investigated intentional and unintentional mind-wandering in patients with Korsakoff syndrome (KS). We invited 31 patients with KS and 33 control participants to answer a questionnaire probing intentional and unintentional mind-wandering. Analysis demonstrated higher intentional and unintentional mind-wandering in patients with KS than in controls. However, no significant differences were observed between intentional and unintentional mind-wandering in patients with KS or in controls. Significant positive correlations were observed between intentional and unintentional mind-wandering and depression in patients with KS but not with cognitive controls. Our results demonstrate a high intentional and unintentional tendency in patients with KS to shift attention away from the external environment to internal thoughts/feelings that are unrelated to the ongoing task. This tendency may be associated with the activation of negative thoughts/beliefs, as observed in depression.

Neuropsychological and Neuroimaging Examinations of Self-Reported Sleep Quality in Alcohol Use Disorder With and Without Korsakoff's Syndrome.

BACKGROUND: Alcohol use disorder (AUD) patients without Korsakoff's syndrome (KS) report a variable self-rated sleep quality. Their ability to accurately judge their sleep quality may be related to their alcohol-related cognitive deficits and brain damage. KS patients, who present severe brain dysfunction, may be cognitively unable to judge their sleep quality. The aim of the present study is to examine, in AUD and KS patients, whether the absence of sleep complaint is associated with altered brain structure and impaired cognitive abilities within specific cerebral networks. METHODS: An assessment of subjective sleep quality was conducted in 20 healthy controls, 37 AUD patients, and 17 KS patients. Patients were first pooled together and then classified into 2 groups (no-complaintAUD + KS and complaintAUD + KS ) according to the total Pittsburg Sleep Quality Index score. Cognitive scores, gray matter (GM) volume, and white matter (WM) integrity were compared between these 2 groups, and then in AUD and KS patients separately. RESULTS: Poor sleep quality was reported by 70% of AUD and 18% of KS patients. Compared to controls, both no-complaintAUD + KS and complaintAUD + KS presented cortical and subcortical alterations as well as episodic memory deficits, which were more severe in patients without sleep complaint. Only no-complaintAUD + KS presented executive deficits. Then, considering the clinical diagnosis, GM volume in frontotemporal regions, WM integrity, and executive functions were affected to the same extent in AUD and KS patients without sleep complaint. CONCLUSIONS: Our results confirm the high prevalence of sleep complaint in AUD patients and the rare complaint in KS patients. In AUD and KS patients, the absence of sleep complaint may not indicate good sleep quality but rather reflect executive deficits and frontothalamic damage. Alcohol-related cognitive deficits may indeed alter the ability to self-evaluate sleep quality, suggesting that the use of sleep questionnaire should be considered with caution in patients with executive deficits.

Wet Beriberi Associated with Hikikomori Syndrome.

Wet beriberi, characterized by high cardiac output with predominantly right-sided heart failure and lactic acidosis, is a disease caused by thiamine deficiency, and is rarely seen in modern society. However, patients with social withdrawal syndrome, also known as hikikomori syndrome, may be a new population at risk of thiamine deficiency. Hikikomori syndrome, first recognized in Japan, is becoming a worldwide issue. A 39-year-old Japanese patient was brought to our hospital, with a 3-week history of progressive shortness of breath and generalized edema. The patient had right-sided high-output heart failure, lactic acidosis, and Wernicke-Korsakoff syndrome. Because of his history of social isolation, we diagnosed hikikomori syndrome according to the Japanese government's definition, which is as follows: lifestyle centered at home; no interest or willingness to attend school or work; persistence of symptoms beyond 6 months; and exclusion of other psychiatric and developmental disorders. Considering his diagnosis of hikikomori syndrome and social isolation, we suspected malnutrition, particularly thiamine deficiency, and successfully treated him. Clinicians should be aware of the potential risk of thiamine deficiency associated with hikikomori syndrome and initiate thiamine replacement in cases of high-output heart failure associated with lactic acidosis.

Wernicke-Korsakoff syndrome complicated by subacute beriberi neuropathy in an alcoholic patient.

Thiamine (vitamin B1) deficiency is a common condition in alcohol abusers, which can lead to damage of both the peripheral and the central nervous systems. Here we describe the case of an alcoholic patient who presented with acute onset of ataxia, severe weakness of the four limbs, and hypoesthesia and dysesthesia of the distal portion of the upper and lower extremities. The clinical picture also included mental confusion and amnesia. A diagnosis of Wernicke-Korsakoff syndrome was made based on clinical symptoms and brain RMI findings. Electromyography and electroneurography revealed signs of subacute axonal sensory-motor polyneuropathy that were compatible with a rare acute presentation of beriberi. Patient immediately received parenteral thiamine administration, which resulted in rapid clinical amelioration of ataxia and confusion and also in a significant improvement of motor and sensory deficits. The association between Wernicke-Korsakoff syndrome and acute axonal polyneuropathy is a very rare condition that could make less recognizable the clinical picture of a thiamine deficiency. However, the diagnosis of thiamine deficiency should be suspected in every alcoholic patient presenting with acute onset symptoms of central and/or peripheral nervous system involvement. This because the immediate replacement treatment can be life-saving and reverse the clinical symptoms.

Non-alcoholic Korsakoff syndrome in psychiatric patients with a history of undiagnosed Wernicke's encephalopathy.

Wernicke's encephalopathy is often undiagnosed, particularly in non-alcoholics. There are very few reports of non-alcoholic patients diagnosed with Korsakoff syndrome in the absence of a prior diagnosis of Wernicke's encephalopathy and no studies of diffusion tensor imaging in non-alcoholic Korsakoff syndrome. We report on three non-alcoholic psychiatric patients (all women) with long-term non-progressive memory impairment that developed after malnutrition accompanied by at least one of the three Wernicke's encephalopathy manifestations: ocular abnormalities, ataxia or unsteadiness, and an altered mental state or mild memory impairment. In neuropsychological examination, all patients had memory impairment, including intrusions. One patient had mild cerebellar vermis atrophy in MRI taken after the second episode of Wernicke's encephalopathy. The same patient had mild hypometabolism in the lateral cortex of the temporal lobes. Another patient had mild symmetrical atrophy and hypometabolism of the superior frontal lobes. Two patients were examined with diffusion tensor imaging. Reduced fractional anisotropy values were found in the corona radiata in two patients, and the uncinate fasciculus and the inferior longitudinal fasciculus in one patient. Our results suggest that non-alcoholic Korsakoff syndrome is underdiagnosed. Psychiatric patients with long-term memory impairment may have Korsakoff syndrome and, therefore, they should be evaluated for a history of previously undiagnosed Wernicke's encephalopathy.

[Wernicke-Korsakoff syndrome]. / Sindrom Vernike-Korsakova.

AIM: To study the diagnosis and treatment of non-alcoholic Wernicke-Korsakoff syndrome (WKS). MATERIAL AND METHODS: Eight patients (5 men and 3 women), mean age 38,9±1,4 years, with WKS developed due to acute gastrointestinal tract (GIT) disease (3 patients), the exacerbation of chronic GIT disease with malabsorption (2 patients) and after surgery on the upper GIT (3 patients) were included in the study. RESULTS: The disease manifested with consciousness disturbance, symptoms of ataxia, eye movement disorders and bulbar syndrome that developed after 24-48 h. Treatment resistant tonic-clonic seizures were developed in 1 patient. MRI revealed hyper intensive signals on T2-weighted images in the hypothalamus, mamillar bodies, brain stem, hippocampus as well as contrast accumulation in the mamillar bodies. Treatment with vitamin B complex (neurobion) and thiamine exerted a positive effect. CONCLUSION: Patients with GIT disease with malabsorption are at risk of WKS. Consciousness disturbance, symptoms of ataxia, eye movement disorders indicate the necessity of treatment with thiamine that allows to prevent the development of stable cognitive deficit.

Nonalcoholic Thiamine-Related Encephalopathy (Wernicke-Korsakoff Syndrome) Among Inpatients With Cancer: A Series of 18 Cases.

BACKGROUND: Wernicke-Korsakoff Syndrome (WKS) is a neuropsychiatric syndrome caused by thiamine deficiency. Cancer predisposes to thiamine deficiency through various mechanisms. Although many case reports exist on nonalcoholic WKS in cancer, larger qualitative studies are lacking. METHOD: Retrospective study of patients admitted to a cancer hospital and diagnosed with WKS during routine care on a psychiatric consultation service. Only patients with at least 1 additional supporting feature (magnetic resonance imaging findings, low serum thiamine concentrations, or response to treatment) were included. Data pertaining to demographics, risk factors, phenomenology, and outcomes were abstracted from medical records by chart review. RESULTS: In all, 18 patients were included. All patients developed WKS during cancer treatment. Hematologic malignancy, gastrointestinal tract tumors, low oral intake, and weight loss were common risk factors. All patients presented with cognitive dysfunction, most commonly impaired alertness, attention, and short-term memory. All were diagnosed by operational criteria proposed by Caine et al., 1997 (where 2 of the following are required: nutritional deficiency, ocular signs, cerebellar signs, and either altered mental status or mild memory impairment). Few exhibited Wernicke's classic triad. Diagnostic and treatment delay were common. Only 3 patients recovered fully. CONCLUSION: Nonalcoholic WKS can occur during cancer treatment and manifests clinically as delirium. Diagnosis should be made using operational criteria, not Wernicke's triad. Most patients were not underweight and had normal serum concentration of vitamin B12 and folate. A variety of mechanisms might predispose to thiamine deficiency and WKS in cancer. Given the high frequency of residual morbidity, studies should focus on decreasing diagnostic and treatment delay.

Reversible alcohol-related dementia: a five-year follow-up study using FDG-PET and neuropsychological tests.

OBJECTIVE: As the pathophysiology of alcohol-related dementia (ARD) is unclear, we examined a patient with reversible ARD using neuropsychological tests and (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET). DESIGN: A five-year follow-up case study with neuropsychological tests and FDG-PET. SETTING: Kyoto University Hospital. Patients A 42-year-old patient who was unable to perform his office duties because of slowly progressive amnesia with executive dysfunction. RESULTS: The initial evaluation with neuropsychological tests showed severe verbal memory disturbance. The patient did not discuss his excessive alcohol consumption in the initial history-taking session and thiamine deficiency was absent; therefore, early-stage Alzheimer's disease was suspected. Later, the patient revealed prior excessive alcohol intake and his cognitive function improved markedly after a period of abstinence. Retrospective analysis of initial FDG-PET images using a voxel-wise statistical method revealed glucose hypometabolism in the diencephalon and basal forebrain. Follow-up for 5 years after the initial evaluation showed improved cognitive function and recovery of glucose metabolism in the two brain regions. CONCLUSION: Hypofunction in the diencephalon and basal forebrain was associated with cognitive decline in our patient. This case may provide evidence for the etiopathic brain regions in reversible type ARD.

Acute Korsakoff-like amnestic syndrome resulting from left thalamic infarction following a right hippocampal hemorrhage.

Korsakoff-like amnestic syndromes have been rarely described following structural lesions of the central nervous system. In this report, we describe a case of acute Korsakoff-like syndrome resulting from the combination of a left anteromedian thalamic infarct and a right hippocampal hemorrhage. We also review the literature relevant to the neuropathology and pathophysiology of Korsakoff syndrome and anterograde amnesia.

Increased cerebellar PET glucose metabolism corresponds to ataxia in Wernicke-Korsakoff syndrome.

AIMS: To investigate a possible relationship between cerebellar glucose metabolism and recovery from ataxia in the first months of acute Wernicke-Korsakoff syndrome. METHODS: Two cases of alcoholic Wernicke-Korsakoff syndrome were followed up with the clinical status and cerebral glucose metabolism over a 4- and 9-month period. RESULTS: Initially both patients showed severe ataxia and elevated cerebellar glucose metabolism that decreased corresponding to the restitution of stance and gait. CONCLUSION: Increased cerebellar glucose metabolism at the onset of the illness may reflect the reorganization process of disturbed motor skills and may indicate cerebellar plasticity.

Persistence of disturbed thalamic glucose metabolism in a case of Wernicke-Korsakoff syndrome.

We report the case of a 40-year-old alcoholic male patient, hospitalized with an acute ataxia of stance and gait, ocular muscle weakness with nystagmus and a global apathetic-confusional state. After admission, an amnestic syndrome with confabulation was also observed and diagnosis of Wernicke-Korsakoff syndrome was made. Under treatment with intravenous thiamine, the patient recovered completely from gaze weakness and ataxia, whereas a severe amnestic syndrome persisted. Fluorodeoxyglucose (FDG) positron emission tomography (PET) showed bilateral thalamic and severe bilateral temporal-parietal hypometabolism resembling a pattern typical for Alzheimer's disease. Longitudinal assessment of the alcohol-abstinent and thiamine-substituted patient revealed improvements of clinical state and neuropsychological performance that were paralleled by recovered cerebral glucose metabolism. In contrast to metabolic rates that increased between 7.1% (anterior cingulate, left) and 23.5% (parietal, left) in cortical areas during a 9-month remission period, thalamic glucose metabolism remained severely disturbed over time (change: left +0.2%, right +0.3%).

FDG-PET findings in the Wernicke-Korsakoff syndrome.

This study reports FDG-PET findings in Wernicke-Korsakoff patients. Twelve patients suffering amnesia arising from the Korsakoff syndrome were compared with 10 control subjects without alcohol-related disability. Subjects received [18F]-fluorodeoxyglucose (FDG-PET) imaging as well as neuropsychological assessment and high-resolution MR imaging with volumetric analysis. Volumetric MRI analysis had revealed thalamic and mamillary body atrophy in the patient group as well as frontal lobe atrophy with relative sparing of medial temporal lobe structures. Differences in regional metabolism were identified using complementary region of interest (ROI) and statistical parametric mapping (SPM) approaches employing either absolute methods or a reference region approach to increase statistical power. In general, we found relative hypermetabolism in white matter and hypometabolism in subcortical grey matter in Korsakoff patients. When FDG uptake ratios were examined with occipital lobe metabolism as covariate reference region, Korsakoff patients showed widespread bilateral white matter hypermetabolism on both SPM and ROI analysis. When white matter metabolism was the reference covariate; Korsakoff patients showed relative hypometabolism in the diencephalic grey matter, consistent with their known underlying neuropathology, and medial temporal and retrosplenial hypometabolism, interpreted as secondary metabolic effects within the diencephalic-limbic memory circuits. There was also evidence of a variable degree of more general frontotemporal neocortical hypometabolism on some, but not all, analyses.

Voxel-based mapping of brain hypometabolism in permanent amnesia with PET.

In this study, we used voxel-based mapping methods to compare the resting cerebral metabolic rate of glucose (CMRglc) measured with PET in five patients with permanent amnesia (three with chronic Wernicke-Korsakoff and two with postanoxia syndrome) to that of nine healthy age-matched subjects. We assessed (i) a group pattern of relative hypometabolism; and (ii) the consistency of this group pattern, if any, in individual subjects, according to etiology. The results from the group analysis documented that permanent amnesia is associated with hypometabolism in the thalamus, posterior cingulate cortex, and mesial prefrontal cortex (near the anterior cingulate gyrus), bilaterally, as well as in the left supramarginal and middle temporal gyri. The individual analysis showed that this group pattern was found in essentially each patient, regardless of the cause of amnesia. Thus, permanent amnesia is subtended by dysfunction in structures belonging to Papez/limbic circuits as well as in left-hemisphere areas typically concerned with verbal functions, probably through a mechanism of thalamo-cortical disconnection and possibly involved in retrograde amnesia. The use of a voxel-based method allowed us to map a common network of synaptic dysfunction in a neuropsychological syndrome regardless of etiology. Our results indicate that this should be a powerful method in functional neuropsychology.

[Brain SPECT in a case of Wernicke Korsakoff syndrome]. / SPECT cerebral en un caso de síndrome de Wernicke Korsakoff.

INTRODUCTION AND CLINICAL CASE: In this article we report a 44 year old male with chronic alcoholism as antecedent and Wernicke Korsakoff s syndrome, studied with brain CT, MR and SPECT. In this work we review the different conclusion obtained with different studies and in different stages of the chronic alcoholism disease. CONCLUSIONS: Although several authors have described impaired frontal blood flow in the Wernicke Korsakoff s syndrome, in our case the parietal, temporal and occipital cortex were the most affected.