Wernicke-Korsakoff Research Articles

Altered learning and transfer abilities in Korsakoff’s syndrome depending on task complexity

Korsakoff’s syndrome (KS) is characterized by episodic memory impairment due to damage to the medial diencephalic structures. Although commonly associated with chronic alcoholism, starvation due to the hunger strike is one of its nonalcoholic causes. Learning the stimulus-response associations and transferring the just-learned associations to novel combinations were previously tested by specific tasks in memory-impaired patients with hippocampal, basal forebrain, and basal ganglia damage. To add to this previous research, we aimed to use the same tasks in a group of patients with hunger strike-related KS presenting a stable isolated amnestic profile. Twelve patients with hunger strike-related KS and matched healthy controls were tested in two tasks varying in task complexity. Each task included two phases: the initial phase is feedback-based learning of (simple vs. complex) stimulus-response associations, and the following phase is transfer generalization (in the presence vs. absence of feedback). On a task involving simple associations, five patients with KS failed to learn the associations, while the other seven patients showed intact learning and transfer. On the other task involving more complex associations, seven patients showed slower learning and failed at transfer generalization, whereas the other five patients failed even at the acquisition phase. These findings of a task-complexity-related impairment on associative learning and transfer represent a distinct pattern from the spared learning but impaired transfer previously observed on these tasks in patients with medial temporal lobe amnesia.

Impaired Global Precedence Effect in Severe Alcohol Use Disorder and Korsakoff's Syndrome: A Pilot Exploration through a Global/Local Visual Paradigm.

In healthy populations, visual abilities are characterized by a faster and more efficient processing of global features in a stimulus compared to local ones. This phenomenon is known as the global precedence effect (GPE), which is demonstrated by (1) a global advantage, resulting in faster response times for global features than local features and (2) interference from global distractors during the identification of local targets, but not vice versa. This GPE is essential for adapting visual processing in everyday life (e.g., extracting useful information from complex scenes). We investigated how the GPE is affected in patients with Korsakoff's syndrome (KS) compared to patients with severe alcohol use disorder (sAUD). Three groups (including healthy controls, patients with KS and patients with sAUD) completed a global/local visual task in which predefined targets appeared at the global or local level during either congruent or incongruent (i.e., interference) situations. The results showed that healthy controls (N = 41) presented a classical GPE, while patients with sAUD (N = 16) presented neither a global advantage nor global interference effects. Patients with KS (N = 7) presented no global advantage and an inversion of the interference effect, characterized by strong interference from local information during global processing. The absence of the GPE in sAUD and the interference from local information in KS have implications in daily-life situations, providing preliminary data for a better understanding of how these patients perceive their visual world.

Eye Movements as Proxy for Visual Working Memory Usage: Increased Reliance on the External World in Korsakoff Syndrome.

In the assessment of visual working memory, estimating the maximum capacity is currently the gold standard. However, traditional tasks disregard that information generally remains available in the external world. Only when to-be-used information is not readily accessible, memory is taxed. Otherwise, people sample information from the environment as a form of cognitive offloading. To investigate how memory deficits impact the trade-off between sampling externally or storing internally, we compared gaze behaviour of individuals with Korsakoff amnesia (n = 24, age range 47-74 years) and healthy controls (n = 27, age range 40-81 years) on a copy task that provoked different strategies by having information freely accessible (facilitating sampling) or introducing a gaze-contingent waiting time (provoking storing). Indeed, patients sampled more often and longer, compared to controls. When sampling became time-consuming, controls reduced sampling and memorised more. Patients also showed reduced and longer sampling in this condition, suggesting an attempt at memorisation. Importantly, however, patients sampled disproportionately more often than controls, whilst accuracy dropped. This finding suggests that amnesia patients sample frequently and do not fully compensate for increased sampling costs by memorising more at once. In other words, Korsakoff amnesia resulted in a heavy reliance on the world as 'external memory'.

VITAMIN B1 AND ITS STATUS IN VEGETARIANS AND VEGANS

Vitamin B1 is a water-soluble vitamin whose alternative name is thiamine or thiamin. The metabolically active form of vitamin B1 is thiamin diphos-phate, also known as thiamin pyrophosphate. Thiamin diphosphate is a coenzyme in the pyruvate dehydrogenase complex and in the Krebs cycle. Thus, it is directly involved in catabolism. In addition, vitamin B1 also takes part in the pentose phosphate shunt, which contributes to the synthesis of nucleotides and their derivatives. Similarly, thiamin diphosphate plays an important role in myelin synthesis, amino acid metabolism, and the metabo-lism of neurotransmitters and hormones. There is also evidence for its direct regulation of ion channel activity. Lack of vitamin B1 affects all organs and tissues, but the earliest manifestations of its deficiency are found in the nervous system. There are several reasons for this. Firstly, the nervous tissue is extremely and continuously dependent on glucose oxidation, which can be disrupted in case of insuffi-ciency of the pyruvate dehydrogenase complex. Secondly, myelin production is interrupted. Thirdly, there is an imbalance of neurotransmitters. The fourth reason is the high activity of transmembrane ion-exchange processes in the nervous tissue. All these lead to damage to the central and periph-eral nervous system and, in severe cases, the development of beriberi or Wernicke-Korsakoff syndrome. B1 hypervitaminosis is an unlikely event. The hydrophilic thiamin diphosphate is rapidly excreted through the urine with an increase in its serum con-centrations. In addition, the intake of large amounts of thiamin with food significantly reduces its intestinal absorption. As thiamin is relatively safe even in high quantities, the high vitamin B1 dose is used to treat symptoms of chronic cluster headaches and some neurodegenerative diseases. Thiamin is quite evenly distributed in both animal- and plant-derived products. Its highest concentrations are found in the outer layer of cereals, leg-umes, seeds, or nuts. As a result, most studies show that thiamin intake is higher in vegans and vegetarians than in omnivores. But, with regard to the status of vitamin B1, not everything is so crystal clear. There are not many studies done on this topic to date. The lack of general consensus on a single accepted methodology for assessing the status of vitamin B1 seems to be the main hurdle. Although most of the data indicate a better supply of vitamin B1 in vegans and vegetarians, further research and standardization of methods are still needed.

Korsakoff's Syndrome and Alzheimer's Disease-Commonalities and Specificities of Volumetric Brain Alterations within Papez Circuit.

Background: Alzheimer's disease (AD) and Korsakoff's syndrome (KS) are two major neurocognitive disorders characterized by amnesia but AD is degenerative while KS is not. The objective is to compare regional volume deficits within the Papez circuit in AD and KS, considering AD progression. Methods: 18 KS patients, 40 AD patients (20 with Moderate AD (MAD) matched on global cognitive deficits with KS patients and 20 with Severe AD (SAD)), and 70 healthy controls underwent structural MRI. Volumes of the hippocampi, thalami, cingulate gyri, mammillary bodies (MB) and mammillothalamic tracts (MTT) were extracted. Results: For the cingulate gyri, and anterior thalamic nuclei, all patient groups were affected compared to controls but did not differ between each other. Smaller volumes were observed in all patient groups compared to controls in the mediodorsal thalamic nuclei and MB, but these regions were more severely damaged in KS than AD. MTT volumes were damaged in KS only. Hippocampi were affected in all patient groups but more severely in the SAD than in the KS and MAD. Conclusions: There are commonalities in the pattern of volume deficits in KS and AD within the Papez circuit with the anterior thalamic nuclei, cingulate cortex and hippocampus (in MAD only) being damaged to the same extent. The specificity of KS relies on the alteration of the MTT and the severity of the MB shrinkage. Further comparative studies including other imaging modalities and a neuropsychological assessment are required.

Impaired Awareness in People with Severe Alcohol-Related Cognitive Deficits Including Korskoff's Syndrome: A Network Analysis.

Impaired awareness of one's own functioning is highly common in people with Korsakoff's syndrome (KS). However, it is currently unclear how awareness relates to impairments in daily functioning and quality of life (QoL). We assessed how impaired awareness relates to cognitive, behavioral, physical, and social functioning and QoL by applying a network analysis. We used cross-sectional data from 215 patients with KS or other severe alcohol-related cognitive deficits living in Dutch long-term care facilities (LTCFs). Apathy has the most central position in the network. Higher apathy scores relate positively to reduced cognition and to a greater decline in activities of daily living and negatively to social participation and the use of antipsychotic drugs. Impaired awareness is also a central node. It is positively related to a higher perceived QoL, reduced cognition and apathy, and negatively to social participation and length of stay in the LTCF. Mediated through apathy and social participation, impaired awareness is indirectly related to other neuropsychiatric symptoms. Impaired awareness is closely related to other domains of daily functioning and QoL of people with KS or other severe alcohol-related cognitive deficits living in LTCFs. Apathy plays a central role. Network analysis offers interesting insights to evaluate the interconnection of different symptoms and impairments in brain disorders such as KS.

Prevalences and Indications of Psychotropic Drug Prescriptions in Nursing Home Residents with Korsakoff Syndrome.

Psychotropic drugs (PD) are often prescribed to nursing home residents with Korsakoff syndrome (KS). It is unknown whether these drugs are prescribed correctly or whether they are prescribed off-label, for example, to treat behavioral symptoms. To get more insight into PD prescriptions, a descriptive study was performed. The type, category and indications of PD prescriptions of 285 participants were analyzed using medication charts and questionnaires. Behavioral symptoms were investigated with the Neuropsychiatric Inventory-Questionnaire. The results showed that atypical antipsychotics (57.1%) were prescribed more frequently than typical antipsychotics (49.3%). Of the antidepressants, selective serotonin/norepinephrine reuptake inhibitors (63.1%) were most frequently prescribed, followed by tricyclic antidepressants (23.4%). Of the benzodiazepines, anxiolytics (85.7%) were more prescribed than hypnotics (24.5%). Besides psychiatric disorders, PD were also prescribed to treat behavioral symptoms varying from 29.9% (antipsycho-tics) to 26.3% (benzodiazepines) and 9.3% (antidepressants). Furthermore, prescriptions were high if behavioral symptoms were present. To conclude, PD are often prescribed to residents with KS for an unapproved indication, namely behavioral symptoms. Additional research is needed to obtain further insight into the current prescribing culture and the effectiveness of PD. The insights thus obtained may, ultimately, contribute to the appropriate prescription of PD for people with KS.

Alcohol use, dementia risk, and sex: a systematic review and assessment of alcohol-attributable dementia cases in Europe

BackgroundHigh-risk alcohol use is an established modifiable risk factor for dementia. However, prior reviews have not addressed sex differences in alcohol-related dementia risk. In this systematic review, we take a sex-specific perspective towards the alcohol-dementia link, taking into account the age of dementia onset.MethodsWe searched electronic databases for original cohort or case–control studies investigating the association between alcohol use and dementia. Two restrictions were considered: First, studies had to report results stratified by sex. Second, given the fact that the age at dementia onset seems to affect the alcohol-dementia link, studies were required to distinguish between early-onset and late-onset dementia (cut-off: 65 years). Additionally, the contribution of alcohol to dementia incidence was quantified for a set of 33 European countries for the year 2019.ResultsWe reviewed 3,157 reports, of which 7 publications were finally included and summarised narratively. A lower dementia risk when drinking alcohol infrequent or at moderate levels was found in men (three studies) and women (four studies). High-risk use and alcohol use disorders increased the risk of mild cognitive impairment and dementia, particularly early-onset dementia. Estimating the alcohol-attributable share of incident dementia cases revealed that 3.2% and 7.8% of incident dementia cases were estimated to be attributable to high-risk alcohol use (at least 24 g of pure alcohol per day) in 45-to-64-year-old women and men, respectively.ConclusionsResearch to date has paid little attention to the sex-specific link of alcohol and dementia. In the absence of sex-specific research, the established recommendations on high-risk alcohol use should be employed to communicate the alcohol-attributable dementia risk.

Nystagmus Response to Thiamine Replacement, a Predictor of Wernicke-Korsakoff (WE) Syndrome Outcome. A 21-patient Cohort Study (S12.002)

<h3>Objective:</h3> To identify an easily recognizable clinical marker of thiamine deficiency to procure timely diagnosis <h3>Background:</h3> Wernicke’s Encephalopathy (WE) treatment outcome depends on genetic factors, duration of insufficient thiamine, metabolic demand and comorbidities. Nystagmus is by far the most frequent ocular motor finding abnormality in thiamine deficiency. Its response to treatment predicts outcome. <h3>Design/Methods:</h3> This is a retrospective series of 21-patient cohort, 16 acute patients, studied as on-going acute vestibular syndrome/ataxia cohort (two telemedicine), and 5 outpatients. All underwent neurological and neurophthalmologic examination and nystagmus recordings, they had at least one abnormal ancillary test; low serum pre-treatment thiamine, or abnormal head MRI. <h3>Results:</h3> Nine patients had horizontal (h) nystagmus (two types: vestibular and gaze holding nystagmus); thiamine replacement led to rapid nystagmus resolution, and prevented encephalopathy in all (including one, who had also upbeat nystagmus/truncal ataxia (UBN/TA), one patient has chronic UBN/TA for one year with improving WE at a slower pace. Six patients had conversion from UBN to permanent downbeat nystagmus/truncal ataxia (DBN/TA), and slower WE recovery; one patient had improved UBN/TA. Three outpatients with permanent DBN/TA had a previous history and labs compatible with thiamine deficiency. One patient did not have nystagmus. None of the study-cohort patients developed Korsakoff’s syndrome (KS). <h3>Conclusions:</h3> In patients at WE risk, h-nystagmus was the earliest sign of thiamine deficiency in this cohort, had the fastest response to thiamine, which also prevented WE. Vertical nystagmus had longer WE recovery, and six patients had enduring DBN/TA. Interestingly, none of the 21 patients developed KS. This series highlight the key role of nystagmus analysis in thiamine deficiency. Adding nystagmus to Caine’s diagnostic criteria may enhance the early features of thiamine deficiency. <b>Disclosure:</b> Dr. Kattah has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Bonezzi, Switzer , Poilitto and Hupp Legal Firm.

Wernicke-Korsakoff Syndrome in pregnancy: a preventable complication (P4-4.005)

<h3>Objective:</h3> NA <h3>Background:</h3> Wernicke’s Encephalopathy (WE) is classically a triad of encephalopathy, ophthalmoplegia and gait ataxia resulting from thiamine (B1) deficiency. MRI shows symmetric white matter hyperintensities in the mammillary bodies, bilateral thalami, tectal plate and periaqueductal gray matter. WE is commonly associated with chronic alcohol use; however it can develop in any condition that limits intake or absorption of thiamine, including pancreatitis. Although rare, a number of cases of hyperemesis gravidarum in pregnancy leading to WE have been reported, however comorbid pancreatitis and progression to Korsakoff in this population have not. <h3>Design/Methods:</h3> NA <h3>Results:</h3> A 29-year-old woman of 11-weeks gestation, with multiple prior admissions for hyperemesis gravidarum and pancreatitis, was admitted for management of acute pancreatitis with a serum lipase over one-thousand. Her family initially noted symptoms of apathy, abulia, and cognitive changes which they ascribed to possession by a djinn (demon or spirit), according to an ethnomedical belief system. She also developed ataxia, identified by her family as a biomedical symptom, for which they sought medical care. Patient and her family speak Soninke, a Gambian dialect initially unavailable on hospital translation services. These factors delayed recognition of the patient’s clinical picture. Neurology was consulted on hospital day three for altered mentation, exam was notable for direction changing nystagmus, abulia, and somnolence. MRI showed a pattern typical in WE as well as cortical hyperintensities in the perirolandic cortex. Intravenous high dose thiamine improved patient’s abulia, but she continues to have residual retrograde and anterograde amnesia consistent with Korsakoff psychosis. <h3>Conclusions:</h3> Pregnant women are uniquely vulnerable to thiamine deficiency. Prompt IV thiamine repletion should be considered in hyperemesis or acute pancreatitis. Language barriers and ethnomedical beliefs can be concurrent with biomedical beliefs and limit communication and delay clinical diagnosis resulting in poor patient outcomes. <b>Disclosure:</b> Mr. Morris has nothing to disclose. Dr. Amirkhanashvili has nothing to disclose. Dr. Bhatia has nothing to disclose. Dr. Fields has nothing to disclose. Dr. Adsule has nothing to disclose. Dr. Haut has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nile AI. Dr. Haut has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB.

Distinct Sleep Alterations in Alcohol Use Disorder Patients with and without Korsakoff's Syndrome: Relationship with Episodic Memory.

Alcohol Use Disorder (AUD) results in sleep disturbances that may have deleterious impacts on cognition, especially on memory. However, little is known about the sleep architecture in patients with Korsakoff's syndrome (KS). This study aims at characterizing sleep disturbances in KS compared to AUD without KS and at specifying the relationships with cognitive impairments. Twenty-nine AUD patients (22 without KS and 7 with KS) and 15 healthy controls underwent a neuropsychological assessment and a polysomnography. The severity of sleep-disordered breathing and sleep fragmentation was similar in AUD and KS patients compared to controls. Sleep architecture differed between both patient groups: the proportion of slow-wave sleep was reduced in AUD patients only, while a lower proportion of rapid-eye movement (REM) sleep was specifically observed in KS patients. The proportion of REM sleep correlated with the severity of episodic memory deficits when AUD and KS were examined together. These data provide evidence for both similarities and specificities regarding sleep alterations in AUD patients with and without KS. They also indicate that altered sleep architecture may contribute to the pathophysiology of alcohol-related memory disorders.

Can thiamine substitution restore cognitive function in alcohol use disorder?

While clinical consequences of thiamine deficiency in alcohol use disorder (AUD) are severe, evidence-based recommendations on dosage, type of administration and duration of thiamine substitution (TS), and its' target levels remain sparse. This study aimed to compare the effect of two best practice TS regimens on thiamine blood levels (i.e. thiamine pyrophosphate, TPP) and cognitive function. In 50 patients undergoing in-patient alcohol-withdrawal treatment, TPP levels were determined at baseline and end of weeks 1, 2 and 8 following administration of oral TS (3 × 100mg/day for 7days followed by 1 × 100mg/day thereafter) either with or without preceding intravenous TS (3 × 100mg/day for 5days). An extensive psychiatric assessment was conducted at baseline, including an evaluation of AUD severity and depressive symptoms. Additionally, cognitive function and depressive symptoms were repeatedly evaluated. Relevant increases (mean increase by 100.2nmol/l [CI 76.5-123.8], P < 0.001) in peripheral blood TPP levels were observed in all patients at the end of weeks 1 and 2. Furthermore, no relevant difference between the intravenous and the oral group was found (average difference between increases: 2.3nmol/l, P = 0.912). Importantly, an association between the 'extent of the response' to TS and the performance in a memory task was revealed in secondary analyses. TS was associated with improving cognitive function in patients with AUD, independently of the substitution regime. Thus, in clinical practice, oral TS might be a sufficient but obligatory medication to prevent cognitive decline in AUD in the absence of Wernicke-Korsakoff Syndrome.

B vitamins in diseases of the nervous system - facts and myths

Introduction: B vitamins are necessary for the proper functioning of the nervous system, taking part in the synthesis of neurotransmitters, RNA and DNA and acting as cofactors in many cellular metabolic pathways. The body does not store them, so they need to be replaced daily. Mild deficiencies can cause non-specific neuropsychiatric disorders, and deep and persistent - serious, fatal disease states that require intensive supplementation, such as beriberi disease or Korsakoff's syndrome. Materials and methods: My work is based on the articles published in PubMed, medical books and websites. I was looking for the key words such as ‘biotin‘, ‘brain’, ‘homocysteine’, ‘niacin’, ‘pantothenic acid’, ‘riboflavin’, ‘thiamin’, ‘neuropathy’. Results: B vitamins seem to enhance the analgesic effect of NSAIDs. There is evidence of supportive action in the treatment of low back pain and diabetic neuropathy. There is no reliable evidence of improved cognitive function in patients with Alzheimer's disease or other types of dementia. Conclusions: due to the low toxicity, very few side effects and experimental findings, it seems reasonable to administer B vitamins in numerous pain syndromes, such as neuropathies and back pain syndromes. However, we need more randomized clinical trials to create universal recommendations and finally confirm the positive effects of these substances in neurological diseases.

Spaced Retrieval Training for Wernicke Korsakoff Syndrome with Long-Term Retrograde Amnesia

Spaced Retrieval Training for Wernicke Korsakoff Syndrome with Long-Term Retrograde Amnesia

Anorexia nervosa and Wernicke-Korsakoff syndrome: case report an literature review

IntroductionWenicke-Korsakoff syndrome (WKS) is a neurological disorder caused by thiamine deficiency. Wernicke Encephalopathy (WE) is the acute phase and the chronic phase is called Korsakoff-syndrome (KS).ObjectivesTo review the current literature on the management of WKS in a patient with anorexia nervosa.MethodsWe report the case of a 63-year-old woman admitted to the Psychiatry Unit after weight loss in the last 3 months (from 39 kg to 33,500 kg). She only made one meal a day. By exploration and analysis, neoplastic disease is ruled out (thoraco-abdomino-pelvic CT without pathological findings). She has maintained restrictive intakes for more than 30 years. A long-term anorexia nervosa (AN) is suspected, with a worsening of restrictive behavior in recent months. Upon admission, she has a weight of 33,500 kg and a BMI of 14,10. She has a left palpebral ptosis and an alteration of the anterograde memory as well as affectation of executive functions. Progressive oral diet is started, and due to the suspicion of a WKS, thiamine ev is started for a week and then continued with oral thiamine. Thiamine levels are extracted once the ev treatment has begun, so we do not have previous levels to know if they were decreased. Brain MRI shows bilateral hyperintensities in white matter and at supratentorial level in T2 and FLAIR. After a month and a half of admission, the patient has progressively regained weight, has managed to make adequate intakes and has improvement in memory.ResultsAn adverse consequence of severe malnutrition in AN due to severe food restriction and purging behavior is thiamine deficiency, and also global cerebral atrophy and concomitant cognitive deficits can be found. Thiamine deficiency occurs in 38% of individuals with AN and is often unrecognized. WKS is caused by thiamine deficiency, and WE is the acute phase of this syndrome (presentation of triad can vary). The chronic phase is KS and consists in amnesia with confabulations. WKS typically develops after malnourishment in alcoholic patients but can be associated in nonalcoholic such as prolonged intravenous feeding, hyperemesis, anorexia nervosa, refeeding after starvation, thyrotoxicosis, malabsorption syndromes; hemodialysis; peritoneal dialysis; AIDS; malignancy. WKS is a clinical diagnosis, and no specific abnormalities have been found in cerebrospinal fluid, brain imaging or electroencephalograms. MRI has a sensitivity of 53%, but high specificity of 93%, and shows an increased signal in T2 and FLAIR sequences, bilaterally symmetrical in the paraventricular regions of the thalamus, the hypothalamus, mamillary bodies, the periaquedutal region, the floor of the fourth ventricle and midline cerebellum.ConclusionsIf the disorder is suspected, thiamine should be initiated immediately in order to prevent irreversible brain damage, with an estimated mortality rate of about 20%, or to the chronic form of the WE in up to 85% of survivorsDisclosure of InterestNone Declared

Alcohol related dementia and Brain Imaging

IntroductionAlcohol is considered a social evil worldwide owing to its vast array of associated problems and complications, which may manifest in medical, legal or social domains. Excessive and prolonged alcohol use may lead to permanent structural and functional damage to the brain. The evidence from neuroimaging, neuropathological reports and autopsy evaluations suggest some degree of brain pathology in individuals diagnosed with an alcohol related disorder.ObjectivesThe aim of this study is to characterize the structural imaging findings on computed tomography (CT) and magnetic resonance (MR) imaging of our sample and provide an overview of the literature on the subject.MethodsRetrospective observational study with inpatients of Coimbra Hospital and University Centre (CHUC), who had alcohol use disorder diagnosis associated with dementia or cognition deficit. Patients were admitted from 2017 to 2021 and submitted to neuroimaging: CT and MR. Data was collected in May 2021 at informatic system.ResultsAmong 38 participants, the median age was 64 years; 86,8% were male. 35 realize CT, 34 with alterations: 23 with microvascular lesions, 17 with cortical atrophy, 8 with white matter hypodensities and 7 with subcortical atrophy. From all patients, only 14 realize MR, 13 with alterations, the most common vascular leukoencephalopathy and cortical atrophy.ConclusionsOur results support the hypothesis of neuroimaging changes resulting from alcohol consumption. The severity of alcohol dependence also correlates with neuropathophysiological and neuroimaging changes. Volume shrinkage, altered glucose metabolism and perfusion along with evidence of markedly decreased neuron density are commonly reported. The evidence of neuro-circuit disturbances is seen in form of significant loss of white matter (most prominent in the prefrontal cortex, cerebellum and corpus callosum) on functional imaging. Greater cognitive impairment has been associated with multiple and repeated withdrawal due to greater neuronal damage, and can limit the psychotherapeutic intervention, the adherence to pharmacological therapy and abstinence maintenance. The sheer presence of alcohol use disorder should encourage a neuroimaging evaluation.Disclosure of InterestNone Declared

Alcohol consumption from midlife and risk of disabling dementia in a large population-based cohort study in Japan.

The association between alcohol consumption and dementia in Japanese is poorly understood, and use of single-point alcohol assessment may cause measurement error. We explored this association in Japanese using repeated alcohol assessments. Participants in the Japan Public Health Center-based Prospective Study (JPHC Study) since 1990 and who were alive in 2006 were followed from 2006 until 2016 for dementia ascertainment. Disabling dementia was identified through long-term care insurance records. Alcohol consumption was assessed at the 5-year questionnaire survey (1995-1999) and drinking patterns were assessed on repeated follow-up (2000-2003). We performed Cox proportional hazards models with age as the time-scale with adjustment for various lifestyle factors and medical history using light consumption (<75g ethanol/week, hereinafter "g") as reference. Analysis considering death as a competing risk was also conducted. Among 42,870 participants aged 54-84years, 4802 cases of disabling dementia were newly diagnosed. Average years from alcohol assessment until dementia incidence was 14.9years. Non-drinkers and regular drinkers with ≥450g at 5years had adjusted HRs (95% CI) of 1.29 (1.12-1.47) and 1.34 (1.12-1.60). Patterns of long-term abstinence, former drinking, and regular heavy weekly consumption of ≥450g showed increased adjusted HRs of 1.61 (1.28-2.03), 2.54 (1.93-3.35), and 1.96 (1.49-2.59), respectively. Competing risk analysis yielded similar results. In Japanese, non-drinking and regular weekly consumption of ≥450g from midlife were associated with high risk of disabling dementia compared with light drinking.

Neuroradiological manifestations of drug use: description of clinical cases

IntroductionDrug use and misuse continue to create public health challenges in the world, leading to overdose deaths, infections, and other chronic health conditions. Illegal addictive drugs can lead to functional or structural impairment of the central nervous system (CNS). Because clinical findings alone are often nonspecific, and some patients are unlikely to admit substance abuse, the neuroimaging may play an important role in establishing the diagnosis and initiating treatment.ObjectivesWe aim to provide an overview of the structural imaging findings on computed tomography (CT), magnetic resonance (MR) imaging related to chronic and acute abuse of commonly addictive substances, including cannabis, alcohol, cocaine, and opioids.MethodsNon systematic review of the literature on the subject and description of three clinical cases.ResultsPathomecanisms of drugs misuse include excitotoxicity, which may lead to an acute or subacute leukoencephalopathy, and vascular complications, including vasoconstriction, vasculitis, or hypertension, which may lead to intracranial hemorrhage or ischemia. Alcohol abuse may lead to Wernicke-Korsakoff syndrome, revealing in MR bilateral symmetrical hyperintense signals on T2-weighted; Marchiafava-Bignami disease (MBD) is a very rare condition which may present hypodense lesions in the corpus callosum; and alcoholic cerebellar degeneration is a common type of acquired cerebellar ataxia and may present cerebellar volume loss localized to the anterior superior vermis. One of our clinical cases is a female, 39 years, and present cocaine induced multifocal leukoencephalopathy, associated with inflammatory/immune mediated mechanism. Other clinical case (female, 24 years) demonstrate spongiform leukoencephalotpathy from “chasing” heroin, with a characteristic presentation.ConclusionsThe main pathomechanisms related to the abuse of drugs are ischemia, hemorrhage, and leukoencephalopathy related to excitotoxicity of the drug or its derivatives. Clinical findings are nonspecific, highlighting the need to recognize these complications at both CT and MR imaging. Therefore, diagnostic imaging modalities can play a pivotal role in the recognition and timely management of drug-related complications in the CNS.Disclosure of InterestNone Declared

THE COMPLEXITY OF DUAL PATHOLOGY: REGARDING A CASE REPORT OF SEIZURES

IntroductionWernicke’s encephalopathy (WE) is a potentially reversible neuropsychiatric emergency caused by thiamine deficiency, whose classical triad consists of acute onset of confusion, gait ataxia, and oculomotor dysfunction. The diagnosis is missed in 75-80% of cases and approximately 80% of untreated patients develop Korsakoff Syndrome, which is characterized by memory impairment associated with confabulation. Early recognition of nutritional deficiency or any portion of the triad is critical and should prompt treatment, since WE is readily reversible if treated with adequate doses of parenteral thiamine.ObjectivesStarting from a case report of suspected WE, we pretend to discuss the differential diagnosis of seizures in dual pathology.MethodsNon-systematic review of the literature was performed in PubMed database using the keywords “Wernicke’s Encephalopathy”, “Seizures”, “Alcohol” and “Benzodiazepines”. The articles were selected according to their relevance. A patient´s clinical record was reviewed and presented.ResultsWe present a case of a 44-year-old Ukrainian man with suspected background of chronic alcohol abuse and psychiatric history of schizoaffective disorder, who presented with acute onset of confusion, psychomotor agitation, gait ataxia and nystagmus. Anamnesis was hampered by the language barrier and absence of past medical history and patient’s alcoholic habits remained unclear. After suspicion of WE it was introduced thiamine and diazepam, with significant improvement. After discontinuation of diazepam, the patient presented with several episodes of tonic-clonic seizures. He was medicated for seizures with clinical stabilization. At time of discharge the diagnostic discussion prevailed.Seizures are a common presentation of various conditions associated with alcohol use, whose differential diagnosis is difficult, especially in patients with dubious alcohol consumption. Alcohol abuse is a major precipitant of status epilepticus as seizure threshold is raised by alcohol drinking. Seizures may also occur during alcohol withdrawal, for which treatment with benzodiazepines is recommended, however carefully, since both abrupt cessation and high-dose use are critical for the appearance of seizures. Although very rare, WE may also present with seizures, whereby overdiagnosis and overtreatment are preferred to prevent persistent neurocognitive impairments.ConclusionsThis case illustrates the complexity of neuropsychiatric diagnoses in dual pathology. It requires a longitudinal assessment for a better understanding of clinical conditions and establishment of the best therapeutic approach.Disclosure of InterestNone Declared

"What Did I Tell This Sad Person?": Memory for Emotional Destinations in Korsakoff's Syndrome.

We investigated destination memory, defined as the ability to remember to whom a piece of information was previously transmitted, for emotional destinations (i.e., a happy or sad person) in Korsakoff's syndrome (KS). We asked patients with KS and control participants to tell facts to neutral, positive, or negative faces. On a subsequent recognition task, participants had to decide to whom they told each fact. Compared with control participants, patients with KS demonstrated lower recognition of neutral, emotionally positive, and emotionally negative destinations. Patients with KS demonstrated lower recognition of emotionally negative than for emotionally positive or neutral destinations, but there were no significant differences between recognition of neutral and emotionally positive destinations. Our study demonstrates a compromised ability to process negative destinations in KS. Our study highlights the relationship between memory decline and impaired emotional processing in KS.