Prion Disease.

Prion diseases are a phenotypically diverse set of disorders characterized by protease-resistant abnormally shaped proteins known as prions. There are three main groups of prion diseases, termed sporadic (Creutzfeldt-Jakob disease [CJD], sporadic fatal insomnia, and variably protease-sensitive prionopathy), genetic (genetic CJD, fatal familial insomnia, and Gerstmann-Straussler-Scheinker syndrome), and acquired (kuru, variant CJD, and iatrogenic CJD). This article will review the pathophysiology, genetics, clinical presentations, and diagnostic challenges in patients with prion disease. Case discussions, images, and tables will be used to highlight important characteristics of prion disease and prion mimics.

[The prevention of Korsakoff's syndrome by offering involuntary care?] / Voorkómen van het syndroom van Korsakov door aanbieden onvrijwillige zorg?

BACKGROUND: The new draft Law on care and coercion focuses on the care of people with a psychogeriatric disorder or intellectual disability. Perhaps this law can be applied to people suffering from chronic alcoholism, associated with an increased risk of Korsakoff's syndrome. AIM: To explore whether the new draft law on care and coercion can be applied to people suffering from chronic alcoholism who still live at home. METHOD: A description of possibilities of involuntary homecare to people suffering from chronic alcoholism based on literature, current legislation and two new draft laws. RESULTS: It seems possible to apply the law care and coercion to people suffering from chronic alcoholism. CONCLUSION: The application of the draft law care and coercion offers the possibility of providing involuntary homecare to people suffering from chronic alcoholism, enabling the administration of thiamine. This reduces the chances of developing Korsakoff's syndrome. Further research is necessary to explore the practical possibilities in offering involuntary care.

Non-alcoholic Wernicke's encephalopathy with cortical involvement and polyneuropathy following gastrectomy.

In this study, we present the clinical manifestations, brain magnetic resonance imaging (MRI) and concurrent polyneuropathies in two patients with non-alcoholic Wernicke's encephalopathy (WE) after gastrojejunostomy (Billroth II) anastomosis procedures. These patients developed sub-acute onset of disorientation and disturbance of consciousness following several weeks of poor intake. Peripheral neuropathy of varying severity was noted before and after the onset of WE. Brain MRI of the patients showed cerebellar vermis and symmetric cortical abnormalities in addition to typical WE changes. Electrophysiological studies demonstrated axonal sensorimotor polyneuropathy. Prompt thiamine supplement therapy was initiated and both patients gradually recovered, however mild amnesia was still noted 6 months later. We reviewed non- alcoholic WE with atypical cortical abnormalities in English language literatures and identified 29 more cases. Eight out of 31 (25.8%) patients died during follow-up. Nine patients with gait disturbance or motor paresis had showed hyporeflexia in neurological examinations. In addition to classic triad, seizure was recorded in seven patients. Dietary deprivation is a risk factor for non-alcoholic WE among elderly patients receiving gastrointestinal surgery. The prognosis is good after thiamine supplement therapy. Recognizing the MRI features and predisposing factors in patients who have undergone gastrectomy can aid in the diagnosis and management.

Wernicke's encephalopathy mimicking neuropsychiatric symptoms in patients with systemic lupus erythematosus: a report of three cases and literature review.

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease that involves many organs and systems. Nervous system involvement in SLE encompasses neurological and psychiatric disorders, and remains a diagnostic and therapeutic challenge. Wernicke's encephalopathy (WE) is a neurological disorder that occurs as a consequence of thiamine deficiency, and its clinical presentation resembles the neuropsychiatric events attributed to SLE (NPSLE). Differentiation between these two entities is crucial because their treatment differs greatly and can change prognosis. We describe three cases of patients with SLE who presented with initial clinical findings suggestive of NPSLE that, at the end of a thorough clinical investigation, were actually found to represent WE. In all of these cases, treatment with thiamine resulted in significant improvement. WE should be considered as a differential diagnosis in SLE patients with neuropsychiatric signs and symptoms, especially when risk factors for thiamine deficiency are present.

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.

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

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

The Korsakoff syndrome: clinical aspects, psychology and treatment.

AIMS: The Korsakoff syndrome is a preventable memory disorder that usually emerges (although not always) in the aftermath of an episode of Wernicke's encephalopathy. The present paper reviews the clinical and scientific literature on this disorder. METHODS: A systematic review of the clinical and scientific literature on Wernicke's encephalopathy and the alcoholic Korsakoff syndrome. RESULTS: The Korsakoff syndrome is most commonly associated with chronic alcohol misuse, and some heavy drinkers may have a genetic predisposition to developing the syndrome. The characteristic neuropathology includes neuronal loss, micro-haemorrhages and gliosis in the paraventricular and peri-aqueductal grey matter. Lesions in the mammillary bodies, the mammillo-thalamic tract and the anterior thalamus may be more important to memory dysfunction than lesions in the medial dorsal nucleus of the thalamus. Episodic memory is severely affected in the Korsakoff syndrome, and the learning of new semantic memories is variably affected. 'Implicit' aspects of memory are preserved. These patients are often first encountered in general hospital settings where they can occupy acute medical beds for lengthy periods. Abstinence is the cornerstone of any rehabilitation programme. Korsakoff patients are capable of new learning, particularly if they live in a calm and well-structured environment and if new information is cued. There are few long-term follow-up studies, but these patients are reported to have a normal life expectancy if they remain abstinent from alcohol. CONCLUSIONS: Although we now have substantial knowledge about the nature of this disorder, scientific questions (e.g. regarding the underlying genetics) remain. More particularly, there is a dearth of appropriate long-term care facilities for these patients, given that empirical research has shown that good practice has beneficial effects.

[Gayet-Wernicke's encephalopathy. A study of 13 cases observed in a refugee population hospitalized at the Conakry Teaching Hospital]. / Encéphalopathie de Gayet-Wernicke. Etude de 13 observations dans une population de patients réfugiés hospitalisés pour affections neurologiques au CHU de Conakry.

The authors report 13 cases of Gayet-Wernicke's encephalopathy observed in 13 patients of a refugee population. 11 presented the classical triad: oculomotor signs, cerebral ataxia and state of confusion and in 2 patients, only 2 symptoms were noted. The etiological factors: chronic alcoholism, malnutrition, uncontrollable vomiting, HIV and tuberculosis were identified. The outcome was evaluated on the basis of the disappearance of symptoms after treatment with 500 mg of thiamine in 7 patients, 1 death and 5 patients progressed toward Korsakoff amnesic syndrome.

An atypical neuropsychological profile of a Korsakoff syndrome patient throughout the follow-up.

The basis of amnesia in alcoholic Wernicke-Korsakoff syndrome (WKS) has been generally associated with diencephalic lesions and more specifically with lesions of the anterior thalamic nuclei. These brain structures are considered to be involved in encoding/consolidation processes of episodic memory. However, frontal lobe damage responsible for executive function deficits has also been documented. The present report details the nature and extent of amnesia in an alcoholic patients with WKS and which appears to be mainly due to frontal lobe (executive) deficits.

Psychotic manifestations of alcoholism.

The psychotic manifestations of alcohol physical and psychiatric disorders have been documented for many centuries; however, the distinction of the various disorders remains less well defined. Individuals often have comorbid elements of several disorders, and the psychotic phenomenon are often diverse. The psychotic manifestations of alcohol withdrawal, delirium tremens, alcohol hallucinosis, Wernicke's-Korsakoff's psychosis, alcohol pellagra and hepatic encephalopathy, Marchiafava-Bignami, central pontine myelinosis, and alcohol dementia are discussed in this article.

Degeneration of anterior thalamic nuclei differentiates alcoholics with amnesia.

The specific neural substrate underlying the amnesia in alcoholic Korsakoff's psychosis is poorly defined because of the considerable brain damage found in many non-amnesic alcoholics, particularly those with Wernicke's encephalopathy. Using operational criteria to identify alcoholics with and without Korsakoff's psychosis, we have shown that many of the cortical and subcortical regions involved in the encoding and retrieval of episodic memory are either unaffected (hippocampus) or damaged to the same extent (prefrontal cortex and the cholinergic basal forebrain) in both amnesic and non-amnesic alcoholics. In the present study we analysed the diencephalic regions involved in episodic memory to determine the neural substrate for the amnesia observed in alcoholic Korsakoff's psychosis. The number of neurons in spaced serial sections containing the hypothalamic mamillary nuclei and the anterior and mediodorsal thalamic nuclei was estimated using unbiased stereological techniques. Neurodegeneration of the hypothalamic mamillary nuclei and the mediodorsal thalamic nuclei was substantial in both non-amnesic and amnesic alcoholics with Wernicke's encephalopathy. However, neuronal loss in the anterior thalamic nuclei was found consistently only in alcoholic Korsakoff's psychosis. This is the first demonstration of a differentiating lesion in alcoholic Korsakoff's psychosis and supports previous evidence that degeneration of thalamic relays are important in this memory disorder.

Evaluation of the role of NMDA-mediated excitotoxicity in the selective neuronal loss in experimental Wernicke encephalopathy.

The goal of the studies described was to evaluate the role of NMDA receptor-mediated glutamate excitotoxicity in the pathogenesis of selective neuronal loss due to thiamine deficiency. Administration of the central thiamine antagonist pyrithiamine to adult male rats resulted in a sequence of neurological symptoms including ataxia and loss of righting reflex followed by convulsions. Prior to the onset of convulsions, neuropathologic evaluation revealed significant neuronal loss in the ventral posterior medial thalamic nucleus. However, in vivo cerebral microdialysis at preconvulsive stages did not demonstrate significant increases of extracellular glutamate in this region and pretreatment with the NMDA receptor antagonist MK801 (1 mg/ kg/12 h, i.p.) did not afford significant neuroprotection. Following the onset of convulsions, microdialysate glutamate concentrations were increased fivefold (P > 0.05) and MK801 treatment resulted in significant attenuation of neuronal loss in some thalamic nuclei. A comparable degree of neuroprotection was afforded by pretreatment with an anticonvulsant dose of diazepam (10 mg/kg/12 h, i.p.) a compound whose action is not NMDA receptor mediated. These findings suggest that NMDA receptor-mediated excitotoxicity is not responsible for early selective neuronal loss in this model of thiamine deficiency encephalopathy and that the neuroprotective effect of MK801 at later stages are at least in part a consequence of its anticonvulsant properties.