Cognitive deficits associated with chronic hepatic encephalopathy and their response to levodopa.

Elithorn, Alick; Lunzer, Michael; Weinman, John

doi:10.1136/jnnp.38.8.794

Cited by 30 publications

(6 citation statements)

References 19 publications

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“…Rats with HE have also reduced ability to learn an object recognition task [29], reduced performance in associative tests [30,31] and in working memory tests in the Morris water maze [32]. Working memory is also altered in patients with HE [33]. In accordance with other findings, our data showed that biliary obstruction after four weeks induced a significant impairment in both spatial and object novelty detection memories.…”

Section: Discussionsupporting

confidence: 89%

Function of opioidergic and dopaminergic antagonists on both spatial and object novelty detection deficits induced in rodent model of hepatic encephalopathy

Nasehi

Mafi

Ebrahimi-Ghiri

et al. 2016

Behavioural Brain Research

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Liver disease has been known for a long time to affect brain function. We now report the function of opioidergic and dopaminergic antagonists on both spatial and object novelty detection deficits induced by hepatic encephalopathy (HE) following bile duct ligation (BDL), a model of chronic liver disease. Assessment of spatial and object novelty detection memories was carried out in the non-associative task. It consists of placing mice in an open field containing five objects and, after three sessions of habituation, examining their reactivity to object displacement (spatial novelty) and object substitution (object novelty). Both spatial and object novelty detection memories were impaired by BDL after 4 weeks. In the BDL mice, pre-test intraperitoneal administration of naloxone (μ-opioidergic receptor antagonist) at dose of 0.9mg/kg restored while sulpiride (D2-like dopamine receptor antagonist) at dose of 40mg/kg potentiated object novelty detection memory deficit. However, SCH23390 (D1-like dopamine receptor antagonist) at dose of 0.04mg/kg or sulpiride (20mg/kg) restored spatial novelty detection memory deficit. Moreover, SCH23390 or sulpiride impaired while naloxone did not alter both memories in sham-operated mice. Furthermore, subthreshold dose co-administration of dopaminergic antagonists together or each one plus naloxone did not alter both memory impairments in BDL mice, while all of three co-administration groups impaired object novelty detection and co-administration of naloxone plus sulpiride impaired spatial detection memory in sham-operated mice. In conclusion, we suggest that opioidergic and dopaminergic systems through separate pathways may contribute in memory impairments induced by BDL in the non-associative task.

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Section: Discussionsupporting

confidence: 89%

Function of opioidergic and dopaminergic antagonists on both spatial and object novelty detection deficits induced in rodent model of hepatic encephalopathy

Nasehi

Mafi

Ebrahimi-Ghiri

et al. 2016

Behavioural Brain Research

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“…In MHE, specific neuropsychological and/or neurophysiological tests allow the examiner to unveil the patient's difficulties [8,9]. From the neuropsychological viewpoint, MHE affects three different areas of cognition: attention and executive functions resulting in inattention and dysexecutive difficulties; motor coordination yielding slowness and inaccuracy; and visuospatial perception leading to visuospatial and possibly visual-constructional difficulties [9][10][11][12][13][14][15][16]. In daily life, this neuropsychological syndrome realizes as disinterest, distraction, clumsiness, falls and fatigue, which inevitably impacts critical activities such as driving a car, working or ensuring a decent socioeconomic living [9,17,18], resulting in lower quality of life [19,20].…”

Section: Introductionmentioning

confidence: 99%

Standardization of the psychometric hepatic encephalopathy score in a French population

Coubard¹,

Ober²,

Gaumet³

et al. 2021

PLoS ONE

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The Psychometric Hepatic Encephalopathy Score (PHES) has previously been standardized in thirteen countries on three continents, confirming its status of gold standard test to detect minimal hepatic encephalopathy (MHE). In the meantime, performance has also been shown to vary with variables such as age, education, and barely sex. The present study aimed at standardizing the PHES in a French population. One hundred and ninety-six French healthy participants completed a French version of the paper-and-pencil PHES, involving five tests and six measures. Importantly, the balance was perfect between all levels of the three controlled factors, which were sex, age (seven decade-levels from 20–29 to 80–89 years), and education (two levels below or above 12 years of education). Raw measures were transformed to fit the normal distribution. ANOVAs on transformed variables showed no effect of sex, but an effect of age on all measures, and of education on five measures. Multiple or simple regressions were completed to build up normograms. Thorough analysis of variability within each test failed to find outliers that may bias the results. Comparison between French and seminal German data showed that they highly fitted though cultural and cognitive style specificities could be observed. This is the first study to standardize the PHES in a French population and to extensively explore the effects of sex, age and education using perfectly balanced samples. Subtle differences between countries of the same continent emphasize the need to build up normative data in each country to get accurate PHES in patients.

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“…logical consequences of HE. In the first place, a similar impairment in working memory has been reported in patients with HE (18). In the second place, the time interval chosen (60 min) seems to involve the activation of hippocampal formation and not the prefrontal cortex (19).…”

Section: Resultsmentioning

confidence: 70%

Evaluation of two experimental models of hepatic encephalopathy in rats

García-Moreno

Conejo

González-Pardo

et al. 2005

Braz J Med Biol Res

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The serious neuropsychological repercussions of hepatic encephalopathy have led to the creation of several experimental models in order to better understand the pathogenesis of the disease. In the present investigation, two possible causes of hepatic encephalopathy, cholestasis and portal hypertension, were chosen to study the behavioral impairments caused by the disease using an object recognition task. This working memory test is based on a paradigm of spontaneous delayed non-matching to sample and was performed 60 days after surgery. Male Wistar rats (225-250 g) were divided into three groups: two experimental groups, microsurgical cholestasis (N = 20) and extrahepatic portal hypertension (N = 20), and a control group (N = 20). A mild alteration of the recognition memory occurred in rats with cholestasis compared to control rats and portal hypertensive rats. The latter group showed the poorest performance on the basis of the behavioral indexes tested. In particular, only the control group spent significantly more time exploring novel objects compared to familiar ones (P < 0.001). In addition, the portal hypertension group spent the shortest time exploring both the novel and familiar objects (P < 0.001). These results suggest that the existence of portosystemic collateral circulation per se may be responsible for subclinical encephalopathy.

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Cognitive deficits associated with chronic hepatic encephalopathy and their response to levodopa.

Cited by 30 publications

References 19 publications

Function of opioidergic and dopaminergic antagonists on both spatial and object novelty detection deficits induced in rodent model of hepatic encephalopathy

Function of opioidergic and dopaminergic antagonists on both spatial and object novelty detection deficits induced in rodent model of hepatic encephalopathy

Standardization of the psychometric hepatic encephalopathy score in a French population

Evaluation of two experimental models of hepatic encephalopathy in rats

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