© Borgis - New Medicine 4/2008, s. 94-99
*Bruno Peixoto1, Laudino Lopez2, Jorge Areias3, Rute Cerqueira4, Jorge Arias2
Executive Functions in Minimal Hepatic Encephalopathy
1Sciences Department of Instituto Superior de Cięncias da Saúde- Norte (Gandra, Portugal); Psychobiology Group of the Psychology and Health Research Unit (UnIPSa)
2Psychology Department of Universidad de Oviedo (Oviedo, Spain)
3Gastroenterology Department of the Santo António General Hospital (Porto, Portugal)
4 Gastroenterology Department of the Săo Sebastiăo Hospital (Santa Maria da Feira, Portugal)
Minimal hepatic encephalopathy (MHE) is a clinical condition of the hepatic encephalopathy spectrum that is not easily identified on a routine neurological examination. Nevertheless, deficits can be exposed through a more detailed neuropsychological or neurophysiological assessment. Executive functioning (EF) in this condition has not been fully explored.
Aim. We aim to identify EF impairments in the spectrum of hepatic cirrhosis and its distribution among mild, moderate and severe levels of the disease.
Materials and methods. Our sample is divided into three experimental groups based on the Child-Pugh classification of hepatic cirrhosis severity: Child A group (n=20), Child B group (n=20) and Child C group (n=20), and a control group (n=20).
Results. All the participants had normal results in the Mini Metal State Examination. The Behavioural Assessment of the Dysexecutive Syndrome battery and the Wisconsin Card Sorting Test were used in order to assess the EF. Our results enabled an executive profile of the MHE in the spectrum of cirrhosis. In the mild and moderate stages of liver dysfunction, we observed deficits in ability to inhibit previous associations and to use feedback in order to correct behaviour. With the progression of the liver disease, there is an increase of those deficits. Meanwhile, considerable deficits in cognitive estimation, organization and maintenance of behaviour through a certain period of time and structured planning were found at all levels of hepatic cirrhosis.
Hepatic Encephalopathy (HE) is a neuropsychiatric syndrome that occurs as a result of acute, subacute or chronic hepatocellular failure, with signs and symptoms ranging from mild personality and cognitive impairments to significant memory and attention impairments, from mild motor and awareness deficits to asterixis, hypertonia, hyperreflexia, positive Babinski sign, lethargy, semi-stupor and coma. This definition reflects the existence of a wide spectrum of neuropsychiatric manifestations related to a considerable set of different pathophysiological mechanisms. It also reflects the need for HE definition and adaptation to different clinical contexts .
Type C HE is the form of encephalopathy associated with hepatic cirrhosis, portal vein hypertension and portal-systemic circuits and encompasses three subtypes. The first two (episodic and persistent HE) can be easily identified on a routine neurological examination; the third subtype (minimal HE, MHE), is more difficult to identify, and its evaluation calls for a more detailed neuropsychological assessment  or the use of electrophysiological tests, such as the electroencephalogram and the related evoked potentials . Different studies  show a high prevalence of MHE among patients with cirrhosis and a severe impairment of their quality of life . These results illustrate the importance of neuropsychological studies aiming to characterize and diagnose MHE.
Neuropsychological studies in this area are generally based on the application of various neuropsychological tests to patients with hepatic cirrhosis without evident signals of episodic or persistent HE. This line of research was initiated by Rikkers and colleagues in 1978 when they observed the presence of visual spatial deficits in a cirrhosis group compared to a group of alcoholics without cirrhosis. Those deficits were the first known feature of MHE. Since this study, several others have confirmed the presence of neurocognitive alterations in patients without overt EH signals. In fact, visual-spatial, psychomotor, visuopraxic and attention deficits are some of the consistent signs reported by researchers . The memory deficits (semantic and working memory) reported by some authors  are thought to be related to impaired attention  and its consequent interference in the encoding phase of the memory process. The observations that suggest driving incapability of these patients are equally relevant .
In this context, MHE is considered a disorder with clinical and social significance. Therefore, the study of neurocognitive impairments is very important, in order to understand hepatic patients and their neurological reality. A brain able to integrate and to deliberate on the information, in a directed and regulated way, is crucial for adjustment to the problems of daily life. These observations reinforce the urge to improve the EF study in the context of hepatic dysfunction, from mild hepatic impairment to more severe levels of liver disease .
The present study aims to identify the distribution of possible EF impairments related to daily life activities, in the spectrum of hepatic dysfunction, in mild, moderate and severe levels of hepatic alterations (Child A, B and C cirrhosis types).
Materials and METHODS
Our sample consisted of 80 participants grouped according to the following conditions: (1) Child A group (n=20) – subjects with severity level A of Child-Pugh hepatic cirrhosis classification; (2) Child B group (n=20) – subjects with severity level B of Child-Pugh hepatic cirrhosis classification; (3) Child C group (n=20) – subjects with severity level C of Child-Pugh hepatic cirrhosis classification; (4) Control group (n= 20) – regular blood donors, controlled for hepatic disease through regular analytical examinations. Child A, B and C groups were identified by gastroenterologists in agreement with several analytical and clinical criteria (Table 1).
Table 1. Sample characteristics.
|Control||Child A||Child B||Child C|
|Gender (Males/ Females)||15/ 5||16/ 4||17/ 3||17/ 3|
|Age (mean ?SD)||45.25?10.74||47.70?10.21||47.55?8.82||47.657?9.01|
|Viral + Alcoholic||-||10||11||9|
|Mini Mental (mean ?SD)||28.95?1.050||28.10?1.119||28?1.026||28?0.725|
The exclusion criteria were the presence of EH at the time of the neuropsychological evaluation or, in the recent medical history, neurological pathology, psychiatric or psychological disturbances, cardiovascular or respiratory pathologies, renal insufficiency, diabetes, infection with HIV and use of any of the following in the period near the neuropsychological assessment: narcotics, benzodiazepines, barbiturates, anti-histamines and alcohol.
The groups did not differ in age and education. The experimental groups did not show differences regarding the cirrhosis aetiology.
The neuropsychological assessment had the objective to evaluate different components of the executive functioning in a short period of time. The characterization and measurement of EF is one of the greatest challenges for neuropsychologists; firstly due to the need to structure a situation where the subjects are required to show how and when they organise themselves; secondly, for the dynamics and complexity of the object of study by itself .
In agreement with the above, the Behavioural Assessment of the Dysexecutive Syndrome (BADS) and a computer version of the Wisconsin Card Sorting Test (WCST) were adopted as central elements in the neuropsychological assessment. The BADS was selected due to its ecological validity and the possibility to selectively identify executive dysfunctions . WCST was selected in addition to BADS in order to study different components of the executive functions such as: planning capability, aptitude to maintain a behavioural strategy and self-regulation of behaviour in response to environmental contingences.
Behavioural Assessment of the Dysexecutive Syndrome (BADS)
BADS construction was influenced by Baddeley´s working memory model  and Norman and Shallice attention supervision system . The battery consists of six tests relating to daily life activities : Rule shift cards test, Action program test, Key search test, Temporal judgement test, Zoo map test and the Six elements test (modified).
In the Rule shift card test the subject must perform a first task with cards following a specific rule and a second task with the same cards but with a different rule. The final result is obtained by adding the errors made in the second task. This test assesses the ability to change rules, that is, the maintenance of the current rule and the inhibition of the response to the previous rule. In the Action program test the subject faces a task with several materials to be manipulated in five steps in order to achieve a final goal. This test is an excellent way to verify how subjects respond to a new problem through the manipulation of a variety of objects . The final result is obtained by subtracting the number of helps provided by the examiner from the number of correct steps. In the Key search test the subject is asked to look for a lost key on a surface represented by a white square drawn on a piece of paper. This task assesses the ability to plan efficient actions and it allows performance monitoring. Total scoring is obtained following a complex analysis of the adopted strategy. The Temporal judgement test is, by excellence, a cognitive estimation test . The patient is asked to answer four questions. The final result is obtained after scoring the answers within a reasonable time interval. In the Zoo map test the individual is asked to show what he would do to visit a set of previously defined places, by drawing an itinerary on a zoo map in accordance to some rules. This test evaluates spontaneous and structured planning ability. The final score depends on the number of visited places, the number of errors that occurred and completion time. Finally, the Six elements test (modified) consists of three tests (dictation, arithmetic and object naming) with two sub-tasks each. The subject is asked to perform some of the six sub-tasks within ten minutes. According to the authors, this test has proven to be an excellent way to assess planning and organization ability, attention focusing through time and behaviour monitoring.
The Wisconsin Card Sorting Test (WCST)
WCST is the most popular test on pre-frontal dysfunction assessment. There are several studies showing the activation of pre-frontal structures while performing this test . A computer version of the WCST was used.
In our study, we took into consideration the number of criteria-categories achieved (from zero to six), the number of times the individuals insisted on pairing cards with an incorrect but previously correct criterion (perseverative error) and the number of times the patients were unable to keep the right answer after having made five good pairings (criterion maintenance error). This test assesses the capability to plan, to perform an organised search, to use feedback in order to change strategies and to modulate or to inhibit the impulse .
The neuropsychological assessment took place at two Portuguese gastroenterology hospital departments. The Ethics Committees issued favourable reports related to the experimental design and informed consent was given. Participants were assessed with the Mini Mental State Inventory (MMSI) in order to control the presence of an overt form of hepatic encephalopathy. Only the subjects who scored above 26 (cut-off point for the Portuguese population) in the MMSI were included in the study.
The statistical analyses were carried out using the computer program SPSS(r) for Windows, version 15.0. The differences in cognitive variables between the different groups in the sample were determined by multivariate analysis of variance (MANOVA), followed by a univariate analysis of variance (ANOVA) and a comparison between the groups by using Scheffe´s test. Differences between the groups were considered significant at p<0.05.
Table 2 shows groups Child A, B and C results. Wilk´s Lambda test (Lambda= 0.097; F=9.040; sig.=0.000) shows a significant effect of liver condition on neuropsychological test scores. ANOVA shows a significant effect of the independent variable on each of the neuropsychological tests (Table 3). No significant differences were found between aetiologies or between genders on test scores.
Table 2. Test results according to groups.
|Control||Child A||Child B||Child C|
|Cards (mean?SD)||2.85?1.63||5.55? 2.74||7.55? 3||9.2? 3.03|
|Action Program (mean?SD)||4.70?0.57||3.50? 0.88||2.90? 1.25||2.65? 0.74|
|Key (mean?SD)||12.75?1.80||10.10? 1.77||8.15? 1.81||7.75? 2.42|
|Judgement (mean?SD)||3.55?0.60||2.65? 0.87||2.25? 0.91||1.90? 0.91|
|Map (mean?SD)||11.50?2.30||9.30? 1.17||8.70? 1.86||7.85? 1.78|
|Six elements (mean?SD)||3.75?1.02||2.50? 0.88||2.10? 0.78||1.70? 0.73|
|WSCT Cat (mean?SD)||4.95?0.82||3.45? 0.94||2.75? 0.85||2.05? 1.05|
|WSCT Persev. (mean?SD)||8.30?3.35||19.35? 7.28||24.20? 6.95||33.40? 12.12|
|WSCT Manut. (mean?SD)||0.15?0.36||1.0? 0.79||1.05?0.68||1.10? 1.071|
Table 3. Univariate analysis.
|Action Program ||3||16,713||20,636||.000|
|Temporal Judgement ||3||10,112||14,487||.000|
|Zoo Map Test||3||48,646||14,558||.000|
|Six elements test||3||15,746||21,087||.000|
|WSCT Cat (mean?SD)||3||33,346||34,504||.000|
|WSCT Persev. (mean?SD)||3||2157,117||54,455||.000|
|WSCT Manut. (mean?SD)||3||4,083||7,167||.000|
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