Study on the Sternberg Paradigm in Cirrhotic Patients Without Overt Hepatic Encephalopathy

Memory dysfunction is reported in cirrhotics. The aim of this paper was to increase insight into memory function of cirrhotic patients without overt hepatic encephalopathy. Eighty-six consecutive cirrhotics without overt hepatic encephalopathy (aged 54±10 yr., mean±s.d.) and 28 controls (52±10 yr.) with comparable education level were enrolled. Seventeen patients were class A, 55 class B, 14 class C according to Child-Pugh classification; 29 had alcoholic cirrhosis. The presence of subclinical signs of central nervous system dysfunction were assessed by Number Connection Test (NCT) and quantified EEG analysis. Memory scanning was evaluated by reaction times (RTs) in the Sternberg paradigm. MANOVA analysis showed that RTs were higher (F_1,99=11, p<0.01) and time outs (TOs) more frequent (F_1,110=10, p<0.01) in cirrhotics than in controls, whereas button press errors (BPEs) did not differ significantly (F_1,110=2, p=n.s.). In cirrhotics, an interaction Child-Pugh class x memory set size was found (F_2,146=4, p<0.05), showing exceedingly delayed RTs with greater memory set size in class C patients. Patients with altered NCT had significantly prolonged RTs (F_1,71=4, p<0.05) and more TOs (F_1,82=11, p<0.01) than patients with normal NCT. Cirrhotics with altered EEG had significantly prolonged RTs (F_2,70=6, p<0.01). RTs were found to be correlated to alpha relative power (r=–0.4, p<0.01) and theta relative power (r=0.4, p<0.01). In conclusion, cirrhotics without over encephalopathy, but with NCT or EEG alterations, perform a computerized digit recognition task more slowly and with higher TOs than cirrhotic patients with normal NCT or EEG. In severe liver insufficiency (class C cirrhotics) also an impairment of memory scanning was detected. Sternberg test performance correlates with NCT and quantitative EEG parameters.     

Attention Dysfunction in Cirrhotic Patients: An Inquiry on the Role of Executive Control,Attention Orienting and Focusing

Attention alterations are reported in cirrhotics. Aiming at clarifying attention functioning in cirrhotics, an inquiry on the functioning of the anterior (AAS) and the posterior (PAS) attention system was performed. Thirty-six cirrhotics without overt hepatic encephalopathy (24 with EEG or TMT-A alterations) and 16 matched control subjects were enrolled. The AAS was studied by the Stroop task measuring selective attention control, the PAS was studied by the Posner task and the Focus task measuring automatic covert orienting and visual focusing of attention respectively.Cirrhotics presented a task-dependent psychomotor slowing (Stroop > Posner > Focus) with an increased percentage of errors in the incongruent condition of the Stroop task [F(1, 57) = 4.9, p < 0.03]. Class C patients had both a selective slowing [F(1, 33) = 4.3, p < 0.05] and an increased percentage of errors in the incongruent condition [F(1, 34) = 5.1, p < 0.05] compared to Class A–B patients and controls. The patients with an altered EEG performed the Stroop test significantly slowly than those without EEG alterations [F(1, 41) = 8.9, p < 0.01] and with a clear trend for a higher number of errors in the incongruent condition [F(1, 39) = 3.8, p < 0.06]. In contrast, attention orienting and focusing were maintained. In conclusion, the AAS is more sensitive than the PAS to the early stages of hepatic encephalopathy.     

Neuropsychological abnormalities in cirrhosis include learning impairment

BACKGROUND/AIMS: Minimal hepatic encephalopathy is a neurocognitive disorder secondary to liver failure that is characterized by a pattern of subcortical impairment. The most conspicuous neuropsychological abnormalities are on attention and psychomotor tests; memory has been inconsistently implicated. We designed a study to assess the presence of memory abnormalities in cirrhotic patients and the effects of liver transplantation. METHODS: Ninety-seven cirrhotics without overt hepatic encephalopathy underwent neuropsychological assessment, including the Auditory Verbal Learning Memory Test. The results were compared to those of healthy controls (n=75) and the assessment was repeated at one year of follow-up (n=33) or after liver transplantation (n=23). RESULTS: Cirrhotic patients exhibited multiple neuropsychological abnormalities, including several disturbances of the Auditory Verbal Learning memory test: learning, long-term memory and recognition. Abnormalities of long-term memory and recognition were corrected after adjusting for learning impairment. Memory abnormalities correlated to attention impairment and to parameters of liver function. Neuropsychological indexes following liver transplantation did not differ from controls. Repeated testing did not have a major effect on neuropsychological tests in healthy subjects and in non-transplanted cirrhotics. CONCLUSIONS: Learning impairment is present in cirrhotic patients with neuropsychological abnormalities. This abnormality is consistent with attention deficit secondary to minimal hepatic encephalopathy.     

Inhibitory control test is a simple method to diagnose minimal hepatic encephalopathy and predict development of overt hepatic encephalopathy

OBJECTIVES: To compare inhibitory control test (ICT), a simple/rapid test of attention, to a standard psychometric battery (SPT) to diagnose minimal hepatic encephalopathy (MHE) and predict development of overt hepatic encephalopathy (OHE) in cirrhotic patients. METHODS: Fifty nonalcoholic cirrhotics and 50 age/educational-status-matched controls were given ICT and SPT in the same sitting. Performance impaired beyond two standard deviations of controls was considered MHE in cirrhotics. ICT results (lure/target response and lures/person) were compared between controls and cirrhotics and within cirrhotics with/without MHE. Receiver-operating characteristic analysis was used to study ICT for MHE diagnosis. Twenty subjects were administered SPT and ICT twice to assess test-retest reliability. All cirrhotics were followed routinely for the development of OHE. RESULTS: Cirrhotics performed worse than controls on SPT and ICT. Using SPT, 39 cirrhotics had MHE. ICT was administered faster than SPT (15 vs 37 min). Cirrhotics with MHE had significantly higher lure (28%vs 3%) and lower target response (91%vs 96%) compared with those without MHE. Lure/person >5 had 90% sensitivity/specificity for MHE diagnosis. AUC for receiver-operating characteristic for lures alone was 95.8%. Lure and target responses were highly correlated (r= 0.9) between sessions showing high test-retest reliability. Five (10%) patients developed OHE on f/u of 26 +/- 10 months; all five had been diagnosed with MHE using ICT and SPT. None of the five patients with discordant results on SPT and ICT developed OHE. CONCLUSIONS: ICT has good sensitivity/specificity for MHE diagnosis, is reliable and is equivalent to SPT for predicting OHE development.     

Auditory P300 event-related potentials and number connection test for evaluation of subclinical hepatic encephalopathy in patients with cirrhosis of the liver: a follow-up study

BACKGROUND AND AIMS: The P300 event-related potentials (P3ERP) have been recently advocated for detection of cognitive disturbances in early encephalopathy. However, no systematic follow-up study has been conducted to understand the clinical significance of subclinical hepatic encephalopathy (SHE) detected by this or other methods. The present study was therefore undertaken to examine the diagnostic usefulness of auditory P3ERP in the detection of SHE, to compare it with that of the number connection test (NCT), and to investigate the clinical outcome of patients with SHE in terms of progression to overt encephalopathy. METHODS: P300 event-related potential latencies were measured and the NCT time was recorded in 81 non-encephalopathic cirrhotic patients (Aged 43.8 +/- 11 years, 23 alcoholic and 58 non-alcoholics) attending the outpatient department at our tertiary care hospital (All India Institute of Medical Sciences Hospital). Cut-off values for abnormality in the tests were developed from age-, sex- and education-matched controls. Patients were followed up at regular intervals for the development of overt encephalopathy, and the identifiable precipitating factors were noted. The P3ERP latencies (363 +/- 34 msec vs 349 +/- 23 msec), as well as NCT time (54.6 +/- 30.6 s vs 39.5 +/- 15.8 s) were significantly prolonged (P< 0.01) in patients with liver cirrhosis when compared with the non-cirrhotic controls. RESULTS: The P3ERP defects were seen in 24.6% of cirrhotic patients, while NCT time was prolonged in 19.7% of the patients. Nearly 43% of the patients with SHE progressed to overt encephalopathy within a mean duration of 5 months, while only 3.9% of the non-SHE patients did so. Of the patients who developed overt encephalopathy, 64.2% had P3ERP latency prolongations while 35.7% had abnormal NCT. CONCLUSIONS: The results of the present study suggest that P3ERP and NCT are valid tools for the screening of SHE in cirrhotic patients as there is a greater likelihood of overt encephalopathy development in patients with an abnormality detected by these tests than in patients with no such abnormality.     

Prevalence of subclinical hepatic encephalopathy in patients with cirrhosis determined by psychometric tests

OBJECTIVE: To investigate the prevalence of subclinical hepatic encephalopathy (SHE) in patients with stable hepatic cirrhosis. METHODS: One hundred and seventy‐five consecutive cirrhotic patients (mean age 53 years, range 27?72 years) without overt clinical encephalopathy were screened for SHE using the number connection test (NCT) part A and symbol digit test (SDT). Subclinical hepatic encephalopathy was defined as the presence of at least one abnormal psychometric test. The age‐corrected normal value was defined as the mean ± 2SD obtained from 356 subjects without liver disease and in normal mental condition. Illiterate patients and patients with concurrent use of alcohol or psychotropic drugs, and those with previous portosystemic shunt and were excluded. RESULTS: In different age subgroups, the NCT scores and SDT quotients for cirrhotic patients were significantly different compared with those for controls (P < 0.05?0.001). Fifty patients (28.6%) were found to be abnormal in both the NCT and SDT, 16 (9.1%) patients were abnormal only in the SDT and 34 patients (19.4%) only in the NCT. Taken together, SHE was diagnosed in 100 patients (57.1%) by using the two tests. The prevalence of SHE increased from 46.8% and 53.0% in Child?Pugh grades A and B, to 76.6% in Child?Pugh grade C (P < 0.05). No significant correlation was found between the development of SHE and the etiology of cirrhosis, patient age and smoking habit. CONCLUSION: By using a combination of NCT and SDT, SHE was diagnosed in 57.1% of cirrhotic patients without overt clinical encephalopathy. The prevalence of SHE was significantly correlated with the severity of liver cirrhosis.     

Correlations Between Cerebral Glucose Metabolism and Neuropsychological Test Performance in Nonalcoholic Cirrhotics

Many cirrhotics have abnormal neuropsychological test scores. To define the anatomical–physiological basis for encephalopathy in nonalcoholic cirrhotics, we performed resting-state fluorodeoxyglucose positron emission tomographic scans and administered a neuropsychological test battery to 18 patients and 10 controls. Statistical parametric mapping correlated changes in regional glucose metabolism with performance on the individual tests and a composite battery score. In patients without overt encephalopathy, poor performance correlated with reductions in metabolism in the anterior cingulate. In all patients, poor performance on the battery was positively correlated (p < 0.001) with glucose metabolism in bifrontal and biparietal regions of the cerebral cortex and negatively correlated with metabolism in hippocampal, lingual, and fusiform gyri and the posterior putamen. Similar patterns of abnormal metabolism were found when comparing the patients to 10 controls. Metabolic abnormalities in the anterior attention system and association cortices mediating executive and integrative function form the pathophysiological basis for mild hepatic encephalopathy.     

Neuropsychological deficits and morphological MRI brain scan abnormalities in apparently healthy non-encephalopathic patients with cirrhosis. A controlled study

By means of psychometric testing, we have determined the frequency of latent hepatic encephalopathy in a group of 19 cirrhotics with no clinical evidence of encephalopathy. Magnetic resonance imaging (MRI) of the brain was performed in order to determine whether morphological cerebral abnormalities were associated with latent encephalopathy. Nineteen age and educationally matched patients with normal liver function acted as controls. Significant differences (P less than 0.05) between cirrhotics and controls were found in tests of short-term visual memory and speed of reaction to light (cirrhotics 316 +/- 132 ms vs. controls 225 +/- 36 ms), sound (cirrhotics 361 +/- 152 ms vs. controls 236 +/- 52 ms) and choice (cirrhotics 651 +/- 190 ms vs. controls 406 +/- 101 ms) stimuli (all values mean +/- S.D.). Reitan trail test performance, however, was similar in both groups. (Trail A: cirrhotics 43 +/- 19 s vs. controls 35 +/- 13 s; Trail B: cirrhotics 105 +/- 66 s vs. controls 93 +/- 36 s.) In patients with cirrhosis, MRI revealed statistically significant increases in the maximum fissure width of right frontal sulci, right and left parietal sulci, inter-hemispheric fissure width and in bicaudate index. These changes, indicating cerebral atrophy, were largely confined to alcoholics. There was poor correlation between measurements of cerebral morphology and neuropsychological performance, only 10% of associations achieving statistical significance.     

Critical flicker frequency test predicts overt hepatic encephalopathy and survival in patients with liver cirrhosis

BackgroundA critical flicker frequency (CFF) ≤39 Hz identifies cirrhotic patients with minimal hepatic encephalopathy (mHE) and predicts the risk of both overt hepatic encephalopathy (oHE) and mortality in patients with previous episodes of decompensation and/or oHE.AimsHerein, we evaluated the effectiveness of CFF in predicting the first episode of oHE and survival in cirrhotics who had never experienced an episode of oHE.MethodsOur cohort study of 134 patients and 150 healthy subjects were examined. A CFF > 39 Hz was considered normal and pathological when ≤39 Hz. The median follow up was 36 months.ResultsAt baseline, all controls had CFF > 39 Hz. Ninety-three patients had a CFF > 39 Hz and 41 had a CFF ≤ 39 Hz. The prevalence of CFF ≤ 39 Hz significantly increased with the progression of the Child–Pugh class (p = 0.003). Moreover, the risk of oHE was increased by CFF ≤ 39 (p < 0.001, by log-rank test) [HR = 7.57; CI(3.27–17.50); p < 0.0001, by Cox model] and ammonia [HR = 1.02 CI(1.01–1.03), p = 0.0009]. Both a CFF value ≤ 39 Hz and Child–Pugh class were independent predictors of mortality by Cox model [HR = 1.97; CI(1.01–3.95), p = 0.049; HR = 3.85 CI(1.68–8.83), p = 0.003].ConclusionsCFF predicts the first episode of oHE in cirrhotics that had never experienced oHE, and predicts mortality risk. These findings suggest that cirrhotic patients should be routinely screened by CFF.     

Use of ImPACT to Diagnose Minimal Hepatic Encephalopathy: An Accurate, Practical, User-Friendly Internet-Based Neuropsychological Test Battery

Background and Aims

An effective, user-friendly neurocognitive test to diagnose minimal hepatic encephalopathy (MHE) is needed. Immediate Post-concussion Assessment and Cognitive Testing (ImPACT) is a brief, validated, Web-based, neuropsychological test battery resulting in four composite scores [Verbal Memory (VrbM), Visual Memory, Visual Motor Speed (VMS), Reaction Time (RT)]. We compared ImPACT to traditional paper-and-pencil tests in patients at risk for MHE versus controls.

Methods

Ninety cirrhotic patients with no history of overt hepatic encephalopathy were compared with 131 controls on standard psychometric tests (SPT) [Trail Making Test-A, Trail Making Test-B, Digit Symbol Test], 4 ImPACT composite scores, and the Sickness Impact Profile (SIP). MHE+ was defined by a score 2 SD below the normative mean on at least one of the SPT. ImPACT (ImP+) scores of patients were defined as 2 SD from the control mean.

Results

Cirrhotic patients scored more poorly than controls on 3/4 of ImPACT scores: VrbM (78.88 vs. 71.37, p < 0.001), VMS (26.47 vs. 22.68, p < 0.001) and RT (0.89 vs. 1.00, p < 0.01), as well as on all 3 SPT. Of the 90 cirrhotics, 16 (18 %) were MHE+, who performed more poorly (p < 0.001) than patients without MHE on VrbM (58.13 vs. 74.19), VMS (16.77 vs. 23.95) and RT (1.24 vs. 0.95). Of the 90 cirrhotics, 25 (27.8 %) were ImP+. MHE+ and ImP+ patients had increased SIP scores versus controls (p < 0.001).

Conclusions

Compared to paper-and-pencil testing, ImPACT provides a brief, user-friendly, neuropsychological evaluation of MHE. ImPACT could become a new standard for MHE diagnosis.     

Altered response to oral glutamine challenge as prognostic factor for overt episodes in patients with minimal hepatic encephalopathy

BACKGROUND/AIMS: We assessed the usefulness of oral glutamine challenge (OGC) and minimal hepatic encephalopathy in evaluating risk of overt hepatic encephalopathy in cirrhotic patients.METHODS: Minimal hepatic encephalopathy (MHE) was inferred using neuro-psychological tests. Venous ammonia concentrations were measured pre- and post-60 min (NH(3)-60m) of a 10 g oral glutamine load. Receiver-operating-characteristic curve analysis indicated a pathological glutamine tolerance cut-off value of NH(3)-60m >128 microg/dl. RESULTS: In healthy control subjects (n=10) ammonia concentrations remained unchanged but increased significantly in cirrhotic patients (from 70.41+/-45.2 to 127.43+/-78.6; P<0.001). In multiple logistic regression analysis, altered OGC was related to Child-Pugh (odds ratio, OR=7.69; 95% confidence interval, CI=1.72-33.3; P<0.01) and MHE (OR=5.45; 95% CI=1.17-25.4; P<0.05). In the follow-up 11 patients (15%) developed overt hepatic encephalopathy (HE). In multivariate analysis OGC (OR=14.5; 95% CI=1.26-126.3) and MHE (OR=1.56; 95% CI=1.02-21.9) were independently related with HE in the follow-up. Patients with MHE and altered OGC showed significantly higher risk of overt HE in the follow-up (60%) than patients without MHE and normal OGC (2.8%) (Log rank test=21.60; P<0.0001). CONCLUSIONS: A pathological OGC in patients with MHE appears to be a prognostic factor for the development of overt hepatic encephalopathy, whereas a normal OGC in patients without MHE could exclude risk of overt HE.     

Effect of sodium benzoate on blood ammonia response to oral glutamine challenge in cirrhotic patients: a note of caution

OBJECTIVE: The administration of sodium benzoate provides an alternative pathway for the disposal of waste nitrogen and this substance has been used to treat patients with urea cycle defects and more recently cirrhotics with hepatic encephalopathy. The aim of the study was to assess the ammonia-lowering effect of benzoate in cirrhotic patients without overt hepatic encephalopathy. METHODS: Glutamine challenge, a method to induce an increase of blood ammonia, was performed in six cirrhotics before and after 5 days of benzoate treatment (10 microg/day). Number Connection Test and Posner's Attention Test were also performed before and after benzoate treatment. RESULTS: Blood ammonia increased after the glutamine load both before (from 66 +/- 12 microg/dl to 123 +/- 34 microg/dl and 179 +/- 53 microg/dl after 30 and 60 min, respectively; ANOVA p = 0.0004) and after benzoate treatment (from 102 +/- 27 microg/dl to 185 +/- 49 microg/dl and 250 +/- 39 microg/dl after 30 and 60 min, respectively; ANOVA p = 0.00001). However, after benzoate treatment, the basal values (102 +/- 27 vs 66 +/- 12 microg/dl; p = 0.01) and peak increments of ammonia (166 +/- 56 microg/dl vs 102 +/- 40 microg/dl; p = 0.04) were significantly higher than before. The Number Connection test and the Posner's test were not altered by benzoate treatment. CONCLUSIONS: Benzoate increased both the basal and post-glutamine ammonia levels. These results confirm what has already been observed in experimental animals and suggest a note of caution in the use of sodium benzoate in cirrhotic patients.     

幽门螺杆菌感染对高氨血症和肝性脑病发病的影响

目的了解幽门螺杆菌(Hp)感染和血氨水平、肝性脑病(HE)发病的关系,并探讨根除Hp对血氨水平和HE发生的影响。方法2003年7月-2005年1月在浙江省5个地区收集肝硬化住院患者,记录患者的一般资料、数字连接试验结果、Hp感染情况、肝功能Child-Pugh分级、血氨水平和HE情况。Hp(+)患者予“奥美拉唑+克拉霉素+替硝唑”1周根除治疗,1个月后查~(14)C尿素呼气试验,并记录患者的神经精神症状和血氨水平。结果(1)共收集肝硬化住院患者457例,Hp感染率60．6%,HE发生率47．5%。检出亚临床肝性脑病(SHE)患者55例,SHE占未发生HE肝硬化患者的47．0%(55/117)。(2)Hp(+)和Hp(-)肝硬化患者血氨浓度分别为(78．4±63．6)μmoL/L和(53．8±51．4)μmol/L(P＜0．01);根除Hp后血氨显著下降至(53．5±37．7)μmol/L(P＜0．01)。Hp(+)和Hp(-)肝硬化患者HE发生率差异有统计学意义(58．5%比30．6%,P＜0．01);根除Hp后HE发生率下降至34．1%(P＜0．01)。(3)HE、SHE和肝硬化患者的Hp感染率分别为74．4%、69．1%和53．2%(P＜0．05)。三组患者的血氨水平分别为(94．5±75．6)μmol/L、(59．9±49．2)μmol/L和(47．3±33．5)μmol/L(P＜0．05)。结论Hp感染是引起肝硬化高氨血症和并发HE的重要因素,根除Hp有利于治疗和预防HE的发生。     

Autonomic nervous system tone measured by baroreflex sensitivity is depressed in patients with end-stage liver disease

OBJECTIVES: Chronic liver disease is often associated with impairment of autonomic nervous system (ANS) reflexes. Baroreflex sensitivity (BRS) testing is an inexpensive, relatively noninvasive test that can be used to assess ANS tone. The aims of the present study were to determine the prevalence of ANS dysfunction in cirrhotics who are being considered for liver transplantation and to explore the potential use of BRS as a prognostic tool in identifying patients awaiting transplantation who are at increased risk for death. METHODS: We studied nine cirrhotics who were awaiting liver transplantation and seven controls without liver disease. BRS (ms/mm Hg) was measured using the phenylephrine method. RESULTS: BRS (mean +/- SEM) (ms/mm Hg) was significantly lower in cirrhotics compared with controls (4.2 +/- 0.9 vs 21.1 +/- 3.8 ms/mm Hg; p < 0.05). Furthermore, BRS was lower in cirrhotics with hepatic encephalopathy compared with those without (2.6 +/- 0.9 vs 6.1 +/- 1.0 ms/mm Hg; p < 0.05) and there was a trend toward lower BRS values in Child-Pugh class C patients as compared with class B (3.8 +/- 1.3 vs 5.3 +/- 1.2 ms/mm Hg; p = 0.3). At follow-up (9 months), one patient had died and one underwent liver transplantation. These two patients also had the most severely impaired vagal tone (BRS = 0 and 1.2 ms/mm Hg, respectively). CONCLUSIONS: Vagal tone, as assessed by BRS, is markedly depressed in cirrhotic patients awaiting liver transplantation.     

Cerebral abnormalities in patients with cirrhosis detected by proton magnetic resonance spectroscopy and magnetic resonance imaging

Hepatic encephalopathy is a common problem in cirrhosis. The pathogenesis of this complication of advanced liver disease still remains unclear. Magnetic resonance spectroscopy was used to assess prospectively cerebral metabolism in 51 patients with histologically proven cirrhosis (Child-Pugh classes A, B, and C, 18, 18, and 15, respectively) and 36 healthy volunteers. According to the results of psychometric tests, overt hepatic encephalopathy, subclinical encephalopathy, and no encephalopathy were found in 14, 21, and 16 patients, respectively. Myoinositol/creatine ratios in gray (.36 +/- .17) and white (.35 +/- .22) matter voxel were reduced significantly (P < .0001) in cirrhotic patients compared with healthy volunteers (gray matter, .51 +/- .11; white matter, .64 +/- .16). In addition, patients showed a significant reduction (P = .024) in white matter choline/creatine ratio (.77 +/- .27) compared with controls (.92 +/- .25), and glutamine/glutamate level was elevated in cirrhotic patients compared with controls (gray matter, P < .0001; white matter, P = .036). Changes in cerebral myoinositol and glutamine/glutamate levels correlated significantly with the severity of hepatic encephalopathy (P < .0001). However, these metabolic alterations were also detected in patients without hepatic encephalopathy (normal psychometric test results). N-acetyl aspartate/creatine ratios did not differ between patients and controls. Magnetic resonance imaging detected bright basal ganglia in 37 patients, which correlated significantly with portal-systemic shunting and elevation of glutamine/glutamate, but not with the degree of hepatic encephalopathy. In conclusion, magnetic resonance imaging and spectroscopy showed that alterations of cerebral metabolism are common in patients with cirrhosis, even without evidence of clinical or subclinical hepatic encephalopathy.(Hepatology 1997 Jan;25(1):48-54)     

Minimal hepatic encephalopathy: a vehicle for accidents and traffic violations

OBJECTIVES: MHE patients have impairment on driving tests. However, it is unclear whether this impairment is restricted to the testing environment or is associated with increased traffic violations and/or motor vehicle accidents. METHODS: An anonymous driving history and driving behavior questionnaire (DBQ: self-scored, best score 104), coded according to MHE status, was sent to 200 cirrhotics without overt hepatic encephalopathy and 100 age/education-matched controls. The questionnaire inquired about demographics, alcohol/illegal drug use, and violations/accidents within 1 and 5 yr. The cirrhotics had been divided into those with MHE (MHE+), without MHE (MHE-), and those not tested for MHE because of psychoactive drug use, on a previous study. RESULTS: Cirrhotics versus controls had similar driving duration, alcohol/illegal drug use but significantly higher percentage with violations within both 1 and 5 yr (25%vs 4%[5 yr]), 13%vs 2%[(1 yr]), accidents (17%vs 4%[5 yr]), 9%vs 1%[1 yr]), and both (34%vs 7%[5 yr], 18%vs 3%[1 yr]). MHE+ cirrhotics had significantly higher percentage with violations (36%[5 yr], 21%[1 yr]), accidents (33%[5 yr]), 17%[1 yr]), and both (53%[5 yr], 33%[1 yr]) versus other cirrhotics. DBQ score was significantly lower in cirrhotics than controls (92 vs 99). Within cirrhotics, DBQ score was highest in MHE-versus other groups. MHE+ status was the only risk factor (odds ratios: 4.2-7.6) for violations and for accidents on multivariate logistic regression. CONCLUSIONS: Cirrhotics have a higher self-reported occurrence of violations and accidents compared to controls. MHE+ a is strong predictor for violations and accidents. Prospective studies investigating the effect of MHE treatment on violations and accidents are warranted.     

Diagnostic tools for the detection of subclinical hepatic encephalopathy: comparison of standard and computerized psychometric tests with spectral-EEG

The prevalence of subclinical hepatic encephalopathy (SHE) varies according to the diagnostic tool used in its detection. Since a standardised approach to the diagnosis of SHE is not yet available, we compared psychometric tests and EEG spectral analysis. On the same day 32 cirrhotic patients without overt hepatic encephalopathy and 18 controls were assessed by psychometric tests, both standard and computerized (CPT), and by EEG spectral analysis (EEG-SA). The CPT, measuring reaction time (Rt) and errors (er), were Font, Choice1, Choice2 and Scan test. The standard psychometric tests were the number connection test (NCT), the Reitan-B test, the Line Tracing Test [for time: LTT(t) and for errors: LTT(er)], and the Symbol Digit test (SD). Both psychometric tests [Reitan-B test, LTT(er) and CPT but Font (Rt) and Choice2 (er)] and EEG-SA parameters [mean dominant frequency (MDF) and theta power (%)] significantly correlated (p<0.05) with albumin plasma levels. LTT(er), Scan, Font, Choice1 and Choice2 were significantly related to % and MDF. There was no control with positive EEG-SA, though one control was positive with LTT(t) and with the number of errors made during Font and Scan tests. The percentage of cirrhotics with positive EEG-SA was 34% (CI_95%=19–53), while 9–66% were positive with psychometric tests, depending on the test considered. In spite of the correlation between neuropsychological and neurophysiological parameters, the diagnostic agreement between EEG-SA and each psychometric test was not high. In conclusion: 1) neurophysiological and neuropsychological impairment in cirrhotics without overt hepatic encephalopathy were found linked to each other and to hepatic dysfunction; 2) psychometric tests were not sufficiently good predictors of EEG alterations; therefore, neuropsychological tools can not substitute neurophysiological ones to detect CNS dysfunction in liver disease.     

Blood Mercaptan and Ammonia Concentrations in Cirrhotics After a Protein Load

Measurements of blood ammonia and methanethiol were made in 17 moderate or severe alcoholic cirrhotics without overt hepatic encephalopathy under fasting conditions and 2, 3 1/2 and 5 hours after ingestion of a hamburger containing 80 gm. protein. At every time interval the average blood methanethiol in the cirrhotics was significantly higher than in 11 normal controls. The average blood ammonia in the citrhotics was also higher than in the controls but only at five hours was the difference statistically significant. Fasting blood ammonia and methanethiol values were not strikingly effective in separating the normals and cirrhotics. After the protein load, however, the peak values of these measutements completely sepa tated the citthotics from normals on a two-dimensional plot of methanethiol vs. ammonia. In our sample of patients, the peak postprotein load measurements were not effective in predicting which cirrhotics may develop overt encephalopathy. Utilization of the area under the curve of values obtained after the protein load did not appreciably improve on the results with the single peak value.     

Efficacy of Lactulose in Cirrhotic Patients with Subclinical Hepatic Encephalopathy

To investigate the role of lactulose in the treatment of cirrhotic patients with subclinical hepatic encephalopathy (SHE), 40 cirrhotic patients, 33 males and 7 females, were included in the study. The diagnosis of SHE was made by quantitative psychometric tests including the number connection test (NCT), figure connection test (FCT) parts A and B, and two performance subtests of Wechsler adult intelligence scale, ie, picture completion (PC) and block design (BD) tests. SHE was diagnosed in 26 (65%) of 40 patients. Of these 26 patients, 14 patients were randomized to treatment group (lactulose 30–60 ml/day for three months, SHE-L) and 12 patients to no treatment group (no lactulose, SHE-NL). Psychometric tests were repeated in all patients in both groups and in six patients with no SHE (group NSHE, N = 14) after three months. The mean scores and number of the abnormal psychometric tests at entry were significantly higher in patients in groups SHE-L and SHE-NL than in patients in group NSHE; however, there was no significant difference between SHE-L and SHE-NL. The mean number of the abnormal psychometric tests decreased in patients in group SHE-L after three months of treatment with lactulose (2.9 ± 0.9 vs 0.8 ± 1.2; P = 0.004); however, there was no change in patients in group SHE-NL after three months (3.7 ± 1.5 vs 3.5 ± 1.3; P = NS). While SHE improved in 8 of 10 patients in group SHE-L, none of the patients in group SHE-NL improved after three months of follow-up (P < 0.001). Two patients in group SHE-NL also developed overt encephalopathy during the study period. We conclude that lactulose treatment in cirrhotic patients with SHE is effective.     

Isokinetic Muscle Strength and Its Association with Neuropsychological Capacity in Cirrhotic Alcoholics

Alcoholic cirrhotics (n = 49), nonalcoholic cirrhotics (n = 42), and normal controls ( n = 50) were compared on measures of isokinetic muscle strength and neuropsychological capacity. Alcoholic cirrhotics were deficient on measures of eccentric and concentric muscle movements, compared with normal controls but were not different from nonalcoholic cirrhotics. Nor were differences observed between the two cirrhotic groups on neuropsychological tests of cognitive and psychomotor capacity, suggesting that cirrhosis rather than alcoholism per se is responsible for the manifest deficits. Psychomotor capacity correlated negatively with isokinetic strength in cirrhotic subjects. These findings suggest that muscle weakness, due either directly to advanced liver disease or mediated by subclinical hepatic encephalopathy, accounts for a portion of the variance on the neuropsychological test performance of cirrhotic alcoholics.