Effects of common chronic medical conditions on psychometric tests used to diagnose minimal hepatic encephalopathy

Many chronic medical conditions are accompanied by cognitive disturbances but these have only to a very limited extent been psychometrically quantified. An exception is liver cirrhosis where hepatic encephalopathy is an inherent risk and mild forms are diagnosed by psychometric tests. The preferred diagnostic test battery in cirrhosis is often the Continuous Reaction Time (CRT) and the Portosystemic Encephalopathy (PSE) tests but the effect on these of other medical conditions is not known. We aimed to examine the effects of common chronic (non-cirrhosis) medical conditions on the CRT and PSE tests. We studied 15 patients with heart failure (HF), 15 with end stage renal failure (ESRF), 15 with dysregulated type II diabetes (DMII), 15 with chronic obstructive pulmonary disease (COPD), and 15 healthy persons. We applied the CRT test, which is a 10-min computerized test measuring sustained attention and reaction time stability and the PSE test, which is a paper-pencil test battery consisting of 5 subtests. We found that a high fraction of the patients with HF (8/15, 0.002) or COPD (7/15, p?=?0.006) had pathological CRT test results; and COPD patients also frequently had an abnormal PSE test result (6/15, p?<?0.0001). Both tests were unaffected by ESRF and DMII. Half of the patients with HF or COPD had psychometrically measurable cognitive deficits, whereas those with ESRF or DMII had not. This adds to the understanding of the clinical consequences of chronic heart- and lung disease, and implies that the psychometric tests should be interpreted with great caution in cirrhosis patients with heart- or lung comorbidity.     

Psychometric tests for diagnosing minimal hepatic encephalopathy

While it is consensus that minimal hepatic encephalopathy (mHE) has significant impact on a patient’s daily living, and thus should be diagnosed and treated, there is no consensus about the optimal diagnostic tools. At present the most frequently used psychometric methods for diagnosing minimal hepatic encephalopathy are the Inhibitory Control Test and the Psychometric Hepatic Encephalopathy Score PHES. Another frequently used method is Critical Flicker Frequency. The PHES and the Repeatable Battery for the Assessment of Neuropsychological Status have been recommended for diagnosing mHE by a working party commissioned by the International Society for Hepatic Encephalopathy and Nitrogen Metabolism. Recently the Continuous Reaction Time Test, which has been used in the 1980ies, has gained new interest. Today, no data are available that allow to decide which of these methods is the most appropriate. In fact, even basic information such as dependence on age, sex and education or influence of diseases that frequently accompany liver cirrhosis upon test results is missing for most of them. Future studies must address these questions to improve diagnosis of mHE.     

Non invasive blood flow measurement in cerebellum detects minimal hepatic encephalopathy earlier than psychometric tests

AIM: To assess whether non invasive blood flow measurement by arterial spin labeling in several brain regions detects minimal hepatic encephalopathy.METHODS: Blood flow (BF) was analyzed by arterial spin labeling (ASL) in different brain areas of 14 controls, 24 cirrhotic patients without and 16 cirrhotic patients with minimal hepatic encephalopathy (MHE). Images were collected using a 3 Tesla MR scanner (Achieva 3T-TX, Philips, Netherlands). Pulsed ASL was performed. Patients showing MHE were detected using the battery Psychometric Hepatic Encephalopathy Score (PHES) consisting of five tests. Different cognitive and motor functions were also assessed: alterations in selective attention were evaluated using the Stroop test. Patients and controls also performed visuo-motor and bimanual coordination tests. Several biochemical parameters were measured: serum pro-inflammatory interleukins (IL-6 and IL-18), 3-nitrotyrosine, cGMP and nitrates+nitrites in plasma, and blood ammonia. Bivariate correlations were evaluated.RESULTS: In patients with MHE, BF was increased in cerebellar hemisphere (P = 0.03) and vermis (P = 0.012) and reduced in occipital lobe (P = 0.017). BF in cerebellar hemisphere was also increased in patients without MHE (P = 0.02). Bimanual coordination was impaired in patients without MHE (P = 0.05) and much more in patients with MHE (P < 0.0001). Visuo-motor coordination was impaired only in patients with MHE (P < 0.0001). Attention was slightly affected in patients without MHE and more strongly in patients with MHE (P < 0.0001). BF in cerebellar hemisphere and vermis correlated with performance in most tests of PHES [(number connection tests A (NCT-A), B (NCT-B)and line tracing test] and in the congruent task of Stroop test. BF in frontal lobe correlated with NCT-A. Performance in bimanual and visuomotor coordination tests correlated only with BF in cerebellar hemisphere. BF in occipital lobe correlates with performance in the PHES battery and with CFF. BF in cerebellar hemisphere correlates with plasma cGMP and nitric oxide (NO) metabolites. BF in vermis cerebellar also correlates with NO metabolites and with 3-nitrotyrosine. IL-18 in plasma correlates with BF in thalamus and occipital lobe.CONCLUSION: Non invasive BF determination in cerebellum using ASL may detect MHE earlier than the PHES. Altered NO-cGMP pathway seems to be associated to altered BF in cerebellum.     

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.     

简易智能测试在诊断轻微肝性脑病中的初步应用

目的建立诊断轻微肝性脑病(MHE)的有效数字连接试验(NCT)-A、数码符号试验(DST)等简易智能测试的正常范围。方法选择至少接受9年以上教育的健康志愿者160名,按年龄分为＜35岁组、35～44岁组、45～54岁组和55～64岁组,全部接受NCT-A、DST等简易智能测试,建立与年龄相关的正常人群均值及标准差,以均数±2标准差作为MHE的诊断标准,用于检测106例肝硬化患者。结果160名健康志愿者的NCT-A在＜35岁组、35～44岁组、45～54岁组和55～64岁组分别为(25．1±4．6)s、(32．1±6．8)s、(38．6±7．1)s和(49．3±6．3)s,DST分数分别为49．9±4．7、44．6±4．8、38．5±5．0和35．4±4．7。106例肝硬化患者以此为标准,诊断出MHE患者31例(29．2%)。结论NCT-A、DST等简易智能测试可用于MHE的诊断,并应建立与年龄相关的正常范围。     

Diagnosis of minimal hepatic encephalopathy in a tertiary care center from eastern Romania: validation of the psychometric hepatic encephalopathy score (PHES)

Metabolic Brain Disease - The psychometric hepatic encephalopathy score (PHES) is frequently used as a “gold standard” for the diagnosis of minimal hepatic encephalopathy (MHE). In...     

门冬氨酸鸟氨酸治疗显性和轻微型肝性脑病

检索2000年至2010年期间在国内外发表的有关门冬氨酸鸟氨酸治疗显性肝性脑病（HE）和轻微型肝性脑病（MHE）的文献,并进行分析综述。结果显示,门冬氨酸鸟氨酸的治疗机制是直接降低血氨,疗效可靠,无明显不良反应,其对显性HE的疗效已得到公认,对MHE的疗效也在国内外研究中得到初步证实。     

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.     

智力测验调查亚临床肝性脑病的发病

目的前瞻性调查肝硬化患者的亚临床肝性脑病(SHE)的发病情况.方法356例正常对照和175例无临床肝性脑病的肝硬化连续病例行数字连接试验(NCT)和数字符号试验(SDT),以对照组相应年龄段的x±2s为标准确定有无SHE.结果肝硬化中单独NCT或SDT异常分别是34例(19.4%)和16例(9.1%),二者均异常有50例(28.6%),合计有100例(57.1%)诊断为SHE.按ChildPugh分级,SHE分别是A级46.8%、B级53.0%和C级76.6%.肝硬化病因和年龄对SHE检出率无显著影响.结论无脑病症状的肝硬化中约57.1%有SHE,发病与肝功能受损程度有关.     

心理智能测验检测原发性肝癌并肝硬化患者并发亚临床肝性脑病的研究

目的 用心理智能测验的方法研究原发性肝癌合并肝硬化患者并发亚临床肝性脑病（ＳＨＥ）的情况。方法 用数字连接试验（ＮＣＴ）、数字符号试验（ＤＳＹ）中心理智能测验对８１例原发性肝癌并肝硬化２及５０例对照进行检测。结果 现代化且的各检测值存在明显差异,８１例患者中检出ＮＣＴ、ＤＳＹ和ＤＳＰ异常例数分别为６１（１９．８％）、１２（１４．８％）和１０（１２．３％）,共检出亚临床肝性病脑病２０例（２４．７％）     

轻微肝性脑病的生命质量评价

目的 研究慢性乙型肝炎、肝硬化,尤其是轻微肝性脑病（MHE）患者的生命质量状况。方法 肝硬化患者106例（33例MHE）、慢性乙型肝炎患者20例和健康对照组160名,通过SF-36和慢性肝病问卷（CLDQ）量表进行生命质量的测评,并对慢性肝病患者的严重程度和有无MHE进行比较。SF-36包括生理机能、生理职能、身体疼痛、总体健康、活力、社会职能、情感职能、精神健康等8个方面,CLDQ量表则包括：腹部症状、疲劳、全身症状、活动、情感职能、焦虑等6个方面。结果 通过测评,健康对照组SF-36在上述8个方面的评分（均数±标准差）分别为96．9±4．5、86．6±18．4、90．1±12．5、89．0±5．7、87．5±4．3、95.8±7．1、88．5±15．9和88．7±5．2,CLDQ的6个方面分别是6．7±0．5、6．1±0．6、6．3±0．6、6．5±0．5、6．3±0．5和6．8±0．4,与之相比,慢性乙型肝炎和肝硬化的生命质量均明显下降（P〈0．01）。随着肝硬化病情的加重（按Child-Pugh分级／是否有MHE）,在SF-36和CLDQ各个领域的评分也依次下降,但Child-Pugh B级和C级之间除了生理职能和活力方面外,差异无统计学意义;若按有无MHE分组,则SF-36的各个领域差异均有统计学意义（P〈0．01）,而CLDQ除腹部症状外,其余各领域均无统计学差异（P〉0．05）。结论 肝硬化以及MHE患者的生命质量下降。SF-36和CLDQ相结合可有效评估肝硬化MHE的生命质量。     

P300 latency for the diagnosis of minimal hepatic encephalopathy: Evidence that spectral EEG analysis and psychometric tests are enough

BACKGROUND: No gold standard exists to detect minimal hepatic encephalopathy. Event-related evoked potentials (P300 latency) were proposed as the best tool to assess this condition. EEG spectral analysis and psychometric evaluation are also used to assess minimal hepatic encephalopathy. AIMS: The present study aims at comparing these three techniques. PATIENTS: Eighty-six cirrhotic patients without overt hepatic encephalopathy were studied. METHODS: Patients underwent EEG spectral analysis, psychometric evaluation and P300. P300 latency was age-adjusted; psychometric tests were age- and education-adjusted. Values >2Z were considered to be altered. The alteration of at least two psychometric tests was considered for cognitive impairment. RESULTS: At least one of the three indexes was altered in 61% (CI95% = 49-71) patients; EEG spectral analysis was altered in 41% (CI95% = 30-52%) patients, psychometric performance in 34% (CI95% = 24-45%) and P300 latency in 13% (CI95% = 7-22%). P300 latency was altered only in the patients having EEG spectral analysis or psychometric alterations, but for two cases. Psychometric performance and EEG spectral analysis, but not P300 latency, were correlated with indexes of liver function. CONCLUSIONS: P300 latency provided little additional information and was less related to liver function than EEG spectral analysis and psychometrical investigation.     

Assessment of health-related quality of life in Chinese patients with minimal hepatic encephalopathy

AIM:To evaluate the health-related quality of life (HRQOL) based on the Chinese version of SF-36 and Chronic Liver Disease Questionnaire (CLDQ) in subjects with chronic hepatitis B,liver cirrhosis,including patients with minimal hepatic encephalopathy (MHE). METHODS:The SF-36 and CLDQ were administered to 160 healthy volunteers,20 subjects with chronic hepatitis B and 106 patients with cirrhosis (33 cases exhibited MHE). HRQOL scores were compared among the different study groups. The SF-36 includes eight health concepts:physical functioning,role-physical,body pain,general health,vitality,social functioning,role-emotion,and mental health. Six domains of CLDQ were assessed:abdominal symptoms,fatigue,systemic symptoms,activity,emotional function and worry. RESULTS:Compared with healthy controls (96.9 ± 4.5,86.6 ± 18.4,90.1 ± 12.5,89.0 ± 5.7,87.5 ± 4.3,95.8 ± 7.1,88.5 ± 15.9,88.7 ± 5.2 in SF-36 and 6.7 ± 0.5,6.1 ± 0.6,6.3 ± 0.6,6.5 ± 0.5,6.3 ± 0.5,6.8 ± 0.4 in CLDQ),patients with chronic hepatitis B (86.3 ± 11.0,68.8 ± 21.3,78.9 ± 14.4,60.8 ± 10.5,70.8 ± 8.6,76.1 ± 12.6,50.0 ± 22.9,72.2 ± 10.6 and 5.5 ± 1.0,4.5 ± 1.0,5.2 ± 1.1,5.3 ± 0.9,4.8 ± 0.9,4.9 ± 1.0) and cirrhosis (52.8 ± 17.4,32.8 ± 27.9,61.6 ± 18.9,30.2 ± 18.3,47.9 ± 20.1,54.0 ± 19.2,28.9 ± 26.1,51.1 ± 17.8 and 4.7 ± 1.2,3.9 ± 1.2,4.7 ± 1.2,4.7 ± 1.3,4.7 ± 1.0,4.4 ± 1.1) had lower HRQOL on all scales of the SF-36 and CLDQ (P < 0.01 for all). Increasing severity of liver cirrhosis (based on the Child-Pugh score/presence or absence of MHE) was associated with a decrease in most components of SF-36 and CLDQ,especially SF-36.CONCLUSION:The Chinese version of SF-36 along with CLDQ is a valid and reliable method for testing MHE in patients with liver cirrhosis. Cirrhosis and MHE are associated with decreased HRQOL.     

轻微肝性脑病的治疗现状

轻微肝性脑病(MHE)是肝性脑病发病的起始阶段,无明显的临床表现,但是对患者的日常生活安全产生了严重的影响,在现代医学中受到越来越多的重视,治疗方法主要包括去除诱因和药物治疗两个部分。介绍了轻微肝性脑病的相关治疗,并对各种治疗方案的疗效进行了客观评价。认为现治疗方案主要是多种治疗方法的联合应用,但没有试验证明联合应用可提高疗效。     

轻微型肝性脑病诊断研究进展

轻微型肝性脑病常并发于肝硬化及各种门体分流术患者。由于缺乏典型的临床表现及生化异常,只能通过心理智能测试及神经电生理等检查发现,其发病率已升至30%～84%。轻微型肝性脑病可对患者的日常生活造成影响,无干预的轻微型肝性脑病易发展为显性肝性脑病。该病尚无公认的诊断“金标准”。本文介绍了国内外对轻微型肝性脑病的诊断方法。     

探讨心理测验和脑诱发电位检测亚临床型肝性脑病的价值

目的评价心理测验和脑诱发电位检查诊断亚临床型肝性脑病（ＳＨＥ）的价值。方法对３６例肝炎肝硬化患者进行心理测验和三种脑诱发电位（ＥＰ）检查,并追踪１年观察临床肝性脑病（ＨＥ）出现情况。结果心理测验异常１６例（４４％）,其中言语智商异常１２例（３３％）,操作智商异常１４例（３８％）,三种ＥＰ总异常为１８例（５０％）,其中听觉诱发电位（ＢＡＥＰ）异常１２例（３３％）、视觉诱发电位（ＶＥＰ）异常３例（８％）、体感觉诱发电位（ＳＥＰ）异常６例（１６％）,心理测验和／或诱发电位异常２８例（７７％）,两者均异常者为１１例（３１％）,追踪观察１年的３４例患者中,２６例心理测验和／或脑诱发电位异常者出现临床肝性脑病１９例（７３％）,无心理测验和／或脑诱发电位检查异常８例中,出现临床肝性脑病２例（２５％）（Ｐ＜００５）。结论同时进行心理测验和脑诱发电位检查可提高ＳＨＥ检出率,检测ＳＨＥ对预测肝性脑病的发生有临床价值。     

Patients with minimal hepatic encephalopathy show impaired mismatch negativity correlating with reduced performance in attention tests

Attention deficit is an early event in the cognitive impairment of patients with minimal hepatic encephalopathy (MHE). The underlying mechanisms remain unclear. Mismatch negativity (MMN) is an auditory event-related potential that reflects an attentional trigger. Patients with schizophrenia show impaired attention and cognitive function, which are reflected in altered MMN. We hypothesized that patients with MHE, similarly to those with schizophrenia, should show MMN alterations related with attention deficits. The aims of this work were to assess whether (1) MMN is altered in cirrhotic patients with MHE, compared to those without MHE, (2) MMN changes in parallel with performance in attention tests and/or MHE in a longitudinal study, and (3) MMN predicts performance in attention tests and/or in the Psychometric Hepatic Encephalopathy Score (PHES). We performed MMN analysis as well as attention and coordination tests in 34 control subjects and in 37 patients with liver cirrhosis without MHE and 23 with MHE. Patients with MHE show reduced performance in selective and sustained attention tests and in visuomotor and bimanual coordination tests. The MMN wave area was reduced in patients with MHE, but not in those without MHE. In the longitudinal study, MMN area improved in parallel with performance in attention tests and PHES in 4 patients and worsened in parallel in another 4. Logistic regression analyses showed that MMN area predicts performance in attention tests and in PHES, but not in other tests or critical flicker frequency. Receiver operating characteristic curve analyses showed that MMN area predicts attention deficits in the number connection tests A and B, Stroop tasks, and MHE, with sensitivities of 75%-90% and specificities of 76%-83%. CONCLUSION: MMN area is useful to diagnose attention deficits and MHE in patients with liver cirrhosis.     

轻微肝性脑病的研究进展

轻微肝性脑病(minimal hepatic encephalopathy,MHE)是并发于各种类型的肝硬化及各种门体分流术患者出现认知功能紊乱的表现,其发病机制仍不清楚,目前所公认的是经典的氨中毒学说。由于MHE缺乏典型的临床表现,只能通过神经心理测试和神经生理测试发现,其发病率已上升至30%～84%,MHE可对患者的日常生活造成影响,很可能发展为症状性肝性脑病(OHE),病死率极高,目前有研究表明益生菌可明显改善MHE症状,防止MHE发展为症状性肝性脑病(OHE)。本文就MHE的流行病学调查、发病机制、临床表现、诊断方法和其与益生菌的关系作一综述。