Number Connection test-A Research Articles

Regression-based Chinese norms of number connection test A and digit symbol test for diagnosing minimal hepatic encephalopathy

Number connection test A (NCT-A) and digit symbol test (DST), the preferential neuropsychological tests to detect minimal hepatic encephalopathy (MHE) in China, haven’t been standardized in Chinese population. We aimed to establish the norms based on a multi-center cross-sectional study and to detect MHE in cirrhotic patients. NCT-A and DST were administered to 648 healthy controls and 1665 cirrhotic patients. The regression-based procedure was applied to develop demographically adjusted norms for NCT-A and DST based on healthy controls. Age, gender, education, and age by education interaction were all predictors of DST, while age, gender, and education by gender interaction were predictors of log10 NCT-A. The predictive equations for expected scores of NCT-A and DST were established, and Z-scores were calculated. The norm for NCT-A was set as Z ≤ 1.64, while the norm for DST was set as Z ≥ − 1.64. Cirrhotic patients with concurrent abnormal NCT-A and DST results were diagnosed with MHE. The prevalence of MHE was 8.89% in cirrhotic patients, and only worse Child–Pugh classification (P = 0.002, OR = 2.389) was demonstrated to be the risk factor for MHE. The regression-based normative data of NCT-A and DST have been developed to detect MHE in China. A significant proportion of Chinese cirrhotic patients suffered from MHE, especially those with worse Child–Pugh classification.

Meta-analysis of the Correlation Between Cognitive Function and Imaging Features in Hepatic Encephalopathy

Objectives: This study aimed to systematically evaluate the correlation between cognitive function and brain imaging findings in patients with hepatic encephalopathy (HE). Methods: We searched PubMed, China National Knowledge Infrastructure, and Wanfang databases to obtain literature on cognitive function and the diagnosis of HE via brain imaging from the establishment of the databases to March 20, 2023. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies. RevMan v. 5.3 software was used in the meta-analysis. Results: A total of 14 articles were included. The meta-analysis showed that digit symbol test (DST) scores and psychometric HE scores (PHES) were positively correlated with the imaging findings of the frontal lobe in patients with HE, with correlation coefficients of 0.49 (Z = 0.53; 95% confidence interval [CI]: 0.23 ~ 0.83) and 0.52 (Fisher’s Z: 0.58; 95% CI: 0.41 ~ 0.76), respectively. The number connection test-A reaction times were negatively correlated with the signal in the globus pallidus, with a correlation coefficient of -0.23 (Z = - 0.23; 95% CI: - 0.43~ - 0.03); DST scores were positively correlated with the signal in the globus pallidus, with a correlation coefficient of 0.45 (Z = 0.49; 95% CI: 0.29 ~ 0.69); and PHES were positively correlated with the mean peak of grey matter, with a correlation coefficient of 0.52 (Z = 0.57; 95% CI: 0.46 ~ 0.73). Conclusions: Imaging findings are related to the cognitive function of patients with HE. Therefore, they can be used to evaluate the cognitive function of these patients and promptly intervene in and prevent the progression of the disease.

Changes in dynamic and static brain fluctuation distinguish minimal hepatic encephalopathy and cirrhosis patients and predict the severity of liver damage.

Minimal hepatic encephalopathy (MHE) is characterized by mild neuropsychological and neurophysiological alterations that are not detectable by routine clinical examination. Abnormal brain activity (in terms of the amplitude of low-frequency fluctuation (ALFF) has been observed in MHE patients. However, little is known concerning temporal dynamics of intrinsic brain activity. The present study aimed to investigate the abnormal dynamics of brain activity (dynamic ALFF; dALFF) and static measures [static ALFF; (sALFF)] in MHE patients and to strive for a reliable imaging neuromarkers for distinguishing MHE patients from cirrhosis patients. In addition, the present study also investigated whether intrinsic brain activity predicted the severity of liver damage. Thirty-four cirrhosis patients with MHE, 28 cirrhosis patients without MHE, and 33 age-, sex-, and education-matched healthy controls (HCs) underwent resting-state magnetic resonance imaging (rs-fMRI). dALFF was estimated by combining the ALFF method with the sliding-window method, in which temporal variability was quantized over the whole-scan timepoints and then compared among the three groups. Additionally, dALFF, sALFF and both two features were utilized as classification features in a support vector machine (SVM) to distinguish MHE patients from cirrhosis patients. The severity of liver damage was reflected by the Child-Pugh score. dALFF, sALFF and both two features were used to predict Child-Pugh scores in MHE patients using a general linear model. Compared with HCs, MHE patients showed significantly increased dALFF in the left inferior occipital gyrus, right middle occipital gyrus, and right insula; increased dALFF was also observed in the right posterior lobe of the cerebellum (CPL) and right thalamus. Compared with HCs, noMHE patients exhibited decreased dALFF in the right precuneus. In contrast, compared with noMHE patients, MHE patients showed increased dALFF in the right precuneus, right superior frontal gyrus, and right superior occipital gyrus. Furthermore, the increased dALFF values in the left precuneus were positively associated with poor digit-symbol test (DST) scores (r = 0.356, p = 0.038); however, dALFF in the right inferior temporal gyrus (ITG) was negatively associated with the number connection test-A (NCT-A) scores (r = -0.784, p = 0.000). A significant positive correlation was found between dALFF in the left inferior occipital gyrus (IOG) and high blood ammonia levels (r = 0.424, p = 0.012). Notably, dALFF values yielded a higher classification accuracy than sALFF values in distinguishing MHE patients from cirrhosis patients. Importantly, the dALFF values predicted the Child-Pugh score (r = 0.140, p = 0.030), whereas sALFF values did not in the current dataset. Combining two features had high accuracy in classification in distinguishing MHE patients from cirrhotic patients and yielded prediction in the severity of liver damage. These findings suggest that combining dALFF and sALFF features is a useful neuromarkers for distinguishing MHE patients from cirrhosis patients and highlights the important role of dALFF feature in predicting the severity of liver damage in MHE.

Altered Cerebral Blood Flow in the Progression of Chronic Kidney Disease.

In chronic kidney disease (CKD), cognitive impairment is a definite complication. However, the mechanisms of how CKD leads to cognitive impairment are not clearly known. Cerebral blood flow (CBF) information was collected from 37 patients with CKD (18 in stage 3; 19 in stage 4) and 31 healthy controls (HCs). For CKD patients, we also obtained laboratory results as well as neuropsychological tests. We conducted brain perfusion imaging studies using arterial spin labeling and calculated the relationship between regional CBF changes and various clinical indicators and neuropsychological tests. We also generated receiver operator characteristic (ROC) curves to explore whether CBF value changes in certain brain regions can be used to identify CKD. Compared with HCs, CBF decreased in the right insula and increased in the left hippocampus in the CKD4 group; through partial correlation analysis, we found that CBF in the right insula was negatively correlated with the number connection test A (NCT-A) (r = -0.544, p = 0.024); CBF in the left hippocampus was positively correlated with blood urea nitrogen (r = 0.649, p = 0.005) and negatively correlated with serum calcium level (r = -0.646, p = 0.005). By comparing the ROC curve area, it demonstrated that altered CBF values in the right insula (AUC = 0.861, p < 0.01) and left hippocampus (AUC = 0.862, p < 0.01) have a good ability to identify CKD. Our study found that CBF alterations in the left hippocampus and the right insula brain of adult patients with stage 4 CKD were correlated with disease severity or laboratory indicators. These findings provide further insight into the relationship between altered cerebral perfusion and cognitive impairment in patients with non-end-stage CKD as well as, additional information the underlying neuropathophysiological mechanisms.

Aberrant gray matter structure in neurosyphilis without conventional MRI abnormality: a pilot study with voxel and surface-based morphology.

The underlying mechanism of neurosyphilis was not fully understood. To assess gray matter (GM) microstructure in patients with early-stage neurosyphilis without overt conventional magnetic resonance imaging (MRI) abnormality using voxel-based morphometry (VBM) and surface-based morphometry (SBM) analyses. Three-dimensional high-resolution T1-weighted imaging data from 19 individuals with neurosyphilis and 19 healthy controls were analyzed. A battery of neuropsychological tests was performed before each MRI examination. The differences of GM volume and cerebral cortical morphological data between the two groups were compared. The correlations between MRI metrics and neuropsychology/laboratory tests in the patient group were investigated. Regional decreased GM volumes in patients with neurosyphilis were found in the left frontal cortices (Rolandic operculum, middle frontal, and precentral) and bilateral temporal/occipital cortices (bilateral middle temporal, left lingual, and right middle occipital) (P < 0.05, FDR correction). SBM analysis showed significant cortical thickness reduction in the right medial orbitofrontal lobe, and reduced gyrification index in the left insula in patients with neurosyphilis (P < 0.05, FDR correction). Additionally, in the patient group, the GM volume in the middle frontal gyrus, the cortical thickness of right medial orbitofrontal lobe, and the gyrification index in the left insula were negatively correlated to the number connection test-A scores. The gyrification index was also negatively correlated to cerebrospinal fluid white blood cell count. Early-stage neurosyphilis without conventional MRI abnormality presented regional GM volume reduction and cortical morphological changes, which might be related to cognitive impairment and intra-cranial infection. VBM and SBM analyses might be useful for understanding the underlying neural trait of neurosyphilis.

The instant impact of a single hemodialysis session on brain morphological measurements in patients with end-stage renal disease.

ObjectiveTo investigate the instant impact of hemodialysis (HD) on the cerebral morphological measurements of patients with end-stage renal disease (ESRD).Materials and methodsTwenty-five patients undergoing maintenance HD and twenty-eight age-, sex-, and education-matched healthy control (HC) were included. The HD group and HC group had 3D high-resolution structural magnetic resonance imaging (MRI) scans twice and once, respectively. Both groups underwent neuropsychologic tests. The morphological measurements of structural MRI were measured using CAT12 and these measures were compared among three groups. The relationship between morphological measures and clinical parameters and neuropsychological tests were investigated through multiple regression analysis.ResultsCompared to the HC group, the cortical thickness before HD significantly decreased in the bilateral temporal lobe and significantly decreased in the left superior temporal gyrus after HD. The cortical thickness significantly increased in the bilateral temporal lobe, frontal lobe and occipital lobe after HD compared to before HD. The sulcus depth in the bilateral insula, frontal lobe, and parietal lobe after HD significantly increased compared to before HD. No significant differences in sulcus depth between HD and HC were detected. After HD, the cortical thickness of the right parsopercularis was positively correlated with the number connection test-A. Cortical thickness in multiple regions were positively correlated with blood flow velocity and cortical thickness in the left parahippocampal gyrus was negatively correlated with ultrafiltration volume. Patients showed better performance in the digit symbol test and line tracing test after HD compared to before HD, but there were no significant differences in the comparison of neuropsychologic tests between patients and HC.ConclusionThe instant morphological changes were captured during a single hemodialysis in HD patients. There was an association between these instant changes in the brain and clinical parameters and neuropsychologic tests. This work implied the instant impact of a single hemodialysis impact on the brain in HD patients.

Prevalence and Consequences of Cerebral Small Vessel Diseases: A Cross-Sectional Study Based on Community People Plotted Against 5-Year Age Strata.

PurposeTo study the variation tendency of cerebral small vessel disease (CSVD) imaging markers and total burden with aging and to research the relationship between aging, CSVD markers and cognitive function.MethodsParticipants in local urban communities were recruited for neuropsychological and magnetic resonance imaging assessments. Montreal Cognitive Assessment (MoCA), Mini-mental State Examination (MMSE), Number Connection Test A (NCT-A) and Digital Symbol Test (DST) were adopted as neuropsychological scale. Age was stratified at 5-year intervals, and the variation tendency of imaging markers and variables of neuropsychological scales in different age groups was studied. We further studied the relationship between aging, image markers and neuropsychological scales by multi-linear regression.ResultsFinally, a total of 401 stroke-free participants (age, 54.83±7.74y; 45.9% were male) were included in the present analysis. With the increase of age, the incidence of imaging markers of CSVD were increased with aging except cerebral microbleeds. The performance results of NCT-A and DST were significant difference in 6 age groups (P < 0.001). In addition, linear decline of the neuropsychological function reflected by NCT-A and DST variables was observed. Linear regression found that age was an independent factor affecting the neuropsychological function reflected by NCT-A and DST variables, and the standard correction coefficients among different age groups increased gradually with age. In addition, brain atrophy is an independent factor affecting neuropsychological variables (odds ratio: −2.929, 95% CI: [−5.094 to −0.765]). There was no correlation between the number of neuroimaging markers and neuropsychological variables after full adjustment.ConclusionThere are many CVSD markers even in younger people, the incidence rate and CVSD marker numbers increase with age. Aging and CSVD may eventually affect cognitive function through brain atrophy.

Construction of an early warning model of hepatic encephalopathy in patients with liver cirrhosis based on psychological testing.

To establish an early warning model of hepatic encephalopathy in patients with liver cirrhosis based on psychological testing. Data including patient demographics, number connection test-A (NCT-A), digit symbol test (DST), Model for End-Stage Liver Disease (MELD) scores were collected for patients admitted to a tertiary hospital in Shanghai with liver cirrhosis between January and December 2019. Patients were divided into two groups based on the development of hepatic encephalopathy (the hepatic encephalopathy group and non-hepatic encephalopathy group). Risk factors for hepatic encephalopathy in patients with liver cirrhosis were determined by using the binary logistic regression. We developed a predictive model in accordance with the STARD statement criteria (Supplementary File S1) with a cut-off value determined by receiver operating characteristic (ROC) curve analysis and calculation of the Youden index. A total of 417 patients with liver cirrhosis were included in the present study. Of these, 33 out of 66 patients with abnormal psychological tests had hepatic encephalopathy during hospitalisation. In contrast, 6 out of 317 patients with normal psychological tests had hepatic encephalopathy. Logistic regression analysis identified age, MELD score, and abnormal psychological tests as risk factors for hepatic encephalopathy in patients with liver cirrhosis. The area under the ROC curve for our prediction model for hepatic encephalopathy in patients with liver cirrhosis was 0.950 and the largest calculated Youden index was 0.804, which corresponds to a cut-off value is 0.0307. Greater age, higher MELD score and abnormal psychological tests were significantly associated with increased risk of hepatic encephalopathy indicating early warning systems and identification of abnormal psychological tests are important components of the clinical nursing care process for cirrhotic patients. Our early warning model based on psychological testing can provide a basis for nursing observation and prevention of hepatic encephalopathy. Risk assessments for hepatic encephalopathy according to liver function and psychological tests, in addition to traditional neurological observations and dietary guidance, have utility in decreasing the incidence of hepatic encephalopathy.

Normalisation of the psychometric encephalopathy score within the Cameroonian population

BackgroundMinimal hepatic encephalopathy (MHE) is the presence of neuropsychological abnormalities detectable by psychometric tests. Psychometric Hepatic Encephalopathy Score (PHES) is a gold standard test for the early diagnosis of MHE in cirrhotic patients. The aim of this study was to standardize the PHES in a healthy Cameroonian population and to evaluate the prevalence of MHE among cirrhotic patients.MethodsThis was a prospective, multicentric study from 1 December 2018 to 31 July 2019 in two groups: healthy volunteers and cirrhotic patients without clinical signs of hepatic encephalopathy. The results of the number connection test-A, number connection test-B, serial dotting test, line tracing test were expressed in seconds and those of the digit symbol test in points.ResultsA total of 102 healthy volunteers (54 men, 48 women) and 50 cirrhotic patients (29 men, 31 women) were included. The mean age was 38.1 ± 12.55 years in healthy volunteers and 49.3 ± 15.6 years in cirrhotic patients. The mean years of education level was 11.63 ± 4.20 years in healthy volunteers and 9.62 ± 3.9 years in cirrhotic patients. The PHES of the healthy volunteer group was − 0.08 ± 1.28 and the cut-off between normal and pathological values was set at − 3 points. PHES of the cirrhotic patients was − 7.66 ± 5.62 points and significantly lower than that of volunteers (p < 0.001). Prevalence of MHE was 74% among cirrhotic patients. Age and education level were associated with MHE.ConclusionPHES cut-off value in Cameroonians is − 3, with MHE prevalence of 74% among cirrhotic patients.

Prevalence and Risk Factors of Minimal Hepatic Encephalopathy in Patients with Compensated Liver Cirrhosis

Background: Minimal hepatic encephalopathy (MHE) is the earliest phase of hepatic encephalopathy. It is associated with increased risk of falls, impaired work and diminished quality of life. Subjects and methods: This study included 302 patients with liver cirrhosis, of which 130 patients had Child A (compensated) liver cirrhosis. All patients were assessed by history taking, clinical examination, routine investigations, serum ammonia level and abdominal ultrasound for porto-systemic shunt (PSS). MHE was diagnosed in 60 patients of compensated liver cirrhosis patients using mini-mental state examination (MMSE) and number connection test A (NCT-A). Results: Our stud showed that Child A patients were 43% of the study group and MHE was present in 46% of compensated liver cirrhosis patients. Our results showed a significant association between lower serum albumin, higher INR, high serum ammonia, presence of PSS in ultrasound examination and MMSE and NCT-A high scores with the development of MHE. MMSE and NCT A showed significantly good performance in diagnosis of MHE. Multiple regression analysis showed that high serum ammonia level (53-61) u/dl, large PSS (> 8 mm in diameter), MMSE score (22-26) and NCT A score (45-56) were the most significant risk factors for MHE. Conclusion: MHE is a major and prevalent manifestation in compensated liver cirrhosis patients. It is associated with significant decrease in work and driving abilities and quality of life. Its major risk factors are high serum ammonia, large PSS and high scores of MMSE and NCT A tests that have a good performance in MHE diagnosis.

Volume changes of subcortical structures in patients with post-hepatitis B cirrhosis: A magnetic resonance imaging study.

To investigate volume changes of subcortical structures in patients with post-hepatitis B cirrhosis. Thirty patients with post-hepatitis B cirrhosis (the cirrhosis group) and 24 age- and sex-matched healthy controls (the control group) were enrolled in this prospective study. All subjects underwent neuropsychological tests, blood biochemical determinations, and cerebral MRI. Volumes of 18 selected subcortical structures were automatically segmented and analyzed by the FreeSurfer. In the cirrhosis group, the relationships between abnormal subcortical volumes and clinical index or neurocognitive performance were investigated. The relationships between globus pallidus volumes and pallidal hyperintensity were also examined. Compared with the healthy controls, patients with post-hepatitis B cirrhosis displayed smaller bilateral putamen, amygdala, and nucleus accumbens volumes and larger bilateral globus pallidus volumes (P<0.001 or P=0.001). In the cirrhosis group, the volumes of left putamen and amygdala were negatively correlated with the number connection test-A (NCT-A)(left putamen r=-0.410, P=0.034; left amygdala r=-0.439, P=0.022), and the volumes of bilateral globus pallidus were positively correlated with pallidal index (PI) (left globus pallidus r=0.889, P<0.001; right globus pallidus r=0.900, P<0.001). Abnormalities of subcortical volumes appear bilaterally symmetrical in patients with post-hepatitis B cirrhosis. Atrophy of left putamen and amygdala might contribute to poor neurocognitive performance, and the manganese deposition might contribute to the increased globus pallidus volumes in patients with post-hepatitis B cirrhosis.

Combined Scores from the EncephalApp Stroop Test, Number Connection Test B, and Serial Dotting Test Accurately Identify Patients With Covert Hepatic Encephalopathy

The EncephalApp Stroop test is a high-sensitivity but low-specificity test that has been used to identify patients with covert hepatic encephalopathy (CHE). We aimed to develop a new strategy to detect CHE, combining EncephalApp Stroop test score with scores from subtests of the psychometric hepatic encephalopathy scoring system (PHES). We performed a survey of 569 adult volunteers (229 men) in 9 communities in Shanghai, China, administering the EncephalApp Stroop test to determine the range of scores in the general population. Data from the standard PHES, including the number connection test-A, number connection test-B (NCT-B), line tracing test, serial dotting test (SDT), and digit symbol test, were used as the reference standard for diagnosis of CHE. A combination of the EncephalApp Stroop with subtests of the PHES was used to establish a new strategy for CHE diagnosis. We validated our findings using data from 160 patients with cirrhosis from 5 centers China. We determined the range of EncephalApp Stroop test scores for the volunteers of different decades of age, education levels, and sexes. Age, education level, and sex were independently associated with EncephalApp Stroop test scores. A combination of scores from the EncephalApp Stroop test, the NCT-B, and the SDT identified patients with CHE with the highest level of accuracy, when the standard PHES was used as the reference standard. A combination of scores of 187 sec for the EncephalApp Stroop test and below -1 for the NCT-B or below -1 for the SDT identified patients with CHE with an area under the curve (AUC) of 0.86, 81.0% sensitivity, and 91.9% specificity, and 87.5% accuracy. In the validation cohort, these cutoff scores identified patients with CHE with an AUC of 0.88, 97.1% sensitivity, 79.3% specificity, and 86.9% accuracy. The average time to calculate this score was 374±140 sec, compared 424±115 sec for the entire PHES. Scores from the EncephalApp Stroop test, NCT-B, and SDT identify patients with CHE with approximately 87% accuracy, and in a much shorter time than the standard PHES. This score combination could be a valid and convenient method for identifying patients with CHE. chictr.org.cn number, ChiCTR-EDC-17012007, ChiCTR1800019954.

Slowing of Alpha Waves on EEG, an Early Marker of Minimal Hepatic Encephalopathy

Introduction: Minimal Hepatic Encephalopathy (MHE) is the mildest form of spectrum of Hepatic Encephalopathy (HE) which remains undiagnosed due to lack of awareness. MHE has a negative effect on patient's daily functioning due to cognitive impairment. Electro-Encephalo-Gram (EEG) and Mini Mental State Examination (MMSE) are useful in early diagnosis and follow up of MHE. Aim: To study evidence of MHE in patients with liver cirrhosis by psychometric tests and also its correlation with EEG changes. Materials and Methods: The study was carried out as a prospective case control study of 70 patients diagnosed with Cirrhosis of liver, over a period of two years in accordance with European Association for the Study of the Liver (EASL) and Asociacion Latinoamericana parael Estudio del Higado (ALEH) criteria with MMSE score &gt;24 and were diagnosed as Minimal Hepatic Encephalopathy if 2 out of 3 psychometric tests were abnormal EEG was performed in them and was compared with 70 healthy controls. Results: Study showed male predominance (90%) with mean age of 45.49 ± 11.76. Alcohol related cirrhosis (70%) was found to be more common than HBV (8.57%) and HCV (2.86%) infection related cirrhosis. Pedal edema, icterus, pallor and ascites were the most common presenting manifestations. Most cirrhotic cases (80%) were under Child Pugh Class-A. On USG of abdomen all cases had Coarse echotexture and nodular surface of liver among them 11 cases had Hepatomegaly, 10 cases had splenomegaly, 42 cases had ascites and 24 cases had increased portal venous diameter of mean size 14.02 ± 0.48 mm. MMSE score of all selected cirrhotic cases was &gt;24. Psychometric Tests i.e. Number Connection Test-A, Number Connection Test-B and Line tracing test were performed in all selected cirrhotic cases and they were not able to perform it within designated time. All cases were subjected to EEG and compared with equal number of comparable healthy controls, which shows change in frequency and amplitude of Alpha wave which was highly significant whereas no significant changes of frequency and amplitude of Beta, Theta and Delta waves between cases and controls. Conclusion: There is significant changes in alpha wave frequency and amplitude in patients with minimal hepatic encephalopathy.

Rifaximin‐altered gut microbiota components associated with liver/neuropsychological functions in patients with hepatic encephalopathy: An exploratory data analysis of phase II/III clinical trials

AimsRifaximin (RFX), a non‐systemic antibiotic, improves liver/neuropsychological functions in patients with hepatic encephalopathy (HE). We aimed to investigate the clinical profiles associated with gut bacterial loads using exploratory data analysis and the effects of RFX on the gut microbiota of patients with HE.MethodsWe analyzed the data from 17 patients with HE who underwent fecal microbiota examination in phase II/III trials in Japan. Profiles associated with genera Streptococcus, Veillonella, and Lactobacillus loads were analyzed using classification and regression trees (CART). Changes in gut microbial consortia of seven patients with HE were then assessed 2 weeks after RFX treatment by principal component analysis.ResultsIn the CART, the first and second divergence variables for each higher bacterial load were as follows: (i) in Streptococcus, the number connection test‐A ≥39.55 s and presence of portal‐systemic shunt; (ii) in Veillonella, serum potassium levels <4.75 mEq/L and total cholesterol level <129.5 mg/dL; and (iii) in Lactobacillus, white blood cell counts ≥3.4 × 103/μL and aspartate aminotransferase level ≥44.5 U/L. There was no significant change in total bacterial load before and after RFX treatment; however, there was a decrease in Streptococcus, Veillonella, and Lactobacillus counts after RFX treatment.ConclusionWe report clinical profiles associated with gut bacterial loads in patients with HE, and showed that RFX altered gut microbiota components associated with liver/neuropsychological functions. Thus, RFX could improve liver/neuropsychological functions through the regulation of the gut microbial consortia in patients with HE.

Role of minimal hepatic encephalopathy in road traffic accidents

BackgroundThe term minimal hepatic encephalopathy (MHE) is defined as encephalopathy that does not lead to clinically overt cognitive dysfunction but can have an impact on quality of life, risk of involvement in road traffic accidents, and ability to function in daily life.ObjectiveTo identify the incidence of minimal hepatic encephalopathy in patients actively involved in a road traffic accident and its role in the increased incidence of road traffic accidents.Patients and methodsWe included 74 patients presented in road traffic accidents (drivers, history of fall, pedestrians whom accidents occur during crossing the road) with clinically proven hepatic cirrhosis, without clinical manifestation of hepatic encephalopathy (HE). Thorough history taking, clinical examinations, routine laboratory investigations, serum IL-6 and ammonia in blood were done. Diagnosis of MHE is based on psychometric hepatic encephalopathy score (PHES) which includes digit symbol test (DST), number connection test-A (NCT-A), number connection test-B (NCT-B), serial dotting test (SDT), and line drawing test (LDT).ResultsThe mean age was 52.0 ± 7.47 in MHE patients. Most of the MHE patients were males. Most of the patients with MHE were working other jobs and were not drivers (63.2% vs 36.8%). MHE was observed in 19 patients (25.7%). Albumin, interleukin-6 (IL-6), and ammonia were statistically significantly different between both groups.ConclusionMinimal hepatic encephalopathy (MHE) was observed in 25.7% of patients which points that we must give attention in the screening of MHE as road traffic accident is considered the main cause of mortality in our community with high incidence of liver disease.

Stroop color-word test in screening of minimal hepatic encephalopathy

Objective To assess the application of Stroop color-word test (SCWT) for screening of minimal hepatic encephalopathy (MHE) in patients with liver cirrhosis. Methods Sixty patients aged 18-65 years with liver cirrhosis and 60 age, education level- matched healthy subjects were examined with SCWT. The SCWT indexes were compared between two groups. MHE was identified when patients had abnormal number connection test-A (NCT-A) and/or digit symbol test (DST). Results Time consuming and errors of card 2, 3, 4 and Stroop interference effects (SIE) reflecting word-interference and color-interference in SCWT were increased significantly in liver cirrhotic patients [(17.28±0.69)sec, (12.96±1.10)sec, (30.30±1.40)sec, (5.00±0.90)sec, (13.74±1.22)sec, (0.36±0.10) times, (0.50±0.11) times, (0.50±0.11) times, (5.00±0.90) times, (1.98±0.23) times, respectively] compared to those in healthy subjects [(10.18±0.57) sec, (7.68±0.39)sec, (15.68±0.33)sec, (1.94±0.37) sec, (6.56±0.70)sec, (0.02±0.02) times, (0.10±0.04)times, (0.10±0.04)times, (0.04±0.02) times, (0.20±0.08)times, respectively; t=12.95, 6.98, 8.19, 7.02, 11.91, 10.09, 8.97, 8.15, 17.94, 11.37, all P=0.00]; while there were no significant differences in time consuming and errors of card 1 between liver cirrhotic patients [(7.10±0.40)sec and (0.04±0.03) times] and healthy subjects [(6.72±0.36)sec and (0.02±0.02) times; t=1.89, 1.91, both P=0.06]. The sensitivity of word SIE, color SIE and word SIE + color SIE of SCWT for primary screening of MHE was 0.83(50/60), 0.88(53/60) and 0.98(59/60) respectively, whereas the specificity was 0.87(52/60), 0.80(48/60) and 0.83(50/60) respectively. Conclusion The SCWT may serve as a convenient, effective and reliable tool for primary screening MHE. Key words: Hepatic encephalopathy; Neuropsyehology; Psychological tests; Stoop color-word test

Study of the sleep quality and psychological state of patients with hepatitis B liver cirrhosis.

We aimed to investigate sleep quality, mild hepatic encephalopathy, anxiety, and depression in patients with hepatitis B cirrhosis by using a variety of scales and questionnaires. A cohort of 341 patients with hepatitis B liver cirrhosis were categorized by Child-Pugh grading (A, B, and C) in this cross-sectional study. Pittsburgh Sleep Quality Index (PSQI), Number Connection Test-A (NCT-A), and Hospital Anxiety and Depression (HAD) evaluated the questionnaires and statistically analyzed the intrinsic correlation. The control group included 50 healthy individuals. Of 341 patients, 213 had a PSQI index >5 points. The PSQI, NCT-A, anxiety scale (HAD [a]), and depression scale (HAD [d]) of the patients were significantly different. The NCT-A-positive patients revealed 214 cases of possible minimal hepatic encephalopathy (MHE) during a preliminary screening of patients. The PSQI score of NCT-A-positive patients was significantly elevated compared to NCT-A-negative patients (P < 0.001). HAD (a) and HAD (d) were significantly different between the NCT-A-positive and NCT-A-negative groups (P = 0.002 and P = 0.006, respectively). Univariate Pearson's correlation analysis found that NCT-A and HAD (a) were positively correlated with PSQI (P < 0.001 and P = 0.045, respectively); however, Child-Pugh score and HAD (d) were not correlated with PSQI (P = 0.061 and P = 0.059, respectively). These results indicated that patients with hepatitis B liver cirrhosis have a disturbed sleep, which might be an MHE symptom, further causing considerable anxiety. Thus, the evaluation of sleep quality and psychological state of patients with hepatitis B liver cirrhosis necessitates further investigation to guide positive intervention.

Validation of a Paper and Pencil Test Battery for the Diagnosis of Minimal Hepatic Encephalopathy in Korea.

The aim of this study was to validate a new paper and pencil test battery to diagnose minimal hepatic encephalopathy (MHE) in Korea. A new paper and pencil test battery was composed of number connection test-A (NCT-A), number connection test-B (NCT-B), digit span test (DST), and symbol digit modality test (SDMT). The norm of the new test was based on 315 healthy individuals between the ages of 20 and 70 years old. Another 63 healthy subjects (n = 31) and cirrhosis patients (n = 32) were included as a validation cohort. All participants completed the new paper and pencil test, a critical flicker frequency (CFF) test and computerized cognitive function test (visual continuous performance test [CPT]). The scores on the NCT-A and NCT-B increased but those of DST and SDMT decreased according to age. Twelve of the cirrhotic patients (37.5%) were diagnosed with MHE based on the new paper and pencil test battery. The total score of the paper and pencil test battery showed good positive correlation with the CFF (r = 0.551, P < 0.001) and computerized cognitive function test. Also, this score was lower in patients with MHE compared to those without MHE (P < 0.001). Scores on the CFF (32.0 vs. 28.7 Hz, P = 0.028) and the computer base cognitive test decreased significantly in patients with MHE compared to those without MHE. Test-retest reliability was comparable. In conclusion, the new paper and pencil test battery including NCT-A, NCT-B, DST, and SDMT showed good correlation with neuropsychological tests. This new paper and pencil test battery could help to discriminate patients with impaired cognitive function in cirrhosis (registered at Clinical Research Information Service [CRIS], https://cris.nih.go.kr/cris, KCT0000955).

Longitudinal Intrinsic Brain Activity Changes in Cirrhotic Patients before and One Month after Liver Transplantation.

ObjectiveTo evaluate the spontaneous brain activity alterations in liver transplantation (LT) recipients using resting-state functional MRI.Materials and MethodsTwenty cirrhotic patients as transplant candidates and 25 healthy controls (HCs) were included in this study. All patients repeated the MRI study one month after LT. Amplitude of low-frequency fluctuation (ALFF) values were compared between cirrhotic patients (both pre- and post-LT) and HCs as well as between the pre- and post-LT groups. The relationship between ALFF changes and venous blood ammonia levels and neuropsychological tests were investigated using Pearson's correlation analysis.ResultsIn the cirrhotic patients, decreased ALFF in the vision-related regions (left lingual gyrus and calcarine), sensorimotor-related regions (left postcentral gyrus and middle cingulate cortex), and the default-mode network (bilateral precuneus and left inferior parietal lobule) were restored, and the increased ALFF in the temporal and frontal lobe improved in the early period after LT. The ALFF decreases persisted in the right supplementary motor area, inferior parietal lobule, and calcarine. The ALFF changes in the right precuneus were negatively correlated with changes in number connection test-A scores (r = 0.507, p < 0.05).ConclusionLT improved spontaneous brain activity and the results for associated cognition tests. However, decreased ALFF in some areas persisted, and new-onset abnormal ALFF were possible, indicating that complete cognitive function recovery may need more time.

Normalization of the psychometric hepatic encephalopathy score for diagnosis of minimal hepatic encephalopathy in Turkey.

To construct normal values for the tests of the psychometric hepatic encephalopathy score (PHES) and evaluate the prevalence of minimal hepatic encephalopathy (MHE) among Turkish patients with liver cirrhosis. One hundred and eighty-five healthy subjects and sixty patients with liver cirrhosis without overt hepatic encephalopathy were included in the study. All subjects underwent psychometric tests, which include number connection test-A and B (NCT-A/B), serial dotting test (DST), line drawing test (LDT), and digit symbol test (DST) in the same day. The variables that affected the results of the test were included in the multiple linear regression models and formulas were constructed to predict the expected results for each tests. The results of all PHES tests, except the LDT in the cirrhotic group were significantly different than center of gravity (CG) (P < 0,001). The score of PHES in the cirrhotic group was -2,18 ± 3,3 (median -2; range: 11 to +4), significantly lower than CG (-0.31 ± 2.18 [median, 0; range, -8 to +5]) (P < 0.001). the cutoff of PHES was set -4 point. Therefore, 19 of the 60 cirrhotic patients were diagnosed with MHE (31.6%). Among the patients with MHE, 11 (11/45, 24,4%) had Child-Pugh classification (CTP) A and 8 (8/15, 53.3%) had CTP B. No differences in age and education years were found between the MHE and non-MHE groups (P > 0.05). Turkish PHES normograms have been developed for detecting patients with MHE. Future multicenter national studies are needed to validate widely applicable norms.