轻微肝性脑病的MRI与^1H-MRS探讨

目的探讨轻微肝性脑病患者颅脑MRI及^1H-MRS的代谢变化。方法 22例经神经心理测试诊断为轻微肝性脑病患者和13例年龄、性别和受教育程度相匹配的健康志愿者,行MRI、^1H-MRS扫描,^1H-MRS兴趣区为双侧基底节。结果 22例患者中17例双侧基底节在T1WI上可见高信号,NAA/Cr值患者组与健康对照组之间差异无显著性（P〉0.05）,而mI/Cr和Cho/Cr值患者组与健康对照组比较显著降低（L：P〈0.01;R：P〈0.01）。结论 T1WI高信号是诊断轻微肝性脑病较为特征性征象,1HMRS能够无创性观察到轻微肝性脑病患者的脑代谢异常,有助于揭示肝性脑病的病理生理机制。     

Metabolic changes of anterior cingulate cortex in patients with hepatic cirrhosis: A magnetic resonance spectroscopy study

Aim: The anterior cingulate cortex (ACC) plays an important role in cognitive functions. The purpose of this study is to compare metabolite concentrations in the ACC of cirrhotic patients with normal controls, and to correlate metabolite changes with Child–Pugh class and with severity of hepatic encephalopathy (HE). Methods: Fifty‐two cirrhotic patients and 30 healthy volunteers were included in this study. All subjects performed the number connection test type A (NCT‐A) and digital symbol test (DST) before multiple resonance (MR) examinations. Single‐voxel proton MR spectroscopy (MRS) data in the ACC were acquired on a 1.5‐T scanner. The ratios of all metabolites to creatine and phosphocreatine (Cr) were obtained. Statistical analysis was performed to evaluate the difference between control and cirrhotic patients, with respect to metabolite ratios. The correlation between metabolite ratios and Child–Pugh scale, severity of HE, venous ammonia and neuropsychiatric test results was analyzed. Results: The ratios of choline (Cho)/Cr and myo‐inositol (mIns)/Cr were significantly lower, and the ratio of glutamine– glutamate (Glx)/Cr was significantly higher in cirrhotic patients than those in controls (P < 0.001). mIns/Cr correlated negatively with Child–Pugh scale (r = −0.496, P < 0.001) and HE degree (r = −0.313, P < 0.05). Venous ammonia had a significant correlation with Cho/Cr (r = −0.329, P < 0.05) and mIns/Cr (r = −0.347, P < 0.05). No statistical correlation between metabolite ratios and neuropsychological tests was found for cirrhotic patients, but mIns/Cr did have a statistical correlation with NCT‐A (r = −0.270, P < 0.05) and DST (r = 0.463, P < 0.001) when all subjects were included in the analysis. Conclusion: Significant metabolite changes were seen in the ACC in cirrhotic patients. Of the metabolites examined, the mIns/Cr level in the ACC was most closely associated with the severity of HE and hepatic functional reserve reflected by Child–Pugh scale.     

Intracellular pH Measurements of the Whole Head and the Basal Ganglia in Chronic Liver Disease: A Phosphorus-31 MR Spectroscopy Study

The purpose of this study was to determine the intracellular pH of the whole head and in voxels localized to the basal ganglia in patients with chronic liver disease using phosphorus-31 magnetic resonance spectroscopy (³¹P MRS). The study group compromised 82 patients with biopsy-proven cirrhosis (43 Child's grade A, 25 Child's grade B and 14 Child's grade C). Eleven subjects showed no evidence of neuropsychiatric impairment on clinical, psychometric and electrophysiological testing, 37 showed evidence of minimal hepatic encephalopathy and 34 had overt hepatic encephalopathy. Unlocalized³¹P MRS of the whole head was performed in 48 patients and 10 healthy volunteers. Localized³¹P MRS of the basal ganglia was performed in the 34 patients and in 20 healthy volunteers. The intracellular pH values were calculated from the chemical shift difference between the inorganic phosphate (P_i) and phosphocreatine (PCr) resonances. The percentage inorganic phosphate (%P_i), phosphocreatine (%PCr) and βNTP signals, relative to the total³¹P signal, and peak area ratios of inorganic phosphate and phosphocreatine, relative to βNTP were also measured. There were no differences between patients and volunteers in intracellular pH in³¹P MR spectra measured from the whole head or the basal ganglia. There was no correlation between the severity of encephalopathy (West Haven criteria) or liver dysfunction (Child score) and intracellular pH values. There was also no significant change in the inorganic phosphate, phosphocreatine or βNTP resonances in spectra acquired from the whole head. However, in spectra localized to the basal ganglia, there was a significant increase in mean P_i/NTP (p=0.02) and PCr/NTP (p=0.009). The mean %P_i and mean %PCr were also increased (p=0.06; p=0.05, respectively), but there was no significant change in mean %βNTP. When the patient population was classified according to the severity of encephalopathy, those with overt disease had a higher mean P_i/NTP and %P_i (p=0.03; p=0.01), compared to the reference population. Our results suggest that there are detectable bioenergetic abnormalities in patients with minimal hepatic encephalopathy or stable, overt chronic hepatic encephalopathy, but any associated intracellular pH change is probably a secondary, rather than a primary phenomenon.     

CASE REPORT: Usefulness of Magnetic Resonance Spectroscopy for Diagnosis of Hepatic Encephalopathy in a Patient with Relapsing Confusional Syndrome

Magnetic resonance spectroscopy allows the assessment of several metabolites in brain tissue. In patients with hepatic encephalopathy, this technique shows a rise in glutamine and a decrease in myoinositol in brain tissue. However, the role of magnetic resonance spectroscopy in the diagnosis of hepatic encephalopathy is not known. We report the case of a patient with a relapsing confusional syndrome who underwent magnetic resonance spectroscopy. Previously, hepatic encephalopathy was ruled out because of the negative results of a transjugular liver biopsy and normal hepatic venous pressure gradient. The results of magnetic resonance were characteristic of hepatic encephalopathy. Abdominal computed tomography demonstrated large portosystemic shunts associated with cirrhosis of the liver. This case shows that magnetic resonance spectroscopy is an useful technique for the diagnosis of hepatic encephalopathy in selected cases, such as those without clinical signs of cirrhosis and/or large portosystemic shunts.     

Correlations between magnetic resonance spectroscopy alterations and cerebral ammonia and glucose metabolism in cirrhotic patients with and without hepatic encephalopathy

Background

Hepatic encephalopathy is considered to be mainly caused by increased ammonia metabolism of the brain. If this hypothesis is true, cerebral glucose utilisation, which is considered to represent brain function, should be closely related to cerebral ammonia metabolism. The aim of the present study was to analyse whether cerebral ammonia and glucose metabolism in cirrhotic patients with early grades of hepatic encephalopathy are as closely related as could be expected from current hypotheses on hepatic encephalopathy.

Methods

¹³N‐ammonia and ¹⁸F‐fluorodesoxyglucose positron emission tomography, magnetic resonance imaging and magnetic resonance spectroscopy (MRS) were performed in 21 cirrhotic patients with grade 0–1 hepatic encephalopathy. Quantitative values of cerebral ammonia uptake and retention rate and glucose utilisation were derived for several regions of interest and were correlated with the MRS data of the basal ganglia, white matter and frontal cortex.

Results

A significant correlation between plasma ammonia levels and cerebral ammonia metabolism, respectively, and MRS alterations could be shown only for white matter. In contrast, MRS alterations in all three regions studied were significantly correlated with the glucose utilisation of several brain regions. Cerebral ammonia and glucose metabolism were not correlated.

Conclusion

Increase of cerebral ammonia metabolism is an important but not exclusive causal factor for the development of hepatic encephalopathy.     

Regional variations in cerebral proton spectroscopy in patients with chronic hepatic encephalopathy

Regional variations in proton magnetic resonance spectroscopy (MRS) were assessed in 26 patients and 14 healthy volunteers using a two dimensional chemical shift imaging technique. Patients were classified as being neuropsychiatrically unimpaired, or as having subclinical or overt chronic hepatic encephalopathy (CHE). Peak area ratios of choline (Cho), glutamine and glutamate (Glx) and N-acetylaspartate (NAA) relative to creatine (Cr) were measured. Significant reductions in mean Cho/Cr and elevations in mean Glx/Cr were observed in the patient population, which correlated with the severity of CHE. There were significant regional variations in these metabolite ratios with the mean Cho/Cr lowest in the occipital cortex and the mean Glx/Cr highest in the basal ganglia. NAA/Cr remained relatively constant in all areas of the brain analysed. The regional variation in the metabolite ratios suggests that spectral information from more than one voxel may be useful in the assessment of patients with CHE.     

Clinical Significance of Basal Ganglia Alterations at Brain MRI and 1H MRS in Cirrhosis and Role in the Pathogenesis of Hepatic Encephalopathy

In hepatic encephalopathy, a progressive and diffuse impairment in brain function is associated with gradual alterations that can be detected by magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (¹H MRS). In some patients, a variety of movement disorders suggestive of extrapyramidal impairment points toward basal ganglia (BG) alterations. Accordingly, (i) hyperintensities at MRI predominant in the pallidum, an important region of BG involved in the motor control, (ii) redistribution of cerebral blood flow from cortical areas to BG structures observed using positron emission tomography studies, and (iii) the preferential pallidal location of Alzheimer astrocytosis, all support this hypothesis. In most clinical studies, little if any correlations have been found between cerebral hyperintensities and neurological manifestations. The application of a test designed to evaluate patients with Parkinson's disease (where extrapyramidal signs are typical) showed significant clinical correlations both with pallidal hyperintensity and with choline/creatine ratio at ¹H MRS in BG structures. Because of complex neuronal connections between BG and many cortical areas, BG dysfunction may influence the neurocognitive manifestations of hepatic encephalopathy. Similarities between chronic Mn intoxication and cirrhosis suggest common pathophysiological mechanisms including altered dopaminergic neurotransmission, although information in chronic liver failure is limited. Clinical observations are presented regarding the evolution of parkinsonian signs in various situations.     

Pathogenesis and diagnosis of hepatic encephalopathy

Hepatic encephalopathy (HE) is a common and potentially devastating neuropsychiatric complication of acute liver failure and cirrhosis. Even in its mildest form, minimal HE (MHE), the syndrome significantly impacts daily living and heralds progression to overt HE. There is maturity in the scientific understanding of the cellular processes that lead to functional and structural abnormalities in astrocytes. Hyperammonemia and subsequent cell swelling is a key pathophysiological abnormality, but this aspect alone is insufficient to fully explain the complex neurotransmitter abnormalities that may be observable using sophisticated imaging techniques. Inflammatory cytokines, reactive oxygen species activation and the role of neurosteroids on neurotransmitter binding sites are emerging pathological lines of inquiry that have yielded important new information on the processes underlying HE and offer promise of future therapeutic targets. Overt HE remains a clinical diagnosis and the neurophysiological and imaging modalities used in research studies have not transferred successfully to the clinical situation. MHE is best characterized by psychometric evaluation, but these tests can be lengthy to perform and require specific expertise to interpret. Simpler computer-based tests are now available and perhaps offer an opportunity to screen, diagnose and monitor MHE in a clinical scenario, although large-scale studies comparing the different techniques have not been undertaken. There is a discrepancy between the depth of understanding of the pathophysiology of HE and the translation of this understanding to a simple, easily understood diagnostic and longitudinal marker of disease. This is a present area of focus for the management of HE.     

MR imaging and spectroscopy of the basal ganglia in chronic liver disease: Correlation of T1-weighted contrast measurements with abnormalities in proton and phosphorus-31 MR spectra

The purpose of this study was to correlate the hyperintensity in the globus pallidus seen on T₁-weighted magnetic resonance imaging (MRI) of the brain in chronic liver disease with changes in metabolite ratios measured from both proton and phosphorus-31 magnetic resonance spectroscopy (MRS) localised to the basal ganglia. T₁-weighted spin echo (T₁ WSE) images were obtained in 21 patients with biopsy-proven cirrhosis (nine Child's grade A, eight Child's grade B and four Child's grade C). Four subjects showed no evidence of neuropsychiatric impairment on clinical, psychometric and electrophysiological testing, four showed evidence of subclinical hepatic encephalopathy and 13 had overt hepatic encephalopathy. Signal intensities of the globus pallidus and adjacent brain parenchyma were measured and contrast calculated, which correlated with the severity of the underlying liver disease, when graded according to the Pugh's score (p<0.05). Proton MRS of the basal ganglia was performed in 12 patients and 14 healthy volunteers. Peak area ratios of choline (Cho), glutamine and glutamate (Glx) and N-acetylaspartate relative to creatine (Cr) were measured. Significant reductions in mean Cho/Cr and elevations in mean Glx/Cr ratios were observed in the patient population. Phosphorus-31 MRS of the basal ganglia was performed in the remaining nine patients and in 15 healthy volunteers. Peak area ratios of phosphomonoesters (PME), inorganic phosphate, phosphodiesters (PDE) and phosphocreatine relative to BATP (ATP) were then measured. Mean values of PME/ATP and PDE/ATP were significantly lower in the patient population. No correlation was found between the T₁WSE MRI contrast measurements of the globus pallidus and the abnormalities in the metabolite ratios measured from either proton or phosphorus-31 MR spectra. Our results suggest that pallidal hyperintensity seen on T₁WSE MR imaging of patients with chronic liver disease is not related to the functional abnormalities of the brain observed in hepatic encephalopathy.     

Pathophysiology and management of hepatic encephalopathy 2014 update: Ammonia toxicity and hyponatremia

Hyperammonemia is a major factor involved in the pathogenesis of hepatic encephalopathy (HE). Ammonia elicits astrocyte swelling and causes brain edema. In addition, hyponatremia, a condition frequently observed in hepatic cirrhosis, also exacerbates brain edema, potentially becoming a factor that exacerbates HE. Therefore, as a treatment strategy for HE, alleviating ammonia toxicity is essential. In addition to restricting protein intake, synthetic disaccharides such as lactulose and lactitol, probiotics that improve gut flora, and rifaximin, an antibiotic with poor bioavailability, are also administrated. Additionally, branched‐chain amino acids and carnitine have also been administrated. Moreover, we investigated the current trend in the concomitant use of drugs with different mechanisms of action. In Japan, the V2 receptor antagonist tolvaptan can be administrated to hepatic cirrhosis patients with fluid retention. This drug is also useful as a countermeasure for hyponatremia in hepatic cirrhosis, and elucidating its effects in HE patients may therefore become an agenda in the future. These observations indicate that ammonia toxicity, gut flora control and low sodium control are major focuses in HE improvement and long‐term prognosis.     

Zinc-α2-Glycoprotein Expression in Adipose Tissue of Obese Postmenopausal Women before and after Weight Loss and Exercise + Weight Loss

Objective

Zinc-Alpha 2-Glycoprotein (ZAG) has recently been implicated in the regulation of adipose tissue metabolism due to its negative association with obesity and insulin resistance. The purpose of this study is to investigate the relationships between adipose tissue ZAG expression and central obesity, and the effects of six-months of weight loss (WL) or aerobic exercise + weight loss (AEX + WL) on ZAG expression.

Design and Methods

A six-month, longitudinal study of 33 healthy, overweight or obese postmenopausal women (BMI: 25–46 kg/m²) was conducted. Abdominal and gluteal adipose tissue samples were obtained before and after AEX + WL (n = 17) and WL (n = 16). ZAG expression was determined by RT-PCR.

Results

Prior to interventions, abdominal ZAG expression was negatively correlated with visceral fat (r = − 0.50, P < 0.005), sagittal diameter (r = − 0.42, P < 0.05), and positively related to VO₂max (r = 0.37, P < 0.05). Gluteal ZAG expression was negatively correlated with weight, fat-free mass, visceral fat, resting metabolic rate, and fasting insulin (r = − 0.39 to − 0.50, all P < 0.05). Abdominal ZAG mRNA levels increased, though not significantly, 5% after AEX + WL and 11% after WL. Gluteal ZAG mRNA levels also did not change significantly with AEX + WL and WL.

Conclusions

Abdominal ZAG expression may be important in central fat accumulation and fitness but only modestly increase (nonsignificantly) with weight reduction alone or with aerobic training in obese postmenopausal women.     

Infection and the progression of hepatic encephalopathy in acute liver failure

BACKGROUND & AIMS: Progression of hepatic encephalopathy (HE) is a major determinant of outcome in acute liver failure (ALF). Our aim was to identify predictive factors of worsening HE, including the relation of encephalopathy with the systemic inflammatory response (SIRS) and infection. METHODS: We included 227 consecutive patients with stage I-II HE prospectively enrolled in the U.S. Acute Liver Failure Study. Univariate and multivariate analysis of 27 variables at admission were performed separately for acetaminophen (n = 96) and nonacetaminophen (n = 131) etiologies. RESULTS: On multivariate analysis, acquisition of infection during stage I-II HE (P < 0.01), increased leukocyte levels at admission (P < 0.01), and decreased platelet count (P < 0.05) were predictive factors of worsening HE in the acetaminophen group. By contrast, only increased pulse rate (P < 0.05) and AST levels (P < 0.05) at admission were predictors in nonacetaminophen patients. In patients who progressed to deep HE, the first confirmed infection preceded progression in 15 of 19 acetaminophen patients compared with 12 of 23 nonacetaminophen patients. In patients who did not demonstrate positive microbiologic cultures, a higher number of components of SIRS at admission was associated with more frequent worsening of HE (25% vs. 35% vs. 50% for 0, 1, and >or=2 components of SIRS, P < 0.05). CONCLUSIONA: This prospective evaluation points to infection and/or the resulting systemic inflammatory response as important factors contributing to worsening HE in ALF, mainly in patients with acetaminophen- induced ALF. The use of prophylactic antibiotics in these patients and the mechanisms by which infection triggers hepatic encephalopathy require further investigation.     

Cerebral oedema in minimal hepatic encephalopathy due to extrahepatic portal venous obstruction

Background: Minimal hepatic encephalopathy (MHE) has recently been reported in patients with extrahepatic portal venous obstruction (EHPVO). Aims: To evaluate brain changes by magnetic resonance studies in EHPVO patients. Methods: Blood ammonia level, critical flicker frequency (CFF), brain metabolites on 1H‐magnetic resonance (MR) spectroscopy and brain water content on diffusion tensor imaging and magnetization transfer ratio (MTR) were studied in 31 EHPVO patients with and without MHE, as determined by neuropsychological tests. CFF and magnetic resonance imaging studies were also performed in 23 controls. Results: Fourteen patients (14/31, 45%) had MHE. Blood ammonia level was elevated in all, being significantly higher in the MHE than no MHE group. CFF was abnormal in 13% (4/31) with EHPVO and in 21% (3/14) with MHE. On 1H‐MR spectroscopy, increased Glx/Cr, decreased mIns/Cr, and no change in Cho/Cr were noted in patients with MHE compared with controls. Significantly increased mean diffusivity (MD) and decreased (MTR) were observed in the MHE group, suggesting presence of interstitial cerebral oedema (ICE). MD correlated positively with blood ammonia level (r=0.65, P=0.003) and Glx (r=0.60, P=0.003). Discussion: MHE was detected in 45% of patients with EHPVO while CFF was abnormal in only 13%. ICE was present in 7/10 brain regions examined, particularly in those with MHE. Hyperammonaemia elevated cerebral Glx levels correlated well with ICE. Conclusions: MHE was common in EHPVO; CFF could identify it only in a minority. ICE was present in EHPVO, particularly in those with MHE. It correlated with blood ammonia and Glx/Cr levels. Hyperammonaemia seems to contribute to ICE in EHPVO.