静息态fMRI技术观察肝性脑病患者双侧苍白球与全脑网络连接的改变研究

目的采用静息态功能MR(fMRI)技术探讨肝性脑病(HE)患者双侧苍白球与全脑网络连接的改变。方法 2015年2月～2017年6月诊治的明显HE患者(OHE)28例,轻微型HE患者(MHE)30例和选择健康人30例,受试者接受静息态fMRI扫描,选取双侧苍白球为种子点并进行全脑功能连接,分析比较各组双侧苍白球区域的脑功能网络连接差异。结果 HE患者苍白球与全脑网络连接出现差异的位置主要集中在额叶、顶叶和颞叶(P均0.05),与健康人比,OHE患者右侧枕下回、右侧额中回、左侧眶部额上回等脑区连接减弱,而在左海马旁回、双侧尾状核、左三角部额下回连接增强;MHE患者左中央前回、左内侧额上回、双侧颞中回等脑区连接减弱;与MHE患者比,OHE患者右侧楔前叶、右侧颞中回、右梭状回、右侧角回连接减弱,而双侧尾状核和右侧颞下回连接增强(P均0.05)。结论 HE患者双侧苍白球区域与多个脑区的功能连接受损,可能与临床出现的认知功能障碍有关。     

脑活素联合微生态制剂治疗肝性脑病患者疗效观察*

目的观察脑活素和微生态制剂联合治疗肝性脑病患者的临床疗效。方法选取2014年3月至2015年4月广东省化州市人民医院收治的76例肝性脑病患者,采用随机数字表法分为对照组和联合用药组,每组38例。给予对照组双歧杆菌乳杆菌三联活菌片,联合用药组则在给予微生态制剂的同时,给予脑活素静脉滴注。两组均观察28 d。采用干片法检测血氨水平,采用ELISA双抗体夹心法检测肿瘤坏死因子-α（ TNF-α）水平;采用数字连接试验（NCT）和数字符号试验（DST）检测受试者智力能力。结果经过4周治疗后,对照组患者NCT和DST评分为（70.47±8.15）和（31.52±8.32）,而联合用药组则分别为（41.06±6.61）和（56.89±9.23）,联合用药组明显优于对照组,差异具有统计学意义（P<0.05）;对照组血氨、ALT、TNF-α、TBIL分别为（69.71±19.56）μmol/L、（66.34±15.82） U/L、（346.75±45.63） pg/ml和（51.32±8.77）μmol/L,而联合用药组则分别为（49.65±18.33）μmol/L、（58.48±12.66） U/L、（142.57±39.51） pg/ml和（40.19±8.24）μmol/L,联合用药组改善更明显,差异具有统计学意义（P<0.05）。结论脑活素联合微生态制剂治疗肝性脑病患者效果更为显著,值得临床进一步验证。     

早期肠内营养联合微生态制剂治疗肝性脑病患者肠道菌群的改变*

目的 探讨早期给予肠内营养联合微生态制剂对肝性脑病（HE）患者肠道菌群的影响。方法 将64例乙型肝炎肝硬化并发HE患者随机分成观察组32例和对照组32例。在抗昏迷治疗的基础上,给予对照组肠内营养治疗,观察组在对照组治疗的基础上给予双歧杆菌乳杆菌三联活菌片治疗。观察两组2 w。结果 在观察2 w末,观察组和对照组分别死亡3例和4例;观察组生存患者粪便酵母样真菌为（3.2±0.4） CFU/g,显著低于对照组的【（3.9±0.5） CFU/g,P<0.05】,需氧肠球菌和厌氧乳杆菌水平分别为（12.3±1.2）CFU/g和（9.7±0.7）CFU/g,显著高于对照组的【（9.3±1.2） CFU/g和（8.2±0.8） CFU/g,P<0.05】;观察组血清内皮素、血氨、白介素-18和肿瘤坏死因子-α水平分别为（9.4±1.8） EU/mL、（75.4±10.2） μmol/L、（365.3±102.5） pg/mL和（26.3±10.7）n g/mL,显著低于对照组【（14.5±2.2） EU/mL、（109.3±5.5） μmol/L、（597.5±155.8） pg/mL和（42.8±11.2） ng/mL,P<0.05】;观察组血清白蛋白、血浆前白蛋白、转铁蛋白和视黄醇结合蛋白水平分别为（35.3±3.5） g/L、（341.1±35.2） mg/L、（2.5±0.4） g/L和（41.3±5.6） μg/L,显著高于对照组【（31.7±2.9） g/L、（310.1±33.4） mg/L、（2.2±0.4） g/L和（36.8±5.2） μg/L,P<0.05】。结论 早期给予肠内营养联合微生态制剂治疗可以有效改善HE患者肠道菌群失调症、抑制炎症应激反应,有利于营养的吸收和肝功能的恢复。     

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。     

肝性脑病大鼠脑超微结构的改变

目的：通过观察肝性脑病大鼠脑部分区域及氨对体外培养大鼠神经元超微结构的改变,讨论其病理发生机制。方法选用健康雄性SD大鼠12只,随机分为肝性脑病模型组和正常对照组两组,每组6只。用电子透射显微镜观察硫代乙酰胺诱导的肝性脑病大鼠和体外氨中毒大鼠皮质神经元的超微结构。结果肝性脑病大鼠神经元细胞数量减少;神经元线粒体肿胀,尼氏体数量明显减少;可见凋亡各期表现。神经胶质细胞细胞器减少,黑质的超微结构改变程度较基底核略重。体外培养氨中毒神经元变化：神经元细胞数量明显减少;细胞明显水肿,线粒体明显肿胀,尼氏体显著减少;可见不同时期的凋亡表现。结论肝性脑病大鼠脑超微结构改变明显,其主要机制可能与氨中毒引起的神经元凋亡有关。     

醒脑静联合纳洛酮治疗肝性脑病患者认知和血清炎症因子水平变化*

目的 探讨应用醒脑静和纳洛酮联合治疗肝性脑病（HE）患者对认知水平和血清细胞因子的影响。方法 2014年1月~2017年1月我院诊治的乙型肝炎肝硬化并发HE患者88例,采用随机数字表法分为观察组44例和对照组44例。分别给予醒脑静或醒脑静联合纳洛酮治疗7~10 d;。采用ELISA法检测血清白细胞介素6（IL-6）、IL-10、β-内啡肽、肿瘤坏死因子α（TNF-α）。应用简易智力状态检查量表（MMSE）和长谷川痴呆量表（HDS）进行认知评分。结果 在治疗结束时,观察组死亡14例（31.8%）,而对照组死亡20例（45.5%,P<0.05）;观察组血清β-内啡肽、血氨和CRP水平分别为（41.2±2.7） μmol/L、（73.1±6.3） μmol/L和（15.5±3.9） ng/L],显著低于对照组的【（51.3±5.8） μmol/L、（110.7±9.1） μmol/L和（18.1±3.8） ng/L,P<0.05】;血清IL-6和TNF-α水平分别为（10.1±3.2） ng/L和（11.2±4.8） ng/L,显著低于对照组的【（15.1±4.7） ng/L和（14.7±4.9） ng/L,P<0.05】;MMSE和HDS评分分别为（25.5±3.7）分和（23.4±3.3）分,显著高于对照组的[（21.7±3.6）分和（18.6±3.5）分,P<0.05]。结论 应用醒脑静与纳洛酮联合治疗乙型肝炎肝硬化并发HE患者有一定的临床疗效,可明显改善患者认知水平,降低血清细胞因子水平。     

肝性脑病的脑磁共振弥散张量成像特点分析

目的评价脑弥散张量成像(DTI)在肝性脑病(HE)诊断中的价值。方法 39例肝炎后肝硬化患者,其中伴HE18例(HE组),不伴HE 21例(肝硬化组),27例健康成人(正常组)。对三组行颅脑DTI扫描,测量分析DTI图像上脑深部灰质或白质区的各感兴趣区6个测量部位中的平均弥散率(MD)及各向异性分数值(FA)。结果肝硬化组与正常组MD与FA值无显著差异。与肝硬化组比较,HE组2个部位的MD值显著升高(P<0.05),4个部位的FA值显著降低(P<0.05);与正常组比较,HE组4个部位的MD值显著升高(P<0.05),4个部位的FA值显著降低(P<0.05)。结论 HE患者脑细胞外间隙水肿及细胞毒性水肿同时存在,DTI诊断HE有一定价值。     

3.0T场强下的磁共振波谱成像对肝性脑病局部脑代谢改变的评价作用

目的探讨3.0T场强下的磁共振波谱成像(MRS)对肝性脑病(HE)局部脑代谢改变的评价作用。方法选择本院2016年1月-2018年7月收治的病毒性肝炎肝硬化患者62例及30例健康志愿者,肝硬化患者分为肝硬化组(失代偿期肝硬化患者,38例)和HE组(肝性脑病并发症的慢性肝性脑病患者,24例)。记录3组患者的颅脑MRI表现,并比较3组脑代谢物峰下面积比值NAA/Cr、Cho/Cr、Glx/Cr和mI/Cr。结果肝硬化组与HE组患者的脑实质T2 WI上均未见明显异常信号,基底节区的苍白球及邻近区域的T1 WI上可见双侧对称性高信影,患者多出现不同程度的脑萎缩,以双侧额叶等部位较为常见。HE组与肝硬化组的Cho/Cr、mI/Cr均明显高于对照组,差异有统计学意义(P0.05),但HE组与肝硬化组Cho/Cr、mI/Cr的差异无统计学意义(P0.05)。HE组Glx/Cr高于肝硬化组与对照组(P0.05),但肝硬化组与对照组Glx/Cr的差异无统计学意义(P0.05)。3组NAA/Cr的差异均无统计学意义(P0.05)。结论肝硬化与HE患者均存在脑代谢异常,证实脑代谢改变早于HE症状,且Glx峰的升高可较准确地预示HE的出现。     

乳果糖治疗肝性脑病和亚临床肝性脑病149例临床观察

目的 进一步评估乳果糖对肝硬化肝性脑病和亚临床肝性脑病的疗效。方法 观察乳果糖治疗前后患者的精神状态、扑翼状震颤、脑电图、静脉血氨浓度和数字连接试验的改善情况。结果 乳果糖对肝性脑病组的脑病表现总有效率达96.5％,治疗前后静脉血氨浓度和数字连接试验的改善均有非常显著性差异(P<0.01);亚临床肝性脑病组治疗前后血氨有非常显著性差异(P<0.01),数字连接试验有显著性差异(P<0.05)。在乳果糖治疗观察期间,无一例亚临床肝性脑病患者发展为肝性脑病。结论 乳果糖适合于肝硬化肝性脑病和亚临床肝性脑病患者长期服用,可作为预防和治疗肝性脑病的常规用药。     

儿童失神性癫痫的静息态fMRI指标一致性分析

目的 观察不同静息态功能磁共振成像(fMRI)指标在反映癫痫活动时的一致性及关系。方法回顾性收集2010年2月至2021年9月于金陵医院明确诊断为儿童失神性癫痫(CAE)的18例患儿(CAE患儿组),行同步EEG-fMRI数据采集后截取44段发放状态fMRI数据,同时纳入并采集94名正常儿童(正常对照组)的静息态fMRI数据。计算每个受试者低频振幅(ALFF)、分数低频振幅(fALFF)、局域一致性(ReHo)、功能连接密度(FCD)、长程功能连接密度(Long FCD)、短程功能连接密度(Local FCD)、流入格兰杰因果连接密度(GCD＿in)、流出格兰杰因果连接密度(GCD＿out)、净流入格兰杰因果连接密度(GCD＿int)、Hurst指数及静息态fMRI滞后分析(RSLA),采用两样本t检验得到各指标的组间差异脑图,并计算所有组间差异脑图的空间分布频次图,将重叠最大的区域作为感兴趣区。使用Pearson相关分析分别探讨两组受试者感兴趣区内各指标的相关性。同时使用SurfStat软件包构建了广义线性模型,探讨疾病状态与各静息态fMRI指标间相关系数的交互效应。结果 各静息态f...     

Current and future applications of magnetic resonance imaging and spectroscopy of the brain in hepatic encephalopathy

Hepatic encephalopathy (HE) is a common neuro-psychiatric abnormality, which complicates the course of patients with liver disease and results from hepatocellular failure and/or portosystemic shunting. The manifestations of HE are widely variable and involve a spectrum from mild subciinical disturbance to deep coma. Research interest has focused on the role of circulating gut-derived toxins, particularly ammonia, the development of brain swelling and changes in cerebral neurotransmitter systems that lead to global CNS depression and disordered function. Until recently the direct investigation of cerebral function has been difficult in man. However, new magnetic resonance imaging (MRI) techniques provide a non-invasive means of assessment of changes in brain volume (coregistered MRI) and impaired brain function (fMRI), while proton magnetic resonance spectroscopy (1H MRS) detects changes in brain biochemistry, including direct measurement of cerebral osmolytes, such as myoinositol, glutamate and glutamine which govern processes intrinsic to cellular homeostasis, including the accumulation of intracellular water. The concentrations of these intracellular osmolytes alter with hyperammonaemia. MRS-detected metabolite abnormalities correlate with the severity of neuropsychiatric impairment and since MR spectra return towards normal after treatment, the technique may be of use in objective patient monitoring and in assessing the effectiveness of various treatment regimens.     

Voxel-based analyses of magnetization transfer imaging of the brain in hepatic encephalopathy

AIM: To evaluate the spatial distribution of cerebral abnormalities in cirrhotic subjects with and without hepatic encephalopathy (HE) found with magnetization transfer imaging (MTI). METHODS: Nineteen cirrhotic patients graded from neurologically normal to HE grade 2 and 18 healthy control subjects underwent magnetic resonance imaging. They gave institutional-review-board-approved written consent. Magnetization transfer ratio (MTR) maps were generated from MTI. We tested for significant differences compared to the control group using statistical non-parametric mapping (SnPM) for a voxelbased evaluation. RESULTS: The MTR of grey and white matter was lower in subjects with more severe HE. Changes were found in patients with cirrhosis without neurological deficits in the basal ganglia and bilateral white matter. The loss in magnetization transfer increased in severity and spatial extent in patients with overt HE. Patients with HE grade 2 showed an MTR decrease in white and grey matter: the maximum loss of magnetization transfer effect was located in the basal ganglia [SnPM (pseudo-)t = 17.98, P = 0.0001]. CONCLUSION: The distribution of MTR changes in HE points to an early involvement of basal ganglia and white matter in HE.     

Multimodality magnetic resonance imaging in hepatic encephalopathy: An update

Hepatic encephalopathy (HE) is a neuropsychiatric complication of cirrhosis or acute liver failure. Currently, HE is regarded as a continuous cognitive impairment ranging from the mildest stage, minimal HE to overt HE. Hyperammonaemia and neuroinflammation are two main underlying factors which contribute to the neurological alterations in HE. Both structural and functional impairments are found in the white mater and grey mater involved in HE. Although the investigations into HE pathophysiological mechanism are enormous, the exact pathophysiological causes underlying HE remain controversial. Multimodality magnetic resonance imaging (MRI) plays an important role in helping to understand the pathological process of HE. This paper reviews the up-to-date multimodality MRI methods and predominant findings in HE patients with a highlight of the increasingly important role of blood oxygen level dependent functional MRI.     

轻度认知功能损害患者静息状态脑默认活动网络的功能磁共振研究

目的 采用静息状态功能磁共振(fMRI)技术,探讨轻度认知功能损害(MCI)患者的脑默认活动网络(DMN)是否存在异常及其可能的神经机制.方法 对20名遗忘型MCI老年患者和25名正常老年人进行简易智能状态检查(MMSE)、听觉词语学习测验(AVLT)和静息状态脑功能成像.利用低频振幅(ALFF)算法,观察MCI患者相对于正常老年人ALFF增强及减弱的区域.结果 MMSE和AVLT测试结果显示MCI患者与正常老年人比较,记忆功能损害较明显,主要以情景记忆的短延迟回忆[(2.4±1.7)分与(6.6±1.4)分,t=3.70,P＜0.01]和长延迟回忆[(2.1±1.6)分与(6.7±1.5)分,t=4.16,P＜0.01]损害为主.静息状态fMRI结果显示与正常老年人比较,MCI患者与情景记忆密切相关的海马、海马旁回和侧颞叶皮层等脑区的ALFF减弱(t=2.58、2.43、1.75,均P＜0.01),颞顶交界和顶下小叶的ALFF增强(t=3.14、2.77,均P＜0.01).结论 MCI患者静息状态DMN与情景记忆密切相关的脑区结点活动强度存在异常,与正常老年人比较,大多活动减低,但是部分区域活动增强,提示MCI患者脑内可能存在代偿机制.

Abstract：

Objective To explore the activity and its possible neural mechanism of brain default mode network by using resting state functional magnetic resonance imaging (fMRI) in patients with mild cognitive impairment (MCI). Methods The 20 amnestic MCI patients and 25 healthy controls were included in this study, and all subjects underwent mini-mental state examination (MMSE), auditory verbal learning test (AVLT) and fMRI. The data were analyzed by amplitude of low frequency fluctuation (ALFF), and the enhanced and weakened regions of ALFF were observed and compared in both MCI patients and healthy controls. Results MMSE and AVLT tests showed that the memory function was seriously impaired in MCI patients compared with healthy controls, which is based on the short and long delayed episodic memory impairment (2.4±1.7 vs. 6.6±1.4, t=3.70, P＜0.01; 2.1±1.6 vs. 6.7±1.5, t=4.16, P＜0.01). The resting state fMRI showed that MCI patients had significant decreases of ALFF in hippocampal formation, parahippocampal cortex and lateral temporal cortex as compared with health controls (t=2.58, 2.43 and 1.75, all P＜0.01), which were closely relevant to the episodic memory. And they had significant increases in temporal-parietal joint and inferior parietal lobule (t=3.14 and 2.77, both P＜0.01). Conclusions MCI patients show significant decreased active intensity of some DMN nodes that is related to episodic memory in resting state. Increased active intensity in MCI patients would be some type of compensation.     

肝性脊髓病并大脑苍白球磁共振成像异常信号1例

患者,男,46岁,因患乙型肝炎16年,反复腹胀8年,加重1 d入院。既往入院已确诊为乙型肝炎后肝硬化失代偿期,脾功能亢进。此次住院期间反复发生肝性脑病,并于住院4月后逐渐出现双下肢乏力僵硬、自觉腓肠肌疼痛、行走障碍,行走时呈剪刀样步态,每于肝性脑病发作后,其双下肢僵硬程度略有加重。查体:面部毛细血管扩张,皮肤巩膜轻度黄染,肝掌( ),胸背部可见蜘蛛痣,双侧胸腔积液征,腹膨隆,腹壁浅表     

Efficacy of long-term rifaximin treatment for hepatic encephalopathy in the Japanese

BACKGROUND Hepatic encephalopathy(HE) is a complication of liver cirrhosis and can result in neuropsychological and neuromuscular dysfunctions in patients. Rifaximin, an antibiotic, has been reported to decrease the occurrence of overt HE and also improve cognitive function in studies from Europe and the United States of America. There is not enough evidence of the relationship between the long-term use of rifaximin and its clinical effects in the Japanese.AIM To determine the clinical effects of long-term rifaximin therapy in decompensated liver cirrhosis patients, with overt HE or hyperammonemia.METHODS In this single-center retrospective observational cohort study, we reviewed the data of 38 patients who had taken rifaximin at the dose of 1200 mg/d for more than 24 wk. The primary outcome measured was the efficacy of long-term rifaximin use, and secondary outcome measured was the safety of its long-term use as determined by its influence on portosystemic shunts as well as Escherichia coli-related infections. Moreover, we compared the prognosis between the rifaximin group and control cases, matched for hepatic elasticity assessed by magnetic resonance ela-stography, age, and Child-Pugh classification.RESULTS Of the 38 patients included in the study, 12(31.6%) had overt HE, 27(71.1%) had complications of esophageal varices, and 9(23.7%) had hepatocellular carcinoma(HCC). The control group was matched for age, Child-Pugh classification, liver stiffness, and presence of HCC. The median of serum ammonia level before treatment was 104 μg/dL(59-297), and 2 wk after treatment, it significantly decreased to 85 μg/dL(34-153)(P = 0.002). A significantly low value of 80.5μg/dL(44-150) was maintained 24 wk after treatment. The long-term use of rifaximin did not cause a decline in liver function. Diarrhea occurred in 2 patients, who improved with the administration of probiotics, and there were no cases of aborted rifaximin therapy owing to adverse events. In patients with Child C, the survival was short, but there was no significant difference compared with that of the control group.CONCLUSION Rifaximin therapy improves overt HE. The long-term use of rifaximin in the Japanese is effective and safe.     

Effects of L-carnitine in patients with hepatic encephalopathy

AIM: To evaluate the influence of L-carnitine on mental conditions and ammonia effects on patients with hepatic encephalopathy (HE). METHODS: One hundred and fifty patients (10 patients with alcoholism, 41 patients with hepatitis virus B infection, 78 patients with hepatitis C virus infection, 21 patients with cryptogenetic cirrhosis) meeting the inclusion criteria were randomized into group A receiving a 90-d treatment with L-carnitine (2 g twice a day) or into group B receiving placebo in double blind. RESULTS: At the end of the study period, a significant decrease in NH4 fasting serum levels was found in patients with hepatic encephalopathy (P<0.05) after the treatment with levocarnitine (LC). Significant differences were also found between symbol digit modalities test and block design in patients with hepatic encephalopathy (P<0.05). CONCLUSION: Results of our study suggest an important protective effect of L-carnitine against ammonia-precipitated encephalopathy in cirrhotic patients.     

门静脉高压状态下门体分流的超声分型及分流量与肝性脑病的关系

门静脉高压门体分流性肝性脑病,常为肝硬化患者致死原因之一,本研究旨在探讨门静脉高压状态下门体分流的超声分型及分流量与肝性脑病的关系,为临床提供诊断、治疗依据。一、资料与方法1.对象:2000年5月至2005年5月我院住院肝硬化患者分为门体分流组和无分流组。分流组:667例存在自发性