Increased glutamate/glutamine compounds in the brains of patients with fibromyalgia: A magnetic resonance spectroscopy study

Objective

Fibromyalgia (FM) has been defined as a systemic disorder that is clinically characterized by pain, cognitive deficit, and the presence of associated psychopathology, all of which are suggestive of a primary brain dysfunction. This study was undertaken to identify the nature of this cerebral dysfunction by assessing the brain metabolite patterns in patients with FM through magnetic resonance spectroscopy (MRS) techniques.

Methods

A cohort of 28 female patients with FM and a control group of 24 healthy women of the same age were studied. MRS techniques were used to study brain metabolites in the amygdala, thalami, and prefrontal cortex of these women.

Results

In comparison with healthy controls, patients with FM showed higher levels of glutamate/glutamine (Glx) compounds (mean ± SD 11.9 ± 1.6 arbitrary units [AU] versus 13.4 ± 1.7 AU in controls and patients, respectively; t = 2.517, 35 df, corrected P = 0.03) and a higher Glx:creatine ratio (mean ± SD 2.1 ± 0.4 versus 2.4 ± 1.4, respectively; t = 2.373, 35 df, corrected P = 0.04) in the right amygdala. In FM patients with increased levels of pain intensity, greater fatigue, and more symptoms of depression, inositol levels in the right amygdala and right thalamus were significantly higher.

Conclusion

The distinctive metabolic features found in the right amygdala of patients with FM suggest the possible existence of a neural dysfunction in emotional processing. The results appear to extend previous findings regarding the dysfunction in pain processing observed in patients with FM.

     

Cardiovascular disorders in patients with congenital portosystemic shunts: 23 years of experience in a tertiary referral centre

Central illustration. Time of occurrence and outcome of cardiovascular disorders in patients (pts) with congenital portosystemic shunt (CPSS). Patients with normal anatomy and those with congenital heart disease (CHD) were distinguished. Heart failure (HF) was the main symptom in both the prenatal and neonatal periods, whereas portopulmonary hypertension (PPH) and hepatopulmonary syndrome (HPS) represented the major concerns beyond the first months of life. CV: cardiovascular; NAS: no additional symptoms; PH: pulmonary hypertension; RD: respiratory distress. ^aFetal diagnosis of CPSS. ^bNeonatal diagnosis of CPSS. ^cDiagnosis of CPSS > 1 month of age

     

Reduced parietooccipital white matter glutamine measured by proton magnetic resonance spectroscopy in treated graves' disease patients

CONTEXT: Graves' disease is an autoimmune disease of the thyroid gland. Patients often have affective and cognitive complaints, whether these disappear after treatment remains disputed. OBJECTIVE: Our objective was to evaluate cerebral biochemistry in acute and treated Graves' disease. DESIGN: We conducted a prospective study, investigating volunteers once and patients before and 1 yr after treatment. SETTING: The study was performed at a radiology department, a memory disorder clinic, and two endocrinology clinics. PATIENTS AND OTHER PARTICIPANTS: Of 53 consecutively referred, newly diagnosed, and untreated patients with Graves' thyrotoxicosis, 27 patients (34 +/- 8 yr) and 33 matched volunteers were included. INTERVENTIONS: Patients were treated with thionamide. MAIN OUTCOME MEASURES: We assessed brain metabolite concentrations. METHODS: Proton magnetic resonance spectroscopy of the brain and a battery of biochemical, affective, and cognitive tests were used. RESULTS: Previously reported findings of reduced choline and myo-inositol in acute Graves' disease were confirmed and reversibility was demonstrated. Parieto-occipital white matter glutamine was and remained significantly reduced (P < 0.01). Acute phase parieto-occipital white matter total choline correlated significantly (r = -0.57; P < 0.01) with impaired thyroid function. Pretreatment total T(3) predicted posttreatment occipital gray matter glutamine (r = -0.52; P < 0.01). Occipital gray matter total choline (r = -0.53; P < 0.01) and parietooccipital white matter glutamate (r = -0.54; P < 0.01) correlated with initial values of selected attention and concentration cognitive scores and predicted them at follow-up. CONCLUSIONS: The persistent reduction of glutamine in white matter, the decreasing glutamate in occipital gray matter, and the correlation with severity of the initial disease as well as with attention and concentration cognitive scores indicated that there was a persistent and possibly progressive disturbance of the glutamate glutamine cycling in Graves' disease.     

Cine magnetic resonance imaging for evaluating flow dynamics in congenital heart diseases with left-to-right shunts]

Cine magnetic resonance imaging (cine MRI) was used to evaluate the cardiac structures and blood flow in congenital heart diseases with left-to-right shunts. Fifteen children with left-to-right shunts which were confirmed by echocardiography or angiography were investigated in the present study. Five children each had atrial septal defect, ventricular septal defect, and complete endocardial cushion defect. Their ages ranged from 4 months to 13 years (mean 5.5 years). Prior to cine MRI, the ECG-gated cardiac imaging using multi-slice acquisition was performed in all the children to localize the optimal slice for cine MRI. To select the optimal imaging planes for various cardiac structures, we used axial, coronal, sagittal and four-chamber views. Cine MRI was demonstrated by a fast low 30 degree flip angle imaging technique, with a 15 msec echo time, a 30-40 msec pulse repetition time, and a 256 x 256 or 128 x 128 acquisition matrix. Abnormalities of cardiac structures were defined extremely well in all the children using ECG-gated cardiac imaging. In 14 of the 15 children (93%), cine MRI clearly detected a left-to-right shunt flow, which was visualized as a low signal intensity area compared to the surrounding blood flow. Noninvasively, cine MRI provides accurate images of the anatomy of the cardiac structures, makes functional assessments of the cardiac chambers and walls, and flow relationships. It has no limitations of imaging planes imposed bones and lung, and is not associated with technical difficulties as required with echocardiography which has small cardiac window.(ABSTRACT TRUNCATED AT 250 WORDS)     

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

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

Evaluation of intracardiac shunts with cardiac magnetic resonance

Intracardiac shunts including atrial septal defect, ventricular septal defect, endocardial cushion defects, and surgical baffles may be identified, localized, and quantified using cardiac MRI methods. Both dark-blood and bright-blood techniques are helpful to identify anatomy. Contrast enhancement is especially useful for identifying associated vascular anomalies. Dynamic first-pass contrast agent signal-time studies may demonstrate rapid recirculation and shunting. Volumetric and phase contrast cine methods are useful to quantify flow. Pulmonary to systemic (Qp/Qs) flow ratios may be calculated noninvasively by comparing the pulmonary artery flow to the aortic flow measurement.     

Subclinical encephalopathy after portosystemic shunts in patients with non-cirrhotic portal fibrosis

Cerebral function was studied in patients with non-cirrhotic portal fibrosis who had no clinically detectable neurological abnormality, 14 before and 29 after a proximal lienorenal shunt operation. In each patient electroencephalography (EEG) and psychometric tests (the number connection test, construction of a five-pointed star and the reverse counting test) were performed. Psychometric tests were also done in an equal number of matched, healthy controls. Subclinical encephalopathy was diagnosed when any of these tests was abnormal. In the unoperated group the EEG was normal in all patients and there was no difference in the psychometric test results between patients and healthy controls. After portosystemic shunt operations, the EEG was abnormal in 10%, the number connection test in 38%, construction of a five-pointed star in 19% and the reverse counting test in 30% of the patients. Detection of subclinical hepatic encephalopathy in such a high proportion of operated patients with non-cirrhotic portal fibrosis suggests that the surgical procedure and its haemodynamic consequences per se could have been responsible.     

Fasting hyperglucagonemia in patients with transjugular intrahepatic portosystemic shunts (TIPS).

BACKGROUND: Hyperglucagonemia has been described to be associated with insulin resistance in patients with liver cirrhosis. Portosystemic shunts may be involved in the etiology of hyperglucagonemia. To test this hypothesis we investigated fasting peripheral plasma glucagon levels before and after portal decompression by transjugular intrahepatic portosystemic shunting (TIPS). METHODS: Glucagon, insulin, plasma glucose, HbA1c, and C-peptide were determined in peripheral venous samples from 21 non-diabetic (ND)- and 15 diabetic patients (D; 3 treated with insulin, 3 with sulfonylurea, 9 with diet alone) with liver cirrhosis, showing comparable clinical features (gender, age, BMI, creatinine, Child-Pugh-score, complications, and etiology of liver cirrhosis) before, 3 and 9 months after elective TIPS implantation. Insulin resistance was calculated as R (HOMA) according to the homeostasis model assessment (HOMA). RESULTS: Glucagon levels before TIPS were elevated in patients with diabetes compared to patients without diabetes (D: 145.4 +/- 52.1 pg/ml vs. ND: 97.3 +/- 49.8 pg/ml; p = 0.057). 3 and 9 months after TIPS implantation glucagon levels increased significantly in ND (188.9 +/- 80.3 pg/ml and 187.2 +/- 87.6 pg/ml) but not in D (169.6 +/- 62.4 pg/ml and 171.9 +/- 58.4 pg/ml). While plasma glucose, HbA1c, and C-peptide were significantly higher in D than in ND, they did not change significantly 3 and 9 months after TIPS implantation. Insulin was increased in D before TIPS (D: 31.6 +/- 15.9 mU/l vs. ND: 14.8 +/- 7.1 mU/l; p = 0.0001). 3 and 9 months after TIPS insulin significantly increased in ND (26.6 +/- 14.7 mU/l and 23.2 +/- 10.9 mU/l vs. 14.8 +/- 7.1 mU/l before TIPS) but not in D. In ND R (HOMA) also increased from 3.5 +/- 2 mU x mmol/l(2) to 5.7 +/- 3.3 mU x mmol/l(2) after 3 and 5.4 +/- 2.6 mU x mmol/l(2) after 9 months. BMI, liver and kidney function did not change with time. CONCLUSION: In non-diabetic cirrhotic patients TIPS implantation is followed by an increase of glucagon. However, this does not result in a worsening of glycemic control, probably because of a simultaneous increase of insulin.     

Safety and efficacy of transarterial chemoembolization in patients with transjugular intrahepatic portosystemic shunts

BackgroundTransarterial chemoembolization (TACE) for the treatment of hepatocellular carcinoma (HCC) is an important option as the majority of patients present with advanced disease. Data regarding treatment outcomes in patients who have undergone transjugular intrahepatic portosystemic shunts (TIPS) are limited. The present study seeks to evaluate the safety and efficacy of TACE in HCC patients with a TIPS.MethodsA retrospective review identifying patients with HCC and concomitant TIPS who were treated with TACE was performed.ResultsFrom 1999 to 2014, 16 patients with HCC underwent a total of 27 TACE procedures; eight patients required multiple treatments. The median patient age at the time of the initial TACE was 60.5 years [interquartile range (IQR) : 52.5–67.5] with the majority being male (n = 12, 75%) and Childs–Pugh Class B (n = 12, 75%). At 6 weeks after TACE, 56.3% of patients achieved an objective response rate (complete and partial response) by mRECIST criteria. Clavien Grade 3 or higher complications occurred in 11.1% of TACE procedures. There were no peri-procedural deaths. The median progression-free (PFS) and overall survival (OS) were 9 and 22 months, respectively, when censored for liver transplantation (median follow-up: 11.5 months).ConclusionTACE is an effective treatment strategy for HCC in TIPS patients; albeit may be associated with higher complication rates.     

Treatment of chronic portosystemic encephalopathy in cirrhotic patients by embolization of portosystemic shunts.

AIMS/BACKGROUNDS: Large spontaneous portal-systemic shunts can occasionally be the cause of chronic and disabling encephalopathy in cirrhotic patients. Shunt embolization has been proposed, however the clinical relevance of this technique remains uncertain. METHODS/RESULTS: We report our results in seven patients treated by shunt embolization. Although the procedure was achieved and technically successful in all patients, the clinical results were poor as long-term improvement was obtained in only one patient. Three patients died within 3 months after the procedure from cirrhoses' end stage complications. CONCLUSION: We believe that optimal management of these patients with chronic spontaneous encephalopathy is liver transplantation.     

质子磁共振波谱分析在白质病变患者中的应用

目的 探讨质子磁共振波谱(proton magnetic resonance spectroscopy,1H-MRS)在脑白质病变(white matter lesion,WML)患者中的应用.方法 纳入WML患者,结合影像学表现和临床症状分为皮质下动脉硬化性脑病(subcortical arteriosclerotic encephalopathy,SAE)组和单纯脑白质疏松(leukoaraiosis,LA)组.所有病例均完成MRI、1 H-MRS和听觉事件相关电位P300检查.1 H-MRS多体素采集范围为侧脑室周围白质区,记录N-乙酰天冬氨酸(N-acetylaspartate,NAA)、肌酐(creatine,Cr)、胆碱(choline,Cho)、NAA/Cr以及P300潜伏期和波幅.结果 共纳入WML患者50例,其中SAE30例,单纯LA 20例.SAE组NAA(中位数,四分位数间距;M,IQR)[0.732 (0.680 ～0.804)对0.915(0.866 ～ 0.963);Z=-5.634,P＜ 0.001]和NAA/Cr(M,IQR)[1.533(1.317～ 1.817)对2.003(1.794～2.387);Z=-3.921,P＜0.001]均较单纯LA组显著性降低.SAE组P300潜伏期(M,IQR)较单纯LA组显著延长[370.50(363.50 ～ 385.25)ms对351.50(342.75 ～ 359.00)ms;Z=-4.382,P＜ 0.001],且波幅(M,IQR)较单纯LA组显著性降低[4.35(2.90 ～7.20)mV对6.95(5.93 ～9.10)mV;Z=-2.942,P=0.003].结论 1 H-MRS可用于鉴别SAE与单纯LA患者,为预防LA进展为SAE提供客观依据.     

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     

Cerebral proton and phosphorus-31 magnetic resonance spectroscopy in patients with subclinical hepatic encephalopathy

Abstract: Background/Aims: In vivo magnetic resonance spectroscopy can be used to study cerebral metabolism non-invasively. We aimed to correlate ¹H and ³¹P magnetic resonance spectral abnormalities in the brains of patients with subclinical hepatic encephalopathy. Methods: Eighteen patients were studied at 1.5T, with combined ¹H and ³¹P magnetic resonance spectra obtained from multiple voxels in the cerebral cortex and basal ganglia. Peak area ratios of choline, glutamine/glutamate, relative to creatine in the ¹H spectra and percentage phosphomonoesters, phosphodiesters and βNTP signals relative to total ³¹P signals in the ³¹P spectra were measured. Results: Six patients did not complete the full examination –³¹P results are available from 12 patients only. Relative to creatine, there were reductions in choline and elevations in glutamine/glutamate, varying across the brain with choline significantly reduced in occipital cortex (p<0.05) and glutamine/glutamate most significantly elevated in temporo-parietal cortex (p<0.0001). Percentage phosphomonoester (p<0.05), phosphodiester (p<0.05) and βNTP (p<0.005) signals were significantly decreased in basal ganglia spectra. No correlation was found between the magnitude of ¹H and ³¹P MRS changes, except between percentage phosphodiester decrease and glutamine/glutamate to creatine increase in occipital cortex. Conclusion: The results of this study point to a multifactorial aetiology for this condition.