Early primary biliary cholangitis is characterised by brain abnormalities on cerebral magnetic resonance imaging

Background Brain change can occur in primary biliary cholangitis (PBC), potentially as a result of cholestatic and/or inflammatory processes. This change is linked to systemic symptoms of fatigue and cognitive impairment. Aim To identify whether brain change occurs early in PBC. If the change develops early and is progressive, it may explain the difficulty in treating these symptoms. Methods Early disease brain change was explored in 13 patients with newly diagnosed biopsy‐proven precirrhotic PBC using magnetisation transfer, diffusion‐weighted imaging and 1H magnetic resonance spectroscopy. Results were compared to 17 healthy volunteers. Results Cerebral magnetisation transfer ratios were reduced in early PBC, compared to healthy volunteers, in the thalamus, putamen and head of caudate with no greater reduction in patients with greater symptom severity. Mean apparent diffusion coefficients were increased in the thalamus only. No 1H magnetic resonance spectroscopy abnormalities were seen. Serum manganese levels were elevated in all PBC patients, but no relationship was seen with imaging or symptom parameters. There were no correlations between neuroimaging data, laboratory data, symptom severity scores or age. Conclusions This is the first study to be performed in this precirrhotic patient population, and we have highlighted that neuroimaging changes are present at a much earlier stage than previously demonstrated. The neuroimaging abnormalities suggest that the brain changes seen in PBC occur early in the pathological process, even before significant liver damage has occurred. If such changes are linked to symptom pathogenesis, this could have important implications for the timing of second‐line‐therapy use

PET Imaging of Microglia Activation and Infection in Neuropsychiatric Disorders with Potential Infectious Origin

The central nervous system (CNS) is an immunoprivileged location for the possible sequestration of latent infections. The presence of pathogens may be involved in the etiology of neuropsychiatric diseases by inducing classical inflammatory responses, hypersensitivity, cellular toxicity, or direct alteration of cellular processes. Infection, persistence, and activation of microbes in the brain are not easy to assess in vivo, and the relation with clinical disease is very difficult to prove. An elegant way to determine an inflammatory response in the brain in vivo is by molecular imaging of microglia activation with [11C]PK11195 and other radiopharmaceuticals that target the translocator protein (TSPO). In this chapter, we summarize the neuroimaging studies that target the TSPO in patients with neuropsychiatric diseases, and we propose positron emission tomography (PET) imaging with radiopharmaceuticals that target the metabolism of infectious agents directly.</p

The why and wherefore of hepatic encephalopathy

Vijay PB Grover, Joshua M Tognarelli, Nicolas Massie, Mary ME Crossey, Nicola A Cook, Simon D Taylor-Robinson Liver Unit, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London, London, UK Abstract: Hepatic encephalopathy is a common neuropsychiatric abnormality, which complicates the course of patients with liver disease. It was probably first described by Hippocrates over 2000 years ago, who said that &quot;those whose madness arises from phlegm are quiet and neither shout nor make a disturbance, while those whose madness arises from bile shout, play tricks and will not keep still, but are always up to some mischief&quot;. He was presumably describing the differences between patients with pneumonia and acute liver failure. Despite the fact that the syndrome was probably first recognized thousands of years ago, the exact pathogenesis still remains unclear. Furthermore, a precise definition of the syndrome is lacking, as are definitive methods of diagnosing this condition. It is important as both patients with cirrhosis and the general population with whom they interact may be affected as a consequence. At a minimum, the individual may be affected by impaired quality of life, impaired ability to work, and slowed reaction times, which are relevant to the population at large if affected individuals operate heavy machinery or drive a car. Pathogenic mechanisms, diagnostic tools, and treatment options are discussed. Keywords: hepatic encephalopathy, cirrhosis, ammonia, pathology, treatment, rifaximin, lactulos

Radiotracer imaging studies in hepatic encephalopathy: ISHEN practice guidelines

There is lack of consensus on radiotracer usage in hepatic encephalopathy (HE). We have focused our attention on three main areas: (i) radiotracer imaging in animal models of HE, (ii) methodological issues of radiotracer imaging in HE and (iii) radiotracer imaging studies on the pathophysiology and (new) therapies in HE. We suggest the following: 1. Positron emission tomography (PET) and single photon emission computed tomography lend themselves to the study of animal models of HE, but the models that are suitable depend on the specific research question. Magnetic resonance imaging (MRI) may be a useful alternative technique. 2. Owing to the cost of the technique, there is a need for multicentre human PET studies to overcome the problem of underpowered small studies being undertaken in individual research centres. There should be a unified PET protocol with central, anonymised data analysis in one centre, using validated methodology, on behalf of all participating centres. Such studies would be useful for the assessment of early intervention in patients with subtle neuropsychiatric symptoms, or for clarification of the effect of liver transplantation on HE. 3. While radiotracer imaging modalities remain useful research tools for the study of pathogenesis and for the assessment of treatment effects, there is no consensus on the use of imaging in routine clinical practice for diagnosis and prognosis. The most promising objective tools appear to be magnetic resonance spectroscopy (MRS) and volumetric MRI, which can be performed in multiple centres without the difficulties that radiotracer imaging entail. © 2009 John Wiley & Sons A/