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  • Early brain temperature elevation and anaerobic metabolism in human acute ischaemic stroke.

    12 December 2017

    Early after acute ischaemic stroke, elevation of brain temperature might augment tissue metabolic rate and conversion of ischaemic but viable tissue to infarction. This might explain the observed link between pyrexia, severe stroke and poor outcome. We tested this hypothesis by measuring brain temperature and lactate concentration with multi-voxel magnetic resonance spectroscopic imaging across the acute ischaemic stroke lesion and normal brain as determined on diffusion imaging. We compared patterns of lactate concentration (reported in 'institutional units') and temperature elevation in diffusion lesion core, potential penumbra, ipsilateral and contralateral normal brain and with stroke severity. Amongst 40 patients with moderate to severe acute stroke imaged up to 26 h after onset, lactate concentration was highest in the ischaemic lesion core (42 versus 26 units in potential penumbra, P < 0.05), whereas temperature was highest in the potential penumbra (37.7 versus 37.3 degrees C in lesion core, P < 0.05). Neither sub-regional temperature nor lactate concentration correlated with stroke severity. With increasing time after stroke, ipsilateral brain temperature did not change, but contralateral hemisphere temperature was higher in patients scanned at later times; lactate remained elevated in the lesion core, but declined in potential penumbral and ipsilateral normal tissue at later times. We conclude that early brain temperature elevation after stroke is not directly related to lactate concentration, therefore augmented metabolism is unlikely to explain the relationship between early pyrexia, severe stroke and poor outcome. Early brain temperature elevation may result from different mechanisms to those which raise body temperature after stroke. Further studies are required to determine why early brain temperature elevation is highest in potential penumbral tissue.

  • Associations between diffusion and perfusion parameters, N-acetyl aspartate, and lactate in acute ischemic stroke.

    15 December 2017

    BACKGROUND AND PURPOSE: In acute ischemic stroke, the amount of neuronal damage in hyperintense areas on MR diffusion imaging (DWI) is unclear. We used spectroscopic imaging to measure N-acetyl aspartate (NAA, a marker of normal neurons) and lactate (a marker of ischemia) to compare with diffusion and perfusion values in the diffusion lesion in acute ischemic stroke. METHODS: We recruited patients with acute ischemic stroke prospectively and performed MR diffusion weighted (DWI), perfusion, and spectroscopic imaging. We coregistered the images, outlined the visible diffusion lesion, and extracted metabolite, perfusion, and apparent diffusion coefficient (ADC) values from the diffusion lesion. RESULTS: 42 patients were imaged, from 1.5 to 24 hours after stroke. In the DWI lesion, although NAA was reduced, there was no correlation between NAA and ADC or perfusion values. However, raised lactate correlated with reduced ADC (Spearman rho=0.32, P=0.04) and prolonged mean transit time (MTT, rho=0.31, P=0.04). Increasing DWI lesion size was associated with lower NAA and higher lactate (rho=-0.44, P=0.003; rho=0.49, P=0.001 respectively); NAA fell with increasing times to imaging (rho=-0.3, P=0.03), but lactate did not change. CONCLUSIONS: Although larger confirmatory studies are needed, the correlation of ADC and MTT with lactate but not NAA suggests that ADC and MTT are better markers of the presence of ischemia than of cumulative neuronal loss. Further studies should define more precisely the rate of neuronal loss and relationship to diffusion and perfusion parameters with respect to the depth and duration of ischemia.

  • Structural changes of the brain in rheumatoid arthritis.

    12 December 2017

    OBJECTIVE: To investigate whether structural changes are present in the cortical and subcortical gray matter of the brains of patients with rheumatoid arthritis (RA). METHODS: We used two surface-based style morphometry analysis programs and a voxel-based style analysis program to compare high-resolution structural magnetic resonance imaging data obtained for 31 RA patients and 25 age- and sex-matched healthy control subjects. RESULTS: We observed an increase in gray matter content in the basal ganglia of RA patients, mainly in the nucleus accumbens and caudate nucleus. There were no differences in the cortical gray matter. Moreover, patients had a smaller intracranial volume. CONCLUSION: Our results suggest that RA is associated with changes in the subcortical gray matter rather than with cortical gray matter atrophy. Since the basal ganglia play an important role in motor control as well as in pain processing and in modulating behavior in response to aversive stimuli, we suggest that these changes may result from altered motor control or prolonged pain processing. The differences in brain volume may reflect either generalized atrophy or differences in brain development.

  • Non-invasive imaging compared with intra-arterial angiography in the diagnosis of symptomatic carotid stenosis: a meta-analysis.

    13 December 2017

    BACKGROUND: Accurate carotid imaging is important for effective secondary stroke prevention. Non-invasive imaging, now widely available, is replacing intra-arterial angiography for carotid stenosis, but the accuracy remains uncertain despite an extensive literature. We systematically reviewed the accuracy of non-invasive imaging compared with intra-arterial angiography for diagnosing carotid stenosis in patients with carotid territory ischaemic symptoms. METHODS: We searched for articles published between 1980 and April 2004; included studies comparing non-invasive imaging with intra-arterial angiography that met Standards for Reporting of Diagnostic Accuracy (STARD) criteria; extracted data to calculate sensitivity and specificity of non-invasive imaging, to test for heterogeneity and to perform sensitivity analyses; and categorised percent stenosis by the North American Symptomatic Carotid Endarterectomy Trial (NASCET) method. RESULTS: In 41 included studies (2541 patients, 4876 arteries), contrast-enhanced MR angiography was more sensitive (0.94, 95% CI 0.88-0.97) and specific (0.93, 95% CI 0.89-0.96) for 70-99% stenosis than Doppler ultrasound, MR angiography, and CT angiography (sensitivities 0.89, 0.88, 0.76; specificities 0.84, 0.84, 0.94, respectively). Data for 50-69% stenoses and combinations of non-invasive tests were sparse and unreliable. There was heterogeneity between studies and evidence of publication bias. INTERPRETATION: Non-invasive tests, used cautiously, could replace intra-arterial carotid angiography for 70-99% stenosis. However, more data are required to determine their accuracy, especially at 50-69% stenoses where the balance of risk and benefit for carotid endarterectomy is particularly narrow, and to explore and overcome heterogeneity. Methodology for evaluating imaging tests should be improved; blinded, prospective studies in clinically relevant patients are essential basic characteristics.

  • Neuroimaging in understanding chronic pain mechanisms and the development of new therapies

    28 November 2017

    This chapter describes how brain imaging methods have been used in studies on pain, what neuroimaging tells us about the role of the central nervous system in pain processing, how being in constant pain affects the brain, and finally, how neuroimaging can be applied to improve the existing analgesic drugs and to discover new therapies. Neuroimaging makes it possible to study pain processing beyond the peripheral nervous system, at the supraspinal level, in a safe, noninvasive way, without interfering with neurophysiological processes. In recent years, studies using brain imaging methods have contributed to our understanding of the mechanisms responsible for the development and maintenance of chronic pain. Moreover, neuroimaging shows promising results in characterizing different types of pain, bringing us closer to the development of mechanism-based treatments for chronic pain. © 2009 Springer-Verlag New York.

  • Investigation into the neural correlates of emotional augmentation of clinical pain.

    14 December 2017

    Although depressive mood is an important psychological determinate of chronic pain, the neural circuitry that mediates its influence on the pain experience is largely unknown. We used functional magnetic resonance imaging (FMRI) to investigate the neurophysiological interactions between depressive symptoms and disease-relevant pain in rheumatoid arthritis (RA) patients. RA is associated with chronic joint pain and swelling, but peripheral joint pathology often does not fully explain the amount of pain a patient experiences. We investigated the neural circuitry that relates joint pain and depressive symptoms and contrasted this with experimental heat pain. We hypothesized that (1) depressive symptoms influence the cerebral processing of provoked joint pain in RA, and (2) the interaction of depressive symptoms with pain processing contributes to the pain RA patients experience on a daily basis. Twenty patients underwent whole brain FMRI during which disease-relevant joint pain was provoked. Depressive symptoms were assessed using the Beck Depression Inventory (BDI). The tender-to-swollen joint ratio (T/S) was assessed as one component of the patients' clinical pain. BDI scores correlated significantly with T/S and medial prefrontal cortex (MPFC) activation during provoked joint pain. The association between BDI scores and T/S was partly mediated by the MPFC activation. Furthermore, the MPFC activation co-varied significantly with the FMRI signal in limbic areas and in areas that process self-relevant information. These results suggest that the MPFC may play an important role in mediating the relationship between depressive symptoms and clinical pain severity in RA, possibly by engaging brain areas important for affective and self-relevant processing.

  • Expression of citrulline and homocitrulline residues in the lungs of non-smokers and smokers: implications for autoimmunity in rheumatoid arthritis.

    12 December 2017

    INTRODUCTION: Smoking is a well-established risk factor for rheumatoid arthritis (RA), and it has been proposed that smoking-induced citrullination renders autoantigens immunogenic. To investigate this mechanism, we examined human lung tissue from 40 subjects with defined smoking status, with or without chronic obstructive pulmonary disease (COPD), and control tissues from other organs for citrullinated proteins and the deiminating enzymes peptidylarginine deiminase type-2 (PAD2) and -4 (PAD4). METHODS: Lung tissue samples, dissected from lobectomy specimens from 10 never smokers, 10 smokers without airflow limitation, 13 COPD smokers and eight COPD ex-smokers, and control tissue samples (spleen, skeletal muscle, liver, ovary, lymph node, kidney and heart), were analysed for citrullinated proteins, PAD2 and PAD4 by immunoblotting. Citrulline and homocitrulline residues in enolase and vimentin were analysed by partial purification by gel electrophoresis followed by mass spectrometry in 12 of the lung samples and one from each control tissues. Band intensities were scored semi-quantitatively and analysed by two-tailed Mann-Whitney T-test. RESULTS: Within the lung tissue samples, citrullinated proteins, PAD2 and PAD4 were found in all samples, with an increase in citrullination in COPD (P = 0.039), but minimal difference between smokers and non-smokers (P = 0.77). Citrullination was also detected at lower levels in the tissues from other organs, principally in lymph node, kidney and skeletal muscle. Mass spectrometry of the lung samples showed that vimentin was citrullinated at positions 71, 304, 346, 410 and 450 in non-smokers and smokers both with and without COPD. A homocitrulline at position 104 was found in four out of six COPD samples and one out of six non-COPD. Citrulline-450 was also found in three of the control tissues. There were no citrulline or homocitrulline residues demonstrated in α-enolase. CONCLUSIONS: We have shown evidence of citrullination of vimentin, a major autoantigen in RA, in both non-smokers and smokers. The increase in citrullinated proteins in COPD suggests that citrullination in the lungs of smokers is mainly due to inflammation. The ubiquity of citrullination of vimentin in the lungs and other tissues suggests that the relationship between smoking and autoimmunity in RA may be more complex than previously thought.