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      Interaction of incidental microbleeds and prior use of antithrombotics with early hemorrhagic transformation: Causative or protective?

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          Abstract

          Background:

          Gradient echo (GRE) sequence of magnetic resonance imaging (MRI) is a sensitive tool to detect hemorrhagic transformation (HT) and old cerebral microbleeds (CMBs). Presence of CMBs and prior use of antithrombotics pose a risk of HT in ischemic stroke. We evaluated the association of CMBs and antithrombotic use with resultant HT in acute ischemic stroke (AIS).

          Methods:

          This retrospective study included AIS patients admitted to our center between January 2009 and August 2010 who underwent GRE-weighted MRI within 48 h of admission. Demographic and clinical data including diabetes mellitus, hypertension, hyperlipidemia, prior intake of antiplatelets/anticoagulants/statins, and presence of CMBs at admission were collected and compared between patients who developed HT and those who did not. We did a multivariate analysis using logistic regression to assess the effect of CMBs and prior use of antithrombotic agents on the risk of development for early HT in ischemic stroke.

          Results:

          Of 529 AIS patients, 81 (15%) were found to have HT during the initial hospital course. CMBs were found in only 9 of 81 patients (11%) with HT and in 40 out of remaining 448 patients (9%) who did not develop HT. The presence of CMBs was not associated with increased risk of HT ( P = 0.53). However, prior use of antiplatelets (33% vs. 47% in the patients without HT, P = 0.02) was associated with decreased risk of HT in ischemic stroke.

          Conclusion:

          Presence of incidental CMBs was not associated with increased risk for early HT of an ischemic stroke. Interestingly, the prior intake of antiplatelets was found to be protective against HT of ischemic stroke.

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          Most cited references 41

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          Cerebral microbleeds: a guide to detection and interpretation.

          Cerebral microbleeds (CMBs) are increasingly recognised neuroimaging findings in individuals with cerebrovascular disease and dementia, and in normal ageing. There has been substantial progress in the understanding of CMBs in recent years, particularly in the development of newer MRI methods for the detection of CMBs and the application of these techniques to population-based samples of elderly people. In this Review, we focus on these recent developments and their effects on two main questions: how CMBs are detected, and how CMBs should be interpreted. The number of CMBs detected depends on MRI characteristics, such as pulse sequence, sequence parameters, spatial resolution, magnetic field strength, and image post-processing, emphasising the importance of taking into account MRI technique in the interpretation of study results. Recent investigations with sensitive MRI techniques have indicated a high prevalence of CMBs in community-dwelling elderly people. We propose a procedural guide for identification of CMBs and suggest possible future approaches for elucidating the role of these common lesions as markers for, and contributors to, small-vessel brain disease.
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            Stroke and bleeding in atrial fibrillation with chronic kidney disease.

            Both atrial fibrillation and chronic kidney disease increase the risk of stroke and systemic thromboembolism. However, these risks, and the effects of antithrombotic treatment, have not been thoroughly investigated in patients with both conditions. Using Danish national registries, we identified all patients discharged from the hospital with a diagnosis of nonvalvular atrial fibrillation between 1997 and 2008. The risk of stroke or systemic thromboembolism and bleeding associated with non-end-stage chronic kidney disease and with end-stage chronic kidney disease (i.e., disease requiring renal-replacement therapy) was estimated with the use of time-dependent Cox regression analyses. In addition, the effects of treatment with warfarin, aspirin, or both in patients with chronic kidney disease were compared with the effects in patients with no renal disease. Of 132,372 patients included in the analysis, 3587 (2.7%) had non-end-stage chronic kidney disease and 901 (0.7%) required renal-replacement therapy at the time of inclusion. As compared with patients who did not have renal disease, patients with non-end-stage chronic kidney disease had an increased risk of stroke or systemic thromboembolism (hazard ratio, 1.49; 95% confidence interval [CI], 1.38 to 1.59; P<0.001), as did those requiring renal-replacement therapy (hazard ratio, 1.83; 95% CI, 1.57 to 2.14; P<0.001); this risk was significantly decreased for both groups of patients with warfarin but not with aspirin. The risk of bleeding was also increased among patients who had non-end-stage chronic kidney disease or required renal-replacement therapy and was further increased with warfarin, aspirin, or both. Chronic kidney disease was associated with an increased risk of stroke or systemic thromboembolism and bleeding among patients with atrial fibrillation. Warfarin treatment was associated with a decreased risk of stroke or systemic thromboembolism among patients with chronic kidney disease, whereas warfarin and aspirin were associated with an increased risk of bleeding. (Funded by the Lundbeck Foundation.).
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              Spontaneous brain microbleeds: systematic review, subgroup analyses and standards for study design and reporting.

              Brain microbleeds (BMBs) are seen as small, homogeneous, round foci of low signal intensity on magnetic resonance imaging gradient echo (GRE) T2 sequences. BMBs might only be a biomarker for microangiopathy, or alternatively BMBs might provide useful diagnostic and prognostic information, potentially with therapeutic implications for the treatment of stroke. Because of the rapid expansion in recent BMB research, we systematically reviewed and critically appraised the published literature according to QUADAS, STARD and Cochrane principles. Our selection criteria were met by 54 studies of 53 case series involving 9073 participants, 4432 of whom were people with cerebrovascular diseases. There were significant biases in many of the studies: variation in MRI magnet strength, flip angle, slice gap and slice thickness; inconsistent definitions of BMB size (23% did not define size at all, and of those that did 44% chose a diameter of < or =5 mm); only 30% included participants who were representative of the disease under study; and only 53% mentioned that BMB evaluation was blinded to other factors of interest. By pooling data from similar studies, we found that the prevalence of BMBs was 5% [95% confidence interval (CI) 4-6] in healthy adults, 34% (95% CI 31-36) in people with ischaemic stroke, and 60% (95% CI 57-64) in people with non-traumatic intracerebral haemorrhage (ICH). In the studies where a distinction could be made, BMBs were more prevalent among recurrent strokes than first-ever strokes: they affected 23% (95% CI 18-29) with first-ever ischaemic stroke but 44% (95% CI 34-54) with recurrent ischaemic stroke, and 52% (95% CI 47-56) with first-ever ICH but 83% (95% CI 71-90) with recurrent ICH. By pooling data that could be extracted from similar studies, it appears that BMBs are associated with hypertension (OR 3.9, 95% CI 2.4-6.4) and diabetes mellitus (OR 2.2, 95% CI 1.2-4.2) in otherwise healthy adults, and that they are associated with hypertension (OR 2.3, 95% CI 1.7-3.0) in adults with cerebrovascular diseases. The association with hypertension was robust in sensitivity analyses. There is a pressing need for better designed studies to assess the diagnostic utility of BMBs, disentangle the many likely influences on their occurrence, and determine their prognostic utility and whether they should influence treatment. We conclude by proposing criteria for ideal study design and reporting.
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                Author and article information

                Affiliations
                Department of Neurology, University of California Los Angeles, Los Angeles, CA, USA
                [1 ]Cleveland Clinic Foundation, Cleveland, OH, USA
                [2 ]Department of Neurology, RUSH University Medical Center, Chicago, IL, USA
                [3 ]Department of Internal Medicine, King Saud University, Riyadh, Saudi Arabia
                Author notes
                For correspondence: Dr. Konark Malhotra, 757 Westwood Plaza, Los Angeles, CA 90095, USA. E-mail: konark.malhotra@ 123456yahoo.com
                Journal
                Ann Indian Acad Neurol
                Ann Indian Acad Neurol
                AIAN
                Annals of Indian Academy of Neurology
                Medknow Publications & Media Pvt Ltd (India )
                0972-2327
                1998-3549
                Oct-Dec 2016
                : 19
                : 4
                : 467-471
                5144467 AIAN-19-467 10.4103/0972-2327.194423
                Copyright: © Annals of Indian Academy of Neurology

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

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