EDITORIAL
Causation of cerebral microbleeds: more work is urgently needed
See paper by Horstmann et al. on page 1355.
Cerebral microbleeds are frequently detected in patients with intracerebral hemorrhages [1] and patients with ischaemic stroke or transient ischaemic attack (TIA) [2,3] but also in seemingly healthy ageing individuals [4]. Lobar microbleeds are considered to reflect amyloid angiopathy while deep microbleeds are thought to associate with small vessel disease [5]. Cerebral microbleeds are usually incidental findings in patients undergoing magnetic resonance (MR) scanning for ischaemic stroke or intracerebral hemorrhage but occasionally appear to be causative in patients presenting with focal neurological symptoms [6]. Prior antithrombotic drug use as well as the recurrent intracerebral hemorrhages are associated with cerebral microbleeds [7]. However, as of yet, cerebral microbleeds have not been conclusively validated as a prognostic marker for future cerebrovascular events. Hence, therapeutic decisions on stroke prevention with antithrombotics or antiplatelet agents should not be based on the presence or absence of cerebral microbleeds alone. In an era of global mobility, determination of ethnic variability is also key when considering future treatment recommendations. Forthcoming research in the field of cerebral microbleeds needs to focus on its relationship with clinical comorbid conditions and the contribution to progressive neurological and/or cognitive deterioration. In their single center database on subsequent ischaemic stroke and TIA admissions, Horstmann and coworkers analyzed the relationship between comorbid characteristics and treatment factors with cerebral microbleed(s) detected on the admission susceptibility weighted imaging scan [8]. The strength of their study is the use of highly sensitive MR sequences; the weakness is probable selection bias and too small a sample size. Only 785 (35%) of 2226 prospective patients had MR scans and those included in the analysis were younger and less likely to be hypertensive, and fewer exhibited atrial fibrillation or received antithrombotics prior to their index stroke. The authors found cerebral microbleed(s) in a prevalence of 23.7% which is in line with the prevalence determined in healthy aged volunteers [4]. In Horstmann and coworkers’ registry only age correlated significantly with the detection of cerebral microbleed(s) on susceptibility weighted MR imaging
© 2015 EAN
using multivariate logistic regression. In their analysis, the age effect surmounts any other single comorbidity or treatment factor to predict cerebral microbleed(s). Patients pre-treated with antithrombotics and antiplatelet agents were more likely to have cerebral microbleeds while there was no difference in terms of pre-treatment with thrombolysis. Furthermore, prior anticoagulation may augment the number of cerebral microbleeds detected in cortical but not deep distribution. Although relatively large in size the registry presented by Horstmann and collaborators teaches us that future investigations zooming into effects of specific biomarkers to prognosticate cerebral microbleeds require much larger sample sizes than currently available. From a clinical perspective it can be deduced that in the absence of conclusive guidelines the patient’s chronological age weighs most heavily when deciding on the use of antiplatelet or antithrombotic agents in presenting with ischaemic stroke or TIA and incidental cerebral microbleeds. Further studies are needed to determine whether anticoagulants are permissive in patients with cerebral microbleeds and whether the cortical versus deep distribution of microbleeds has implications for the choice of secondary stroke prevention. The growing impact of atrial fibrillation as a stroke risk factor and the increasing popularity of antithrombotics, such as the novel oral anticoagulants in the elderly, urges further investigations into the most reliable stroke prevention for these patients.
D. W. Krieger Department of Neurology, Cerebrovascular Diseases, Stroke Center at Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
(e-mail: [email protected])
References 1. Greenberg SM, Eng JA, Ning M, Smith EE, Rosand J. Hemorrhage burden predicts recurrent intracerebral hemorrhage after lobar hemorrhage. Stroke 2004; 35: 1415–1420. 2. Cordonnier C, Al-Shahi Salman R, Wardlaw J. Spontaneous brain microbleeds: systematic review, subgroup analyses and standards for study design and reporting. Brain 2007; 130: 1988–2003.
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EUROPEAN JOURNAL OF NEUROLOGY
doi:10.1111/ene.12634
1328
EDITORIAL
3. Charidimou A, Kakar P, Fox Z, Werring DJ. Cerebral microbleeds and recurrent stroke risk: systematic review and meta-analysis of prospective ischemic stroke and transient ischemic attack cohorts. Stroke 2013; 44: 995–1001. 4. Vernooij MW, van der Lugt A, Ikram MA, et al. Prevalence and risk factors of cerebral microbleeds: the Rotterdam Scan Study. Neurology 2008; 70: 1208–1214. 5. Greenberg SM, Vernooij MW, Cordonnier C, et al. Cerebral microbleeds: a guide to detection and interpretation. Lancet Neurol 2009; 8: 165–174.
6. Werring DJ. Cerebral microbleeds: clinical and pathophysiological significance. J Neuroimaging 2007; 17: 193– 203. 7. Lovelock CE, Cordonnier C, Naka H, et al. Antithrombotic drug use, cerebral microbleeds, and intracerebral hemorrhage: a systematic review of published and unpublished studies. Stroke 2010; 41: 1222–1228. 8. Horstmann S, M€ uhlenbruch M, Wegele C, et al. Prevalence of atrial fibrillation and association of previous antithrombotic treatment in patients with cerebral microbleeds. Eur J Neurol 2015; 22: 1355–1362.
© 2015 EAN
Causation of cerebral microbleeds: more work is urgently needed
See paper by Horstmann et al. on page 1355.
Cerebral microbleeds are frequently detected in patients with intracerebral hemorrhages [1] and patients with ischaemic stroke or transient ischaemic attack (TIA) [2,3] but also in seemingly healthy ageing individuals [4]. Lobar microbleeds are considered to reflect amyloid angiopathy while deep microbleeds are thought to associate with small vessel disease [5]. Cerebral microbleeds are usually incidental findings in patients undergoing magnetic resonance (MR) scanning for ischaemic stroke or intracerebral hemorrhage but occasionally appear to be causative in patients presenting with focal neurological symptoms [6]. Prior antithrombotic drug use as well as the recurrent intracerebral hemorrhages are associated with cerebral microbleeds [7]. However, as of yet, cerebral microbleeds have not been conclusively validated as a prognostic marker for future cerebrovascular events. Hence, therapeutic decisions on stroke prevention with antithrombotics or antiplatelet agents should not be based on the presence or absence of cerebral microbleeds alone. In an era of global mobility, determination of ethnic variability is also key when considering future treatment recommendations. Forthcoming research in the field of cerebral microbleeds needs to focus on its relationship with clinical comorbid conditions and the contribution to progressive neurological and/or cognitive deterioration. In their single center database on subsequent ischaemic stroke and TIA admissions, Horstmann and coworkers analyzed the relationship between comorbid characteristics and treatment factors with cerebral microbleed(s) detected on the admission susceptibility weighted imaging scan [8]. The strength of their study is the use of highly sensitive MR sequences; the weakness is probable selection bias and too small a sample size. Only 785 (35%) of 2226 prospective patients had MR scans and those included in the analysis were younger and less likely to be hypertensive, and fewer exhibited atrial fibrillation or received antithrombotics prior to their index stroke. The authors found cerebral microbleed(s) in a prevalence of 23.7% which is in line with the prevalence determined in healthy aged volunteers [4]. In Horstmann and coworkers’ registry only age correlated significantly with the detection of cerebral microbleed(s) on susceptibility weighted MR imaging
© 2015 EAN
using multivariate logistic regression. In their analysis, the age effect surmounts any other single comorbidity or treatment factor to predict cerebral microbleed(s). Patients pre-treated with antithrombotics and antiplatelet agents were more likely to have cerebral microbleeds while there was no difference in terms of pre-treatment with thrombolysis. Furthermore, prior anticoagulation may augment the number of cerebral microbleeds detected in cortical but not deep distribution. Although relatively large in size the registry presented by Horstmann and collaborators teaches us that future investigations zooming into effects of specific biomarkers to prognosticate cerebral microbleeds require much larger sample sizes than currently available. From a clinical perspective it can be deduced that in the absence of conclusive guidelines the patient’s chronological age weighs most heavily when deciding on the use of antiplatelet or antithrombotic agents in presenting with ischaemic stroke or TIA and incidental cerebral microbleeds. Further studies are needed to determine whether anticoagulants are permissive in patients with cerebral microbleeds and whether the cortical versus deep distribution of microbleeds has implications for the choice of secondary stroke prevention. The growing impact of atrial fibrillation as a stroke risk factor and the increasing popularity of antithrombotics, such as the novel oral anticoagulants in the elderly, urges further investigations into the most reliable stroke prevention for these patients.
D. W. Krieger Department of Neurology, Cerebrovascular Diseases, Stroke Center at Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
(e-mail: [email protected])
References 1. Greenberg SM, Eng JA, Ning M, Smith EE, Rosand J. Hemorrhage burden predicts recurrent intracerebral hemorrhage after lobar hemorrhage. Stroke 2004; 35: 1415–1420. 2. Cordonnier C, Al-Shahi Salman R, Wardlaw J. Spontaneous brain microbleeds: systematic review, subgroup analyses and standards for study design and reporting. Brain 2007; 130: 1988–2003.
1327
EUROPEAN JOURNAL OF NEUROLOGY
doi:10.1111/ene.12634
1328
EDITORIAL
3. Charidimou A, Kakar P, Fox Z, Werring DJ. Cerebral microbleeds and recurrent stroke risk: systematic review and meta-analysis of prospective ischemic stroke and transient ischemic attack cohorts. Stroke 2013; 44: 995–1001. 4. Vernooij MW, van der Lugt A, Ikram MA, et al. Prevalence and risk factors of cerebral microbleeds: the Rotterdam Scan Study. Neurology 2008; 70: 1208–1214. 5. Greenberg SM, Vernooij MW, Cordonnier C, et al. Cerebral microbleeds: a guide to detection and interpretation. Lancet Neurol 2009; 8: 165–174.
6. Werring DJ. Cerebral microbleeds: clinical and pathophysiological significance. J Neuroimaging 2007; 17: 193– 203. 7. Lovelock CE, Cordonnier C, Naka H, et al. Antithrombotic drug use, cerebral microbleeds, and intracerebral hemorrhage: a systematic review of published and unpublished studies. Stroke 2010; 41: 1222–1228. 8. Horstmann S, M€ uhlenbruch M, Wegele C, et al. Prevalence of atrial fibrillation and association of previous antithrombotic treatment in patients with cerebral microbleeds. Eur J Neurol 2015; 22: 1355–1362.
© 2015 EAN
