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ARTICLES: C. Cordonnier, W. M. van der Flier, J. D. Sluimer, D. Leys, F. Barkhof, and P. Scheltens Prevalence and severity of microbleeds in a memory clinic setting Neurology 2006; 66: 1356-1360 [Abstract] [Full text] [PDF]

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Prevalence and severity of microbleeds in a memory clinic setting

Joseph S Jeret, MD, FAAN   (17 July 2006)

Reply from the authors

Charlotte Cordonnier, Wiesje M. van der Flier, Jasper D. Sluimer, Frederik Barkhof and Philip Scheltens   (17 July 2006)

Prevalence and severity of microbleeds in a memory clinic setting 17 July 2006
Joseph S Jeret, MD, FAAN, Mercy Medical Center 220 Maple Ave, Rockville Centre, NY 11570 Send Correspondence to journal: Re: Prevalence and severity of microbleeds in a memory clinic setting BrainsRus2{at}aol.com Joseph S Jeret, MD, FAAN	I read with interest the article by Cordonnier et al [1] outlining the association between cerebral microbleeds (MBs) and Alzheimer disease (AD) or mild cognitive impairment (MCI). In their final paragraph, they write that "MBs may be a predictor of future intracranial hemorrhages. Furthermore, detection of MBs may influence therapeutic decisions." This important discovery allows deeper insight into the plight of Ariel Sharon. In an article written by Sharon's physicians, including Dr. Ben-Hur, the head of Neurology at Hadassah University Medical Center [2], the authors state that there were "scattered old deep and subcortical microbleeds." As we know, Sharon was anticoagulated with low molecular weight heparin and suffered a massive cerebral hemorrhage 13 days later. There is a paucity of data on the safety of long-term anticoagulation in patients with MBs, and there is even less data on the short-term risks. Although the Israeli physicians carefully weighed risks and benefits, the new data from Cordonnier et al may have swayed their decision in favor of anti-platelet agents. Furthermore, I was troubled by Mr. Sharon's inconsistent behavior during the past several years. How could the man who risked his life to gain land and security for Israel have such a complete change in personality? There are hawks and there are doves--but they do not morph from one to the other. Could there be an underlying organic etiology? We know that Ronald Reagan had clinical signs of AD during portions of his presidency. The association of MBs with AD and MCI, as outlined by Cordonnier et al, may suggest that Sharon was also afflicted with cognitive dysfunction prior to his devastating strokes. References 1. Cordonnier C, van der Flier WM, Sluimer JD, Leys D, Barkhof F, Scheltens P. Prevalence and severity of microbleeds in a memory clinic setting Neurology 2006;66:1356-1360. 2. Ben-Hur T, Lotan C, Naparstek Y. Ariel Sharon's Stroke: The treatment he received - and why. Neurology Today 2006;6:8. Disclosure: The author reports no conflicts of interest.
Reply from the authors 17 July 2006
Charlotte Cordonnier, Department of Neurology and Alzheimer center Vrije Universteit Medical center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands, Wiesje M. van der Flier, Jasper D. Sluimer, Frederik Barkhof and Philip Scheltens Send Correspondence to journal: Re: Reply from the authors charlotte.cordonnier2{at}wanadoo.fr Charlotte Cordonnier, et al.	We read with interest Dr. Jeret’s comments on our article. Although beyond the scope of our article, he raises the interesting but difficult topic of risk/benefit of anticoagulation in patients with MBs. Based on the histologic data available on MBs, [3] there is a reason to suggest that MBs could predict future intracranial hemorrhages. This currently remains a hypothesis to be tested and proven. Six studies have examined the influence of MBs on the future risk of stroke, four in Asian populations [4-7] and only two in Caucasian populations. [8,9] The methods of analysis and the numbers of outcomes in these studies precluded a thorough analysis of future risk stratified by differences in drug treatment. No prospective study has ever assessed whether the risk of future intracranial hemorrhages in people treated with antiplatelet agents or anticoagulants is raised by the presence of MBs. As underlined by Dr Jeret, decision of treatment with anticoagulants, but also with antiplatets or thrombolytic agents, is difficult. Although MBs might be biomarkers of increased fragility of intracranial arteries, this has not been proven. Based on current evidence, there is no reason to preclude treatment with anticoagulants in the presence of MBs. Regarding the second point raised by Dr Jeret, our study pointed out that MBs are also frequent in neurodegenerative diseases such as Alzheimer’s disease and we interpreted this result as underlining the importance of vascular pathology in neurodegenerative processes. There is no data supporting that having MBs increases the likelihood of cognitive dysfunction; MBs are found in other non-dementing disorders too (Rendu-Osler; postraumatic; various cerebrovascular disorders). We hope our study has fuelled the interest and study into the clinical impact of MBs. References 3.Fazekas F, Kleinert R, Roob G, et al. Histopathologic analysis of foci of signal loss on gradient-echo T2*-weighted MR images in patients with spontaneous intracerebral hemorrhage: evidence of microangiopathy- related microbleeds. Ajnr: American Journal of Neuroradiology 1999;20:637- 642. 4.Fan YH, Zhang L, Lam WWM, Mok VCT, Wong KS. Cerebral microbleeds as a risk factor for subsequent intracerebral hemorrhages among patients with acute ischemic stroke. Stroke 2003;34:2459-2462. 5.Imaizumi T, Horita Y, Hashimoto Y, Niwa J. Dotlike hemosiderin spots on T2*-weighted magnetic resonance imaging as a predictor of stroke recurrence: a prospective study. Journal of Neurosurgery 2004;101:915-920. 6. Tsushima Y, Aoki J, Endo K. Brain microhemorrhages detected on T2*- weighted gradient-echo MR images. Ajnr: American Journal of Neuroradiology 2003;24:88-96. 7. Naka H, Nomura E, Takahashi T, et al. Combinations of the presence or absence of cerebral microbleeds and advanced white matter hyperintensity as predictors of subsequent stroke types. AJNR Am J Neuroradiol 2006;27:830-835. 8.Greenberg SM, Eng JA, Ning M, Smith EE, Rosand J. Hemorrhage burden predicts recurrent intracerebral hemorrhage after lobar hemorrhage. Stroke 2004;35:1415-1420. 9.Boulanger JM, Coutts SB, Eliasziw M, et al. Cerebral microhemorrhages predict new disabling or fatal strokes in patients with acute ischemic stroke or transient ischemic attack. Stroke 2006;37:911- 914. Disclosure: The authors report no conflicts of interest.