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ARTICLES: W. T. Kimberly, A. Gilson, N. S. Rost, J. Rosand, A. Viswanathan, E. E. Smith, and S. M. Greenberg Silent ischemic infarcts are associated with hemorrhage burden in cerebral amyloid angiopathy Neurology 2009; 72: 1230-1235 [Abstract] [Full text] [PDF]

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Silent ischemic infarcts are associated with hemorrhage burden in cerebral amyloid angiopathy

Yoko Okamoto, Yoko Okamoto, Masafumi Ihara, and Hidekazu Tomimoto.   (31 July 2009)

Reply from the authors

W. Taylor Kimberly, Steven M. Greenberg   (31 July 2009)

Silent ischemic infarcts are associated with hemorrhage burden in cerebral amyloid angiopathy 31 July 2009
Yoko Okamoto, Department of Neurology, Graduate School of Medicine, Kyoto University 54 Kawaharacho Shogoin Sakyo-ku, Kyoto City 606-8507, Japan, Yoko Okamoto, Masafumi Ihara, and Hidekazu Tomimoto. Send Correspondence to journal: Re: Silent ischemic infarcts are associated with hemorrhage burden in cerebral amyloid angiopathy yoko416{at}kuhp.kyoto-u.ac.jp Yoko Okamoto, et al.	We read the manuscript by Kimberly et al. [1] who showed that small subacute infarcts were detected on MRI in patients with advanced cerebral amyloid angiopathy (CAA). The authors retrospectively detected 17 DWI-hyperintense lesions in 78 subjects with probable CAA, but found no lesions in 55 subjects with Alzheimer disease (AD) or mild cognitive impairment. An association was not found between leukoaraiosis and the 17 ischemic lesions including four lesions found in the cortical gray matter. The distribution of microvascular lesions and the absence of their relation to leukoaraiosis is notable since CAA is usually observed in the subarachnoid and intracortical vessels, frequently accompanied by leukoaraiosis. In AD brains, cerebral microbleeds have shown occipital predominance and correspondence to parieto-occipital leukoaraiosis. [2] In addition, microinfarcts are typically found in the cortical borderzone with occipital predominance in demented subjects. [3] We further reported that microinfarcts were frequently detected in the cerebral cortices of postmortem AD brains, whereas they were rarely found in subcortical vascular dementia. [4] These cortical microinfarcts were distributed predominantly in proximity to amyloid b (A b )-deposited vessels with severe morphological changes. In terms of arterial supply and cortical layers, most were distributed in the posterior superficial borderzone, and mainly in the cortical layers 2-3. Predilection of microinfarcts in the borderzone may be attributed to insufficient Ab clearance in these regions, because pulsation of the vessels plays an important role in perivascular lymphatic drainage of Ab . [5] Taken together, differences may exist in regional distribution and relation to leukoaraiosis between CAA-related microvascular lesions with or without AD. References 1. Kimberly WT, Gilson A, Rost NS, et al. Silent ischemic infarcts are associated with hemorrhage burden in cerebral amyloid angiopathy. Neurology 2009;72:1230-1235. 2. Pettersen JA, Sathiyamoorthy G, Gao FQ, et al. Microbleed topography, leukoaraiosis, and cognition in probable Alzheimer disease from the Sunnybrook dementia study. Arch Neurol 2008;65:790-795. 3. Kövari E, Gold G, Herrmann FR, et al. Cortical microinfarcts and demyelination affect cognition in cases at high risk for dementia. Neurology 2007;68:927-931. 4. Okamoto Y, Ihara M, Fujita Y, et al. Cortical microinfarcts in Alzheimer's disease and subcortical vascular dementia. NeuroReport 2009;20:990-996. 5. Weller RO, Djuanda E, Yow HY, Carare RO. Lymphatic drainage of the brain and the pathophysiology of neurological disease. Acta Neuropathol 2009;117:1–14. Disclosure: The authors report no disclosures.
Reply from the authors 31 July 2009
W. Taylor Kimberly, MGH, Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital 175 Cambridge St, Boston, MA 02114, Steven M. Greenberg Send Correspondence to journal: Re: Reply from the authors sgreenberg{at}partners.org W. Taylor Kimberly, et al.	Okamoto et al. comment on their observation that microinfarcts are common in brains with AD, with predilection for the borderzone regions of the brain and for occurring near vascular amyloid deposits. The relation between these lesions and the microinfarcts observed in association with advanced cerebral amyloid angiopathy (CAA) is intriguing. Pathological specimens of CAA patients have not supported any specific vascular distribution for these lesions [6-8], but have generally not provided quantitative analysis of stroke burden within each region of the brain. Similarly, our cross-sectional MRI-based study did not demonstrate a borderzone predominance. This question is difficult to assess, however, since our analysis is limited by the small number of events and difficulty defining the precise location of the borderzone. We note that our control AD group excluded patients with microbleeds, thus minimizing the severity of CAA in this group. Our MRI data may therefore underestimate the incidence of microinfarcts in AD. References 6. Okazaki H, Reagan TJ, Campbell RJ. Clinicopathologic studies of primary cerebral amyloid angiopathy. Mayo Clinic Proceedings 1979;54:22-31. 7. Cadavid D, Mena H, Koeller K, Frommelt RA. Cerebral beta amyloid angiopathy is a risk factor for cerebral ischemic infarction. A case control study in human brain biopsies. Journal of Neuropathology & Experimental Neurology 2000;59:768-773. 8. Haglund M, Passant U, Sjobeck M, Ghebremedhin E, Englund E. Cerebral amyloid angiopathy and cortical microinfarcts as putative substrates of vascular dementia. Int J Geriatr Psychiatry 2006;21:681-687. Disclosures: Dr. Greenberg serves on the scientific advisory board for Hoffman-LaRoche and is funded by NIH RO1 AG026484 and K24 NS056207. Dr. Kimberly reports no disclosures.