(Stroke. 1997;28:652-659.)
© 1997 American Heart Association, Inc.
Articles |
Pathogenesis of Leukoaraiosis
A Review
From the Department of Pathology (Neuropathology), Henry Ford Hospital, Detroit, Mich (L.P., J.H.G.); the Department of Neurological and Psychiatric Sciences, University of Florence (Italy) (L.P.); and the Department of Pathology (Neuropathology), Case Western Reserve University, Cleveland, Ohio (J.H.G.).
Correspondence to Julio H. Garcia, MD, Department of Pathology (Neuropathology), Henry Ford Hospital/K-6, 2799 W Grand Blvd, Detroit, MI 48202.
Background Changes in the cerebral hemispheric white matter, detectable with increasing frequency by modern neuroimaging methods, are associated with aging and conceivably may contribute to the development of specific cognitive deficits. The pathogenesis of these cerebral white matter abnormalities (sometimes described as leukoaraiosis) is unknown. This review evaluates the available evidence in support of the hypothesis that the etiology of leukoaraiosis is related to a specific type of cerebral ischemia and highlights mechanisms by which ischemic injury to the brain may induce selected structural alterations limited to the cerebral white matter.
Summary of Review The review is based on the critical analysis of over 100 publications (most appearing in the last decade) dealing with the anatomy and physiology of the arterial circulation to the cerebral white matter and with the pathogenesis of leukoaraiosis.
Conclusions A significant number of clues support the hypothesis that some types of leukoaraiosis may be the result of ischemic injury to the brain. Structural changes affecting the small intraparenchymal cerebral arteries and arterioles that are associated with aging and with stroke risk factors, altered cerebral blood flow autoregulation, and the conditions created by the unique arterial blood supply of the hemispheric white matter each seem to contribute to the development of leukoaraiosis. To the best of our ability to interpret current information, the type of ischemic injury that is most likely responsible for these white matter changes involves transient repeated events characterized by moderate drops in regional cerebral blood flow that induce an incomplete form of infarction. This hypothesis could be tested in appropriate experimental models.
Key Words: cerebral ischemia • small-vessel disease • leukoaraiosis • leukoencephalopathy • white matter
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M. Torn, W. L. E. M. Bollen, F. J. M. van der Meer, E. E. van der Wall, and F. R. Rosendaal Risks of Oral Anticoagulant Therapy With Increasing Age Arch Intern Med, July 11, 2005; 165(13): 1527 - 1532. [Abstract] [Full Text] [PDF]
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S. Soljanlahti, T. Autti, K. Lauerma, R. Raininko, P. Keto, H. Turtola, and A. F. Vuorio Familial Hypercholesterolemia Patients Treated With Statins at No Increased Risk for Intracranial Vascular Lesions Despite Increased Cholesterol Burden and Extracranial Atherosclerosis Stroke, July 1, 2005; 36(7): 1572 - 1574. [Abstract] [Full Text] [PDF]
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H. S. Markus, B. Hunt, K. Palmer, C. Enzinger, H. Schmidt, and R. Schmidt Markers of Endothelial and Hemostatic Activation and Progression of Cerebral White Matter Hyperintensities: Longitudinal Results of the Austrian Stroke Prevention Study Stroke, July 1, 2005; 36(7): 1410 - 1414. [Abstract] [Full Text] [PDF]
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T. H. Mosley Jr, D. S. Knopman, D. J. Catellier, N. Bryan, R. G. Hutchinson, C. A. Grothues, A. R. Folsom, L. S. Cooper, G. L. Burke, D. Liao, et al. Cerebral MRI findings and cognitive functioning: The Atherosclerosis Risk in Communities Study Neurology, June 28, 2005; 64(12): 2056 - 2062. [Abstract] [Full Text] [PDF]
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M. D. Hill and J. D. Bisognano Leukoaraiosis: The brain under pressure: Target for treatment? Neurology, June 14, 2005; 64(11): 1832 - 1833. [Full Text] [PDF]
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I. B. Goldstein, G. Bartzokis, D. Guthrie, and D. Shapiro Ambulatory blood pressure and the brain: A 5-year follow-up Neurology, June 14, 2005; 64(11): 1846 - 1852. [Abstract] [Full Text] [PDF]
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J H Fu, C Z Lu, Z Hong, Q Dong, Y Luo, and K S Wong Extent of white matter lesions is related to acute subcortical infarcts and predicts further stroke risk in patients with first ever ischaemic stroke J. Neurol. Neurosurg. Psychiatry, June 1, 2005; 76(6): 793 - 796. [Abstract] [Full Text] [PDF]
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M. Ouhlous, H. Z. Flach, T. T. de Weert, J. M. Hendriks, M. R. H. M. van Sambeek, D. W. J. Dippel, P. M. T. Pattynama, and A. van der Lugt Carotid Plaque Composition and Cerebral Infarction: MR Imaging Study AJNR Am. J. Neuroradiol., May 1, 2005; 26(5): 1044 - 1049. [Abstract] [Full Text] [PDF]
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M. A. Ritter, D. W. Droste, K. Hegedus, R. Szepesi, D. G. Nabavi, L. Csiba, and E. B. Ringelstein Role of cerebral amyloid angiopathy in intracerebral hemorrhage in hypertensive patients Neurology, April 12, 2005; 64(7): 1233 - 1237. [Abstract] [Full Text] [PDF]
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S. T. Turner, M. Fornage, C. R. Jack Jr, T. H. Mosley, S. L. R. Kardia, E. Boerwinkle, and M. de Andrade Genomic Susceptibility Loci for Brain Atrophy in Hypertensive Sibships From the GENOA Study Hypertension, April 1, 2005; 45(4): 793 - 798. [Abstract] [Full Text] [PDF]
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P S Sachdev, W Wen, H Christensen, and A F Jorm White matter hyperintensities are related to physical disability and poor motor function J. Neurol. Neurosurg. Psychiatry, March 1, 2005; 76(3): 362 - 367. [Abstract] [Full Text] [PDF]
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 M. Alchanatis, N. Deligiorgis, N. Zias, A. Amfilochiou, E. Gotsis, A. Karakatsani, and A. Papadimitriou Frontal brain lobe impairment in obstructive sleep apnoea: a proton MR spectroscopy study Eur. Respir. J., December 1, 2004; 24(6): 980 - 986. [Abstract] [Full Text] [PDF]
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D. M. Moody, C. R. Thore, J. A. Anstrom, V. R. Challa, C. D. Langefeld, and W. R. Brown Quantification of Afferent Vessels Shows Reduced Brain Vascular Density in Subjects with Leukoaraiosis Radiology, December 1, 2004; 233(3): 883 - 890. [Abstract] [Full Text] [PDF]
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E. E. Smith, M. E. Gurol, J. A. Eng, C. R. Engel, T. N. Nguyen, J. Rosand, and S. M. Greenberg White matter lesions, cognition, and recurrent hemorrhage in lobar intracerebral hemorrhage Neurology, November 9, 2004; 63(9): 1606 - 1612. [Abstract] [Full Text] [PDF]
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M. Shibata, R. Ohtani, M. Ihara, and H. Tomimoto White Matter Lesions and Glial Activation in a Novel Mouse Model of Chronic Cerebral Hypoperfusion Stroke, November 1, 2004; 35(11): 2598 - 2603. [Abstract] [Full Text] [PDF]
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E. J. van Dijk, M. M.B. Breteler, R. Schmidt, K. Berger, L.-G. Nilsson, M. Oudkerk, A. Pajak, S. Sans, M. de Ridder, C. Dufouil, et al. The Association Between Blood Pressure, Hypertension, and Cerebral White Matter Lesions: Cardiovascular Determinants of Dementia Study Hypertension, November 1, 2004; 44(5): 625 - 630. [Abstract] [Full Text] [PDF]
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J. van der Grond, A. F. van Raamt, Y. van der Graaf, W. P.T.M. Mali, and R. H.C. Bisschops A fetal circle of Willis is associated with a decreased deep white matter lesion load Neurology, October 26, 2004; 63(8): 1452 - 1456. [Abstract] [Full Text] [PDF]
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N. D. Prins, E. J. van Dijk, T. den Heijer, S. E. Vermeer, P. J. Koudstaal, M. Oudkerk, A. Hofman, and M. M. B. Breteler Cerebral White Matter Lesions and the Risk of Dementia Arch Neurol, October 1, 2004; 61(10): 1531 - 1534. [Abstract] [Full Text] [PDF]
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D. J. Werring, D. W. Frazer, L. J. Coward, N. A. Losseff, H. Watt, L. Cipolotti, M. M. Brown, and H. R. Jager Cognitive dysfunction in patients with cerebral microbleeds on T2*-weighted gradient-echo MRI Brain, October 1, 2004; 127(10): 2265 - 2275. [Abstract] [Full Text] [PDF]
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S Artero, H Tiemeier, N D Prins, R Sabatier, M M B Breteler, and K Ritchie Neuroanatomical localisation and clinical correlates of white matter lesions in the elderly J. Neurol. Neurosurg. Psychiatry, September 1, 2004; 75(9): 1304 - 1308. [Abstract] [Full Text] [PDF]
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P. Sachdev, R. Parslow, C. Salonikas, O. Lux, W. Wen, R. Kumar, D. Naidoo, H. Christensen, and A. Jorm Homocysteine and the Brain in Midadult Life: Evidence for an Increased Risk of Leukoaraiosis in Men Arch Neurol, September 1, 2004; 61(9): 1369 - 1376. [Abstract] [Full Text] [PDF]
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 H. Shibata, T. Nabika, H. Moriyama, J. Masuda, and S. Kobayashi Correlation of NO Metabolites and 8-Iso-Prostaglandin F2a With Periventricular Hyperintensity Severity Arterioscler Thromb Vasc Biol, September 1, 2004; 24(9): 1659 - 1663. [Abstract] [Full Text] [PDF]
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H.-K. Kuo and L. A. Lipsitz Cerebral White Matter Changes and Geriatric Syndromes: Is There a Link? J. Gerontol. A Biol. Sci. Med. Sci., August 1, 2004; 59(8): M818 - M826. [Abstract] [Full Text] [PDF]
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L. H. Kuller, W.T. Longstreth Jr, A. M. Arnold, C. Bernick, R. Nick Bryan, N. J. Beauchamp Jr, and for the Cardiovascular Health Study Collaborative White Matter Hyperintensity on Cranial Magnetic Resonance Imaging: A Predictor of Stroke Stroke, August 1, 2004; 35(8): 1821 - 1825. [Abstract] [Full Text] [PDF]
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