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Cerebral Microbleeds, Small-Vessel Disease of the Brain, Hypertension, and Cognition

  • Anand Viswanathan
  • Hugues Chabriat
  • Steven M. Greenberg
Chapter
Part of the Clinical Hypertension and Vascular Diseases book series (CHVD)

Abstract

Cerebral microbleeds (CMB) have been increasingly recognized on neuroimaging since the widespread application of magnetic resonance imaging (MRI) techniques tailored to detect foci of magnetic susceptibility. CMB are most often clinically asymptomatic and are a result of rupture of small blood vessels in basal ganglia or subcortical white matter (AJNR Am J Neuroradiol. 1999;20:637–42; Lancet Neurol. 2009;8:165–74; Stroke. 2006;37:550–5; Brain. 2007;130:1988–2003). CMB were first described after the clinical use of gradient-echo (GRE) or T2*-weighted MRI (AJNR Am J Neuroradiol. 1999;20:637–42; Neuroradiology. 1994;36:504–8; AJNR Am J Neuroradiol. 1996;17:573–8). GRE MRI is a technique highly sensitive in the detection of old and recent cerebral hemorrhage (AJNR Am J Neuroradiol. 1999;20:637–42; AJNR Am J Neuroradiol. 1996;17:573–8). The reduction of the signal on GRE sequences is caused by hemosiderin, a blood breakdown product which causes magnetic susceptibility-induced dephasing leading to T2* signal loss. CMB appear larger on GRE sequences as compared to the actual tissue lesions because of the so-called blooming effect of the MR signal at the border of these lesions (Neuroradiology. 2004;46:435–43; Acta Radiol. 2003;44:199–205). GRE MRI can detect millimeter-sized paramagnetic blood products (including hemosiderin) in brain parenchyma (Radiology. 1988;168:803–7). As hemosiderin remains in macrophages for many years after hemorrhage (Neurology. 1996;46:1751–4; Curr Opin Neurol. 2000;13:69–73), GRE sequences allow for reliable assessment of an individual’s hemorrhagic burden over time. Furthermore, more recent technical advances in MRI software and hardware have yielded significant improvements in sensitivity, which has led to increased detection of CMB in different populations (AJNR Am J Neuroradiol. 2007;28:316–7; AJNR Am J Neuroradiol. 2009;30:19–30; AJNR Am J Neuroradiol. 2009;30(2):338–43; Neurology. 2008;70:1208–14). Novel techniques such as susceptibility-weighted imaging (SWI) have considerably increased CMB detection rates.

Keywords

Microbleeds Cerebral microhemorrhage Small-vessel disease Hypertension Petechial hemorrhage Hemorrhage in small-vessel disease Cerebral microbleeds 

Notes

Acknowledgment

The authors have no financial disclosures to report.

References

  1. 1.
    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 Am J Neuroradiol. 1999;20:637–42.PubMedGoogle Scholar
  2. 2.
    Greenberg SM, Vernooij MW, Cordonnier C, et al. Cerebral microbleeds: a guide to detection and interpretation. Lancet Neurol. 2009;8:165–74.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Viswanathan A, Chabriat H. Cerebral microhemorrhage. Stroke. 2006;37:550–5.CrossRefPubMedGoogle Scholar
  4. 4.
    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.CrossRefPubMedGoogle Scholar
  5. 5.
    Scharf J, Brauherr E, Forsting M, Sartor K. Significance of haemorrhagic lacunes on MRI in patients with hypertensive cerebrovascular disease and intracerebral haemorrhage. Neuroradiology. 1994;36:504–8.CrossRefPubMedGoogle Scholar
  6. 6.
    Offenbacher H, Fazekas F, Schmidt R, Koch M, Fazekas G, Kapeller P. MR of cerebral abnormalities concomitant with primary intracerebral hematomas. AJNR Am J Neuroradiol. 1996;17:573–8.PubMedGoogle Scholar
  7. 7.
    Alemany Ripoll M, Stenborg A, Sonninen P, Terent A, Raininko R. Detection and appearance of intraparenchymal haematomas of the brain at 1.5 T with spin-echo, FLAIR and GE sequences: poor relationship to the age of the haematoma. Neuroradiology. 2004;46:435–43.CrossRefPubMedGoogle Scholar
  8. 8.
    Ripoll MA, Siosteen B, Hartman M, Raininko R. MR detectability and appearance of small experimental intracranial hematomas at 1.5 T and 0.5 T. A 6-7-month follow-up study. Acta Radiol. 2003;44:199–205.CrossRefPubMedGoogle Scholar
  9. 9.
    Atlas SW, Mark AS, Grossman RI, Gomori JM. Intracranial hemorrhage: gradient-echo MR imaging at 1.5 T. Comparison with spin-echo imaging and clinical applications. Radiology. 1988;168:803–7.CrossRefPubMedGoogle Scholar
  10. 10.
    Greenberg SM, Finklestein SP, Schaefer PW. Petechial hemorrhages accompanying lobar hemorrhage: detection by gradient-echo MRI. Neurology. 1996;46:1751–4.CrossRefPubMedGoogle Scholar
  11. 11.
    Roob G, Fazekas F. Magnetic resonance imaging of cerebral microbleeds. Curr Opin Neurol. 2000;13:69–73.CrossRefPubMedGoogle Scholar
  12. 12.
    Haacke EM, DelProposto ZS, Chaturvedi S, et al. Imaging cerebral amyloid angiopathy with susceptibility-weighted imaging. AJNR Am J Neuroradiol. 2007;28:316–7.PubMedGoogle Scholar
  13. 13.
    Haacke EM, Mittal S, Wu Z, Neelavalli J, Cheng YC. Susceptibility-weighted imaging: technical aspects and clinical applications, part 1. AJNR Am J Neuroradiol. 2009;30:19–30.CrossRefPubMedGoogle Scholar
  14. 14.
    Nandigam RN, Viswanathan A, Delgado P, et al. MR imaging detection of cerebral microbleeds: effect of susceptibility-weighted imaging, section thickness, and field strength. AJNR Am J Neuroradiol. 2009;30(2):338–43.CrossRefPubMedGoogle Scholar
  15. 15.
    Vernooij MW, van der Lugt A, Ikram MA, et al. Prevalence and risk factors of cerebral microbleeds: the Rotterdam Scan Study. Neurology. 2008;70:1208–14.CrossRefPubMedGoogle Scholar
  16. 16.
    Greenberg SM, Eng JA, Ning M, Smith EE, Rosand J. Hemorrhage burden predicts recurrent intracerebral hemorrhage after lobar hemorrhage. Stroke. 2004;35:1415–20.CrossRefPubMedGoogle Scholar
  17. 17.
    Tanaka A, Ueno Y, Nakayama Y, Takano K, Takebayashi S. Small chronic hemorrhages and ischemic lesions in association with spontaneous intracerebral hematomas. Stroke. 1999;30:1637–42.CrossRefPubMedGoogle Scholar
  18. 18.
    Fisher CM. Pathological observations in hypertensive cerebral hemorrhage. J Neuropathol Exp Neurol. 1971;30:536–50.CrossRefPubMedGoogle Scholar
  19. 19.
    Vinters HV, Natte R, Maat-Schieman ML, et al. Secondary microvascular degeneration in amyloid angiopathy of patients with hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA-D). Acta Neuropathol. 1998;95:235–44.CrossRefPubMedGoogle Scholar
  20. 20.
    Vonsattel JP, Myers RH, Hedley-Whyte ET, Ropper AH, Bird ED, Richardson Jr EP. Cerebral amyloid angiopathy without and with cerebral hemorrhages: a comparative histological study. Ann Neurol. 1991;30:637–49.CrossRefPubMedGoogle Scholar
  21. 21.
    Vinters HV. Cerebral amyloid angiopathy. A critical review. Stroke. 1987;18:311–24.CrossRefPubMedGoogle Scholar
  22. 22.
    Viswanathan A, Guichard JP, Gschwendtner A, et al. Blood pressure and haemoglobin A1c are associated with microhaemorrhage in CADASIL: a two-centre cohort study. Brain. 2006;129:2375–83.CrossRefPubMedGoogle Scholar
  23. 23.
    Dichgans M, Holtmannspotter M, Herzog J, Peters N, Bergmann M, Yousry TA. Cerebral microbleeds in CADASIL: a gradient-echo magnetic resonance imaging and autopsy study. Stroke. 2002;33:67–71.CrossRefPubMedGoogle Scholar
  24. 24.
    Lesnik Oberstein SA, van den Boom R, van Buchem MA, et al. Cerebral microbleeds in CADASIL. Neurology. 2001;57:1066–70.CrossRefPubMedGoogle Scholar
  25. 25.
    van den Boom R, Lesnik Oberstein SA, Ferrari MD, Haan J, van Buchem MA. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: MR imaging findings at different ages--3rd-6th decades. Radiology. 2003;229:683–90.CrossRefPubMedGoogle Scholar
  26. 26.
    Copenhaver BR, Hsia AW, Merino JG, et al. Racial differences in microbleed prevalence in primary intracerebral hemorrhage. Neurology. 2008;71:1176–82.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Zhang JB, Liu LF, Li ZG, Sun HR, Ju XH. Associations between biomarkers of renal function with cerebral microbleeds in hypertensive patients. Am J Hypertens. 2015;28:739–45.CrossRefPubMedGoogle Scholar
  28. 28.
    Wolf PA. Cerebrovascular risk. In: Izzo JL, Black HR, editors. Hypertension primer: the essentials of high blood pressure. New York: Lippincott, Williams & Wilkins; 2003. p. 239–42.Google Scholar
  29. 29.
    Wolf PA. Epidemiology of stroke. In: Mohr JP, Choi DW, Grotta JC, Weir B, Wolf PA, editors. Stroke: pathophysiology, diagnosis, and management. Philadelphia: Churchill Livingstone; 2004. p. 13–34.CrossRefGoogle Scholar
  30. 30.
    Kato H, Izumiyama M, Izumiyama K, Takahashi A, Itoyama Y. Silent cerebral microbleeds on T2*-weighted MRI: correlation with stroke subtype, stroke recurrence, and leukoaraiosis. Stroke. 2002;33:1536–40.CrossRefPubMedGoogle Scholar
  31. 31.
    Kinoshita T, Okudera T, Tamura H, Ogawa T, Hatazawa J. Assessment of lacunar hemorrhage associated with hypertensive stroke by echo-planar gradient-echo T2*-weighted MRI. Stroke. 2000;31:1646–50.CrossRefPubMedGoogle Scholar
  32. 32.
    Kwa VI, Franke CL, Verbeeten Jr B, Stam J. Silent intracerebral microhemorrhages in patients with ischemic stroke. Amsterdam Vascular Medicine Group. Ann Neurol. 1998;44:372–7.CrossRefPubMedGoogle Scholar
  33. 33.
    Fan YH, Mok VC, Lam WW, Hui AC, Wong KS. Cerebral microbleeds and white matter changes in patients hospitalized with lacunar infarcts. J Neurol. 2004;251:537–41.CrossRefPubMedGoogle Scholar
  34. 34.
    Lee SH, Bae HJ, Yoon BW, Kim H, Kim DE, Roh JK. Low concentration of serum total cholesterol is associated with multifocal signal loss lesions on gradient-echo magnetic resonance imaging: analysis of risk factors for multifocal signal loss lesions. Stroke. 2002;33:2845–9.CrossRefPubMedGoogle Scholar
  35. 35.
    Tsushima Y, Aoki J, Endo K. Brain microhemorrhages detected on T2*-weighted gradient-echo MR images. AJNR Am J Neuroradiol. 2003;24:88–96.PubMedGoogle Scholar
  36. 36.
    Lee SH, Park JM, Kwon SJ, et al. Left ventricular hypertrophy is associated with cerebral microbleeds in hypertensive patients. Neurology. 2004;63:16–21.CrossRefPubMedGoogle Scholar
  37. 37.
    Roob G, Lechner A, Schmidt R, Flooh E, Hartung HP, Fazekas F. Frequency and location of microbleeds in patients with primary intracerebral hemorrhage. Stroke. 2000;31:2665–9.CrossRefPubMedGoogle Scholar
  38. 38.
    Lee SH, Bae HJ, Kwon SJ, et al. Cerebral microbleeds are regionally associated with intracerebral hemorrhage. Neurology. 2004;62:72–6.CrossRefPubMedGoogle Scholar
  39. 39.
    Jeong SW, Jung KH, Chu K, Bae HJ, Lee SH, Roh JK. Clinical and radiologic differences between primary intracerebral hemorrhage with and without microbleeds on gradient-echo magnetic resonance images. Arch Neurol. 2004;61:905–9.CrossRefPubMedGoogle Scholar
  40. 40.
    Lee SH, Kim SM, Kim N, Yoon BW, Roh JK. Cortico-subcortical distribution of microbleeds is different between hypertension and cerebral amyloid angiopathy. J Neurol Sci. 2007;258:111–4.CrossRefPubMedGoogle Scholar
  41. 41.
    Knudsen KA, Rosand J, Karluk D, Greenberg SM. Clinical diagnosis of cerebral amyloid angiopathy: validation of the Boston criteria. Neurology. 2001;56:537–9.CrossRefPubMedGoogle Scholar
  42. 42.
    Martinez-Ramirez SRJ, Shoamanesh A, McKee AC, Van-Etten E, Pontes-Neto O, Macklin EA, Ayres AM, Auriel E, Himali JJ, Beiser AS, DeCarli C, Stein TD, Alvarez VE, Frosch MP, Rosand J, Greenberg SM, Gurol ME, Seshadri S, Viswanathan A. Diagnostic value of lobar microbleeds in individuals without intracerebral hemorrhage. Alzheimers Dement. 2015;11(12):1480–8.CrossRefPubMedGoogle Scholar
  43. 43.
    Rosand J, Muzikansky A, Kumar A, et al. Spatial clustering of hemorrhages in probable cerebral amyloid angiopathy. Ann Neurol. 2005;58(3):459–62.CrossRefPubMedGoogle Scholar
  44. 44.
    Ropper AH, Davis KR. Lobar cerebral hemorrhages: acute clinical syndromes in 26 cases. Ann Neurol. 1980;8:141–7.CrossRefPubMedGoogle Scholar
  45. 45.
    Kase CS, Williams JP, Wyatt DA, Mohr JP. Lobar intracerebral hematomas: clinical and CT analysis of 22 cases. Neurology. 1982;32:1146–50.CrossRefPubMedGoogle Scholar
  46. 46.
    Pfeifer LA, White LR, Ross GW, Petrovitch H, Launer LJ. Cerebral amyloid angiopathy and cognitive function: the HAAS autopsy study. Neurology. 2002;58:1629–34.CrossRefPubMedGoogle Scholar
  47. 47.
    Vinters HV, Gilbert JJ. Cerebral amyloid angiopathy: incidence and complications in the aging brain. II. The distribution of amyloid vascular changes. Stroke. 1983;14:924–8.CrossRefPubMedGoogle Scholar
  48. 48.
    Chabriat H, Bousser MG. CADASIL. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Adv Neurol. 2003;92:147–50.PubMedGoogle Scholar
  49. 49.
    Singhal S, Bevan S, Barrick T, Rich P, Markus HS. The influence of genetic and cardiovascular risk factors on the CADASIL phenotype. Brain. 2004;127:2031–8.CrossRefPubMedGoogle Scholar
  50. 50.
    Ruchoux MM, Maurage CA. CADASIL: cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. J Neuropathol Exp Neurol. 1997;56:947–64.CrossRefPubMedGoogle Scholar
  51. 51.
    Lee JS, Kang CH, Park SQ, Choi HA, Sim KB. Clinical significance of cerebral microbleeds locations in CADASIL with R544C NOTCH3 mutation. PLoS One. 2015;10:e0118163.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Vernooij MW, Ikram MA, Wielopolski PA, Krestin GP, Breteler MM, van der Lugt A. Cerebral microbleeds: accelerated 3D T2*-weighted GRE MR imaging versus conventional 2D T2*-weighted GRE MR imaging for detection. Radiology. 2008;248:272–7.CrossRefPubMedGoogle Scholar
  53. 53.
    Cheng AL, Batool S, McCreary CR, et al. Susceptibility-weighted imaging is more reliable than T2*-weighted gradient-recalled echo MRI for detecting microbleeds. Stroke. 2013;44(10):2782–6.CrossRefPubMedGoogle Scholar
  54. 54.
    Goos JD, van der Flier WM, Knol DL, et al. Clinical relevance of improved microbleed detection by susceptibility-weighted magnetic resonance imaging. Stroke. 2011;42:1894–900.CrossRefPubMedGoogle Scholar
  55. 55.
    Tsushima Y, Tanizaki Y, Aoki J, Endo K. MR detection of microhemorrhages in neurologically healthy adults. Neuroradiology. 2002;44:31–6.CrossRefPubMedGoogle Scholar
  56. 56.
    Roob G, Schmidt R, Kapeller P, Lechner A, Hartung HP, Fazekas F. MRI evidence of past cerebral microbleeds in a healthy elderly population. Neurology. 1999;52:991–4.CrossRefPubMedGoogle Scholar
  57. 57.
    Lee SH, Bae HJ, Ko SB, Kim H, Yoon BW, Roh JK. Comparative analysis of the spatial distribution and severity of cerebral microbleeds and old lacunes. J Neurol Neurosurg Psychiatry. 2004;75:423–7.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Horita Y, Imaizumi T, Niwa J, et al. Analysis of dot-like hemosiderin spots using brain dock system. No Shinkei Geka. 2003;31:263–7.PubMedGoogle Scholar
  59. 59.
    Jeerakathil T, Wolf PA, Beiser A, et al. Cerebral microbleeds: prevalence and associations with cardiovascular risk factors in the Framingham Study. Stroke. 2004;35:1831–5.CrossRefPubMedGoogle Scholar
  60. 60.
    Romero JR, Preis SR, Beiser A, et al. Risk factors, stroke prevention treatments, and prevalence of cerebral microbleeds in the Framingham Heart Study. Stroke. 2014;45:1492–4.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Sveinbjornsdottir S, Sigurdsson S, Aspelund T, et al. Cerebral microbleeds in the population based AGES-Reykjavik study: prevalence and location. J Neurol Neurosurg Psychiatry. 2008;79:1002–6.CrossRefPubMedGoogle Scholar
  62. 62.
    Poels MM, Ikram MA, van der Lugt A, et al. Incidence of cerebral microbleeds in the general population: the Rotterdam Scan Study. Stroke. 2011;42:656–61.CrossRefPubMedGoogle Scholar
  63. 63.
    O’Donnell HC, Rosand J, Knudsen KA, et al. Apolipoprotein E genotype and the risk of recurrent lobar intracerebral hemorrhage. N Engl J Med. 2000;342:240–5.CrossRefPubMedGoogle Scholar
  64. 64.
    Tatsumi S, Shinohara M, Yamamoto T. Direct comparison of histology of microbleeds with postmortem MR images: a case report. Cerebrovasc Dis. 2008;26:142–6.CrossRefPubMedGoogle Scholar
  65. 65.
    Greenberg SM, O’Donnell HC, Schaefer PW, Kraft E. MRI detection of new hemorrhages: potential marker of progression in cerebral amyloid angiopathy. Neurology. 1999;53:1135–8.CrossRefPubMedGoogle Scholar
  66. 66.
    Viswanathan A, Godin O, Jouvent E, et al. Impact of MRI markers in subcortical vascular dementia: a multi-modal analysis in CADASIL. Neurobiol Aging. 2010;31(9):1629–36.CrossRefPubMedGoogle Scholar
  67. 67.
    Werring DJ, Frazer DW, Coward LJ, et al. Cognitive dysfunction in patients with cerebral microbleeds on T2*-weighted gradient-echo MRI. Brain. 2004;127:2265–75.CrossRefPubMedGoogle Scholar
  68. 68.
    Henneman WJ, Sluimer JD, Cordonnier C, et al. MRI biomarkers of vascular damage and atrophy predicting mortality in a memory clinic population. Stroke. 2009;40:492–8.CrossRefPubMedGoogle Scholar
  69. 69.
    Yakushiji Y, Noguchi T, Charidimou A, et al. Basal ganglia cerebral microbleeds and global cognitive function: the Kashima Scan Study. J Stroke Cerebrovasc Dis. 2015;24:431–9.CrossRefPubMedGoogle Scholar
  70. 70.
    Kivipelto M, Helkala EL, Laakso MP, et al. Midlife vascular risk factors and Alzheimer’s disease in later life: longitudinal, population based study. BMJ. 2001;322:1447–51.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Skoog I, Lernfelt B, Landahl S, et al. 15-year longitudinal study of blood pressure and dementia. Lancet. 1996;347:1141–5.CrossRefPubMedGoogle Scholar
  72. 72.
    Mielke MM, Rosenberg PB, Tschanz J, et al. Vascular factors predict rate of progression in Alzheimer disease. Neurology. 2007;69:1850–8.CrossRefPubMedGoogle Scholar
  73. 73.
    Tzourio C, Anderson C, Chapman N, et al. Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease. Arch Intern Med. 2003;163:1069–75.CrossRefPubMedGoogle Scholar
  74. 74.
    Dufouil C, Chalmers J, Coskun O, et al. Effects of blood pressure lowering on cerebral white matter hyperintensities in patients with stroke: the PROGRESS (Perindopril Protection Against Recurrent Stroke Study) Magnetic Resonance Imaging Substudy. Circulation. 2005;112:1644–50.CrossRefPubMedGoogle Scholar
  75. 75.
    Firbank MJ, Wiseman RM, Burton EJ, Saxby BK, O’Brien JT, Ford GA. Brain atrophy and white matter hyperintensity change in older adults and relationship to blood pressure. Brain atrophy, WMH change and blood pressure. J Neurol. 2007;254:713–21.CrossRefPubMedGoogle Scholar
  76. 76.
    Saxby BK, Harrington F, Wesnes KA, McKeith IG, Ford GA. Candesartan and cognitive decline in older patients with hypertension: a substudy of the SCOPE trial. Neurology. 2008;70:1858–66.CrossRefPubMedGoogle Scholar
  77. 77.
    Uiterwijk R, Huijts M, Staals J, et al. Subjective cognitive failures in patients with hypertension are related to cognitive performance and cerebral microbleeds. Hypertension. 2014;64:653–7.CrossRefPubMedGoogle Scholar
  78. 78.
    van Norden AG, van Uden IW, de Laat KF, et al. Cerebral microbleeds are related to subjective cognitive failures: the RUN DMC study. Neurobiol Aging. 2013;34:2225–30.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Anand Viswanathan
    • 1
  • Hugues Chabriat
    • 2
  • Steven M. Greenberg
    • 3
  1. 1.Stroke Service and Memory Disorders UnitDepartment of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical SchoolBostonUSA
  2. 2.Department of NeurologyCHU Lariboisière, Assistance Publique des Hôpitaux de ParisParisFrance
  3. 3.Stroke Service, Department of NeurologyMassachusetts General Hospital Stroke Research Center, Harvard Medical SchoolBostonUSA

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