Neuroradiology

, Volume 55, Issue 6, pp 655–674 | Cite as

Cerebral microbleeds: a guide to detection and clinical relevance in different disease settings

  • Andreas Charidimou
  • Anant Krishnan
  • David J. Werring
  • H. Rolf Jäger
CONTINUING EDUCATION

Abstract

Cerebral microbleeds have emerged as an important new imaging marker of cerebral small vessel disease. With the development of MRI techniques that are exquisitely sensitive to paramagnetic blood products, such as T2*-weighted gradient-recalled echo and susceptibility-weighted sequences, microbleeds have been detected in ever-increasing numbers of patients in stroke and cognitive clinics, as well as in healthy older people and in a variety of other rarer diseases and syndromes. Detection of cerebral microbleeds has clinical implications with respect to the diagnosis of the underlying small vessel disease, the safety of antithrombotic use, and the risk of symptomatic intracerebral haemorrhage, cognitive impairment and dementia. This article provides a guide to the detection and clinical relevance of cerebral microbleeds in different conditions based on a comprehensive review of the literature and own findings in research and clinical practice.

Keywords

Cerebral microbleeds Cerebral small vessel disease Susceptibility-weighted imaging Cerebral amyloid angiopathy Intracerebral haemorrhage 

Notes

Acknowledgments

AC receives research support from the Greek State Scholarship Foundation, Stroke Association and British Heart Foundation. DW is supported by a Department of Health and Higher Educational and Funding Council for England Clinical Senior Lectureship Award, the Stroke Association and British Heart Foundation. This work was undertaken at UCLH/UCL, who received a proportion of funding from the UK Department of Health’s National Institute for Health Research Biomedical Research Centres funding scheme. HRJ is supported by the National Institute for Health Research, University College London Hospitals Biomedical Research Centre, Stroke Association and British Heart Foundation.

Conflict of interest

We declare that we have no conflict of interest.

References

  1. 1.
    Scharf J, Brauherr E, Forsting M, Sartor K (1994) Significance of haemorrhagic lacunes on MRI in patients with hypertensive cerebrovascular disease and intracerebral haemorrhage. Neuroradiology 36(7):504–508PubMedCrossRefGoogle Scholar
  2. 2.
    Offenbacher H, Fazekas F, Schmidt R, Koch M, Fazekas G, Kapeller P (1996) MR of cerebral abnormalities concomitant with primary intracerebral hematomas. AJNR Am J Neuroradiol 17(3):573–578PubMedGoogle Scholar
  3. 3.
    Werring D (2011) Cerebral microbleeds: pathophysiology to clinical practice. University Press, CambridgeCrossRefGoogle Scholar
  4. 4.
    Greenberg SM, Vernooij MW, Cordonnier C, Viswanathan A, Al-Shahi Salman R, Warach S, Launer LJ, Van Buchem MA, Breteler MM, Microbleed Study G (2009) Cerebral microbleeds: a guide to detection and interpretation. Lancet Neurol 8(2):165–174PubMedCrossRefGoogle Scholar
  5. 5.
    Cordonnier C, Al-Shahi Salman R, Wardlaw J (2007) Spontaneous brain microbleeds: systematic review, subgroup analyses and standards for study design and reporting. Brain 130(Pt 8):1988–2003PubMedCrossRefGoogle Scholar
  6. 6.
    Fazekas F, Kleinert R, Roob G, Kleinert G, Kapeller P, Schmidt R, Hartung HP (1999) 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 20(4):637–642PubMedGoogle Scholar
  7. 7.
    Shoamanesh A, Kwok CS, Benavente O (2011) Cerebral microbleeds: histopathological correlation of neuroimaging. Cerebrovasc Dis 32(6):528–534PubMedCrossRefGoogle Scholar
  8. 8.
    Schrag M, McAuley G, Pomakian J, Jiffry A, Tung S, Mueller C, Vinters HV, Haacke EM, Holshouser B, Kido D, Kirsch WM (2009) Correlation of hypointensities in susceptibility-weighted images to tissue histology in dementia patients with cerebral amyloid angiopathy: a postmortem MRI study. Acta Neuropathol 119(3):291–302CrossRefGoogle Scholar
  9. 9.
    Charidimou A, Werring DJ (2011) Cerebral microbleeds: detection, mechanisms and clinical challenges. Futur Neurol 6(5):587–611CrossRefGoogle Scholar
  10. 10.
    Poels MM, Vernooij MW, Ikram MA, Hofman A, Krestin GP, van der Lugt A, Breteler MM (2010) Prevalence and risk factors of cerebral microbleeds: an update of the Rotterdam scan study. Stroke 41(10 Suppl):S103–106PubMedCrossRefGoogle Scholar
  11. 11.
    Sveinbjornsdottir S, Sigurdsson S, Aspelund T, Kjartansson O, Eiriksdottir G, Valtysdottir B, Lopez OL, van Buchem MA, Jonsson PV, Gudnason V, Launer LJ (2008) Cerebral microbleeds in the population based AGES-Reykjavik study: prevalence and location. J Neurol Neurosurg Psychiatry 79(9):1002–1006PubMedCrossRefGoogle Scholar
  12. 12.
    Werring DJ, Coward LJ, Losseff NA, Jager HR, Brown MM (2005) Cerebral microbleeds are common in ischemic stroke but rare in TIA. Neurology 65(12):1914–1918PubMedCrossRefGoogle Scholar
  13. 13.
    Pettersen JA, Sathiyamoorthy G, Gao FQ, Szilagyi G, Nadkarni NK, St George-Hyslop P, Rogaeva E, Black SE (2008) Microbleed topography, leukoaraiosis, and cognition in probable Alzheimer disease from the Sunnybrook dementia study. Arch Neurol 65(6):790–795PubMedCrossRefGoogle Scholar
  14. 14.
    Cordonnier C, van der Flier WM (2011) Brain microbleeds and Alzheimer’s disease: innocent observation or key player? Brain 134(Pt 2):335–344PubMedCrossRefGoogle Scholar
  15. 15.
    Cordonnier C, van der Flier WM, Sluimer JD, Leys D, Barkhof F, Scheltens P (2006) Prevalence and severity of microbleeds in a memory clinic setting. Neurology 66(9):1356–1360PubMedCrossRefGoogle Scholar
  16. 16.
    Pantoni L (2010) Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol 9(7):689–701PubMedCrossRefGoogle Scholar
  17. 17.
    Werring DJ (2007) Cerebral microbleeds: clinical and pathophysiological significance. J Neuroimaging 17(3):193–203PubMedCrossRefGoogle Scholar
  18. 18.
    Gregoire SM, Brown MM, Kallis C, Jager HR, Yousry TA, Werring DJ (2010) MRI detection of new microbleeds in patients with ischemic stroke: five-year cohort follow-up study. Stroke 41(1):184–186PubMedCrossRefGoogle Scholar
  19. 19.
    Poels MM, Ikram MA, van der Lugt A, Hofman A, Krestin GP, Breteler MM, Vernooij MW (2011) Incidence of cerebral microbleeds in the general population: the Rotterdam Scan Study. Stroke 42(3):656–661PubMedCrossRefGoogle Scholar
  20. 20.
    Goos JD, Henneman WJ, Sluimer JD, Vrenken H, Sluimer IC, Barkhof F, Blankenstein MA, Scheltens PH, van der Flier WM (2010) Incidence of cerebral microbleeds: a longitudinal study in a memory clinic population. Neurology 74(24):1954–1960PubMedCrossRefGoogle Scholar
  21. 21.
    Jeon SB, Kwon SU, Cho AH, Yun SC, Kim JS, Kang DW (2009) Rapid appearance of new cerebral microbleeds after acute ischemic stroke. Neurology 73(20):1638–1644PubMedCrossRefGoogle Scholar
  22. 22.
    Kidwell CS, Greenberg SM (2009) Red meets white: do microbleeds link hemorrhagic and ischemic cerebrovascular disease? Neurology 73(20):1614–1615PubMedCrossRefGoogle Scholar
  23. 23.
    Kakar P, Charidimou A, Werring D (2012) Cerebral microbleeds: a new dilemma in stroke medicine. JRSM Cardiovascular Disease. doi:10.1177/2048004012474754 Google Scholar
  24. 24.
    Haacke EM, Mittal S, Wu Z, Neelavalli J, Cheng YC (2009) Susceptibility-weighted imaging: technical aspects and clinical applications, part 1. AJNR Am J Neuroradiol 30(1):19–30PubMedCrossRefGoogle Scholar
  25. 25.
    Atlas SW, Mark AS, Grossman RI, Gomori JM (1988) Intracranial hemorrhage: gradient-echo MR imaging at 1.5 T. Comparison with spin-echo imaging and clinical applications. Radiology 168(3):803–807PubMedGoogle Scholar
  26. 26.
    Greenberg SM, Finklestein SP, Schaefer PW (1996) Petechial hemorrhages accompanying lobar hemorrhage: detection by gradient-echo MRI. Neurology 46(6):1751–1754PubMedCrossRefGoogle Scholar
  27. 27.
    Gregoire SM, Werring DJ, Chaudhary UJ, Thornton JS, Brown MM, Yousry TA, Jager HR (2010) Choice of echo time on GRE T2*-weighted MRI influences the classification of brain microbleeds. Clin Radiol 65(5):391–394PubMedCrossRefGoogle Scholar
  28. 28.
    Tatsumi S, Ayaki T, Shinohara M, Yamamoto T (2008) Type of gradient recalled-echo sequence results in size and number change of cerebral microbleeds. AJNR Am J Neuroradiol 29(4):e13PubMedCrossRefGoogle Scholar
  29. 29.
    Vernooij MW, Ikram MA, Wielopolski PA, Krestin GP, Breteler MM, van der Lugt A (2008) Cerebral microbleeds: accelerated 3D T2*-weighted GRE MR imaging versus conventional 2D T2*-weighted GRE MR imaging for detection. Radiology 248(1):272–277PubMedCrossRefGoogle Scholar
  30. 30.
    Nandigam RN, Viswanathan A, Delgado P, Skehan ME, Smith EE, Rosand J, Greenberg SM, Dickerson BC (2009) MR imaging detection of cerebral microbleeds: effect of susceptibility-weighted imaging, section thickness, and field strength. AJNR Am J Neuroradiol 30(2):338–343PubMedCrossRefGoogle Scholar
  31. 31.
    Stehling C, Wersching H, Kloska SP, Kirchhof P, Ring J, Nassenstein I, Allkemper T, Knecht S, Bachmann R, Heindel W (2008) Detection of asymptomatic cerebral microbleeds: a comparative study at 1.5 and 3.0 T. Acad Radiol 15(7):895–900PubMedCrossRefGoogle Scholar
  32. 32.
    Conijn MM, Geerlings MI, Biessels GJ, Takahara T, Witkamp TD, Zwanenburg JJ, Luijten PR, Hendrikse J (2011) Cerebral microbleeds on MR imaging: comparison between 1.5 and 7 T. AJNR Am J Neuroradiol 32(6):1043–1049PubMedCrossRefGoogle Scholar
  33. 33.
    Haacke EM, Boikov AS, Barnes E, Neelavalli J, Khan MA (2011) Susceptibility-weighted imaging. In: Werring DJ (ed) Cerebral microbleeds: pathophysiology to clinical Practice. Cambridge University Press, Cambridge, pp 22–33CrossRefGoogle Scholar
  34. 34.
    Haacke EM, Xu Y, Cheng YC, Reichenbach JR (2004) Susceptibility weighted imaging (SWI). Magn Reson Med 52(3):612–618PubMedCrossRefGoogle Scholar
  35. 35.
    Ayaz M, Boikov AS, Haacke EM, Kido DK, Kirsch WM (2010) Imaging cerebral microbleeds using susceptibility weighted imaging: one step toward detecting vascular dementia. J Magn Reson Imaging 31(1):142–148PubMedCrossRefGoogle Scholar
  36. 36.
    Wu Z, Mittal S, Kish K, Yu Y, Hu J, Haacke EM (2009) Identification of calcification with MRI using susceptibility-weighted imaging: a case study. J Magn Reson Imaging 29(1):177–182PubMedCrossRefGoogle Scholar
  37. 37.
    Mittal S, Wu Z, Neelavalli J, Haacke EM (2009) Susceptibility-weighted imaging: technical aspects and clinical applications, part 2. AJNR Am J Neuroradiol 30(2):232–252PubMedCrossRefGoogle Scholar
  38. 38.
    Goos JD, van der Flier WM, Knol DL, Pouwels PJ, Scheltens P, Barkhof F, Wattjes MP (2011) Clinical relevance of improved microbleed detection by susceptibility-weighted magnetic resonance imaging. Stroke 42(7):1894–1900PubMedCrossRefGoogle Scholar
  39. 39.
    Poels MM, Ikram MA, Vernooij MW (2012) Improved MR imaging detection of cerebral microbleeds more accurately identifies persons with vasculopathy. AJNR Am J Neuroradiol 33(8):1553–1556PubMedCrossRefGoogle Scholar
  40. 40.
    Greenberg SM (2006) Small vessels, big problems. N Engl J Med 354(14):1451–1453PubMedCrossRefGoogle Scholar
  41. 41.
    Charidimou A, Gang Q, Werring DJ (2012) Sporadic cerebral amyloid angiopathy revisited: recent insights into pathophysiology and clinical spectrum. J Neurol Neurosurg Psychiatry 83(2):124–137PubMedCrossRefGoogle Scholar
  42. 42.
    Vernooij MW, van der Lugt A, Ikram MA, Wielopolski PA, Niessen WJ, Hofman A, Krestin GP, Breteler MM (2008) Prevalence and risk factors of cerebral microbleeds: the Rotterdam Scan Study. Neurology 70(14):1208–1214PubMedCrossRefGoogle Scholar
  43. 43.
    Maxwell SS, Jackson CA, Paternoster L, Cordonnier C, Thijs V, Al-Shahi Salman R, Sudlow CL (2011) Genetic associations with brain microbleeds: systematic review and meta-analyses. Neurology 77(2):158–167PubMedCrossRefGoogle Scholar
  44. 44.
    Dierksen GA, Skehan ME, Khan MA, Jeng J, Nandigam RN, Becker JA, Kumar A, Neal KL, Betensky RA, Frosch MP, Rosand J, Johnson KA, Viswanathan A, Salat DH, Greenberg SM (2010) Spatial relation between microbleeds and amyloid deposits in amyloid angiopathy. Ann Neurol 68(4):545–548PubMedCrossRefGoogle Scholar
  45. 45.
    Lee SH, Bae HJ, Kwon SJ, Kim H, Kim YH, Yoon BW, Roh JK (2004) Cerebral microbleeds are regionally associated with intracerebral hemorrhage. Neurology 62(1):72–76PubMedCrossRefGoogle Scholar
  46. 46.
    Roob G, Lechner A, Schmidt R, Flooh E, Hartung HP, Fazekas F (2000) Frequency and location of microbleeds in patients with primary intracerebral hemorrhage. Stroke 31(11):2665–2669PubMedCrossRefGoogle Scholar
  47. 47.
    Smith EE, Nandigam KR, Chen YW, Jeng J, Salat D, Halpin A, Frosch M, Wendell L, Fazen L, Rosand J, Viswanathan A, Greenberg SM (2010) MRI markers of small vessel disease in lobar and deep hemispheric intracerebral hemorrhage. Stroke 41(9):1933–1938PubMedCrossRefGoogle Scholar
  48. 48.
    Lummel N, Lutz J, Bruckmann H, Linn J (2012) The value of magnetic resonance imaging for the detection of the bleeding source in non-traumatic intracerebral haemorrhages: a comparison with conventional digital subtraction angiography. Neuroradiology 54(7):673–680PubMedCrossRefGoogle Scholar
  49. 49.
    Knudsen KA, Rosand J, Karluk D, Greenberg SM (2001) Clinical diagnosis of cerebral amyloid angiopathy: validation of the Boston criteria. Neurology 56(4):537–539PubMedCrossRefGoogle Scholar
  50. 50.
    Rosand J, Muzikansky A, Kumar A, Wisco JJ, Smith EE, Betensky RA, Greenberg SM (2005) Spatial clustering of hemorrhages in probable cerebral amyloid angiopathy. Ann Neurol 58(3):459–462PubMedCrossRefGoogle Scholar
  51. 51.
    van Rooden S, van der Grond J, van den Boom R, Haan J, Linn J, Greenberg SM, van Buchem MA (2009) Descriptive analysis of the Boston criteria applied to a Dutch-type cerebral amyloid angiopathy population. Stroke 40(9):3022–3027PubMedCrossRefGoogle Scholar
  52. 52.
    Linn J, Herms J, Dichgans M, Bruckmann H, Fesl G, Freilinger T, Wiesmann M (2008) Subarachnoid hemosiderosis and superficial cortical hemosiderosis in cerebral amyloid angiopathy. AJNR Am J Neuroradiol 29(1):184–186PubMedCrossRefGoogle Scholar
  53. 53.
    Raposo N, Viguier A, Cuvinciuc V, Calviere L, Cognard C, Bonneville F, Larrue V (2011) Cortical subarachnoid haemorrhage in the elderly: a recurrent event probably related to cerebral amyloid angiopathy. Eur J Neurol 18(4):597–603PubMedCrossRefGoogle Scholar
  54. 54.
    Linn J, Halpin A, Demaerel P, Ruhland J, Giese AD, Dichgans M, van Buchem MA, Bruckmann H, Greenberg SM (2010) Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy. Neurology 74(17):1346–1350PubMedCrossRefGoogle Scholar
  55. 55.
    Sperling RA, Jack CR Jr, Black SE, Frosch MP, Greenberg SM, Hyman BT, Scheltens P, Carrillo MC, Thies W, Bednar MM, Black RS, Brashear HR, Grundman M, Siemers ER, Feldman HH, Schindler RJ (2011) Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: recommendations from the Alzheimer’s Association Research Roundtable Workgroup. Alzheimers Dement 7(4):367–385PubMedCrossRefGoogle Scholar
  56. 56.
    Charidimou A, Law R, Werring DJ (2012) Amyloid “spells” trouble. Lancet 380(9853):1620PubMedCrossRefGoogle Scholar
  57. 57.
    Greenberg SM, Vonsattel JP, Stakes JW, Gruber M, Finklestein SP (1993) The clinical spectrum of cerebral amyloid angiopathy: presentations without lobar hemorrhage. Neurology 43(10):2073–2079PubMedCrossRefGoogle Scholar
  58. 58.
    Roch JA, Nighoghossian N, Hermier M, Cakmak S, Picot M, Honnorat J, Derex L, Trouillas P (2005) Transient neurologic symptoms related to cerebral amyloid angiopathy: usefulness of T2*-weighted imaging. Cerebrovasc Dis 20(5):412–414PubMedCrossRefGoogle Scholar
  59. 59.
    Smith DB, Hitchcock M, Philpott PJ (1985) Cerebral amyloid angiopathy presenting as transient ischemic attacks. Case report. J Neurosurg 63(6):963–964PubMedCrossRefGoogle Scholar
  60. 60.
    Charidimou A, Peeters A, Fox Z, Gregoire SM, Vandermeeren Y, Laloux P, Jager HR, Baron JC, Werring DJ (2012) Spectrum of transient focal neurological episodes in cerebral amyloid angiopathy: multicentre magnetic resonance imaging cohort study and meta-analysis. Stroke 43(9):2324–2330PubMedCrossRefGoogle Scholar
  61. 61.
    Menon RS, Kidwell CS (2009) Neuroimaging demonstration of evolving small vessel ischemic injury in cerebral amyloid angiopathy. Stroke 40(12):e675–677PubMedCrossRefGoogle Scholar
  62. 62.
    Kimberly WT, Gilson A, Rost NS, Rosand J, Viswanathan A, Smith EE, Greenberg SM (2009) Silent ischemic infarcts are associated with hemorrhage burden in cerebral amyloid angiopathy. Neurology 72(14):1230–1235PubMedCrossRefGoogle Scholar
  63. 63.
    Smith EE, Schneider JA, Wardlaw JM, Greenberg SM (2012) Cerebral microinfarcts: the invisible lesions. Lancet Neurol 11(3):272–282PubMedCrossRefGoogle Scholar
  64. 64.
    Ellis RJ, Olichney JM, Thal LJ, Mirra SS, Morris JC, Beekly D, Heyman A (1996) Cerebral amyloid angiopathy in the brains of patients with Alzheimer’s disease: the CERAD experience, Part XV. Neurology 46(6):1592–1596PubMedCrossRefGoogle Scholar
  65. 65.
    De Reuck J, Deramecourt V, Cordonnier C, Leys D, Maurage CA, Pasquier F (2011) The impact of cerebral amyloid angiopathy on the occurrence of cerebrovascular lesions in demented patients with Alzheimer features: a neuropathological study. Eur J Neurol 18(6):913–918PubMedCrossRefGoogle Scholar
  66. 66.
    Joutel A, Corpechot C, Ducros A, Vahedi K, Chabriat H, Mouton P, Alamowitch S, Domenga V, Cecillion M, Marechal E, Maciazek J, Vayssiere C, Cruaud C, Cabanis EA, Ruchoux MM, Weissenbach J, Bach JF, Bousser MG, Tournier-Lasserve E (1996) Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature 383(6602):707–710PubMedCrossRefGoogle Scholar
  67. 67.
    Tournier-Lasserve E, Joutel A, Melki J, Weissenbach J, Lathrop GM, Chabriat H, Mas JL, Cabanis EA, Baudrimont M, Maciazek J et al (1993) Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy maps to chromosome 19q12. Nat Genet 3(3):256–259PubMedCrossRefGoogle Scholar
  68. 68.
    Dichgans M, Mayer M, Uttner I, Bruning R, Muller-Hocker J, Rungger G, Ebke M, Klockgether T, Gasser T (1998) The phenotypic spectrum of CADASIL: clinical findings in 102 cases. Ann Neurol 44(5):731–739PubMedCrossRefGoogle Scholar
  69. 69.
    Viswanathan A, Chabriat H, Dichgans M (2011) Cerebral Microbleeds in CADASIL. In: Werring DJ (ed) Cerebral microbleeds: pathophysiology to clinical practice. Cambridge University Press, Cambridge, pp 135–141CrossRefGoogle Scholar
  70. 70.
    O’Sullivan M, Jarosz JM, Martin RJ, Deasy N, Powell JF, Markus HS (2001) MRI hyperintensities of the temporal lobe and external capsule in patients with CADASIL. Neurology 56(5):628–634PubMedCrossRefGoogle Scholar
  71. 71.
    Labauge P (2009) Magnetic resonance findings in leucodystrophies and MS. Int MS J 16(2):47–56PubMedGoogle Scholar
  72. 72.
    Lesnik Oberstein SA, van den Boom R, van Buchem MA, van Houwelingen HC, Bakker E, Vollebregt E, Ferrari MD, Breuning MH, Haan J, Dutch CRG (2001) Cerebral microbleeds in CADASIL. Neurology 57(6):1066–1070PubMedCrossRefGoogle Scholar
  73. 73.
    Dichgans M, Holtmannspotter M, Herzog J, Peters N, Bergmann M, Yousry TA (2002) Cerebral microbleeds in CADASIL: a gradient-echo magnetic resonance imaging and autopsy study. Stroke 33(1):67–71PubMedCrossRefGoogle Scholar
  74. 74.
    Viswanathan A, Guichard JP, Gschwendtner A, Buffon F, Cumurcuic R, Boutron C, Vicaut E, Holtmannspotter M, Pachai C, Bousser MG, Dichgans M, Chabriat H (2006) Blood pressure and haemoglobin A1c are associated with microhaemorrhage in CADASIL: a two-centre cohort study. Brain 129(Pt 9):2375–2383PubMedCrossRefGoogle Scholar
  75. 75.
    Liem MK, Lesnik Oberstein SA, Haan J, van der Neut IL, Ferrari MD, van Buchem MA, Middelkoop HA, van der Grond J (2009) MRI correlates of cognitive decline in CADASIL: a 7-year follow-up study. Neurology 72(2):143–148PubMedCrossRefGoogle Scholar
  76. 76.
    Viswanathan A, Godin O, Jouvent E, O’Sullivan M, Gschwendtner A, Peters N, Duering M, Guichard JP, Holtmannspotter M, Dufouil C, Pachai C, Bousser MG, Dichgans M, Chabriat H (2010) Impact of MRI markers in subcortical vascular dementia: a multi-modal analysis in CADASIL. Neurobiol Aging 31(9):1629–1636PubMedCrossRefGoogle Scholar
  77. 77.
    Lanfranconi S, Markus HS (2010) COL4A1 mutations as a monogenic cause of cerebral small vessel disease: a systematic review. Stroke 41(8):e513–518PubMedCrossRefGoogle Scholar
  78. 78.
    Gould DB, Phalan FC, van Mil SE, Sundberg JP, Vahedi K, Massin P, Bousser MG, Heutink P, Miner JH, Tournier-Lasserve E, John SW (2006) Role of COL4A1 in small-vessel disease and hemorrhagic stroke. N Engl J Med 354(14):1489–1496PubMedCrossRefGoogle Scholar
  79. 79.
    Alamowitch S, Plaisier E, Favrole P, Prost C, Chen Z, Van Agtmael T, Marro B, Ronco P (2009) Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome. Neurology 73(22):1873–1882PubMedCrossRefGoogle Scholar
  80. 80.
    Klein I, Iung B, Wolff M, Brochet E, Longuet P, Laissy JP, Duval X (2007) Silent T2* cerebral microbleeds: a potential new imaging clue in infective endocarditis. Neurology 68(23):2043PubMedCrossRefGoogle Scholar
  81. 81.
    Nandigam RN (2008) Re: Silent T2* cerebral microbleeds: a potential new imaging clue in infective endocarditis. Neurology 70(4):323, author reply 323–324PubMedCrossRefGoogle Scholar
  82. 82.
    Klein I, Iung B, Labreuche J, Hess A, Wolff M, Messika-Zeitoun D, Lavallee P, Laissy JP, Leport C, Duval X, Group IS (2009) Cerebral microbleeds are frequent in infective endocarditis: a case–control study. Stroke 40(11):3461–3465PubMedCrossRefGoogle Scholar
  83. 83.
    Okazaki S, Sakaguchi M, Hyun B, Nagano K, Tagaya M, Sakata Y, Sakaguchi T, Kitagawa K (2011) Cerebral microbleeds predict impending intracranial hemorrhage in infective endocarditis. Cerebrovasc Dis 32(5):483–488PubMedCrossRefGoogle Scholar
  84. 84.
    Vanacker P, Nelissen N, Van Laere K, Thijs VN (2009) Images in neurology. Scattered cerebral microbleeds due to cardiac myxoma. Arch Neurol 66(6):796–797PubMedCrossRefGoogle Scholar
  85. 85.
    Jeon SB, Lee JW, Kim SJ, Chung CH, Kwon SU, Choi CG, Choo SJ, Nah HW, Kim JS, Kang DW (2010) New cerebral lesions on T2*-weighted gradient-echo imaging after cardiac valve surgery. Cerebrovasc Dis 30(2):194–199PubMedCrossRefGoogle Scholar
  86. 86.
    Kim GM, Kim CH, Kim BS (2009) Multiple cerebral infarction and microbleeds associated with adult-onset paroxysmal cold hemoglobinuria. J Clin Neurosci 16(2):348–349PubMedCrossRefGoogle Scholar
  87. 87.
    Llufriu S, Cervera A, Capurro S, Chamorro A (2008) Neurological picture. Familial Sneddon’s syndrome with microbleeds in MRI. J Neurol Neurosurg Psychiatry 79(8):962PubMedCrossRefGoogle Scholar
  88. 88.
    Yokoyama S, Hirano H, Uomizu K, Kajiya Y, Tajitsu K, Kusumoto K (2005) High incidence of microbleeds in hemodialysis patients detected by T2*-weighted gradient-echo magnetic resonance imaging. Neurol Med Chir (Tokyo) 45(11):556–560, discussion 560CrossRefGoogle Scholar
  89. 89.
    Cho AH, Lee SB, Han SJ, Shon YM, Yang DW, Kim BS (2009) Impaired kidney function and cerebral microbleeds in patients with acute ischemic stroke. Neurology 73(20):1645–1648PubMedCrossRefGoogle Scholar
  90. 90.
    Ryu WS, Lee SH, Kim CK, Kim BJ, Yoon BW (2012) The relation between chronic kidney disease and cerebral microbleeds: difference between patients with and without diabetes. Int J Stroke 7(7):551–557PubMedCrossRefGoogle Scholar
  91. 91.
    Kikuta K, Takagi Y, Nozaki K, Hanakawa T, Okada T, Mikuni N, Miki Y, Fushmi Y, Yamamoto A, Yamada K, Fukuyama H, Hashimoto N (2005) Asymptomatic microbleeds in moyamoya disease: T2*-weighted gradient-echo magnetic resonance imaging study. J Neurosurg 102(3):470–475PubMedCrossRefGoogle Scholar
  92. 92.
    Ishikawa T, Kuroda S, Nakayama N, Terae S, Kudou K, Iwasaki Y (2005) Prevalence of asymptomatic microbleeds in patients with moyamoya disease. Neurol Med Chir (Tokyo) 45(10):495–500, discussion 500CrossRefGoogle Scholar
  93. 93.
    Kikuta K, Takagi Y, Nozaki K, Sawamoto N, Fukuyama H, Hashimoto N (2008) The presence of multiple microbleeds as a predictor of subsequent cerebral hemorrhage in patients with moyamoya disease. Neurosurgery 62(1):104–111, discussion 111–102PubMedCrossRefGoogle Scholar
  94. 94.
    Tanaka M, Sakaguchi M, Miwa K, Kitagawa K (2012) Cerebral microbleeds in patients with moyamoya-like vessels secondary to atherosclerosis. Intern Med 51(2):167–172PubMedCrossRefGoogle Scholar
  95. 95.
    Bartynski WS (2008) Posterior reversible encephalopathy syndrome, part 1: fundamental imaging and clinical features. AJNR Am J Neuroradiol 29(6):1036–1042PubMedCrossRefGoogle Scholar
  96. 96.
    McKinney AM, Short J, Truwit CL, McKinney ZJ, Kozak OS, SantaCruz KS, Teksam M (2007) Posterior reversible encephalopathy syndrome: incidence of atypical regions of involvement and imaging findings. AJR Am J Roentgenol 189(4):904–912PubMedCrossRefGoogle Scholar
  97. 97.
    McKinney AM, Sarikaya B, Gustafson C, Truwit CL (2012) Detection of microhemorrhage in posterior reversible encephalopathy syndrome using susceptibility-weighted imaging. AJNR Am J Neuroradiol 33(5):896–903PubMedCrossRefGoogle Scholar
  98. 98.
    Lupo JM, Chuang CF, Chang SM, Barani IJ, Jimenez B, Hess CP, Nelson SJ (2012) 7-Tesla susceptibility-weighted imaging to assess the effects of radiotherapy on normal-appearing brain in patients with glioma. Int J Radiat Oncol Biol Phys 82(3):e493–500PubMedCrossRefGoogle Scholar
  99. 99.
    Scheid R (2011) Cerebral microbleeds in relation to brain trauma. In: Werring DJ (ed) Cerebral microbleeds: pathophysiology to clinical Practice. Cambridge University Press, Cambridge, pp 125–134CrossRefGoogle Scholar
  100. 100.
    Charidimou A, Jager HR, Werring DJ (2012) Cerebral microbleed detection and mapping: principles, methodological aspects and rationale in vascular dementia. Exp Gerontol 47(11):843–852PubMedCrossRefGoogle Scholar
  101. 101.
    Raychaudhuri R, Batjer HH, Awad IA (2005) Intracranial cavernous angioma: a practical review of clinical and biological aspects. Surg Neurol 63(4):319–328, Discussion 328PubMedCrossRefGoogle Scholar
  102. 102.
    Samarasekera N, Potter G, Al-Shahi Salman R (2011) Cerebral microbleed mimics. In: Werring DJ (ed) Cerebal microbleeds: pathophysiology to clinical practice. Cambridge University Press, Cambridge, pp 44–48CrossRefGoogle Scholar
  103. 103.
    Teo JTH, Ramadan H, Gregoire SM, Mufti S, Lipman G, Jäger HR, Losseff N, Werring D (2011) Can cerebral microbleeds cause an acute stroke syndrome? Neurology Clinical Practice 1(1):75–77CrossRefGoogle Scholar
  104. 104.
    Watanabe A, Kobashi T (2005) Lateral gaze disturbance due to cerebral microbleed in the medial lemniscus in the mid-pontine region: a case report. Neuroradiology 47(12):908–911PubMedCrossRefGoogle Scholar
  105. 105.
    Gorelick PB, Scuteri A, Black SE, Decarli C, Greenberg SM, Iadecola C, Launer LJ, Laurent S, Lopez OL, Nyenhuis D, Petersen RC, Schneider JA, Tzourio C, Arnett DK, Bennett DA, Chui HC, Higashida RT, Lindquist R, Nilsson PM, Roman GC, Sellke FW, Seshadri S (2011) Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 42(9):2672–2713PubMedCrossRefGoogle Scholar
  106. 106.
    Hachinski V, Iadecola C, Petersen RC, Breteler MM, Nyenhuis DL, Black SE, Powers WJ, DeCarli C, Merino JG, Kalaria RN, Vinters HV, Holtzman DM, Rosenberg GA, Wallin A, Dichgans M, Marler JR, Leblanc GG (2006) National Institute of Neurological Disorders and Stroke–Canadian Stroke Network vascular cognitive impairment harmonization standards. Stroke 37(9):2220–2241PubMedCrossRefGoogle Scholar
  107. 107.
    Charidimou A, Werring DJ (2012) Cerebral microbleeds and cognition in cerebrovascular disease: an update. J Neurol Sci 15(322(1–2):50–55CrossRefGoogle Scholar
  108. 108.
    Werring DJ, Frazer DW, Coward LJ, Losseff NA, Watt H, Cipolotti L, Brown MM, Jager HR (2004) Cognitive dysfunction in patients with cerebral microbleeds on T2*-weighted gradient-echo MRI. Brain 127(Pt 10):2265–2275PubMedCrossRefGoogle Scholar
  109. 109.
    Seo SW, Hwa Lee B, Kim EJ, Chin J, Sun Cho Y, Yoon U, Na DL (2007) Clinical significance of microbleeds in subcortical vascular dementia. Stroke 38(6):1949–1951PubMedCrossRefGoogle Scholar
  110. 110.
    Yakushiji Y, Nishiyama M, Yakushiji S, Hirotsu T, Uchino A, Nakajima J, Eriguchi M, Nanri Y, Hara M, Horikawa E, Kuroda Y (2008) Brain microbleeds and global cognitive function in adults without neurological disorder. Stroke 39(12):3323–3328PubMedCrossRefGoogle Scholar
  111. 111.
    van Es AC, van der Grond J, de Craen AJ, Westendorp RG, Bollen EL, Blauw GJ, Greenberg SM, van Buchem MA (2011) Cerebral microbleeds and cognitive functioning in the PROSPER study. Neurology 77(15):1446–1452PubMedCrossRefGoogle Scholar
  112. 112.
    van Norden AG, van den Berg HA, de Laat KF, Gons RA, van Dijk EJ, de Leeuw FE (2011) Frontal and temporal microbleeds are related to cognitive function: the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort (RUN DMC) Study. Stroke 42(12):3382–3386PubMedCrossRefGoogle Scholar
  113. 113.
    Poels MM, Ikram MA, van der Lugt A, Hofman A, Niessen WJ, Krestin GP, Breteler MM, Vernooij MW (2012) Cerebral microbleeds are associated with worse cognitive function: the Rotterdam Scan Study. Neurology 78(5):326–333PubMedCrossRefGoogle Scholar
  114. 114.
    Greenberg SM, Eng JA, Ning M, Smith EE, Rosand J (2004) Hemorrhage burden predicts recurrent intracerebral hemorrhage after lobar hemorrhage. Stroke 35(6):1415–1420PubMedCrossRefGoogle Scholar
  115. 115.
    Biffi A, Halpin A, Towfighi A, Gilson A, Busl K, Rost N, Smith EE, Greenberg MS, Rosand J, Viswanathan A (2010) Aspirin and recurrent intracerebral hemorrhage in cerebral amyloid angiopathy. Neurology 75(8):693–698PubMedCrossRefGoogle Scholar
  116. 116.
    Thijs V, Lemmens R, Schoofs C, Gorner A, Van Damme P, Schrooten M, Demaerel P (2010) Microbleeds and the risk of recurrent stroke. Stroke 41(9):2005–2009PubMedCrossRefGoogle Scholar
  117. 117.
    Flaherty ML, Kissela B, Woo D, Kleindorfer D, Alwell K, Sekar P, Moomaw CJ, Haverbusch M, Broderick JP (2007) The increasing incidence of anticoagulant-associated intracerebral hemorrhage. Neurology 68(2):116–121PubMedCrossRefGoogle Scholar
  118. 118.
    Flaherty ML (2010) Anticoagulant-associated intracerebral hemorrhage. Semin Neurol 30(5):565–572PubMedCrossRefGoogle Scholar
  119. 119.
    Lovelock CE, Molyneux AJ, Rothwell PM (2007) Change in incidence and aetiology of intracerebral haemorrhage in Oxfordshire, UK, between 1981 and 2006: a population-based study. Lancet Neurol 6(6):487–493PubMedCrossRefGoogle Scholar
  120. 120.
    Fan YH, Mok VC, Lam WW, Hui AC, Wong KS (2004) Cerebral microbleeds and white matter changes in patients hospitalized with lacunar infarcts. J Neurol 251(5):537–541PubMedCrossRefGoogle Scholar
  121. 121.
    Imaizumi T, Horita Y, Hashimoto Y, Niwa J (2004) Dotlike hemosiderin spots on T2*-weighted magnetic resonance imaging as a predictor of stroke recurrence: a prospective study. J Neurosurg 101(6):915–920PubMedCrossRefGoogle Scholar
  122. 122.
    Naka H, Nomura E, Takahashi T, Wakabayashi S, Mimori Y, Kajikawa H, Kohriyama T, Matsumoto M (2006) Combinations of the presence or absence of cerebral microbleeds and advanced white matter hyperintensity as predictors of subsequent stroke types. AJNR Am J Neuroradiol 27(4):830–835PubMedGoogle Scholar
  123. 123.
    Soo YO, Yang SR, Lam WW, Wong A, Fan YH, Leung HH, Chan AY, Leung C, Leung TW, Wong LK (2008) Risk vs benefit of anti-thrombotic therapy in ischaemic stroke patients with cerebral microbleeds. J Neurol 255(11):1679–1686PubMedCrossRefGoogle Scholar
  124. 124.
    Lovelock CE, Cordonnier C, Naka H, Al-Shahi Salman R, Sudlow CL, Sorimachi T, Werring DJ, Gregoire SM, Imaizumi T, Lee SH, Briley D, Rothwell PM (2010) Antithrombotic drug use, cerebral microbleeds, and intracerebral hemorrhage: a systematic review of published and unpublished studies. Stroke 41(6):1222–1228PubMedCrossRefGoogle Scholar
  125. 125.
    Rosand J, Hylek EM, O’Donnell HC, Greenberg SM (2000) Warfarin-associated hemorrhage and cerebral amyloid angiopathy: a genetic and pathologic study. Neurology 55(7):947–951PubMedCrossRefGoogle Scholar
  126. 126.
    Nicoll JA, Burnett C, Love S, Graham DI, Dewar D, Ironside JW, Stewart J, Vinters HV (1997) High frequency of apolipoprotein E epsilon 2 allele in hemorrhage due to cerebral amyloid angiopathy. Ann Neurol 41(6):716–721PubMedCrossRefGoogle Scholar
  127. 127.
    Biffi A, Sonni A, Anderson CD, Kissela B, Jagiella JM, Schmidt H, Jimenez-Conde J, Hansen BM, Fernandez-Cadenas I, Cortellini L, Ayres A, Schwab K, Juchniewicz K, Urbanik A, Rost NS, Viswanathan A, Seifert-Held T, Stoegerer EM, Tomas M, Rabionet R, Estivill X, Brown DL, Silliman SL, Selim M, Worrall BB, Meschia JF, Montaner J, Lindgren A, Roquer J, Schmidt R, Greenberg SM, Slowik A, Broderick JP, Woo D, Rosand J (2010) Variants at APOE influence risk of deep and lobar intracerebral hemorrhage. Ann Neurol 68(6):934–943PubMedCrossRefGoogle Scholar
  128. 128.
    Charidimou A, Shakeshaft C, Werring DJ (2012) Cerebral microbleeds on magnetic resonance imaging and anticoagulant-associated intracerebral hemorrhage risk. Front Neurol 3:133PubMedCrossRefGoogle Scholar
  129. 129.
    Vinters HV (1987) Cerebral amyloid angiopathy. A critical review. Stroke 18(2):311–324PubMedCrossRefGoogle Scholar
  130. 130.
    Passero S, Burgalassi L, D’Andrea P, Battistini N (1995) Recurrence of bleeding in patients with primary intracerebral hemorrhage. Stroke 26(7):1189–1192PubMedCrossRefGoogle Scholar
  131. 131.
    Kidwell CS, Saver JL, Villablanca JP, Duckwiler G, Fredieu A, Gough K, Leary MC, Starkman S, Gobin YP, Jahan R, Vespa P, Liebeskind DS, Alger JR, Vinuela F (2002) Magnetic resonance imaging detection of microbleeds before thrombolysis: an emerging application. Stroke 33(1):95–98PubMedCrossRefGoogle Scholar
  132. 132.
    Fiehler J, Albers GW, Boulanger JM, Derex L, Gass A, Hjort N, Kim JS, Liebeskind DS, Neumann-Haefelin T, Pedraza S, Rother J, Rothwell P, Rovira A, Schellinger PD, Trenkler J (2007) Bleeding risk analysis in stroke imaging before thromboLysis (BRASIL): pooled analysis of T2*-weighted magnetic resonance imaging data from 570 patients. Stroke 38(10):2738–2744PubMedCrossRefGoogle Scholar
  133. 133.
    Shoamanesh A, Kwok CS, Lim PA, Benavente OR (2012) Postthrombolysis intracranial hemorrhage risk of cerebral microbleeds in acute stroke patients: a systematic review and meta-analysis. Int J Stroke. doi:10.1111/j.1747-4949.2012.00869.x PubMedGoogle Scholar
  134. 134.
    Charidimou A, Kakar P, Fox Z, Werring DJ (2012) Cerebral microbleeds and the risk of intracerebral haemorrhage after thrombolysis for acute ischaemic stroke: systematic review and meta-analysis. J Neurol Neurosurg Psych 84(3):277–280CrossRefGoogle Scholar
  135. 135.
    McCarron MO, Nicoll JA (2004) Cerebral amyloid angiopathy and thrombolysis-related intracerebral haemorrhage. Lancet Neurol 3(8):484–492PubMedCrossRefGoogle Scholar
  136. 136.
    Sloan MA, Price TR, Petito CK, Randall AM, Solomon RE, Terrin ML, Gore J, Collen D, Kleiman N, Feit F et al (1995) Clinical features and pathogenesis of intracerebral hemorrhage after rt-PA and heparin therapy for acute myocardial infarction: the Thrombolysis in Myocardial Infarction (TIMI) II Pilot and Randomized Clinical Trial combined experience. Neurology 45(4):649–658PubMedCrossRefGoogle Scholar
  137. 137.
    Sperling R, Salloway S, Brooks DJ, Tampieri D, Barakos J, Fox NC, Raskind M, Sabbagh M, Honig LS, Porsteinsson AP, Lieberburg I, Arrighi HM, Morris KA, Lu Y, Liu E, Gregg KM, Brashear HR, Kinney GG, Black R, Grundman M (2012) Amyloid-related imaging abnormalities in patients with Alzheimer’s disease treated with bapineuzumab: a retrospective analysis. Lancet Neurol 11(3):241–249PubMedCrossRefGoogle Scholar
  138. 138.
    Nicoll JA, Wilkinson D, Holmes C, Steart P, Markham H, Weller RO (2003) Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report. Nat Med 9(4):448–452PubMedCrossRefGoogle Scholar
  139. 139.
    Ferrer I, Boada Rovira M, Sanchez Guerra ML, Rey MJ, Costa-Jussa F (2004) Neuropathology and pathogenesis of encephalitis following amyloid-beta immunization in Alzheimer’s disease. Brain Pathol 14(1):11–20PubMedCrossRefGoogle Scholar
  140. 140.
    Staekenborg SS, Koedam EL, Henneman WJ, Stokman P, Barkhof F, Scheltens P, van der Flier WM (2009) Progression of mild cognitive impairment to dementia: contribution of cerebrovascular disease compared with medial temporal lobe atrophy. Stroke 40(4):1269–1274PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Andreas Charidimou
    • 1
  • Anant Krishnan
    • 2
  • David J. Werring
    • 1
  • H. Rolf Jäger
    • 2
    • 3
    • 4
  1. 1.Stroke Research Group, UCL Institute of NeurologyThe National Hospital for Neurology and NeurosurgeryLondonUK
  2. 2.Lysholm Department of NeuroradiologyThe National Hospital for Neurology and NeurosurgeryLondonUK
  3. 3.Department of Brain Repair and RehabilitationUCL Institute of NeurologyLondonUK
  4. 4.UCL Institute of Neurology. The National Hospital for Neurology and NeurosurgeryUniversity College Hospital (UCH)LondonUK

Personalised recommendations