Journal of Neurology

, Volume 265, Issue 3, pp 567–577 | Cite as

Pathological examination of cerebral amyloid angiopathy in patients who underwent removal of lobar hemorrhages

  • Chien-Min Lin
  • Hidetaka ArishimaEmail author
  • Ken-ichiro Kikuta
  • Hironobu Naiki
  • Ryuhei Kitai
  • Toshiaki Kodera
  • Ken Matsuda
  • Norichika Hashimoto
  • Makoto Isozaki
  • Kenzo Tsunetoshi
  • Hiroyuki Neishi
  • Yoshifumi Higashino
  • Ayumi Akazawa
  • Hiroshi Arai
  • Shinsuke Yamada
Original Communication


Cerebral amyloid angiopathy (CAA) is a degenerative disorder characterized by amyloid-β (Aβ) deposition in the brain microvessels. CAA is also known to contribute not only to cortical microbleeds but also lobar hemorrhages. This retrospective study examined CAA pathologically in patients who underwent direct surgeries for lobar hemorrhage. Thirty-three patients with lobar hemorrhage underwent open surgery with biopsy from 2007 to 2016 in our hospital. Cortical tissues over hematomas obtained surgically were pathologically examined using hematoxylin, eosin stain, and anti-Aβ antibody to diagnose CAA. We also investigated the advanced degree of CAA and clinical features of each patient with lobar hemorrhage. In the 33 patients, 4 yielded specimens that were insufficient to evaluate CAA pathologically. Twenty-four of the remaining 29 patients (82.8%) were pathologically diagnosed with CAA. The majority of CAA-positive patients had moderate or severe CAA based on a grading scale to estimate the advanced degree of CAA. About half of the CAA-positive patients had hypertension, and four took anticoagulant or antiplatelet agents. In five patients who were not pathologically diagnosed with CAA, one had severe liver function disorder, three had uncontrollable hypertension, and one had no obvious risk factor. Our pathological findings suggest that severe CAA with vasculopathic change markedly contributes to lobar hemorrhage. The coexistence of severe CAA and risk factors such as hypertension, anticoagulants or antiplatelets may readily induce lobar hemorrhage.


Cerebral amyloid angiopathy Lobar hemorrhages Pathological examination 


Compliance with ethical standards

Conflicts of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical standards

The authors declare that they complied with ethical standards and the study was in accord with the Helsinki Declaration.


  1. 1.
    Biffi A, Greenberg S (2011) Cerebralamyloidangiopathy: a systematic review. J Clin Neurol 7:1–9CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Charidimou A, Gang Q, Werring DJ (2012) Sporadic cerebral amyloid angiopathy revisited: recent insights into pathophysiology and clinical spectrum. J Neurol Neurosurg Psychiatry 83:124–137CrossRefPubMedGoogle Scholar
  3. 3.
    Revesz T, Ghiso J, Lashley T et al (2003) Cerebral amyloid angiopathies: a pathologic, biochemical, and genetic view. J Neuropathol Exp Neurol 62:885–898CrossRefPubMedGoogle Scholar
  4. 4.
    Viswanathan A, Greenberg SM (2011) Cerebral amyloid angiopathy in the elderly. Ann Neurol 70:871–980CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Attems J, Lauda F, Jellinger KA (2008) Unexpectedly low prevalence of intracerebral hemorrhages in sporadic cerebral amyloid angiopathy: an autopsy study. J Neurol 255:70–76CrossRefPubMedGoogle Scholar
  6. 6.
    Lovelock CE, Molyneux AJ, Rothwell PM, Oxford Vascular Study (2007) Change in incidence and aetiology of intracerebral haemorrhage in Oxfordshire, UK, between 1981 and 2006: a population-based study. Lancet Neurol 6:487–493CrossRefPubMedGoogle Scholar
  7. 7.
    Mendel TA, Wierzba-Bobrowicz T, Lewandowska E, Stępień T, Szpak GM (2013) The development of cerebral amyloid angiopathy in cerebral vessels. A review with illustrations based upon own investigated post mortem cases. Pol J Pathol 64:260–267CrossRefPubMedGoogle Scholar
  8. 8.
    Yamada M (2001) Cerebral amyroid angiopathy: an overview. Neuropathology 20:8–22CrossRefGoogle Scholar
  9. 9.
    Olichney JM, Hansen LA, Hofstetter CR, Grundman M, Katzman R, Thal LJ (1995) Cerebral infarction in Alzheimer’s disease is associated with severe amyloid angiopathy and hypertension. Arch Neurol 52:702–708CrossRefPubMedGoogle Scholar
  10. 10.
    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 46:1592–1596CrossRefPubMedGoogle Scholar
  11. 11.
    Vinters HV, Wang ZZ, Secor DL (1996) Brain parenchymal and microvascular amyloid in Alzheimer’s disease. Brain Pathol 6:179–195CrossRefPubMedGoogle Scholar
  12. 12.
    Greenberg SM, Vonsattel JP, Stakes JW, Gruber M, Finklestein SP (1993) The clinical spectrum of cerebral amyloid angiopathy: presentations without lobar hemorrhage. Neurology 43:2073–2079CrossRefPubMedGoogle Scholar
  13. 13.
    Hirohata M, Yoshita M, Ishida C, Ikeda SI, Tamaoka A, Kuzuhara S, Shoji M, Ando Y, Tokuda T, Yamada M (2010) Clinical features of non-hypertensive lobar intracerebral hemorrhage related to cerebral amyloid angiopathy. Eur J Neurol 17:823–829CrossRefPubMedGoogle Scholar
  14. 14.
    Greenberg SM, Vernooij MW, Cordonnier C, Viswanathan A, Al-Shahi Salman R, Warach S, Launer LJ, Van Buchem MA, Breteler MM, Microbleed Study Group (2009) Cerebral microbleeds: a guide to detection and interpretation. Lancet Neurol 8:165–174CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Pantoni L (2010) Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol 9:689–701CrossRefPubMedGoogle Scholar
  16. 16.
    Pezzini A, Del Zotto E, Volonghi I et al (2009) Cerebral amyloid angiopathy: a common cause of cerebral hemorrhage. Curr Med Chem 16:2498–2513CrossRefPubMedGoogle Scholar
  17. 17.
    Greenberg SM, Finklestein SP, Schaefer PW (1996) Petechial hemorrhages accompanying lobar hemorrhage: detection by gradient-echo MRI. Neurology 46:1751–1754CrossRefPubMedGoogle Scholar
  18. 18.
    Greenberg SM, Vonsattel JP (1997) Diagnosis of cerebral amyloid angiopathy. Sensitivity and specificity of cortical biopsy. Stroke 28:1418–1422CrossRefPubMedGoogle Scholar
  19. 19.
    Vonsattel JP, Myers RH, Hedley-Whyte ET, Ropper AH, Bird ED, Richardson EP Jr (1991) Cerebral amyloid angiopathy without and with cerebral hemorrhages: a comparative histological study. Ann Neurol 30:637–649CrossRefPubMedGoogle Scholar
  20. 20.
    Charidimou A, Martinez-Ramirez S, Reijmer YD, Oliveira-Filho J, Lauer A, Roongpiboonsopit D, Frosch M, Vashkevich A, Ayres A, Rosand J, Gurol ME, Greenberg SM, Viswanathan A (2016) Total magnetic resonance imaging burden of small vessel disease in cerebral amyloid angiopathy: an imaging-pathologic study of concept validation. JAMA Neurol 73:994–1001CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Lammie GA (2002) Hypertensive cerebral small vessel disease and stroke. Brain Pathol 12:358–370PubMedGoogle Scholar
  22. 22.
    Takebayashi S (1985) Ultrastructural morphometry of hypertensive medial damage in lenticulostriate and other arteries. Stroke 16:449–453CrossRefPubMedGoogle Scholar
  23. 23.
    Apoil M, Cogez J, Dubuc L, Bataille M, de la Sayette V, Touzé E, Viader F (2013) Focal cortical subarachnoid hemorrhage revealed by recurrent paresthesias: a clinico-radiological syndrome strongly associated with cerebral amyloid angiopathy. Cerebrovasc Dis 36:139–144CrossRefPubMedGoogle Scholar
  24. 24.
    Izumihara Al, Suzuki M, Ishihara T (2005) Recurrence and extension of lobar hemorrhage related to cerebral amyloid angiopathy: multivariate analysis of clinical risk factors. Surg Neurol 64:160–164CrossRefPubMedGoogle Scholar
  25. 25.
    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 18:597–603CrossRefPubMedGoogle Scholar
  26. 26.
    Ishii N, Nishihara Y, Horie A (1984) Amyloid angiopathy and lobar cerebral haemorrhage. J Neurol Neurosurg Psychiatry 47:1203–1210CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Jellinger K (1977) Cerebrovascular amyloidosis with cerebral hemorrhage. J Neurol 214:195–206CrossRefPubMedGoogle Scholar
  28. 28.
    Itoh Y, Yamada M, Hayakawa M, Otomo E, Miyatake T (1993) Cerebral amyloid angiopathy: a significant cause of cerebellar as well as lobar cerebral hemorrhage in the elderly. J Neurol Sci 116:135–141CrossRefPubMedGoogle Scholar
  29. 29.
    Lee SS, Stemmermann GN (1978) Congophilic angiopathy and cerebral hemorrhage. Arch Pathol Lab Med 102:317–321PubMedGoogle Scholar
  30. 30.
    Revesz T, Holton JL, Lashley T, Plant G, Rostagno A, Ghiso J, Frangione B (2002) Sporadic and familial cerebral amyloid angiopathies. Brain Pathol 12:343–357CrossRefPubMedGoogle Scholar
  31. 31.
    Bolívar JJ (2013) Essential hypertension: an approach to its etiology and neurogenic pathophysiology. Int J Hypertens 2013:547809CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Rosand J, Hylek EM, O’Donnell HC (2000) Greenberg SM (2000) Warfarin-associated hemorrhage and cerebral amyloid angiopathy: a genetic and pathologic study. Neurology 55:947–951CrossRefPubMedGoogle Scholar
  33. 33.
    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 41:716–721CrossRefPubMedGoogle Scholar
  34. 34.
    Charidimou A, Baron JC, Werring DJ (2013) Transient focal neurological episodes, cerebral amyloid angiopathy, and intracerebral hemorrhage risk: looking beyond TIAs. Int J Stroke 8:105–108CrossRefPubMedGoogle Scholar
  35. 35.
    Biffi A, Halpin A, Towfighi A, Gilson A, Busl K, Rost N, Smith EE, Greenberg MS, Rosand J, Viswanathan V (2010) Aspirin and recurrent intracerebral hemorrhage in cerebral amyloid angiopathy. Neurology 75:693–698CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Woo D, Haverbusch M, Sekar P, Kissela B, Khoury J, Schneider A, Kleindorfer D, Szaflarski J, Pancioli A, Jauch E, Moomaw C, Sauerbeck L, Gebel J, Broderick J (2004) Effect of untreated hypertension on hemorrhagic stroke. Stroke 35:1703–1708CrossRefPubMedGoogle Scholar
  37. 37.
    Woo D, Sauerbeck LR, Kissela BM, Khoury JC, Szaflarski JP, Gebel J, Shukla R, Pancioli AM, Jauch EC, Menon AG, Deka R, Carrozzella JA, Moomaw CJ, Fontaine RN, Broderick JP (2002) Genetic and environmental risk factors for intracerebral hemorrhage: preliminary results of a population-based study. Stroke 33:1190–1195CrossRefPubMedGoogle Scholar
  38. 38.
    Love S, Chalmers K, Ince P, Esiri M, Attems J, Jellinger K, Yamada M, McCarron M, Minett T, Matthews F, Greenberg S, Mann D, Kehoe PG (2014) Development, appraisal, validation and implementation of a consensus protocol for the assessment of cerebral amyloid angiopathy in post-mortem brain tissue. Am J Neurodegener Dis 3:19–32PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Chien-Min Lin
    • 1
  • Hidetaka Arishima
    • 2
    Email author
  • Ken-ichiro Kikuta
    • 2
  • Hironobu Naiki
    • 3
  • Ryuhei Kitai
    • 2
  • Toshiaki Kodera
    • 2
  • Ken Matsuda
    • 2
  • Norichika Hashimoto
    • 2
  • Makoto Isozaki
    • 2
  • Kenzo Tsunetoshi
    • 2
  • Hiroyuki Neishi
    • 2
  • Yoshifumi Higashino
    • 2
  • Ayumi Akazawa
    • 2
  • Hiroshi Arai
    • 2
  • Shinsuke Yamada
    • 2
  1. 1.Department of Neurosurgery, Shuang Ho HospitalTaipei Medical UniversityTaipei CityTaiwan
  2. 2.Department of NeurosurgeryUniversity of FukuiFukuiJapan
  3. 3.Department of PathologyUniversity of FukuiFukuiJapan

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