Cerebrovascular pathology in cerebral amyloid angiopathy presenting as intracerebral haemorrhage
Cerebral amyloid angiopathy (CAA) is the second most common cause of non-traumatic intracerebral haemorrhage (ICH) accounting for 12–15% of lobar haemorrhages in the elderly. Definitive diagnosis of CAA requires histological evaluation. We aimed to evaluate the spectrum of cerebrovascular changes in CAA-related ICH. Between 2011 and 2015, biopsy-confirmed cases of CAA were retrieved and clinical, radiological and pathological features were reviewed. The spectrum of vascular alterations was evaluated and amyloid deposition was graded in accordance with the Greenberg and Vonsattel scale. Seven cases of sporadic CAA [5 males and 2 females] were diagnosed, none of whom were suspected to have CAA pre-operatively. Six presented with large intracerebral haematoma (ICH) requiring neurosurgical intervention (age range: 56–70 years) and one had episodic headache and multiple microhaemorrhages requiring a diagnostic brain biopsy (45 years). In the presence of large ICH, vascular amyloid deposits were of moderate to severe grade (grade 4 in 4, grades 2 and 3 in 1 case each) with predominant involvement of medium (200–500 μm) to large (> 500 μm) leptomeningeal vessels. Fibrinoid necrosis was noted in four. Two were hypertensive and on antiplatelet agents. β-Amyloid plaques were detected in two, one of whom had symptomatic dementia. MRI performed in 3 of 6 cases with ICH did not reveal any microhaemorrhages. Amyloid deposits in small (50–200 μm) to medium (200–500 μm) calibre intracortical vessels produced parenchymal microhemorrhages. Histopathological examination of ICH is essential for diagnosing CAA. The vascular calibre rather than grade of amyloid deposits dictates size of the bleed. Presence of co-morbidities such as antiplatelet agents may predispose to haemorrhage.
KeywordsAmyloid deposits Grade Aβ Lobar hematoma Microhemorrhage
We would like to acknowledge Dr. Natarajan M, Neurosugeon, K G Hospital, Coimbatore, Tamil Nadu, India for referring a case for histopathological diagnosis.
Author 1, Rajalakshmi Poyuran, -analysed the cases; performed data collection, analysis and interpretation; drafted the manuscript and reviewed the literature.
Author 2, Anita Mahadevan, conceived and designed the study, performed data interpretation and analysis and critically reviewed and finalized the manuscript.
Authors 3 and 7, Arimappamagan Arivazhagan and K V L Narasinga Rao, are neurosurgeons who operated and managed the patients and performed clinical data acquisition, analysis and review of the manuscript with intellectual inputs.
Authors 4 and 8, Nandeesh BN and Yasha T Chickabasaviah, performed diagnosis of cases, data analysis and interpretation; reviewed the manuscript and provided inputs.
Author 5, Madhu Nagappa, is a neurologist who managed the patients, provided and interpreted clinical data, performed clinicopathological analysis and reviewed the manuscript with intellectual inputs.
Author 6, Jitender Saini, is a neuroradiologist who carried out neuroimaging studies, reviewed imaging findings and analysed and interpreted the neuroimaging data and reviewed the manuscript providing critical inputs.
All the authors gave final approval for publication and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Corresponding author takes full responsibility for the work as a whole, including the study design, access to data and the decision to submit and publish the manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 5.Oppenheim G (1909) Über “drusige Nekrosen” in der Grosshirnrinde. Neurol Centralbl 28:410–413Google Scholar
- 6.Pantelakis S (1954) A particular type of senile angiopathy of the central nervous system: congophilic angiopathy cerebral amyloid angiopathy without and with cerebral hemorrhages: a comparative histological study, topography and frequency. Monatsschr Psychiatr Neurol 128:219–256CrossRefGoogle Scholar
- 7.Okazaki H, Reagan TJ, Campbell RJ (1979) Clinicopathologic studies of primary cerebral amyloid angiopathy. Mayo Clin Proc 54:22–31Google Scholar
- 14.Meretoja A, Strbian D, Putaala J, Curtze S, Haapaniemi E, Mustanoja S, Sairanen T, Satopää J, Silvennoinen H, Niemelä M, Kaste M, Tatlisumak T (2012) SMASH-U: a proposal for etiologic classification of intracerebral hemorrhage. Stroke 43:2592–2597. https://doi.org/10.1161/STROKEAHA.112.661603 CrossRefGoogle Scholar
- 16.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 17:823–829. https://doi.org/10.1111/j.1468-1331.2009.02940.x CrossRefGoogle Scholar
- 20.Gurol ME, Dierksen G, Betensky R, Gidicsin C, Halpin A, Becker A, Carmasin J, Ayres A, Schwab K, Viswanathan A, Salat D, Rosand J, Johnson KA, Greenberg SM (2012) Predicting sites of new hemorrhage with amyloid imaging in cerebral amyloid angiopathy. Neurology 79:320–326. https://doi.org/10.1212/WNL.0b013e31826043a9 CrossRefGoogle Scholar
- 21.Wagle WA, Smith TW, Weiner M (1984) Intracerebral hemorrhage caused by cerebral amyloid angiopathy: radiographic-pathologic correlation. Am J Neuroradiol 5:171–176Google Scholar
- 23.Charidimou A, Jaunmuktane Z, Baron J, Burnell M, Varlet P, Peeters A, Xuereb J, Jäger R, Brandner S, Werring DJ (2014) White matter perivascular spaces an MRI marker in pathology-proven cerebral amyloid angiopathy? Neurology 82:57–62. https://doi.org/10.1212/01.wnl.0000438225.02729.04 CrossRefGoogle Scholar
- 28.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 68:545–548. https://doi.org/10.1002/ana.22099 CrossRefGoogle Scholar
- 30.Greenberg SM, Eng JA, Ning M, Smith EE, Rosand J (2004) Hemorrhage burden predicts recurrent intracerebral hemorrhage after lobar hemorrhage. Stroke 35:1415–1420. https://doi.org/10.1161/01.STR.0000126807.69758.0e CrossRefGoogle Scholar
- 31.Charidimou A, Kakar P, Fox Z, Werring DJ (2013) Cerebral microbleeds and the risk of intracerebral haemorrhage after thrombolysis for acute ischaemic stroke: systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 84:277–280. https://doi.org/10.1136/jnnp-2012-303379 CrossRefGoogle Scholar
- 35.Gregoire SM, Charidimou A, Gadapa N, Dolan E, Antoun N, Peeters A, Vandermeeren Y, Laloux P, Baron JC, Jäger HR, Werring DJ (2011) Acute ischaemic brain lesions in intracerebral haemorrhage: multicentre cross-sectional magnetic resonance imaging study. Brain 134:2376–2386. https://doi.org/10.1093/brain/awr172 CrossRefGoogle Scholar
- 36.Arima H, Tzourio C, Anderson C, Woodward M, Bousser MG, MacMahon S, Neal B, Chalmers J (2010) Effects of perindopril-based lowering of blood pressure on intracerebral hemorrhage related to amyloid angiopathy: the PROGRESS trial. Stroke 41:394–396. https://doi.org/10.1161/STROKEAHA.109.563932 CrossRefGoogle Scholar
- 38.Tang YJ, Wang S, Zhu MW, Sun YL, Zhao JZ (2013) Severe pathological manifestation of cerebral amyloid angiopathy correlates with poor outcome from cerebral amyloid angiopathy related intracranial hemorrhage. Chin Med J 126:603–608Google Scholar