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Vascular Disorders: Angiopathies

  • Serge Weis
  • Michael Sonnberger
  • Andreas Dunzinger
  • Eva Voglmayr
  • Martin Aichholzer
  • Raimund Kleiser
  • Peter Strasser
Chapter
  • 421 Downloads

Abstract

Other angiopathies include sporadic and familial angiopathies. Sporadic angiopathies include among others cerebral amyloid (congophilic) angiopathy, fibromuscular dysplasia, Moyamoya angiopathy, Binswanger disease, and Fahr disease. Familial angiopathies are CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), CARASIL (cerebral recessive dominant arteriopathy with subcortical infarcts and leukoencephalopathy), CARASAL (cathepsin A-related arteriopathy with strokes and leukoencephalopathy), hereditary vascular retinopathy, HERNS (hereditary endotheliopathy with retinopathy, nephropathy, and stroke), and COL4A1 mutations (combined small vessel and large arterial disease).

Cerebral amyloid angiopathy (CAA) is a heterogeneous disease clinically characterized by ischemic or hemorrhagic changes. Amyloid deposits in the wall of leptomeningeal and cortical vessels are the histopathological hallmark. Micro- and macrobleedings, cortical siderosis, and leukoencephalopathy are features seen with brain imaging techniques. The deposition of Aβ-protein which is 42 amino acids long and cleaved from the amyloid precursor protein leads to damage of the medial smooth muscle cell disrupting the vascular architecture and weakening the arterial wall. There is a dose-dependent association between APOE ɛ4 and sporadic CAA. Treatment includes surgical removal of hemorrhage while clinical outcome is poor as recurrent hemorrhages are frequent.

Binswanger disease is a rare neurodegenerative disorder showing leukoencephalopathy, lacunar infarcts and mircobleeds, myelin pallor, regions of necrotic tissue damage, and axonal damage. Arterioles of the white matter with hyalinotic thickening of the vessel wall and widening of the perivascular spaces are a prominent feature of the disease. Pathogenesis is unknown. Treatment consists of the management of hypertension and diabetes with calcium channel blocker nimodipine and cerebral vasodilators. Clinical outcome is variable; usually, the disease is progressive.

Familial idiopathic basal ganglia calcification (Fahr disease) is a rare neurodegenerative disorder characterized by symmetrical and bilateral calcification of the basal ganglia. It is encountered in patients presenting with hypo- or hyperparathyroid disorders (phosphate imbalance disorder). It is associated with some genes (e.g., PDGFRß (encodes a member of the platelet-derived growth factor receptor family type β).

CADASIL is a cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy presenting with typical and atypical clinical manifestations. The pathognomonic ultrastructural change consists of deposition of granular osmiophilic material (GOM) commonly found in small-sized arterioles (seldomly small capillaries or veins). CADASIL is due to mutations of the gene encoding the transmembrane receptor Notch 3. Symptomatic treatment of migraine, cognitive decline, and primary and secondary stroke prevention is used. Clinical outcome is variable.

Selected References

  1. Andre C (2010) CADASIL: pathogenesis, clinical and radiological findings and treatment. Arq Neuropsiquiatr 68(2):287–299Google Scholar
  2. Attems J, Jellinger K, Thal DR, Van Nostrand W (2011) Review: sporadic cerebral amyloid angiopathy. Neuropathol Appl Neurobiol 37(1):75–93.  https://doi.org/10.1111/j.1365-2990.2010.01137.xGoogle Scholar
  3. Auer DP, Putz B, Gossl C, Elbel G, Gasser T, Dichgans M (2001) Differential lesion patterns in CADASIL and sporadic subcortical arteriosclerotic encephalopathy: MR imaging study with statistical parametric group comparison. Radiology 218(2):443–451.  https://doi.org/10.1148/radiology.218.2.r01fe24443Google Scholar
  4. Auriel E, Greenberg SM (2012) The pathophysiology and clinical presentation of cerebral amyloid angiopathy. Curr Atheroscler Rep 14(4):343–350.  https://doi.org/10.1007/s11883-012-0254-zGoogle Scholar
  5. Bottcher J, Sauner D, Jentsch A, Mentzel HJ, Becker H, Reichenbach JR, Kaiser WA (2004) [Visualization of symmetric striopallidodentate calcinosis by using high-resolution susceptibility-weighted MR imaging. An account of the impact of different diagnostic methods of M. Fahr]. Nervenarzt 75(4):355–361.  https://doi.org/10.1007/s00115-003-1667-2
  6. Carare RO, Hawkes CA, Jeffrey M, Kalaria RN, Weller RO (2013) Review: cerebral amyloid angiopathy, prion angiopathy, CADASIL and the spectrum of protein elimination failure angiopathies (PEFA) in neurodegenerative disease with a focus on therapy. Neuropathol Appl Neurobiol 39(6):593–611.  https://doi.org/10.1111/nan.12042Google Scholar
  7. Chabriat H, Joutel A, Dichgans M, Tournier-Lasserve E, Bousser MG (2009) Cadasil. Lancet Neurol 8(7):643–653.  https://doi.org/10.1016/s1474-4422(09)70127-9Google Scholar
  8. Chao CP, Kotsenas AL, Broderick DF (2006) Cerebral amyloid angiopathy: CT and MR imaging findings. Radiographics 26(5):1517–1531.  https://doi.org/10.1148/rg.265055090Google Scholar
  9. Charidimou A, Boulouis G, Gurol ME, Ayata C, Bacskai BJ, Frosch MP, Viswanathan A, Greenberg SM (2017) Emerging concepts in sporadic cerebral amyloid angiopathy. Brain J Neurol 140(7):1829–1850.  https://doi.org/10.1093/brain/awx047Google Scholar
  10. Choi EJ, Choi CG, Kim JS (2005) Large cerebral artery involvement in CADASIL. Neurology 65(8):1322–1324.  https://doi.org/10.1212/01.wnl.0000180965.79209.50Google Scholar
  11. Di Donato I, Bianchi S, De Stefano N, Dichgans M, Dotti MT, Duering M, Jouvent E, Korczyn AD, Lesnik-Oberstein SA, Malandrini A, Markus HS, Pantoni L, Penco S, Rufa A, Sinanovic O, Stojanov D, Federico A (2017) Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) as a model of small vessel disease: update on clinical, diagnostic, and management aspects. BMC Med 15(1):41.  https://doi.org/10.1186/s12916-017-0778-8Google Scholar
  12. Federico A, Bianchi S, Dotti MT (2005) The spectrum of mutations for CADASIL diagnosis. Neurol Sci 26(2):117–124.  https://doi.org/10.1007/s10072-005-0444-3Google Scholar
  13. Grinberg LT, Korczyn AD, Heinsen H (2012) Cerebral amyloid angiopathy impact on endothelium. Exp Gerontol 47(11):838–842.  https://doi.org/10.1016/j.exger.2012.08.005Google Scholar
  14. Jang SH, Seo YS (2015) Injuries of neural tracts in a patient with CADASIL: a diffusion tensor imaging study. BMC Neurol 15:176.  https://doi.org/10.1186/s12883-015-0434-xGoogle Scholar
  15. Kalaria RN, Viitanen M, Kalimo H, Dichgans M, Tabira T (2004) The pathogenesis of CADASIL: an update. J Neurol Sci 226(1-2):35–39.  https://doi.org/10.1016/j.jns.2004.09.008Google Scholar
  16. Kirshner HS, Bradshaw M (2015) The inflammatory form of cerebral amyloid Angiopathy or “Cerebral Amyloid Angiopathy-Related Inflammation” (CAARI). Curr Neurol Neurosci Rep 15(8):54.  https://doi.org/10.1007/s11910-015-0572-yGoogle Scholar
  17. 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):1346–1350.  https://doi.org/10.1212/WNL.0b013e3181dad605Google Scholar
  18. Lotz PR, Ballinger WE Jr, Quisling RG (1986) Subcortical arteriosclerotic encephalopathy: CT spectrum and pathologic correlation. AJR Am J Roentgenol 147(6):1209–1214.  https://doi.org/10.2214/ajr.147.6.1209Google Scholar
  19. Love S, Miners S, Palmer J, Chalmers K, Kehoe P (2009) Insights into the pathogenesis and pathogenicity of cerebral amyloid angiopathy. Front Biosci (Landmark edition) 14:4778–4792Google Scholar
  20. Miller-Thomas MM, Sipe AL, Benzinger TL, McConathy J, Connolly S, Schwetye KE (2016) Multimodality review of amyloid-related diseases of the central nervous system. Radiographics 36(4):1147–1163.  https://doi.org/10.1148/rg.2016150172Google Scholar
  21. Miller JH, Wardlaw JM, Lammie GA (1999) Intracerebral haemorrhage and cerebral amyloid angiopathy: CT features with pathological correlation. Clin Radiol 54(7):422–429Google Scholar
  22. Oide T, Takahashi H, Yutani C, Ishihara T, Ikeda S (2003) Relationship between lobar intracerebral hemorrhage and leukoencephalopathy associated with cerebral amyloid angiopathy: clinicopathological study of 64 Japanese patients. Amyloid 10(3):136–143Google Scholar
  23. Rannikmae K, Samarasekera N, Martinez-Gonzalez NA, Al-Shahi Salman R, Sudlow CL (2013) Genetics of cerebral amyloid angiopathy: systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 84(8):901–908.  https://doi.org/10.1136/jnnp-2012-303898Google Scholar
  24. Rutten JW, Haan J, Terwindt GM, van Duinen SG, Boon EM, Lesnik Oberstein SA (2014) Interpretation of NOTCH3 mutations in the diagnosis of CADASIL. Expert Rev Mol Diagn 14(5):593–603.  https://doi.org/10.1586/14737159.2014.922880Google Scholar
  25. Safriel Y, Sze G, Westmark K, Baehring J (2004) MR spectroscopy in the diagnosis of cerebral amyloid angiopathy presenting as a brain tumor. AJNR Am J Neuroradiol 25(10):1705–1708Google Scholar
  26. Samarasekera N, Rodrigues MA (2017) Imaging features of intracerebral hemorrhage with cerebral amyloid angiopathy: systematic review and meta-analysis. PLoS One 12(7):e0180923.  https://doi.org/10.1371/journal.pone.0180923Google Scholar
  27. Schrag M, Kirshner H (2016) Neuropsychological effects of cerebral amyloid angiopathy. Curr Neurol Neurosci Rep 16(8):76.  https://doi.org/10.1007/s11910-016-0674-1Google Scholar
  28. Tang SC, Jeng JS, Lee MJ, Yip PK (2009) Notch signaling and CADASIL. Acta Neurol Taiwanica 18(2):81–90Google Scholar
  29. Thal DR, Ghebremedhin E, Orantes M, Wiestler OD (2003) Vascular pathology in Alzheimer disease: correlation of cerebral amyloid angiopathy and arteriosclerosis/lipohyalinosis with cognitive decline. J Neuropathol Exp Neurol 62(12):1287–1301Google Scholar
  30. Thal DR, Ghebremedhin E, Rub U, Yamaguchi H, Del Tredici K, Braak H (2002) Two types of sporadic cerebral amyloid angiopathy. J Neuropathol Exp Neurol 61(3):282–293Google Scholar
  31. Tikka S, Baumann M, Siitonen M, Pasanen P, Poyhonen M, Myllykangas L, Viitanen M, Fukutake T, Cognat E, Joutel A, Kalimo H (2014) CADASIL and CARASIL. Brain Pathol (Zurich, Switzerland) 24(5):525–544.  https://doi.org/10.1111/bpa.12181Google Scholar
  32. Wang C, Li Y, Shi L, Ren J, Patti M, Wang T, de Oliveira JR, Sobrido MJ, Quintans B, Baquero M, Cui X, Zhang XY, Wang L, Xu H, Wang J, Yao J, Dai X, Liu J, Zhang L, Ma H, Gao Y, Ma X, Feng S, Liu M, Wang QK, Forster IC, Zhang X, Liu JY (2012) Mutations in SLC20A2 link familial idiopathic basal ganglia calcification with phosphate homeostasis. Nat Genet 44(3):254–256.  https://doi.org/10.1038/ng.1077Google Scholar
  33. Yamada M (2004) Cerebral amyloid angiopathy and gene polymorphisms. J Neurol Sci 226(1-2):41–44.  https://doi.org/10.1016/j.jns.2004.09.009Google Scholar
  34. Yamada M (2013) Brain hemorrhages in cerebral amyloid angiopathy. Semin Thromb Hemost 39(8):955–962.  https://doi.org/10.1055/s-0033-1357489Google Scholar
  35. Yamada M (2015) Cerebral amyloid angiopathy: emerging concepts. J Stroke 17(1):17–30.  https://doi.org/10.5853/jos.2015.17.1.17Google Scholar
  36. Yamada M, Naiki H (2012) Cerebral amyloid angiopathy. Prog Mol Biol Transl Sci 107:41–78.  https://doi.org/10.1016/b978-0-12-385883-2.00006-0Google Scholar
  37. Zhu S, Nahas SJ (2016) CADASIL: imaging characteristics and clinical correlation. Curr Pain Headache Rep 20(10):57.  https://doi.org/10.1007/s11916-016-0584-6Google Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  • Serge Weis
    • 1
  • Michael Sonnberger
    • 2
  • Andreas Dunzinger
    • 3
  • Eva Voglmayr
    • 2
  • Martin Aichholzer
    • 4
  • Raimund Kleiser
    • 2
  • Peter Strasser
    • 5
  1. 1.Division of Neuropathology, Neuromed CampusKepler University Hospital, Johannes Kepler UniversityLinzAustria
  2. 2.Department of Neuroradiology, Neuromed CampusKepler University Hospital, Johannes Kepler UniversityLinzAustria
  3. 3.Department of Neuro-Nuclear Medicine, Neuromed CampusKepler University Hospital, Johannes Kepler UniversityLinzAustria
  4. 4.Department of Neurosurgery, Neuromed CampusKepler University Hospital, Johannes Kepler UniversityLinzAustria
  5. 5.PMU University Institute for Medical & Chemical Laboratory DiagnosticsSalzburgAustria

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