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Fibrinoid necrosis of small brain arteries and arterioles and miliary aneurysms as causes of hypertensive hemorrhage: a critical reappraisal

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Abstract

Cerebral hemorrhage in hypertensive patients is still an important source of morbidity and death. Understanding its underlying pathological basis is essential for the development of fact-based attempts to prevent the hemorrhage. Fibrinoid necrosis and miliary aneurysms are associated with and are the probable underlying causative lesions. Unfortunately much misunderstanding and confusion surrounds understanding of both lesions. This review clarifies several points. These include the following: the nature of fibrinoid necrosis and the susceptibility of small brain arteries and arterioles to this lesion even in the so-called benign hypertension; the relationship of fibrinoid necrosis to lipohyalinosis and the reasons for preferring the term fibrinoid; the existence of miliary aneurysms; the distinction between these aneurysms and pseudo-aneurysms or fibrin globes; the importance of, and basis for, recognizing healed miliary aneurysms; the relationship of fibrinoid necrosis to these aneurysms.

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References

  1. Amano S (1977) Vascular changes in the brain of spontaneously hypertensive rats: Hyaline and fibrinoid degeneration. J Pathol 121:119–128. doi:10.1002/path.1711210209

    Article  PubMed  CAS  Google Scholar 

  2. Auer RN, Sutherland GR (2005) Primary intracerebral hemorrhage: pathophysiology. Can J Neurosci 32(Suppl 2):S3–S12

    Google Scholar 

  3. Beilin LJ, Goldby FS (1977) High arterial pressure versus humoral factors in the pathogenesis of the vascular lesions of malignant hypertension. The case for pressure alone. Clin Sci Mol Med 52:111–113

    PubMed  CAS  Google Scholar 

  4. Challa VL, Moody DM, Bell MA (1992) The Charcot-Bouchard aneurysm controversy: impact of a new histologic technique. J Neuropathol Exp Neurol 51:264–271. doi:10.1097/00005072-199205000-00004

    Article  PubMed  CAS  Google Scholar 

  5. Charcot JM, Bouchard C (1868) Nouvelles recherches sur la pathogene de l’hemorrhage cerebrale. Arch Physiol Norm et Path 1:110–127; 643–665; 725–755

    Google Scholar 

  6. Cole FM, Yates P (1967) Intracererbal microaneurysms and small cerebrovascular lesions. Brain 90:759–768. doi:10.1093/brain/90.4.759

    Article  PubMed  CAS  Google Scholar 

  7. Cole FM, Yates PO (1967) Pseudo-aneurysms in relationship to massive cerebral haemorrhage. J Neurol Neurosurg Psychiatr 30:61–66

    Article  Google Scholar 

  8. Cone AH, Nast CC (1996) Ch 65 Kidney. In: Domjanov I, Linder J (eds) Andersons’s pathology, 10th edn. Mosby, St Louis, pp 2073–2142

    Google Scholar 

  9. Cotran RS, Kumar V Collins T ed. (1974) Robins pathologic basis of disease, 6th edn Ch 21 The kidney. Saunders, Philadelphia, pp 930–996

  10. Feigin I, Prose P (1959) Hypertensive fibrinoid arteritis of the brain and gross cerebral hemoorrhage. J Neuropathol Exp Neurol 1:98–110

    CAS  Google Scholar 

  11. Ferrer I, Kaste M, Kalimo H (2008) Ch 3, Vascular diseases. In: Love S, Louis DN, Ellison DW (eds) Greenfield’s neuropathology, 7th edn. Arnold Publ, London, pp 121–240

  12. Fisher CM (1971) Pathological observations in hypertensive cerebral hemorrhage. J Neuropathol Exp Neurol 30:536–550. doi:10.1097/00005072-197107000-00015

    Article  PubMed  CAS  Google Scholar 

  13. Fisher CM (2001) A career in cerebrovascular disease: a personal account. Stroke 32:2719–2724. doi:10.1161/hs1101.098765

    Article  PubMed  CAS  Google Scholar 

  14. Fisher CM (2003) Hypertensive cerebral hemorrhage. Demonstration of source of bleeding. J Neuropathol Exp Neurol 62:104–107

    PubMed  Google Scholar 

  15. Fredericksson K, Nordburg C, Kalimo H et al (1988) Cerebral microangiopathy in stroke prone spontaneously hypertensive rats. Acta Neuropathol 75:241–252. doi:10.1007/BF00690532

    Article  Google Scholar 

  16. Frohlich ED (1983) Hemodynamics and other determinants in development of left ventricular hypertrophy. Fed Proc 42:2709–2715

    PubMed  CAS  Google Scholar 

  17. Ganau A, Devereux RB, Roman MJ et al (1992) Patterns of left ventricular hypertrophy and geometric remodeling in essential hypertension. J Am Coll Cardiol 19:1550–1558

    Article  PubMed  CAS  Google Scholar 

  18. Giacomelli F, Rooney J, Wiener J (1978) Cerebrovascular ultrastructure and permeability after carotid artery constriction in experimental hypertension. Exp Mol Pathol 28:309–321. doi:10.1016/0014-4800(78)90005-9

    Article  PubMed  CAS  Google Scholar 

  19. Green FHK (1930) Miliary aneurysms in the brain. J Pathol Bacteriol 33:71–77. doi:10.1002/path.1700330107

    Article  Google Scholar 

  20. Lammie GA (2001) Hypertensive cerebral small vessel disease and stroke. Brain Pathol 12:358–370

    Google Scholar 

  21. Lip GYH, Beevers M, Beevers DG (1995) Complications and survival of 315 patients with malignant-phase hypertension. J Hypertens 13:915–924. doi:10.1097/00004872-199508000-00013

    Article  PubMed  CAS  Google Scholar 

  22. McCarthy A Malignant Hypertension http://www.massgeneral.org/vascularcenter/page.asp.Accessed 28 May 2008

  23. Mohring J (1977) High arterial pressure versus humoral factors in the pathogenesis of the vascular lesions of malignant hypertension. The case for humoral factors as well as pressure. Clin Sci Mol Med 52:113–117

    Google Scholar 

  24. Ooneda G, Oomaya Y, Matsuyama K et al (1965) Electron microscopic studies on the morphogenesis of fibrinoid degeneration in the mesenteric arteries of hypertensive rats. Angiology 16:8–17. doi:10.1177/000331976501600102

    Article  PubMed  CAS  Google Scholar 

  25. Quereshi AI, Tuhrim S, Broderick JP et al (2001) Spontaneous intracerebral hemorrhage. N Engl J Med 344:1450–1460. doi:10.1056/NEJM200105103441907

    Article  Google Scholar 

  26. Rosenblum WI (1977) Miliary Aneurysms and “fibrinoid” degeneration of cerebral blood vessels. Hum Pathol 8:133–1392. doi:10.1016/S0046-8177(77)80076-2

    Article  PubMed  CAS  Google Scholar 

  27. Rosenblum WI (1999) Small chronic hemorrhages and ischemic lesions in association with spontaneous intracerebral hematomas. Stroke 30:2761

    PubMed  CAS  Google Scholar 

  28. Rosenblum WI (2003) Cerebral hemorrhage produced by ruptured dissecting aneurysm in miliary aneurysm. Ann Neurol 54:376–378. doi:10.1002/ana.10664

    Article  PubMed  Google Scholar 

  29. Ross Russell RW (1963) Observations on intracerebral aneurysms. Brain 86:425–442. doi:10.1093/brain/86.3.425

    Article  CAS  Google Scholar 

  30. Schrier RW (ed) (2004) Manual of nephrology, 6th edn, chap. 15: the patient with hypertension, Williams and Wilkins, Baltimore publ, pp 257–258

  31. Simko F (1996) Left ventricular hypertrophy regression as a process with variable biological implications. Can J Cardiol 12:507–513

    PubMed  CAS  Google Scholar 

  32. Takebayashi S, Kaneko M (1983) Electron microscopic studies of ruptured arteries in hypertensive intracerebral hemorrhage. Stroke 14:28–36

    PubMed  CAS  Google Scholar 

  33. Tanaka A, Takebayashi S (1999) Response to letter. Stroke 31:2762

    Google Scholar 

  34. Tanaka A, Ueno Y, Nakayama Y, Takano K et al (1999) Small chronic hemorrhages and ischemic lesions in association with spontaneous intracerebral hematomas. Stroke 30:1637–1642

    PubMed  CAS  Google Scholar 

  35. van den Born BH, Koopmans RP, Groeneveld JO et al (2006) Ethnic disparities in the incidence, presentation and complications of malignant hypertension. J Hypertens 24:2299–2304

    Article  PubMed  CAS  Google Scholar 

  36. Vonsattel JP, Myers RH, Hedley-Whyte ET et al (1991) Cerebral amyloid angiopathy without and with cerebral hemorrhages: a comparative histological study. Ann Neurol 30:637649. doi:10.1002/ana.410300503

    Article  Google Scholar 

  37. Wiener J, Spiro D, Lattes RB (1965) The cellular pathology of experimental hypertension II. Arteriolar hyalinosis and fibrinoid change. Am J Pathol 47:457–485

    PubMed  CAS  Google Scholar 

  38. Zia E, Hedblad B, Pessah-Rasmussen H, Berglund G et al (2007) Blood pressure in relation to the incidence of cerebral infarction and intracerebral hemorrhage. Stroke 38:2681–2685. doi:10.1161/STROKEAHA.106.479725

    Article  PubMed  Google Scholar 

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Correspondence to William I. Rosenblum.

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Rosenblum, W.I. Fibrinoid necrosis of small brain arteries and arterioles and miliary aneurysms as causes of hypertensive hemorrhage: a critical reappraisal. Acta Neuropathol 116, 361–369 (2008). https://doi.org/10.1007/s00401-008-0416-9

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