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Cerebral amyloid angiopathy

INTRODUCTION

Cerebral amyloid angiopathy (CAA) is characterized by amyloid beta peptide deposits within small to medium-sized blood vessels of the brain and leptomeninges. Although CAA is usually asymptomatic, it is an important cause of primary lobar intracerebral hemorrhage in the elderly [1,2]. It can occur as a sporadic disorder, sometimes in association with Alzheimer disease (AD), or as a certain familial syndrome. In addition to intracerebral hemorrhage, CAA may present with transient neurological symptoms, an inflammatory leukoencephalopathy, as a contributor to cognitive impairment, or with incidental microhemorrhages or hemosiderosis on MRI.

EPIDEMIOLOGY

The incidence of cerebral amyloid angiopathy (CAA), like Alzheimer disease (AD), is strongly age dependent. Based upon a series of 784 autopsy cases, we estimated the prevalence of moderate to severe CAA as 2.3 percent for patients between the ages of 65 and 74, 8.0 percent between the ages of 75 and 84, and 12.1 percent over the age of 85 [3]. Although sporadic, CAA-related symptoms are uncommon at ages younger than 60 to 65 they can more rarely affect individuals in their 50s as well.

There is no strong predilection for gender. Although the association of CAA with hypertension is debated, it is clear that many patients with CAA-related hemorrhage are normotensive [4-6].

PATHOGENESIS

Vascular amyloid deposits in sporadic cerebral amyloid angiopathy (CAA) are biochemically similar to the material comprising senile plaques in Alzheimer disease (AD) [1]. The primary constituent of each is amyloid beta-peptide, a 39 to 43 amino acid fragment of the amyloid precursor protein. There is essentially no clinical overlap between CAA and the non-CNS systemic amyloidoses, such as primary (amyloid AL) and secondary (amyloid AA) amyloidosis.

Mutant amyloid precursor protein — Mutations in the gene that encodes the amyloid precursor protein (APP) are responsible for some cases of "presenile" CAA. While most of these mutations are also associated with at least some of the neuropathologic features of AD, at least one APP mutation (Leu34Val) has been reported to cause autosomal dominant CAA without parenchymal amyloid plaques or neurofibrillary tangles [7].

                        

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Literature review current through: Oct 2014. | This topic last updated: Oct 31, 2013.
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References
Top
  1. Viswanathan A, Greenberg SM. Cerebral amyloid angiopathy in the elderly. Ann Neurol 2011; 70:871.
  2. Charidimou A, Gang Q, Werring DJ. Sporadic cerebral amyloid angiopathy revisited: recent insights into pathophysiology and clinical spectrum. J Neurol Neurosurg Psychiatry 2012; 83:124.
  3. Greenberg SM, Vonsattel JP. Diagnosis of cerebral amyloid angiopathy. Sensitivity and specificity of cortical biopsy. Stroke 1997; 28:1418.
  4. Ferreiro JA, Ansbacher LE, Vinters HV. Stroke related to cerebral amyloid angiopathy: the significance of systemic vascular disease. J Neurol 1989; 236:267.
  5. Broderick J, Brott T, Tomsick T, Leach A. Lobar hemorrhage in the elderly. The undiminishing importance of hypertension. Stroke 1993; 24:49.
  6. Arima H, Tzourio C, Anderson C, et al. Effects of perindopril-based lowering of blood pressure on intracerebral hemorrhage related to amyloid angiopathy: the PROGRESS trial. Stroke 2010; 41:394.
  7. Obici L, Demarchi A, de Rosa G, et al. A novel AbetaPP mutation exclusively associated with cerebral amyloid angiopathy. Ann Neurol 2005; 58:639.
  8. Melchor JP, McVoy L, Van Nostrand WE. Charge alterations of E22 enhance the pathogenic properties of the amyloid beta-protein. J Neurochem 2000; 74:2209.
  9. Van Nostrand WE, Melchor JP, Cho HS, et al. Pathogenic effects of D23N Iowa mutant amyloid beta -protein. J Biol Chem 2001; 276:32860.
  10. Tsubuki S, Takaki Y, Saido TC. Dutch, Flemish, Italian, and Arctic mutations of APP and resistance of Abeta to physiologically relevant proteolytic degradation. Lancet 2003; 361:1957.
  11. Davis J, Xu F, Deane R, et al. Early-onset and robust cerebral microvascular accumulation of amyloid beta-protein in transgenic mice expressing low levels of a vasculotropic Dutch/Iowa mutant form of amyloid beta-protein precursor. J Biol Chem 2004; 279:20296.
  12. Greenberg SM, Briggs ME, Hyman BT, et al. Apolipoprotein E epsilon 4 is associated with the presence and earlier onset of hemorrhage in cerebral amyloid angiopathy. Stroke 1996; 27:1333.
  13. Premkumar DR, Cohen DL, Hedera P, et al. Apolipoprotein E-epsilon4 alleles in cerebral amyloid angiopathy and cerebrovascular pathology associated with Alzheimer's disease. Am J Pathol 1996; 148:2083.
  14. Nicoll JA, Burnett C, Love S, et al. High frequency of apolipoprotein E epsilon 2 allele in hemorrhage due to cerebral amyloid angiopathy. Ann Neurol 1997; 41:716.
  15. Greenberg SM, Vonsattel JP, Segal AZ, et al. Association of apolipoprotein E epsilon2 and vasculopathy in cerebral amyloid angiopathy. Neurology 1998; 50:961.
  16. Greenberg SM, Rebeck GW, Vonsattel JP, et al. Apolipoprotein E epsilon 4 and cerebral hemorrhage associated with amyloid angiopathy. Ann Neurol 1995; 38:254.
  17. Biffi A, Sonni A, Anderson CD, et al. Variants at APOE influence risk of deep and lobar intracerebral hemorrhage. Ann Neurol 2010; 68:934.
  18. Maxwell SS, Jackson CA, Paternoster L, et al. Genetic associations with brain microbleeds: Systematic review and meta-analyses. Neurology 2011; 77:158.
  19. Rannikmäe K, Samarasekera N, Martînez-Gonzâlez NA, et al. Genetics of cerebral amyloid angiopathy: systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 2013; 84:901.
  20. O'Donnell HC, Rosand J, Knudsen KA, et al. Apolipoprotein E genotype and the risk of recurrent lobar intracerebral hemorrhage. N Engl J Med 2000; 342:240.
  21. Biffi A, Anderson CD, Jagiella JM, et al. APOE genotype and extent of bleeding and outcome in lobar intracerebral haemorrhage: a genetic association study. Lancet Neurol 2011; 10:702.
  22. Woo D, Kaushal R, Chakraborty R, et al. Association of apolipoprotein E4 and haplotypes of the apolipoprotein E gene with lobar intracerebral hemorrhage. Stroke 2005; 36:1874.
  23. Rosand J. Epistasis is coming: are we ready? Stroke 2005; 36:1879.
  24. McCarron MO, Nicoll JA, Ironside JW, et al. Cerebral amyloid angiopathy-related hemorrhage. Interaction of APOE epsilon2 with putative clinical risk factors. Stroke 1999; 30:1643.
  25. Schmechel DE, Saunders AM, Strittmatter WJ, et al. Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease. Proc Natl Acad Sci U S A 1993; 90:9649.
  26. McCarron MO, Nicoll JA, Stewart J, et al. The apolipoprotein E epsilon2 allele and the pathological features in cerebral amyloid angiopathy-related hemorrhage. J Neuropathol Exp Neurol 1999; 58:711.
  27. Nicoll JA, Roberts GW, Graham DI. Apolipoprotein E epsilon 4 allele is associated with deposition of amyloid beta-protein following head injury. Nat Med 1995; 1:135.
  28. Wyss-Coray T, Masliah E, Mallory M, et al. Amyloidogenic role of cytokine TGF-beta1 in transgenic mice and in Alzheimer's disease. Nature 1997; 389:603.
  29. Biffi A, Shulman JM, Jagiella JM, et al. Genetic variation at CR1 increases risk of cerebral amyloid angiopathy. Neurology 2012; 78:334.
  30. Samarasekera N, Smith C, Al-Shahi Salman R. The association between cerebral amyloid angiopathy and intracerebral haemorrhage: systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 2012; 83:275.
  31. Itoh Y, Yamada M, Hayakawa M, et al. Cerebral amyloid angiopathy: a significant cause of cerebellar as well as lobar cerebral hemorrhage in the elderly. J Neurol Sci 1993; 116:135.
  32. Rosand J, Muzikansky A, Kumar A, et al. Spatial clustering of hemorrhages in probable cerebral amyloid angiopathy. Ann Neurol 2005; 58:459.
  33. Weller RO, Nicoll JA. Cerebral amyloid angiopathy: both viper and maggot in the brain. Ann Neurol 2005; 58:348.
  34. Yamada M, Itoh Y, Otomo E, et al. Subarachnoid haemorrhage in the elderly: a necropsy study of the association with cerebral amyloid angiopathy. J Neurol Neurosurg Psychiatry 1993; 56:543.
  35. Okazaki H, Reagan TJ, Campbell RJ. Clinicopathologic studies of primary cerebral amyloid angiopathy. Mayo Clin Proc 1979; 54:22.
  36. Greenberg SM, Finklestein SP, Schaefer PW. Petechial hemorrhages accompanying lobar hemorrhage: detection by gradient-echo MRI. Neurology 1996; 46:1751.
  37. Rosand J, Hylek EM, O'Donnell HC, Greenberg SM. Warfarin-associated hemorrhage and cerebral amyloid angiopathy: a genetic and pathologic study. Neurology 2000; 55:947.
  38. Sloan MA, Price TR, Petito CK, et al. 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 1995; 45:649.
  39. Hylek EM, Singer DE. Risk factors for intracranial hemorrhage in outpatients taking warfarin. Ann Intern Med 1994; 120:897.
  40. Gore JM, Sloan M, Price TR, et al. Intracerebral hemorrhage, cerebral infarction, and subdural hematoma after acute myocardial infarction and thrombolytic therapy in the Thrombolysis in Myocardial Infarction Study. Thrombolysis in Myocardial Infarction, Phase II, pilot and clinical trial. Circulation 1991; 83:448.
  41. Kase CS, Williams JP, Wyatt DA, Mohr JP. Lobar intracerebral hematomas: clinical and CT analysis of 22 cases. Neurology 1982; 32:1146.
  42. Massaro AR, Sacco RL, Mohr JP, et al. Clinical discriminators of lobar and deep hemorrhages: the Stroke Data Bank. Neurology 1991; 41:1881.
  43. Gurol ME, Dierksen G, Betensky R, et al. Predicting sites of new hemorrhage with amyloid imaging in cerebral amyloid angiopathy. Neurology 2012; 79:320.
  44. Biffi A, Halpin A, Towfighi A, et al. Aspirin and recurrent intracerebral hemorrhage in cerebral amyloid angiopathy. Neurology 2010; 75:693.
  45. Jeerakathil T, Wolf PA, Beiser A, et al. Cerebral microbleeds: prevalence and associations with cardiovascular risk factors in the Framingham Study. Stroke 2004; 35:1831.
  46. Walker DA, Broderick DF, Kotsenas AL, Rubino FA. Routine use of gradient-echo MRI to screen for cerebral amyloid angiopathy in elderly patients. AJR Am J Roentgenol 2004; 182:1547.
  47. Sveinbjornsdottir S, Sigurdsson S, Aspelund T, et al. Cerebral microbleeds in the population based AGES-Reykjavik study: prevalence and location. J Neurol Neurosurg Psychiatry 2008; 79:1002.
  48. Vernooij MW, van der Lugt A, Ikram MA, et al. Prevalence and risk factors of cerebral microbleeds: the Rotterdam Scan Study. Neurology 2008; 70:1208.
  49. Park JH, Seo SW, Kim C, et al. Pathogenesis of cerebral microbleeds: In vivo imaging of amyloid and subcortical ischemic small vessel disease in 226 individuals with cognitive impairment. Ann Neurol 2013; 73:584.
  50. Poels MM, Ikram MA, van der Lugt A, et al. Incidence of cerebral microbleeds in the general population: the Rotterdam Scan Study. Stroke 2011; 42:656.
  51. Goos JD, Henneman WJ, Sluimer JD, et al. Incidence of cerebral microbleeds: a longitudinal study in a memory clinic population. Neurology 2010; 74:1954.
  52. Dierksen GA, Skehan ME, Khan MA, et al. Spatial relation between microbleeds and amyloid deposits in amyloid angiopathy. Ann Neurol 2010; 68:545.
  53. Yates PA, Sirisriro R, Villemagne VL, et al. Cerebral microhemorrhage and brain β-amyloid in aging and Alzheimer disease. Neurology 2011; 77:48.
  54. Vernooij MW, Haag MD, van der Lugt A, et al. Use of antithrombotic drugs and the presence of cerebral microbleeds: the Rotterdam Scan Study. Arch Neurol 2009; 66:714.
  55. Gregoire SM, Jäger HR, Yousry TA, et al. Brain microbleeds as a potential risk factor for antiplatelet-related intracerebral haemorrhage: hospital-based, case-control study. J Neurol Neurosurg Psychiatry 2010; 81:679.
  56. Greenberg SM, Nandigam RN, Delgado P, et al. Microbleeds versus macrobleeds: evidence for distinct entities. Stroke 2009; 40:2382.
  57. Feldman HH, Maia LF, Mackenzie IR, et al. Superficial siderosis: a potential diagnostic marker of cerebral amyloid angiopathy in Alzheimer disease. Stroke 2008; 39:2894.
  58. Linn J, Herms J, Dichgans M, et al. Subarachnoid hemosiderosis and superficial cortical hemosiderosis in cerebral amyloid angiopathy. AJNR Am J Neuroradiol 2008; 29:184.
  59. Vernooij MW, Ikram MA, Hofman A, et al. Superficial siderosis in the general population. Neurology 2009; 73:202.
  60. Linn J, Halpin A, Demaerel P, et al. Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy. Neurology 2010; 74:1346.
  61. Charidimou A, Jäger RH, Fox Z, et al. Prevalence and mechanisms of cortical superficial siderosis in cerebral amyloid angiopathy. Neurology 2013; 81:626.
  62. Greenberg SM, Vonsattel JP, Stakes JW, et al. The clinical spectrum of cerebral amyloid angiopathy: presentations without lobar hemorrhage. Neurology 1993; 43:2073.
  63. Charidimou A, Peeters A, Fox Z, et al. Spectrum of transient focal neurological episodes in cerebral amyloid angiopathy: multicentre magnetic resonance imaging cohort study and meta-analysis. Stroke 2012; 43:2324.
  64. Eng JA, Frosch MP, Choi K, et al. Clinical manifestations of cerebral amyloid angiopathy-related inflammation. Ann Neurol 2004; 55:250.
  65. Kinnecom C, Lev MH, Wendell L, et al. Course of cerebral amyloid angiopathy-related inflammation. Neurology 2007; 68:1411.
  66. Greenberg SM, Rapalino O, Frosch MP. Case records of the Massachusetts General Hospital. Case 22-2010. An 87-year-old woman with dementia and a seizure. N Engl J Med 2010; 363:373.
  67. Chung KK, Anderson NE, Hutchinson D, et al. Cerebral amyloid angiopathy related inflammation: three case reports and a review. J Neurol Neurosurg Psychiatry 2011; 82:20.
  68. Oide T, Tokuda T, Takei Y, et al. Serial CT and MRI findings in a patient with isolated angiitis of the central nervous system associated with cerebral amyloid angiopathy. Amyloid 2002; 9:256.
  69. Le Coz P, Mikol J, Ferrand J, et al. Granulomatous angiitis and cerebral amyloid angiopathy presenting as a mass lesion. Neuropathol Appl Neurobiol 1991; 17:149.
  70. Wengert O, Harms L, Siebert E. Cerebral amyloid angiopathy-related inflammation: a treatable cause of rapidly-progressive dementia. J Neuropsychiatry Clin Neurosci 2012; 24:E1.
  71. Hermann DM, Keyvani K, van de Nes J, et al. Brain-reactive β-amyloid antibodies in primary CNS angiitis with cerebral amyloid angiopathy. Neurology 2011; 77:503.
  72. Piazza F, Greenberg SM, Savoiardo M, et al. Anti-amyloid β autoantibodies in cerebral amyloid angiopathy-related inflammation: implications for amyloid-modifying therapies. Ann Neurol 2013; 73:449.
  73. Kimura A, Sakurai T, Yoshikura N, et al. Corticosteroid therapy in a patient with cerebral amyloid angiopathy-related inflammation. J Neuroinflammation 2013; 10:39.
  74. Oh U, Gupta R, Krakauer JW, et al. Reversible leukoencephalopathy associated with cerebral amyloid angiopathy. Neurology 2004; 62:494.
  75. Fountain NB, Eberhard DA. Primary angiitis of the central nervous system associated with cerebral amyloid angiopathy: report of two cases and review of the literature. Neurology 1996; 46:190.
  76. Scolding NJ, Joseph F, Kirby PA, et al. Abeta-related angiitis: primary angiitis of the central nervous system associated with cerebral amyloid angiopathy. Brain 2005; 128:500.
  77. Schwab P, Lidov HG, Schwartz RB, Anderson RJ. Cerebral amyloid angiopathy associated with primary angiitis of the central nervous system: report of 2 cases and review of the literature. Arthritis Rheum 2003; 49:421.
  78. Arvanitakis Z, Leurgans SE, Wang Z, et al. Cerebral amyloid angiopathy pathology and cognitive domains in older persons. Ann Neurol 2011; 69:320.
  79. Auriel E, Greenberg SM. The pathophysiology and clinical presentation of cerebral amyloid angiopathy. Curr Atheroscler Rep 2012; 14:343.
  80. Gray F, Dubas F, Roullet E, Escourolle R. Leukoencephalopathy in diffuse hemorrhagic cerebral amyloid angiopathy. Ann Neurol 1985; 18:54.
  81. Smith EE, Nandigam KR, Chen YW, et al. MRI markers of small vessel disease in lobar and deep hemispheric intracerebral hemorrhage. Stroke 2010; 41:1933.
  82. Gurol ME, Viswanathan A, Gidicsin C, et al. Cerebral amyloid angiopathy burden associated with leukoaraiosis: a positron emission tomography/magnetic resonance imaging study. Ann Neurol 2013; 73:529.
  83. Poels MM, Ikram MA, van der Lugt A, et al. Cerebral microbleeds are associated with worse cognitive function: the Rotterdam Scan Study. Neurology 2012; 78:326.
  84. van Norden AG, van den Berg HA, de Laat KF, et al. Frontal and temporal microbleeds are related to cognitive function: the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort (RUN DMC) Study. Stroke 2011; 42:3382.
  85. Gregoire SM, Scheffler G, Jäger HR, et al. Strictly lobar microbleeds are associated with executive impairment in patients with ischemic stroke or transient ischemic attack. Stroke 2013; 44:1267.
  86. Kimberly WT, Gilson A, Rost NS, et al. Silent ischemic infarcts are associated with hemorrhage burden in cerebral amyloid angiopathy. Neurology 2009; 72:1230.
  87. Dumas A, Dierksen GA, Gurol ME, et al. Functional magnetic resonance imaging detection of vascular reactivity in cerebral amyloid angiopathy. Ann Neurol 2012; 72:76.
  88. Peca S, McCreary CR, Donaldson E, et al. Neurovascular decoupling is associated with severity of cerebral amyloid angiopathy. Neurology 2013; 81:1659.
  89. Ellis RJ, Olichney JM, Thal LJ, et al. Cerebral amyloid angiopathy in the brains of patients with Alzheimer's disease: the CERAD experience, Part XV. Neurology 1996; 46:1592.
  90. Pfeifer LA, White LR, Ross GW, et al. Cerebral amyloid angiopathy and cognitive function: the HAAS autopsy study. Neurology 2002; 58:1629.
  91. Goos JD, Kester MI, Barkhof F, et al. Patients with Alzheimer disease with multiple microbleeds: relation with cerebrospinal fluid biomarkers and cognition. Stroke 2009; 40:3455.
  92. Greenberg SM. Cerebral amyloid angiopathy: prospects for clinical diagnosis and treatment. Neurology 1998; 51:690.
  93. Cheng AL, Batool S, McCreary CR, et al. Susceptibility-weighted imaging is more reliable than T2*-weighted gradient-recalled echo MRI for detecting microbleeds. Stroke 2013; 44:2782.
  94. Knudsen KA, Rosand J, Karluk D, Greenberg SM. Clinical diagnosis of cerebral amyloid angiopathy: validation of the Boston criteria. Neurology 2001; 56:537.
  95. van Rooden S, van der Grond J, van den Boom R, et al. Descriptive analysis of the Boston criteria applied to a Dutch-type cerebral amyloid angiopathy population. Stroke 2009; 40:3022.
  96. Klein I, Iung B, Labreuche J, et al. Cerebral microbleeds are frequent in infective endocarditis: a case-control study. Stroke 2009; 40:3461.
  97. Greenberg SM, Eng JA, Ning M, et al. Hemorrhage burden predicts recurrent intracerebral hemorrhage after lobar hemorrhage. Stroke 2004; 35:1415.
  98. Altmann-Schneider I, Trompet S, de Craen AJ, et al. Cerebral microbleeds are predictive of mortality in the elderly. Stroke 2011; 42:638.
  99. Mandybur TI. Cerebral amyloid angiopathy: the vascular pathology and complications. J Neuropathol Exp Neurol 1986; 45:79.
  100. Vonsattel JP, Myers RH, Hedley-Whyte ET, et al. Cerebral amyloid angiopathy without and with cerebral hemorrhages: a comparative histological study. Ann Neurol 1991; 30:637.
  101. Natté R, Vinters HV, Maat-Schieman ML, et al. Microvasculopathy is associated with the number of cerebrovascular lesions in hereditary cerebral hemorrhage with amyloidosis, Dutch type. Stroke 1998; 29:1588.
  102. Verbeek MM, Kremer BP, Rikkert MO, et al. Cerebrospinal fluid amyloid beta(40) is decreased in cerebral amyloid angiopathy. Ann Neurol 2009; 66:245.
  103. Johnson KA, Gregas M, Becker JA, et al. Imaging of amyloid burden and distribution in cerebral amyloid angiopathy. Ann Neurol 2007; 62:229.
  104. Ly JV, Donnan GA, Villemagne VL, et al. 11C-PIB binding is increased in patients with cerebral amyloid angiopathy-related hemorrhage. Neurology 2010; 74:487.
  105. Graf CJ, Perret GE, Torner JC. Bleeding from cerebral arteriovenous malformations as part of their natural history. J Neurosurg 1983; 58:331.
  106. Izumihara A, Ishihara T, Iwamoto N, et al. Postoperative outcome of 37 patients with lobar intracerebral hemorrhage related to cerebral amyloid angiopathy. Stroke 1999; 30:29.
  107. Hart RG, Boop BS, Anderson DC. Oral anticoagulants and intracranial hemorrhage. Facts and hypotheses. Stroke 1995; 26:1471.
  108. Morgenstern LB, Hemphill JC 3rd, Anderson C, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2010; 41:2108.
  109. Thrift AG, McNeil JJ, Forbes A, Donnan GA. Risk factors for cerebral hemorrhage in the era of well-controlled hypertension. Melbourne Risk Factor Study (MERFS) Group. Stroke 1996; 27:2020.
  110. Giroud M, Creisson E, Fayolle H, et al. Risk factors for primary cerebral hemorrhage: a population-based study--the Stroke Registry of Dijon. Neuroepidemiology 1995; 14:20.
  111. Iribarren C, Jacobs DR, Sadler M, et al. Low total serum cholesterol and intracerebral hemorrhagic stroke: is the association confined to elderly men? The Kaiser Permanente Medical Care Program. Stroke 1996; 27:1993.
  112. González-Duarte A, Cantú C, Ruíz-Sandoval JL, Barinagarrementeria F. Recurrent primary cerebral hemorrhage: frequency, mechanisms, and prognosis. Stroke 1998; 29:1802.
  113. Segal AZ, Chiu RI, Eggleston-Sexton PM, et al. Low cholesterol as a risk factor for primary intracerebral hemorrhage: A case-control study. Neuroepidemiology 1999; 18:185.
  114. Yano K, Reed DM, MacLean CJ. Serum cholesterol and hemorrhagic stroke in the Honolulu Heart Program. Stroke 1989; 20:1460.
  115. Shinkawa A, Ueda K, Hasuo Y, et al. Seasonal variation in stroke incidence in Hisayama, Japan. Stroke 1990; 21:1262.
  116. Noda H, Iso H, Irie F, et al. Low-density lipoprotein cholesterol concentrations and death due to intraparenchymal hemorrhage: the Ibaraki Prefectural Health Study. Circulation 2009; 119:2136.
  117. Wang X, Dong Y, Qi X, et al. Cholesterol levels and risk of hemorrhagic stroke: a systematic review and meta-analysis. Stroke 2013; 44:1833.
  118. Woo D, Kissela BM, Khoury JC, et al. Hypercholesterolemia, HMG-CoA reductase inhibitors, and risk of intracerebral hemorrhage: a case-control study. Stroke 2004; 35:1360.
  119. Amarenco P, Labreuche J, Lavallée P, Touboul PJ. Statins in stroke prevention and carotid atherosclerosis: systematic review and up-to-date meta-analysis. Stroke 2004; 35:2902.
  120. Baigent C, Keech A, Kearney PM, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 2005; 366:1267.
  121. Leker RR, Khoury ST, Rafaeli G, et al. Prior use of statins improves outcome in patients with intracerebral hemorrhage: prospective data from the National Acute Stroke Israeli Surveys (NASIS). Stroke 2009; 40:2581.
  122. Hackam DG, Austin PC, Huang A, et al. Statins and intracerebral hemorrhage: a retrospective cohort study. Arch Neurol 2012; 69:39.
  123. Hackam DG, Woodward M, Newby LK, et al. Statins and intracerebral hemorrhage: collaborative systematic review and meta-analysis. Circulation 2011; 124:2233.
  124. McKinney JS, Kostis WJ. Statin therapy and the risk of intracerebral hemorrhage: a meta-analysis of 31 randomized controlled trials. Stroke 2012; 43:2149.
  125. Westover MB, Bianchi MT, Eckman MH, Greenberg SM. Statin use following intracerebral hemorrhage: a decision analysis. Arch Neurol 2011; 68:573.
  126. Goldstein LB. Statins after intracerebral hemorrhage: to treat or not to treat. Arch Neurol 2011; 68:565.
  127. Amarenco P, Labreuche J. Lipid management in the prevention of stroke: review and updated meta-analysis of statins for stroke prevention. Lancet Neurol 2009; 8:453.
  128. Kloppenborg RP, Richard E, Sprengers ME, et al. Steroid responsive encephalopathy in cerebral amyloid angiopathy: a case report and review of evidence for immunosuppressive treatment. J Neuroinflammation 2010; 7:18.
  129. Sakaguchi H, Ueda A, Kosaka T, et al. Cerebral amyloid angiopathy-related inflammation presenting with steroid-responsive higher brain dysfunction: case report and review of the literature. J Neuroinflammation 2011; 8:116.
  130. Fountain NB, Lopes MB. Control of primary angiitis of the CNS associated with cerebral amyloid angiopathy by cyclophosphamide alone. Neurology 1999; 52:660.
  131. Mandybur TI, Balko G. Cerebral amyloid angiopathy with granulomatous angiitis ameliorated by steroid-cytoxan treatment. Clin Neuropharmacol 1992; 15:241.