Die sporadische zerebrale Amyloidangiopathie – eine aktuelle Übersicht mit klinischen Fallbeispielen

Zusammenfassung

Die sporadische zerebrale Amyloidangiopathie (CAA) ist eine im fortgeschrittenen Lebensalter auftretende Mikroangiopathie. Neuropathologisch gekennzeichnet ist die CAA durch die Ablagerung von ß-Amyloid (Aß) in dünn- bis mittelkalibrigen Arteriolen, Kapillaren und Venolen des Hirnkortex sowie der Leptomeningen. Vor allem in den letzten Jahren wurde evident, dass die CAA eine wichtige Ursache spontaner intrazerebraler Blutungen sowie auch kognitiver Beeinträchtigungen im höheren Lebensalter darstellt. Die klinischen und bildgebenden Manifestationen können sehr unterschiedlich sein und reichen von akut auftretenden fokalen neurologischen Defiziten infolge einer intrazerebralen Lobärblutung (ICB) bis hin zu einem Symptomkomplex aus subakut auftretenden kognitiven und psychischen Veränderungen, Kopfschmerzen sowie epileptischen Anfällen aufgrund multifokaler, teilweise konfluierender Marklagerödeme durch einen Aß-vermittelten Entzündungsprozess. In dieser Übersichtsarbeit sollen die aktuellen Erkenntnisse über die CAA strukturiert und ausführlich anhand eigener Fallbeispiele dargestellt werden.

Abstract

Sporadic cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease in the elderly. Neuropathologically, it is characterized by deposition of amyloid-ß (Aß) in the wall of small to medium-sized arteries, capillaries and venules of the cerebral cortex and leptomeninges. Over the last years it was recognized as an important cause of spontaneous intracerebral hemorrhage and cognitive deficits in the elderly. The clinical and radiological manifestations are diverse ranging from acute onset focal neurological deficits due to intracerebral lobar hemorrhage to subacute progressive cognitive impairment due to Aß-mediated inflammation confluent subcortical edema. The wide clinico-radiological spectrum of CAA is a major challenge for the neurologist and stroke physician. This review provides a structured and detailed look at recent developments in CAA, and is illustrated with case studies.

Schlüsselwörter

sporadische zerebrale Amyloidangiopathie - inflammatorische Amyloidangiopathie - „amyloid spells“ - intrazerebrale Blutung - kognitive Defizite

Key words

sporadic cerebral amyloid angiopathy - inflammatory amyloid angiopathy - amyloid spells - intracerebral bleeding - cognitive impairment

• Literatur

• 1 Vinters HV. Cerebral amyloid angiopathy. A critical review. Stroke J Cereb Circ 1987; 18: 311-324
• 2 Attems J, Jellinger K, Thal DR et al. Review: sporadic cerebral amyloid angiopathy. Neuropathol Appl Neurobiol 2011; 37: 75-93
• 3 Adeoye O, Broderick JP. Advances in the management of intracerebral hemorrhage. Nat Rev Neurol 2010; 6: 593-601
• 4 Qureshi AI, Mendelow AD, Hanley DF. Intracerebral haemorrhage. Lancet Lond Engl 2009; 373: 1632-1644
• 5 Coria F, Rubio I. Cerebral amyloid angiopathies. Neuropathol Appl Neurobiol 1996; 22: 216-227
• 6 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: 135-141
• 7 Campbell DM, Bruins S, Vogel H et al. Intracerebral hemorrhage caused by cerebral amyloid angiopathy in a 53-year-old man. J Neurol 2008; 255: 597-598
• 8 Okazaki H, Reagan TJ, Campbell RJ. Clinicopathologic studies of primary cerebral amyloid angiopathy. Mayo Clin Proc 1979; 54: 22-31
• 9 Haglund M, Passant U, Sjöbeck M et al. Cerebral amyloid angiopathy and cortical microinfarcts as putative substrates of vascular dementia. Int J Geriatr Psychiatry 2006; 21: 681-687
• 10 Charidimou A, Gang Q, Werring DJ. Sporadic cerebral amyloid angiopathy revisited: recent insights into pathophysiology and clinical spectrum. J Neurol Neurosurg Psychiatry 2012; 83: 124-137
• 11 Anderson NE, Chung K, Willoughby E et al. Neurological manifestations of phaeochromocytomas and secretory paragangliomas: a reappraisal. J Neurol Neurosurg Psychiatry 2013; 84: 452-457
• 12 Kimura A, Sakurai T, Yoshikura N et al. Corticosteroid therapy in a patient with cerebral amyloid angiopathy-related inflammation. J Neuroinflammation 2013; 10: 39
• 13 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
• 14 Mastaglia FL, Byrnes ML, Johnsen RD et al. Prevalence of cerebral vascular amyloid-beta deposition and stroke in an aging Australian population: a postmortem study. J Clin Neurosci Off J Neurosurg Soc Australas 2003; 10: 186-189
• 15 Keage HAD, Carare RO, Friedland RP et al. Population studies of sporadic cerebral amyloid angiopathy and dementia: a systematic review. BMC Neurol 2009; 9: 3
• 16 Pfeifer LA, White LR, Ross GW et al. Cerebral amyloid angiopathy and cognitive function: the HAAS autopsy study. Neurology 2002; 58: 1629-1634
• 17 Jellinger KA. Alzheimer disease and cerebrovascular pathology: an update. J Neural Transm Vienna Austria 1996 2002; 109: 813-836
• 18 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: 1592-1596
• 19 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: 637-649
• 20 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: 702-709
• 21 Montaner J. Genetics of intracerebral haemorrhage: a tsunami effect of APOE ε2 genotype on brain bleeding size?. Lancet Neurol 2011; 10: 673-675
• 22 Biffi A, Anderson CD, Battey TWK et al. Association Between Blood Pressure Control and Risk of Recurrent Intracerebral Hemorrhage. JAMA 2015; 314: 904-912
• 23 Glenner GG, Wong CW. Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. 1984. Biochem Biophys Res Commun 2012; 425: 534-539
• 24 Roher AE, Lowenson JD, Clarke S et al. beta-Amyloid-(1–42) is a major component of cerebrovascular amyloid deposits: implications for the pathology of Alzheimer disease. Proc Natl Acad Sci U S A 1993; 90: 10836-10840
• 25 Gravina SA, Ho L, Eckman CB et al. Amyloid beta protein (A beta) in Alzheimer’s disease brain. Biochemical and immunocytochemical analysis with antibodies specific for forms ending at A beta 40 or A beta 42(43). J Biol Chem 1995; 270: 7013-7016
• 26 Attems J, Lintner F, Jellinger KA. Amyloid beta peptide 1–42 highly correlates with capillary cerebral amyloid angiopathy and Alzheimer disease pathology. Acta Neuropathol (Berl) 2004; 107: 283-291
• 27 Puchtler H, Waldrop FS, Meloan SN. A review of light, polarization and fluorescence microscopic methods for amyloid. Appl Pathol 1985; 3: 5-17
• 28 Attems J. Sporadic cerebral amyloid angiopathy: pathology, clinical implications, and possible pathomechanisms. Acta Neuropathol (Berl) 2005; 110: 345-359
• 29 Love S, Miners S, Palmer J et al. Insights into the pathogenesis and pathogenicity of cerebral amyloid angiopathy. Front Biosci Landmark Ed 2009; 14: 4778-4792
• 30 Burgermeister P, Calhoun ME, Winkler DT et al. Mechanisms of cerebrovascular amyloid deposition. Lessons from mouse models. Ann N Y Acad Sci 2000; 903: 307-316
• 31 Fryer JD, Simmons K, Parsadanian M et al. Human apolipoprotein E4 alters the amyloid-beta 40:42 ratio and promotes the formation of cerebral amyloid angiopathy in an amyloid precursor protein transgenic model. J Neurosci Off J Soc Neurosci 2005; 25: 2803-2810
• 32 Herzig MC, Van Nostrand WE, Jucker M. Mechanism of cerebral beta-amyloid angiopathy: murine and cellular models. Brain Pathol Zurich Switz 2006; 16: 40-54
• 33 Bu G. Apolipoprotein E and its receptors in Alzheimer’s disease: pathways, pathogenesis and therapy. Nat Rev Neurosci 2009; 10: 333-344
• 34 Preston SD, Steart PV, Wilkinson A et al. Capillary and arterial cerebral amyloid angiopathy in Alzheimer’s disease: defining the perivascular route for the elimination of amyloid beta from the human brain. Neuropathol Appl Neurobiol 2003; 29: 106-117
• 35 Weller RO, Nicoll JAR. Cerebral amyloid angiopathy: both viper and maggot in the brain. Ann Neurol 2005; 58: 348-350
• 36 Rosand J, Muzikansky A, Kumar A et al. Spatial clustering of hemorrhages in probable cerebral amyloid angiopathy. Ann Neurol 2005; 58: 459-462
• 37 Passero S, Burgalassi L, Andrea PD et al. Recurrence of bleeding in patients with primary intracerebral hemorrhage. Stroke J Cereb Circ 1995; 26: 1189-1192
• 38 Flaherty ML, Kissela B, Woo D et al. The increasing incidence of anticoagulant-associated intracerebral hemorrhage. Neurology 2007; 68: 116-121
• 39 Eckman MH, Wong LKS, Soo YOY et al. Patient-specific decision-making for warfarin therapy in nonvalvular atrial fibrillation: how will screening with genetics and imaging help?. Stroke J Cereb Circ 2008; 39: 3308-3315
• 40 Biffi A, Halpin A, Towfighi A et al. Aspirin and recurrent intracerebral hemorrhage in cerebral amyloid angiopathy. Neurology 2010; 75: 693-698
• 41 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: 679-684
• 42 Goldstein LB. Statins after intracerebral hemorrhage: to treat or not to treat. Arch Neurol 2011; 68: 565-566
• 43 Westover MB, Bianchi MT, Eckman MH et al. Statin use following intracerebral hemorrhage: a decision analysis. Arch Neurol 2011; 68: 573-579
• 44 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 J Cereb Circ 2010; 41: 394-396
• 45 Werring DJ. Cerebral Microbleeds and Thrombolysis-Associated Intracerebral Hemorrhage: Cause for Concern, or Just a Distraction?. Stroke J Cereb Circ 2015; 46: 2403-2405
• 46 Turc G, Sallem A, Moulin S et al. Microbleed Status and 3-Month Outcome After Intravenous Thrombolysis in 717 Patients With Acute Ischemic Stroke. Stroke J Cereb Circ 2015; 46: 2458-2463
• 47 Campbell BCV, Donnan GA, Lees KR et al. Endovascular stent thrombectomy: the new standard of care for large vessel ischaemic stroke. Lancet Neurol 2015; 14: 846-854
• 48 Emberson J, Lees KR, Lyden P et al. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet Lond Engl 2014; 384: 1929-1935
• 49 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: 20-26
• 50 Charidimou A, Law R, Werring DJ. Amyloid “spells” trouble. Lancet Lond Engl 2012; 380: 1620
• 51 Greenberg SM, Vonsattel JP, Stakes JW et al. The clinical spectrum of cerebral amyloid angiopathy: presentations without lobar hemorrhage. Neurology 1993; 43: 2073-2079
• 52 Roch JA, Nighoghossian N, Hermier M et al. Transient neurologic symptoms related to cerebral amyloid angiopathy: usefulness of T2*-weighted imaging. Cerebrovasc Dis Basel Switz 2005; 20: 412-414
• 53 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 J Cereb Circ 2012; 43: 2324-2330
• 54 Kloppenborg RP, Richard E, Sprengers MES et al. Steroid responsive encephalopathy in cerebral amyloid angiopathy: a case report and review of evidence for immunosuppressive treatment. J Neuroinflammation 2010; 7: 18
• 55 Linn J, Halpin A, Demaerel P et al. Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy. Neurology 2010; 74: 1346-1350
• 56 Knudsen KA, Rosand J, Karluk D et al. Clinical diagnosis of cerebral amyloid angiopathy: validation of the Boston criteria. Neurology 2001; 56: 537-539
• 57 Auriel E, Charidimou A, Gurol ME et al. Validation of Clinicoradiological Criteria for the Diagnosis of Cerebral Amyloid Angiopathy-Related Inflammation. JAMA Neurol 2016; 73: 197-202
• 58 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: 449-458