Journal of

J. Neurol. 214, 195--206 (1977)

Neurology © by Springer-Verlag 1977

Cerebrovascular Amyloidosis with Cerebral Hemorrhage* K. Jellinger Division of Neuropathology, Neurological Institute of the University of Vienna, Schwarzspanierstr. 17, A-1090 Wien, and Dept. of Neurology, Lainz-Hospital Vienna, Wolkersbergenstr. 1, A-1130 Wien, Austria

Summary. More than 1400 necropsies performed on patients with either a nontraumatic cerebral hemorrhage (400 cases) or with dementia over the age of 55 (1010 cases), or both, have been reviewed. There were 15 cases in which a cerebral hemorrhage had occurred together with cerebral amyloid angiopathy all of whom had been demented. Eight of the 15 patients were hypertensive. The 7 non-hypertensives showing only the amyloid change included two cases of "atypical" Alzheimer's disease with acute neurological features, and 5 cases of senile dementia (aged 72 to 78 years) coupled with focal neurological disorders. In the hypertensive patients, aged 67 to 86 years, with a progressive dementing syndrome and acute neurological signs, multiple ball-like hemorrhages (7 cases) and / or cerebral hematomas (3 cases) were associated with a combination of amyloid and hyalinar (hypertensive) angiopathy, often affecting segments of the same pial and cortical vessels. From these data and recent reports on lethal cerebral hemorrhage occurring spontaneously or after neurosurgical procedures in demented old people, cerebral amyloid angiopathy, which is not necessarily associated with systemic amyloidosis or severe (pre)senile cerebral degeneration, may be considered a rare but important cause of cerebral hemorrhage in the aged. The "vascular" type of presenile dementia, occasionally complicated by focal cerebrovascular lesions or bleeds, is considered a variant of Alzheimer's disease. The mechanism leading to formation of cerebral amyloid is unknown.

Key words: Cerebrovascular amyloidosis - Congophilic angiopathy - Cerebral hemorrhage - Alzheimer's disease - Senile dementia. Zusammenfassung. Ober 1400 Autopsien an Patienten mit nicht-traumatischen Hirnblutungen (400 F~ille) oder mit organischer Demenz jenseits des 55. Lebensjahres (1010 F~ille) bzw. deren Kombination wurden untersucht. Es fanden sich 15 F~ille, bei denen Hirnblutungen bei cerebraler Amyloidangiopathie aufgetreten waren. Bei allen Patienten bestand eine Demenz. 8 der 15 Dedicated to Prf. St. K/~rnyeyon the occasion of his 75th anniversary

196

K. Jellinger Patienten hatten Hochdruck; in 7 bestand ein solcher nicht. Die nichthypertone Gruppe, die ausschliel]lich Amyloidver~inderungen bot, umfal]te 2 F~lle yon ,,atypischem" M. Alzheimer mit akuten neurologischen Ausf~illen und 5 F~lle von seniler Demenz (Alter 72--78 Jahre) mit fokalen neurologischen Zeichen. Bei den hypertonen Patienten (Alter 67--86 Jahre), die klinisch progrediente Demenz mit akuten neurologischen Ausf~llen boten, bestanden multiple Kugelblutungen (7 F~lle) und/oder Massenblutungen (3 F~ille) bei Kombination von Amyloid- und Hochdruckangiopathie, die oft Segmente derselben pialen oder Rindengef~l]e betrafen. Aufgrund dieser Befunde sowie neuerer Beobachtungen tiber t~dliche Hirnblutungen mit spontanem Auftreten oder im AnschluB an neurochirurgische Eingriffe bei dementen alten Menschen kann die zerebrale Amyloidangiopathie, die nicht mit genereller Amyloidose oder schweren (pra)senilen Hirnsch~den verbunden sein muB, als seltene, aber wichtige Ursache yon Hirnblutungen im Alter angesprochen werden. Der ,,vaskul~ire" Typ der pr~tsenilen Demenz, der mitunter durch fokale zerebrovaskul~re L~sionen oder Blutungen kompliziert ist, gilt als Variante der Alzheimerschen Krankheit. Die zur Bildung zerebralen Amyloids ftihrenden Mechanismen sind unklar.

Introduction

Cerebral amyloid angiopathy [8] or congophilic angiopathy [27], also referred to as plaque-like ["drusige"] angiopathy [31] or dyshoric angiopathy [24, 36], in which amyloid deposits within and around the walls of the small pial and intracerebral vessels have been demonstrated by both light [4, 8, 22, 31, 32, 41] and electronmicroscopy [23, 29, 30, 39, 44], is a common but inconstant finding in Alzheimer's disease and senile dementia [6, 10, 22, 27, 32, 36, 43], and appears as well in nondemented old people [4, 9, 22, 27, 43], and in aged dogs [4, 29, 37, 44]. Cerebrovascular amyloidosis (CVA) in younger patients is rare [ 12], but has been observed in a demented boxer [3] and in elderly mongols [28, 32]. Recently, the importance of CVA as a cause of non-hypertensive hemorrhage has been stressed [9, 15, 16, 39, 42], and hereditary cerebral hemorrhage associated with amyloid deposits in the brain arteries has been described [12]. CVA, which is often combined with senile parenchymal changes, may give rise to multiple small hemorrhages and cortical microinfarcts or even to large hematomas which are the common CNS complications in hypertensive disease [1, 26, 41]. While hypertensive angiopathy, usually seen in malignant hypertension [ 1], is rare in old demented people with or without hypertensive cardiovascular disease [9], a simultaneous affection of the pia-cortical vessels by hyalinosis and amyloid angiopathy has been observed [10, 14, 22, 27, 40]. The purpose of this report is to study the incidence and clinical significance of CVA complicated by hemorrhage. The material consists of 15 cases with congophilic angiopathy, eight of which were associated with massive cerebral hemorrhage, while small old and/or recent bleeds were present in 11 of these brains.

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Material and Methods The 15 cases reported here were selected from two independent, but partly overlapping post mortem series collected at the Neurological Institute, University of Vienna. One series included 400 consecutive autopsy cases of non-traumatic cerebral hematomas of various origin [17]; the other concerns a non-selected autopsy series of 1010demented people over the age of 55, derived from various sources. The techniques of formalin fixation, embedding and staining for light microscopy were standard, and included periodic acid-Schiff (PAS), Congo red, and Bodian methods in most cases.

Results In the post mortem series of organic dementias in advanced age, 52.8% showed the histological features of presenile and senile cerebral degeneration, including 92 cases of Alzheimer's disease, 23 of Pick's disease, and 412 cases of senile dementia; 21.5% were cerebrovascular diseases with mild (two-thirds) or negligible senile parenchymal changes (one-third); 16.5% were mixed senile-vascular encephalopathies, and the remainder were disorders of various origin [16]. In this material, with similar relative percentages of the main diagnostic groups as other autopsy series of demented old people [33, 38], 15 cases of CVA with hemorrhages were observed. Eight brains demonstrated large hematomas which were located in the frontal and temporal lobes (3 cases each), and in the parietal or occipital lobes, and basal ganglia (one case each). These eight instances of "atypiear' hematomas associated with congophilic angiopathy were found among 400 cases of nontraumatic cerebral mass hemorrhages, CVA thus accounting for two percent of cerebral bleeds. None of these patients had had a previous brain biopsy or shunting although both neurosurgical procedures have recently been reported to be complicated by lethal hemorrhagic episodes in cases with congophilic angiopathy [39]. Clinically, all patients had been demented; eight were non-hypertensive (Table 1), seven were hypertensive (Table 2). The non-hypertensive group showed only the amyloid change, while the hypertensive group revealed a hyaline angiopathy in addition to the congophilic angiopathy.

Group 1. CVA complicated by cerebral hemorrhage was seen in two cases of Alzheimer's disease with focal neurological features. They were selected from 92 autopsy cases of Alzheimer's disease, 78% of which showed amyloid angiopathy without very much vascular damage in all the other brains. In a 64 year old woman who, after 3 months of mental illness, developed acute hemiparesis and an agnostic-aphasic syndrome, in addition to some recent cherry-sized bleeds in the frontal and temporal lobes (Fig. 1A), there were multiple small foci of old and recent cortical hemorrhages associated with amyloid deposits in the pial and cortical arterioles (Fig. 1 B), with frequent occurrence of paravascular amyloidcontaining plaques (Fig. 1 C). A male aged 65 years who developed subacute dementia and paraparesis of the legs, and died in uremic coma, at autopsy showed deposits of amyloid in various organs including the cardiovascular system,

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Fig. 1 A--C. "Atypical" Alzheimer's disease with focal neurological signs in female aged 64 years. A Recent subcortical hemorrhages (H) in frontal and temporal gyri. Luxol-fast-blue. B Congophilic angiopathy of leptomeningeal (L) and cortical (C) arterioles; senile plaques (P) in the cerebral cortex showing marginal gliosis (G) with hemosiderin. C.V. × 120. C Senile plaque (P) attached to amyloid degenerated cortical arterioles. Bodian silver impregnation × 260 Fig. 1 D and E. Demented female aged 78 years with small cortical hemorrhages in left frontal region (D) and ball-like bleed around degenerated cortical arteriole (E), van Gieson's elastic stain x45

Fig. 1 F--H. Demented male aged 75 years with acute mass hemorrhage in left temporoinsular region (F). G PAS-positive material in the wall of cortical metaarteriole extending into adjacent parenchyma PAS × 240. CortiCal arteriole with amyloid deposits extending into adjacent parenchyma with paravascular plaques (P). Congored--polarized × 400

Cerebrovascular Amyloidosis with Cerebral Hemorrhage

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pancreas, kidneys and brain, associated with multiple small old and recent hemorrhages and microinfarctions in the cortex. This case was the only one of the present series in which extracerebral amyloid was observed. Five cases of senile dementia, including 3 males and 2 females ranging in age from 72 to 78 years (mean 76 years), after 2 to 4 years of mental illness, developed acute neurological disorders with hemiparesis, aphasia (3 cases each) or hemianopia (one patient), leading to death within 2 days to 2 months. Neither high blood pressure nor any morbid anatomical signs of hypertensive cardiovascular disease or severe renal damage were reported in these patients, and there was only mild atherosclerosis of the main cerebral arteries. All brains, in addition to severe diffuse atrophy, with brain weights ranging from 1040 to 1420 g showed considerable senile parenchymal changes, with large numbers of neuritic plaques and neurofibrillary tangels associated with amyloid deposits in the pia-cortical arteries, arterioles, and intracerebral capillaries, often extending into the parenchyma (Figs. 1 G and H). Senile plaques were often attached to vessels affected by amyloidosis (Figs. 1 C and H). In the two cases of Alzheimer's disease and in one senile dementia with striatal hemorrhage, the basal ganglia and cerebellum were also involved, but much less than the pia-cortical vasculature. All 5 brains showed hematomas in the left hemispheres, affecting the peripheral white matter mainly and cortex of the temporal (2 cases), frontotemporal and occipital lobes (one case each). Rupture of the bleed into the subarachnoid space was seen in two brains with concurrent multiple small cortical hemorrhages (Figs 1 D - - F ) . One of them, a demented hypotensive male aged 75 years with acute hemiplegia and aphasia, died 2 days after partial evacuation of a large hematoma of the left temporal region extending into the insula (Fig. 1 F). A 72 year old woman with a 2 year history of progressive dementia died in coma about one month after a fall due to an apoplectic episode, Autopsy disclosed a walnutsized subacute hematoma in the left corpus striatum and insula penetrating into the sylvian fissure, without any evidence of traumatic damage to the brain.

Group 2. In 8 patients, 5 females and 3 males, aged 67 to 86 years (average 74.1 years), progressive dementia with a duration of mental illness between one and 6 years was coupled with acute hemiparesis a n d / o r aphasia (6 cases) or other acute and recurrent neurological disorders with terminal coma (2 cases) occurring between 2 days and 3 months prior to death. In each case high blood pressure had been recorded, and autopsy revealed vascular damage to the kidneys in all, and cardiomegaly in at least 3 of them. The cerebral vascular tree showed moderate to severe atherosclerosis, associated with a lacunar state of the basal ganglia in 4 cases, multiple old vascular infarcts in the brain and cerebellum in a 79 year old male, and multiple glial scars in the cerebral cortex in another case. Multiple old a n d / o r recent small ball-like cortical bleeds were seen in 7 cases, and were associated with recent mass hemorrhages in two, while a demented woman aged 86 years presenting with acute hemiparesis and aphasia died within 5 days from a large frontoparietal hematoma. Moderate to severe CVA, with amyloid deposits in the small pial arteries and perforating cortical vessels showing frequent duplication of their wails [35], was often accompanied by onion skin intimal proliferation (obliterative angiosclerosis)

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Fig. 2 A and B. Occurrence of congophilic and hyalinar angiopathy in hypertensive female aged 75 with senile dementia. A Perforating cortical artery showing segmental deposition of hyalin (H) and amyloid material (arrows). Other perforating arteriole (right) with slight congophilic degeneration. Senile plaque (P) in superficial cortex. Congo red x 90. B Hyalinosis of small cortical artery (H) with adjacent arterioles showing congophilic degeneration (C); senile plaque (P). Congored/polarized × 120

Fig. 2 C. Occasional hyalin (H) and severe congophilic degeneration with duplicated walls (D) of small pial and cortical vessels (C) in demented male aged 79years with multiple infarctions and acute mass hemorrhage. C. V. xl00.

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or marked thickening of the walls of small meningeal, cortical and subcortical arteries (Fig. 2C) with deposition of hyalin or fibrin material and subsequent fibrosis, referred to as hypertensive angiopathy of fibrinoid angionecrosis [ 1, 26]. Not infrequently, the same vascular channel of pial and particularly perforating cortical arteries and arterioles showed hyaline degeneration (Congo red negative, isotropic material) along one segment and amyloid (Congo red positive, birefringent) deposits along another (Fig. 2 A, B), or coincidence of both types of deposits within the same segment. While cortical microinfarctions with arterioles displaying amyloid and/or hyaline degeneration were seen in 3 cases, no eongophilic angiopathy of the basal ganglia and cerebellum was observed in this group.

Discussion

The present study and other recent reports on demented old people who died from a spontaneous cerebrovascular episode [10, 25, 42] or lethal cerebral hemorrhage subsequent to diagnostic neurosurgical procedures [39], without recognition of hypertension, indicated that congophilic angiopathy, which is not necessarily associated with generalized amyloidosis or severe (pre)senile dementia, may be considered a rare but important cause of intracranial hemorrhage in the aged. In another small group of hypertensive patients presenting with dementing syndromes, the coincidence of CVA with hyalinar angiopathy, occasionally observed in both "unusual" forms [7, 10] and typical cases of Alzheimer's disease [22, 27, 40], could have been responsible for the focal neurological features or lethal cerebral bleeds. Mandybur [22] reviewing the incidence of CVA in Alzheimer's disease had observed similar arteriolar necrosis in some of his cases and had attributed this to hypertension, although no cerebral hemorrhage was found in his material nor in the majority of cases in other autopsy series of Alzheimer's disease [4, 6, 33]. Gerhard et al. [10], on the other hand, pointed out that high blood pressure had never been found in the reported cases presenting a combination of congophilic angiopathy and hyalinar degeneration of the pia-cortical arterioles, with miliary aneurysms and old and fresh hemorrhages. They proposed that the "cortical type" of hypertensive vascular disease, seen in this"atypical" form of Alzheimer's disease, is related rather to the intense degree of amyloid change in the small cerebral vessels, probably associated with some rheumatoid disease [10, 42]. Congophilic cerebral angiopathy, previously postulated to be more common in the familial form of Alzheimer's disease [2, 7, 21, 46], has been shown by systematic studies to be a frequent but inconstant finding both in non-familial cases of Alzheimer's disease [4, 22] and in senile dementia [9, 36]. The clinical features of the patients with CVA are either an acute onset of dementia [14] or a progressive dementing syndrome coupled with acute stroke-like catastrophes or other focal neurological signs which are rather uncommon in "classical" Alzheimer's disease [6, 10, 37]. The neurohistological features of these cases of "atypical" Alzheimer's disease are those of presenile cerebral degeneration combined with amyloid angiopathy [6]. The occurrence of dementia, senile plaques and neurofibrillary degeneration with congophilic angiopathy prompted most investigators to c o n -

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sider this entity a variant of Alzheimer's disease or a special "vascular" type of presenile dementia [10, 22, 42], although hemorrhage complicating CVA may also occur in non-demented patients [12, 25]. Sytematical studies indicate that there is a close association between senile plaques, particularly the amyloid-rich forms, and the severity of congophilic angiopathy, while there is no indication of a direct interrelationship between CVA and neurofibrillary tangles, which do not accumulate amyloid filaments but consist of bifilar helices made up of 100 A filaments [ 18, 45], although both lesions often appear together in senile brains and Alzheimer's disease [4, 9, 22, 73, 42]. In spite of the different clinical patterns and the more frequently related occurrence of focal cerebrovascular lesions or hemorrhages with congophilic angiopathy, its nosological distinction from Alzheimer's disease without amyloid angiopathy [39] does not appear reasonable, because both syndromes are closely related to each other. Senile plaques and congophilic angiopathy, both containing amyloid, are considered as expressions o f " p r i m a r y " or isolated cerebral amyloidosis [22, 30, 32, 42, 44], which is not necessarily correlated with other senile changes, particularly neurofibrillary degeneration, and systemic amyloidosis. Since both these syndromes frequently occur together, some c o m m o n pathogenetic factors are assumed, although the origin of amyloid in the central nervous system remains obscure. The brain is rarely affected by the primary, secondary or familial forms of systemic amyloidosis and, apart from some rare exceptions with unequivocal brain involvement in systemic disease [ 13, 19, 20], the existence of cerebral amyloid in the form of plaques or in the cerebral vessels in any of these conditions is rare. On the other hand, a mild degree of vascular amyloidosis in the internal organs of some senile patients with cerebral congophile angiopathy has been reported [27, 23, 37], and was seen in one of our cases o f Alzheimer's disease with miliary bleeds. In addition, there may be concomitant occurrence of cerebral amyloid and of the senile type of cardiovascular and pancreatic amyloidosis commonly accompanying ageing [32, 34]. The primary mechanism leading to the various forms of cerebral amyloid are unknown. Amyloid may be synthesized locally or brought to the brain in a plasma precursor form; each of these mechanisms has been a matter of discussion [22, 30, 37, 44]. There is some evidence that the amyloid associated with ageing is amyloid B, an immunoglobulin, the degradation of which by lysosomes leads to extracellular amyloid formation [11]. The hypothesis of the significance of immune complexes in the pathogenesis of amyloid and plaque formation in the brain has gained support by the E.M. demonstration of amyloid in the plaques of experimental scrapie in mice [5], and in Kuru and Creutzfeldt-Jakob disease [20], although no conventional immunological responses are so far known in these slow-virus diseases. From the frequent close association between vessels and plaques it has been suggested that because of permeability changes of the blood-brain barrier, antigen-antibody complexes leak out from the blood and stream into the perivaseular space producing various changes according to the amount of extravascular complexes and their neurotoxicity [37, 44]; leakage of small amounts leads to focal deposits of amyloid in perieytes and basement membranes, a large quantity can give the picture of congophilic angiopathy, while toxic complexes may be responsible for the degeneration of neurites and formation of senile plaques. While the crucial importance of hypertension in the origin of brain hemorrhage, particularly in the younger age groups, is well documented [1, 17, 26], hypertensive

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cerebral angiopathy is rather rare in Alzheimer's disease [6, 10, 22], and senile dementia, where CVA, producing severe structural changes of the vessel wall, is a rare but important background of local cerebrovascular damage and hemorrhage. Further statistical and correlative clinicopathological studies are warranted in order to provide better information on the actual incidence and clinical relevance of CVA and its relationship to focal neurological disease in old demented individuals. References I. Anders, H. E., Eicke, W. J.: Die GehirngePAB¢beim Hochdruck. Arch. Psychiat. Nervenkr. 112, l 44 (1940 2. Bogaert, L. van, Maere, M., de Smedt, E.: Sur le formes familiales pr~coces de la maladie d'Alzheimer. Mschr. Psychiat. Neurol. 102, 249--301 (1940) 3. Brandenburg, E., HaUervorden, J.: Dementia pugilistica mit anatomischem Befund. Virchows Arch. path. Anat. 325, 680--709 (1954) 4. BraunmOhl, A. yon: Alterserkrankungen des Zentralnervensystems. In: Handb. spez. path. Anat. Histol., Bd. 13, I A, pp. 337--539. Berlin-G6ttingen-Heidelberg: Springer 1956 5. Bruce, M. E., Fraser, H.: Amyloid plaques in the brains of mice infected with scrapie. Morphological variation and staining properties. Neuropath. Appl. Neurobiol. 1, 189--202 (1975) 6. Corsellis, J. A. N.: Ageing and the dementias. In: Greenfield's Neuropathology (eds. W. Blackwood, J. A. N. Corsellis), pp. 796--848. London: Arnold 1976 7. Corsellis, J. A. N., Brierley, J. H.: An unusual type of presenile dementia (atypical Alzhelmet's disease with amyloid vascular change). Brain 77, 571--587 (1954) 8. Divry, P.: Consid6ration sur la vieiUissement c6r6bral. J. belge Neurol. Psychiat. 2, 65--81 (1947) 9. Gerhard, L.: Zur Frage der Abgrenzung hypertonischer Encephalopathien von kongophiler Angiopathie bei seniler Demenz oder ,,atypischer Alzheimerscher Krankheit". 1. DonauSymposium f. Neuropathologie, pp. 87--92. Wien: Wien. Med. Akademie 1969 10. Gerhard, L., Bergener, M., Homayun, S.: Angiopathie bei Aizheimerscher Krankheit. Z. Neurol. 201, 43--61 (1972) 11. Glenner, G. G., Terry, R. D., Isersky, C.: Amyloidosis: Its nature and pathogenesis. Semin. Hematol. 10, 65--86 (1973) 12. Gudmundsson, G., Hallgrimsson, J., Jonasson, T. A., Bjarnason, O.: Hereditary cerebral haemorrhage with amyloidosis. Brain 95, 387--404 (1972) 13. Haberland, C.: Primary systemic amyloidosis: Cerebral involvement and senile plaque formation. J. Neuropath. exp. Neurol. 23,135--150 (1964) 14. Hollander, D., Strich, S. J.: Atypical Alzheimer's disease with congophilic angiopathy presenting with dementia of acute onset. In: Alzheimer's disease and related conditions (eds. G. E. W. Wolstenholme, M. O'Connor), pp. 105--124. London: Churchill 1970 15. Jellinger, K.: Morphologische Gesichtspunkte zur Differenzierung sog. hirnatrophischer Prozesse. In: Gerontopsychiatrie I (eds. M. Bergener, C. Kulenkampff), pp. 111--152. Janssen Symposien, Diisseldorf 1971 16. Jellinger, K.: Neuropathological aspects of dementias resulting from abnormal blood and cerebrospinal fluid dynamics. Acta neurol, belg. 76, 83--102 (1976) 17. Jellinger, K.: Pathology ofintracerebralhemorrhage. 3rd European Course in Neurosurgery, P6cs, 6.--12. 7. 1976 18. Kidd, M.: Alzheimer's disease. An electron microscopic study. Brain 87, 307--320 (1964) 19. KrUcke, W.: Zur pathologischen Anatomie der Paramyeloidose. Acta neuropath., suppl. II, 74--93 (1963) 20. Krticke, W.: Zur Pathogenese der Plaques im Zentralnervensystem bei der generalisierten Amyloidose und bei der Creutzfeld-Jakobschen Krankheit. In: Aktuelle Probleme der Neuropathologie, Bd. 2 (eds. K. Jellinger, H. Gross), pp. 26--32. Wien: Facultas 1976

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21. LUers, Th.: ~ber die familfftre juvenile Form der Alzheimerschen Krankheit mit neurologischen Herderscheinungen. Arch. Psychiat. Z. Neurol. 179, 132--145 (1948) 22. Mandybur, T. I.: The incidence of cerebral amyloid angiopathy in Alzheimer's disease. Neurology (Minneap.) 25, 120--126 (1975) 23. Miyakawa, T., Sumiyoshi, S., Murayama, E., Deshimaru, M.: Ultrastructure of capillary plaque-like degeneration in senile dementia. Acta neuropath. (Berl.) 29, 229--236 (1974) 24. Morel, F., Wildi, E.: General and cellular pathochemistry ofsenile and presenilealterations of the brain. Proc. Ist Int. Congr. Neuropath., Vol. 2, pp. 347--374. Turin: Rosenberg & Sellier 1952 25. Neumann, M. A.: Combined amyloid vascular changes and argyrophilic plaques in the central nervous system. J. Neuropath. exp. Neurol. 19, 370--382 (1960) 26. Ooneda, G., Yoshida, Y., Suzuki, K., Sekiguchi, T.: Morphogenesis of plasmatic arterionecrosis as the cause of hypertensive intracranial hemorrhage. Virchows Arch. Abt. A. Path. Anat. 361, 31--38 (1973) 27. Pantelakis, S.: Un type particulier d'angiopathie s6nile du syst~me nerveux central: l'angiopathie congophile. Topographic et fr~quence. Mschr. Psychiat. Neurol. 128, 219--256 (1954) 28. Reid, A. H., Maloney, A. F. J.: Giant cell arteriitis and arteriolitis associated with amyloid angiopathy in an elderly mongol. Acta neuropath. (Berl.) 27, 131--137 (1974) 29. Pauli, B., Lunginbtihl, H.: Fluoreszenzmikroskopische Untersuchungen der cerebralen Amyloidose bei alten Hunden und senilen Menschen. Acta neuropath. (Berl.) 19, 121--128 (1971) 30. Schlote, W.: Die Amyloidnatur der kongophilen drusigen Entartung der Hirnarterien (Scholz) im Senium. Acta neuropath. (Berl.) 4, 449--468 (1965) 31. Scholz, W.: Studien zur Pathologic der HirngePdfle. II. Die drusige Entartung der Hirnarterien und Kapillaren. Z. ges. Neurol. 162, 694--715 (1938) 32. Schwartz, Ph.: Amyloidosis: Cause and manifestation of senile deterioration. Springfield (Ill.): Thomas 1970 33. Sourander, P., SjOgren, H.: The concept of Alzheimer's disease and its clinical implication. In: Alzheimer's disease and related conditions, pp. 11--32. London: Churchill 1970 34. Stiller, K., Katenkamp, D.: Zur Pathogenese der senilen Amyloidose. Virchows Arch. Abt. A. Path. Anat. 352, 209--218 (1971) 35. Stochdorph, O.: Zur nosologischen Stellung der kongophilen Angiopathie (sog. Altersamyloidose) des Gehirns. Verh. dtsch. Ges. Path. 52, 233--237 (1968) 36. Surbeck, B.: L'angiopathie dyshorique (Morel) de l'~corce c~r~brale. Acta neuropath. (Berl.) 1, 168--197 (1961) 37. Terry, R. D., Wisniewski, H. M.: Structural and chemical changes of aged human brains. In: Aging (eds. S. Gershon, A. R. Askin), pp. 127--142, vol. 2. New York: Raven Press 1975 38. Tomlinson, B. E., Blessed, G., Roth, M.: Observations on the brains of demented old people. J. neurol. Sci. 11, 205--242 (1970) 39. Torack, R. M.: Congophilic angiopathy complicated by surgery and massive hemorrhage. Amer. J. Pathol. 81, 349--366 (1975) 40. Torvik, A.: Aspects of the pathology ofpresenile dementia. Acta neurol, stand. 46, suppl. 43, 19--31 (1970) 41. Ule, G., Kolkmann, F.-W.: Pathologische Anatomic. In: Der Hirnkreislauf (ed. H. G~inshirt), pp. 47--160. Stuttgart: Thieme 1972 42. Ulrich, G , Taghavy, A., Schmidt, H.: ZurNosologieund,~tiologiederkongophilenAngiopathie (Gef'~tBform der cerebralen Amyloidose). Z. Neurol. 206, 39--59 (1973) 43. Wildi, E., Dago-Akribi, A.: Alt6rations c6r6brales chez l'homme ag6. Bull. Suisse Acad. Med. Sci. 24, 107--132 (1968) 44. Wisniewski, H., Johnson, A. B., Raine, C. S., Kay, W. J., Terry, R. D.: Senile plaques and cerebral amyloidosis in aged dogs. Lab. Invest. 23, 287--296 (1970) 45. Wisniewski, H. M., Narang, H. K., Terry, R. D.: Neurofibrillary tangles of paired helical filaments. J. neurol. Sci. 27, 173--181 (1976) 46. Worster-Drought, C., Greenfield, J. G., McMenemey, W. H.: A form of familial presenile dementia with spastic paralysis. Brain 63, 237--254 (1940); 67, 38--43 (1944) Received July 27, 1976

Cerebrovascular amyloidosis with cerebral hemorrhage.

Journal of J. Neurol. 214, 195--206 (1977) Neurology © by Springer-Verlag 1977 Cerebrovascular Amyloidosis with Cerebral Hemorrhage* K. Jellinger D...
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