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Cerebral amyloid angiopathy in Chinese: Incidence and significance
Cerebral amyloid angiopathy in Chinese: incidence and significance Thomas H.K. Ng, Suet Y. Leung, and Maria P. Wang*
Introduction Summary Cerebral amyloid angiopathy (CAA), also referred to as congophilic angiopathy, is a special form of microvascular amyloidosis affecting cerebral vessels mainly in the leptomeninges and superficial cerebral cortex of the elderly’,*. Since the description of the condition early this century3,4, it has been found in frequent association
with Alzheimer’s disease (AD), senile dementia of Alzheimer type (SDAT) and other neurodegenerative disorders1s5. Other recognised presentations include cerebrovascular haemorrhage’,’ or cerebral microinfarcts of spontaneous or hereditary nature. Despite numerous reported cases2.8,9,CAA as a specific pathologic finding in the Chinese population has never been described until recently when we reported a sporadic case in a young Chinese”‘. Little is known about the prevalence of CAA among Orientals, although it is thought that there is a lower prevalence of ‘senile’ cerebral alterations in Chinese than in Caucasians”. On the other hand, Chinese are prone to cerebral haemorrhage. A recent prospective study conducted in Hong Kong Chinese reveals that at least 30.5% of all strokes are due to cerebral haemorrhage’*, a figure much higher than the 9-10.9% reported in Caucasians’3,14,15. Recognition of this entity has specific clinical significance. As the heavily amyloid-laden microvessels are brittle, haemorrhage may be pre-
‘Department
of Pathology, Univekty
Histological sections of 210 randomly selected autopsy brains and 49 consecutive autopsy cases of spontaneous intracerebral haemorrhage in the Chinese population aged over 40 years were examined by H&E and congo red stain with and without polarized light. In the randomly selected group, 10% of cases are positive for cerebral amyloid angiopathy (CAA) while 8.2% of cases are positive in the group with haemorrhage. The incidence is strongly age-related. Compared with Western figures, Chinese are less frequently and less severely affected by CAA. Although CAA does account for some cases of spontaneous intracerebral haemorrhage, it cannot account for the high incidence of cerebral haemorrhage among Chinese. Its significance in Chinese is much lower than in Caucasians. Key words: cerebral amyloid angiopathy, congophilic angiopathy, incidence, Chinese
cipitated by minor trauma or neurosurgical procedures such as shunt replacement”. Thus, conis servative (nonsurgical) management advocated for this group of patients whenever posssible”. In the present study, we hope to provide useful information by asking: How common is CAA in the aging Chinese population, and is it contributory to the high incidence of cerebral haemorrhage?
of Hong Kong
Address for correspondence and reprint requests: Thomas H. K. Ng, Department of Pathology, University of Hong Kong, Queen Mary Hospital, Hong Kong. Accepted 22.3.90 Clin Neural Neurosurg 1991. Vol. 93-I
19
Material and Methods The study was carried out in two parts. In the first part, a retrospective survey was performed on 210 postmortem brains from patients over 40 years of age, irrespective of the clinical diagnosis, taken from consecutive complete necropsies carried out in a large general hospital. Cases were included if the parieto-occipital cortical blocks and hippocampal blocks were available for study. Sections were stained with H&E and congo red, and were then examined with and without polarized light. Individual vessels within the brain and in the leptomeninges that demonstrated any congophilic material with apple green birefringence in their walls were labeled as amyloid containing blood vessels. The relative severity of CAA in a given section was assessed using the method by Vinterslx. The leptomeningeal and intraparenchymal vessels were graded separately. A score of 1 to 3+ was assigned to each section according to increasing abundance of CAA positive blood vessels (1 + if l-2 vessels were positive, 2+ if 3-5 vessels and 3+ if more than 5 vessels were positive). Cases with scores of 3+ were arbitrarily taken to represent severe CAA (Fig. 1). The number of senile plaques in each section was also noted by counting the extravascular amyloid cores. The total number of brains examined in each age group and their results were tabulated in Table 1. The second part of the study aims to assess the contribution of CAA in patients aged over 40 who died of spontaneous intracerebral haemor-
rhage. A total of 49 consecutive cases with complete necropsies and available tissue blocks adjacent to the haemorrhage were selected. Cases of head injury were excluded. The tissue sections were stained with H&E and congo red, followed by examination with and without polarized light. The presence or apsence of amyloid-containing vessels was noted. The age, sex distribution and results were tabulated in Table
Results Incidence 21 cases of CAA (9 male, 12 female) were iden-
tified from the 210 randomly selected brains, yielding an incidence of 10% (Table 1). The % incidence of CAA as a function of age irrespective of severity is summarized in Table 4. The incidence of CAA is strongly age-related. While it is not seen in the fifth decade, there is a steady
Fig. 1. Leptomeningeal and intracerebral medium-sized vessels with hyaiine eosinophilic wall due to amyloid deposition (fig. la). They show apple-green birefringence under polarised light in Congo red stained section (fig. lb). fig. la- H&E; fig. lb- Congo red under polarised light; both x50.
Table 7. Age-Sex Incidence of CAA in Haemorrhage Group Age
No. of CGA+ cases CAA- casts cases M F M F 0 0 0
2 6 10
8
0
1 1 0
0
I 5 4 4 2 1
2
2
28
17
40-49 50-59 60-69 70-79 SO-89 90+
3 11 15 13 6
n u 1 0 1
I
Total
49
2
Severity Parenchymal involvement by CAA tends to be less severe compared with the ieptomeninges. Only 2 of 21 brains have severe (3+ score) parenchymal CAA while 6 of 2 1 brains have severe leptomeningeal involvement. In no case is the parenchymal involvement more severe than the leptomeninges.
Table 3. Causes of Spontaneous Intracerebral Haemorrhage in the 49 patients Hypertension Ruptured berry aneurysm Congophilic angiopathy Septic Bleeding tendency Metastatic tumour Meningioma Leukaemia Arterio-venous malformation Unknown
22 5 4 3 2 2 1 2 1 7
Table -1. Incidence of CAA Age 40-49 so-59 60-69 70-79 80-89 9u+
Vinters
Tomonaga
Ng 0%
4.3%
4.8% 42.8% 46.4% 57%
8% 23% 37% 58%
lobe is involved in every case while only 4 show concomitant hippocampal involvement.
6.1% 9.8% 19.4% 25%
increase reaching 25% (2 of 8 brains) in the tenth decade. There is no significant sex preponderance. In none of these 21 cases studied was there any evidence of systemic amyloidosis. Topographic distribution All the 21 patients with identifiable CAA show both leptomeningeal and intracerebral invoIvement. Moreover, the parieto-occipital lobe is more frequently involved than the hippocampus. Of the 21 patients, the parieto-occipital
Relationship with Al~heimer’s disease 15 of the 21 cases of CAA have at least some senile plaques in the cerebral cortex and the hippocampus. flowever, only one patient has sufficient plaques to satisfy the histologic criteria of Alzheimer’s disease”. Relationship with spontaneol~s i~tracerebral haemorrha~e 4 of 49 cases of spontaneous intracerebral haemorrhage were attributed to CAA by finding amyloid containing blood vessels at the edge of the haematoma (Table 2). One of them had coexisting hypertension. The causes of haemorrhage were listed in Table 3. Discussion Amyloid can be detected by a number of histochemical, immunological and electron microscopic methods. The tinctorial characteristic of congophitia, and the demonstration of apple green birefringence under polarized light remains one of the simplest and most reliable methods of amyloid detection”,“‘. CAA is a very common finding in the brains of Caucasians over 70 years of agelX.“. It is only rarely reported in Chinese and the incidence of CAA in the general population is not known. The first case of CAA in a Chinese patient was only reported recently”‘. The present study further confirms the lower incidence of CAA in Chinese compared with Caucaisans (Table 4). Our resnlts not only show a lower incidence of CAA in Chinese, the involvement also tends to be less severe. Using the same method of assessment as Vinters’. only 2 of our 21 CAA cases are severely involved compared to his series where 14 out of 30 cases (47%) have severe CAA. On 21
the other hand, the topographic distribution of CAA in Chinese is not different from that reported in the literatureis. CAA is often reported in association with the clinical and pathological features of Alzheimer’s disease7,‘“. Review of the clinical history of our 21 CAA patients revealed symptomatology of dementia in only one patient. Using the semiquantitative criteria suggested by KhachaturiarP, another 1 of the 21 cases of CAA satisfies the histologic criteria of Alzheimer’s disease. The other 19 patients did not qualify clinically and pathologically as suffering from Alzheimer’s disease. Thus the uncommon coexistence of CAA with Alzheimer’s disease is different from the Occidental experience, and the relationship between them remains speculative. Our findings are in accordance with a recent study which shows that in Chinese, there is a lower prevalence of senile plaques, neurofibrillary tangles and other senile cerebral alterations”. Furthermore, it agrees with the clinical observation amongst physicians in Hong Kong that with 98% of the population being Chinese, senile dementia is less common in Chinese than in Caucasians**. CAA is documented as an important etiologic factor in primary non-traumatic brain haemorrhage in Caucasians2”. Of the 21 cases of CAA, 2 presented with spontaneous ~ntracerebral haemorrhage and the rest died of unrelated illnesses. In the series of 49 patients with spontaneous haemorrhage, 4 cases were thought to be due to CAA although in one of them,, there was coexisting hypertension. The prevalence of CAA among this group of patients is thus 8.2%, which is not statistically significantly different from the 10% of the randomly selected group. It may be argued that not ail CAA-related intracerebral haemorrhage are fatal, hence the prevalence rate of 8.2% based on autopsy material may be deceivingly low. Indeed, many CAA patients seem to make a surprisingly excellent recovery from numerous successive episodes of intracranial bleeding*‘. The relatively mild degree of involvement of vessels by CAA in Chinese may also help to explain the low incidence of haemorrhage. Observation of heavily amyloid-laden microvessels suggests that they are structurally brittle’*, and are unable to stand trauma or blood pressure changes. Extrapolat22
ing from this observation, the less severely mvolved blood vessels in Chinese are ~~r~~bably less fragile and hence do not bleed as frequently. In conclusion, it appears from this study that Chinese are less frequently and less severely affected by CAA. Although CAA does account for some cases of spontaneous intracerebral haemorrhage, it cannot account for the high incidence of cerebral haemorrhage among Chinese. Its significance in Chinese is much less than in Caucasians.
References VINT~RS
HV. Cerebral amyloid angiopathy. A critical review. Stroke 1987: 18:31 l-24. OKAZAKI H. WAGAN TJ. CAMPBELL RJ. Chnicopathologic studies of primary cerebral amyloid angiopathy. Mayo Clin Proc 197Y; S4:22-31. SCHOLZ w. Studien zur Pathologic der Hirngefaesse II. Die drusigc Entartung der Hirnarterien und Kapillaren. (Eine form senile Gefaesserkrankung) Z Ges Neural Psychiat lY3.8; 162-694. MOKI:I. f,. WILDI L. Genera1 and cellular path~hemist~ of senile and presenile alterations of the brain. Proc 1st Int Cong Neuropath (Rome). Turin 1.52; 2:347. MAWYBVR ~1.7he incidence of cerebral amyloid angiopathy in Alzheimer’s disease. Neurology 1975: 25:120-6. Case records of the Massachusetts General Hospital (Case 10-1988). N Engl J Med 1988; 318:623-31. GILBEK’I’ JJ. VINTERS HV. Cerebral amyloid angiopathy: Incidence and complications in the aging brain. 1. Cerebral haemorrhage. Stroke 1983; 14:915-23. MAWYHUR .rr. Cerebral amyloid angiopathy: The vascular pathology and complications. J Neur~~pathol Exp Neural 1986; 45:7%90. ISHII N. NWWIARA Y. HOKI~ A. Amyloid angiopathy and lobar cerebral haemorrhage. J Neural Neurosurg Psychiatry 1984; 47:1203-10. WON<; PM. NG THK, CHAN KII. Cerebral amyloid BI’IgiOpathy and spontaneous intraccrebral haemorrhage: report of a sporadic case in a young Chinese. Chn Neural Neurosurg (accepted). NG HI;. LEE JcK. Degenerative cerebral alterations in Chinese aged 65 years or older. Clinical Neuropathology 1988: ‘?:6:280-4. HLANG c‘y. YI. YL. ~00 KW, (‘HAN FL. Cerebral haemorrhage in an urban Chinese population. Funct Neural 1986: 1:3:213-21. GROSS CR, WE.
KASE CS, MOHH
Jp, CUNNINGHAM
SC, BAKER
Stroke in South Alabama: incidence and diagnostic features- a population based study. Stroke 1984; 15:24955. KIINI’I’I SI , GROSS CR. HLYMAN A, KASE C‘S, .WOHK JP, PRICE TR. WOLF PA. The pilot stroke data bank: definition. design and data. Stroke 1984; 1574~6. SANDF.H~~~K P. M~LYNEUX A, WARLOW c. Value of eomputed tomography in patients with stroke: Oxfordshire Community Stroke Project. Br Med J 1985; 290: 193-7. r0RAC’K KM. Congophilic angiopathy complicated by surgery and massive haemorrhage. A light and electron microscopic study. Am J Pathol 1975; 81:349&L
RH. RICHARDSON EPJR,HEROS RC. Case491982. N Engl J Med 1982; 307:1507-14. ” VINTERS HV, GILBERT JJ. Cerebral amyloid angiopathy: Incidence and complication in the aging brain II. The distribution of amyloid vascular changes. Stroke 1983; 14:924-B. ” KHACHATUKIAN zs. Diagnosis of Alzheimer’s disease. Arch Neurol 1985; 42:1097-105. “I GLENNER GG. HENRYJH.FUJIHARA s. Congophilicangiopathy in the pathogenesis of Alzheimer’s degeneration. "
ACKERMAN
Ann Pathol 1981; 1:120-9. TOMONAGA M. Cerebral amyloid angiopathy in the elderly. J Am Geriatr Sot 1981; 29:151-7. ‘* LO WH. Issues in psychiatric care of the elderly in Hong Kong. J Hong Kong Psychiatric Assoc 1982; 2:6-9. ” OJEMANN RG, HEROS RC. Spontaneous brain haemorrhage. Stroke 1983; 14:468-75. 24 FINELLI PF, KESSIMIAN N,BERNSTEIN PW. Cerebral amyloid angiopathy manifesting as recurrent intracerebral haemorrhage. Arch Neurol 1984; 41:330-3. ”
23
Introduction Summary Cerebral amyloid angiopathy (CAA), also referred to as congophilic angiopathy, is a special form of microvascular amyloidosis affecting cerebral vessels mainly in the leptomeninges and superficial cerebral cortex of the elderly’,*. Since the description of the condition early this century3,4, it has been found in frequent association
with Alzheimer’s disease (AD), senile dementia of Alzheimer type (SDAT) and other neurodegenerative disorders1s5. Other recognised presentations include cerebrovascular haemorrhage’,’ or cerebral microinfarcts of spontaneous or hereditary nature. Despite numerous reported cases2.8,9,CAA as a specific pathologic finding in the Chinese population has never been described until recently when we reported a sporadic case in a young Chinese”‘. Little is known about the prevalence of CAA among Orientals, although it is thought that there is a lower prevalence of ‘senile’ cerebral alterations in Chinese than in Caucasians”. On the other hand, Chinese are prone to cerebral haemorrhage. A recent prospective study conducted in Hong Kong Chinese reveals that at least 30.5% of all strokes are due to cerebral haemorrhage’*, a figure much higher than the 9-10.9% reported in Caucasians’3,14,15. Recognition of this entity has specific clinical significance. As the heavily amyloid-laden microvessels are brittle, haemorrhage may be pre-
‘Department
of Pathology, Univekty
Histological sections of 210 randomly selected autopsy brains and 49 consecutive autopsy cases of spontaneous intracerebral haemorrhage in the Chinese population aged over 40 years were examined by H&E and congo red stain with and without polarized light. In the randomly selected group, 10% of cases are positive for cerebral amyloid angiopathy (CAA) while 8.2% of cases are positive in the group with haemorrhage. The incidence is strongly age-related. Compared with Western figures, Chinese are less frequently and less severely affected by CAA. Although CAA does account for some cases of spontaneous intracerebral haemorrhage, it cannot account for the high incidence of cerebral haemorrhage among Chinese. Its significance in Chinese is much lower than in Caucasians. Key words: cerebral amyloid angiopathy, congophilic angiopathy, incidence, Chinese
cipitated by minor trauma or neurosurgical procedures such as shunt replacement”. Thus, conis servative (nonsurgical) management advocated for this group of patients whenever posssible”. In the present study, we hope to provide useful information by asking: How common is CAA in the aging Chinese population, and is it contributory to the high incidence of cerebral haemorrhage?
of Hong Kong
Address for correspondence and reprint requests: Thomas H. K. Ng, Department of Pathology, University of Hong Kong, Queen Mary Hospital, Hong Kong. Accepted 22.3.90 Clin Neural Neurosurg 1991. Vol. 93-I
19
Material and Methods The study was carried out in two parts. In the first part, a retrospective survey was performed on 210 postmortem brains from patients over 40 years of age, irrespective of the clinical diagnosis, taken from consecutive complete necropsies carried out in a large general hospital. Cases were included if the parieto-occipital cortical blocks and hippocampal blocks were available for study. Sections were stained with H&E and congo red, and were then examined with and without polarized light. Individual vessels within the brain and in the leptomeninges that demonstrated any congophilic material with apple green birefringence in their walls were labeled as amyloid containing blood vessels. The relative severity of CAA in a given section was assessed using the method by Vinterslx. The leptomeningeal and intraparenchymal vessels were graded separately. A score of 1 to 3+ was assigned to each section according to increasing abundance of CAA positive blood vessels (1 + if l-2 vessels were positive, 2+ if 3-5 vessels and 3+ if more than 5 vessels were positive). Cases with scores of 3+ were arbitrarily taken to represent severe CAA (Fig. 1). The number of senile plaques in each section was also noted by counting the extravascular amyloid cores. The total number of brains examined in each age group and their results were tabulated in Table 1. The second part of the study aims to assess the contribution of CAA in patients aged over 40 who died of spontaneous intracerebral haemor-
rhage. A total of 49 consecutive cases with complete necropsies and available tissue blocks adjacent to the haemorrhage were selected. Cases of head injury were excluded. The tissue sections were stained with H&E and congo red, followed by examination with and without polarized light. The presence or apsence of amyloid-containing vessels was noted. The age, sex distribution and results were tabulated in Table
Results Incidence 21 cases of CAA (9 male, 12 female) were iden-
tified from the 210 randomly selected brains, yielding an incidence of 10% (Table 1). The % incidence of CAA as a function of age irrespective of severity is summarized in Table 4. The incidence of CAA is strongly age-related. While it is not seen in the fifth decade, there is a steady
Fig. 1. Leptomeningeal and intracerebral medium-sized vessels with hyaiine eosinophilic wall due to amyloid deposition (fig. la). They show apple-green birefringence under polarised light in Congo red stained section (fig. lb). fig. la- H&E; fig. lb- Congo red under polarised light; both x50.
Table 7. Age-Sex Incidence of CAA in Haemorrhage Group Age
No. of CGA+ cases CAA- casts cases M F M F 0 0 0
2 6 10
8
0
1 1 0
0
I 5 4 4 2 1
2
2
28
17
40-49 50-59 60-69 70-79 SO-89 90+
3 11 15 13 6
n u 1 0 1
I
Total
49
2
Severity Parenchymal involvement by CAA tends to be less severe compared with the ieptomeninges. Only 2 of 21 brains have severe (3+ score) parenchymal CAA while 6 of 2 1 brains have severe leptomeningeal involvement. In no case is the parenchymal involvement more severe than the leptomeninges.
Table 3. Causes of Spontaneous Intracerebral Haemorrhage in the 49 patients Hypertension Ruptured berry aneurysm Congophilic angiopathy Septic Bleeding tendency Metastatic tumour Meningioma Leukaemia Arterio-venous malformation Unknown
22 5 4 3 2 2 1 2 1 7
Table -1. Incidence of CAA Age 40-49 so-59 60-69 70-79 80-89 9u+
Vinters
Tomonaga
Ng 0%
4.3%
4.8% 42.8% 46.4% 57%
8% 23% 37% 58%
lobe is involved in every case while only 4 show concomitant hippocampal involvement.
6.1% 9.8% 19.4% 25%
increase reaching 25% (2 of 8 brains) in the tenth decade. There is no significant sex preponderance. In none of these 21 cases studied was there any evidence of systemic amyloidosis. Topographic distribution All the 21 patients with identifiable CAA show both leptomeningeal and intracerebral invoIvement. Moreover, the parieto-occipital lobe is more frequently involved than the hippocampus. Of the 21 patients, the parieto-occipital
Relationship with Al~heimer’s disease 15 of the 21 cases of CAA have at least some senile plaques in the cerebral cortex and the hippocampus. flowever, only one patient has sufficient plaques to satisfy the histologic criteria of Alzheimer’s disease”. Relationship with spontaneol~s i~tracerebral haemorrha~e 4 of 49 cases of spontaneous intracerebral haemorrhage were attributed to CAA by finding amyloid containing blood vessels at the edge of the haematoma (Table 2). One of them had coexisting hypertension. The causes of haemorrhage were listed in Table 3. Discussion Amyloid can be detected by a number of histochemical, immunological and electron microscopic methods. The tinctorial characteristic of congophitia, and the demonstration of apple green birefringence under polarized light remains one of the simplest and most reliable methods of amyloid detection”,“‘. CAA is a very common finding in the brains of Caucasians over 70 years of agelX.“. It is only rarely reported in Chinese and the incidence of CAA in the general population is not known. The first case of CAA in a Chinese patient was only reported recently”‘. The present study further confirms the lower incidence of CAA in Chinese compared with Caucaisans (Table 4). Our resnlts not only show a lower incidence of CAA in Chinese, the involvement also tends to be less severe. Using the same method of assessment as Vinters’. only 2 of our 21 CAA cases are severely involved compared to his series where 14 out of 30 cases (47%) have severe CAA. On 21
the other hand, the topographic distribution of CAA in Chinese is not different from that reported in the literatureis. CAA is often reported in association with the clinical and pathological features of Alzheimer’s disease7,‘“. Review of the clinical history of our 21 CAA patients revealed symptomatology of dementia in only one patient. Using the semiquantitative criteria suggested by KhachaturiarP, another 1 of the 21 cases of CAA satisfies the histologic criteria of Alzheimer’s disease. The other 19 patients did not qualify clinically and pathologically as suffering from Alzheimer’s disease. Thus the uncommon coexistence of CAA with Alzheimer’s disease is different from the Occidental experience, and the relationship between them remains speculative. Our findings are in accordance with a recent study which shows that in Chinese, there is a lower prevalence of senile plaques, neurofibrillary tangles and other senile cerebral alterations”. Furthermore, it agrees with the clinical observation amongst physicians in Hong Kong that with 98% of the population being Chinese, senile dementia is less common in Chinese than in Caucasians**. CAA is documented as an important etiologic factor in primary non-traumatic brain haemorrhage in Caucasians2”. Of the 21 cases of CAA, 2 presented with spontaneous ~ntracerebral haemorrhage and the rest died of unrelated illnesses. In the series of 49 patients with spontaneous haemorrhage, 4 cases were thought to be due to CAA although in one of them,, there was coexisting hypertension. The prevalence of CAA among this group of patients is thus 8.2%, which is not statistically significantly different from the 10% of the randomly selected group. It may be argued that not ail CAA-related intracerebral haemorrhage are fatal, hence the prevalence rate of 8.2% based on autopsy material may be deceivingly low. Indeed, many CAA patients seem to make a surprisingly excellent recovery from numerous successive episodes of intracranial bleeding*‘. The relatively mild degree of involvement of vessels by CAA in Chinese may also help to explain the low incidence of haemorrhage. Observation of heavily amyloid-laden microvessels suggests that they are structurally brittle’*, and are unable to stand trauma or blood pressure changes. Extrapolat22
ing from this observation, the less severely mvolved blood vessels in Chinese are ~~r~~bably less fragile and hence do not bleed as frequently. In conclusion, it appears from this study that Chinese are less frequently and less severely affected by CAA. Although CAA does account for some cases of spontaneous intracerebral haemorrhage, it cannot account for the high incidence of cerebral haemorrhage among Chinese. Its significance in Chinese is much less than in Caucasians.
References VINT~RS
HV. Cerebral amyloid angiopathy. A critical review. Stroke 1987: 18:31 l-24. OKAZAKI H. WAGAN TJ. CAMPBELL RJ. Chnicopathologic studies of primary cerebral amyloid angiopathy. Mayo Clin Proc 197Y; S4:22-31. SCHOLZ w. Studien zur Pathologic der Hirngefaesse II. Die drusigc Entartung der Hirnarterien und Kapillaren. (Eine form senile Gefaesserkrankung) Z Ges Neural Psychiat lY3.8; 162-694. MOKI:I. f,. WILDI L. Genera1 and cellular path~hemist~ of senile and presenile alterations of the brain. Proc 1st Int Cong Neuropath (Rome). Turin 1.52; 2:347. MAWYBVR ~1.7he incidence of cerebral amyloid angiopathy in Alzheimer’s disease. Neurology 1975: 25:120-6. Case records of the Massachusetts General Hospital (Case 10-1988). N Engl J Med 1988; 318:623-31. GILBEK’I’ JJ. VINTERS HV. Cerebral amyloid angiopathy: Incidence and complications in the aging brain. 1. Cerebral haemorrhage. Stroke 1983; 14:915-23. MAWYHUR .rr. Cerebral amyloid angiopathy: The vascular pathology and complications. J Neur~~pathol Exp Neural 1986; 45:7%90. ISHII N. NWWIARA Y. HOKI~ A. Amyloid angiopathy and lobar cerebral haemorrhage. J Neural Neurosurg Psychiatry 1984; 47:1203-10. WON<; PM. NG THK, CHAN KII. Cerebral amyloid BI’IgiOpathy and spontaneous intraccrebral haemorrhage: report of a sporadic case in a young Chinese. Chn Neural Neurosurg (accepted). NG HI;. LEE JcK. Degenerative cerebral alterations in Chinese aged 65 years or older. Clinical Neuropathology 1988: ‘?:6:280-4. HLANG c‘y. YI. YL. ~00 KW, (‘HAN FL. Cerebral haemorrhage in an urban Chinese population. Funct Neural 1986: 1:3:213-21. GROSS CR, WE.
KASE CS, MOHH
Jp, CUNNINGHAM
SC, BAKER
Stroke in South Alabama: incidence and diagnostic features- a population based study. Stroke 1984; 15:24955. KIINI’I’I SI , GROSS CR. HLYMAN A, KASE C‘S, .WOHK JP, PRICE TR. WOLF PA. The pilot stroke data bank: definition. design and data. Stroke 1984; 1574~6. SANDF.H~~~K P. M~LYNEUX A, WARLOW c. Value of eomputed tomography in patients with stroke: Oxfordshire Community Stroke Project. Br Med J 1985; 290: 193-7. r0RAC’K KM. Congophilic angiopathy complicated by surgery and massive haemorrhage. A light and electron microscopic study. Am J Pathol 1975; 81:349&L
RH. RICHARDSON EPJR,HEROS RC. Case491982. N Engl J Med 1982; 307:1507-14. ” VINTERS HV, GILBERT JJ. Cerebral amyloid angiopathy: Incidence and complication in the aging brain II. The distribution of amyloid vascular changes. Stroke 1983; 14:924-B. ” KHACHATUKIAN zs. Diagnosis of Alzheimer’s disease. Arch Neurol 1985; 42:1097-105. “I GLENNER GG. HENRYJH.FUJIHARA s. Congophilicangiopathy in the pathogenesis of Alzheimer’s degeneration. "
ACKERMAN
Ann Pathol 1981; 1:120-9. TOMONAGA M. Cerebral amyloid angiopathy in the elderly. J Am Geriatr Sot 1981; 29:151-7. ‘* LO WH. Issues in psychiatric care of the elderly in Hong Kong. J Hong Kong Psychiatric Assoc 1982; 2:6-9. ” OJEMANN RG, HEROS RC. Spontaneous brain haemorrhage. Stroke 1983; 14:468-75. 24 FINELLI PF, KESSIMIAN N,BERNSTEIN PW. Cerebral amyloid angiopathy manifesting as recurrent intracerebral haemorrhage. Arch Neurol 1984; 41:330-3. ”
23