Diagnosis Of Cerebral Amyloid Angiopathy Research Articles

Abstract 48: Cerebral Amyloid Angiopathy in Asymptomatic Community-Dwelling Older Adults

Background: Cerebral amyloid angiopathy (CAA), characterized by accumulation of β-amyloid in cortical vessels, is an established cause of hemorrhagic and ischemic brain damage. Although Boston criteria can accurately diagnose CAA in patients who had lobar intracerebral hemorrhage (ICH), its value in asymptomatic older adults is unknown. Objective: We aimed to compare the amyloid load, structural MRI measures and risk factors between asymptomatic subjects who would qualify for a diagnosis of probable CAA based on lobar microbleeds (LMB) and superficial siderosis (SS) to subjects without these MRI findings. Methods: Healthy older adults (n=181) prospectively enrolled in Harvard Aging Brain study had research MRIs and Pittsburgh Compound B (PiB) PET scans. Probable CAA was diagnosed based on presence of 2 or more LMBs or a combination of LMB/SS. Distribution volume ratio (DVR) of PiB-retention, white matter hyperintensity (WMH) and hippocampal volume (HV) were calculated. Demographics, APOE status, risk factors, and imaging markers were compared between subjects with and without probable CAA diagnosed based on LMB/SS. Results: Participants had mean age 74.5±5.8 and 56% were female. Forty-six (25%) subjects had lobar MBs, 11(6%) had deep and 4(2%) cerebellar MBs. The 22 subjects diagnosed with probable CAA had higher occipital DVR (1.35 vs 1.28, p=0.004) and higher WMH (0.51 vs 0.16, p=0.005) when compared to persons without MB. These associations remained significant after adjustment for age and gender. Age, HV, ApoE status and vascular risk factors were similar between probable CAA and no MB/SS subjects (all p>0.2). Conclusions: Probable CAA diagnosis based on presence of lobar MBs and/or SS on MRI of healthy elderly volunteers is associated with other radiologic markers of CAA (posterior amyloid load, WMH) but not with vascular risk factors or markers of Alzheimer’s Disease (HV, ApoE 4). Boston criteria and amyloid imaging thus may allow early diagnosis of CAA even in asymptomatic subjects without ICH or dementia.

Abstract 123: Correlation of Cerebral Microbleeds Distribution to Amyloid Burden in Patients With Spontaneous Intracerebral Hemorrhage

Background and Purpose: The diagnosis of cerebral amyloid angiopathy (CAA) mainly depends on clinical estimation such as the location of ICH or cerebral microbleeds (CMBs). We aimed to use [11C]PiB PET to image cerebral β-amyloid deposition and validate the CAA diagnosis in patients with ICH. Methods: Twenty six patients with spontaneous ICH received cerebral [11C]PiB PET to measure the amyloid burden and 3-T magnetic resonance susceptibility weighted imaging (SWI) to analyze the distribution of CMBs. Seven patients with Alzheimer’s disease (AD) and 7 healthy subjects were included for a comparison. The lobar amyloid burden was expressed as average standardized uptake value (SUV) using the commercial software package PMOD. The number of CMBs was counted using the Microbleed Anatomical Rating Scale (MARS). Results: The amyloid burden in patients with ICH (0.72±0.27) was significantly higher than that of heathy controls (0.47±0.17, p=0.03), but lower than that of AD patients (1.31±0.38, p=0.001). The amyloid burden was not significantly different between the patients with cortico-subcortical (frontal, temporal, parietal and occipital lobes) ICH and those with deep (putamen, thalamus, caudate and cerebellum) ICH (0.77±0.32 vs. 0.67±0.20, p=0.66). CMBs were present in 23 of 26 patients (88.5%). The amyloid burden was higher in patients with CMBs located predominantly at the cortico-subcortical areas (n=8) than those with CMBs located predominantly at the deep regions (n=9) (0.96±0.30 vs. 0.54±0.13, p=0.009). The ratio of cortico-subcortical CMB number to deep CMB number was positively correlated with the amyloid burden (γ=0.65, p=0.004). Conclusion: The distribution of CMBs is a better indicator than the ICH location to predict cerebral β-amyloid deposition in patients with ICH.

Cerebral amyloid angiopathy related inflammation: is susceptibility weighted imaging the clue for diagnosis?

Background - Cerebral amyloid angiopathy-related inflammation (CAA-ri) is characterized by various neurological symptoms such as gradually developing confusion, progressive cognitive decline, seizure or headaches; T2 hyperintensities on magnetic resonance imaging (MRI); and neuropathological evidence of cerebral amyloid angiopathy (CAA) and associated vascular or perivascular inflammation. Although histological confirmation is necessary for accurate diagnosis, in case of typical clinical features and neuroimaging, the diagnosis can be established without biopsy. Case summary - We present the case of a 57-year-old man with a history of hypertension who presented to the emer¬gency department 3-week history of progressive headache and a gradually developing altered mental status. On examination, he was found to have left sided weakness and decreased pscyhomotility. Routine clinical work-up (lab investigations, CT, cerebrospinal fluid analysis) did not show obvious diagnosis, so we performed an MRI. It raised the suspicion of CAA-ri which diagnosis was verified by neuroradiological evaluation. High dose steroid treatment was initiated. The patient rapidly responded to treatment, his focal neurological signs resolved. Control MRI after 1.5 months showed multiple haemorrhagic laesions in the field of previous inflammation which posteriorly supported the previous supposed work-diagnosis. Conclusions - Although histopathology is the gold standard for the diagnosis of cerebral amyloid angiopathy, the typical clinical presentation, good response to steroids and accurate neuroradiological criteria make biopsy unnecessary to diagnose CAA-ri.

Intracerebral Hemorrhage

Intracerebral hemorrhage can be classified as either secondary (due to trauma, vascular malformations, aneurysms, tumors, or hemorrhagic transformation of ischemic stroke) or primary (without a clear secondary cause). Intracerebral hemorrhage is a neurologic emergency, and leads to significant death and disability each year; care should be expedited and emergency departments should be equipped to appropriately care for and manage these patients. This review covers the risk factors, natural history, pathophysiology, stabilization and assessment, diagnosis and treatment, and disposition and outcomes for patients with intracerebral hemorrhage. Figures show head computed tomographic scans demonstrating a left basal ganglia intracerebral hemorrhage, and an algorithm of management of intracerebral hemorrhage in the emergency department. Tables list some common causes of intracerebral hemorrhage, Boston criteria for diagnosis of cerebral amyloid angiopathy, mechanism of action of common anticoagulants, and suggested reversal agents. This review contains 2 highly rendered figures, 4 tables, and 79 references.

Cerebrospinal Fluid Biomarkers in Dementia Patients with Cerebral Amyloid Angiopathy.

To study the changes of biomarkers in cerebrospinal fluid (CSF) in cerebral amyloid angiopathy (CAA) dementia and Alzheimer(')s disease. Levels of amyloid protein β (Aβ42, Aβ40) and phosphorylated Tau-protein (P-tau) in CSF and ratio of Aβ42/Aβ40 were tested in 5 cases with CAA dementia and 20 cases with Alzheimer's disease collected at Peking Union Medical College Hospital from December 2001 to March 2011. The levels of Aβ42, Aβ40, and P-tau in CSF and ratio of Aβ42/Aβ40 were (660.4 ± 265.2) ng/L, (7111.0 ± 1033.4) ng/L, (71.8 ± 51.5) ng/L, and 0.077 ± 0.033, respectively in CAA dementia and (663.6 ± 365.6) ng/L, (5115.0 ± 2931.1) ng/L, (47.7 ± 38.8) ng/L, and 0.192 ± 0.140, respectively in Alzheimer's disease patients. There were no statistically significant differences between CAA dementia and Alzheimer's disease in terms of these CSF biomarkers (all P>0.05). Measurements of CSF biomarkers may not be helpful in differential diagnosis of CAA and Alzheimer's disease.

Diagnostic value of lobar microbleeds in individuals without intracerebral hemorrhage

IntroductionThe Boston criteria are the basis for a noninvasive diagnosis of cerebral amyloid angiopathy (CAA) in the setting of lobar intracerebral hemorrhage (ICH). We assessed the accuracy of these criteria in individuals with lobar microbleeds (MBs) without ICH. MethodsWe identified individuals aged >55 years having brain magnetic resonance imaging (MRI) and pathological assessment of CAA in a single academic hospital and a community-based population (Framingham Heart Study [FHS]). We determined the positive predictive value (PPV) of the Boston criteria for CAA in both cohorts, using lobar MBs as the only hemorrhagic lesion to fulfill the criteria. ResultsWe included 102 individuals: 55 from the hospital-based cohort and 47 from FHS (mean age at MRI 74.7 ± 8.5 and 83.4 ± 10.9 years; CAA prevalence 60% and 46.8%; cases with any lobar MB 49% and 21.3%; and cases with ≥2 strictly lobar MBs 29.1% and 8.5%, respectively). PPV of “probable CAA” (≥2 strictly lobar MBs) was 87.5% (95% confidence interval [CI], 60.4–97.8) and 25% (95% CI, 13.2–78) in hospital and general populations, respectively. DiscussionStrictly lobar MBs strongly predict CAA in non-ICH individuals when found in a hospital context. However, their diagnostic accuracy in the general population appears limited.

Cerebral amyloid angiopathy: emerging concepts.

Cerebral amyloid angiopathy (CAA) involves cerebrovascular amyloid deposition and is classified into several types according to the amyloid protein involved. Of these, sporadic amyloid β-protein (Aβ)-type CAA is most commonly found in older individuals and in patients with Alzheimer's disease (AD). Cerebrovascular Aβ deposits accompany functional and pathological changes in cerebral blood vessels (CAA-associated vasculopathies). CAA-associated vasculopathies lead to development of hemorrhagic lesions [lobar intracerebral macrohemorrhage, cortical microhemorrhage, and cortical superficial siderosis (cSS)/focal convexity subarachnoid hemorrhage (SAH)], ischemic lesions (cortical infarction and ischemic changes of the white matter), and encephalopathies that include subacute leukoencephalopathy caused by CAA-associated inflammation/angiitis. Thus, CAA is related to dementia, stroke, and encephalopathies. Recent advances in diagnostic procedures, particularly neuroimaging, have enabled us to establish a clinical diagnosis of CAA without brain biopsies. Sensitive magnetic resonance imaging (MRI) methods, such as gradient-echo T2* imaging and susceptibility-weighted imaging, are useful for detecting cortical microhemorrhages and cSS. Amyloid imaging with amyloid-binding positron emission tomography (PET) ligands, such as Pittsburgh Compound B, can detect CAA, although they cannot discriminate vascular from parenchymal amyloid deposits. In addition, cerebrospinal fluid markers may be useful, including levels of Aβ40 for CAA and anti-Aβ antibody for CAA-related inflammation. Moreover, cSS is closely associated with transient focal neurological episodes (TFNE). CAA-related inflammation/angiitis shares pathophysiology with amyloid-related imaging abnormalities (ARIA) induced by Aβ immunotherapies in AD patients. This article reviews CAA and CAA-related disorders with respect to their epidemiology, pathology, pathophysiology, clinical features, biomarkers, diagnosis, treatment, risk factors, and future perspectives.

Abstract W P246: Diagnostic Value of Lobar Hemorrhages for Cerebral Amyloid Angiopathy in Hospital and Community-based Individuals: A Pathological Correlation Study

Objectives: To determine and compare the accuracy of the Boston criteria for the diagnosis of cerebral amyloid angiopathy (CAA) applied to: 1) a large hospital-based cohort; 2) a cohort of community-dwelling individuals. Methods: Among patients seen at a single academic medical center and participants enrolled in the Framingham Heart Study (FHS) we identified all individuals having had brain MRI (including hemosiderin-specific sequences) and pathological assessment of CAA at age ≥55. CAA was defined as Vonsattel degree ≥2, except in non-autopsy studies, where any vascular amloyid deposition was considered diagnostic of CAA. We excluded cases with: 1) non-lobar ICH; 2) alternative clinical diagnosis for the lobar hemorrhage/es; 3) CAA-negative studies based on small brain biopsy samples (greater diameter <1 cm) or clot evacuations with none or rare vessels identified; 4) autopsy studies not grading CAA. We determined sensitivity and specificity of “possible CAA” (1 lobar hemorrhage) and “probable CAA” (>1 strictly lobar hemorrhage) in both cohorts. Results: The study included 143 cases: 96 from the hospital cohort (mean age at time of MRI 74.1±8.2 years, 47.9% women, 47.9% autopsy studies, 54.2% cases with any lobar microbleed, 44.8% with any lobar ICH) and 47 from FHS (mean age at time of MRI 83.4±10.9 years, 48.9% women, 100% autopsy studies, 17% cases with any lobar microbleed, no lobar ICH cases). Hospital cohort: CAA prevalence was 72.6%. Specificity/sensitivity of “possible CAA” and “probable CAA” were 78.2%/33.3% and 92%/57.7%. Community cohort: CAA prevalence was 47%. Specificity/sensitivity of “probable CAA” were 88%/3%. Discussion: Specificity of detection of multiple lobar hemorrhages on MRI (“probable CAA”) for moderate-severe CAA is similarly high in both hospital and community cohorts. This increases the opportunity to identify individuals with CAA for observational studies and emerging anti-amyloid therapeutic trials. In view of its poor sensitivity, “probable CAA” diagnosis represents an inadequate screening tool for exclusion of CAA in both populations.

White matter perivascular spaces

We investigated whether severe, MRI-visible perivascular spaces (PVS) in the cerebral hemisphere white matter (centrum semiovale) are more common in patients with pathology-proven cerebral amyloid angiopathy (CAA) than in those with pathology-proven non-CAA-related intracerebral hemorrhage (ICH). Using a validated 4-point scale on axial T2-weighted MRI, we compared PVS in patients with pathology-proven CAA to PVS in those with spontaneous ICH but no histopathologic evidence of CAA. In a preliminary analysis restricted to patients with T2*-weighted gradient-recalled echo MRI, we also investigated whether including severe centrum semiovale PVS increases the sensitivity of existing diagnostic criteria for probable CAA. Fourteen patients with CAA and 10 patients with non-CAA-related ICH were included. Eight of the patients with CAA were admitted for symptomatic, spontaneous lobar ICH, 1 because of ischemic stroke, 1 with transient focal neurologic episodes, and 4 due to cognitive decline. Severe (>20) centrum semiovale PVS were more frequent in patients with CAA compared to controls (12/14 [85.7%; 95% confidence interval (CI): 57.2%-98.2%] vs 0/10 [1-sided 95% CI: 0%-30.8%], p < 0.0005); this was robust to adjustment for age. The original Boston criteria for probable CAA showed a sensitivity of 76.9% (95% CI: 46.2%-95%), which increased to 92.3% (95% CI: 64%-99.8%), without loss of specificity, after including severe centrum semiovale PVS. Severe centrum semiovale PVS on MRI may be a promising new neuroimaging marker for the in vivo diagnosis of CAA. However, our findings are preliminary and require confirmation and external validation in larger cohorts of pathology-proven CAA.

Increased Number of Microinfarcts in Alzheimer Disease at 7-T MR Imaging

To assess the prevalence and number of cortical microinfarcts in patients with Alzheimer disease (AD) by using a 7-T magnetic resonance (MR) imaging system, to assess the independent association of cortical microinfarcts with cognitive dysfunction, and to investigate potential confounding effects of the coexisting presence of cerebral amyloid angiopathy (CAA). The local institutional review board approved this study. In all cases, informed consent was obtained. High-spatial-resolution fluid-attenuated inversion recovery and T2*-weighted images were acquired in 14 AD patients and 18 control subjects to assess the presence of microinfarcts and microbleeds. Presence of CAA was assessed according to the Boston criteria. Image analysis was performed independently by two reviewers. Mann-Whitney U test was performed to assess differences in number of microinfarcts between groups. Negative binomial regression models were used to assess the association between diagnosis of AD and diagnosis of CAA and number of microinfarcts, between diagnosis of AD and number of microbleeds and number of microinfarcts, and between cognitive function and number of microinfarcts, all corrected for age and sex. Interobserver agreement was excellent for detecting microinfarcts (κ = 0.91) (P < .001). Patients with AD demonstrated higher number (P = .005) of microinfarcts (mean, 7.2) compared with control subjects (mean, 1.8). Negative binomial regression models showed an independent association between AD and number of microinfarcts (P = .006) and a trend for CAA and microinfarcts (P = .052). A negative correlation was found between cognitive function and the number of microinfarcts (P = .009). Patients with AD show more microinfarcts than do control subjects, the number of microinfarcts correlates with global cognitive performance, and the presence of microinfarcts was mainly AD rather than CAA related.

Nontraumatic Convexity Subarachnoid Hemorrhage: Different Etiologies and Outcomes

Nontraumatic convexity subarachnoid hemorrhage (cSAH) is a rarely reported condition with multiple etiologies. We report the clinical presentation, imaging findings, etiologies, and long-term outcomes of a case series of cSAH. We retrospectively analyzed consecutive cases of cSAH, admitted at a Stroke Unit of a tertiary hospital (January 2006 to March 2012). Recorded variables were demographics, clinical presentation, complementary investigation, etiology, and outcome. We included 15 patients (9 men, median age of 65years), 7% of the 210 nontraumatic SAH patients in this period. The most common clinical manifestation was a focal neurologic deficit. Predominant location of the cSAH was frontal. In 5 cases, there was a clinical significant internal carotid artery (ICA) atheromatous stenosis, ipsilateral to cSAH. Two patients had a possible cerebral amyloid angiopathy (CAA) at presentation. There were 2 cases of reversible cerebral vasoconstriction syndrome, 1 cerebral venous thrombosis, 2 dural fistulae, and 3 undetermined. Short-term outcomes were good in most patients. At follow-up (24.3months), 2 of the patients with undetermined etiology had a lobar hematoma conferring a severe disability, and the diagnosis of CAA was made. There were no other relevant events or added disability in the other patients. Significant ICA atherosclerotic stenosis was the most frequent cause of cSAH in our series, reinforcing that cSAH should prompt vascular imagiological evaluation including cervical vessels. Outcomes in cSAH seem to be related to etiology. Patients with undetermined etiology should be followed up because cSAH may be the first manifestation of CAA.

Abstract TP301: Warfarin Increases Risk of Future Intracerebral Hemorrhage in Patients Presenting with Isolated Lobar Microbleeds on MRI

BACKGROUND/OBJECTIVES: Lobar microbleeds (LMB) are increasingly identified on brain MRI of older adults, suggesting a diagnosis of cerebral amyloid angiopathy (CAA) in the absence of intracerebral hemorrhage (ICH). Identifying the baseline characteristics and risk of future ICH of these subjects is important to understand their prognosis and safety of antithrombotic use in this setting. METHODS: Baseline characteristics (demographics, risk factors, APOE genotype), markers of CAA severity (LMB counts, white matter hyperintensity volume), and finally outcomes during a mean follow up of 4 years (incidence rate of ICH and case-fatality) were compared between 62 CAA patients without and 747 with ICH diagnosed using Boston criteria upon enrollment. The association between antithrombotic use and risk of incident ICH was explored in patients presenting with isolated LMBs after adjusting for covariates listed above. RESULTS: Female gender (52% vs. 37% p=0.023) and hypertension (67% vs. 53% p=0.025) were more common in patients presenting with ICH, other baseline characteristics did not differ. Patients presenting without ICH had more LMBs (median 10 vs. 1 p&lt;0.001), and higher white matter hyperintensity volume (38cc±32 vs. 27cc ±24 p=0.008) than patients with ICH even after correction for other covariates. Patients without ICH on enrollment had a lower but non-trivial incidence rate of ICH during follow-up (4.8 per 100 person-years vs. 9 per 100 person-years; RR: 0.56, 95%CI 0.27-0.97). The case-fatality rates were similar between these groups (p=0.5). In patients presenting without ICH, the use of Warfarin was an independent predictor of future ICH (p=0.02) in the multivariate model. Patients using either ASA 325mg/day OR Clopidogrel OR ASA/Dipyridamol had higher risk of future ICH (p=.049) but this association did not remain significant in multivariate model. Use of ASA 81mg daily was not a predictor of incident ICH risk. CONCLUSIONS: Patients presenting with LMBs on MRI have a clinical, genetic, and neuroimaging profile suggestive of severe CAA pathology. They have a considerable risk of incident ICH albeit lower than patients who had a prior lobar ICH. The use of warfarin increases the risk of future ICH in patients with isolated LMBs on MRI.

Abstract TP295: Different Patterns of Subcortical White Matter Disease in Patients with Cerebral Amyloid Angiopathy and Hypertensive Intracerebral Hemorrhage

Objective: We aimed to identify the potential contributions of cerebral amyloid angiopathy (CAA) and hypertensive microvasculopathy on periventricular (PV) and subcortical (SC) white matter disease (WMD). Methods: Total, SC and PV WMD volumes of 359 CAA patients and 102 patients with hypertensive intracerebral hemorrhage (htn-ICH) were quantitatively measured on FLAIR MRI. The presence of 6 different subcortical WMD patterns (detailed under Results and Figure 1) was recorded. The independent predictors of each of these WMD variables were explored using multivariate models that included the diagnosis (CAA vs htn-ICH), age, gender, ApoE genotype, vascular risk factors, total WMD volume as well as lobar and deep microbleed (MB) counts from T2*MRI. Results: CAA patients were older (mean 74 vs 68, p&lt;0.001) with a higher WMD burden (p&lt;0.05 for total, PV and SC WMD) than htn-ICH cases. Older age, higher lobar and deep MB counts were independent predictors of both total and PV WMH (p&lt;0.01 for all predictors) whereas only high lobar MB count was independently associated with SC WMD (p&lt;0.001). CAA-related covariates (CAA diagnosis and/or lobar MB counts) were independently associated with large posterior SC WMD (Fig 1a, frequency 16% in CAA vs 5% in htn-ICH, p&lt;0.001) and anterior SC WMD (Fig 1b, 46% vs 24%, p&lt;0.01). Peri-basal ganglia WMD (Fig 1c) pattern was more frequent in htn-ICH (29% vs 10%, p&lt;0.001) and independently associated with deep MB count. The SC spots (Fig 1d, p=0.16), U-shaped SC WMD pattern (Fig 1e, p=0.17) and severe-coalescent WMD (Fig 1f, p=0.5) were not independently related to CAA or htn-ICH. Conclusions: Our results show that CAA pathology is associated with the severity of both PV and SC WMD as well as presence of severe posterior and anterior SC disease. A pattern of deep peri-basal ganglia WMD is mostly associated with hypertensive disease. Recognition of these patterns might help understand the dominant type of microvasculopathy in older individuals with WMD.

Abstract WP214: Cortical Microinfarcts as a Putative MRI Marker for Cerebral Amyloid Angiopathy

Background: Cortical microinfarcts (CMIs) are frequently detected in autopsy brains of elderly subjects, and distributed predominantly in the area of predilection for cerebral amyloid angiopathy (CAA). Recently these lesions have been detected on high-filed MRI using double inversion recovery (DIR) and 3D-fluid attenuated inversion recovery (FLAIR). Radiological diagnosis according to Boston criteria for CAA may be reinforced by detecting CMIs. Methods: We performed a prospective analysis of 36 patients diagnosed as clinically probable CAA by Boston criteria, including multiple strictly lobar microbleeds as a diagnostic indicator. These patients were recruited at the Department of Neurology, Mie University Hospital from August 2009 to April 2012. 3-tesla MR images including susceptibility-weighted imaging (SWI), DIR and 3D- FLAIR were reviewed. Results: CMIs were found in 9 of 36 (25%) patients. Most CMIs were located in close proximity to lobar microbleeds. Cortical superficial siderosis was observed in 6 of 36 (16.6%) patients, among which 5 (83.3%) showed CMIs. There were 5 patients with symptomatic subcortical hemorrhage, and 3 of these (60%) showed both CMIs and superficial siderosis. Conclusions: These results indicate that CMIs strengthen radiological diagnosis of CAA if these lesions coexist with multiple strictly lobar microbleeds and cortical superficial siderosis.

Zerebrale Amyloidangiopathie – ein Update

Cerebral amyloid angiopathy (CAA) belongs to the group of amyloidoses and is characterised by the deposition and accumulation of beta-amyloid (Aβ) in small arterial vessels of the brain. Hereditary forms of CAA exist but sporadic CAA is much more frequent. Deposition of Aβ induces degenerative changes of the cerebral vascular system (thickening of the vessel wall, constriction of vascular lumen, microaneurysms, dissection) that trigger the development of the typical clinical presentation of CAA, that is spontaneous intracerebral haemorrhage. Apart from haemorrhages, also cerebral ischaemia, transient neurological symptoms, leukencephalopathy as well as cognitive decline and dementia can occur in association with CAA. The definite diagnosis of CAA is only possible by means of pathological examination, even though neuroimaging and clinical findings allow the diagnosis of a probable CAA. Currently, no specific causal therapy exists. Although CAA is located in the range of neurological diseases psychiatric symptoms might occur. In the review, we discuss epidemiological, pathogenetic, clinical and diagnostic aspects and possible psychiatric implications of CAA.

Clinical manifestations and diagnosis of cerebral amyloid angiopathy

Objective To analyze the clinical manifestations and diagnosis methods of cerebral amyloid angiopathy ( CAA ).Methods The clinical data of 55 patients with spontaneous intracerebral hemorrhage were analyzed. The pathological specimen were stained by Congo red and accepted immunohistochemistry staining for beta- amyloid protein.Then the pathological diagnoses were established.Results 6 patients were first diagnosed as CAA depend on the clinical manifestation,but one patient was later excluded by pathological staining. Two patients were first diagnosed as hypertensive intracerebral hemorrhage,and then were identified as CAA by pathological staining.Conclusions CAA could be the first diagnosis depended on its clinical features.But as for the atypical patient,the diagnosis should be determined by pathological diagnosis,which remained to be the gold standard for CAA.The diagnosis methods of CAA need further research and improvement. Key words: Cerebral amyloid angiopathy; Clinical manifestations; Diagnosis

Abstract 2891: Severity of Amyloid Deposition is Associated with Ischemic White Matter Disease in Cerebral Amyloid Angiopathy but Not in Healthy Elderly: a PET/MRI Correlative Study

Background and Purpose: Cerebral Amyloid Angiopathy (CAA), characterized by accumulation of amyloid beta proteins in the walls of cortical/leptomeningeal vessels, is increasingly recognized as a cause of ischemic brain injury in addition to its classical role in lobar cerebral hemorrhages (ICH). Pittsburgh Compound B (PiB) is a PET ligand that has been shown to label the vascular amyloid deposits of CAA, allowing invivo quantification of the severity of CAA pathology. We hypothesized that there would be a dose-dependent relationship between vascular amyloid burden (measured by PiB) and brain ischemia (measured by extent of MRI markers of chronic ischemia) in patients diagnosed with CAA but not in healthy elderly without evidence of advanced CAA. Methods: Thirty-five non-demented patients (9 women) with a diagnosis of CAA according to Boston Criteria and 50 healthy elderly subjects (29 women) without lobar microhemorrhages or history of stroke/dementia who underwent a brain MRI scan and PiB-PET imaging were analyzed. Global cortical PiB retention was calculated using cerebellar cortex as the reference tissue input function and expressed as the distribution volume ratio (DVR). Quantitative analysis of white matter T2-hyperintensity (WMH) volume on MRI FLAIR sequences was performed using computer-assisted techniques. Presence of lacunar infarcts was also recorded in each subject. Multivariate linear regression was used to assess the association between PiB retention and WMH volume while controlling for other vascular risk factors within each group. Results: CAA patients were younger than healthy elderly (67±10 vs 73±7, p=0.004) but had higher amounts of WMH (19ml IQR:6.7-31.8 vs 3.2ml IQR:2-5.6, p&lt;0.001) and mean global DVR (1.34±0.19 vs 1.17±0.13, p&lt;0.001). In bivariate analyses, global DVR and WMH showed a strong correlation (Spearman's rho=0.52, p&lt;0.001) in the CAA cohort. This association did not substantially change in a multivariate model that included age, gender, and vascular risk factors as covariates. Global DVR and WMH were not correlated (Spearman's rho=0.01, p=0.95) in the healthy elderly group. Nine CAA patients (26%) had a lacunar infarction on imaging against only 1 healthy control (2%), p=0.001. CAA patients with lacunes had higher mean DVR (p=0.03), but this association did not remain independent after adjustment for age. Conclusions: Our results indicate that global PiB retention independently correlates with volume of white matter disease on FLAIR in patients with CAA but not in healthy elderly. These findings support the idea that vascular amyloid burden directly contributes to chronic cerebral ischemia in the CAA population and highlights the possible utility of amyloid imaging as a marker of CAA severity.

Plasma β-Amyloid Levels in Cerebral Amyloid Angiopathy-Associated Hemorrhagic Stroke

Background: Cerebral amyloid angiopathy (CAA) is one of the main causes of intracerebral hemorrhage (ICH) in the elderly. Objective: To analyze β-amyloid (Aβ) species in plasma in order to uncover biological markers that may contribute to improve the diagnosis of CAA in life. Methods: We determined the level of Aβ(1–40), Aβ(N–40), Aβ(1–42) and Aβ(N–42) in plasma of CAA-related ICH patients (n = 29) and healthy controls (n = 21) using xMAP® technology. Hemorrhages were identified and classified using a CT scan and brain MRI. Patients were clinically classified as probable or possible CAA according to the Boston criteria. Results: We found that plasma full-length Aβ(1–42) and truncated fragments Aβ(N–42) were higher in probable CAA patients than in controls (p < 0.001 and p = 0.046, respectively), and full-length Aβ(1–40) was selectively elevated in probable CAA compared to possible cases (p = 0.015) and controls (p = 0.005). In addition, plasma Aβ(N–42) levels were also higher in patients that presented multiple lobar macrohemorrhages compared to patients that had one symptomatic hemorrhagic event (p = 0.022), indicating that a certain degree of CAA severity is necessary to show increased Aβ fragments in peripheral circulation. Conclusion: Our results suggest that specific Aβ fragments in plasma might be considered as potential biomarkers for the diagnosis of CAA.

Cerebral amyloid angiopathy with frequent intracerebral hemorrhage: A pitfall for neurosurgeons

Summary A 69-year-old man, who was formerly fit and well without precipitating risk factors such as hypertension, suffered a right frontal lobar intracerebral hemorrhage (ICH). The hematoma was removed, and histopathology showed blood clots with no evidence of malignancy. Two days after the craniotomy, a new lobar ICH occurred in the right parietal lobe with subfalcine cerebral herniation. The hematoma was again removed via a decompressive craniectomy. Histopathology of the brain tissue overlying the hematoma demonstrated cerebral amyloid angiopathy (CAA). Four weeks after this, a recurrent ICH in the right parietal lobe was noted during a cystoscopic procedure. This time the hematoma was treated conservatively. One year later, another ICH in the left frontal lobe developed following a right femoral neck fracture. This ICH was again treated conservatively. From this example, we have learnt that histopathological diagnosis can be very helpful for atypical recurrent intracerebral hemorrhage. Once the diagnosis of CAA is confirmed, conservative treatment is the rule, and prompt alleviation of physical or psychological stress could minimize the chance of recurrent ICH.

A case of cerebral amyloid angiopathy with reversible white matter lesions and multiple cerebral microbleeds

A 59-year-old woman presented with a 7-year history of headache. She showed no neurological abnormality. T(2) weighted magnetic resonance (MR) images showed a hyperintense signal in the white matter in the bilateral parieto-occipital lobe without abnormal enhancement. A small amount of prednisolone was administered for rheumatoid arthritis. After prednisolone was discontinued, the T(2) weighted images showed an expansion of the hyperintense signal lesions seen in the white matter, and T(2) weighted image showed multiple foci of petechial bleeding in the cortex and subcortex of the bilateral occipital lobe. A brain biopsy specimen from the right occipital lobe revealed deposition of amyloid in the subarachnoidal and cortical vessel walls and transmural infiltration of a few lymphocytes, eosinophils, and giant histiocytes. Subsequently the patient was diagnosed with central nervous system vasculitis associated with cerebral amyloid angiopathy (CAA). After 5 months, the T(2) weighted images showed a remarkable regression of the hyperintense signal lesions in the white matter of the bilateral parieto-occipital lobe without the administration of any maintenance immunosuppressive agents. However, T(2) weighted image showed an increase of multiple cortico-subcortical foci of petechial bleeding. Her headache did not improve during the illness. Thus, we should consider the diagnosis of CAA when patients present with reversible white matter lesions and multiple cerebral microbleeds simultaneously.