Validation of Clinicoradiological Criteria for the Diagnosis of Cerebral Amyloid Angiopathy–Related Inflammation

Auriel, Eitan; Charidimou, Andreas; Gurol, M. Edip; Ni, Jun; Etten, Ellis S. van; Martínez-Ramírez, Sergi; Boulouis, Grégoire; Piazza, Fabrizio; DiFrancesco, Jacopo C.; Frosch, Matthew P.; Shoamanesh, Ashkan; Reijmer, Yaël D.; Vashkevich, Anastasia; Ayres, Alison; Schwab, Kristin; Viswanathan, Anand; Greenberg, Steven M.

doi:10.1001/jamaneurol.2015.4078

Cited by 249 publications

(323 citation statements)

References 24 publications

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“…107 This hypothesis was recently tested by comparing reconstructed structural brain networks in non-demented patients with probable CAA and aged control participants, where it was found that there was lower global efficiency of the networks in the group with probable CAA, and that this correlated with increased number of CMBs and increased volume of WM ischaemia and infarction. 75 In addition to gradual chronic cognitive decline, patients with CAA can also experience acute stepwise decline in cognitive function after lobar ICH, 30 or may present with a rapidly progressing cognitive decline caused by CAA-ri, 109 which will be discussed later in this review. 75 In addition to gradual chronic cognitive decline, patients with CAA can also experience acute stepwise decline in cognitive function after lobar ICH, 30 or may present with a rapidly progressing cognitive decline caused by CAA-ri, 109 which will be discussed later in this review.…”

Section: Cognitive Impairmentmentioning

confidence: 99%

“…Histopathologically, it represents a spectrum of disease, ranging from perivascular inflammation consisting of lymphocytes, macrophages and multinucleated giant cells, to an inflammatory process consisting of granuloma formation and inflammation confined to the Abladen vessel wall itself. 109,117 On CT, CAA-ri manifests as asymmetric hypodense subcortical lesions, while on T2 FLAIR MRI, these lesions have high signal and involve the subcortical U fibres, 33,119 as appreciable in Figure 7. [116][117][118] Clinically, CAA-ri can present with subacute or rapidly progressive cognitive decline, headache, hallucinations, focal neurological signs, focal seizures or decreased consciousness.…”

Section: Cerebral Amyloid Angiopathy-related Inflammationmentioning

confidence: 99%

“…109 Hence, to diagnose CAA-ri in the absence of biopsy, susceptibility-sensitive MRI has a role to detect radiological evidence for underlying CAA, such as lobar ICH, CMBs, cSS, and potentially CSO-DPVS, and WM ischaemia and infarcts, which could then strengthen the likelihood of CAA-ri being the diagnosis. 109 Hence, to diagnose CAA-ri in the absence of biopsy, susceptibility-sensitive MRI has a role to detect radiological evidence for underlying CAA, such as lobar ICH, CMBs, cSS, and potentially CSO-DPVS, and WM ischaemia and infarcts, which could then strengthen the likelihood of CAA-ri being the diagnosis.…”

Section: Cerebral Amyloid Angiopathy-related Inflammationmentioning

confidence: 99%

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Cerebral amyloid angiopathy: Review of clinico‐radiological features and mimics

et al. 2018

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Cerebral amyloid angiopathy (CAA) is an important cause of lobar intracerebral haemorrhage (ICH) in the elderly, but has other clinico-radiological manifestations. In the last two decades, certain magnetic resonance imaging (MRI) sequences, namely gradient-recalled echo imaging and the newer and more sensitive susceptibility-weighted imaging, have been utilised to detect susceptibility-sensitive lesions such as cerebral microbleeds and cortical superficial siderosis. These can be utilised sensitively and specifically by the Modified Boston Criteria to make a diagnosis of CAA without the need for 'gold-standard' histopathology from biopsy. However, recently, other promising MRI biomarkers of CAA have been described which may further increase precision of radiological diagnosis, namely chronic white matter ischaemia, cerebral microinfarcts and lobar lacunes, cortical atrophy, and increased dilated perivascular spaces in the centrum semiovale. However, the radiological manifestations of CAA, as well as their clinical correlates, may have other aetiologies and mimics. It is important for the radiologist to be aware of these clinico-radiological features and mimics to accurately diagnose CAA. This is increasingly important in a patient demographic that has a high prevalence for use of antiplatelet and antithrombotic medications for other comorbidities which inherently carries an increased risk of ICH in patients with CAA.

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Section: Cognitive Impairmentmentioning

confidence: 99%

Section: Cerebral Amyloid Angiopathy-related Inflammationmentioning

confidence: 99%

Section: Cerebral Amyloid Angiopathy-related Inflammationmentioning

confidence: 99%

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Cerebral amyloid angiopathy: Review of clinico‐radiological features and mimics

et al. 2018

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“…In humans, idiopathic CAA-related inflammation is a rare disorder [36, 37] that manifests in various ways [38] and has been given a number of monikers, such as Aβ-related angiitis (ABRA), cerebral amyloid inflammatory vasculopathy, and others [39]. CAA-related inflammation in humans involves the incursion of inflammatory cells [36], and in many (but not all) cases, CAA-related inflammation responds favorably to immunosuppressive agents [36, 39, 40]. The extent to which the cellular inflammatory reaction per se contributes to the aberrant MRI signal hyperintensities in T2-weighted scans (as opposed to the contribution of vasogenic edema alone) is unknown.…”

Section: Discussionmentioning

confidence: 99%

Amyloid-Related Imaging Abnormalities in an Aged Squirrel Monkey with Cerebral Amyloid Angiopathy

Heuer

Jacobs

et al. 2017

JAD

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Amyloid-related imaging abnormalities (ARIA) in magnetic resonance imaging scans have emerged as indicators of potentially serious side effects in clinical trials of therapeutics for Alzheimer’s disease. These anomalies include an edematous type (ARIA-E) that appears as hyperintense (bright) regions by T2-weighted MRI, and a type characterized by the deposition of hemosiderin (ARIA-H) that elicits a hypointense signal, especially in T2* and susceptibility-weighted imaging. ARIA in general has been linked to the presence of Aβ-type cerebral amyloid angiopathy, an accumulation of misfolded Aβ protein in the vascular wall that impairs the integrity of brain blood vessels. However, the pathobiology of ARIA remains poorly understood, in part due to the absence of an animal model of the disorder that would enable a contemporaneous analysis of tissue integrity in the affected region. Here we describe both ARIA-E and ARIA-H in an aged squirrel monkey (Saimiri sciureus), a nonhuman primate model of naturally occurring cerebral amyloid angiopathy. Histopathologic examination of the anomalous region revealed reactive astrocytosis and microgliosis, infiltration of systemic inflammatory/immune cells, damage to axons and myelin, and hemosiderin deposition. The disruption of axons in particular suggests that ARIA-E could have functional consequences for affected regions. The squirrel monkey model can be useful for studying the pathogenesis and long-term effects of ARIA, and for testing the safety and efficacy of emerging therapies for Alzheimer’s disease.

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“…Of particular interest is the elevated predisposition of older African-Americans to lobar hemorrhage[25], a disorder that has been linked to cerebral amyloid angiopathy (CAA)[26, 27]. Neuropathologically, CAA is characterized by the deposition of amyloid in and around the walls of cerebral blood vessels[28–30].…”

Section: Introductionmentioning

confidence: 99%

Cerebral Amyloid Angiopathy: Similarity in African-Americans and Caucasians with Alzheimer’s Disease

Kamara

Gangishetti

Gearing

et al. 2018

JAD

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Cerebral amyloid angiopathy (CAA) of the Aβ type is variably present in the brains of patients with Alzheimer’s disease (AD). CAA contributes to cognitive decline and increases the risk of lobar hemorrhage; because both AD-typical dementia and lobar hemorrhage are more common in African-Americans than in Caucasians, we postulated that African-Americans with AD might be particularly susceptible to CAA. To test this hypothesis, we analyzed CAA histopathologically in the large vessels and capillaries of autopsy-derived frontal, temporal, parietal and occipital cortical samples from African-Americans (n=18) and Caucasians (n=19) with end-stage AD. In the combined cohort of 37 subjects, 22% of the subjects had severe CAA in large vessels, and 11% had severe CAA in capillaries. However, the prevalence and histopathologic characteristics of CAA were similar in the African-Americans and Caucasians. This conclusion was substantiated in an independent sample from the National Alzheimer’s Coordinating Center database, in which the degree of CAA was comparable in 1554 Caucasians and 68 African-Americans with end-stage AD. These findings support a growing consensus that the fundamental histopathologic features of Alzheimer’s disease are largely impartial to the race of the afflicted.

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Validation of Clinicoradiological Criteria for the Diagnosis of Cerebral Amyloid Angiopathy–Related Inflammation

Cited by 249 publications

References 24 publications

Cerebral amyloid angiopathy: Review of clinico‐radiological features and mimics

Cerebral amyloid angiopathy: Review of clinico‐radiological features and mimics

Amyloid-Related Imaging Abnormalities in an Aged Squirrel Monkey with Cerebral Amyloid Angiopathy

Cerebral Amyloid Angiopathy: Similarity in African-Americans and Caucasians with Alzheimer’s Disease

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