Cortical superficial siderosis and first-ever cerebral hemorrhage in cerebral amyloid angiopathy

Wilisch‐Neumann

Neuropathology Appl Neurobio

et al. 2019

Invited Review: The spectrum of age-related small vessel diseases: potential overlap and interactions of amyloid and nonamyloid vasculopathiesDeep perforator arteriopathy (DPA) and cerebral amyloid angiopathy (CAA) are the commonest known cerebral small vessel diseases (CSVD), which cause ischaemic stroke, intracebral haemorrhage (ICH) and vascular cognitive impairment (VCI). While thus far mainly considered as separate entities, we here propose that DPA and CAA share similarities, overlap and interact, so that 'pure' DPA or CAA are extremes along a continuum of age-related small vessel pathologies. We suggest blood-brain barrier (BBB) breakdown, endothelial damage and impaired perivascular b-amyloid (Ab) drainage are hallmark common mechanisms connecting DPA and CAA. We also suggest a need for new biomarkers (e.g. high-resolution imaging) to deepen understanding of the complex relationships between DPA and CAA.

Section: Neuroimaging Biomarkers Of Sporadic Csvdmentioning

confidence: 99%

Invited Review: The spectrum of age‐related small vessel diseases: potential overlap and interactions of amyloid and nonamyloid vasculopathies

Wilisch‐Neumann

Neuropathology Appl Neurobio

et al. 2019

“…16 However, as approximately 50% of patients with CAA aged over 80 years report no clinical manifestations, the role of the radiologist in recognition of CAA's radiological features is vital in its early diagnosis. [40][41][42][43] Cerebral microbleeds and cSS have been incorporated into the Modified Boston Criteria (Table 1) which allows for reliable diagnosis of CAA without the need for histopathology. 24 These are not only markers of CAA, but have also each been shown to be independent risk factors for lobar ICH and its recurrence.…”

Section: Lobar Intracerebral Haemorrhagementioning

confidence: 99%

“…24 These are not only markers of CAA, but have also each been shown to be independent risk factors for lobar ICH and its recurrence. [40][41][42][43] Cerebral microbleeds and cSS have been incorporated into the Modified Boston Criteria (Table 1) which allows for reliable diagnosis of CAA without the need for histopathology. 44 These criteria expand on earlier work by Greenberg et al who created the original Boston Criteria in 1995, 45 and the diagnosis of 'probable CAA' has a sensitivity of 95% and specificity of 81% in a validation study using GRE.…”

Section: Lobar Intracerebral Haemorrhagementioning

confidence: 99%

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

et al. 2018

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.

“…The exact relative contribution of each of these systems to the overall Aβ clearance is currently unknown, but alterations in any of them contribute to extracellular Aβ accumulation (47). HA is supposed to interfere with the normal Aβ clearance processes due to severe vessel wall alterations, potentially facilitating perivascular Aβ accumulations (33,54). Due to anatomical and physiological similarities in brain and retina these considerations could be true for both organs.…”

Section: Discussionmentioning

confidence: 99%

Retinal Vascular Pathology in a Rat Model of Cerebral Small Vessel Disease

et al. 2020

Introduction: The initial disease stages of hypertensive arteriopathy (HA) and cerebral amyloid angiopathy (CAA), the two main forms of sporadic human cerebral small vessel diseases (CSVD), are too subtle to be detectable on clinical routine imaging. Small vessel disease (SVD) is a systemic condition, affecting not only the brain, but also other organs. The retina appears as an ideal marker for the early detection of incipient CSVD. We therefore investigated the retinal microvasculature of the spontaneously hypertensive stroke-prone rat (SHRSP), an animal model of sporadic CSVD. Materials and Methods: The brains and retinas of 26 male SHRSP (18-44 weeks) were examined histologically and immunohistochemically for the presence of HA phenomena (erythrocyte thrombi, small perivascular bleeds) and amyloid angiopathy (AA). Results: CAA and AA in the retina showed a significant correlation with age (CAA: rho = 0.55, p = 0.005; AA: rho = 0.89, p < 0.001). The number of erythrocyte thrombi in the brain correlated with the severity of retinal erythrocyte thrombi (rho = 0.46, p = 0.023), while the occurrence of CAA correlated with the appearance of AA in the retina (rho = 0.51, p = 0.012). Retinal SVD markers predicted CSVD markers with good sensitivity. Conclusions: These results indicate that SVD also occurs in the retinal microvasculature of SHRSP and the prediction of cerebral erythrocyte thrombi and CAA might be possible using retinal biomarkers. This underlines the important role of the investigation of the retina in the early diagnosis of CSVD.