Sporadic cerebral amyloid angiopathy revisited: recent insights into pathophysiology and clinical spectrum

Abstract

Sporadic cerebral amyloid angiopathy (CAA) is a common age related cerebral small vessel disease, characterised by progressive deposition of amyloid-b (Ab) in the wall of small to medium sized arteries, arterioles and capillaries of the cerebral cortex and overlying leptomeninges. Previously considered to be a rare neurological curiosity, CAA is now recognised as an important cause of spontaneous intracerebral haemorrhage and cognitive impairment in the elderly, two fundamental challenges in the field of cerebrovascular disease. Our understanding of the pathophysiology and clinical manifestations of CAA continues to evolve rapidly, with the use of transgenic mouse models and advanced structural and/or molecular neuroimaging techniques. Yet, despite remarkable recent interest, CAA remains under-recognised by neurologists and stroke physicians. In this review, a fresh look at key developments in understanding the complex pathophysiology, important clinical and radiological features, diagnostic approaches and prospects for rational therapies for this enigmatic small vessel disorder is provided.

Diagnostic Utility of Amyloid PET in Cerebral Amyloid Angiopathy-Related Symptomatic Intracerebral Hemorrhage

“…1,2 With aging of the population, CAA has become a major cause of intracerebral hemorrhage (ICH) and is the main cause of lobar ICH (l-ICH). 1 Furthermore, CAA contributes significantly to cognitive and gait dysfunction in the elderly. 1 The clinical diagnosis of CAA-related ICH is currently based on the Boston operational criteria, which have been validated against pathologic gold standard.…”

“…1 Furthermore, CAA contributes significantly to cognitive and gait dysfunction in the elderly. 1 The clinical diagnosis of CAA-related ICH is currently based on the Boston operational criteria, which have been validated against pathologic gold standard. 3 According to these criteria, after symptomatic lobar ICH (sl-ICH), diagnosing probable CAA requires the occurrence of a second sl-ICH or the presence of at least one definite lobar microbleed (lMB) or cortical superficial siderosis (cSS) on gradient echo (GRE) magnetic resonance imaging (MRI), and no other cause identified.…”

“…Given the risk of brain distortions from previous hemorrhage in CAA affecting spatial normalization of the PET and magnetic resonance images, state-of-the-art image processing was also applied here. 1 …”

Chronic renal failure due to amyloid nephropathy caused by chronic infection after total hip replacement

“…While cerebral amyloid angiopathy may have been caused amyloidosis, the amyloid proteins associated with amyloid angiopathy are Ab type, which are different from the AA type. Genetic familial amyloidosis can be ruled out in the case of our patient, because it is usually a localized lesion mostly occurring in the eyes and peripheral nerves, and this pattern of involvement was not found in our patient [17][18][19][20].…”

Convexity Subarachnoid Hemorrhage in Cerebral Amyloid Angiopathy: The Saga Continues

“…1,2 In vivo knowledge on CAA has developed largely as a result of progress in neuroimaging, which has allowed the characterization of the spectrum of hemorrhagic and ischemic brain injury associated with CAA as well as different clinical phenotypes. 1,3 The entity of CAA now encompasses not only a specific cerebrovascular pathologic trait and disorder, but also a clinical syndrome (or syndromes) and brain parenchymal lesions seen on neuroimaging (including a set of validated imaging diagnostic criteria-the Boston criteria). 4 In this issue of the Journal, Martínez-Lizana et al 5 report on a multicenter biomarker and neuroimaging study, which focused on the increasingly recognized imaging feature of acute nontraumatic convexity subarachnoid hemorrhage (cSAH) in the context of CAA.…”