Cerebral amyloid angiopathy

Anand Viswanathan MD PhD (Dr. Viswanthan of Harvard Medical School has no relevant financial relationships to disclose.)
Steven M Greenberg MD PhD (Dr. Greenberg of Harvard Medical School has no relevant financial relationships to disclose.)
Steven R Levine MD, editor. (Dr. Levine of the SUNY Health Science Center at Brooklyn has received honorariums from Genentech for service on a scientific advisory committee and a research grant from Genentech as a principal investigator.)
Originally released May 16, 1997; last updated February 1, 2017; expires February 1, 2020

This article includes discussion of cerebral amyloid angiopathy, congophilic angiopathy, cerebrovascular amyloidosis, angiopathy dyshorique, familial amyloidosis, familial oculoleptomeningeal amyloidosis, and hereditary cerebral hemorrhage with amyloidosis. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

Cerebral amyloid angiopathy is increasingly recognized as a major cause of hemorrhagic stroke in the elderly as well as an important contributor to the growing challenge of vascular cognitive impairment, even in cerebral amyloid angiopathy patients without hemorrhagic stroke. Among the advances highlighted in this update are: (1) the importance of sulcal bleeding events in early recurrent hemorrhagic stroke in cerebral amyloid angiopathy; (2) the varied clinical presentations and associated neuroimaging profiles of the disease; (3) the cognitive profile of cerebral amyloid angiopathy; (4) the cumulative importance of different pathologic lesions in cerebral amyloid angiopathy that contribute to cognitive decline and the emergence of techniques to measure this cumulative effect by assessing structural connectivity in the disease; (5) the role of impaired vascular reactivity early in disease course; and (6) the role of vascular amyloid in causing cerebral microbleeds in the disease.

Key points

 

• Cerebral amyloid angiopathy is a common pathology in the aging brain, most often recognized in clinical practice as the cause of multiple, strictly lobar intracerebral hemorrhages, microbleeds, or superficial sulcal/meningeal bleeding.

 

• Cerebral amyloid angiopathy-related microbleeds and superficial sulcal/meningeal bleeding are sensitively detected by T2*-weighted gradient-echo MRI techniques.

 

• Advanced cerebral amyloid angiopathy is also associated with nonhemorrhagic brain lesions such as white matter T2-hyperintensities and microinfarcts.

 

• Reasonable steps for limiting the risk of recurrent cerebral amyloid angiopathy-related hemorrhage are blood pressure control, avoidance of anticoagulation, and withholding of other antithrombotics in the absence of clear-cut indication.

 

• A subset of cerebral amyloid angiopathy presents with subacute mental status changes, headache, seizures, and amyloid-related vascular inflammation, related in at least some instances to antiamyloid autoantibodies in the cerebrospinal fluid and often improving with immunosuppressive treatment.

Historical note and terminology

Cerebral amyloid angiopathy has been recognized since the early part of this century. In the German literature in 1907 and 1909, Fischer and Oppenheim described cases that, in retrospect, probably were cerebral amyloid angiopathy (Fischer 1910). Early labels for this clinicopathologic condition included “drusige Entartung der Artien und Kapillaren” and “amyloidose cerebrale et meningee.” In 1927, Divry described amyloid in vessel walls and neuritic plaques, based on birefringence when viewed under polarized light with Congo red staining, leading to the term “congophilic angiopathy.” In 1952, Morel and Wildi coined the term “dyshoric angiopathy” to describe vascular amyloid that invades the surrounding parenchyma. In 1935, the occurrence of a familial form of cerebral amyloid angiopathy in Iceland was described by Arnason and later labeled “hereditary cerebral hemorrhage with amyloid—Icelandic type” (Arnason 1935). A second familial form was recognized in the Netherlands in 1964 by Luyendijk and later labeled “hereditary cerebral hemorrhage with amyloid—Dutch type.” Although an association of cerebral amyloid angiopathy with Alzheimer disease was recognized in the 1940s, it was not until the 1970s that Jellinger and others realized that cerebral amyloid angiopathy is an integral part of Alzheimer disease (Jellinger 1977). Also in the 1970s, several groups suggested a relation between cerebral amyloid angiopathy and nontraumatic intracerebral hemorrhage. Perhaps the most pivotal event in the history of cerebral amyloid occurred in 1984 when Glenner and Wong isolated and partially sequenced the amyloid protein found in meningeal arteries of brains of patients with Alzheimer disease and Down syndrome (Glenner and Wong 1984). In 1987, Pardridge and colleagues isolated and partially sequenced the same amyloid peptide from intraparenchymal arterioles in patients with Alzheimer disease (Pardridge et al 1987). Currently, more than 10 central nervous system diseases have been associated with various forms of cerebral amyloid angiopathy. Over the last decades, interest in cerebral amyloid angiopathy has escalated, spurred by the development of molecular biological techniques and neuroimaging methods to dissect the cerebral amyloidoses, including cerebral amyloid angiopathy–related hemorrhage and Alzheimer disease.

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