Amyloid- β –related angiitis: a report of 2 cases with unusual presentations

Abstract

Amyloid-β-related angiitis (ABRA) is a rare complication of cerebral amyloid angiopathy in which amyloid-β deposition in the leptomeningeal and cortical vessels is associated with vasculitis characterized by transmural lymphohistiocytic, often granulomatous, inflammation. Patients usually present with acute to subacute cognitive dysfunction, headaches, and focal neurologic deficits. We report 2 cases of ABRA with unusual clinical presentations, including one case with fatal cerebral edema leading to herniation and Duret hemorrhages, and another associated with both lobar and deep parenchymal hemorrhages with intraventricular extension as well as hypercoagulability. Both showed extensive vascular amyloid-β deposition associated with granulomatous angiitis and foreign body-type multinucleated giant cells. One of our cases demonstrates the likely effects of ABRA on impairment of fluid regulation leading to severe cerebral edema, which is an uncommon manifestation of ABRA, and may be a result of impaired blood-brain barrier function or malfunction of the neurovascular unit.

A challenging diagnosis of reversible “vascular” dementia: Cerebral amyloid angiopathy-related inflammation

“…Based on histopathology of brain biopsy, two forms of CAA-ri can be distinguished: inflammatory CAA (ICAA) and Amyloid-β-Related Angiitis (ABRA). Specifically, while ICAA is characterized by a perivascular inflammation, ABRA is characterized by transmural and intramural inflammation, often with granulomas formation (Moussaddy et al, 2015;Ng et al, 2017;Chu et al, 2016). ICAA and ABRA share several clinical and neuroradiological features and are indistinguishable from each other without histopathological data (Salvarani et al, 2016;Chu et al, 2016).…”

“…Although a validation of cut-offs has not yet been performed, previous studies reported significantly higher values of CSF anti-Aβ antibodies in subjects affected by CAA-ri compared to control subjects (Piazza et al, 2013), just as in our cases. Therefore, the research of anti-Aβ antibodies not only focuses on the possible pathogenic mechanism of the disease but also represents a possible useful biomarker for the diagnosis and non-invasive monitoring of CAA-ri (DiFrancesco et al, 2011;Moussaddy et al, 2015;Ng et al, 2017;Salvarani et al, 2016;Chu et al, 2016;Charidimou, 2016;Sakaguchi et al, 2011).…”

“…Obviously, the lack of pathological data prevents any conclusions regarding the differential diagnosis between the two disease entities ABRA and ICAA. Notwithstanding, both forms require prompt immunosuppression and show a similar response to treatment (Auriel et al, 2016;Moussaddy et al, 2015;Ng et al, 2017).…”

The role of biopsies and autopsies in the diagnosis of cognitive impairment, with emphasis on small vessel diseases: A critical appraisal enriched by personal experience

“… 11 , 17 It is worth mentioning that Amyloid b-related angiitis, caused by amyloid-b peptide deposition in the brain leading to vessel wall breakdown, is a subset of PACNS but patients tend to present the condition at an older age. 18 The histological differential diagnosis of PACNS includes sarcoidosis and infectious meningitides, but these have distinctive patterns such as viral inclusions, neuronophagia, parenchymal inflammation, and/or demyelination and are not restricted to blood vessels. The angiocentric accumulation of lymphoid cells may also bear a superficial resemblance to primary CNS lymphoma, especially well-differentiated lymphoplasmacytoid variants, but infiltrates of neoplastic cells tend to be more extensive, may be partly necrotic, contain much more reticulin, lack a granulomatous component, and have a characteristic immunophenotype.…”

Cerebral Amyloid Angiopathy-Related Inflammation in the Immunosuppressed: A Case Report

“…Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a rare disorder of the central nervous system (CNS) that arises from development of autoantibodies to amyloid-beta protein (Aβ) within the walls of the leptomeningeal and cortical blood vessels (1–5). It affects immunocompetent individuals who present with non-specific symptoms or focal neurological deficits, which typically elicits a broad etiological investigation until the condition is recognized (6–8). The presumptive diagnosis is based on clinical and neuroimaging data, whereas the definitive diagnosis is histological (9).…”