A -related angiitis: primary angiitis of the central nervous system associated with cerebral amyloid angiopathy

Abstract

Idiopathic or primary angiitis of the CNS (PACNS) and cerebral amyloid angiopathy (CAA) are unusual vasculopathies generally regarded as unrelated disorders. A few case reports have, however, described granulomatous angiitis in patients with sporadic, amyloid beta peptide (Abeta)-related CAA. Here we describe the clinical, neuroradiological and neuropathological features of nine patients with Abeta-related angiitis (ABRA). Combining these with the individual case reports drawn from the literature has allowed us to define ABRA as a clinical entity and to compare its features with those of PACNS. The mean age of presentation of ABRA (67 years) is higher than that of PACNS but lower than that of sporadic non-inflammatory Abeta-related CAA. Alterations in mental status (59%), headaches (35%), seizures and focal neurological deficits (24%) are common. Hallucinations are a presenting manifestation in 12% of cases. Most patients have white matter hyperintensities on MRI but these are of similar appearance to those in PACNS. Cerebrospinal fluid usually shows modest elevation of protein and pleocytosis. Neuropathology reveals angiodestructive inflammation, often granulomatous, and meningeal lymphocytosis. Abeta is consistently present in abundance in affected blood vessels but usually scanty within the parenchyma of the cerebral cortex. However, the cortex includes numerous activated microglia, occasionally in a plaque-like distribution and containing cytoplasmic Abeta. The cerebral white matter shows patchy gliosis and rarefaction, in some cases marked. Our findings (i) help to dissect one separate clinicopathological entity from what is likely to be a spectrum of primary angiitides of the CNS; (ii) have important therapeutic implications for one category of patients with amyloid-related vasculopathy; and (iii) may provide valuable insights into the development of amyloid-associated inflammation, of relevance not only to ABRA but also to Abeta-immunization-related encephalitis and to Alzheimer's disease.

Primary central nervous system vasculitis: analysis of 101 patients

“…␤-Amyloid peptide deposition was identified during biopsy only in specimens with a granulomatous histological pattern. Scolding and coworkers 33 suggested that ␤-amyloid peptide-related PCNSV is a recognizable clinicopathological entity. The different histological patterns did not appear to result from different treatments.…”

Clinical phenotypes of Cerebral Amyloid Angiopathy

“…In such instances the Aβ vascular deposits or CAA seem to become associated with a full blown angiitis, where there is a profuse inflammatory response including multinucleated giant cells in vessel walls and where macrophages can be seen to have internalized amyloid [49,50]. There have been a total of 41 cases with such a CAA associated angiitis wherein a rapidly progressive dementia has been the most frequent presentation.…”

Cerebral Vasculitis Associated With Amyloid Angiopathy -Case Report-

“…6) On the other hand, sustained or dramatic improvements are rarely observed. 8) Among six patients with histology-positive primary angiitis of the CNS, two died, one suffered severe disability, two had moderate disability, and one had minor disability. All had received steroid and/or further immunosuppression therapy with no clear pattern of response to the treatment.…”

“…The most common clinical features in cerebral vasculitis associated with CAA are changes in the mental status (confusion states, poor memory/concentration or impaired conscious level), often leading to frank dementia, headache, hallucinations, and seizures. 8) Diagnostic imaging can be difficult in such patients. Cerebral vasculitis associated with CAA and vascular inflammation often appears as prominent white matter changes on computed tomography and MR imaging.…”