Inflammatory Cerebral Amyloid Angiopathy: A Broad Clinical Spectrum

Abstract

Cerebral amyloid angiopathy (CAA) is a common central nervous system (CNS) vasculopathy, which in some cases is associated with subacute encephalopathy, seizures, headaches, or strokes due to vascular inflammation directed against vascular amyloid accumulation. The pathological subtypes of inflammatory CAA include CAA-related inflammation (CAAri) with mostly perivascular lymphocytic infiltrates, or amyloid-beta (Aβ)-related angiitis (ABRA) with transmural granulomatous inflammation. CAAri and ABRA probably represent part of the spectrum of CNS vasculopathies, intermediate between CAA and primary CNS vasculitis, and they are closely related to Aβ-related imaging abnormalities and other manifestations of an inflammatory response directed against Aβ in the leptomeninges and cerebral parenchyma. As treatment strategies in Alzheimer's disease shift toward potentially effective antiamyloid immunotherapy, the incidence rate of inflammatory CAA (which is probably an underrecognized condition) is likely to increase. Its clinical features are varied and include subacute encephalopathy, behavioral symptoms, headaches, seizures, and focal neurological deficits, which necessitate a high degree of suspicion for this disorder that often responds to treatment. The recent definition of the typical clinical and radiological syndrome has increased its recognition and may eliminate the need for invasive histological sampling in at least some affected patients. Here we review the pathophysiology, clinical spectrum, and approach to diagnosis, and discuss illustrative cases that highlight the wide range of clinical presentations.

Neurologic Manifestations of Rheumatologic Disorders

“…With the increased use of monoclonal antibodies targeting amyloid for the treatment of Alzheimer disease, more cases of cerebral amyloid angiopathy with related inflammation or amyloid beta-related angiitis may be encountered, given these are documented complications of these therapies. 98 Another important inflammatory disease to consider in the differential diagnosis of primary angiitis of the CNS is Susac syndrome. Susac syndrome is a microvascular endotheliopathy characterized by the triad of encephalopathy, branch retinal artery occlusions, and sensorineural hearing loss.…”

“…Brain MRI may reveal restricted diffusion, edema with T2 hyperintensities, leptomeningeal enhancement ( figure 9-1 ), and meningeal or parenchymal hemorrhages, which are best identified on susceptibility-weighted imaging ( figure 9-1 ) or gradient recalled echo (GRE) imaging. With the increased use of monoclonal antibodies targeting amyloid for the treatment of Alzheimer disease, more cases of cerebral amyloid angiopathy with related inflammation or amyloid beta-related angiitis may be encountered, given these are documented complications of these therapies 98 …”