Comparing cerebral amyloid angiopathy related inflammation and primary angiitis of the central nervous system in pathophysiology, diagnosis, and treatment

Abstract Cerebral amyloid angiopathy–related inflammation (CAA-RI) and primary angiitis of the central nervous system (PACNS) are rare inflammatory cerebrovascular disorders that frequently present with overlapping clinical, radiological, and laboratory features. Despite similarities, they differ substantially in pathophysiology, diagnosis, treatment, and outcomes, making their distinction a major clinical challenge critical for management. This paper compares their pathophysiology, clinical manifestations, diagnostics, therapeutics, and prognosis, while highlighting diagnostic dilemmas and future research priorities. A literature review examined immunopathogenesis, neuroimaging, cerebrospinal fluid (CSF) biomarkers, histopathology, treatments, and outcomes, emphasizing overlap and divergence. CAA-RI is characterized by an autoimmune inflammatory response against amyloid-β–laden cerebral vessels, producing perivascular inflammation, blood–brain barrier dysfunction, and vasogenic edema. PACNS, conversely, is an idiopathic vasculitis driven by adaptive immune mechanisms without vascular amyloid deposition. Clinically, both may present with cognitive impairment, headache, seizures, focal deficits, and encephalopathy. However, CAA-RI typically affects older individuals and is more strongly associated with cerebral microbleeds, cortical superficial siderosis, and asymmetric white matter hyperintensities on MRI. PACNS more commonly demonstrates multifocal ischemic lesions and angiographic vessel irregularity. CSF anti-amyloid-β autoantibodies, reduced CSF amyloid levels, and APOE ε4 homozygosity are promising CAA-RI biomarkers, whereas PACNS lacks disease-specific markers. Brain biopsy remains the gold standard but is increasingly reserved for cases of uncertainty. High-dose corticosteroids are first-line therapy, with additional immunosuppressants for refractory or relapsing disease. Compared with PACNS, CAA-RI generally shows lower relapse rates and more favorable functional outcomes. Despite overlap, distinctions in immunopathology, imaging, biomarkers, and prognosis enable differentiation through a multimodal diagnostic approach.