Inflammatory Cerebral Amyloid Angiopathy, Amyloid-β-Related Angiitis, and Primary Angiitis of the Central Nervous System: Similarities and Differences.

Abstract

Cerebral amyloid angiopathy (CAA) results from deposition of amyloid-β fibrils in the wall of the small and medium-sized blood vessels, mostly arteries of the leptomeninges and cerebral cortex. Architectural disruption of amyloid-β laden vessels, occasionally with fibrinoid necrosis, leads to perivascular leakage. Vascular rupture causes lobar microbleeds or hematomas and high-convexity subarachnoid hemorrhages. The accumulation of amyloid-β causes vessel lumen obliteration, thereby leading to ischemic leukoencephalopathy and cerebral infarction. Varying amounts of perivascular inflammation may be present, involving multinucleated giant cells in the most severe cases.1 However, frank vasculitic destruction of the vessel wall such as is found in amyloid-β–related angiitis (ABRA)2 and primary angiitis of the central nervous system (PACNS)3 is absent in the inflammatory form of CAA (I-CAA). There is substantial clinical overlap in the phenotypes of I-CAA, ABRA, and PACNS. A proper diagnosis of these 3 conditions is necessary because their individual treatment differ. Through 3 cases, we summarize similarities and differences between I-CAA, ABRA, and PACNS. A 52-year-old woman complained about limb paresthesias lasting 3 days. She reported cognitive decline and fatigue lasting 3 months, a relentless headache that had lasted for a year, in addition to episodic migraine and tension-type headaches. Past medical history was unremarkable, except for active cigarette smoking. Physical and neurological examination was normal. Brain magnetic resonance imaging (MRI) showed nonspecific lobar, white matter, nonenhancing hyperintensities on T2-weighted sequences. No treatment was initiated in the absence of a specific diagnosis. Blood tests, including inflammatory and prothrombotic work-up, cardiac ultrasound, Holter monitoring, digital subtraction cerebral angiography, and cerebrospinal fluid (CSF) analysis were normal. She remained stable clinically. Three months later, repeat brain MRI revealed new lobar T2-hyperintensities (Figure 1A) and several lobar microbleeds on gradient-echo sequences. CNS biopsy revealed extensive amyloid-β deposits in the wall of small leptomeningeal and cortical …