Cerebral Amyloid Angiopathy With Progressive Cortical Superficial Siderosis and Convexity Subarachnoid Hemorrhage in an Apolipoprotein E (APOE) ε2/ε2 Homozygous Patient: A Case Report and Literature Review.

Abstract

Sporadic cerebral amyloid angiopathy (CAA) is characterized by progressive amyloid β-protein (Aβ) deposition in small cortical and leptomeningeal vessels. It is associated with intracerebral hemorrhage (ICH), cognitive decline, and gait disturbance. Among its hemorrhagic manifestations, cortical superficial siderosis (cSS) and convexity subarachnoid hemorrhage (cSAH) are gaining increasing attention, particularly in individuals carrying the apolipoprotein E (APOE) ε2 allele. A cSAH typically represents an acute-phase lesion caused by blood leakage into the subarachnoid space, often presenting as a single linear hypointensity on MRI. In contrast, cSS is a chronic-phase lesion characterized by hemosiderin deposition in the superficial cortex, typically appearing as a double-line hypointensity. Both lesions are believed to originate from the rupture or leakage of structurally fragile small vessels in the leptomeninges and superficial cortex. The accumulation of iron-containing blood products may trigger inflammatory responses and secondary damage to vessels and brain parenchyma, promoting recurrent hemorrhage and cognitive decline. The APOE ε2 allele is hypothesized to exacerbate vascular fragility through Aβ-mediated mechanisms and to increase the severity of hemorrhagic complications in CAA. Homozygosity for APOE ε2 is rare in the general population and has been associated with an elevated risk of hemorrhage in CAA, making this case particularly noteworthy. We report the case of a probable CAA in a man in his 60s who was homozygous for APOE ε2. Over a 10-month period, he experienced progression from mild cognitive impairment and subtle gait abnormality to severe dementia and marked limping. Imaging revealed recurrent cSAH and progressive cSS, along with simultaneous ICH and cSAH in opposite hemispheres. In particular, atypical cSAH-characterized by larger volume or prolonged blood retention-was followed by more extensive cSS in the same regions. Brain perfusion single-photon emission computed tomography (SPECT) showed hypoperfusion in cortical areas affected by these lesions, particularly in the bilateral frontal lobes, more pronounced on the left, and in the bilateral parietal lobes. This case highlights the aggressive course of CAA in a patient with APOE ε2/ε2 homozygote, where repeated hemorrhagic events and iron accumulation may result in both vascular injury and parenchymal dysfunction. We discuss imaging, clinical progression, and pathophysiological implications, with a focus on the role of APOE ε2 in exacerbating hemorrhagic lesions and promoting cognitive and motor decline.