Inflammation in Cerebral Amyloid Angiopathy-Related Transient Focal Neurological Episodes

Abstract

Transient focal neurological episodes (TFNE), often associated with convexity subarachnoid hemorrhage (cSAH), are common in cerebral amyloid angiopathy (CAA), but their pathophysiology remains incompletely understood. In six patients with unremitting TFNE, using high-resolution post-contrast magnetic resonance imaging and vessel wall imaging (VWI), we found various combinations of transient leptomeningeal, parenchymal and vessel wall enhancement; in 5 of 6 the enhancement included regions corresponding anatomically to symptoms. Three patients had resolution of TFNE and enhancement (2 with corticosteroid treatment, 1 without). Our observations suggest that inflammation might contribute to the pathophysiology of CAA-related TFNE and cSAH, with potential wider relevance for the associated high risks of recurrent ICH in CAA more generally. ANN NEUROL 2025;97:475-482.

FIGURE 1

Each column contains magnetic resonance images for cases 1 to 4. In case 1, susceptibility‐weighted imaging showed extensive superficial siderosis (A). Vessel wall imaging (VWI) showed scattered foci of leptomeningeal enhancement over both cerebral hemispheres (B, red arrows). This enhancement resolved on follow‐up imaging performed 3 months later (C). In case 2, there was bilateral superficial siderosis and many lobar microhemorrhages (D). VWI showed thick leptomeningeal enhancement mainly in the right occipital lobe (E,F, red arrows). In case 3, there was superficial siderosis that was most apparent over the right frontal lobe (G). VWI maximum intensity projections showed punctate parenchymal enhancement in the right temporal and occipital lobes (H,I, red arrows). In case 4, there was extensive superficial siderosis (J) and lobar microhemorrhages (not shown). VWI showed punctate cortical and leptomeningeal enhancement in the right parietal lobe and within the right calcarine sulcus (K,L, red arrows). [Color figure can be viewed at www.annalsofneurology.org]

FIGURE 2

Each row contains magnetic resonance imaging for cases 5 and 6. In case 5, there was extensive superficial siderosis and many enlarged subcortical perivascular spaces (A). Vessel wall imaging showed irregular mural enhancement in a distal branch of the left anterior cerebral artery (red arrows, B), as well as a wider region of leptomeningeal enhancement, which resolved on follow‐up imaging 5 months later (C). In case 6, there was also extensive superficial siderosis and many enlarged perivascular spaces (D). A distal right middle cerebral artery branch showed a short segment of mural enhancement (E, red arrow) that resolved on follow‐up imaging 4 months later (F). [Color figure can be viewed at www.annalsofneurology.org]