CD4⁺ T Cells Predominate in Cerebrospinal Fluid and Leptomeningeal and Parenchymal Infiltrates in Cerebral Amyloid β–Related Angiitis

Figure 1. CD4⁺ T cells predominate in the cerebrospinal fluid in amyloid β–related angiitis. A-C, Magnetic resonance imaging reveals extensive leptomeningeal infiltration of the parietal and temporal lobes on gadolinium-enhanced fluid-attenuated inversion recovery sequences (A, white arrows) and T1-weighted sequences (B, white arrows); T2*-weighted sequences show hemosiderin in a sulcal pattern (C, white arrows). D, Gross aspect of the meningeal and cortical surface on leptomeningeal biopsy; note the xanthochromic cerebrospinal fluid (CSF) within the subarachnoid space. E-J, Flow cytometry of the peripheral blood (E, G, and I) and CSF (F, H, and J) shows lymphocytic pleocytosis (F), predominantly by CD4⁺ T cells (H), a substantial fraction of which are positive for the activation marker CD69 (J). These changes were not detected in the peripheral blood (E, G, and I). K and L, Cerebrospinal fluid cell count, CSF protein level, serum to CSF albumin ratio (K), CD4/CD8 ratio, and fraction of CD69⁺ CD4⁺ T cells (L) regressed on combined therapy with intravenous and oral steroids and cyclophosphamide, as revealed by serial analysis for the first 2 months after admission (H). FSC indicates forward scatter; gran, granulocytes; lymph, lymphocytes; mono, monocytes.

Figure 2. CD4⁺ T cells and macrophages predominate in leptomeningeal and cortical (peri)vascular infiltrates in amyloid β (Aβ)–related angiitis. A-D, Hematoxylin-eosin (HE) staining of the superficial brain biopsy specimens shows inflammation and vasculitis of the leptomeninges (A, arrow) and of cortical vessels (A, arrowheads) (A, original magnification ×5); the rectangle in panel A is represented in panel B (original magnification ×25), showing cortical arteries with pronounced inflammatory infiltrates (B); within the leptomeningeal infiltrates, most of the cells are lymphocytes and histiocytes, and some of them appear as multinucleated giant cells (C, arrows) (original magnification ×50); fibrinoid necrosis (D, arrow) and thick hyaline-appearing pathologic vessel walls (triangles) are also shown (D) (original magnification ×25). E, Immunohistochemically, anti-Aß staining shows depositions within the arachnoidal vessel walls and many primitive cortical amyloid plaques (original magnification ×25). F, Arrows indicate Aß-laden giant cells (original magnification ×50). G, Anti-CD68 immunohistochemical staining indicates the high percentage of macrophages (original magnification ×50) and many giant cells (insert [original magnification ×100]). H, Among the lymphocyte population, CD4⁺ T cells are dominating, as shown by anti-CD4 immunohistochemical analysis (alkaline phosphatase anti-alkaline phosphatase technique) (original magnification ×50). Conversely, immunohistochemical analysis for CD3⁺ T lymphocytes (I [original magnification ×50] and K [original magnification ×25]) reveals a low percentage (about 20%) of cytotoxic CD8⁺ T cells (J [original magnification ×50] and L [original magnification ×25]) comparing the same detail of the respective infiltrates; thus, about 80% of the T-lymphocyte population is made up of CD4⁺ T cells. M and N, Immunohistochemical analysis for major histocompatibility complex class II (MHCII) demonstrates intense staining of parenchymal microglia (M; original magnification ×25) and perivascular macrophages (M and N [original magnification ×100]). O and P, Giant cells (O, arrow [original magnification ×100]) also intensely stained for MHCII (P [original magnification ×100]), visible when comparing the same detail marked by a rectangle in O and P.