Reversible Encephalopathy after Cardiac Transplantation: Histologic Evidence of Endothelial Activation, T-Cell Specific Trafficking, and Vascular Endothelial Growth Factor Expression

Early microscopic pathologic features of reversible encephalopathy, hematoxylin-eosin stain. A, Hematoxylin- eosin–stained sections showed many small blood vessels with reactive endothelial cells (black arrow) in the white matter demonstrating cellular and nuclear enlargement as well as mild interstitial edema (white arrow). Some vessels appeared nonreactive and are visible as a comparison (arrowhead). No vasculitis, demyelination, or axonal swelling was seen. Some scattered erythrocytes are present from the biopsy procedure, but no hemosiderin-laden macrophages were seen. B, These reactive blood vessels were also present in the gray matter, seen adjacent to a neuron (arrow), along with reactive astrocytes (arrowheads).

Early microscopic pathologic feature of reversible encephalopathy on immunohistochemical examination. A, CD45 (leukocyte common antigen) shows scattered lymphocytes in the intravascular (arrowhead) and perivascular (arrow) areas. The vessels identified by the arrows are shown in higher magnification in Figs B and C. B, Higher magnification of arrowhead in Fig 3A. Lymphocytes (T-cells) are regularly noted within the intravascular space (arrows) surrounded by endothelium (arrowhead). Other leukocytes (polymorphonuclear leukocytes, monocytes, macrophages) were not identified, suggesting selective T-lymphocyte adherence. C, Higher magnification of arrowhead in Fig 3A. Lymphocytes (T-cells) have traversed the endothelium (end point of the lymphocyte trafficking process) and are in the perivascular space (arrow). D, These lymphocytes were CD3-positive T-cells (arrow). No CD20-positive B-cells were present, and CD68 immunostaining identified only a modest number of activated microglia with no macrophages (not shown). Results of immunohistochemical and in situ hybridization studies were negative for toxoplasmosis, herpes simplex virus 1 and 2, Epstein-Barr virus, and JC virus (not shown). Results of tissue cultures were also negative.