Zika Virus Meningoencephalitis in an Immunocompromised Patient Pedro V. Schwartzmann, MD, PhD, Leandra N.Z. Ramalho, MD, PhD, Luciano Neder, MD, PhD, Fernando C. Vilar, MD, PhD, Sílvia M. Ayub-Ferreira, MD, PhD, Marília F. Romeiro, MSc, Osvaldo M. Takayanagui, MD, PhD, Antonio C. dos Santos, MD, PhD, André Schmidt, MD, PhD, Luiz T.M. Figueiredo, MD, PhD, Ross Arena, PhD, PT, Marcus V. Simões, MD, PhD  Mayo Clinic Proceedings  Volume 92, Issue 3, Pages 460-466 (March 2017) DOI: 10.1016/j.mayocp.2016.12.019 Copyright © 2017 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 1 Magnetic resonance images from an immunocompromised patient with Zika virus infection showing hypointense and hyperintense lesions with cortical and subcortical involvement of the cingulate and superior frontal gyrus by a meningoencephalitis focus. A, Axial T1-weighted spin-echo image showing hypointense lesion (arrow). Axial T2-weighted turbo spin-echo image (B) and axial fluid-attenuated inversion recovery image (C) show cytotoxic cortical edema with diffusion restriction (arrows). D, Diffusion imaging shows low apparent diffusion coefficient (arrow). E-G, Orthogonal reconstructions of 3-dimensional magnetization-prepared rapid acquisition and multiple gradient echo images T1-weighted after gadolinium injection show no gadolinium enhancement (arrows). H, Cerebral blood volume perfusion map showing hypoperfusion (arrow). Mayo Clinic Proceedings 2017 92, 460-466DOI: (10.1016/j.mayocp.2016.12.019) Copyright © 2017 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 2 Autopsy studies from an immunocompromised patient with Zika virus meningoencephalitis. A, Axial cut of the heart. Note the darker area in the myocardium next to the pericardium (arrow) and a paler color next to the endocardium. B, Histologically, a moderate amount of mononuclear inflammatory cells was observed permeating the cardiac muscle fibers. C, Coronal T1-weighted spin-echo magnetic resonance image of the brain. Note the cytotoxic edema with diffusion restriction but no gadolinium enhancement (arrow). D, Gross specimen showing the corresponding area in the brain. Mayo Clinic Proceedings 2017 92, 460-466DOI: (10.1016/j.mayocp.2016.12.019) Copyright © 2017 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 3 Photomicrographs of autopsy specimens from an immunocompromised patient with Zika virus meningoencephalitis. A, Panoramic view of posterior right frontal cortex. Note the inflammatory cell infiltrate in the subarachnoid space and in the Virchow-Robin space in deeper veins (hematoxylin-eosin, original magnification ×10). B, Closer view of perivascular lymphomononuclear infiltrate and microglial nodules (hematoxylin-eosin, original magnification ×80). C, Negative control of the immunohistochemical (IHC) stain. D, The inflammatory infiltrate was mainly composed of CD8+ T lymphocytes (anti-CD8+ IHC, ×80). E, Activated microglia forming microglial nodules (arrows) and ramified microglial cells (inset) (anti-CD68 IHC, ×200). F, Negative control of the immunofluorescence study presented in part G. G, Immunofluorescence showing ZIKV labeling in macrophages in the central nervous system (arrows). H, Transmission electron micrograph showing clusters of spherical virions (arrows) harboring morphological features consistent with Flaviviridae viruses. Note that the virions are associated with endoplasmic reticulum (original magnification ×4400). WM = white matter. Mayo Clinic Proceedings 2017 92, 460-466DOI: (10.1016/j.mayocp.2016.12.019) Copyright © 2017 Mayo Foundation for Medical Education and Research Terms and Conditions