Contributed by Peter Kang, MD1, Robert E. Schmidt, MD, PhD2, Sonika Dahiya, MD2, Arun S Varadhachary, M, PhD1
1Department of Neurology, 2Division of Neuropathology, Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri
CLINICAL HISTORY AND NEUROIMAGING
A previously healthy 42-year-old man presented with two weeks of confusion, lethargy, headache, and malaise. He was diagnosed with AIDS three months prior (CD4 count 198 cells/microliter; viral load 87,100 copies/mL) and was on trimethoprim/sulfamethoxazole prophylaxis but had not started highly active antiretroviral therapy. Neurologic exam was notable for a sleepy man lacking orientation to location or date, perseveration on simple phrases and overall paucity of speech, and generalized weakness. He could not stand unassisted. Reflexes were 3+ throughout.
MRI was notable for numerous hyperintense T2/FLAIR lesions in multiple regions within the bilateral cerebral hemispheres (Figs. 1a and 1b, FLAIR sequences) as well as the right cerebellum. These lesions demonstrated T1 hypointensity and contrast-enhancement, often in incomplete ring-enhancing patterns (Figs. 1c and 1d).
Serum antitoxoplasma IgG/IgM antibodies, blastomyces antibody and urine histoplasma antigen were negative. CSF analysis showed 10 red blood cells/ml, 41 nucleated cells/microliter (99% lymphocytes), normal glucose, protein 184 mg/dL, 6 oligoclonal bands (<4 normal), and IgG index 0.96 (<0.21 normal). CSF flow cytometry and cytology was negative. CSF was negative for Toxoplasma gondii, Cryptococcus, and VZV, HSV, JC, EBV, and CMV. CSF cultures including fungal and acid-fast bacilli cultures were negative. Stereotactic brain biopsy was performed.
H&E and LFB-PAS stains (Figs. 1e, 1f, 1g, 1h) show a sharply demarcated area of pallor (arrow, Fig. 1e) and loss of myelin, with relative preservation of axons by neurofilament immunostain (Figs 1i, 1j). The lesion also has numerous CD68-positive macrophages (Figs. 1k, 1l). Additionally, the lesion has many CD4-positive lymphocytes (Figs. 1m, 1n) and surrounding an adjacent blood vessel (Fig. 1m, arrow, magnification bar: 500 microns). There was no evidence of neoplasia or infection. What is your diagnosis?