Contributed by Cristina Vincentelli, MD1, Matthew J. Schniederjan, MD2 and Daniel J. Brat, MD, PhD.2
1Department of Pathology and Laboratory Medicine, Mount Sinai Medical Center, Miami Beach, FL
2Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA
The patient was a 35-year-old African American woman with HIV/AIDS (CD4 count 95/ml) and no history of HAART therapy, who was admitted from an outside hospital for further management of altered mental status and hypercarbic respiratory failure. Upon admission, the patient was unresponsive and ventilator dependent. On neurologic exam she had no response to painful stimuli, as well as decreased deep tendon and pupillary reflexes. A chest X-ray failed to demonstrate any pulmonary lesions. A CT of the head without IV contrast revealed an infiltrating hypodense mass within the basal forebrain extending inferiorly to the level of the basilar cisterns, involving the thalami and cerebral peduncles bilaterally (Figure 1). Diffuse brain volume loss was also noted. A lumbar puncture was performed for CSF analysis, which showed lymphocytic pleocytosis (56 nucleated cells/ml with 92% lymphocytes), low glucose (23 mg/dl) and elevated protein (208 mg/dl). An infectious disease was suspected. PCR analysis of the CSF was negative for Mycobacterium tuberculosis, HSV, VZV, CMV and JC virus. There was low positivity for EBV DNA. Serologic studies were consistent with past infections with EBV and CMV and were negative for toxoplasmosis, histoplasmosis, Cryptococcus and West Nile virus. VDRL was non-reactive. CSF and blood cultures for bacteria, fungal organisms and acid fast bacilli were negative. The patient received empiric therapy for bacterial meningitis, including Mycobacterium tuberculosis, HSV/VZV encephalitis and coverage for fungi with amphotericin. Her neurologic status progressively deteriorated. She lost all deep tendon reflexes and her left pupil became fixed and dilated. The presence of corneal reflexes was the only sign of remaining brain stem function. The decision to end life sustaining treatment was made and the patient expired. Consent for limited autopsy of the brain was obtained from the family.
The brain weight in the fresh state was 1,220 g. Gross examination of the external surface was unremarkable. Serial coronal sections revealed a poorly circumscribed area of softening with surrounding hemorrhage within the basal forebrain, measuring 2.7 x 2.3 x 1.2 cm (Figure 2). Similar lesions were identified bilaterally in the middle temporal lobes within the anterior hippocampi measuring 1.0 cm each. The ventricles were slightly dilated. The cortical ribbon and deep gray structures appeared unremarkable, as well as the brainstem and cerebellum.
Microscopic examination of the areas of softening demonstrated necrotizing encephalitis with a predominantly lymphocytic inflammatory infiltrate in a perivascular pattern and marked reactive gliosis (Figure 3). Many of the reactive glia showed a variety of intranuclear and intracytoplasmic inclusions, ranging from amorphous and basophilic to discreet and eosinophilic (Figure 4). Similar changes were identified around the fourth ventricle, at the level of the mid-pons. Numerous microglial nodules without multinucleated giant cells were present around the lesions and in the grossly normal brain.
Stains for JC virus (SV40), HSV, CMV and EBV were negative. Beta amyloid and tau protein stains were also negative. Diagnostic immunohistochemistry showed strong nuclear and cytoplasmic positivity within neurons and glia (Figure 5) and the diagnosis was confirmed by electron microscopy (Figure 6).