35‐YEAR‐OLD HIV‐POSITIVE WOMAN WITH BASAL FOREBRAIN MASS

CLINICAL HISTORY

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.

Figure 1.

PATHOLOGY

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 × 2.3 × 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.

Figure 2.

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.

Figure 3.

Figure 4.

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).

Figure 5.

Figure 6.

What is the diagnosis?

DIAGNOSIS

Acute adenovirus encephalitis.

Immunohistochemistry for adenovirus showed strong nuclear and cytoplasmic positivity within neurons and glia. Electron microscopy of tissue from the basal forebrain lesion revealed numerous non‐enveloped virions with icosahedral symmetry that ranged in diameter from 70 to 75 nm, consistent with adenovirus (Figure 6). No other virions were identified.

DISCUSSION

Patients with HIV/AIDS frequently present with neurological signs and symptoms and require neuroimaging studies as part of their diagnostic workup. The detection of intracranial pathology consisting of a focal brain lesion raises the possibility of an opportunistic infection versus a neoplastic process. The major diagnoses in these patients include Toxoplasma gondii infection, primary CNS lymphoma, progressive multifocal leukoencephalopathy (PML) and focal HIV encephalopathy, with some variation seen in the frequency of these entities with the advent of highly active antiretroviral therapy. CD4+ T lymphocyte counts and a history of ongoing prophylaxis for opportunistic infections are also factors that may influence the differential diagnosis of a focal brain lesion in HIV/AIDS patients. Other well known infectious etiologies of focal brain lesions in HIV/AIDS patients are fungal organisms, CNS tuberculosis and neurosyphilis. In rare cases, ring‐enhancing and space occupying lesions have been described with cytomegalovirus (CMV) infection of the CNS.

In the present case, the patient was a neurologically impaired woman with HIV/AIDS who was found to have a brain mass in a CT scan of the head. The extensive workup performed to rule out the major causes of this clinical scenario failed to reveal an etiology. With this unusual presentation, CNS adenoviral infection was not suspected.

Adenoviruses are common pathogens which may cause a wide spectrum of diseases depending on the infecting serotype. Clinical entities include respiratory illnesses, pharyngitis, conjunctivitis, gastroenteritis and cystitis, and may produce severe disease in immunosuppressed hosts. Although known to be capable of causing meningoencephalitis, CNS infection by adenovirus (ADV) is infrequent in both immunocompetent and immunosuppressed patients. Of the 51 known adenovirus serotypes, some that have been implicated in CNS infections are 2, 3, 7 and 26, as well as serotype 31 in mixture with 49 1, 2, 3, 4. Adenoviral meningoencephalitis has most frequently been reported in the setting of pneumonia or as one component of a disseminated infection in immunocompromised patients. Only rarely does adenovirus infection present primarily as a CNS disease (1).

Neuroimaging patterns of CNS adenoviral infection depend on the patient age, location and clinical course. In children, hydrocephalus with periventricular radiolucency and multiple parenchymal hypodensities have been described on CT scan, as well as necrotic changes resembling herpes encephalitis (5). Mild brain atrophy has also been reported. In the adult population, some findings described on MRI imaging include linear high‐signal intensity in the hippocampi on T1, and hyperintense signaling on FLAIR sequencing in both temporal lobes 1, 2. Zagardo et al reported a case of adenoviral rhombencephalitis in an immunosuppressed patient which was found to have T2 signal abnormalities in the brain stem and cerebellum with mild patchy enhancement and mass effect on MRI (5). To our knowledge, the CT findings of an infiltrating mass due to adenovirus has not been previously described. We conclude that adenovirus is a rare and sometimes unsuspected cause of encephalitis that may present as a mass lesion, and should be considered in the differential diagnosis once the major etiologies have been ruled out.

ABSTRACT

A 35‐year‐old African American woman with HIV/AIDS presented with altered mental status. A CT of the head revealed an infiltrating hypodense intra‐axial mass within the basal forebrain. Lumbar puncture showed a lymphocytic pleocytosis, elevated protein and low glucose. 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 were negative. She soon expired. Post‐mortem examination of the patient's brain showed a poorly delineated area of softening and hemorrhage within the basal forebrain. Histologic examination revealed necrotizing encephalitis with perivascular lymphocytes and glial cells with numerous cytoplasmic and intranuclear inclusions. Immunohistochemistry was strongly positive for adenovirus and negative for HSV, CMV, SV40 and EBV. Electron microscopy confirmed the presence virions consistent with adenovirus. We conclude that adenovirus is a rare and sometimes unsuspected cause of encephalitis that may present as a forebrain mass lesion.