Brain Pathology Case of the Month - August 2009

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.


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 (HAART) (1). 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 (12). In rare cases, ring-enhancing and space occupying lesions have been described with cytomegalovirus (CMV) infection of the CNS (3,7).

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 (5,6). 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 (2,4,6,8-11). 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 (2).

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 (13). Mild brain atrophy has also been reported (9). 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 (8,2). 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 (13). To our knowledge, the CT findings of an infiltrating mass due to adenovirus within the basal forebrain, such as the case presented here, has not been previously described.

In our case, the diagnosis of acute viral encephalitis was made on microscopic examination of postmortem tissue from the forebrain mass. Electron microscopy identified virions consistent with adenovirus, a pathogen that was not suspected to be the cause of encephalitis in this patient. 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.


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Contributed by Cristina Vincentelli, MD, Matthew J. Schniederjan, MD and Daniel J. Brat, MD, PhD

International Society of Neuropathology