Monday, July 18, 2016

A 60-year-old man presents with acute confusion, aggressive behavior, and aphasia


T2-weighted FLAIR MRI 

A 60-year-old man presents with acute confusion, aggressive behavior, and aphasia. Imaging reveals a heterogeneously enhancing mass (5 x 2 x 2 cm) in the left medial temporal lobe with extensive peripheral edema (image above), but no significant contrast enhancement. A subtotal temporal lobectomy was performed on suspicion of a low-grade glioma.


High-power view of biopsy from left temporal lobe

The diagnosis is herpes simplex encephalitis. PCR amplification of DNA from the specimen more specifically identified the causative agent as herpes simplex virus, type 1 (HSV1). The most common identifiable cause of viral encephalitis in hospitalized patients, HSV1 classically exhibits tropism for the orbitofrontal and temporal lobes bilaterally, but can on occasion present as a unifocal mass mimicking neoplasm as exemplified in this case. Untreated cases have a mortality rate of up to 70%, while in patients treated with a 14- to 21-day course of acyclovir the mortality rate is less than 10%. Although the patient in this case clinically improved while on a four-week course of acyclovir, he did not return to baseline functioning and was discharged to a nursing home.

Primary infection with HSV1 is usually subclinical. Symptomatic primary infection may manifest as gingivostomatitis, pharyngitis, or a mononucleosis-like syndrome. During the initial infection, the virus undergoes retrograde transport along sensory axons and becomes established in latent form in sensory ganglia, especially the trigeminal ganglion. Reactivation of latent virus produces recurrent mucocutaneous lesions most commonly involving the vermilion border of the lips (herpes labialis) that are recognized as cold sores or fever blisters. About one-third of herpes encephalitis cases are associated with primary infection, while the remainder result from reactivation of latent virus. It remains unclear whether viral reactivation occurs within the brain itself (herpes simplex viral DNA has been detected in normal brain) or in peripheral sensory ganglia, such as the trigeminal ganglion, with secondary axonal transport to the CNS. Olfactory pathways are also likely routes of retrograde viral transport. In contrast, HSV2 infection is more commonly encountered in newborns, acquired via genital infection from the mother during vaginal birth.

A hypercellular specimen with reactive astrocytes and occasional mitotic figures can raise the specter of astrocytoma. However, demonstration of extravasated blood and ischemic necrosis with infiltration by neutrophils, lymphocytes, and CD68-positive macrophages leads to a diagnosis of hemorrhagic necrotizing encephalitis.  Although the presence of haloed Cowdry A viral inclusions provide diagnostic reassurance (see photomicrograph), they are not always seen and are not specific to HSV. Immunohistochemistry for HSV1/2 is positive in infected cells.

Diagnosis:  Herpes simplex virus type 1 (HSV1) encephalitis

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