A Fatal Case of Herpes Simplex Encephalitis with Two False-Negative Polymerase Chain Reactions

Abstract

An 88-year-old man presented with a 1-month history of altered mental status and seizures. His electrographic and imaging findings were suggestive of herpes simplex encephalitis (HSE), for which he was empirically treated with acyclovir. He underwent two lumbar punctures 3 days apart; both cerebrospinal fluid analyses tested negative for herpes simplex virus (HSV) by polymerase chain reaction (PCR). These negative results and his continued deterioration after 9 days of acyclovir therapy prompted treatment with steroids for possible autoimmune encephalitis. Shortly after the change in management, the patient died from cardiac arrest. At autopsy, his brain showed both gross and microscopic evidence of encephalitis and was positive for HSV by immunohistochemistry. This fatal case of HSE emphasizes the limitations of HSV PCR and the importance of clinical suspicion in the diagnosis and management of this disease.

Keywords: Encephalitis; False-negative results; Herpes simplex virus; Polymerase chain reaction.

Fig. 1.

a The brain at autopsy was grossly unremarkable except for slight atrophy in the right temporal lobe cortex (asterisk). b, c Photomicrographs of hematoxylin and eosin-stained brain parenchyma from hippocampus and temporal lobe at ×100 (b) and ×400 (c) original magnification demonstrating subacute necrosis and mixed perivascular lymphocytic infiltrate. d Immunohistochemical staining for herpes simplex virus 1 at ×400 original magnification highlights neurons, glia, and macrophages positively. Overall, these findings are consistent with necrotizing viral encephalitis, more specifically herpes simplex encephalitis.

Fig. 2.

a Magnetic resonance imaging-fluid-attenuated inversion recovery, axial image; hyperintense signal involving the medial and anterior lateral right temporal lobe. b A 10-s interval of electroencephalography displayed using a longitudinal bipolar montage at a sensitivity of 7 mV with a time constant of 0.1 s and high-frequency filter of 70 Hz, demonstrating 40–50 mV 1.5 Hz right temporal lateralized periodic discharges (black arrows) with superimposed rhythmic delta activity.