Reader Response: Rabies encephalitis presenting with new-onset refractory status epilepticus (NORSE)

We read the recent case report by Villamar et al.¹ and have concerns about the conclusion that the patient died of rabies. First, it would be useful to know when the case occurred and whether there was any history of an animal exposure. This is basic historical information that should be sought in a case of suspected rabies and could be obtained postmortem if the diagnosis was not considered during life. Second, the initial 1-month history of personality change and declining academic performance and the 2-week gap between the initial seizure and the status epilepticus are incompatible with rabies encephalitis, which is characterized by rapid progressive neurologic deterioration once neurologic symptoms and signs are present.² Third, the illustrated eosinophilic body associated with a neuron is not indisputably a Negri body. Its location could be paraneuronal rather than intracytoplasmic. Negri bodies are intraneuronal cytoplasmic inclusion bodies that contain rabies virus RNA and proteins.³ Negri body–like inclusions, some consisting of endoplasmic reticulum distended by proteinaceous material, have been described in other conditions.^4-6 Fourth, detailed studies of human cases showed that all neurons with Negri bodies also expressed detectable rabies virus antigen.^7,8 Rabies virus antigens are easily detected using immunohistochemical methods in formalin-fixed paraffin-embedded tissues using polyclonal or monoclonal anti–rabies virus antibodies.³ Failure to detect rabies virus antigens in a fatal case would need to be explained by improper tissue preparation involving excessive fixation. The report of a positive in situ reverse transcription PCR (RT-PCR) result with no supporting images and a detailed description of the anatomical localization is inadequate. There was no mention made of conventional RT-PCR results for rabies virus RNA.⁹ There was no description of positive or negative controls for the immunohistochemistry and in situ RT-PCR studies. Could other standard cellular (e.g., neuronal) antigens be detected in the tissues? With the available information reported, the evidence that the patient died of rabies is unconvincing.