A 65-year-old man is brought to the emergency department due to high fevers and confusion. His family says that he has been acting strangely and has been disoriented over the last 2 days. He has also had severe headaches. This morning he was difficult to arouse and reportedly had a seizure on the way to the hospital. His temperature is 39.4 C (103 F), blood pressure is 140/90 mm Hg, and pulse is 112/min. The patient is obtunded with preserved brainstem reflexes and reduced motor responses to pain. CT scan of the head without contrast is negative. Cerebrospinal fluid analysis reveals an elevated opening pressure with a hemorrhagic lymphocytic pleocytosis, increased protein, and normal glucose. An MRI of the brain reveals an abnormal signal in the bilateral temporal lobes. Inhibition of which of the following would be most effective for treating this patient's condition?
This patient has herpes simplex virus (HSV) encephalitis, which can cause acute/subacute changes in mental status, seizures, headache, and, in some cases, focal neurologic deficits. Cerebrospinal fluid (CSF) analysis usually reveals a hemorrhagic lymphocytic pleocytosis with increased protein and normal glucose. On neuroimaging, the classic finding is the presence of an abnormal MRI signal in the bilateral temporal lobes.
The treatment for HSV encephalitis is intravenous acyclovir, a nucleoside analog that, once activated, competes with deoxyguanosine triphosphate for viral DNA polymerase; when acyclovir triphosphate becomes incorporated into the replicating viral DNA chain, viral DNA synthesis is terminated.
(Choices A, B, C, and D) Bacterial meningitis can present similarly to HSV encephalitis; however, unlike HSV encephalitis, there is no predilection for the temporal lobes and CSF analysis typically shows a nonhemorrhagic neutrophilic pleocytosis with low glucose.
(Choice F) Viral proteases are responsible for cleavage of protein precursors necessary for the production of infectious viral particles. Protease inhibitors are important in the treatment of HIV and hepatitis C, not HSV.
(Choices G and H) Viral RNase H (removes the RNA primers during viral DNA replication) and viral reverse transcriptase (generates complementary DNA from an RNA template) are important pharmaceutical targets for the treatment of retroviruses such as HIV.
Educational objective:
The most effective treatment for herpes simplex virus encephalitis is intravenous acyclovir. Acyclovir is a nucleoside analogue whose active component is incorporated into replicating viral DNA, leading to termination of viral synthesis.