A 65-year-old man is brought to the emergency department due to high fevers and confusion. His family says that for the past couple of days, he has been acting strangely and has been disoriented. 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. A drug that inhibits which of the following would be most effective in treating this patient's condition?

Question

A 65-year-old man is brought to the emergency department due to high fevers and confusion.  His family says that for the past couple of days, he has been acting strangely and has been disoriented.  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.  A drug that inhibits which of the following would be most effective in treating this patient's condition?

Quizplus · Accepted Answer

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 includes 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. 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 (Choice F). Viral RNase H (removes the RNA primer, allowing for completion of newly synthesized DNA) and viral reverse transcriptase (generates complementary DNA from an RNA template) are important pharmaceutical targets for the treatment of retroviruses such as HIV (Choices G and H). (Choices A, B, C, and D) Bacterial meningitis can present similarly to HSV encephalitis; however, unlike HSV encephalitis, CSF analysis typically shows a nonhemorrhagic neutrophilic pleocytosis with low glucose and elevated protein and there is no predilection for the temporal lobes. Educational objective: The most effective treatment for herpes simplex virus encephalitis is intravenous acyclovir; whose mechanism of action is complete inhibition of the viral DNA polymerase (synthesizes viral DNA). __________ References: Herpes simplex encephalitis: from virus to therapy. (http://www.ncbi.nlm.nih.gov/pubmed/21488834)

A 65-Year-Old Man Is Brought to the Emergency Department Due