A 35-year-old man presents to the emergency department with a 3-day history of fever, severe headache, and progressive confusion. On examination, he has altered mental status, dysphasia, and complex partial seizures. MRI brain shows T2/FLAIR hyperintensity in the left mesial temporal lobe with hemorrhage. An EEG is performed and shows the pattern marked **A** in the diagram — periodic lateralized epileptiform discharges over the temporal lobe at 1–2 second intervals. CSF analysis reveals lymphocytic pleocytosis with elevated protein and normal glucose. Based on this clinical presentation and EEG finding, which of the following is the most likely diagnosis and the pathophysiological basis of the temporal lobe involvement?

Explanation

## Why option 1 is correct Herpes simplex encephalitis (HSE) is the most common cause of sporadic fatal viral encephalitis in adults, caused by HSV-1 in >90% of adult cases. The pathophysiology is reactivation of latent HSV-1 from the trigeminal ganglion with retrograde spread along olfactory and trigeminal pathways into the mesial temporal and orbitofrontal lobes, causing hemorrhagic necrotizing encephalitis. The clinical triad of fever, altered mental status, and focal neurological deficits (dysphasia, behavioral changes) combined with the characteristic EEG finding of periodic lateralized epileptiform discharges (PLEDs) over the temporal lobe at 1–2 second intervals is highly characteristic of HSE. The MRI showing asymmetric T2/FLAIR hyperintensity with hemorrhage in the mesial temporal lobe and the CSF lymphocytic pleocytosis with elevated protein further support this diagnosis. Empiric IV acyclovir must be started immediately on clinical suspicion, as untreated mortality exceeds 70% and early treatment reduces mortality to 20–30%. ## Why each distractor is wrong - **Option 2 (Enteroviral meningitis)**: While enteroviruses cause meningitis with CSF lymphocytic pleocytosis, they do not characteristically cause hemorrhagic necrotizing encephalitis with mesial temporal lobe involvement or produce the distinctive periodic lateralized epileptiform discharges pattern on EEG. Temporal lobe involvement is not typical of enteroviral disease. - **Option 3 (Tuberculous meningitis)**: TB meningitis typically affects the basal cisterns and basilar meninges, sparing the mesial temporal lobes. The EEG pattern of PLEDs is not characteristic of TB meningitis, and the acute presentation with hemorrhagic changes on MRI is atypical for tuberculosis, which usually has a more insidious course. - **Option 4 (Cryptococcal meningitis)**: Cryptococcal meningitis typically presents with subacute meningitis and does not cause hemorrhagic necrotizing encephalitis with mesial temporal lobe involvement. The characteristic EEG finding of periodic lateralized epileptiform discharges is not associated with cryptococcal disease. **High-Yield:** Temporal lobe PLEDs + fever + altered mental status + mesial temporal hemorrhage on MRI = HSV encephalitis; start acyclovir empirically without waiting for CSF PCR confirmation. [cite: Harrison 21e Ch 138; Adams Neurology 11e Ch 32]