Herpes simplex encephalitis (HSE) is commonly treated empirically with
acyclovir without confirmatory brain biopsy. Three consecutive adults
with molecularly verified mitochondrial encephalomopathy, lactic acid
osis, and stroke-like episodes (MELAS) syndrome presented with, and we
re treated for, apparent HSE. MELAS syndrome in adults may present as
an atypical, recurrent form of HSE and should be added to the list of
neurologic diseases that can mimic HSE.