Objective: To determine the frequency of mild/atypical herpes simplex
virus encephalitis (HSVE) among patients with CSF specimens submitted
to a university diagnostic virology laboratory for HSV PCR. Background
: HSVE is the most commonly recognized cause of acute sporadic encepha
litis in the United States. Recognized clinical features are based on
autopsy- or brain biopsy-confirmed cases. This is likely to produce as
certainment bias for features associated with severe disease and under
-recognition of mild or atypical cases. Amplification of HSV DNA by PC
R. from CSF provides a sensitive and specific method for diagnosis of
HSVE. Methods: Results of all HSV CSF PCR tests sent to a university d
iagnostic virology laboratory (January 1, 1993, to December 31, 1996)
were reviewed. Clinical information was prospectively collected and re
trospectively reviewed. Patients with positive HSV CSF PCR tests were
classified as having meningitis, encephalitis, or neonatal infection.
Encephalitis was considered typical or atypical based on published cri
teria. Results: A total of 7.6% of 1,224 CSF specimens were positive f
or HSV DNA. CSF HSV DNA-positive patients had meningitis (52%), enceph
alitis (26%), neonatal infection (17%), or nonclassifiable disease (5%
). A total of 17% of HSVE patients had mild or atypical disease charac
terized by the absence of focal findings and slow progression in the a
bsence of antiviral therapy. Atypical HSVE was associated with HSV-2 i
nfection (two of the four patients), immunosuppression by steroid ther
apy or coexisting HIV infection (three of the four patients), or disea
se predominantly involving the nondominant temporal lobe (two of the f
our patients). Conclusion: Approximately one-fifth of HSVE patients ha
ve mild or atypical disease. CSF PCR for HSV DNA should be performed i
n patients with febrile encephalopathy even in the absence of focal fe
atures, initial CSF pleocytosis, or abnormal CT. Mild or atypical HSVE
may be associated with infection with either HSV-1 or HSV-2. Mild or
atypical HSVE was frequently associated with immunocompromise or asymm
etric HSV infection affecting predominantly the nondominant temporal l
obe.