LETTER TO THE EDITOR

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Screening Cerebrospinal Fluid Prior to

Herpes Simplex Virus PCR Testing Might
Miss Cases of Herpes Simplex
Encephalitis

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Benjamin T. Galen
Albert Einstein College of Medicine and Montefiore Medical Center, Department of Internal Medicine, Division
of Hospital Medicine, Bronx, New York, USA

KEYWORDS encephalitis, herpes simplex virus

H auser et al. make a compelling financial argument for their cost-saving approach
to cerebrospinal fluid (CSF) herpes simplex virus (HSV) PCR testing using the CSF
white blood cell (WBC) count and CSF total protein as a screen for the appropriate use
Citation Galen BT. 2017. Screening
cerebrospinal fluid prior to herpes simplex
virus PCR testing might miss cases of herpes
of PCR (1). The authors do not report any instances of HSV central nervous system (CNS) simplex encephalitis. J Clin Microbiol
infection (defined by PCR positivity) with a normal CSF WBC count in their series 55:3142–3143. https://doi.org/10.1128/JCM
.01129-17.
from two nearby institutions; however, cases of “normocellular CSF” with normal total
Editor Alexander J. McAdam, Boston Children's
protein have been widely reported in the literature on herpes simplex encephalitis Hospital
(2–4). One recent series from Thailand found that 6 of 23 (26.1%) cases of herpes Copyright © 2017 American Society for
simplex encephalitis had normal CSF WBC counts (⬍5 cells/mm3), only 1 of whom had Microbiology. All Rights Reserved.
HIV infection (4). Other experts place the rate of initially normal CSF WBC counts in Address correspondence to
BGalen@montefiore.org.
herpes simplex encephalitis at closer to 10% (5). I have significant concerns that
For the author reply, see https://doi.org/10
restricting the CSF HSV PCR assay to samples with a CSF pleocytosis or elevated total .1128/10.1128/JCM.01144-17.
protein might miss cases of herpes simplex encephalitis and have devastating conse-
quences for patients.
CSF HSV PCR is widely accepted to be the test of choice for herpes simplex
encephalitis, but 98% sensitivity compared to the actual gold standard of brain biopsy
means that false-negative PCR results can occur (6). Furthermore, CSF HSV PCR has
been described to be negative early on in cases of herpes simplex encephalitis (7). A
potential limitation of modeling retrospective laboratory data is that a patient with
herpes simplex encephalitis but a false-negative CSF HSV PCR result might have been
missed by Hauser et al. in their study (1).
Given the significant mortality and neurologic benefit of early acyclovir initiation in
herpes simplex encephalitis without delay and this disease’s varied clinical presenta-
tions, it is the standard of care to treat cases of suspected encephalitis with empirical
acyclovir until HSV has been sufficiently ruled out by PCR testing (4). Delaying the HSV
PCR assay until CSF cell count and total protein results are obtained can result in
unnecessary acyclovir exposure. The side effects of high-dose acyclovir (particularly
nephrotoxicity) were not accounted for in the cost model proposed by Hauser et al. (8).
CSF HSV PCR is a critically important assay in the workup of encephalopathy with
concern for encephalitis; despite Hauser et al.’s model for cost reduction in this area,
clinicians cannot afford to miss a case of herpes simplex encephalitis and should not
rely on a normal CSF WBC or normal CSF total protein as screening tests.

ACKNOWLEDGMENT
I have no conflicts of interest to disclose or any financial disclosures to report.

October 2017 Volume 55 Issue 10 Journal of Clinical Microbiology jcm.asm.org 3142

Letter to the Editor
REFERENCES
1. Hauser RG, Campbell SM, Brandt CA, Wang S. 2017. Cost-effectiveness
study of criteria for screening cerebrospinal fluid to determine the need
for herpes simplex virus PCR testing. J Clin Microbiol 55:1566 –1575.
https://doi.org/10.1128/JCM.00119-17.
2. Kaeley N, Bansal S, Bhatia R, Ahmad S. 2016. Herpes simplex encephalitis:
an uncommon presentation. J Clin Diagn Res 10:OD25–OD26. https://doi
.org/10.7860/JCDR/2016/19040.7801.
3. Rawal G, Yadav S, Wani UR, Ambastha AK. 2015. HSV encephalitis with
normal CSF—a case report with review of literature. J Clin Diagn Res
9:OD06 –OD07. https://doi.org/10.7860/JCDR/2015/16999.6966.
4. Saraya AW, Wacharapluesadee S, Petcharat S, Sittidetboripat N, Ghai S,
Wilde H, Hemachudha T. 2016. Normocellular CSF in herpes simplex
encephalitis. BMC Res Notes 9:95-016-1922-9. https://doi.org/10.1186/
s13104-016-1922-9.
October 2017 Volume 55 Issue 10
Journal of Clinical Microbiology
5. Gilden DH, Mahalingam R, Cohrs RJ, Tyler KL. 2007. Herpesvirus infections
of the nervous system. Nat Clin Pract Neurol 3:82–94. https://doi.org/10
.1038/ncpneuro0401.
6. Tyler KL. 2004. Herpes simplex virus infections of the central nervous
system: encephalitis and meningitis, including Mollaret’s. Herpes
11(Suppl 2):57A– 64A.
7. Weil AA, Glaser CA, Amad Z, Forghani B. 2002. Patients with suspected
herpes simplex encephalitis: rethinking an initial negative polymerase
chain reaction result. Clin Infect Dis 34:1154 –1157. https://doi.org/10
.1086/339550.
8. Sawyer MH, Webb DE, Balow JE, Straus SE. 1988. Acyclovir-induced renal
failure: clinical course and histology. Am J Med 84:1067–1071. https://doi
.org/10.1016/0002-9343(88)90313-0.
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