Herpes Simplex Virus Infection as a Cause of Benign Recurrent Lymphocytic Meningitis

doi:10.1059/0003-4819-121-5-199409010-00004

Herpes Simplex Virus Infection as a Cause of Benign Recurrent Lymphocytic Meningitis

From the University of Colorado Health Sciences Center, The Children's Hospital, and the Denver Veterans Affairs Medical Center, Denver, Colorado; the University of Washington, Seattle, Washington. Requests for Reprints: Myron J. Levin, MD, Department of Pediatric Infectious Diseases, University of Colorado Health Sciences Center, 4200 East 9th Avenue C227, Denver, CO 80262. Acknowledgments: The authors thank Dr. Valerie G. Preston for providing the pGX146 construct and Cathie Wren for assistance with PCR studies. Grant Support: In part by a grant (NIH AI-20381) from the National Institute of Aging and by the Louis and Sydell Bruckner Memorial Fund of the University of Colorado School of Medicine. Dr. Tyler is supported by a merit grant from the Department of Veterans Affairs and by NINCDS Research Program Project grant P1NS32228A.

Abstract

Objective: To identify the role of herpes simplex virus (HSV) in causing benign recurrent lymphocytic meningitis.

Design: Prospective cohort study.

Setting: Tertiary referral center.

Patients: 20 consecutive patients with a provisional diagnosis of benign recurrent lymphocytic meningitis had cerebrospinal fluid specimens submitted between 1990 and 1993 to the diagnostic virology laboratory. Thirteen patients met our criteria for benign recurrent lymphocytic meningitis.

Measurements: Herpes simplex virus DNA was detected in cerebrospinal fluid specimens using the polymerase chain reaction, followed by hybridization with a HSV-specific DNA probe. Herpes simplex virus type 1 and type 2 DNA products were distinguished by digestion with restriction enzymes and analysis by gel electrophoresis. Anti-HSV antibodies in cerebrospinal fluid were detected by immunoblot.

Results: The patients had 3 to 9 attacks (mean, 4.6 attacks) of benign recurrent lymphocytic meningitis during periods ranging from 2 to 21 years (mean, 8.4 years). Three of 13 patients had known recurrent genital herpes. Cerebrospinal fluid analysis showed 48 to 1600 cells/µL, glucose levels of more than 2.22 mmol/L (40 mg/dL), and protein levels of 41 to 240 mg/dL (0.41 to 2.4 g/L). Herpes simplex virus DNA and anti-HSV antibodies were detected in cerebrospinal fluid samples in 11 of 13 patients (84.6%; 95% CI, 55% to 98%). Ten of these 11 patients had HSV type 2 DNA and HSV type 2 antibodies. One patient had HSV type 1 DNA and HSV type 1 antibodies in the cerebrospinal fluid. The remaining two patients had only anti-HSV type 2 antibodies.

Conclusions: Herpes simplex virus, predominantly HSV type 2, was the major agent causing benign recurrent lymphocytic meningitis that met our specified diagnostic criteria.