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From the Departments of Medicine (Drs. Levin, Weinberg, and Tyler), Microbiology and Immunology (Dr. Tyler), Neurology (Drs. Fodor, Sylman, and Tyler), Pediatrics (Drs. Levin and Weinberg), Psychiatry (Dr. Fodor), and Radiology (Dr. Sandberg), University of Colorado Health Sciences Center, Denver; Departments of Neurology (Drs. Fodor, Sylman, and Tyler), Psychiatry (Dr. Fodor), and Radiology (Dr. Sandberg), Denver Veterans Affairs Medical Center, Denver; and Department of Neurology (Dr. Sylman), Kaiser Permanente of Colorado, Denver, CO.
Address correspondence and reprint requests to Dr. Kenneth L. Tyler, Neurology (127), Denver VA Medical Center, 1055 Clermont Street, Denver, CO 80220.
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 encephalitis in the United States. Recognized clinical features are based on autopsy- or brain biopsy-confirmed cases. This is likely to produce ascertainment bias for features associated with severe disease and under-recognition of mild or atypical cases. Amplification of HSV DNA by PCR from CSF provides a sensitive and specific method for diagnosis of HSVE.
Methods: Results of all HSV CSF PCR tests sent to a university diagnostic virology laboratory (January 1, 1993, to December 31, 1996) were reviewed. Clinical information was prospectively collected and retrospectively 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 criteria.
Results: A total of 7.6% of 1,224 CSF specimens were positive for HSV DNA. CSF HSV DNA-positive patients had meningitis (52%), encephalitis (26%), neonatal infection (17%), or nonclassifiable disease (5%). A total of 17% of HSVE patients had mild or atypical disease characterized by the absence of focal findings and slow progression in the absence of antiviral therapy. Atypical HSVE was associated with HSV-2 infection (two of the four patients), immunosuppression by steroid therapy or coexisting HIV infection (three of the four patients), or disease predominantly involving the nondominant temporal lobe (two of the four patients).
Conclusions: Approximately one-fifth of HSVE patients have mild or atypical disease. CSF PCR for HSV DNA should be performed in patients with febrile encephalopathy even in the absence of focal features, 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 asymmetric HSV infection affecting predominantly the nondominant temporal lobe.
Supported in part by grants from the National Institute on Allergy and Infectious Diseases (AI 20381) and by the Louis and Sydell Bruckner Memorial Fund (M.J.L.). Dr. Tyler is supported in part by grants from the Department of Veterans Affairs (MERIT) and the National Institute on Aging (R01 AG14071).
Presented in part at the 48th annual meeting of the American Academy of Neurology, San Francisco, CA, March 1996.
Received January 28, 1998. Accepted in final form April 10, 1998.
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