Cessation of antiviral therapy for herpes simplex encephalitis

Abstract

Troendle-Atkins et al.1Troendle-Atkins J Demmler GJ Buffone GJ Rapid diagnosis of herpes simplex virus encephalitis by using the polymerase chain reaction.J PEDIATR. 1993; 123: 376-380Abstract Full Text PDF PubMed Scopus (108) Google Scholar stated that the detection of herpes simplex virus (HSV) DNA in the cerebrospinal fluid (CSF) by means of polymerase chain reaction (PCR) can be useful for rapid diagnosis of herpes simplex encephalitis (HSE), showing a sensitivity of 75% and a specificity of 100%. This result would help clinicians to start, without delay, antiviral therapy with acyclovir in children in whom the diagnosis of HSE is suspected. However, we are, confronted with another question concerning the duration of acyclovir therapy, because recent observations reported relapses of HSE.2VanLandingham KE Marsteller HB Ross GW Hayden FG Relapse of herpes simplex encephalitis after conventional acyclovir therapy.JAMA. 1988; 259: 1051-1053Crossref PubMed Scopus (114) Google Scholar, 3Nicolaidou P Iacovidou N Youroukos S Liacopoulou-Tsitsipi T Kattamis C Relapse of herpes simplex encephalitis after acyclovir therapy.Eur J Pediatr. 1993; 152: 737-738Crossref PubMed Scopus (11) Google Scholar We describe a boy with HSE who was treated successfully for a prolonged period with acyclovir because HSV DNA was found in the CSF by the PCR test. A 9-year-old boy was referred to us because of a 1-day history of somnolence and disorientation and a 10-day history of persistent fever. The patient had had a traumatic subdural hematoma at the age of 6 months, for which a ventriculoperitoneal shunt had been placed, but development was nevertheless normal. The patient was semicomatose and, shortly after admission, had a left-sided convulsion. Stiffness of the neck was present; vital signs were unremarkable. The CSF contained 15 × 106 cells/L with 95% lymphocytes. A computed tomographic scan of the brain on the day of admission showed a low-density area on the right temporal to occipital lobe with generalized edema. An electroencephalogram on the second day showed abnormalities consisting of diffuse, high-voltage delta-wave activity and right-sided predominance. The presumptive diagnosis of HSE was made and was confirmed by isolation of HSV type 1 from the CSF. Treatment with acyclovir, 10 mg/kg body weight every 8 hours, was started on the day of admission. The patient's condition improved after 10 days of therapy. However, CSF taken 2 weeks after admission still contained HSV DNA, although cultures no longer grew the virus. We decided to extend the duration of acyclovir therapy until we could find no HSV DNA in the CSF by PCR. The patient received intravenously administered acyclovir for 22 days, followed by orally administered acyclovir for 25 days. The patient was well at discharge 1 month after onset, although mild mental retardation was recognized. Several authors have claimed, on the basis of clinical observations but without evidence of eradication of the virus,2VanLandingham KE Marsteller HB Ross GW Hayden FG Relapse of herpes simplex encephalitis after conventional acyclovir therapy.JAMA. 1988; 259: 1051-1053Crossref PubMed Scopus (114) Google Scholar, 3Nicolaidou P Iacovidou N Youroukos S Liacopoulou-Tsitsipi T Kattamis C Relapse of herpes simplex encephalitis after acyclovir therapy.Eur J Pediatr. 1993; 152: 737-738Crossref PubMed Scopus (11) Google Scholar that 10 days of acyclovir therapy for HSE is not sufficient to prevent relapse. The high degree of sensitivity and specificity of the detection of HSV DNA by PCR could be applied as an index of eradication of virus and might be useful to determine adequacy of antiviral therapy; our case demonstrated the discrepancy between the positivity of virus isolate and that of HSV DNA. Our experience and the result obtained by Troendle-Atkins et al.,1Troendle-Atkins J Demmler GJ Buffone GJ Rapid diagnosis of herpes simplex virus encephalitis by using the polymerase chain reaction.J PEDIATR. 1993; 123: 376-380Abstract Full Text PDF PubMed Scopus (108) Google Scholar have prompted us to conduct a controlled study to determine whether prolonged acyclovir therapy on the basis of the presence of HSV DNA in the CSF can prevent relapse. 9/35/52954