The role of laboratory investigation in the diagnosis and management of patients with suspected herpes simplex encephalitis: a consensus report. The EU Concerted Action on Virus Meningitis and Encephalitis.

Abstract

As effective therapies for the treatment of herpes simplex encephalitis (HSE) have become available, the virology laboratory has acquired a role of primary importance in the early diagnosis and clinical management of this condition. Several studies have shown that the polymerase chain reaction (PCR) of CSF for the detection of herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2) DNA provides a reliable method for determx ining an aetiological diagnosis of HSE. The use of PCR in combination with the detection of a specific intrathecal antibody response to HSV currently represents the most reliable strategy for the diagnosis and monitoring of the treatment of adult patients with HSE. The use of these techniques has also led to the identification of atypical presentations of HSV infections of the nervous system and permits the investigation ofpatients who develop a relapse of encephalitic illness after an initial episode of HSE. A strategy for the optimal use of the investigative laboratory in the diagnosis of HSE and subsequent management decisions is described. (7 Neurol Neurosurg Psychiatry 1996;61:339-345 centres in the brainstem. In the most severe cases death occurs after seven to 14 days. In a double blind placebo controlled study of treatment of HSE, the mortality in patients treated with placebo was 70% and moderate to severe neurological sequelae affected the great majority of the survivors. 16 A range of clinical presentations of HSV infection of the nervous system, including mild disease courses, relapsing and remitting encephalitis, or unusual neurological syndromes, sometimes related to specific anatomic locations, have now been described Unusual presentations ofHSV infections of the nervous system The role of laboratory investigation in the diagnosis and management ofpatients with suspected herpes encephalitis: a consensus reportThe specificity in this study was assessed on CSF samples from 60 patients with non-HSE encephalitis. None of these samples were found to be HSV PCR positive.22 The use of PCR in this context represents one of the most successful diagnostic test procedures ever described in clinical neurology. To date the limited data available suggest that the HSV PCR remains positive for at least five days after the initiation of acyclovir therapy. Data from PCR obtained from patients who are receiving acyclovir must therefore be interpreted with caution.It is still a matter of debate whether the HSV DNA detected in CSF is derived from intact virions or from viral DNA not associated with mature virions.57 Detection of HSV DNA is, however considered to be associated with viral replication and HSV infection of the CNS.60Demonstration of a humoral immune response within the CNS The intrathecal synthesis of antibody against HSV during the course of HSE can be demonstrated by testing CSF and serum samples collected at the same time. An increased CSF:serum quotient for the HSV antibody titre, adjusted for CSF-blood barrier integrity, indicates a specific intrathecal antibody response....

Herpes Simplex Virus-1 Encephalitis in Adults: Pathophysiology, Diagnosis, and Management

“…Though the initial studies provided aciclovir for 10 days, relapses beyond this were subsequently reported [123,124], prompting most physicians to provide a longer duration of therapy (notably, many cases of apparent relapse may be immune mediated rather than infectious-see below). Some advocate repeat CSF PCR at 14-21 days, with longer treatment if PCR is positive [125,126], though we generally reserve this for patients who have had a complicated course or have not responded to therapy as well as expected. A recently completed trial noted a lack of benefit from an additional 3 months of oral valaciclovir for the reduction of post-HSVE neuropsychiatric complications in 87 adults with PCR-proven HSVE [127].…”

Neuroimaging of infections

“…Detection of HSV DNA in the CSF by PCR remains the mainstay for the diagnosis of HSV encephalitis, 38 although results of this laboratory test may be false negative or may arrive belatedly. Thus, results of imaging studies are important to decide whether antiviral treatment has to be started in patients with suspected HSV encephalitis.…”

Laboratorial diagnosis of lymphocytic meningitis

“…The sensitivity of the PCR reaction depends on a series of factors. The sensitivity of PCR for HSV is 94%, the specificity is 98%, positive predictive value is 95% and negative predictive value is 98% [33,38,[44][45][46][47][48].…”