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....

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Theiler's virus is a picornavirus of mouse which causes an acute encephalomyelitis followed by a persistent infection of the white matter of the spinal cord with chronic inflammation and demyelination. This late disease is studied as a model for multiple sclerosis. Inbred strains of mice differ in their susceptibility to persistent infection and demyelination. Resistant strains clear the infection after the acute encephalomyelitis. This observation is the basis of genetic studies which we used as a thread for this review. The H-2D locus has a major effect on susceptibility. The H-2Db gene is involved in a fast and intense CTL response which confers resistance. The Tcrb locus is also implicated, although there is no proof that the susceptibility gene in this region codes for the T-cell receptor. A complete screen of the genome uncovered the role of the Ifng locus and led to the demonstration that IFN-gamma limits viral spread in the white matter. The roles of NK cells and B cells in limiting the infection are discussed. CD4+ T cells participate both in protection against the infection and in demyelination. Finally, the effect of non-immune factors in resistance is illustrated by mice with mutations in the MBP or PLP gene.