VIRAL ENCEPHALITIS: CAUSES, DIFFERENTIAL DIAGNOSIS, AND MANAGEMENT

Abstract

ncephalitis refers to an acute, usually diffuse, inflammatory process affecting the brain.While meningitis is primarily an infection of the meninges, a combined meningoencephalitis may also occur.An infection by a virus is the most common and important cause of encephalitis, although other organisms may sometimes cause an encephalitis.An encephalitic illness caused by alteration of normal immune function in the context of a previous viral infection or following vaccination is also well recognised (acute disseminated encephalomyelitis, ADEM).An infectious encephalitis may also be difficult to distinguish from an encephalopathy that may be associated with numerous metabolic causes.Among the factors which have helped to focus attention on viral encephalitis over the last few years have been: c the development of effective antiviral agents for this condition, most notably acyclovir for herpes simplex virus encephalitis (HSE) which is caused by herpes simplex virus (HSV)-1 or HSV-2 c the advent of human immunodeficiency virus (HIV) infection of the central nervous system (CNS) with its wide range of associated acute viral infections c the recent recognition of emerging viral infections of the CNS such as West Nile encephalitis and Nipah virus encephalitis.This article will address three broad areas of viral encephalitis-its causes, differential diagnosis, and management.While the approach will be a general one, I shall focus particularly on HSE which is the most frequent cause of sporadic fatal encephalitis in humans in the western world. CAUSES OF VIRAL ENCEPHALITIS cThe various causes of acute infectious viral encephalitis are shown in table 1.While precise figures for the incidence of encephalitis following these various viruses are not available, estimates have been given for some of them.For example, it has been estimated that HSE, the most important treatable viral encephalitis, has an incidence of about one case per million per year. 1 About 2000 cases occur annually in the USA. 2 About 90% of cases of cases of HSE are caused by HSV-1, with 10% due to HSV-2, the latter usually being the cause of HSE in immunocompromised individuals and neonates in which it causes a disseminated infection.Molecular analyses of paired oral/labial and brain sites have indicated that HSE can be the result of a primary infection, a reactivation of latent HSV, or a re-infection by a second HSV. 1 These estimates of HSE may well be underestimates as judged by the experience of individual neurological centres and detailed studies using the polymerase chain reaction (PCR).Thus, a small PCR based study suggested that up to a fifth of patients with HSE may have mild or atypical disease caused by either HSV-1 or HSV-2, occurring especially in immunocompromised individuals such as those with HIV infection.3 A recent study in Finland also used PCR to detect various viruses in the CSF of over 3000 patients who had infections of the CNS including encephalitis, meningitis, and myelitis.4 It was found that, rather surprisingly, varicella zoster virus (VZV), the cause of chickenpox and herpes zoster, was the most frequently detected virus at 29%, with HSV and enteroviruses accounting for 11% of cases each, and influenza A virus found in 7% of cases.If one assumes a cause-and-effect relation between the detected virus and the CNS condition in a significant proportion of these cases, then it indicates that VZV has been generally underestimated, and HSV perhaps overestimated in frequency.Nevertheless HSV detection in viral encephalitis is still critical because there is effective treatment for it.Further prospective PCR based studies will be needed to answer these questions.While HIV has not been listed as it usually causes a type of subacute encephalitis, it is important in so far as its associated immunosuppression predisposes the individual to viral encephalitis caused by, for example, HSV-1, HSV-2, VZV, and cytomegalovirus (CMV).The frequency and distribution of these viruses clearly varies according to the geographical region, with large differences seen between Europe, Asia, and the USA.Thus, St Louis virus encephalitis, which is caused by a mosquito borne arbovirus, occurs in the midwestern and eastern states of the i10 www.jnnp.com