Adult Encephalitis: What Are We Really Talking About?


The ultimate cause is found in only about half of patients, so improved understanding of the prognostic and diagnostic features is of high priority.

Improved understanding of adult encephalitis is of high priority, says the author.

Encephalitis is a serious syndrome marked by acute inflammation of the brain. It is commonly associated with headache, altered mental status, and seizures, and it frequently may present with focal neurologic deficits as well. Since it is inflammatory, encephalitis is also commonly associated with indices of inflammation in the cerebrospinal fluid (CSF).

The most common etiologies are infectious and autoimmune. Although encephalitis frequently is acute in onset, its consequences often are quite long-lasting, with significant sequelae of the acute attack or with chronic disease, especially in cases caused by autoimmunity.

Despite the importance and severity of acute encephalitis, the ultimate cause is found in only about 50% of patients, so improved understanding of the prognostic and diagnostic features in significant series of patients is of high priority.

A recent retrospective series of patients reported in Neurology1 provides some interesting insights and useful lessons. The series consisted of 198 patients with just about equal gender distribution. Almost half of the patients had infectious etiologies and the remainder were about equally divided between autoimmune and unknown etiologies. Among patients with infectious etiologies, there was an equal gender distribution, but, unsurprisingly, women were overrepresented among the patients with autoimmune etiologies.

The most common identified pathogens were herpes simplex virus, varicella-zoster virus, West Nile virus, Epstein-Barr virus, and HIV. They were identified either by polymerase chain reaction from CSF or the presence of antibodies in CSF. In CSF studies, there was little that was commonly distinctive between autoimmune and infectious causes in the aggregate except that infectious causes tended to have more elevated protein levels. The cell counts and differentials were similar in these 2 groups. 

The diagnostic decision to place patients in either the infectious or the autoimmune category proved of very high importance given the very different courses of therapy. But in this series there was little evidence that anything other than casting a wide diagnostic net is a really useful strategy.

The authors examined the distribution of a variety of factors associated with good vs poor outcome. In a multivariate analysis, they found that older age and immunocompromised status were predictors of poor outcome. In addition, not surprisingly, patients with more severe coma scores or a requirement for mechanical ventilation also had poor outcomes.

One of the more fascinating aspects of this study is that in this large series only about 25% of patients have unclear etiologies. It will be important to further improve this, but this is still a significant improvement over the consensus that half of patients never have a clear etiology. I suspect that as the spectrum of autoimmune encephalitis continues to expand, some of these patients will clearly end up falling into this category.


1. Singh TD, Fugate JE, Rabinstein AA. The spectrum of acute encephalitis: causes, management, and predictors of outcome. Neurology. 2015;84:359-366.

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