Diagnosing infectious encephalitis: a narrative review.

Background: Diagnosing infectious encephalitis can be challenging as it can be caused by a wide range of pathogens, with viruses being the most common cause. In a substantial number of patients, no pathogen is identified despite a clinical diagnosis of infectious encephalitis. Recent advancements in diagnostic testing have introduced new methods to address this diagnostic challenge and improve pathogen detection.

Objectives: The objective of this study is to provide a comprehensive clinical approach for diagnosing infectious encephalitis and explore novel diagnostic methods.

Sources: We searched PubMed to identify relevant literature on diagnosing encephalitis in English up to 1 September 2024, as well as included articles known by the authors.

Content: Clinical characteristics may suggest a specific cause of infectious encephalitis, but are insufficient to guide treatment decisions. Therefore, cerebrospinal fluid (CSF) examination remains the cornerstone of the diagnostic process, with CSF leucocyte count being the most reliable predictor for central nervous system infections. CSF features can be normal, however, in a proportion of patients presenting with infectious encephalitis. A definite diagnosis of infectious encephalitis is established by microbiological or histopathological tests in ∼50% of patients. Additional investigations, including neuroimaging or electroencephalography, can provide evidence for encephalitis or help to identify alternate conditions, although their role is primarily supportive. Emerging diagnostic techniques, including next-generation sequencing metagenomics and unbiased serology (Phage ImmunoPrecipitation Sequencing), have the potential to increase the proportion of patients with a confirmed diagnosis. However, these techniques are not yet practical because of their complex analysis, long turnaround times and high costs.

Implications: Microbiological confirmation is paramount in the diagnosis of infectious encephalitis, but it is currently established in about half of cases. Although novel techniques show promise to increase the proportion of cause-specific diagnoses, they are not yet suitable for routine use. This highlights the ongoing need for advancements in diagnostic methods.