Improving prognosis by using innovative methods to diagnose causes of encephalitis
Background: Encephalitis is a severe inflammation of the brain that can be caused by viruses, bacteria and other microorganisms, or autoimmune disease. The impact is high: the case fatality rate is 10-20% and half of patients have neurological deficits. Identifying the cause of encephalitis is essential for early initiation of therapy and thereby improves outcome.

The clinical challenge: Current diagnostics for encephalitis are insufficient. My prospective pilot study showed that the cause of encephalitis could be identified in only half of patients. 

Aim: The aim of I-PACE is to improve the cause-specific diagnosis of encephalitis using innovative diagnostic methods.

Methods: I will use my encephalitis network of Dutch hospitals to study innovative diagnostic methods in 3000 patients with suspected encephalitis and validate the results in 2000 patients from Denmark, the UK and Zambia. I will collect clinical data, cerebrospinal fluid (CSF) and blood to enable state-of-the-art diagnostic studies and identify novel causes of encephalitis. First, I will perform virus discovery and DNA metagenomics sequencing to identify new infectious causes of encephalitis, combined with phage-display antibody sequencing. Second, I will perform CSF single cell gene expression studies to identify transcription patterns specific for the cause of encephalitis. Third, single cell immune profiling and anti-neuronal antibody detection assays will be used to identify new causes of autoimmune encephalitis. Finally, I will perform extensive metabolite and lipid analysis in the CSF to identify new biomarkers enabling a syndromic diagnosis to quickly differentiate between causes.

Impact: With I-PACE I aim to increase the proportion of patients with a cause-specific diagnosis of encephalitis from 50% to 80%, facilitating direct and targeted treatment to improve the prognosis. I will discover novel causes of infectious and autoimmune encephalitis, and provide insights in its pathophysiology.